Influence of temperature of incubation and type of growth medium on pigmentation in Serratia marcescens.

Maximal amounts of prodigiosin were synthesized in either minimal or complete medium after incubation of cultures at 27 C for 7 days. Biosynthesis of prodigiosin began earlier and the range of temperature for formation was greater in complete medium. No prodigiosin was formed in either medium when cultures were incubated at 38 C; however, after a shift to 27 C, pigmentation ensued, provided the period of incubation at 38 C was not longer than 36 hr for minimal medium or 48 hr for complete medium. Washed, nonpigmented cells grown in either medium at 38 C for 72 hr could synthesize prodigiosin when suspended in saline at 27 C when casein hydrolysate was added. These suspensions produced less prodigiosin at a slower rate than did cultures growing in casein hydrolysate at 27 C without prior incubation at 38 C. Optimal concentration of casein hydrolysate for pigment formation by suspensions was 0.4%; optimal temperature was 27 C. Anaerobic incubation, shift back to 38 C, killing cells by heating, or chloramphenicol (25 mug/ml) inhibited pigmentation. Suspensions of washed cells forming pigment reached pH 8.0 to 8.3 rapidly and maintained this pH throughout incubation for 7 days. Measurements of viable count and of protein, plus other data, indicated that cellular multiplication did not occur in suspensions of washed cells during pigment formation. By this procedure utilizing a shift down in temperature, biosynthesis of prodigiosin by washed cells could be separated from multiplication of bacteria.

LY2109761, a novel transforming growth factor beta receptor type I and type II dual inhibitor, as a therapeutic approach to suppressing pancreatic cancer metastasis.

Most pancreatic cancer patients present with inoperable disease or develop metastases after surgery. Conventional therapies are usually ineffective in treating metastatic disease. It is evident that novel therapies remain to be developed. Transforming growth factor beta (TGF-beta) plays a key role in cancer metastasis, signaling through the TGF-beta type I/II receptors (TbetaRI/II). We hypothesized that targeting TbetaRI/II kinase activity with the novel inhibitor LY2109761 would suppress pancreatic cancer metastatic processes. The effect of LY2109761 has been evaluated on soft agar growth, migration, invasion using a fibroblast coculture model, and detachment-induced apoptosis (anoikis) by Annexin V flow cytometric analysis. The efficacy of LY2109761 on tumor growth, survival, and reduction of spontaneous metastasis have been evaluated in an orthotopic murine model of metastatic pancreatic cancer expressing both luciferase and green fluorescence proteins (L3.6pl/GLT). To determine whether pancreatic cancer cells or the cells in the liver microenvironment were involved in LY2109761-mediated reduction of liver metastasis, we used a model of experimental liver metastasis. LY2109761 significantly inhibited the L3.6pl/GLT soft agar growth, suppressed both basal and TGF-beta1-induced cell migration and invasion, and induced anoikis. In vivo, LY2109761, in combination with gemcitabine, significantly reduced the tumor burden, prolonged survival, and reduced spontaneous abdominal metastases. Results from the experimental liver metastasis models indicate an important role for targeting TbetaRI/II kinase activity on tumor and liver microenvironment cells in suppressing liver metastasis. Targeting TbetaRI/II kinase activity on pancreatic cancer cells or the cells of the liver microenvironment represents a novel therapeutic approach to prevent pancreatic cancer metastasis.

Skeletal abnormalities in mice lacking extracellular matrix proteins, thrombospondin-1, thrombospondin-3, thrombospondin-5, and type IX collagen.

