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Biomedical subjects

T Seki

Publications and source records attributed to T Seki.

At least 415 records · Page 23Linked to original sources
PubMed1992

Mechanism of skin penetration-enhancing effect by laurocapram.

In order to clarify the mechanism of action of laurocapram (Azone) on the skin permeation of drugs, the following experiments were done. First, the effect of Azone on the skin components was compared with that of other penetration enhancers. Azone markedly fluidized liposomal lipids (as a model lipid system) compared with other enhancers. Ethanol extracted large amounts of the stratum corneum lipids, whereas Azone did not. These results suggest that the effect of Azone on the lipids in the stratum corneum is not the same as that of ethanol. In addition, ethanol increased the amount of free sulfhydryl (SH) group of keratin in the stratum corneum, whereas Azone did not directly affect the stratum corneum protein. Azone increased water content in the stratum corneum, as measured by skin conductance. This effect might be a reason for the action of Azone. For further understanding, the enhancing effects of Azone on the skin permeation of several model compounds (alcohols, sugars, and inorganic ions) were compared with the effects of pretreatment with distilled water, which was thought to increase water-holding capacity, and pretreatment with ethanol, which was thought to affect the lipids and protein in the skin barrier (i.e., stratum corneum). Pretreatment with water or ethanol enhanced skin permeation of hydrophilic compounds, whereas they decreased that of octanol, a hydrophobic compound. The tendency of Azone to increase or decrease the skin permeation rate of most compounds was similar to that of pretreatment with water or ethanol. However, the effect of Azone on the skin permeation of inorganic ions was relatively low, whereas that of pretreatment with water or ethanol was high.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcohols↗
PubMed1992

Control of drug release with a combination of prodrug and polymer matrix: antitumor activity and release profiles of 2',3'-diacyl-5-fluoro-2'-deoxyuridine from poly(3-hydroxybutyrate) microspheres.

Drug release was controlled by a combination of prodrug and polymer matrix. Prodrugs of 5-fluoro-2'-deoxyuridine with different physicochemical properties were synthesized by esterification with aliphatic acids (propionate, n-butyrate, and n-pentanoate). Microspheres containing these ester prodrugs were prepared with poly(3-hydroxybutyrate) of three molecular weights (65,000, 135,000, and 450,000). The release rates from the spheres depended on both the lipophilicity of the prodrug and the molecular weight of the polymer. Regardless of the polymer, the relative release rates were propionate greater than butyrate greater than pentanoate. The release of butyrate and pentanoate from the spheres consisting of low-molecular-weight polymer (M(r), 65,000) was faster than that from the spheres of higher molecular weight (M(r), 135,000 or 450,000). A single intraperitoneal injection of spheres of the highest molecular weight polymer containing butyrate or pentanoate resulted in higher antitumor effects against P388 leukemia in mice than did free prodrugs given over a period of five consecutive days. The polymer sphere itself showed low toxicity to and good biocompatibility with mice and rats.

Animals↗
PubMed1992

A possible association between basic amino acids of position 13 of DRB1 chains and autoimmune hepatitis.

Fifty-one patients with autoimmune hepatitis have been studied for HLA association by conventional serology and also by modified polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) genotyping. HLA-DR4 was significantly associated with autoimmune hepatitis (46 of 51 patients, 90.2%). DNA typing of the DRB1 gene for 43 DR4-positive patients by using the PCR-RFLP technique revealed that of 43 patients, 33 had DRB1*0405 (Dw15), five had DRB1*0406 (DwKT2), four had DRB1*0403 (Dw13a), two had DRB1*0401 (Dw4), two of 43 had DRB1*0407 (Dw13b) and one had DRB1*0408 (Dw14b). Thus, there was no significant difference in Dw frequencies between DR4-positive patients and DR4-positive healthy subjects. These findings suggest that the DR4-specific sequence (Val 11 and His 13 at amino acid positions 11 and 13, respectively), but not particular Dw-associated DR4 sequence, in the first domain of the DRB1 chain contributes to susceptibility to autoimmune hepatitis among Japanese. Interestingly, all five of the DR4-negative patients had the DR2 specificity (DRB1*1502 or 1601). Taken together, these results imply that the basic amino acids at position 13, which is present only on the DR2 and DR4 B1 molecules (Arg on DR2 and His on DR4), are most important for determining the predisposition to autoimmune hepatitis.

Amino Acid Sequence↗
PubMed1992

Angiographic demonstration of no-flow anatomical patency of internal thoracic-coronary artery bypass grafts.

