The eyes of deep-sea fish II. Functional morphology of the retina

Three different aspects of the morphological organisation of deep-sea fish retinae are reviewed: First, questions of general cell biological relevance are addressed with respect to the development and proliferation patterns of photoreceptors, and problems associated with the growth of multibank retinae, and with outer segment renewal are discussed in situations where there is no direct contact between the retinal pigment epithelium and the tips of rod outer segments. The second part deals with the neural portion of the deep-sea fish retina. Cell densities are greatly reduced, yet neurohistochemistry demonstrates that all major neurotransmitters and neuropeptides found in other vertebrate retinae are also present in deep-sea fish. Quantitatively, convergence rates in unspecialised parts of the retina are similar to those in nocturnal mammals. The differentiation of horizontal cells makes it unlikely that species with more than a single visual pigment are capable of colour vision. In the third part. the diversity of deep-sea fish retinae is highlighted. Based on the topography of ganglion cells, species are identified with areae or foveae located in various parts of the retina, giving them a greatly improved spatial resolving power in specific parts of their visual fields. The highest degree of specialisation is found in tubular eyes. This is demonstrated in a case study of the scopelarchid retina, where as many as seven regions with different degrees of differentiation can be distinguished, ranging from an area giganto cellularis, regions with grouped rods to retinal diverticulum. (C) 1998 Elsevier Science Ltd. All rights reserved.

H-ras activation is an early event in the ptaquiloside-induced carcinogenesis: Comparison of acute and chronic toxicity in rats

Bracken fern (Pteridium spp.) produces cancer of the urinary bladder and oesophagus in grazing animals and is a suspected human carcinogen, The carcinogenic principle ptaquiloside (PT), when activated to a dienone (APT), forms DNA adducts which eventually leads to tumor. Two groups of female Sprague-Dawley rats were given a chronic dose of 3 mg APT weekly for 10 weeks either by intravenous (iv) tail vein or by intragastric (ig) route, A third group was given a weekly dose of 6 mg of APT for 3 weeks by the ig route corresponding to acute dosing. Both chronic iv and ig dosed animals showed ischemic tubular necrosis in the kidney but only iv dosed animals developed adenocarcinomas of the mammary glands. Acutely dosed ig animals produced apoptotic bodies in the liver, necrosis of blood cell precursors in the bone marrow and ischemic tubular necrosis in the kidney but they did not develop tumors, No mutations were found in the H-ras and p53 genes in the mammary glands of either the ig rats or the tumor-bearing iv rats. However, the mammary glands of a fourth group of rats, which received APT by iv and killed before tumor development, carried Pu to Pu and Pu to Py double mutations in codons 58 and 59 of H-ras. This study indicates that the route of administration plays a role in the nature of the disease expression from ptaquiloside exposure. In addition to confirming the role of APT in the PT-induced carcinogenesis our finding suggests that activation of H-ras is an early event in the PT-carcinogenesis model. (C) 1998 Academic Press.

Identification of the coupling between skeletal muscle store-operated Ca2+ entry and the inositol trisphosphate receptor

Examination of store-operated Ca2+ entry (SOC) in single, mechanically skinned skeletal muscle cells by confocal microscopy shows that the inositol 1,4,5-trisphosphate (IP3) receptor acts as a sarcoplasmic reticulum [Ca2+] sensor and mediates SOC by physical coupling without playing a key role in Ca2+ release from internal stores, as is the case with various cell types in which SOC was investigated previously. The results have broad implications for understanding the mechanism of SOC that is essential for cell function in general and muscle function in particular. Moreover, the study ascribes an important role to the IN receptors in skeletal muscle, the role of which with respect to Ca2+ homeostasis was ill defined until now.

Urine Volume in Acute Kidney Injury: How Much Is Enough?