Thrombospondin-5 (TSP5) is a large extracellular matrix glycoprotein found in musculoskeletal tissues. TSP5 mutations cause two skeletal dysplasias, pseudoachondroplasia and multiple epiphyseal dysplasia; both show a characteristic growth plate phenotype with retention of TSP5, type IX collagen (Col9), and matrillin-3 in the rough endoplasmic reticulum. Whereas most studies focus on defining the disease process, few functional studies have been performed. TSP5 knockout mice have no obvious skeletal abnormalities, suggesting that TSP5 is not essential in the growth plate and/or that other TSPs may compensate. In contrast, Col9 knockout mice have diminished matrillin-3 levels in the extracellular matrix and early-onset osteoarthritis. To define the roles of TSP1, TSP3, TSP5, and Col9 in the growth plate, all knockout and combinatorial strains were analyzed using histomorphometric techniques. While significant alterations in growth plate organization were found in certain single knockout mouse strains, skeletal growth was only mildly disturbed. In contrast, dramatic changes in growth plate organization in TSP3/5/Col9 knockout mice resulted in a 20% reduction in limb length, corresponding to similar short stature in humans. These studies show that type IX collagen may regulate growth plate width; TSP3, TSP5, and Col9 appear to contribute to growth plate organization; and TSP1 may help define the timing of growth plate closure when other extracellular proteins are absent.

Concomitant Mycobacterium tuberculosis infection and type 2 diabetes: A descriptive model with global health implications

The type 2 diabetes (diabetes) pandemic is recognized as a threat to tuberculosis (TB) control worldwide. This secondary data analysis project estimated the contribution of diabetes to TB in a binational community on the Texas-Mexico border where both diseases occur. Newly-diagnosed TB patients > 20 years of age were prospectively enrolled at Texas-Mexico border clinics between January 2006 and November 2008. Upon enrollment, information regarding social, demographic, and medical risks for TB was collected at interview, including self-reported diabetes. In addition, self-reported diabetes was supported by blood-confirmation according to guidelines published by the American Diabetes Association (ADA). For this project, data was compared to existing statistics for TB incidence and diabetes prevalence from the corresponding general populations of each study site to estimate the relative and attributable risks of diabetes to TB. In concordance with historical sociodemographic data provided for TB patients with self-reported diabetes, our TB patients with diabetes also lacked the risk factors traditionally associated with TB (alcohol abuse, drug abuse, history of incarceration, and HIV infection); instead, the majority of our TB patients with diabetes were characterized by overweight/obesity, chronic hyperglycemia, and older median age. In addition, diabetes prevalence among our TB patients was significantly higher than in the corresponding general populations. Findings of this study will help accurately characterize TB patients with diabetes, thus aiding in the timely recognition and diagnosis of TB in a population not traditionally viewed as at-risk. We provide epidemiological and biological evidence that diabetes continues to be an increasingly important risk factor for TB.^

Changes in 911 call volume and type during Hurricane Ike and the implementation and usefulness of the TeleHealth Nurse system for the Houston Fire Department

This study examined both changing call volume and type with resulting effect of TeleHealth Nurse, the Houston Fire Department's (HFD) telephone nurse line, on call burden during Hurricane Ike. On September 13, 2008, Hurricane Ike made landfall in the Galveston area and continued north through Houston resulting in catastrophic damages in infrastructure and posing a public health threat. The overall goal of this study looked at data from Houston Fire Department to obtain a better understanding of the needs of citizens before, during, and after a hurricane. This study looked at four aspects of emergency response from HFD. The first section looked at call volumes surrounding the time of Hurricane Ike in 2008 compared to the same time period in 2007. The data showed a 12% increase in calls surrounding Hurricane Ike compared to previous years with a p value <.001. Next, the study evaluated the types of calls prevalent during Hurricane Ike compared to the same time period in 2007. The data showed a statistically significant increase in chronic health problems such as diabetes and cardiac events, Obstetric calls and an increase in breathing problems, falls, and lacerations during the days following Hurricane Ike. There was also a statistically significant increase in auto med alerts and check patients surrounding Hurricane Ike's landfall. The third section analyzed the change in call volume sent to HFD's Telephone Nurse Line during Hurricane Ike and compares this to earlier time periods while the fourth and final section looks at the types of calls sent to the nurse line during Hurricane Ike. The data showed limited use of the TeleHealth Nurse line before Hurricane Ike, but when the winds were at their strongest and ambulances were unable to leave the station, the nurse line was the only functioning medical help some people were able to receive. These studies bring a better understanding to the number and types of calls that a city might experience during a natural disaster, such as a hurricane. This study also shows the usefulness of an EMS Telephone Nurse Line during a natural disaster.^

