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Biomedical subjects

H Kikuchi

Publications and source records attributed to H Kikuchi.

At least 1,027 records · Page 57Linked to original sources

Bile acid malabsorption as a cause of hypocholesterolemia seen in patients with chronic pancreatitis.

A determination of caloric consumption based on a dietary survey table, fat and cholesterol intake, and analyses of fecal fatty acids and neutral sterols, and bile acid analysis (gas chromatographic method) were conducted on 33 subjects (including 17 patients with chronic pancreatitis and 16 normal controls). The factors related to hypocholesterolemia in chronic pancreatitis (CP) patients were investigated and the following conclusions were obtained: (1) The total caloric intake and fat consumption by the CP patients were significantly lower with the exception of cholesterol consumption. (2) Significant increases were noted in fecal fat, neutral sterols, and bile acid excretion by the CP patients. (3) A significant positive correlation was noted between the total cholesterol and body mass index (BMI), reaffirming that the cholesterol level can be used as an indicator of nutritional status. (4) A significant negative correlation was noted between the serum total cholesterol and fecal bile acid excretion. These findings indicate that CP patients suffer from neutral sterol malabsorption, in addition to dietary fat maldigestion and bile acid malabsorption. Furthermore, bile acid malabsorption is cited as a factor in the development of hypocholesterolemia in CP patients.

Adult↗

Effect of omeprazole on changes in gastric and upper small intestine pH levels in patients with chronic pancreatitis.

Gastric and upper small intestine pH levels were measured continuously over 24 hours in patients with chronic pancreatitis, and values obtained before and after the administration of omeprazole were compared. Additionally, omeprazole was administered for 2 weeks and the fecal excretion of fat was compared before and after drug therapy. Postprandial gastric pH levels, initially 2.9 to 3.2, increased by 1.6 to 2.1 after treatment. Postprandial upper small intestine pH levels, initially 5.1 to 5.5, increased by 0.7 to 1.0. The lowest pH value of the upper small intestine was 2.2 to 2.4 postprandially; this was increased by > 1.0 after omeprazole, and the amplitude of pH variation was reduced. The cumulative proportions of intraintestinal pH strata of < or = 3, < or = 4, or < or = 5, and higher, initially being 16.4% to 17.1%, 27.4% to 31.7%, and 52.6% to 57.8%, respectively, were remarkably improved after drug treatment. Gastric pH and upper small intestine pH levels showed a positive correlation; an increase in gastric pH levels by 2 corresponded to an increase in small intestine pH levels by 1. After omeprazole administration, mean fecal excretion of fat was decreased to 4.1 +/- 2.6 g/d (range, 1.1 to 9.8 g/d) from 6.5 +/- 3.9 g/d (range, 1.6 to 13.5 g/d). Decreases in excretion of fat averaged 3.4 g/d (range, 2.2 to 4.5 g/d) in patients with steatorrhea. It was concluded that steatorrhea due to chronic pancreatitis can be improved to some extent by improving upper small intestine pH levels following the elevation of gastric pH levels after administration of omeprazole.

Adult↗

Fecal excretions of hydroxy fatty acid and bile acid in diabetic diarrheal patients.

Thirteen normal subjects, 5 diarrheal controls (Group I) and 13 diabetics without peripheral neuropathy (Group II) were compared with 7 diabetic patients (Group III) with respect to fecal excretions of bile acids and hydroxy fatty acids for pathogenesis of diabetic diarrhea. The mean fecal excretions of bile acids per day were 304.9 mg for the normal controls, 297.8 mg for Group I, and 382.4 mg for Group II, while those of Group III were significantly higher (958.2 mg, p < 0.01) than the foregoing groups, and nearly three times as much as the controls. As to the fecal fatty acid excretion, there were no significant differences observed among these groups. The percentages of fecal hydroxy fatty acids were not significantly different in normal subjects (1.5%), Group I (2.0%), and Group II (1.2%). In contrast, the percentage of hydroxy fatty acid for Group III was greatly (p < 0.01) increased (13.2%). From the above results, the percentage of hydroxy fatty acid in diabetic diarrheal patients was high, suggesting that there is bacterial overgrowth. Meanwhile, the fecal bile acid level was increased about three times, indicative of poor absorption of bile acid from mild to moderate degree. Therefore, it is considered improbable that fecal hydroxy fatty acids and bile acids are the cause of diabetic diarrhea.

Adult↗

8-1A, a human monoclonal antibody that reacts with intact human chorionic gonadotropin.