Eight hundred and seventy-nine patients with acute kidney injury were retrospectively studied over year and eleven months for evaluation of urine volume as a risk factor for death. They were divided into five groups, according to the 24 h urine volume (UV): anuric (UV <= 50 mL/24 h, group 1), oliguric (UV > 50 mL/24 h and < 400 mL/24 h, group 2), and non-oliguric (UV >= 400 mL/24 h). Nonoliguric group was subdivided in three subgroups: UV > 400 mL/24 h and <= 1000 mL/24 h (group 3, reference group), UV > 1000 mL/24 h and <= 2000 mL/24 h (group 4), and UV > 2000 mL/24 h (group 5). Linear tendency test (Mantel extension) pointed out a significant increase in mortality with UV decrease (p < 0.001), confirmed by multivariate analysis. Anuric and oliguric patients had increased risk of respectively 95% and 76% times for death compared to controls (p < 0.05). Patients from groups 4 and 5 presented a reduced risk for death of 50% and 70%, respectively, p = 0.004 and p = 0.001. In conclusion, urine volume was a strong independent factor for mortality in this cohort of AKI patients.

Synchronous adenocarcinoma of the major and minor duodenal papilla

A 50-year-old woman presented with pancreatitis, fluctuant jaundice, weight loss, and abdominal pain. Contrast-enhanced computed tomography and abdominal ultrasound showed slight dilatation of the biliary tree and gallbladder without calculi. Endoscopy demonstrated a tumor protruding from the papilla of Vater. First endoscopically biopsy diagnosed no tumor, and a second biopsy diagnosed as papillary adenocarcinoma. The patient underwent duodenopancreatectomy. The specimen was fixed in formalin (10%). The tissue was processed routinely, and paraffin sections were stained with hematoxylin-eosin and periodic acid Schiff. Gross examination showed two tumors seen as prolapsed nodules growing isolated from the minor and major duodenal papillae measuring 1.5 and 1.0 cm, respectively, both covered by duodenal mucosa and the histologic study of both lesions demonstrated a moderately differentiated tubular adenocarcinoma, which invaded duodenal wall. After surgery, she is alive 24 months without evidence of recurrence.

Use of methotrexate in older patients - A risk-benefit assessment

Methotrexate is eliminated almost entirely by the kidneys. The risk of methotrexate toxicity is therefore increased in patients with poor renal function, most likely as a result of drug accumulation. Declining renal function with age may thus be an important predictor of toxicity to methotrexate. Up to 60% of all patients who receive methotrexate for rheumatoid arthritis (RA) discontinue taking it because of adverse effects, most of which occur during the first year of therapy. Gastrointestinal complications are the most common adverse effects of methotrexate, but hepatotoxicity, haematological toxicity, pulmonary toxicity, lymphoproliferative disorders and exacerbation of rheumatic nodules have all been reported, Decreased renal function as a result of disease and/or aging appears to be an important determinant of hepatic, lymphoproli ferative and haematological toxicity, Concomitant use of low doses of folic acid has been recommended as an approach to limiting toxicity. Interactions between methotrexate and several nonsteroidal anti-inflammatory drugs have been reported, but they may not be clinically significant. However, caution is advised in the use of such combinations in patients with reduced renal function. More serious toxicities (e.g. pancytopenia) may result when other inhibitors of folate utilisation [e.g. cotrimoxazole (trimethoprim-sulfamethoxazole)] or inhibitors of renal tubular secretion (e.g. probenecid) are combined with methotrexate. Before starting low dose methotrexate therapy in patients with RA, a full blood count, liver function tests, renal function tests and chest radiography should be performed. Blood counts and liver function tests should be repeated at regular intervals. Therapeutic drug monitoring of methotrexate has also been suggested as a means of limiting toxicity. Patients with RA usually respond very favourably to low dose methotrexate therapy, and the probability of patients continuing their treatment beyond 5 years is greater than for other slow-acting antirheumatic drugs. Thus, given its sustained clinical utility and relatively predictable toxicity profile, low dose methotrexate is a useful addition to the therapy of RA.

