The study was to develop a method of discrimination to predict the ambulatory acquisition of mentally retarded children at the ages of 7, 10 and 13, by combining the Developmental Quotient (DQ) and sideways equilibrium reaction of postural reflexes (SER) . Ninety-three subjects, 52 males and 41 females, participated in this study. All subjects were: 1) 10 years of age or older as of March 31, 1991, 2) 18 months of age or above and unable to walk at the first admission interview, 3) without physical impairments. By combining two DQ groups classified at a certain value line and two SER groups, the sample was categorized into four groups. Based on the cross tables of this categorization and the ambulatory capacity, the AIC was computed and the optimum value line that provided the minimum AIC was calculated. Among the SER negative with a DQ of 21 or below, the percentage of ambulatory acquisition was 0%, 1.8%, and 4.3% at ages 7, 10 and 13, respectively. The ambulatory acquisition of the two combined categories, one with a DQ of 21 or below and positive SER and another with a DQ of 22 or above and negative SER, was 42.9%, 81.0%, and 100% at ages 7, 10 and 13, respectively. In the category with a DQ of 22 or above and positive SER, 82.4% acquired ambulatory capacity at age 7 and 100% were walking at ages 10 and 13. This study demonstrated that the DQ and SER were applicable in discriminating the probability of ambulatory acquisition at ages 7, 10 and 13.

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Peritoneal carcinomatosis is regarded as an uniformly lethal disease process. When it is present, significantly worsen the prognosis and quality of life (QOL) and the treatment is difficult. This study was undertaken to evaluate the effect of intraperitoneal administration of CDDP+dopamine+furosemide (CDF) in 42 patients with ascites due to peritoneal dissemination in inoperable advanced or recurrent gastric cancer. Patients with advanced cancer typically have the potential for asymptomatic hypotension and poor complementary function of the circulatory system and kidney. In addition to large loss of body fluid due to severe vomiting caused by CDDP, the use of diuretics for preventing renal damage may cause blood pressure to incline. For this reason and the mutually affected property of f urosemide and exogenous dopamine by intravenous injection, we administered furosemide and dopamine simultaneously ip. For the results, 22 patients (52.4%) showed a complete response in which ascites disappeared completely and 14 patients (33.3%) showed a partial response in which ascites disappeared partially, 6 patients (14.3%) had no response. The complete response rate, 66.7% (16/24), in inoperable patients was better than that, 33.3% (6/18), in recurrent patients (p<0.05) . Following this therapy, 10 inoperable patients undertook laparotomy after ascites disappeared, 8 patients had relatively noncurable gastrectomy and, 2 of 3 patients survived more than 500 days; renal toxicity and serious myelosuppression was not recognized in any patient. Thus, we consider that CDF therapy is effective for the treatment of gastric cancer with ascites, improvement of QOL and prolongation of the life span.

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Expansion and maintenance of hematopoietic progenitor cells (BFU-E, CFU-GM) ex vivo were examined using bone marrow mononuclear cells obtained from children with malignant solid tumors and acute leukemias during the recovery phase of bone marrow after chemotherapy. Bone marrow mononuclear cells were cultured in serum-free liquid culture system containing stem cell factor (SCF), IL-3, and IL-6. The number of hematopoietic progenitor cells before the starting of liquid culture (day 0) was compared with that of colonies derived from progenitor cells after liquid cultures which contained various combinations of cytokine (day 7) . Viability of mononuclear cells on day 7 showed a 55% decrease when cultured without cytokine and the maximum of a 134% increase when cultured with cytokine. The number of CFU-GM increased 4.2-10.9 fold (range), 7.8±4.9 (mean±SD) and BFU-E increased 4.2-10.9 fold (range), 7.8±4.9 (mean±SD) in the presence of IL-3 +IL-6+SCF. The results indicate that it is possible to expand and maintain ex vivo the hematopoietic progenitor cells of bone marrow taken during the recovery phase after conventional chemotherapy from pediatric patients with malignant solid tumors and acute leukemias.

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A type of abnormal B cells was obtained from young NZB/n mice, a well-known experimental model for lupus type autoimmune disease, by immunization with sheep red blood cells (SRBC) . NZB mice of both sexes were immunized i.p with 4×10⁹of SRBC. Two weeks later, B cells were obtained by treatment of spleen cells with anti-Thy-1, 2 plus complement to remove T cells. Unlike B cells prepared from normal BALB/c mice by the same procedure, the B cells from NZB mice responded to SRBC with or without small numbers of T cells duringin vitroculture. The abnormal B cells were positive for Ly-1 (Lyt-1, CD5) as confirmed by depletion of the cells with anti-Ly-1 plus complement. Plaque-forming cell (PFC) response of the abnormal B cells was enhanced by β-estradiol but not by testosterone. The above results suggest that the Ly-1⁺B cells from NZB mice might be long-lived or memory B cells.

