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Biomedical subjects

S Okada

Publications and source records attributed to S Okada.

At least 757 records · Page 42Linked to original sources

Chronic effects of intracerebral ventricular enterostatin in Osborne-Mendel rats fed a high-fat diet.

Enterostatin, a pentapeptide found in the procolipase molecule of the pancreas, has been infused chronically into the lateral ventricle of Osborne-Mendel rats for 11 days. Treatment with enterostatin acutely lowered food intake more in the treated animals than in the vehicle-treated controls. Weight gain and serum insulin were significantly reduced by enterostatin. Corticosterone was significantly increased in rats receiving chronic infusions of enterostatin into the lateral ventricle and was also increased following an acute ICV injection of enterostatin. CRH antagonist did not block the acute feeding response to enterostatin in Sprague-Dawley rats. The elevation of corticosterone during chronic infusion of enterostatin reduced the level of hepatic glucocorticoid receptor as measured by Western blot. We conclude that body weight gain of OM rats is reduced by centrally administered enterostatin, and that the acute effects of enterostatin on food intake are not mediated through stimulation of CRH secretion.

Animals↗

Medialbasal hypothalamic deafferentation modulates feeding response to insulin in rats.

Medialbasal hypothalamic (MBH) deafferentation induces hypothalamic obesity accompanied by hyperphagia and hyperinsulinemia. Insulin is essential in developing and maintaining obesity, but the role of insulin in food intake in hypothalamic obesity is still unclear. The present study demonstrated that exogenous insulin increased food intake dose relatedly in MBH deafferented diabetic rats without developing hypoglycemia. Insulin administrations suppressed hyperphagia in the sham-operated diabetic rats. In contrast, in the MBH deafferented diabetic rats, insulin increased food intake in sow-related manner concomitant with a greater increased body weight gain than the sham-operated diabetic rats. The blood glucose levels of the MBH deafferented diabetic rats were at all time higher than those of the sham-operated diabetic rats and were hyperglycemic throughout the insulin treatment. These data indicate that insulin action on food intake mediated through the central nervous system is modulated by MBH deafferentation. This modulated insulin action may contribute to the pathogenesis on obesity in MBH deafferented animals.

Afferent Pathways↗

Tumor imaging with technetium-99m-DTPA encapsulated in RES-avoiding liposomes.

For passive targeting of liposomes to tumor tissues, we earlier developed reticuloendothelial system (RES)-avoiding liposomes modified with a uronic acid derivative, palmityl-D-glucuronide (PGlcUA). In the present study, we encapsulated technetium-99m (99mTc)-diethylenetriaminepentaacetic acid (DTPA) in PGlcUA-liposomes (dipalmitoylphosphatidylcholine:cholesterol:PGlcUA = 40:40:20 as a molar ratio) and studied the biodistribution of the liposomes in tumor-bearing mice. 99mTc-DTPA encapsulated in liposomes effectively accumulated in tumor tissues after intravenous administration. Corresponding to these results, tumor was strongly imaged by a gamma-camera when 99mTc-DTPA-encapsulated PGlcUA-liposomes were used.

1,2-Dipalmitoylphosphatidylcholine↗

Liver distribution of 99mTc-DL-homocysteine in experimental hepatitis rats.

Liver accumulation of 99mTc-DL-homocysteine (99mTc-Hcy), which had been found to accumulate in several experimental tumors, was studied using experimental hepatitis models of rats. The distribution of this compound in liver of rats treated with CCl4 (25-100 microL/100 g body weight) was more than five times higher than that of non-treated rats, corresponding to the accumulation of Evans Blue, a marker dye for capillary permeability. Furthermore, in vitro experiments indicated that the liver accumulation of 99mTc-Hcy was due to some changes in the plasma membranes caused by CCl4 administration. These results indicate that lesional accumulation of 99mTc-Hcy is due to, at least in part, an enlarged capillary permeability similar to the case of malignant tissues reported previously.

Animals↗

Primary mucinous carcinoma of the renal pelvis.

A case of primary mucinous carcinoma originating in the renal pelvis associated with renal lithiasis is reported. The left kidney removed was mostly occupied by mucinous carcinoma with areas of signet ring cell carcinoma. The epithelium covering the pelvis consisted of a single layer of columnar epithelium with scattered goblet cells and mucous glands. A series of careful examinations of the abdominal viscera failed to disclose any other primary lesion. The patient died with multiple peritoneal tumor disseminations eight months after the operation despite additional chemotherapy.