To clarify the no-flow situation of the stringlike internal thoracic artery graft, we angiographically examined such grafts by temporarily occluding the recipient coronary artery with a percutaneous transluminal coronary angioplasty balloon and were able to reveal anatomical patency of the internal thoracic artery graft in 2 patients 1 year and 3 years after the operations. Thus, there is a possibility that internal thoracic artery grafts may continuously maintain anatomical patency even under no-flow situations just like nonfunctioning collateral vessels and may function properly later as a graft when the native coronary flow decreases. Also, this angiographic technique can be a new method for detecting anatomical patency of no-flow and functionally closed internal thoracic artery grafts.

Anastomosis, Surgical↗
PubMed1992

Differential effects of cyclosporin A on diverse B cell activation phenomena triggered by crosslinking of membrane IgM.

Cyclosporin A (CsA) was tested for its modulatory effects on the mIgM-mediated signaling of G0*-associated increases in class II MHC expression, G1-related RNA synthesis, and S phase-related DNA synthesis in human B cells. While CsA at concentrations as low as 10-100 ng/ml could completely ablate anti-IgM-induced DNA synthesis, earlier G1-associated RNA synthesis was only partially inhibited, and signaling of increased membrane class II MHC expression was unaffected by up to 1000 ng/ml of CsA. Similar phenomena were observed in a clonal population of leukemic B lymphocytes susceptible to anti-IgM-mediated activation in the absence of T cells and T cell factors indicating (a) that the inhibitory effects are not due to CsA-mediated suppression of cytokine production by contaminating T cells, and (b) that the varying effects of CsA on the diverse activation phenomena do not reflect B cell subpopulation diversity. Pulsing studies revealed that while maximal suppression of anti-IgM-induced G1-associated RNA synthesis required CsA at culture initiation, near maximal suppression of DNA synthesis occurred when CsA, or soluble human IgM, was added up to 30 hr after the initial exposure of resting B cells to the anti-IgM ligand. These latter findings are consistent with the possibility that the CsA-mediated suppression of S phase entry is due to the inhibition of a signaling event proximal to mIgM ligation which must be repeatedly initiated throughout the first 30 hr of activation.

Antibodies, Anti-Idiotypic↗
PubMed1992

HLA class II molecules and autoimmune hepatitis susceptibility in Japanese patients.

To investigate the association between autoimmune hepatitis and HLA alleles in Japanese patients, serological typing and class II genotyping were performed using the polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) method. Serological typing showed that HLA-B54, -DR4, -DR53, and -DQ4 were significantly more frequent in patients with autoimmune hepatitis than in controls. HLA-DR4 was most frequently associated with autoimmune hepatitis (88.7%). In PCR-RFLP typing, the frequency of DRB1*0405 was significantly higher in autoimmune hepatitis than in controls. However, there was no significant difference in the frequency of Dw between the patients and the controls who were DR4-positive. The significant increase observed in DQA1*0301 and DQB1*0401 was explained by a linkage disequilibrium with DR4. Six DR4-negative patients had DR2, but there was no significant difference in the frequency of the DR2-associated Dw-alleles compared with the DR2-positive controls. No DPB1 allele was significantly associated with autoimmune hepatitis. These findings suggest that the basic amino acid at position 13, which is present only on the DR2 and DR4 B1 molecules (Arg on DR2 and His on DR4), contributes to the susceptibility to autoimmune hepatitis among the Japanese.

Adult↗
PubMed1992

Bilateral internal drainage of biliary hilar malignancy via a single percutaneous track. Role of percutaneous transhepatic cholangioscopy.

Strictures of the hepatic bifurcation were bilaterally drained via a single percutaneous tract in 24 patients with hilar cholangiocarcinoma. This was achieved under percutaneous transhepatic cholangioscopic (PTCS) guidance which allowed for an excellent manipulation of the guidewire. Placement of two guidewires, one in the contralateral hepatic duct and the other in the common duct, was successful in 19 (79%) of patients at the first attempt. In the remaining cases the better accessible stricture was dilated, followed by negotiation of the other stricture under direct cholangioscopic control. After placement of guidewires into both hepatic ducts, bilateral drainage with a single Y-shaped catheter could be achieved in all 24 patients. There were no procedure-related complications. We conclude that this technique might be useful also for application of other intraluminal adjuvant treatment modalities.

Adenoma, Bile Duct↗
PubMed1992

Chromosome condensation caused by loss of RCC1 function requires the cdc25C protein that is located in the cytoplasm.

