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Biomedical subjects

S Tsuchiya

Publications and source records attributed to S Tsuchiya.

At least 253 records · Page 14Linked to original sources

Role of N-acetylneuraminic acid in rat renal brush-border membrane vesicle aggregation by aminoglycosides.

Interaction between aminoglycosides (AGs) and rat renal brush-border membrane (BBM) vesicles was investigated by the aggregation technique. The order of aggregation was gentamicin greater than dibekacin not equal to netilmicin greater than amikacin, and this order corresponds to the strength of the nephrotoxicity of the aminoglycosides in vivo rather than the number of amino groups in the aminoglycosides. BBM vesicles were aggregated through ionic interaction, as evident from the finding that aggregation ceased to occur at alkaline pH. By addition of N-acetylneuraminic acid (NANA) to the incubation medium, the vesicle aggregation induced by gentamicin was significantly inhibited. To affect the liberation of the NANA residue from BBM vesicles, the vesicles were treated with neuraminidase, resulting in an about 60% release with a significant decrease in the uptake of gentamicin into the vesicles. The decrease in the degree of vesicle aggregation was in proportion to the amount of NANA liberated. It follows from the findings that the NANA residue may in some way be responsible for the accumulation of aminoglycosides in renal proximal tubular cells.

Aminoglycosides↗

The medical, nutritional and surgical treatment of fistulae in Crohn's disease.

Of a total 44 patients with Crohn's disease, 10 patients with 9 internal and 15 external fistulae, some of which were recurrent, were analyzed at the Department of Surgery, Yokohama City University between 1973 and 1988. Twenty-two fistulae were treated with medical and nutritional therapy using either total parenteral or enteral hyperalimentation by which the closure rate of the internal and external fistulae was 0 (0/9) and 42 per cent (9/14), respectively. The nutritional status of all the patients with fistulae treated by nutritional therapy improved, especially those whose fistulae were closed. However, 8 of 9 internal fistulae and 5 of 15 external fistulae finally required resection of the fistula with the distal stenotic bowel segment. The re-opening rate of fistulae following successful medical/nutritional therapy and surgical therapy was 88.9 per cent (8/9) and 53.8 per cent (7/13), respectively, and the mean interval until recurrence was shorter in the patients who underwent medical and nutritional therapy (4.5 months) than in those who underwent surgical therapy (19.4 months). Thus, using medical and nutritional therapy, none of the internal fistulae were closed, but 9 of 14 external fistulae were. The optimal management of internal fistulae is therefore thought to be bowel resection to include the distal stenotic lesion, while medical and nutritional therapy is thought to be of value for external fistulae.

Adult↗

Effect of dextran sulfate on renal accumulation of gentamicin.

The effect of dextran sulfate of three molecular weights (1000, 5000, and 90,000) on the accumulation of gentamicin in rat kidney was investigated using a continuous infusion technique. During the infusions of both gentamicin and gentamicin-dextran sulfate mixtures, the gentamicin plasma concentration was maintained at 10 microgram/ml. The renal cortical accumulation of gentamicin was significantly lower when dextran sulfate (1000, 5000) was coadministered. The inhibition of cortical gentamicin accumulation increased with increasing dextran sulfate dose, and it was proportional to the amount of dextran sulfate excreted into the urine. Analysis by electrophoresis on cellulose acetate membrane indicated that gentamicin binds to dextran sulfate in rat urine. Therefore, gentamicin-dextran sulfate binding within the lumen of the proximal tubules may reduce the renal reabsorption and possibly the renal toxicity of gentamicin.

Animals↗

Preparation of asialofetuin-labeled liposomes with encapsulated human interferon-gamma and their uptake by isolated rat hepatocytes.

The selective delivery of human recombinant interferon (IFN)-gamma to isolated rat hepatocytes was studied with asialofetuin (AF)-labeled liposomes. AF-liposomes containing buffer solution were initially prepared by the detergent removal method, and IFN-gamma was subsequently encapsulated by the freeze-thawing method without loss of activity. Virtually no free [32P]IFN-gamma was internalized into isolated rat hepatocytes, whereas AF-liposomes containing [32P]IFN-gamma were taken up to a significant degree. Liposomal binding to the hepatocytes (estimated at 4 degrees C) was one-fifth of the uptake (estimated at 37 degrees C). Since the uptake was inhibited by the addition of free AF, AF-liposomes may be taken up by the action of galactose-binding protein on the hepatocytic cell surface. The liposome preparation method reported in this paper provides a useful means for the encapsulation of unstable macromolecules into AF-liposomes. AF-liposomes were found effectively to carry IFN-gamma into hepatocytes in vitro.