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A method of enzyme-linked immunosorbent assay (ELISA) has been established for fractions of cholic acid (CA), chenodeoxycholic acid (CDCA), deoxycholic acid (DCA), and ursodeoxycholic acid (UDCA) . With this method we have obtained serum bile acid fractions of 307 healthy individuals and 37 patients with liver disease; 6 cases of acute hepatitis (AH), 13 cases of chronic hepatitis (CH), 13 cases of liver cirrhosis (LC), and 5 cases of hepatocellular carcinoma (HCC) . Using these fractions, we then calculated the ratios of CA/CDCA, CDCA/DCA, CA/DCA, CA+CDCA/DCA, and CA+CDCA/ DCA+UDCA. Further, we have set up reference values from healthy individuals, and then studied the clinical significance of each componential ratio for each liver disease group. The fraction of each bile acid, especially CDCA, DCA, and UDCA, showed an abnormally high value in all liver diseases. With respect to componential ratios, the CA/CDCA ratio was recognized to be within reference values of healthy individuals in almost all liver diseases. However, among LC patients, the ratio was significantly higher than that of healthy individuals. With respect to the CDCA/DCA ratio, the number of abnormal cases was the smallest among AH patients, followed by CH patients, LC patients, and HCC patients in the ascending order. This tendency appears to suggest qualitative differences in these liver diseases. A similar tendency was found in the ratio of CA+ CDCA/DCA, although it was not as significant as the CDCA/DCA ratio. The above results indicate that the method which enables us to obtain serum bile acid fractions and their componential ratios of CDCA/DCA and CA+CDCA/ DCA provides useful information on the pathophysiological analysis and prognostic observations of liver disease.

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To investigate the progression of neuronal damage after cerebral ischemia, the protein-alterations in rat cerebral cortex was qualitatively and quantitatively analyzed using a transient focal cerebral ischemia model. The cerebral cortex was fractionated into nuclear, mitochondrial, microsomal, and cytosolic fractions following transient ischemia. Proteins contained in each fraction were analyzed using sodium dodecyl sulfate polyacrylamide slab gel electrophoresis (SDS-PAGE) . Two proteins (molecular mass: 67 kDa and 80 kDa) were markedly increased in the cytosolic fraction 16 hr and 8 days following transient ischemia. Levels returned to baseline 2 weeks after lesioning. No significant differences were observed in the other fractions. The 67 kDa protein was purified by ion-exchange chromatography followed by gel permeation chromatography and partial amino acid sequences were determined. As a result, a 67 kDa protein that was increased following transient ischemia was identified as serum albumin. Moreover, in the cytosolic fraction of cerebral cortex following transient ischemia and subjection to immunoblot analysis using polyclonal antibody against rat whole serum. The results of this analysis revealed nine proteins, including the 67 and 80 kDa proteins, derived from serum. Six of these proteins showed a similar pattern of transient increase 16 hr and 8 days following transient ischemia. The 80 kDa protein was identified as transferrin in terms of its molecular mass and cross-reactivity against an anti-human transf errin polyclonal antibody.

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The time course of changes in activity of nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d), a marker for nitric oxide (NO) synthase, was studied histochemically in the rat cerebral cortex after focal Ischemia induced by middle cerebral artery occlusion. In the cerebral cortex of sham-operated animals, NADPH-d activity was present mostly in scattered, isolated cells that resembled medium-to-large neurons. Granular cells of the cerebral cortex showed abundant NADPH-d activity, but few pyramidal cells of layers III or V were stained. Most NADPH-d-positive neurons were located in the white matter immediately below the cerebral cortex; only a small number of NADPH-d-positive cells were detected in the superficial layers. Most of the heavily stained neurons were located in the proximity of blood vessels; in some instances, cell bodies were apposed to the vascular profiles and their processes encircled the vessel walls. NADPH-d activity was not detected in vascular endothelial cells in the cerebral cortex of sham-operated rats. After 5 min of Ischemia, the number of NADPH-d-positive neurons was increased markedly in the parietal cortex. After 60 min of Ischemia, the number of NADPH-d-positive neurons in the parietal cortex had decreased to below that detected in sham-operated animals; however, the number of stained neurons in the piriform and cingulate cortex was increased. NADPH-d-positive endothelial cells were detected in small vessels and capillaries in all layers of the parietal cortex after 5 min of Ischemia. NADPH-d activity in endothelial cells had decreased to almost basal levels after 60 min of ischemia. Pretreatment animals with N-nitro-L-arginine methyl ester (a NO synthase inhibitor) or MK-801 (a N-methyl-D-asparate-sensitive glutamate receptor antagonist) markedly inhibited the ische-mia-induced increase in NADPH-d activity in both neurons and endothelial cells. These results suggest that NO synthesized by neurons or endothelial cells contributes to the regulation of cerebral blood flow. Moreover, glutamate may be an important determinant of NO synthase expression after focal cerebral ischemia.