Adenocarcinoma, Mucinous↗

Morphological assessment of polycystic ovary using transvaginal ultrasound.

A total of 104 patients with bilateral polycystic ovaries (PCO) diagnosed by transvaginal ultrasound were classified into four groups (A < 5 cysts, B 5-10 cysts, C > 10 cysts located under ovarian capsule, D numerous cysts distributed all over the ovary) according to the number of microcysts. Ovarian volume, clinical features (menstrual disturbance, obesity and hirsutism), endocrine levels [luteinizing hormone (LH), LH/follicle stimulating hormone ratio, testosterone, androstenedione and dehydroepiandrosterone-sulphate] and response to clomiphene were compared for each group and 17 control subjects with normal ovulatory cycles. Ovarian volume in PCO subjects was significantly larger than that in control subjects. As the number of microcysts increased, the ovarian volume enlarged and the endocrine abnormality worsened. All endocrine parameters in PCO subjects with menstrual disturbances were significantly higher than those in PCO subjects without menstrual disturbances and controls. In PCO subjects without menstrual disturbances only androstenedione was significantly higher than in controls. Among PCO subjects, the frequency of menstrual disturbances, the percentage of response to clomiphene and the pregnancy rate in groups C and D were significantly higher than in groups A and B. Therefore, screening the ovaries in infertile patients by means of transvaginal ultrasound and subsequent assessment of morphology in PCO may suggest endocrine abnormality and help in selecting the proper treatment.

Adult↗

Overview of tritium: characteristics, sources, and problems.

Tritium has certain characteristics that present unique challenges for dosimetry and health-risk assessment. For example, in the gas form, tritium can diffuse through almost any container, including those made of steel, aluminum, and plastics. In the oxide form, tritium can generally not be detected by commonly used survey instruments. In the environment, tritium can be taken up by all hydrogen-containing molecules, distributing widely on a global scale. Tritium can be incorporated into humans through respiration, ingestion, and diffusion through skin. Its harmful effects are observed only when it is incorporated into the body. Several sources contribute to the inventory of tritium in our environment. These are 1) cosmic ray interaction with atmospheric molecules; 2) nuclear reactions in the earth's crust; 3) nuclear testing in the atmosphere during the 1950s and 1960s; 4) continuous release of tritium from nuclear power plants and tritium production facilities under normal operation; 5) incidental releases from these facilities; and 6) consumer products. An important future source will be nuclear fusion facilities expected to be developed for the purpose of electricity generation. The principal health physics problems associated with tritium are 1) the determination of the parameters for risk estimation with further reduction of their uncertainties (e.g., relative biological effectiveness and dose-rate dependency); 2) risk estimation from complex exposures to tritium in gas form, tritium in oxide form, tritium surface contamination, and other tritium-contaminated forms, with or without other ionizing radiations and/or nonionizing radiations; 3) the dose contributions of elemental tritium in the lung and from its oxidized tritium in the gastrointestinal tract; 4) prevention of tritium (in oxide form) intake and enhancement of tritium (oxide form) excretion from the human body; 5) precise health effects information for low-level tritium exposure; and 6) public acceptance of tritium leakage and waste disposal from reactors and fuel reprocessing plants.

Environmental Pollutants↗

Transforming growth factor-alpha expression of renal proximal tubules in Wistar rats treated with ferric and aluminum nitrilotriacetate.

