The adult ventral nerve cord as a phylogenetic character in brachyceran Diptera

Insect ganglia are often composed of fused segmental units or neuromeres. We estimated the evolution of the ventral nerve cord (VNC) in higher Diptera by comparing the patterns of neuromere fusion among 33 families of the Brachycera. Variation within families is uncommon, and VNC architecture does not appear to be influenced by body shape. The outgroup pattern, seen in lower Diptera, is fusion of neuromeres belonging to thoracic segments 1 and 2 (T1 and T2), and fusion of neuromeres derived from T3 and abdominal segment 1 (A1). In the abdomen, neuromeres A7-10 are fused into the terminal abdominal ganglion (TAG). Increased neuromere fusion is a feature of the Brachycera. No brachyceran shows less fusion than the outgroups. We established six pattern elements; (1) fusion of T1 and T2, (2) fusion of T3 and A1, (3) fusion of the T1/T2 andT3/A1 ganglia, (4) increase in the number of neuromeres comprising the TAG, (5) anteriorward fusion of abdominal neuromeres, and (6) the complete fusion of thoracic and abdominal neuromeres into a synganglion. States 1 and 2 are present in the outgroup lower Diptera, and state 3 in the Xylophagomorpha, Stratiomyomorpha, Tabanomorpha and Cyclorrhapha. State 4 is a feature of all Eremoneura. State 5 is present in Cyclorrhapha only, and state 6, fusion into a synganglion, has evolved at least 4 times in the Eremoneura. Synapomorphies are provided for the Cyclorrhapha and Muscoidea, and a grouping of three basal brachyceran infraorders Xylophagomorpha, Stratiomyomorpha and Tabanomorpha. The patterns of fusion suggest that VNC architecture has evolved irreversibly, in accordance with Dollo's law.

Responses to a clinical test of mechanical provocation of nerve tissue in whiplash associated disorder

Involvement of nerve tissue may contribute to the persistence of pain following a whiplash injury. This study aimed to investigate responses to the brachial plexus provocation test (BPPT) in 156 subjects with chronic whiplash associated disorder (WAD) with and without associated arm pain and 95 asymptomatic control subjects. The range of elbow extension (ROM) and visual analogue scale (VAS) pain scores were measured. Subjects with chronic WAD demonstrated significantly less ROM and higher VAS scores with the BPPT than the asymptomatic subjects (P

Arsenic inhibits the repair of DNA damage induced by benzo(a)pyrene

In order to study the effect of arsenic on DNA damage, Sprague-Dawley rats were dosed with sodium arsenite (10 mg/kg) with or without 800 mug of benzo(a)pyrene (BP) by intramammilary injection. The animals were sacrificed on day 1, 3, 5, 10 and 27 and the mammary gland tissues were collected for DNA adduct measurement using a P-32 post-labeling assay. Animals dosed with arsenic alone did not show any DNA adducts. DNA adduct levels in rats dosed with BP alone reached a maximum level by day 5, reducing to 13% of this level by day 27. Adduct levels in rats dosed with arsenic and BP also reached a maximum by day 5 but only 80% of the level observed in the BP group. However, 84% of this amount still remained by day 27. The First Nucleotide Change (FNC) technique was used for the screening of 115 samples of various tissues from mice that had been chronically exposed to sodium arsenate for over 2 years revealed that inorganic arsenic did not attack the two putative hotspots (codons 131 and 154) of the hOGG1 gene. These results support the hypothesis that arsenic exerts its biological activity through DNA repair inhibition. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.

Axonal regeneration of retinal ganglion cells after optic nerve pre-lesions and attachment of normal or pre-degenerated peripheral nerve grafts