Animals↗

Association of hypercholesterolemia and apolipoprotein E4 in school children.

To investigate the association of apolipoprotein (APO) E4 and hypercholesterolemia in children, we studied the APOE phenotypes of 51 school-age children with hypercholesterolemia and of 51 age, sex and obesity index-matched controls with normocholesterolemia by two-dimensional gel electrophoresis APOE4 was present in 21 of 51 hypercholesterolemic children (41.2%), and in nine of 51 control subjects (17.6%). The difference was significant (p less than 0.01). This finding indicates that APOE4 is associated with hypercholesterolemia in children.

Adolescent↗

Allergic rhinitis model with Brown Norway rat and evaluation of antiallergic drugs.

An animal disease model of allergic rhinitis was developed with Brown Norway (BN) rat, a high immunoglobulin E responder strain. BN rats were immunized with ovalbumin (OA) and made to suffer from allergic rhinitis. The severity of allergic rhinitis was assessed by determining the extent of the three kinds of markers, Evan's blue, histamine and N-acetyl-beta-D-glucosaminidase, released into the nasal perfusate following the OA challenge to the nasal cavity of OA-sensitized BN rats. This experimental system was appreciated by antiallergic drugs; chlorpheniramine maleate inhibited the release of Evan's blue and elevated that of histamine, but did not affect the N-acetyl-beta-D-glucosaminidase level. Halopredone acetate inhibited the releases of all the three markers. The estimation of the released markers using allergic rhinitis brought about in BN rats was found to be a useful experimental system for evaluating the effect of drugs on allergic rhinitis.

Acetylglucosaminidase↗

[Skin surface pH of hemodialysis patients].

The skin surface pH of 88 patients undergoing hemodialysis was investigated. The average of skin surface pH as measured at four different sites (forehead, forearm, palm and lower leg) was 4.5-5.0 and 5.0-6.0 in normal subjects and patients respectively. The difference in the two results was regarded as significant by Student's t test (p less than 0.01).

Adolescent↗

[Continuous hepatic arterial infusion chemotherapy using implantable reservoir in liver metastases from colorectal cancer].

Continuous hepatic arterial infusion chemotherapy using implantable reservoir was performed for liver metastases from colorectal cancer, and the therapeutic effects, side effects, and complications were evaluated. 9 patients with unresectable liver metastases were as follows, 1. Group A; 3 patients, MMC 2 mg.one shot + 5-FU 250 mg/day.continuous infusion x 14 days, and then 5-FU tablets 150 mg/day.p.o. x 14 days, 2. Group B; 4 patients, MMC 2 mg.one shot + 5-FU 500 mg/day.continuous infusion x 7 days, and then 5-FU tablets 150 mg/day.p.o. x 14 days, 3. Group C; 2 patients, 5-FU 500 mg/day.continuous infusion x 14 days, and then free from agents for 14 days. In 2 of 3 group A patients, the catheters became dislocated and one died of perforation of duodenum. In group A and group B, no severe side effects were noted. But both of group C patients showed nausea, vomiting and diarrhea. In 8 of 9 patients (89%), serum CEA level fell below the preoperative level. In 4 of 7 patients who underwent CT scan, the size of the tumor regressed. Total infused dose of 5-FU was 8.17 +/- 7.56 g in group A, 16.9 +/- 2.88 g in group B, and 21.0 +/- 9.90 g in group C on average. In 2 patients of group B, therapy was repeated seven times.

Antineoplastic Combined Chemotherapy Protocols↗

[Family study of primary hypercholesterolemia in school children--the Tsukuba Study].