Assessing the relationship between obesity and type II diabetes among South Asian Indians in Houston A population based study

Objective: My study aimed at determining the association between obesity and diabetes prevalence in South Asian Indian immigrants in Houston, Texas. To also compare the prevalence odds of diabetes given obesity, using WHO-BMI criteria and recommended Asian ethnic-specific BMI criteria for obesity, as well as using WHO-standard waist circumference criteria and ethnic-specific criteria for abdominal obesity, across gender and age, in this population. ^ Methods: My study was a secondary data analysis based on a cross-sectional study carried out on adult South Asian Indians who attended a local community health fair in Houston, in 2007. They recruited 213 voluntary, eligible, South Asian Indian participants aged between 18 to 79 years. Self reported history of Diabetes was obtained and height, weight, waist and hip circumference were measured. I classified BMI based on WHO-standard and ethnic-specific criteria, according to gender and age groups of 18–35 years, 36–64 years and 65 years and over. Waist circumference was also classified based on WHO-standard NCEP criteria and currently recommended ethnic-specific IDF criteria and analysis was done stratifying by gender and age groups. ^ Results: The prevalence of diabetes in this population was 14.6%, significantly higher in older age groups (25.8%) and males (19.2%). The prevalence of DM was statistically similar in individuals who were overweight/obese compared to those not overweight/obese, however in overweight/obese individuals, there was a statistically significant difference in the prevalence of DM between WHO and ethnic-specific criteria for both BMI and waist circumference. In older adults and in males, ethnic-specific criteria identified significantly more as overweight/obese compared to WHO-standard criteria. ^ Conclusions: Ethnic-specific criteria for both BMI and waist circumference give a better estimate for obesity in this South Asian Indian population. Diabetes is highly prevalent in migrant South Asian Indians even at low BMI or waist circumference levels and significantly more in males and older age groups, hence adequate awareness should be created for early prevention and intervention.^

Ascorbic acid effects on the immune system and type -1 /type -2 cytokine balance in humans

Vitamin C (ascorbic acid--AA) can have a substantial impact on human health by reducing the incidence and/or severity of coryza. Studies also suggest it has immunomodulatory functions in humans. Immune function is controlled by cytokines, such as type-1 cytokines (IFNγ) that promote antiviral immunity and type-2 cytokines (IL-4, IL-10) that promote humoral immunity. Knowing the mechanisms responsible for both antiviral immunity and type-1/type-2 cytokine balance, we sought to identify AA-induced alterations of human peripheral blood mononuclear cells (PBMC) in vivo and in vitro . We hypothesized that AA modulates the immune system, altering both number and function of PBMC. We first described the effect of 14 days of oral (1 gram) AA in healthy subjects. AA increased circulating natural killer (NK) cells, CD25+ and HLA-DR+ T cells, and PMA/ionomycin-stimulated intracellular IFNγ. We subsequently developed models for in vitro use. We determined that AA was toxic in vitro to T cells when used at doses found intracellularly but doses found in plasma from individuals taking 1gm/day AA were nontoxic. The model that most fully reproduced our in vivo intracellular cytokine findings used dehydroascorbic acid and buffers to deliver AA intracellularly. This model generated the largest increase in IFNγ at physiologic plasma concentrations. Previous studies demonstrate that chronic psychological stress is associated with a type-2 cytokine response. We hypothesized that vitamin C could prevent the type-2 cytokine shift associated with stress. In a study of medical students taking 1 g AA or placebo, a significant increase in IFNγ was seen intracellularly in CD4+ and CD8+ cells and in tetanus-stimulated cultures in the AA group only. We also observed increases in IFNγ/IL-4 and IFNγ/IL-10 ratios with AA supplementation, indicating a type-1 shift. Furthermore, we noted increased numbers of NK cells and activated T cells in the peripheral blood in the AA treated group only. Lastly, we investigated the role of the CD40L/CD40 and CD28/B7 costimulatory pathway in these cytokine alterations. AA did not have any effect on either pathway studied. Thus costimulatory pathways are not contributing to AA induced modulation of the type-1/type-2 immune balance. ^

5-HT and GABA modulate intrinsic excitability of type I interneurons in Hermissenda.