The incidence of choriocarcinoma has decreased over time and therapeutic results have improved about 90% complete remission in patients without extensive metastasis. However, some choriocarcinomas metastasize to other organs and show resistance to chemotherapy, having a poor prognosis despite multidisciplinary treatment. Better methods of early diagnosis for recurrence or micrometastasis, and treatment against cases with intractable gestational trophoblastic neoplasia (GTN) are needed to improve the prognosis. Human chorionic gonadotropin (hCG) is a glycoprotein hormone composed of two dissimilar subunits and a tumor marker to make a diagnosis and monitor therapeutic effect in GTN. Even when hCG levels in the serum become too low to measure with the hCG beta-CTP system which is the most sensitive assay, there are estimated to be approximately 10,000 trophoblastic cells in the body. Residual trophoblast cells may cause symptoms such as bleeding or undergo malignant transformation to choriocarcinoma. Since most monoclonal antibodies developed so far are murine, administration creates human anti-mouse antibodies, resulting in clinical failure. More recent mouse/human chimeric antibodies or humanized antibodies still possess substantial immunogenicity that makes repeated administration difficult. In the present study, KM mice that can produce completely human monoclonal antibodies were used to prepare hCG-specific human monoclonal antibody. This yielded 8-1A, a human monoclonal antibody capable of reacting with intact hCG. In the future, new diagnostic techniques and treatments for chorionic diseases may be developed using this kind of human monoclonal antibody.

Animals↗

Effects of a functional agar surface on in vitro dentinogenesis induced in proteolytically isolated, agar-coated dental papillae in rat mandibular incisors.

In an attempt to study the effects of a three-dimensional agar surface on in vitro dentinogenesis both in the growing end and in incisally cross-cut pulp, the possible expression of odontoblast phenotype was investigated morphologically, autoradiographically and immunohistochemically. Explants were incubated for 8 days. In the growing end, during the last 4 days, mitotic cells differentiated into [3H]-thymidine-labelled, tubular matrix-forming cells. In cross-cut pulp, however, during the first 4 days, mitotic cells differentiated into [3H]-thymidine-labelled, tubular matrix-forming cells. Electron microscopy demonstrated that, in both regions, tubular matrix-forming cells had characteristics similar to those of primary odontoblasts. When agar was incubated alone, exogenous fibronectin was deposited on it rapidly. After 12 h, endogenous fibronectin appeared on explant peripheral cells. Collagen and materials reacting positively to periodic acid-Schiff (PAS) were first interposed between agar and explant after 4 days. After 8 days, an inner immunonegative layer corresponding to materials reacting positively to PAS or toluidine blue and an outer immunopositive layer of fibronectin or collagen were visible adjacent to the rows of elongated columnar cells. In the presence of Gly-Arg-Gly-Asp-Ser-Pro (GRGDSP), a competitive inhibitor of attachment of cells to fibronectin, explants became detached from the agar surface, and no dentinogenesis occurred. These results indicate that, when in contact with an agar surface that becomes modified by fibronectin and/or by a complex of fibronectin with deposited matrix, dental mesenchymal cells progressively differentiate into tubular matrix-forming cells. Possibly the functional agar surface has the important role of providing a foothold for cell attachment, which is the first step towards in vitro odontoblast differentiation. This system of inducing tubular matrix-forming cells constitutes a useful model for the study of in vitro dentinogenesis.

Agar↗

Method for evaluation of immunotoxicity of dioxin compounds using human T-lymphoblastic cell line, L-MAT.

Caspase-3 was activated in apoptotic L-MAT cells by treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Treatment with tributyltin, which has been reported to induce apoptosis in rat thymocytes, also activated caspase-3 and led to cell death in L-MAT cells. Blocking caspase-3 activity with the peptide inhibitor, DEVE-CHO, prevented TCDD from inducing subsequent apoptotic changes. The potent Ah receptor ligand, 2,3,7,8-tetrachlorodibenzofuran (TCDF), the low acute toxicity compound, 1,2,3,4,6,7,9-heptachlorodibenzo-p-dioxin (HCDD), and one of the major contaminants in human milk, 3,3',4,4',5-pentachlorobiphenyl (PCBP), increased the activation level of caspase-3, each in a dose-dependent manner. Thus, we propose that measuring caspase-3 activation in the human T-lymphoblastic cell line, L-MAT, is a useful evaluation method for the immunotoxicity of dioxin compounds.

Apoptosis↗

Bone regeneration by basic fibroblast growth factor complexed with biodegradable hydrogels.