A high incidence of renal adenocarcinoma has been observed in rats treated with ferric nitrilotriacetate (Fe-NTA) but not in rats treated with aluminum nitrilotriacetate (Al-NTA). Transforming growth factor (TGF)-alpha is one of the several cytokines that is known to be expressed in human and rat renal adenocarcinomas. However, its role in neoplastic transformation is still questionable. Therefore, we investigated the effect of repeated Fe-NTA and Al-NTA administration on renal TGF-alpha expression. Male Wistar rats were given Fe-NTA (n = 16, 5-10 mg Fe/kg) and Al-NTA (n = 19, 1-2 mg Al/kg) i.p., three times a week for 3 or 12 weeks. Another group of rats (n = 4) was given Fe-NTA (5-10 mg Fe/kg) three times a week for 12 weeks and then left untreated for one year. Immunoreactivity for TGF-alpha was positive in the collecting ducts and on the apical surface of proximal tubules in the outer stripe of the outer medulla in all the animals including NTA-injected control animals. However, TGF-alpha immunoreactivity in the regenerative proximal tubular epithelium was observed only in the animals treated with Fe-NTA for 12 weeks. Northern blot analysis also showed expression of TGF-alpha mRNA only in animals treated with Fe-NTA for 12 weeks. The expression of TGF-alpha mRNA in the kidney was stronger than that in the liver or brain. TGF-alpha was also positive in renal cell carcinoma found in animals treated with Fe-NTA for 12 weeks and left untreated for one year. These results suggest that TGF-alpha expression may play an important role in renal carcinogenesis and that it may be a sensitive marker during the induction stage of renal cell carcinoma.

Animals↗

Isolation of human herpesvirus 7 from a child with symptoms mimicking chronic Epstein-Barr virus infection.

Human herpesvirus-7 (HHV-7), which is a newly identified human herpesvirus with an unknown pathologic role, was isolated from a 5-year-old boy suffering from fever, hepatosplenomegaly and pancytopenia. Although the clinical course was similar to that of chronic active Epstein-Barr virus infection, no viruses other than HHV-7 were isolated. This finding raises the possibility that HHV-7 played a pathogenic role in the present patient.

Child, Preschool↗

Different clinical features in monozygotic twins: a case of 7q--syndrome.

We present male monozygotic twins who showed quite different clinical features. Blood chromosome analysis revealed 46,XY/46,XY,del(7) (q32-->qter) mosaicism in both twins. However, cultured skin fibroblasts from the twins showed different karyotypes. Twin 1, with a normal phenotype, had normal chromosomes and was 46,XY. Twin 2, on the other hand, had the characteristic manifestations of 7q- syndrome and chromosomes of 46,XY,del(7) (q32-->qter). DNA fingerprint analysis of their peripheral blood samples revealed the same pattern. However, DNA fingerprint patterns of cultured skin fibroblasts and buccal mucosal cells were different when a 7q terminal marker, probe g3, was used. These identical twins with discordant phenotypes can be explained by the occurrence of twinning and simultaneous erroneous mitosis. In addition, there might be a vascular communication which probably resulted in blood exchange and chromosomal mosaicism of the lymphocytes of the monozygotic twins.

Abnormalities, Multiple↗

Stereoselective binding of beta-blockers to purified rat alpha 1-acid glycoprotein.

The stereoselectivity of binding of four beta-blockers, pindolol, propranolol, oxprenolol and acebutolol, to purified rat alpha 1-acid glycoprotein (AAG) was examined using equilibrium dialysis. Pindolol and propranolol were bound stereoselectively to AAG, whereas binding of oxprenolol was non-stereospecific. Neither of the enantiomers of acebutolol bound to either AAG or any other plasma protein. The affinity of (+)-pindolol was 25 times that of (-)-pindolol, as determined in a single enantiomer experiment. Both enantiomers of propranolol demonstrated two classes of binding sites in AAG, the total binding for the high affinity site for (+)-propranolol being double that of (-)-propranolol, which could explain the higher binding of the (+)-enantiomer in racemate experiments. These results further showed that stereoselective binding to a rat AAG is not a property common to all beta-blockers.

Acebutolol↗

Effects of turpentine oil pretreatment on beta-blocker pharmacokinetic parameters in rats.

Turpentine oil treatment (0.2 mL kg-1, s.c.) was used to increase the plasma concentration of alpha 1-acid glycoprotein (0.13 mg mL-1 in control rats) to 1.72 mg mL-1 after 2 days, and allow assessment of its effects on the pharmacokinetics and stereoselective binding of three beta-blockers. Racemates (5 mg kg-1) were administered intravenously to control and turpentine oil-pretreated rats and the plasma concentrations were determined up to 90 min. Stereoselective analysis showed the apparent distribution volume and the area under plasma concentration-time curves (AUC) of R-(+)-propranolol to be, respectively, one-quarter and twice those of the S-(-)-enantiomer and differences in pharmacokinetic parameters between the two were magnified by turpentine oil pretreatment. Pharmacokinetic parameters of oxprenolol enantiomers were essentially similar for the controls but after turpentine oil pretreatment, a higher affinity of the R-(+)-enantiomer for plasma was observed. Acebutolol enantiomers behaved non-stereospecifically throughout. These results were consistent with predictions from the in-vitro stereospecific binding properties of these agents to purified rat alpha 1-acid glycoprotein.