The sensory neurons (photoreceptors) in the visual system of Hermissenda are one site of plasticity produced by Pavlovian conditioning. A second site of plasticity produced by conditioning is the type I interneurons in the cerebropleural ganglia. Both photoreceptors and statocyst hair cells of the graviceptive system form monosynaptic connections with identified type I interneurons. Two proposed neurotransmitters in the graviceptive system, serotonin (5-HT) and gamma-aminobutyric acid (GABA), have been shown to modify synaptic strength and intrinsic neuronal excitability in identified photoreceptors. However, the potential role of 5-HT and GABA in plasticity of type I interneurons has not been investigated. Here we show that 5-HT increased the peak amplitude of light-evoked complex excitatory postsynaptic potentials (EPSPs), enhanced intrinsic excitability, and increased spike activity of identified type I(e(A)) interneurons. In contrast, 5-HT decreased spike activity and intrinsic excitability of type I(e(B)) interneurons. The classification of two categories of type I(e) interneurons was also supported by the observation that 5-HT produced opposite effects on whole cell steady-state outward currents in type I(e) interneurons. Serotonin produced a reduction in the amplitude of light-evoked complex inhibitory PSPs (IPSPs), increased spontaneous spike activity, decreased intrinsic excitability, and depolarized the resting membrane potential of identified type I(i) interneurons. In contrast to the effects of 5-HT, GABA produced inhibition in both types of I(e) interneurons and type I(i) interneurons. These results show that 5-HT and GABA can modulate the intrinsic excitability of type I interneurons independent of the presynaptic effects of the same transmitters on excitability and synaptic efficacy of photoreceptors.

Glucocorticoid alterations in the human type-1/type-2 cytokine balance and the role of CD28/B7 costimulation

We have recently reported that psychological stress is associated with a shift in the human type-1/type-2 cytokine balance toward a type-2 cytokine response. The mechanisms of these cytokine alterations are unknown, but likely involve glucocorticoid (GC) modulation of cytokine production. Therefore we sought to characterize the effects of GC on the in vitro human type-1/type-2 cytokine balance. We hypothesized that GC induce a type-2 cytokine shift through modulation of critical regulatory cytokines and alterations in the CD28/B7 costimulatory pathway. ^ We first sought to characterize the effect of the GC, dexamethasone (DEX), on type-1 (IFN-γ, IL-12) and type-2 (IL-4, IL-10) cytokine production by human peripheral blood mononuclear blood cells (pBMC) stimulated with a variety of T-lymphocyte and monocyte stimuli. DEX, at concentrations mimicking stress and supraphysiologic levels of cortisol, decreased IFN-γ and IL-12 production and increased IL-4 and IL-10 production, indicating a shift in the type-1/type-2 cytokine balance toward a type-2 response. Furthermore, both CD4+ and CD8+ T-lymphocytes were susceptible to the cytokine modulating effects of DEX. Furthermore, in the absence of the monocyte, the DEX-induced alterations in T-lymphocyte cytokine production were reduced, indicating that the interaction between the monocyte and T-lymphocyte plays a significant role. ^ We next determined the role of regulatory cytokines, known to modulate the type-1/type-2 cytokine balance, in the DEX-induced cytokine alterations. The addition of the recombinant IL-12p70 and IFN-γ, but not the neutralization of IL-4, IL-10 or IL-13 using monoclonal antibodies, attenuated the DEX-induced type-1/type-2 cytokine alterations. These data suggest that the DEX-induced cytokine alterations are mediated, at least in part, through the initial inhibition type-1 cytokines. Lastly, we investigated the role of the CD28/B7 costimulatory pathway in these cytokine alterations. DEX decreased the expression of CD80 and CD86 on THP-1 cells, a monocyte cell line, and the expression of CD28 and CTLA-4 on PHA-stimulated pBMC. The DEX-induced decrease in CD28 and CTLA-4 expression was attenuated by rhIL-12. Finally, CD28 activation attenuated the DEX-induced decrease in IFN-γ production, suggesting that modulation of the CD28/B7 costimulatory pathway may contribute to the DEX-induced type-1/type-2 cytokine alterations. ^

