The non-obese diabetic (NOD) mouse has been developed as an animal model of insulin-dependent diabetes mellitus (IDDM) . The islet cell autoantibody and autoantibodies to glutamic acid decarboxylase, heat shock protein, and insulin can be detected and are thought to participate in the auto-immune reaction that leads to IDDM. We found that pancreatic α-amylase decreased after the onset of diabetes and an autoantibody to amylase in the sera of NOD mice could be detected by enzyme-linked immunosorbent assay. An increase in the autoantibody was usually followed by the onset of diabetes, and the concentration of the autoantibody in diabetic mice was significantly higher than in prediabetic mice. Although an autoantibody to amylase as a component of macroamylase has been known for several decades, no consistent pattern of disease association has been reported. Our findings suggest that the amylase autoantibody may play a role in the autoimmune reaction leading to IDDM in the NOD mouse and might be used as a predictive marker of diabetes.

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Five clones of mouse monoclonal antibody (mAb) against human C-reactive protein (CRP) were established by the hybridoma technique. Each of these mAbs formed a precipitin line with CRP, showing a spur to the line produced by rabbit polyclonal antiserum against CRP. Five mAbs were divided into two groups: the precipitin lines formed by mAbs in one group fused completely with each other, and those formed by mAbs in the other group formed spurs. Mixtures of the two groups of mAbs produced precipitin lines identical to those produced by the polyclonal antibodies. On the other hand, ethylene glycol-bis (2-aminoethyl ether) tetraacetic acid and phosphorylcholine, which are known to bind with CRP, inhibited the formation of complexes by CRP with the mAbs of one group, but not of the other group. However, N-acethyl-galactosamine, which is also known to bind with CRP, showed no blocking effect on the mAbs of either group. The findings suggest that there are at least two different epitopes on a CRP molecule, each of which is recognized by mAbs of either group. The mAbs might be useful for the clinical assay of serum CRP and for the study of the structure of epitopes of CRP.

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We have previously reported that transient ischemia induced by the bilateral occlusion of the carotid arteries elicits an increase in dopamine (DA) release in the gerbil striatum. To investigate the role of energy failure in ischemia-induced DA release, we compared the effects of sodium cyanide (NaCN, 2 mM) applied through a microdialysis membrane on extracellular levels of DA in the striatum of gerbils with the effects of transient ischemia. Extracellular levels of DA increased markedly after both ischemia (141-fold) and NaCN (115-fold), and rapidly returned to baseline. Extracellular levels of 3-methoxytyramine, a metabolite of DA, was similarly increased by both ischemia (120-fold) and NaCN (85-fold) . Changes in other metabolites were similar after both treatments. These findings indicate that energy failure plays a major role in the release of large amounts of DA during transient ischemia in the gerbil striatum. Furthermore, because the changes induced by high-K⁺ stimulation were still present 3 hours later in the ischemia group but not in the NaCN group, it is suggested that energy failure induced by short-term ischemia is transient and reversible.

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There have been few morphometric studies of age-related changes in the human spinal cord. Therefore, the purpose of the present study was to determine whether changes occur in the dimensions of the human spinal cord during the aging process. Spinal cords were removed from 22 male cadavers aged 41 to 97 years (average, 70.3 years) at the time of death. Spinal cord segments were embedded in celloidin after secondary fixation and dehydration. Sections were stained with the Luxol fast blue-periodic acid-Schiff-hematoxylin and Klüver-Barrera methods. Morphometric analysis was performed with a microscope, an electronic optical planimeter and a computer. The cross-sectional area and diameters of the spinal cord at the segment C6 were measured. The transverse area of the spinal cord was not correlated with age, but the ratio of the area of the posterior funiculus to the area of the entire transverse section and the flatness ratio decreased with increasing age. Amyloid bodies were observed in the posterior funiculus, near the entrance of the dorsal roots or both, and tended to increase with age. Our results suggest that degenerative changes occur in the spinal cord with aging.

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We previously established a system for induction of mucosal-type mast cells from mouse spleen cells by long-term culture without exogenous interleukin 3 (IL-3) . Fetal calf serum (FCS) was important and could be divided into mast cell-inducible and non-mast cell-inducible sera. Lipopolysaccharide (LPS) -contaminating FCS was responsible for mast cell induction. Further experiments revealed that IL-3 alone could not induce mast cells, and that mast cell induction by LPS was mediated through endogenous IL-3 and prostaglandin E (PGE) . However, it is not clear whether LPS from various gram-negative bacteria, polysaccharides, and muramyl dipeptide (MDP) are able to induce mast cells. In the present study, LPS from Escherichia coli, Vibrio cholerae, Salmonella Typhinmurium, and Rhodobacter sphaeroides and synthetic lipid A induced mast cells, although higher concentrations of LPS from Rhodobacter sphaeroides were necessary. Polysaccharides (schizophyllan and mannoglucan) from fungi and actinomyces induced mast cells in a dose-dependent and a molecular weight-dependent manner. However, MDP of Mycobacterium tuberculosis failed to induce mast cells. Mast cell induction by the polysaccharides was not due to LPS contamination, since polymyxin B did not suppress the action of the poly-saccharides. Indomethacin, a selective inhibitor for PGE synthesis, suppressed mast cell induction by the polysaccharides. This finding indicates that mast cell induction by the polysaccharides is also mediated through endogenous PGE.