Axonal regeneration of retinal ganglion cells (RGCs) into a normal or pre-degenerated peripheral nerve graft after an optic nerve pre-lesion was investigated. A pre-lesion performed 1-2 weeks before a second lesion has been shown to enhance axonal regeneration in peripheral nerves (PN) but not in optic nerves (ON) in mammals. The lack of such a beneficial pre-lesion effect may be due to the long delay (1-6 weeks) between the two lesions since RGCs and their axons degenerate rapidly 1-2 weeks following axotomy in adult rodents. The present study examined the effects of the proximal and distal ON pre-lesions with a shortened delay (0-8 days) on axonal regeneration of RGCs through a normal or pre-degenerated PN graft. The ON of adult hamsters was transected intraorbitallv at 2 mm. (proximal lesion) or intracranially at 7 mm (distal lesion) from the optic disc. The pre-lesioned ON was re-transected at 0.5 mm from the disc after 0, 1, 2, 4, or 8 days and a normal or a pre-degenerated PN graft was attached onto the ocular stump. The number of RGCs regenerating their injured axons into the PN graft was estimated by retrograde labeling with FluoroGold 4 weeks after grafting. The number of regenerating RGCs decreased significantly when the delay-time increased in animals with both the ON pre-lesions (proximal or distal) compared to control animals without an ON pre-lesion. The proximal ON pre-lesion significantly reduced the number of regenerating RGCs after a delay of 8 days in comparison with the distal lesion. However, this adverse effect can be overcome, to some degree, by a pre-degenerated PN graft applied 2, 4, or 8 days after the distal ON pre-lesion enhanced more RGCs to regenerate than the normal PN graft. Thus, in order to obtain the highest number of regenerating RGCs, a pre-degenerated PN should be grafted immediately after an ON lesion.

Macrophages, myofibroblasts and neointimal hyperplasia after coronary artery injury and repair

Macrophages participate in the restenosis process through the release of cytokines, metalloproteinases and growth factors. Studies of peritoneal granulation tissue suggest that macrophages may be precursors of myofibroblasts. This study examined the contribution of monocyte/macrophage lineage cells to neointimal cellular mass in a porcine model of thermal vascular injury. Thermal coronary artery injury caused medial smooth muscle cell necrosis and transformation of the media into an extracellular matrix barrier. The neointimal hyperplasia that developed over the injury sites was evaluated by light microscopy, electron microscopy and immunohistochemistry. At day 3, blood monocytes were adhered to the vessel wall and infiltrated the fibrotic media. At day 14, 42 +/- 3.9% of neointimal cells had a monocytic nuclear morphology and expressed macrophage-specific antigen SWC3 (identified by monoclonal antibody DH59B). Moreover, 9.2+/-1.8% of neointimal cells co-expressed SWC3 and alpha-smooth muscle actin and had ultrastructural characteristics intermediate between macrophages and myofibroblasts. At day 28, 10.5 +/- 3.5%, of cells expressed SWC3 and 5.2+/-1.8% of cells co-expressed SWC3 and alpha-smooth muscle actin. This study indicates that hematopoietic cells of monocyte/macrophage lineage abundantly populate the neointima in the process of lesion formation and may be precursors of neointimal myofibroblasts after thermal vascular injury. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.

Roles of fibroblast growth factors in the inner ear

The basic biology of the fibroblast growth factor (FGF) receptors and their splice variants is first reviewed, followed by a review of the known roles of FGFs in the inner ear. They include induction of the otocyst by FGF19, followed by FGF3 in further development of the otocyst. In later development, FGF3 or FGF10 acting on FGF receptor 2b is likely to be involved in development of the walls of the cochlear spaces, while FGF receptor 3 is involved in differentiation of the pillar cells of the organ of Corti. FGF1 and FGF2 act as trophic factors for the developing cochlear nerve fibres. Copyright (C) 2002 S. Karger AG, Basel.

Synaptic vesicle transport and synaptic membrane transporter sites in excitatory amino acid nerve terminals in Alzheimer disease

The apparent L-[H-3]glutamate uptake rate (v') was measured in synaptic vesicles isolated from cerebral cortex synaptosomes prepared from autopsied Alzheimer and non-Alzheimer dementia cases, and age-matched controls. The initial synaptosome preparations exhibited similar densities of D-[H-3]aspartate membrane binding sites (B-MAX values) in the three groups. In control brain the temporal cortex D-[H-3]aspartate B-MAX was 132% of that in motor cortex, parallel with the L- [H-3]glutamate v' values (temporal = 139% of motor; NS). Unlike D- [H-3]aspartate B-MAX values, L- [H-3]glutamate v' values were markedly and selectively lower in Alzheimer brain preparations than in controls, particularly in temporal cortex. The difference could not be attributed to differential effects of autopsy interval or age at death. Non-Alzheimer dementia cases resembled controls. The selective loss of vesicular glutamate transport is consistent with a dysfunction in the recycling of transmitter glutamate.

