Anatomical organization of the sexually dimorphic perineal neuromuscular system in the house mouse

The anatomy of the sexually dimorphic motoneuron nuclei of the bulbocavernosus (BC) and ischiocavernosus (IC) muscles, as well as the non-sexually dimorphic external anal sphincter (EAS), was examined in hybrid B6D2F1 mice using the retrograde tracer, cholera toxin-bound horseradish peroxidase. Motoneurons innervating the BC were located in the dorsomedial nucleus (DM), as well as in the ventral nucleus (V) and in the mid-region of the ventral horn (MVH). Following injections restricted to the IC, labelled neurons were found in the dorsolateral nucleus (DL), as well as in V, DM and MVH. Cells innervating the EAS in both males and females were located in the DM, as well as in the V and MVH. An elaborate network of dendrites extended between all labelled nuclei. The present results demonstrate that the anatomical specificity of the sexually dimorphic neuromuscular system of the mouse differs from that observed in other species.     

Chemical and thyroid hormone profile of the bone marrow interstitial fluid in hematologic disorders and patients without primary hematologic disorders

Bone marrow interstitial fluid (BMIF) has not been well characterized. BMIF was isolated from 60 patients including plasma cell dyscrasias (PCD, n = 33), other primary hematologic disorders (OHD, n = 15), and patients with secondary or nonhemtologic disorders (NHD, n = 12) and analyzed for an array of chemical constituents. These included total cholesterol, glucose, phosphate, creatinine, urea, total protein, albumin, globulins, total bilirubin, aspartate aminotransferase, lactate dehydrogenase, sodium, osmolarity, free triiodothyronine (free T3), total triiodothyronine (total T3), and free tetraiodothyronine (free T4). Levels of BMIF components were compared between patient groups and to plasma levels. Compared with plasma, total cholesterol, total protein, total bilirubin, sodium, and calculated osmolarity were lower in BMIF in all groups (P < 0.05). Calculated globulins and aspartate aminotransferase were lower in BMIF of PCD patients and patients with NHD. Albumin was lower in BMIF of patients with PCD and patients with OHD. Lastly, free T4 was significantly higher in BMIF of patients with PCD and patients with OHD. Similar results were demonstrated in a separate analysis performed in patients with multiple myeloma. To conclude, the chemical and thyroid hormone composition of BMIF differs significantly from plasma in several key constituents.     

Chain reaction of amyloid fibril formation with induction of basement membrane in familial amyloidotic polyneuropathy

Familial amyloidotic polyneuropathy (FAP) is characterized by extracellular deposition of amyloid fibrils caused by a point mutation in the transthyretin (TTR) gene. Despite data from a number of in vitro studies of TTR amyloidogenesis, many questions, including where and how these fibrils form in vivo and what is the impact of amyloid deposition on tissues, remain unanswered. Here, we analysed the relationship between amyloid fibril formation and micro‐environmental changes by using autopsy cardiac tissues from 11 patients with FAP and a smooth muscle cell line. Ultrastructural studies of cardiomyocytes and vascular smooth muscle cells showed that amyloid fibrils formed first at the basement membrane and that amorphous non‐fibrillar TTR deposits and premature fibrils predominated during the early stage of amyloid deposition. Immunohistochemical analyses revealed that expression of major components of the basement membrane, such as collagen IV, laminin, and fibronectin, increased in parallel with the accumulation of TTR amyloid fibrils. In vitro studies with a vascular smooth muscle cell line revealed that synthetic TTR aggregates increased expression of these basement membrane components. Serum levels of collagen IV in FAP patients were significantly higher than those in healthy controls. Our data thus indicate that TTR amyloid fibrils formed first at the basement membrane and that expression of basement membrane components that was induced by amyloid deposition contributed to further amyloid deposition. This chain reaction may have important implications for FAP pathogenesis. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Evaluation of autonomic dysfunction by novel methods

The autonomic nervous system innervates every organ in the body. Since autonomic disturbances affect patient survival, an understanding and recognition of these disturbances are important. We adopted several new methods to evaluate autonomic function accurately. 123I-metaiodobenzylguanidine scintigraphy can assess the cardiac autonomic function even in the presence of cardiac arrhythmia. Laser-Doppler flowmetry, ultrasonographic study in the vessels and near-infrared spectrophotoscopy techniques serve as useful markers for screening the dysfunction of vasomotor neurons and blood circulation. Electrogastrography and the circadian rhythms of protein C secretion could be markers of the visceromotor nerves in the abdomen. Electrogastrography is a particularly useful tool for reflecting on functional changes in gastrointestinal motility. The evaluation of anemia could be a marker of autonomic dysfunction in the kidney and bone marrow in patients with familial amyloidotic polyneuropathy, pandysautonomia, and multiple system atrophy. Normocytic and normochromic anemia correlated with the severity of autonomic dysfunction were shown in these patients. We also evaluated the dysfunction of the neuroendocrine system and sudomotor neuron using our new autonomic function tests. The glucose-tolerance test could become one of the most useful clinical tools for detecting autonomic dysfunction in the endocrine system. Microhydrography and thermography could be useful tools for diagnosing the lesion site of dyshidrosis. Moreover, it is clinically important to check the systemic circulation and autonomic function in patients treated with sildenafil citrate and organ transplantation to save their lives. Our new autonomic function tests, such as laser-Doppler flowmetry and 123I-metaiodobenzylguanidine scintigraphy, are crucial tools in supplying the best symptomatic treatment for such patients.     