Acebutolol↗

A new way of producing isomalto-oligosaccharide syrup by using the transglycosylation reaction of neopullulanase.

A new way of producing isomalto-oligosaccharide syrup from starch was developed. Isomalto-oligosaccharides contain one or more alpha-(1-->6)-glucosidic linkages with or without alpha-(1-->4)-glucosidic linkages. The isomalto-oligosaccharide syrups are receiving increased attention as food additives because it is thought that they help prevent dental caries and improve human intestinal microflora, acting as a growth factor for bifidobacteria. The new system for production of isomalto-oligosaccharide syrup is based on the strong alpha-(1-->6)-transglycosylation reaction of neopullulanase. Bacillus subtilis saccharifying alpha-amylase was simultaneously used with neopullulanase to improve the yield of isomalto-oligosaccharides. The yield of isomalto-oligosaccharides was increased to more than 60%, compared with a yield of 45.0% obtained by the conventional system. To reduce the costs, the use of immobilized neopullulanase was investigated. Almost the same yield of isomalto-oligosaccharides was obtained by using immobilized neopullulanase.

Journal Article↗

Adrenalectomy of the obese Zucker rat: effects on the feeding response to enterostatin and specific mRNA levels.

The effects of adrenalectomy on the feeding response to enterostatin and the mRNA levels of its parent protein, pancreatic colipase, have been investigated in lean (fa/?) and genetically obese (fa/fa) rats. Adrenalectomy reduced body weight gain and food intake of obese rats. Enterostatin inhibited the intake of high-fat diet in obese rats but not in lean rats. Adrenalectomy reduced food intake of all rats and abolished the response to enterostatin in the obese group. Obese rats had low levels of colipase mRNA, but these were normalized after adrenalectomy. The ability to respond to exogenous enterostatin is possibly linked to low levels of production of the peptide. The effects of adrenalectomy on brown adipose tissue uncoupling protein (UCP) mRNA and beta 3-adrenergic receptor (beta 3-AR) mRNA were also investigated. Northern blot analysis showed low levels of both UCP mRNA and beta 3-AR mRNA in obese rats that were restored to or toward the normal levels of lean rats by adrenalectomy. Adrenalectomy had no significant effects on mRNA levels in lean rats.

Adipose Tissue, Brown↗

A phase 2 study of cisplatin in patients with hepatocellular carcinoma.

A phase 2 study of cisplatin was performed in 28 previously untreated patients with unresectable hepatocellular carcinoma. The drug was given intravenously at a dose of 80 mg/m2/day every 4 weeks. Of 26 patients evaluated, 4 (15.4%) showed partial responses lasting for > 3 months, while no patient achieved a complete response. Of 22 patients whose serum level of alpha-fetoprotein (AFP) was high (> 400 ng/ml) before treatment, 6 (27.3%) showed a > 50% reduction in serum AFP levels after treatment. The current study indicates that cisplatin is an anticancer agent worthy of further testing in patients with this disease.

Adult↗

Adjuvant effect of interleukin-1 on the development of late asthmatic response in guinea pigs.

The adjuvant effect of silica and IL-1 in the development of late asthmatic responses (LARs) in guinea pigs was studied. Different doses of silica or recombinant human (rh) IL-1 (1 microgram) with Ascaris suum were used for the immunization. The serum IL-1 concentration was measured after the immunization. One week after the immunization, antigen was challenged and respiratory resistance (Rrs) was measured. Rrs increased silica dose dependently in the late phase, and the increment of Rrs in the late phase was significantly correlated with the serum IL-1 concentration (p < 0.05). In addition, rhIL-1 administration showed an increase in Rrs at the late phase. Antigen-specific IgE and IgG1 were also measured and were increased in guinea pigs immunized both with silica and rhIL-1.

Adjuvants, Immunologic↗