17-beta estradiol and progesterone-induced alterations in human type-1/type-2 cytokine balance and the role of costimulatory and apoptotic mechanisms

Evidence suggests that sex-based differences in immune function may predispose women to numerous hypersensitivity conditions such as Systemic lupus erythematosus (SLE), Hashimoto's thyroiditis and asthma. To date, the exact mechanisms of sexual dimorphism in immunity are not fully characterized but sex hormones such as 17-β estradiol (E2) and progesterone (PR) are believed to be involved. Since E2 and PR may modulate the production of critical regulatory cytokines, we sought to characterize their effects on the in vitro human type-1/type-2 cytokine balance. We hypothesized that E2 and/or PR vary cytokine production and influence costimulatory molecule expression and apoptosis. We first described the effect of E2 and/or PR on type-1 (IFN-γ and IL-12) and type-2 (IL-4 and IL-10) cytokine production by human peripheral blood mononuclear cells (PBMC) treated with various T-lymphocyte and monocyte stimuli. E2 and/or PR were each used at concentrations similar to those found at the maternal-fetal interface during pregnancy. At this dose, E2 increased IFN-γ and IL-12 production and PR decreased IFN-γ production and tended to increase IL-4 production. Furthermore, the combination of E2+PR decreased IL-12 production. This suggests that E2 shifts the type-1/type-2 cytokine balance towards a type-1 response and that PR and E2+PR shift the balance towards a type-2 response. Next, we used intracellular cytokine detection to demonstrate that E2 and/or PR are capable of altering cytokine production of CD3+ T-cells and the CD3+CD4+ and CD3+CD8+ subsets. In addition, we used the H9 T-lymphocyte cell line and the THP-1 monocyte cell line to show that E2 and/or PR can induce cytokine effects in both T-cells and monocytes independent of their interaction. Lastly, we determined the effect of E2 and/or PR on costimulatory molecule expression and apoptosis as potential mechanisms for the cytokine-induced alterations. E2 increased and PR decreased CD80 expression on THP-1 cells and PR and E2+PR decreased CD28 expression in PBMC and Jurkat cells. Furthermore, E2, PR and E2+PR increased Fas-mediated apoptosis in Jurkat cells and E2 increased FasL expression on THP-1 cells. Thus, E2 and/or PR may alter the cytokine balance by modulating the CD28/CD80 costimulatory pathway and apoptosis. ^

Delayed Thrombus Resolution and Fibroproliferative Vascular Wound Healing From Deficiency of Type III Collagen: a Paradoxical Mechanism for Tissue Fragility