Ninety-one children were determined to have hypercholesterolemia from a screening of 1,469 school children in the community near University of Tsukuba, and family studies of these children were performed. More than 50% of the parents participated in the study. The mean cholesterol levels of parents of hypercholesterolemic children were significantly higher than that of controls. Hypercholesterolemia in parents of hypercholesterolemic children was more frequent than that in controls. Nine families with autosomal dominant hyperlipidemia including familial hypercholesterolemia and familial combined hyperlipidemia were detected by further family studies. These results indicate that genetic factors are important as causes of hypercholesterolemia of school children and that family studies of hypercholesterolemic children is an efficient method for screening for persons with increased risk for cardiovascular diseases.

Age Factors↗

Effects of a concanavalin A-binding biliary glycoprotein on nucleation time of gallbladder bile.

A study was performed to determine quantitative differences in the total protein concentration of gallbladder bile from gallstone patients and to isolate nucleation-promoting factors from the bile. Total protein concentrations in cholesterol gallstone bile (3.6 +/- 0.6 mg/ml, mean +/- SD, n = 10), calcium bilirubinate gallstone bile (4.2 +/- 1.1 mg/ml, n = 10), black pigment gallstone bile (1.9 +/- 0.6 mg/ml, n = 4) and control gallbladder bile (2.3 +/- 0.5 mg/ml, n = 9) were not significantly different. Also no statistically significant differences in cholesterol saturation index were found among these groups. Gallbladder bile from cholesterol gallstone patients showed significantly faster nucleation than that of controls, calcium bilirubinate gallstone, or black pigment gallstone patients. We partially purified biliary glycoproteins proteins from cholesterol gallstone bile or calcium bilirubinate gallstone bile by chromatography on concanavalin A Sepharose. Nucleation time was measured following the addition of these proteins to control bile in vitro. The glycoproteins obtained from cholesterol gallstone bile had significant nucleation-promoting activity, but nucleation time was not changed following the addition of biliary glycoproteins from calcium bilirubinate gallstone patients. These results suggest that qualitative differences in individual proteins of gallbladder bile are responsible for nucleation-promoting activity in vitro.

Bile↗

[Primary lung cancer in young adults].

Despite a recent trend of rapid increase in the incidence of lung cancer in Japan, lung cancer has been detected rarely among young patients. The findings in 15 patients under 40 years of age who underwent surgery for primary lung cancer at Cancer Institute Hospital (C.I.H.) are presented. Fourteen were located in the region of the periphery. Ten of the 14 peripheral lesions were adenocarcinoma. The chances of cure or even long survival are very small. The case report presents a case with lung cancer in a 22-year-old woman who was the youngest in C.I.H. On histological examination, the excised tumor proved to be moderately differentiated adenocarcinoma.

Adult↗

Clinical effects of cepharanthin (Ceph.) on leukopenia by chemotherapy in lung cancer patients.

In order to examine the clinical efficacy of cepharanthin (Ceph.) for preventing leukopenia caused by chemotherapy in lung cancer patients, a randomized trial was carried out. Subjects were 45 patients with non-small cell lung cancer (NSCLC) receiving initial treatment with cisplatin (CDDP) +adriamycin (ADM) +mitomycin C (MMC). Ceph. was given at a dose of 1 mg/kg to the administration group (Ceph. group) and changes in the peripheral leukocyte count were examined in both the Ceph. and non-Ceph. groups. The Ceph. group showed a reduction in the number of cases with a count nadir less than 3,000/microliters (p less than 0.05), a shortening of the time that leukocyte counts stayed under 2,000/microliters, corresponding to the time in which granulocyte counts were less than 500/microliters (p less than 0.05), and also a reduction of the time for leukocyte counts to recover from nadir to 2,000 or 3,000/microliters (p less than 0.05) measured from the commencement of chemotherapy. These results suggest that administration of Ceph. has an antileukopenic effect in anticancer treatment, and makes it possible to reduce the period of risk for infection, allowing effective regimens to be administered repeatedly in shorter intervals.

Adult↗

Macrophage chemotactic factor (MCF) produced by a human T cell hybridoma clone.