Interstitial expression of angiotensin II and AT1 receptor are increased in patients with progressive glomerulopathies

In animal models, interstitial angiotensin II (ang II) and AT1 receptor (AT1R) are key mediators of renal inflammation and fibrosis in progressive chronic nephropathies. We hypothesized that these molecules were overexpressed in patients with progressive glomerulopathies. In this observational retrospective study, we described the expression of ang II and AT1R by immunohistochemistry in kidney biopsies of 7 patients with minimal change disease (MCD) and in 25 patients with progressive glomerulopathies (PGPs). Proteinuria, serum albumin, and serum creatinine were not statistically different between MCD and PGP patients. Total expression of ang II and AT1R was not statistically different between MCD (108.7 +/- 11.5 and 73.2 +/- 13.6 cells/mm(2), respectively) and PGN patients (100.7 +/- 9.0 and 157.7 +/- 13.8 cells/mm(2), respectively; p>0.05). Yet, interstitial expression of ang II and AT1R (91.6 +/- 16.0 and 45.6 +/- 5.4 cells/mm(2), respectively) was higher in patients with PGN than in those with MCD (22.0 +/- 4.1 and 17.9 +/- 2.9 cells/mm(2), respectively, p<0.05), as was the proportion of interstitial fibrosis (11.0 +/- 0.7% versus 6.1 +/- 1.2%, p<005). In patients with MCD, ang II and AT1R expressions predominate in the tubular compartment (52% and 36% of the positive cells, respectively). In those with PGP, the interstitial expression of ang II and AT1R predominates (58% and 45%, respectively). In conclusion, interstitial expression of ang II and AT1R is increased in patients with progressive glomerulopathies. The relationship of these results and interstitial fibrosis and disease progression in humans warrants further investigations.

Postlepidapedon Zdzitowiecki, 1993 and Gibsonivermis n g (Digenea: Lepocreadiidae) from fishes of the southern Great Barrier Reef, Australia, and their relationship to Intusatrium Durio & Manter, 1968

The genus Intusatrium Durio & Manter, 1968 is redefined based on a re-examination of paratypes of the type-species, I. robustum Durio & Manter, 1968, and is considered monotypic with characteristic terminal genitalia: internal seminal vesicle elongate tubular, with rather thick wall, divided by slight change in wall thickness into longer proximal and shorter distal region; pars prostatica subcylindrical; ejaculatory duct relatively short, with wrinkled/wall. The genus Postlepidapedon Zdzitowiecki, 1993 is redefined and Intusatrium secundum Durio & Manter, 1968 is attributed to it as a new combination. Postlepidapedon secundum n. comb. is redescribed from a paratype and new material from Choerodon graphicus. P. spissum n. sp. from Choerodon venustus, C. cyanodus, C. fasciatus and C. schoenleinii is recognised on the basis of its thick-walled internal seminal vesicle. I! uberis n. sp. from Choerodon schoenleinii and C. venustus is distinguished by the shape and contents of the cirrus-sac with narrow, convoluted internal seminal vesicle, large vesicular pars prostatica and short, muscular ejaculatory duct. A new genus, Gibsonivermis, erected for Intusatrium berryi Gibson, 1987, is characterised by the elongate narrow cirrus-sac and a uroproct. G. berryi n. comb. is redescribed from Sillago ciliata, S. maculata and Sillago sp.

Annexin 1 mimetic peptide protects against renal ischemia/reperfusion injury in rats

Inflammation is currently recognized as a key mechanism in the pathogenesis of renal ischemia-reperfusion (I/R) injury. The importance of infiltrating neutrophil, lymphocytes, and macrophage in this kind of injury has been assessed with conflicting results. Annexin 1 is a protein with potent neutrophil anti-migratory activity. In order to evaluate the effects of annexin A1 on renal I/R injury, uninephrectomized rats received annexin A1 mimetic peptide Ac2-26 (100 mu g) or vehicle before 30 min of renal artery clamping and were compared to sham surgery animals. Annexin A1 mimetic peptide granted a remarkable protection against I/R injury, preventing glomerular filtration rate and urinary osmolality decreases and acute tubular necrosis development. Annexin A1 infusion aborted neutrophil extravasation and attenuated macrophage infiltration but did not prevent tissue lymphocyte traffic. I/R increased annexin A1 expression (assessed by transmission electron microscopy) in renal epithelial cells, which was attenuated by exogenous annexin A1 infusion. Additionally, annexin A1 reduced I/R injury in isolated proximal tubules suspension. Annexin A1 protein afforded striking functional and structural protection against renal I/R. These results point to an important role of annexin A1 in the epithelial cells defense against I/R injury and indicate that neutrophils are key mediators for the development of tissue injury after renal I/R. If these results were confirmed in clinical studies, annexin A1 might emerge as an important tool to protect against I/R injury in renal transplantation and in vascular surgery.

