Correspondence: Nerve–muscle specificity

A correspondence item entitled 'A warning against revival of the classic tenets of gross anatomy related to nerve–muscle specificity' was recently published in the Journal of Anatomy (Shinohara, 1996 a ). The present correspondent fully agrees with some aspects of his opinion, in particular, the 3 laws about applications which he described, and he also appreciates his approach to the argument based on the results of embryology and experimentation. However, his denial of morphological interpretations based on the theory of nerve–muscle specificity may be due to an incomplete understanding of the current status of the theory.     

Productin of Basic Fetoprotein in Human Peripheral Lymphocytes during Blastic Transformation

To clarify the significance of basic fetoprotein (BFP) in lymphocytes, we investigated whether BFP is produced in lymphocytes during blastic transformation. Peripheral blood lymphocytes obtained from 14 adults were cultured under the stimulation of lectins. The concentration of BFP in the culture medium (extracellular BFP) was estimated serially. The incorporation of [6-³ H] thymidine was assayed simultaneously. The intracellular BFP was measured by dual flow cytometry for DNA and BFP. A lymph node was studies immunohistochemically. Serum BFP was measured in four cases of lumphocytic leukaemia. In two cases, dual staining was performed. The intracellular BFP of the mitogen-stimulated lymphocytes was increased within 24 h. The extracellular BFP was increased exponentially from 72 h. The extracellular BFP at 96 h did not correlate with the [³H]-thymidine incorporation. The intracellular BFP increase began in G₁ phase. Immunostaining showed that the B cells also produced BFP. The
serum BFP level in leukaemia was high in 1 of 4 cases and the leukaemic cells in two cases showed high intracellular BFP content. These observations indicate that BFP is produced in activated human lymphocytes and in lymphocytic leukaemic cells. The production of BFP during blastic transformation will be a useful new in vitro model for studying the biological role of BFP, and BFP labelling may offer some new possibilities for study of lymphocytes.     

HPLC-studies on nonmercapt-mercapt conversion of human serum albumin

Human mercaptalbumin (HMA) and nonmercaptalbumin (HNA) could be separated by high-performance liquid chromatography (HPLC) at neutral pH. Using HPLC, the present authors found the nonmercapt-mercapt conversion (HNA ← HMA) during hemodialysis and the mercapt-nonmercapt conversion (HMA ← HNA) after hemodialysis in chronic renal failure, indicating HMA as the covalent carrier protein for sulfur-containing amino acids.     

Actions of peroxovanadate or tungstate on glucose transport by isolated rat adipocytes

The effects of peroxovanadate or tungstate on 3-O-methylglucose uptake were characterized using isolated rat adipocytes to elucidate the mechanism(s) of their actions. The stimulatory effect of peroxovanadate was observed from 1 μmol/L and reached the maximum at about 100 μmol/L. The concentration showing the half-maximal effect was approximately 16 μmol/L. The maximal response of peroxovanadate was 1.19 times higher than that of insulin significantly (P < 0.01). On the other hand, the stimulatory effect of tungstate was seen only at the higher concentrations of 10–30 mmol/L Judging from the experiments using different tungsten compounds, tungstic acid (WO₄^2-) appeared responsible for the effect. The effects of 20 mmol/L tungstate and 20 nmol/L insulin were not additive. The stimulatory effects of 1 mmol/L peroxovanadate, 20 mmol/L tungstate or 20 nmol/L insulin were not seen in the adipocytes deprived of ATP by exposure to 2 mmol/L KCN. The adipocytes which had been stimulated with insulin and further exposed to 2 mmol/L KCN were used to test whether or not peroxovanadate works directly on the function of glucose transporters. In such cells on which GLUT4-rich transporters were rendered immobile, the effect of peroxovanadate was not observed. These results indicate that the effects of peroxovanadate or tungstate are ATP or energy dependent and may be exerted through the mechanism analogous to that of insulin action, and suggest that peroxovanadate does not directly activate the function of GLUT4.     

A case of Kabuki make-up syndrome with central diabetes insipidus and growth hormone neurosecretory dysfunction

A case of a 6 year old boy with Kabuki make-up syndrome with central diabetes insipidus and growth hormone neurosecretory dysfunction is reported. Magnetic resonance imaging revealed abnormal findings of the pituitary gland and stalk. Good catch-up growth was obtained by treatment with growth hormone. These findings suggest that hypothalamic-pituitary dysfunction might be involved in Kabuki make-up syndrome.     

T cell subsets In peripheral blood and cerebrospinal fluid from children with aseptic meningitis

T cell subsets in peripheral blood (PB) and cerebrospinal fluid (CSF) obtained from patients with aseptic meningitis were studied using quantitative two-color fluorescence analysis with a flow cytometer. The percentage of HLA-DR⁺/CD3⁺ lymphocytes (activated T cells) in CSF was significantly increased in the recovery phase when compared to the acute phase, while no significant change in the activated T cells in PB was observed. More interestingly, CD4⁺ T lymphocytes in CSF were increased in the acute phase and subsequently decreased in the recovery phase. Instead, CD8⁺ T lymphocytes gradually accumulated into the CSF in the recovery phase, resulting in a successive decrease in the CD4/CD8 ratio. On the other hand, the CD4/CD8 ratio in PB remained normal during the course of aseptic meningitis. The present results suggest that T lymphocytes (CD4⁺ subset in the acute phase and CD8⁺ in the recovery phase) could be infiltrated and further activated at the site of inflammation, possibly in the subarachnoid space in the patients with aseptic meningitis.     