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In patients with unilateral or bilateral cleft lip, the prolabial mucosa of the upper lip often remains adherent to the premaxilla. This adherence creates both functional and aesthetic problems. Therefore, we developed a technique in which the adherent mucosa is cut and fixed to the nostril floor. With this technique, 92 of 120 patients (76.6%) showed a deep sulcus more than 10 mm deep and 114 of 120 patients (95.0%) showed a sulcus. more than 5 mm deep with minimal postoperative discomfort.

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Myelinated nerve fibers of the human oculomotor nerve were analyzed with a new staining method that permits simultaneous observation of the axon and surrounding myelin sheath. The folowing equipment was employed for the measurements: an image-analyzing digitizer, a microscope equipped with a drawing tube (or camera lucida), and a computer for data storage and statistical analysis. The numbers, transverse areas, and circularity ratios of axons were measured in 20 human oculomotor nerves. The average number of axons in an oculomotor nerve was 18, 329, and the average area of aoxns was 6.43 μm². The number of axons decreased with age, although the average transverse area of axons did not change. The aging process might differ depending on the nerve.

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In-phase vibration, applied to the contracting chest wall respiratory muscles, has been shown to reduce dyspnea in patients with chronic obstructive pulmonary disease (COPD) . In the present study, respiratory muscle stretch gymnastics (RMSG) were developed to stretch the chest wall respiratory muscles during the contraction phase. Thirty-four patients with COPD consecutively performed four RMSG patterns, four times each. The dyspnea rating on a 150-mm visual analog scale, was 11.6±3.4 mm before RMSG and was signifi-cantly decreased to 6.2±2.2 mm (p<0.01) 5 minutes after RMSG. Arterial oxygen saturation, systolic and diastolic blood pressures, and pulse rate remained unchanged. Forced vital capacity and peak expiratory flow rate were significantly increased from 1807±141 ml to 1923±145 ml (p<0.01) and from 2.03±0.27 L/sec to 2.26±0.27 L/sec (p<0.05), respectively. Other spirometric values remained unchanged. Our results suggest that RMSG is a safe and effective physical conditioning method to improve pulmonary function and to decrease dyspnea at rest in patients with COPD.

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A new human somatostatinoma cell line, Soma-1, was established from a surgical specimen of a 64-year-old man. Soma-1 cells showed polygonal morphology with neurites and proliferated as an adherent monolayer with an approximate population doubling time of 48 hours. Electron microscopic observation revealed that Soma-1 cells have large nuclei with several nucleoli, scant cytoplasm with dense bodies (possibly secretion granules), and scattered Golgi apparatus and mitochondria. Cell surface microvilli were not apparent. Xenotransplantation of Soma-1 into BALB/c nude mice did not produce visible tumors. Significant somatostatin and neuron-specific enolase activities were observed in both extracellular (by radioimmunoassay) and intracellular fractions (by immunohistochemistry), suggesting neuronal differentiation. Soma-1 is more resistant to various apoptosis-inducing agents than are human myelogenous leukemic cell lines. This cell line provides a useful in vitro model for the pathophysiologic analysis of somatostatinoma.

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We have previously reported a mitogenic effect of a tea catechin, epigallocatechin gallate, on B cells. In the present study, we found that tea catechin enhances plaque-forming cell responses to sheep red blood cells in mice in vitro and in vivo. Tea catechin showed a mitogenic effect on spleen cells of nude mice. Removal of macrophages from spleen cells did not diminish the mitogenic activity of tea catechin. Therefore, tea catechin may directly promote the proliferation and differentiation of B cells. Preliminary experiments show that, as with lipopolysaccharide, signal transduction through tyrosine kinase may play a role in the enhancement by tea catechin, since a tyrosine kinase inhibitor, genistein, inhibited the mitogenic effect of epigallocatechin gallate while inhibi-tors of protein kinase A and C failed to do so. The above results suggest that tea catechin enhances immune functions both in vitro and in vivo.

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2', 3'-Dideoxy-l-N-isoseryl kanamycin A (ISDK) is one of the derivatives synthesized from 2', 3'-dideoxy kanamycin A. In the present study, the ototoxic effect of ISDK on the inner ear of guinea pigs was investigated by comparing it with the effect of amikacin. The antibiotics were administered intramuscularly to male guinea pigs for 3 weeks at dosages of 100 or 200 mg/kg/ day. The ototoxic effect of ISDK is weaker than that of amikacin, which is synthesized from kanamycin A by substitution of a 1N- (s) -4-amino-1-hydroxy-butyl moiety.