Sonographic Diagnosis of a Ureteral Inguinal Hernia in a Renal Transplant

Complications related to renal transplants have been widely reported in the literature. The most common complications include acute tubular necrosis, rejection, perirenal fluid collections, vascular complications, and urinary tract obstruction, which are promptly identified by imaging studies. Here we report a case of a patient with a rare cause of obstruction: a ureteral inguinal hernia. This is the sixth report of this condition, and, to our knowledge, no previous case has been reported in which sonography played an important role in promptly identifying the underlying condition and allowing additional less hazardous studies, therefore aiding case management.

Effect of saponin treatment on the sarcoplasmic reticulum of rat, cane toad and crustacean (yabby) skeletal muscle

1. Mechanically skinned fibres from skeletal muscles of the rat, toad and yabby were used to investigate the effect of saponin treatment on sarcoplasmic reticulum (SR) Ca2+ loading properties. The SR was loaded submaximally under control conditions before and after treatment with saponin and SR Ca2+ was released with caffeine. 2. Treatment with 10 mu g ml(-1) saponin greatly reduced the SR Ca2+ loading ability of skinned fibres from the extensor digitorum longus muscle of the rat with a rate constant of 0.24 min(-1). Saponin concentrations up to 150 mu g ml(-1) and increased exposure time up to 30 min did not further reduce the SR Ca2+ loading ability of the SR, which indicates that the inhibitory action of 10-150 mu g ml(-1) saponin is not dose dependent. The effect of saponin was also not dependent on the state of polarization of the transverse-tubular system. 3. Treatment with saponin at concentrations up to 100 mu g ml(-1) for 30 min did not affect the Ca2+ loading ability of SR in skinned skeletal muscle fibres from the twitch portion of the toad iliofibularis muscle but SR Ca2+ loading ability decreased markedly with a time constant of 0.22 min(-1) in the presence of 150 mu g ml(-1) saponin. 4. The saponin dependent increase in permeability could be reversed in both rat and toad fibres by short treatment with 6 mu M Ruthenium Red, a potent SR Ca2+ channel blocker, suggesting that saponin does affect the SR Ca2+ channel properties in mammalian and anuran skeletal muscle. 5. Treatment of skinned fibres of long sarcomere length (> 6 mu m) from the claw muscle of the yabby (a freshwater decapod crustacean) with 10 mu g ml(-1) saponin for 30 min abolished the ability of the SR to load Ca2+, indicating that saponin affects differently the SR from skeletal muscles of mammals, anurans and crustaceans. 6. is concluded that at relatively low concentrations, saponin causes inhibition of the skeletal SR Ca2+ loading ability in a species dependent manner, probably by increasing the Ca2+ loss through SR Ca2+ release channels.

Observations on the Female Internal Reproductive Organs of the Brown Howler Monkey (Alouatta guariba clamitans)

Alouatta guariba clamitans (brown howler monkey) is an endemic primate from the southeastern Brazil tropical forests, classified as near threatened by the IUCN Red List 2007. The genus Aloualta is one of the most difficult New World monkeys to breed and rear in captivity. In this study we examined the macroscopic and histological aspects of the female genital tract of wild brown howler monkeys to provide baseline information for future reproduction research. The anatomical relationship between the vagina, uterus, broad ligament, oviducts and ovaries are those of a typical primate reproductive tract. The fundic portion of the uterus is globoid, the cervix is well developed, which confers to the uterus an elongated shape, and the vagina is a long flattened channel. Histological analysis conducted in females in the follicular phase revealed large quantities of interstitial luteinized tissue in the ovaries, a stratified nonkeratinized vaginal epithelium, lack of glands in the vaginal mucosa and simple tubular endometrial glands. The observed anatomical features should be considered in the adaptation and application of assisted reproductive techniques aimed at improving captive reproduction for species conservation. Am. J. Primatol. 71:145-152, 2009. (C) 2008 Wiley-Liss, Inc.