A human T cell hybridoma clone, D6-18, producing high levels of macrophage chemotactic factor (MCF) was established by the emetine-actinomycin D selection method. MCF was found to be present not only in the culture medium but also in the cell lysate of D6-18 cells. The secretion of the MCF from D6-18 cells was effectively inhibited by disodium cromoglycate, which is an inhibitor of the degranulation of mast cells, suggesting that MCF is stored in granules. The MCF of D6-18 cells was purified from the sonicated cell lysate by ion-exchange chromatographies and high-performance liquid chromatography. The amino acid sequence of the purified MCF was revealed to be WLGREDGSE or WLGRQDGSE. The synthetic peptide WLGREDGSE showed chemotactic activity against guinea pig macrophages and human monocytes at the concentration of about 10(-8) M.

Amino Acid Sequence↗

Preparation of EGF labeled liposomes and their uptake by hepatocytes.

The preparation of epidermal growth factor (EGF) bearing liposomes (EGF-liposomes) and their uptake by rat hepatocytes were described. EGF was bound to the liposomal surface by the disulfide bridge linkage using a heterobifunctional cross-linking reagent, N-hydroxysuccinimidyl-3-(2-pyridyl-dithio) propionate. EGF-liposomes were taken up in a significant amount by rat hepatocytes in an EGF receptor mediated manner, and their uptake was dependent on the amount of labeled EGF coupled to the liposomal surface. These results raise the possibility that the EGF-liposomes may be an effective drug carrier to the cells having EGF-receptors like some cancer cells.

Animals↗

Three novel partial deletions of the low-density lipoprotein (LDL) receptor gene in familial hypercholesterolemia.

The low-density lipoprotein (LDL) receptor genes from 18 unrelated Japanese heterozygotes and 1 homozygote with classical familial hypercholesterolemia were analyzed by Southern blot hybridization using fragments of the human LDL receptor cDNA as probes. Four different deletion mutations were detected among 20 mutant LDL receptor genes (20%); they were characterized by restriction mapping. None of these mutations has previously been reported in Caucasian patients with FH: three of the mutations were novel and one was similar to the deletion mutation of FH-Tonami described previously in Japanese patients. In three of the four deletion mutations, the rearrangements were related to intron 15 of the LDL receptor gene, in which many Alu sequences exist. The data suggest that a wide range of molecular heterogeneity exists even in major rearrangements resulting in deletions in the LDL receptor gene. The data also support the hypothesis that there are preferential sites within the LDL receptor gene for major rearrangements resulting in deletions. The possibility that a higher frequency of deletion mutations occurs in classical FH than previously suspected is discussed.

Blotting, Southern↗

Primary cholesterol hepatolithiasis.

Stones extracted from patients with hepatolithiasis were analysed by infrared spectrophotometry. Cholesterol stones containing 70% or more cholesterol were found in 12 out of 55 cases. Judging from the lodging site of the stones, the degree of dilatation of the cystic duct, and the presence of cholecystitis, five of the cases were considered to be cholesterol stones produced in the liver. Two out of the five cases were a 44-year-old female and a 46-year-old female, respectively, with normal bifurcation of intrahepatic ducts, and stones were found in the lateral branches of dilated cystic bile ducts. The other three were 2 males and 1 female with an average age of 33. In these cases, the posterior descending branch bifurcated from the left hepatic duct, and stones were lodged in the dilated bile ducts distal to the junction of the left hepatic duct and the posterior descending branch. It is our conclusion that at least the former two were cases of "primary cholesterol hepatolithiasis" in view of the shape of the stones conforming to the hepatic duct, their easy morcellation, and the high cholesterol contents.

Adult↗

Effects of cyclosporin A on active Crohn's disease.

Seven patients with active Crohn's disease were treated with cyclosporin A orally for 16 weeks. The initial dose was 8 mg/kg/day and the subsequent dose was adjusted to maintain the plasma concentration of cyclosporin A of approximately 200 ng/ml. The mean value of the Crohn's disease activity index before treatment was 194.3 +/- 57.4. It was gradually decreased reaching a nadir at 12 weeks (139.0 +/- 45.6, p less than 0.05) and one enterocutaneous fistula was closed. White blood cell counts, hemoglobin and alpha-2-globulin did not significantly improve during treatment. Cyclosporin A could be indicated when steroids, sulfasalazine or azathioprine are not effective or not tolerated.

Administration, Oral↗