The objective of this study is to enhance the bone induction activity of basic fibroblast growth factor (bFGF) for reconstruction of skull bone defects which has been clinically recognized as almost impossible. For this purpose, we prepared biodegradable hydrogels from gelatin with an isoelectric point of 4.9 which is capable of polyionic complexing with basic bFGF. When implanted in rabbit skull defects of 6 mm in diameter (6 defects per experimental group), the gelatin hydrogels incorporating 100 microg of bFGF promoted bone regeneration at the defect in marked contrast to free bFGF of the same dose, finally closing the bone defects after 12 weeks of implantation as is apparent from histological examination. In dual energy X-ray absorptometry analysis, the bone mineral density at the skull defects enhanced by the hydrogels was significantly higher than that by free bFGF at doses ranging from 2 to 200 microg/defect (P < 0.05). The extent of bone regeneration induced by gelatin hydrogels incorporating 100 microg of bFGF increased with a decrease in their water content. Histological examination indicated that more slowly degrading hydrogels of lower water content prolonged the retention period of osteoblasts in the bone defects. This led to enhanced bone regeneration compared with faster degrading hydrogels of higher water content. It was concluded that this biodegradable hydrogel system was a promising surgical tool to assist self-reconstruction of the skull bone.

Animals↗

Ipsilateral atrophy in children with hemispheric cerebral tumors: CT findings.

The CT findings of 19 children under 16 years of age with primary brain tumors in the cerebral hemisphere were investigated with special reference to the existence of cerebral hemiatrophy ipsilateral to the side of the tumor. "Ipsilateral cerebral hemiatrophy" was observed in four of 19 cases (21%). These included two cases with germinoma in the basal ganglia and two with low-grade astrocytoma in the frontal and occipital cortex. This peculiar CT finding was not specific to the location or histology of the tumor. The four cases were characterized by slow progression, which contrasted with the rapid progression of tumors shown in seven cases with a mass effect on CT.

Adolescent↗

Differentiation of suprasellar nonneoplastic cysts from cystic neoplasms by Gd-DTPA MRI.

Magnetic resonance imaging in 9 cases of surgically confirmed nonneoplastic intra- and/or suprasellar cysts was analyzed and compared with that from 17 cases of craniopharyngioma and 12 of cystic pituitary adenoma. Signal intensity did not help in distinguishing nonneoplastic cysts from cystic neoplasms. No postcontrast (Gd-DTPA) cyst wall enhancement was observed among the nonneoplastic cysts, although all 6 craniopharyngiomas and 12 cystic pituitary adenomas that underwent postcontrast study did enhance. Three nonneoplastic cysts were surrounded by the pituitary gland, thus mimicking wall enhancement in the postcontrast studies. Rapid enhancement in the early postcontrast-administration phase (dynamic studies) helped avoid confusion between the normal pituitary tissue and cyst wall enhancement. Magnetic resonance studies with contrast enhancement play an essential role in differentiating nonneoplastic cysts from cystic neoplasms in the sella region.

Adenoma↗

Comparison of the cardiovascular effect of FR34235, a new dihydropyridine, with other calcium antagonists.

We compared the cardiovascular effect of FR34235, a new dihydropyridine derivative, with the effects of nifedipine, nicardipine, and diltiazem on the dog using in vitro and in vivo preparations. FR34235 reduced the amplitude of coronary arterial contraction induced by K+ more so than that induced by norepinephrine in in vitro preparations. The ID50 values of FR34235 for various arterial strips contracted by K+ were smaller (1/5-1/426) than those of nifedipine and diltiazem, and almost the same as those of nicardipine. There was a greater increase in both the coronary and vertebral blood flow than in the other peripheral arterial flow in anesthetized dogs administered FR34235 (0.32-100 micrograms/kg i.v.), and the duration of effect was about two to three times longer than that of the other drugs. To obtain a vasodilating effect by the intraduodenal route, 10-30 times the intravenous dose of FR34235 was required, far lower than that required of nicardipine. In atrioventricular (AV) and sinoatrial node preparations, FR34235 was weaker in impairing AV conduction than nifedipine, in spite of their similar potencies in increasing coronary flow and decreasing sinus rate. FR34235 was more potent than diltiazem in increasing coronary flow, in spite of their similar potencies on AV conduction. It is concluded that FR34235 has: (a) potent vasodilating activity, probably due to inhibition of Ca2+ influx into the cells; (b) selective and long-lasting effects on the coronary and cerebral arteries in vivo; (c) a wide difference between doses that cause vasodilation and an impairing effect on AV conducting tissues; and (d) therapeutic effects after absorption from the intestinal tract.

Anesthesia↗