Vascular Ehlers-Danlos syndrome is a heritable disease of connective tissue caused by mutations in COL3A1, conferring a tissue deficiency of type III collagen. Cutaneous wounds heal poorly in these patients, and they are susceptible to spontaneous and catastrophic rupture of expansible hollow organs like the gut, uterus, and medium-sized to large arteries, which leads to premature death. Although the predisposition for organ rupture is often attributed to inherent tissue fragility, investigation of arteries from a haploinsufficient Col3a1 mouse model (Col3a1+/-) demonstrates that mutant arteries withstand even supraphysiologic pressures comparably to wild-type vessels. We hypothesize that injury that elicits occlusive thrombi instead unmasks defective thrombus resolution resulting from impaired production of type III collagen, which causes deranged remodeling of matrix, persistent inflammation, and dysregulated behavior by resident myofibroblasts, culminating in the development of penetrating neovascular channels that disrupt the mechanical integrity of the arterial wall. Vascular injury and thrombus formation following ligation of the carotid artery reveals an abnormal persistence and elevated burden of occlusive thrombi at 21 post-operative days in vessels from Col3a1+/- mice, as opposed to near complete resolution and formation of a patent and mature neointima in wild-type mice. At only 14 days, both groups harbor comparable burdens of resolving thrombi, but wild-type mice increase production of type III collagen in actively resolving tissues, while mutant mice do not. Rather, thrombi in mutant mice contain higher burdens of macrophages and proliferative myofibroblasts, which persist through 21 days while wild-type thrombi, inflammatory cells, and proliferation all regress. At the same time that increased macrophage burdens were observed at 14 and 21 days post ligation, the medial layer of mutant arterial walls concurrently harbored a significantly higher incidence of penetrating neovessels compared with those in wild-type mice. To assess whether limited type III collagen production alters myofibroblast behavior, fibroblasts from vEDS patients with COL3A1 missense mutations were seeded into three-dimensional fibrin gel constructs and stimulated with transforming growth factor-β1 to initiate myofibroblast differentiation. Although early signaling events occur similarly in all cell lines, late extracellular matrix- and mechanically-regulated events like transcriptional upregulation of type I and type III collagen secretion are delayed in mutant cultures, while transcription of genes encoding intracellular contractile machinery is increased. Sophisticated imaging of collagen synthesized de novo by resident myofibroblasts visualizes complex matrix reorganization by control cells but only meager remodeling by COL3A1 mutant cells, concordant with their compensatory contraction to maintain tension in the matrix. Finally, administration of immunosuppressive rapamycin to mice following carotid ligation sufficiently halts the initial inflammatory phase of thrombus resolution and fully prevents both myofibroblast migration into the thrombus and the differential development of neovessels between mutant and wild-type mice, suggesting that pathological defects in mutant arteries develop secondarily to myofibroblast dysfunction and chronic inflammatory stimulation, rather than as a manifestation of tissue fragility. Together these data establish evidence that pathological defects in the vessel wall architecture develop in mutant arteries as sequelae to abnormal healing and remodeling responses activated by arterial injury. Thus, these data support the hypothesis that events threatening the integrity of type III collagen-deficient vessels develop not as a result of inherent tissue weakness and fragility at baseline but instead as an episodic byproduct of abnormally persistent granulation tissue and fibroproliferative intravascular remodeling.

The functional and structural interactions between v-{\it mos\/} proteins and cell cycle control elements

The v-mos gene of Moloney murine sarcoma virus (Mo-MuSv) encodes a serine/threonine protein kinase capable of inducing cellular transformation. The c-mos protein is an important cell cycle regulator that functions during meiotic cell division cycles in germ cells. The overall function of c-mos in controlling meiosis is becoming better understood but the role of v-mos in malignant transformation of cells is largely unknown.^ In this study, v-mos protein was shown to be phosphorylated by M phase kinase in vitro and in vivo. The kinase activity and neoplastic transforming ability of v-mos is positively regulated by the phosphorylation. Together with the earlier finding of activation of M phase kinase by c-mos, these results raise the possibility of mutual regulation between M phase kinase and mos kinases.^ In addition to its functional interaction with the M phase kinase, the v-mos protein was shown to be present in the same protein complex with a cyclin-dependent kinase (cdk). In addition, an antibody that recognizes the cdk proteins was shown to co-precipitate the v-mos proteins in the interphase and mitotic cells transformed by p85$\sp{\rm gag-mos}$. Cdk proteins have been shown to be associated with nonmitotic cyclins which are potential oncogenes. The perturbation of cdk kinase or the activation of non-mitotic cyclins as oncogenes by v-mos could contribute directly to v-mos induced cellular transformation. v-mos proteins were also shown to interact with tubulin and vimentin, the essential components of microtubules and type IV intermediate filaments, respectively. The organizations of both microtubules and intermediate filaments are cell cycle-regulated. These results suggest that the v-mos kinase could be directly involved in inducing morphological changes typically seen in transformed cells.^ The interactions between the v-mos protein and these cell cycle control elements in regards to v-mos induced neoplastic transformation are discussed in detail in the text. ^

