To evaluate the relationship among the induction of nitric oxide synthase (NOS), advanced glycation end products (AGEs) and NF-κB for vascular damage in hyperglycemia, we injected Mongolian gerbils intravenously with 150 mg/kg streptozotocin (STZ) and observed over the next one year the resulting aortic changes by immunohistochemical and electron microscopical techniques. After STZ treatment, hyperglycemia was confirmed and body weight transiently decreased. Morphological observation revealed no remarkable changs in vascular endothelial cells or vascular smooth muscle cells in the aorta at one week after STZ administration. After 4 weeks increased collagen fibrils were observed in the pericellular spaces of media. At one year after STZ administration, increased collagen fibrils and thickened elastic fibers were found around the vascular smooth muscle cells with vacuolization and increased cytoplasmic organellae compared with non-treated animals of the same age. Immunohistochemically endothelial constitutive NOS (ecNOS) was localized in the endothelium of the aorta of Mongolian gerbils. At one year after STZ administration, the reaction products of iNOS, AGEs and NF-κB in vascular endothelial cells and smooth muscle cells were much more greatly increased than at one week and 4 weeks. After STZ administration, the localization of NOS, AGEs and NF-κB was observed in the aorta, which suggests these factors play important roles in the pathogenesis of vasculopathy in diabetes mellitus. (J Nippon Med Sch 1999; 66: 166-175)

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An experimental study was performed to investigate the influence of hypothyroidism on wound healing. A state of severe hypothyroidism was induced initially by performing a total thyroidectomy on rat models; subsequently wounds were made by making long midline abdominal incisions and then suturing them. The parameters used to evaluate the process of wound healing of these incisions were the assay of type - I collagen, type-III collagen (procollagen peptide PIPC and P III P, each being the precursor of collagen), type-IV collagen, and hydroxyproline. The assays were repeated at specific times and compared to assays of similar parameters taken from a control group. In the state of hypothyroidism, a decrease was observed in type-IV collagen and hydroxyproline during the proliferative phase of wound healing. This indicated that the state of hypothyroidism constitutes an important factor in delaying wound healing. (J Nippon Med Sch 1999; 66: 176-180)

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In order to elucidate the relationship between tumor growth and various kinds of gene expression and the occurrence of apoptosis in the front portion of neoplastic invasion, 57 advanced colorectal cancers were studied by immunohistochemical staining of p53, c-erb B-2, the TUNEL method and electron microscopy. Light microscopically, the columnar epithelial cells of adenocarcinoma frequently showed a decrease in high and a fall off into the lumen in tumor invasive forefront. Immunohistochemically the positive rate of p 53 and c-erb B-2 in tumors with high vascular invasion were higher (p<0.05) than in those with low vascular invasion. There was a close correlation between the vascular or lymphatic invasion and positive immunoreactivity of p 53 and c-erb B-2. The apoptosis index was demonstrated to be related to vessel invasion, over expression of p53 and inflammatory cell infiltration around the front portion of the tumor invasion. These results suggested that p53, c-erb B-2 and the apoptosis index should be evaluated in conjunction with the prognostic factors in colorectal cancer. The infiltrative inflammatory cells may induce apoptosis of the tumor cells. (J Nippon Med Sch 1999; 66: 181-187)

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We present a case of autosomal recessive polycystic kidney disease diagnosed at 28 weeks' gestation by ultrasonographic examination and magnetic resonance imaging (MRI). The fetal kidneys were symmetrically enlarged and highly echogenic by ultrasonographic examination and showed high-signal intensity on T₂-weighted images by MRI. Cystic leasions were recognized by neither examination. In addition, the pulsatility index of the fetal renal artery was normal. These findings suggest a high water content in the renal parenchyma with tiny cysts and normal blood flow in autosomal recessive polycystic kidney disease. (J Nippon Med Sch 1999; 66: 188-190)

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