Tenascin and fibronectin expression in carcinoma ex pleomorphic adenoma

This study was conducted to analyze the participation of tenascin and fibronectin, components of the extracellular matrix. in different types of carcinoma ex pleomorphic adenoma (CXPA). Seventeen cases of CXPA, classified according to the presence of epithelial and myoepithelial cells and the degree of invasion-intracapsular, minimally, and frankly invasive carcinoma-were immunohistochemically labeled for tenascin and fibronectin. Normal salivary gland included in the specimens showed tenascin only around the excretory duct, and fibronectin slightly expressed all over the stroma of the gland. In reminiscent pleomorphic adenoma, tenascin and fibronectin were observed around tubular structures and in the stroma. Both tenascin and fibronectin were expressed in all the CXPA studied. In areas of in situ carcinoma of the intracapsular type, the expression of these extracellular matrix proteins was enhanced compared with areas of residual pleomorphic adenoma. In intracapsular and minimally invasive types of CXPA, some areas of the tumor border presented tenascin and no fibronectin, pattern that may represent the real invasive front. In frankly invasive CXPA type with only epithelial component, fibronectin was strongly observed in a fibrillar network pattern, and tenascin was only focal. In frankly invasive type with myoepithelial component, tenascin staining was very strong and diffuse. This study showed different patterns of expression of tenascin and fibronectin along the process of tumorigenesis and tumor progression in CXPA, a fact that might play a role in invasion properties of these tumors.

Fatal gemcitabine-induced pulmonary toxicity in metastatic gallbladder adenocarcinoma

Gemcitabine is a chemotherapy agent that may cause unpredictable side effects. In this report, we describe a fatal gemcitabine-induced pulmonary toxicity in a patient with gallbladder metastatic adenocarcinoma. A 72-year-old patient was submitted to an elective laparoscopic cholecystectomy, and a tubular adenocarcinoma in the gallbladder was incidentally diagnosed. CT scan and ultrasound before the surgery did not show any tumor. After the surgery a Pet scan was positive for a hot-spot in the left colon. The colonic lesion was conveniently removed and the histology evaluation confirmed the diagnosis of adenocarcinoma tubular. The patient was then submitted to three sections of 1,600 mg/m(2) of gemcitabine with intervals of 1 week. Three weeks later he developed severe respiratory distress. A helicoidal CT scan showed diffuse and severe interstitial pneumonitis, and lung biopsy confirmed accelerated usual interstitial pneumonia consistent with drug-induced toxicity. The patient presented unfavorable evolution with progressive worsening of respiratory function, hypotension, and renal failure. He died 1 month later in spite of methylprednisolone pulse therapy, large spectrum antimicrobial therapy, and full support of respiratory, hemodynamic and renal systems. Gemcitabine-induced pulmonary toxicity is usually a dramatic condition. Physicians should suspect pulmonary toxicity in patients with respiratory distress after gemcitabine chemotherapy, mainly in elderly patients.

Coordinated expression of ER, PR and HER2 define different prognostic subtypes among poorly differentiated breast carcinomas

Aims: Histological grade is one of the most important prognostic factors in breast carcinomas, but poorly differentiated neoplasms still have quite heterogeneous biological behaviour, since they can be genetically classified as basal-like, HER2+ or even luminal. The aim was to analyse the frequency of oestrogen receptor (ER), progesterone receptor (PR) and HER2 expression profiles among breast carcinomas with < 10% tubular formation, and their correlation with classic prognostic factors. Methods and results: One hundred and thirty-four samples of paraffin-embedded tumours were studied retrospectively. The tumours were classified in to four groups by their ER/PR/HER2 profile: (i) ER+ and/or PR+ but HER2-; (ii) ER+ and/or PR+ and HER2+; (iii) ER- and/or PR- but HER2+; and (iv) ER-, PR- and HER2- (triple-negative). The histological features of triple-negative and HER2+ carcinomas overlap. The only difference was the expression of basal cytokeratins (basal CK), which was more frequent among triple-negative carcinomas. Basal-CK expression defined a more aggressive group of tumours, according to the pathological features, regardless of the immunohistochemical profile. Conclusions: Group 1 and 2 tumours (ER+ and/or PR+ tumours with or without HER2 expression) were not statistically different, suggesting that poorly differentiated carcinomas with hormone receptors correspond to the luminal B type of tumour. Among poorly differentiated breast carcinomas, the classic profile associated with basal-CK identifies distinct subtypes equivalent to those seen by genetic classification.