Neuromuscular disuse and atrophy: {\it In vivo\/} magnetic resonance studies of intramuscular lipid metabolism and fluid shift changes

We postulated that neuromuscular disuse results in deleteriously affected tissue-vascular fluid exchange processes and subsequently damages the important oxidative bioenergetic process of intramuscular lipid metabolism. The in-depth research reported in the literature is somewhat limited by the ex vivo nature and sporadic time-course characterization of disuse atrophy and recovery. Thus, an in vivo controlled, localized animal model of disuse atrophy was developed in one of the hindlimbs of laboratory rabbits (employing surgically implanted tetrodotoxin (TTX)-filled mini-osmotic pump-sciatic nerve superfusion system) and tested repeatedly with magnetic resonance (MR) throughout the 2-week period of temporarily induced disuse and during the recovery period (following explantation of the TTX-filled pump) for a period of 3 weeks. Controls consisted of saline/"sham"-implanted rabbit hindlimbs. The validity of this model was established with repeated electrophysiologic nerve conduction testing using a clinically appropriate protocol and percutaneously inserted small needle stimulating and recording electrodes. Evoked responses recorded from proximal (P) and distal (D) sites to the sciatic nerve cuff in the TTX-implanted group revealed significantly decreased (p $<$ 0.001) proximal-to-distal (P/D) amplitude ratios (as much as 50-70% below Baseline/pre-implanted and sham-implanted group values) and significantly increased (p $<$ 0.01) differential latency (PL-DL) values (as much as 1.5 times the pre- and sham-implanted groups). By Day 21 of recovery, observed P/D and PL-DL levels matched Baseline/sham-implemented levels. MRI-determined cross-sectional area (CSA) values of Baseline/pre-implanted, sham- or TTX-implanted, and recovering/explanted and the corresponding contralateral hindlimb tibialis anterior (TA) muscles normalized to tibial bone (TB) CSA (in TA/TB ratios) revealed that there was a significant decline (indicative of atrophic response) from pre- and sham-implanted controls by as much as 20% (p $<$ 0.01) at Day 7 and 50-55% (p $<$ 0.001) at Day 13 of TTX-implantation. In the non-implanted contralaterals, a significant increase (indicative of hypertrophic response) by as much as 10% (p $<$ 0.025) at Day 7 and 27% (p $<$ 0.001) at Day 13 + TTX was found. The induced atrophic/hypertrophic TA muscles were observed to be fully recovered by Day 21 post-explantation as evidenced by image TA/TB ratios. End-point biopsy results from a small group of rabbits revealed comprehensive atrophy of both Type I and Type II fibers, although the heterogeneity of the response supports the use of image-guided, volume-localized proton magnetic resonance spectroscopy (MRS) to noninvasively assess tissue-level metabolic changes. MRS-determined results of a 0.25cc volume of tissue within implanted limb TA muscles under resting/pre-ischemic, ischemic-stressed, and post-ischemic conditions at timepoints during and following disuse atrophy/recovery revealed significantly increased intramuscular spectral lipid levels, as much as 2-3 times (p $<$ 0.01) the Baseline/pre-implanted values at Day 7 and 6-7 times (p $<$ 0.001) at Day 13 + TTX, which approached normal levels (compared to pre- and sham-implanted groups) by Day 21 of post-explanation recovery. (Abstract shortened by UMI.) ^