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Ten patients who had undergone surgery for malignant astrocytoma were studied to evaluate the effect of immunochemoradiation therapy on postoperative tumor volume. The patient's average age was 64.8 years, and the mean preoperative Karnof sky performance rating was 76%. Eight patients had glioblastoma and two patients had anaplastic astrocytoma. Tumor volumes before and after surgery were compared using computer tomographic and magnetic resonance imaging scans with contrast enhancement and a micro-computer-assisted image analysis system. In five patients, tumor volume decreased or was unchanged (effective group), and in another five patients tumor volume increased (ineffective group) . The proliferative activity of the tumor was examined by staining of argyrophilic nucleolar organizer regions (AgNORs) . The mean number of AgNORs was 2.67 in the effective group and 2.61 in the ineffective group. Differences between the two groups in preoperative tumor volume, residual tumor volume, survival time, mean number of AgNORs, and the percentage of nuclear area occupied by AgNORs (% A/N) were examined by the Mann-Whitney U test. There was no significant difference between the two groups in proliferative potential. Only postoperative residual tumor volume was significantly different between the two groups (p<0.05) . In the effective group the postoperative tumor volume was less than 10 cm³. Therefore, extensive surgery in which postoperative residual tumor volume is less than 10 cm³ may increase the efficacy of postoperative immunochemoradiation therapy and may be the most important component of the same multidisciplinary therapy.

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The morphometric anatomy of the superficial cerebral veins in relation to cerebral gyri was studied in 244 cadaveric cerebral hemispheres. Our morphometry revealed that the position of the central sulcus and that of the parieto-occipital sulcus near the superior sagittal sinus were at 55% and 83.6% respectively of the half-perimeter running from the frontal pole to the occipital pole (FO) . The drainage position of the central sulcal vein (of Rolando) into the superior sagittal sinus was about 65% of the FO half-perimeter on each side. The three main drainage veins among the superficial cerebral veins are classified into four types: (1) left predominant, (2) right predominant, (3) no laterality, and (4) absent. No laterality predominance was observed regarding the superficial middle cerebral vein (of Sylvius) . The inferior anastomotic vein (of Labbe), however, was predominant on the left hemisphere. The superior anastomotic vein (of Trolard) was observed with similar frequency in each type. In conclusion, the superficial cerebral veins can be classified into eight different types according to venous drainages.

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Calcitonin gene-related peptide (CGRP) is a recently discovered amino peptide that induces vasodilation, hypotension, and tachycardia. Tachycardia elicited by CGRP may be partly due to sympathetic stimulation in the alert state. However, the endocrrne effects of CGRP during halothane anesthesia still remain to be elucidated. Endocrine effects of two doses of CGRP (4 μg ⋅ kg^-1 and 40 μg ⋅ kg^-1) on plasma levels of catecholamines and aldosterone and plasma renin activity (PRA), were measured in halothane-anesthetized dogs. With 40 μg ⋅ kg^-1 of CGRP, norepinephrine and epinephrine concentrations significantly increased during the infusion period, but no significant changes in catecholamines occurred at 4μg ⋅ kg^-1 of CGRP throughout observation. PRA significantly increased at doses of 4 and 40μg ⋅ kg^-1 of CGRP during the infusion period. With 40 μg ⋅ kg^-1 of CGRP, aldosterone increased significantly throughout observation. In contrast, there were no significant changes in plasma aldosterone during and after the infusion with 4 μg ⋅ kg^-1 of CGRP. The two doses of CGRP used produced no consistent changes in aldosterone despite significant increases in PRA. The results of the present study suggest that CGRP may be an endocrine modulator. In addition, halothane anesthesia may partially suppress activation of the sympathetic nervous system and of the renin-angiotensin-aldosterone system caused by infusion of CGRP.

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A 39-year-old man, with a saccular aneurysm arising from the proximal end of a fenestration at the vertebrobasilar junction is presented. Considering the location, posterosuperior projection of the aneurysm, and the relationships between the aneurysm and its surrounding structures, we selected a subtemporal transpetrosal approach with resection of a part of the petrosal ridge anterosuperior to the internal auditory foramen. The aneurysm was completely clipped without difficulty. The patient had temporal abducens palsy and facial hypesthesia postoperatively, but he eventually recovered completely and returned to his previous job. Aneurysms at the fenestration of the basilar artery are rare. A total of 52 cases have been reported and most were operated on via the suboccipital approach. We emphasize that the subtemporal transpetrosal approach is a useful route to reach a basilar artery aneurysm at the midclivus and that the internal auditory foramen is a reliable landmark for safe and accurate removal of the petrosal ridge.

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