A Quarter Century of Thalidomide Embryopathy*

Abstract Some 137 patients with thalidomide embryopathy have been registered. Of them, 65 were male and 72 female. The age of patients who had a medical examination from 1976 to 1983, ranged from 7 to 22 years. The mean age was 17.0 ± 2.3 (mean ± SD) years. The number of hearing impairments were 35 (25.6%), limb defects were 55 (40.1%) and combined defects were 47 (34.3%). In order to determine the mutual relationships of 34 abnormal symptoms, the correlation coefficient was calculated, and cluster analysis was carried out by utilizing the result. There was a strong inverse correlation between deformities and hearing impairments. The 34 symptoms were divided into three groups. In the first group 11 symptoms were included, but there was little mutual relationship. Fifteen symptoms belonged to the second group, which evidenced strong mutual relationships. The 8 symptoms belonging to the third group were central to all of the symptoms.     

Morphological and biochemical re-evaluation of the process of cavitation in the rat knee joint: cellular and cell strata alterations in the interzone

To assess the contribution of apoptosis to the mechanism of synovial joint cavitation, and to clarify morphological cellular changes during cavitation, we investigated the development of the rat knee joint by light and electron microscopy, TUNEL methods, and electrophoresis of DNA fragments. Although cavitation occurred within the interzone, which consists of 2 outer and a middle layer termed the intermediate zone, no morphological or biochemical signs of cell death, in particular apoptosis, were seen in the interzone at any embryonic stage. Microscopic and ultrastructural alterations affecting cell differentiation were clearly observed in the interzone, i.e. mesenchymal cells gradually showed elongation, cytoplasmic vacuolation and pyknosis in the intermediate zone where the elongated cells were arranged in parallel in some strata. Some of these cells were further flattened into spindle cells and the number of strata decreased to 2. The rest of the cells were incorporated secondarily into the outer layers, becoming chondroblasts. Collagen fibrils were arranged in a network structure in the outer layers, which obviously differed from the directional pattern parallel to the long axis of elongated cells in the intermediate zone. In addition, the density of collagen fibrils was higher in the outer layers than in the intermediate zone. During cavitation, the initial separation was detected between the elongated cells in the intermediate zone in paraffin sections at E16.5 and the spindle cells in epoxy sections at E18.5. The spindle cells lining the cavity, namely, the surfaces of the epiphysis and meniscus, finally became chondrocytes. The diminution of proteoglycans and collagen fibrils and the synthesis of hyaluronan in the extracellular matrix are now generally believed to be parts of the mechanism for cavitation based on the concept of ‘loss of cohesion’. The microscopic and ultrastructural alterations in the interzone seemed to reflect differences in the arrangement and density of collagen fibrils and the developmental condition of the extracellular matrix between layers. Also it did not seem likely that these alterations inhibit the synthesis of hyaluronan at the presumptive joint line because this synthesis takes place at the plasma membrane. Separation between spindle cells should therefore represent the mechanism for developmentally programmed cavitation. Reorganization of the extracellular matrix is probably necessary for the cellular metamorphoses in the interzone involved in the process of cavitation.     

Albumin gene encoding free fatty acid and β-amyloid transporter is genetically associated with Alzheimer disease

Abstract  Alzheimer disease (AD), the major cause of dementia in the elderly, is characterized by β-amyloid deposition in senile plaques and hyperphosphorylated tau in neurofibrillary tangles. Since albumin, binding and transporting free fatty acids is also the major transporter of β-amyloid, we examined the association between the albumin ( ALB ) gene and the occurrence of late-onset AD (LOAD). We found that the allele distribution of the intron 4 microsatellite of the ALB gene showed a significant difference ( P  < 0.05) between LOAD ( n  = 285) and control group ( n  = 656). An allele with 11 CA repeat, termed (CA)₁₁ allele, was significantly predominant in the control group ( P  < 0.005), and the odds ratio carrying the (CA)₁₁ allele was 0.43 ( P  < 0.01, 95% CI = 0.24–0.79). Logistic regression indicated that this effect was independent of age and the ɛ4 dose of the apolipoprotein E gene ( P  < 0.01), while the ALB gene was supposed to be related to aging. Our results indicate that the ALB gene is genetically related with the occurrence of LOAD, supporting the link between fatty acid and β-amyloid transport in the development of LOAD.     

Minute Rectal Cancer Associated with Nodular Involvement —A Case Study—

Abstract: This study presents the case of a patient with minute type Ha rectal cancer with a diameter at its largest of only 5 mm, with infiltration as far as the submucosal layer (sm) and positive parietal lymph node metastasis. The patient was a 54 year-old male who visited Yasuda Medical Hospital because of diarrhea which appeared in early May 1988. During sigmoidscopy, a small protruding lesion was seen in the rectum (Rs) about 12 cm from the margin of the anus, and the patient was referred to the authors' surgical service for an endoscopic polypectomy because of a biopsy diagnosis of adenocarcinoma. The polyp had a smooth, shiny surface, and had a well demarcated hemispherical shape. A histopathological examination of the polypectomized specimen, showed that it was an invasive carcinoma extending into the submucosal layer without any adenoma component. Since the cut end of the specimen strongly suggested positive cancer cells and lymphatic permeation was also confirmed from the polypectomized specimen, a low anterior resection was performed on August 4, 1988. The postoperative histological examination revealed a small amount of residual cancer cells in the submucosal layer which appeared to be at the cut end of the resected polyp. One metastatic focal point was seen in the pararectal lymphnode, and this patient's case provided valuable suggestions for deciding upon therapeutic policies for early cancer of the large intestine.