Haemodynamic response to TENS applied to upper thoracic nerve roots in normal subjects

This study investigated the haemodynamic response to the 90-minute application of 85 Hz transcutaneous electrical nerve stimulation (TENS) to the T1 and T5 nerve roots. Comparison was made between 20 healthy subjects who had TENS stimulation and a separate group of 20 healthy subjects who rested for 90 minutes. Pulse and blood pressure were measured just prior to the start of TENS stimulation, after 30 minutes of stimulation, and after 90 minutes of stimulation (immediately after stopping TENS) or at completion of the rest time depending on group allocation. The rate pressure product was calculated from the pulse and systolic blood pressure data. Multivariate repeated measures analysis showed a significant group effect for TENS (p = 0.048). Univariate repeated measures analyses showed a significant group by time effect due to TENS on systolic blood pressure over the 90-minute time period (p = 0.028). Separate group repeated measures ANOVA showed a significant decline in heart rate (p = 0.000), systolic blood pressure (p = 0.013) and rate pressure product (p = 0.000) for the TENS group, while the control resting group showed a significant decline in heart rate only (p = 0.04). The application of 85 Hz TENS to the upper thoracic nerve roots causes no adverse haemodynamic effects in healthy subjects.

Repair-replace strategies for two-dimensional warranty policies

For repairable items sold with free replacement warranty, the actions available to the manufacturer to rectify failures under warranty are to (1) repair the failed item or (2) replace it with a new one. A proper repair-replace strategy can reduce the expected cost of servicing the warranty. In this paper, we study repair-replace strategies for items sold with a two-dimensional free replacement warranty. (C) 2003 Elsevier Ltd. All rights reserved.

Linkage and Association Analysis of Radiation Damage Repair Genes XRCC3 and XRCC5 with Nevus Density in Adolescent Twins

Previous studies have shown that a deficiency in DNA damage repair is associated with increased cancer risk, and exposure to UV radiation is a major risk factor for the development of malignant melanoma. High density of common nevi (moles) is a major risk factor for cutaneous melanoma. A nevus may result from a mutation in a single UV-exposed melanocyte which failed to repair DNA damage in one or more critical genes. XRCC3 and XRCC5 may have an effect on nevus count through their function as components of DNA repair processes that may be involved directly or indirectly in the repair of DNA damage due to UV radiation. This study aims to test the hypothesis that the frequency of flat or raised moles is associated with polymorphism at or near these DNA repair genes, and that certain alleles are associated with less efficient DNA repair, and greater nevus density. Twins were recruited from schools in south eastern Queensland and were examined close to their 12th birthday. Nurses examined each individual and counted all moles on the entire body surface. A 10cM genome scan of 274 families (642 individuals) was performed and microsatellite polymorphisms in XRCC3 and adjacent to XRCC5 were also typed. Linkage and association of nevus count to these loci were tested simultaneously using a structural-equation modeling approach implemented in MX. There is weak evidence for linkage of XRCC5 to a QTL influencing raised mole count, and also weak association. There is also weak evidence for association between flat mole count and XRCC3. No tests were significant after correction for testing multiple alleles, nor were any of the tests for total association significant. If variation in XRCC3 or XRCC5 influences UV sensitivity, and indirectly affects nevus density, then the effects are small.

Nerve growth factor overexpression and autocrine loop in breast cancer cells

We show here that nerve growth factor (NGF), the canonical neurotrophic factor, is synthesized and released by breast cancer cells. High levels of NGF transcript and protein were detected in breast cancer cells by reverse transcription-PCR, Western blotting, ELISA assay and immunohistochemistry. Conversely, NGF production could not be detected in normal breast epithelial cells at either the transcriptional or protein level. Confocal analysis indicated the presence of NGF within classical secretion vesicles. Breast cancer cell-produced NGF was biologically active, as demonstrated by its ability to induce the neuronal differentiation of embryonic neural precursor cells. Importantly, the constitutive growth of breast cancer cells was strongly inhibited by either NGF-neutralizing antibodies or K-252a, a pharmacological inhibitor of NGF receptor TrkA, indicating the existence of an NGF autocrine loop. Together, our data demonstrate the physiological relevance of NGF in breast cancer and its potential interest as a marker and therapeutic target.

Repair of three pathologic fractures in a dog with multiple myeloma

Three pathological fractures occurred secondary to osteolytic lesions of multiple myeloma. Two long bone fractures were each stabilised using interlocking nail fixation augmented with polymethyl meth acral ate bone cement. One vertebral fracture was stabilised using Steinmann pins and PMMA. Successful stabilisation, rapid return to function and improvement in quality of life occurred in all fractures. The patient survived approximately eight months on concurrent chemotherapy.