Lack of HER-2/neu expression in Hodgkin and non-Hodgkin lymphoma

OBJECTIVE: Overexpression of HER-2/neu oncoprotein, a tyrosine kinase receptor, occurs in a variety of human cancers and has been shown to play a critical role in their development. This overexpression is usually associated with poor clinical outcome. The significance of HER-2/neu in lymphomas is unknown. The aim of this study was to evaluate the expression of HER-2/neu in the malignant lymphomas: non-Hodgkin and Hodgkin lymphomas. METHODS: We studied formalin-fixed, paraffin-embedded tissue from 50 patients with lymphoma. Forty-two specimens were from patients with various types of non-Hodgkin lymphoma, and 8 were from patients with Hodgkin lymphoma. HER-2/neu expression was examined by an immunohistochemical technique using the HercepTest. RESULTS: None of the specimens demonstrated overexpression or even any expression of HER-2/neu. Reactive plasma cells showed cytoplasmic staining, which was not found in malignant plasma cells from patients with multiple myeloma. CONCLUSIONS: Non-Hodgkin and Hodgkin lymphomas do not express the HER-2/neu oncoprotein. This finding suggests that HER-2/neu does not play a role in these diseases.     

AHI1, a pivotal neurodevelopmental gene, and C6orf217 are associated with susceptibility to schizophrenia

Schizophrenia, a severe neuropsychiatric disorder, is believed to involve multiple genetic factors. A significant body of evidence supports a pivotal role for abnormalities of brain development in the disorder. Linkage signals for schizophrenia map to human chromosome 6q. To obtain a finer localization, we genotyped 180 single nucleotide polymorphisms (SNPs) in a young, inbred Arab-Israeli family sample with a limited number of founders. The SNPs were mostly within a approximately 7 Mb region around the strong linkage peak at 136.2 Mb that we had previously mapped. The most significant genetic association with schizophrenia for single SNPs and haplotypes was within a 500 kb genomic region of high linkage disequilibrium (LD) at 135.85 Mb. In a different, outbred, nuclear family sample that was not appropriate for linkage analysis, under-transmitted haplotypes incorporating the same SNPs (but not the individual SNPs) were significantly associated with schizophrenia. The implicated genomic region harbors the Abelson Helper Integration Site 1 (AHI1) gene, which showed the strongest association signal, and an adjacent, primate-specific gene, C6orf217. Mutations in human AHI1 underlie the autosomal recessive Joubert Syndrome with brain malformation and mental retardation. Previous comparative genomic analysis has suggested accelerated evolution of AHI1 in the human lineage. C6orf217 has multiple splice isoforms and is expressed in brain but does not seem to encode a functional protein. The two genes appear in opposite orientations and their regulatory upstream regions overlap, which might affect their expression. Both, AHI1 and C6orf217 appear to be highly relevant candidate genes for schizophrenia.     

Association between exercise and other preventive health behaviors among diabetics

Two hundred and seventy patients were studied to investigate the cross sectional association between exercise and other preventive health behaviors in a diabetic population. Patients included both insulin and noninsulin dependent diabetics and were recruited from the Family Practice and Pediatrics Clinics at Bowman Gray School of Medicine. During screening, patients underwent a physical examination as well as completing a survey to assess exercise and health behavior habits. Three exercise groups were compared: (a) patients who expended more than 600 kilocalories per week during exercise, (b) patients who expended 600 kilocalories or less, and (c) patients who did not exercise. The mean body weights of both exercise groups were found to be less than the nonexercise group, and the heavy exercise group also had a lower mean body mass index. Heavy exercisers reported greater caloric intakes than both moderate and nonexercisers. There were no differences found concerning the composition of their diets among groups. The heavy exercise group reported wearing their seatbelts a greater percentage of the time and visited the dentist more often compared with the sedentary group. There were no significant differences found among exercise groups concerning blood sugar monitoring, alcohol consumption, smoking, or in obtaining periodic health examinations. It was concluded that exercise was associated with several, but not a majority, of other healthful behaviors in a population of diabetics.