Exploring the role of viral infection in type 2 diabetes

Viral infection is known to play a role in type I diabetes, but there is a paucity of information on the role of viruses in type 2 diabetes. This research examined the seroprevalence of selected viruses in a group of predominantly Mexican-American patients with End Stage Renal Disease (ESRD). Using a case control design, patients with type 2 diabetes were compared with a group of non-diabetic controls. ^ One hundred and thirteen patients, 83 with type 2 diabetes and 30 controls without diabetes, underwent hemodialysis at the same chronic dialysis facility in San Antonio, Texas. AD subjects were tested for IgG, IgM, and neutralizing antibodies against Coxsackie B viruses (CBV), and IgG and IgM antibodies against cytomegalovirus (CMV) and parvovirus B19 (PVB19). Hepatitis B virus antigen (HBVAg), Hepatitis B virus antibody (HBVAb), Hepatitis C virus antibody (HCVAb), and Rubella (IgG) were also measured. A subset of 91 patients, 66 with diabetes and 25 controls, were tested bimonthly for six months. There was a significant difference (P = 0.04) in the seroprevalence of IgG antibodies to CMV between patients with type 2 diabetes (98%) and non-diabetic controls (87%) in the initial sample (OR = 6.2, 95% CI:1.1–36.0). A greater seroprevalence of CMV IgG antibodies was observed over the six month period among patients with type 2 diabetes (M) compared to controls (84%). This difference was also statistically (P < 0.03), with a greater odds ratio (OR = 12.4, 95% CI: 1.3–116.9), but with larger confidence interval related to the small number of subjects. However, when adjusted for age by logistic regression analysis there was no difference between the groups (OR = 1). ^ After one sample, there was a greater seroprevalence of HCVAb in the group without diabetes (28%), compared to those with type 2 diabetes (10%) (P = 0.04). This difference was no longer significant when adjusted for patient age. The prevalence of antibodies to PVB19, HBSAg, HBV, and Rubella was not significantly different in patients with type 2 diabetes and controls. There were significantly more vascular complications (P < 0.02) among patients with diabetes. ^ These results indicate that the significant associations observed in this population between viral infection with CMV, HCV, and type 2 diabetes are confounded by age. Accelerated atherosclerosis has been associated with age, diabetes, as well as CMV. Latent infection may be a factor that links these processes. ^

GENERAL WELL-BEING AND USE OF SOCIAL SUPPORT

Research interest on well-being and social support has focused largely on social factors as related to attaining and maintaining well-being, self-perceptions of well-being and to a lesser extent the relationship of current level of self-perceived well-being to use of formal or informal sources of social support. This study analyzed responses to the General Well-Being Schedule of 6,913 subjects (25-74 years) interviewed during the National Health and Nutrition Examination Survey (1971-1975). The purpose of this analysis was to relate the level of GWBS scores to the use of social support, both informal (family and friends) and formal (community professionals).^ Study questions addressed were whether well-being level was related to selection of a specific social support resource and/or rate of use of resources and whether gender differences were apparent in level of well-being and social support use. Because age, sex, race, socioeconomic status (income and education) and marital status may confound the relation between level of GWB and type of social support chosen, the association between these variables with GWB and use of social support were considered. For analysis, test scores were grouped into four categories and for detailed analysis, two categories: low (0-70) and high (71-110). Cross tabulations and percentages were computed and the chi-square test of significance was used.^ Although 16 to 25 percent of the sample population reported low well-being, less than 10 percent used formal resources to discuss emotional, mental or behavior problems. Medical resources, mostly physicians, were the most used formal social supports. Informal social support was important for all well-being levels where 65-77% of each category reported using this resource.^ While well-being level does not appear to serve as a screener/selector of type of formal social support used, it is related to rates of use. Females reported slightly lower well-being than males, and except in the lowest well-being group, had higher rates of social support use. Findings support the conclusion that perceived well-being is related to use of social support such that the lower the well-being, the greater tendency to use formal and/or informal social support. ^