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We studied the mechanism of the preconditioning (PC) on ischemic cellular injury based on the specific biochemical characteristics of the sarcoplasmic reticulum (SR) and mitochondria (Mt) . Forty dogs were divided into two groups: 1) PC group (four times of LAD occlusion for 5 min with each 10 min interval), 2) I group (no preconditioning) . Then 60 min ischemia and reperfusion with continuous on-line recordings of hemodynamics and % segment shortening (SS) were performed. Myocardial ischemic injury was quantitated by the biochemical analyses of SR and Mt. After 60 min reflow, % SS of the ischemic portion was reduced to -32.5 ± 18.6% of the previous control level in the I group. In the PC group this was kept at -16.3±11.9% of control. Ca++-ATPase activity of the SR showed a significantly higher value in the PC group (11.1 ± 1.1 μmoles Pi/mg protein/hr) than in the I group (9.5±1.9) . Also on SDS gel electrophoresis of SR, major ATPase protein was well maintained in the PC group. Both respiratory and dinitrophenol-ATPase activities of mitochondria were also higher in the PC group than in the I group. Ischemic preconditioning inhibited degradations of membranous microorgans and maintained contractile function in the ischemic myocardium.

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We studied the contribution of intracellular microorgan dysfunction in the post ischemic stunned myocardium. In 47 mongrel dogs, LAD occlusion for 15 min (I-15m) and subsequent reperfusion for 60 min (R-60m) were performed with simultaneous records of hemodynamics, coronary blood flow (CBF), regional myocardial blood flow (MBF) and segment shortening (SS) . Sarcoplasmic reticulum (SR) and mitochondria (Mt) were analyzed using biochemical procedures. Hemodynamics indicated no remarkable changes throughout the experiment. CBF showed reactive hyperemia to 370% of control transiently after reprefusion, then returned to control level at R-1 Sm. SS diminished to -22% of control at I-1 5m, and it was still depressed at 58% at R-60m (stunning) . Ca-ATPase activity of SR was reduced to 57% of control at I-15m, and remained depressed at 78% at R-60m. State III respiration of Mt decreased to 75% of control, and dinitrophenol-stimulated ATPase activity of Mt was 72% of control at I-15m. These activities did not recover completely at R-60m (77% and 75%, respectively) . Both Ca-ATPase activity of SR and state III respiration of Mt were positively correlated to SS. SDS-gel electrophoresis of SR protein revealed no irreversible changes. These results suggested that contractile dysfunction after brief ischemia is related to the energy demand and supply, and the transient dysfunction of microorgans is one of the main causes of stunned myocardium.

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A novel predictive prognostic factor is still required to determine the regimen of postoperative chemotherapy in advanced gastric cancer patients. Recently, epidermal growth factor (EGF) has been reported to be a potential prognostic factor. In the present study, histochemical expression of EGF was investigated in primary gastric cancer lesions and metastatic lesions of lymph node in 90 advanced gastric cancer patients. The expression of EGF was investigated by histochemical enzyme assay using a human EGF monoclonal antibody. The five-year survival rate in the EGF-positive group was 36.3%, relative to 77.4% in the EGF-negative group (p<0.05) . However, in limiting it to the patients with curative surgery as well as more than or equal to conclusive stage II, a significant difference was not shown in the survival analysis. Limiting to 31 patients with curative surgery as well as lymph node metastasis, the 5-year survival rate of the EGF-positive group with metastatic lesions of the lymph node was 40.0%, relative to 79.5% of the EGF-negative group (p<0.05) . A high grade of blood vessel invasion (v₃) was significantly detected in the EGF-positive group compared to the EGF-negative group (50.0% and 22.6%, respectively; p<0.05) . The patients with recurrence of liver metastasis in the EGF-positive group investigated in the primary cancer lesions were significantly greater than in the EGF-negative group (p<0.05) . These findings suggested that the assessment of EGF in lymph node metastatic lesions is a potential predictive prognostic factor in advanced gastric cancer patients with curative surgery, and that the EGF expression in the primary cancer lesions may be predictive for the recurrence of liver metastasis.

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In 20 controls and 47 patients with chronic tension-type headache (TTH), we investigated the exteroceptive suppression period (ES), selfrating depression scale, and a questionnaire regarding symptoms. Early (ES1) and late (ES2) exteroceptive suppressions were observed. The mean duration of ES2 was significantly reduced in chronic TTH when compared with controls. Although no statistical significance of ES2 duration was found in the various clinical parameters, patients with severe headache, and a high score of the self-rating depression scale showed a shortening tendency of E52 duration. The depressive trend of patients with TTH might be responsible for modifying the descending input to the brainstem and reducing ES. To date, there have been no reports concerning ES2 and the severity of headache and score of self-rating depression scale.

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Nerve projections from the anteroventral periventricular nucleus (AVPV) to the vasopressin (VP) containing magnocellular and parvocellular neurosecretory neurons in the paraventricular nucleus (PVN) of the rat and its synaptic inputs to VP containing neurons were examined. A double labeling technique was used by combining anterograde tracing after iontophoretic injection of wheat germ agglutinin-coupled horseradish peroxidase (WGA-HRP) with VP immunocytochemistry. WGA-HRP-labeled and unlabeled axon terminals were found to make synaptic contacts with VP-like immunoreactive cell bodies and processes in the PVN. This indicates a direct synaptic influence of AVPV on the secretory activity of the VP-containing neurons in the hypothalamic PVN of the rat.

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In treating congenital dislocation of the hip, the importance of early screening should be emphasized. We summarized the results of orthopaedic examination for neonates who were born from Oct. 1977 to Dec. 1994. During this time 11370 babies were born in the maternity ward of Showa University Fujigaoka Hospital. A total of 8886 babies (78.2%) were examined, including 4506 male babies and 4380 female babies. Regarding the click sign, in which the instability of the hip joint can be felt by allowing the femoral head to slip in and out of the joint cavity, Ortolan's click sign was positive in 6 cases (6 joints) and Barlow's click sign was positive in 8 cases (10 joints) . Of the cases tested by Barlow's click sign, 0.1 % were positive. In these cases one was affected with Larsen's syndrome. Three cases that tested negative using the click sign were found to be dislocated at the follow-up time during infancy. In the click sign-positive cases, plaster cast fixation was performed in two patients, the remaining five patients were treated by a Pavlik harness and one patient was treated by abducted diaper. From follow-up examinations at an average age of 5.4 years satisfactory results were obtained in seven cases; only one case treated by plaster cast fixation showed bilateral slight aseptic necrosis of the femoral head. Although click sign-positive cases have been decreased due to primary prophylaxis from birth, the neonatal examination is essential for detecting the dislocation of the hip in early life.

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Articular cartilage taken from secondary osteoarthritic hip joints presented for surgical reconstruction was analyzed. Proteoglycans (PG) were isolated from the articular cartilage. Isolation of PG was done as described by Hascall and Sajdera (J Biol Chem, 244: 2384, 1969) . The aggregative PG were analyzed for chondroitin 4-sulfate (Ch-4S) and chondroitin 6-sulfate (Ch-6S) by physicochemical methods. Content of Ch-4S and Ch-6S in PG was analyzed by high performance liquid chromatography (HPLC) and the viscosity of PG monomer was analyzed by a Cannon-Manning semimicro viscometer. The relative viscosity (η_rel), specific viscosity (η_sp), and reduced viscosity (η_red) were calculated. Statistical analyse were performed. Pearson's correlation coefficient between parameters was calculated. The mathematical relationships between cartilage weight and reduced viscosity (η_red), between cartilage weight and Sum Ch.S, and between Sum Ch.S and Ch-6S/Ch-4S were calculated. There were significant correlations between these variables. The osteoarthritic femoral head PG molecules were smaller and the content of Sum Ch.S higher, for advanced osteoarthritis. The PG side chains were shorter and the number of chains per core-protein was higher, as the osteoarthritis was progressed. Changes in articular cartilage composition, proteoglycan molecular structure, and the ultrastructural arrangement of these macromolecules associated with osteoarthritis causes a deterioration in cartilage properties and hence a loss of functional capacity of the joint.

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