We cloned the hamster cdc25C cDNA by using the human cdc25C cDNA as a probe and prepared an antibody to Escherichia coli-produced hamster cdc25C protein that is specific to the human cdc25C protein. The microinjected antibody inhibited a chromosome condensation induced by tsBN2 mutation, indicating that the cdc25C protein is required for an activation of p34cdc2 kinase caused by loss of RCC1 function. The hamster cdc25C protein located in the cytoplasm, prominently in a periphery of the nuclei of cells arrested with hydroxyurea, and seemed to move into the nuclei by loss of RCC1 function. Also, we found a molecular shift of the cdc25C protein in cells showing premature chromosome condensation (PCC), in addition to normal mitotic cells. This molecular-shift appeared depending on an activation of p34cdc2 kinase.

Amino Acid Sequence↗
PubMed1992

HLA-DRB1 genotyping by modified PCR-RFLP method combined with group-specific primers.

We previously introduced HLA-DQA1, -DPB1 and DQB1 genotyping with the modified PCR-RFLP method using some informative restriction enzymes which have either a single cleavage site or alternatively no cleavage site in the amplified DNA region, depending on the HLA alleles, making reading of RFLP band patterns much easier. In this study, 43 HLA-DRB1 alleles, excluding DRB1*1103 and *1104 for which no restriction enzymes are available to distinguish each from the other, could be defined by this modified PCR-RFLP method combined with 7 pairs of group-specific primers. It is impossible to distinguish DRB1*0701 and DRB1*0702 as they are identical for the second exon of DRB1. For DR1-DRB1, DR2-DRB1, DR4-DRB1, DR7-DR1, DR9-DRB1, DRw10-DRB1 or DRw52 associated antigens (DR3, w11, w12, w13, w14, and DRw8)-DRB1 gene amplification, the second exon of the DRB1 gene was selectively amplified using each group-specific primer from genomic DNAs of 70 HLA-homozygous B-cell lines and healthy Japanese by PCR. Amplified DNAs were digested with restriction endonucleases and then subjected to electrophoresis assaying simply for cutting, or no cutting, of the DNA, although some alleles can be distinguished only after examination of RFLP band patterns generated and in some cases using double digestion technique with two restriction enzymes. This modified PCR-RFLP method can be successfully applied to all possible DRB1 heterozygotes, despite the fact that 15 pairs of heterozygotes among them cannot be distinguished theoretically by the PCR-SSO method, because the PCR-RFLP method can tell whether two polymorphic sites are linked to each other (cis position) or located on a different chromosome (trans position) by checking the length of RFLP bands generated with double digestion. Thus, the PCR-RFLP method is technically simple, practical and inexpensive for determination of the HLA-DRB1 alleles for routine HLA typing work.

Alleles↗
PubMed1992

Association of HLA-B51 and lack of association of class II alleles with Behçet's disease.

Eighty-one Behcet's disease patients have been studied for HLA association by HLA-DRB1, -DQA1, -DQB1 and -DPB1 genotyping with the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique and for NcoI RFLP in the tumor-necrosis factor (TNF beta) gene by Southern hybridization in addition to serological typing. In serological typing, the frequency of HLA-B51 was significantly increased in the patients. In PCR genotyping, there was a significant increase in the HLA-DRB1*0802, DQA1*0301 and DQB1*0303 alleles, whereas the frequencies of DRB1*1502, DQA1*0103, DQA1*0101, DQB1*0601 and DQB1*0501 showed a significant decrease in the patients. No significant difference was observed in any HLA-DPB1 alleles. Among them, B51 was found to be a genetic marker most strongly associated with Behcet's disease (p less than 0.00005, chi 2 = 46.47, pc[corrected p] less than 0.005). The positive and negative associations of class II alleles with the disease can be explained by linkage disequilibrium with B51, and do not reach statistical significance by the corrected p-value test. In NcoI RFLP typing in the TNF beta gene, 250 kb centromeric of the HLA-B gene, the frequency of a 5.5 kb fragment was considerably decreased in the patients when compared to the controls, although the decrease was not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Alleles↗
PubMed1992

Genetic relatedness of Bradyrhizobium japonicum field isolates as revealed by repeated sequences and various other characteristics.

Forty-nine isolates of Bradyrhizobium japonicum indigenous to a field where soybeans were grown for 45 years without inoculation were characterized by using four DNA hybridization probes from B. japonicum. nifDK-specific hybridization clearly divided the isolates into two divergent groups. Diversity in repeated-sequence (RS)-specific hybridization was observed; 44 isolates derived from 41 nodules were divided into 33 different RS fingerprint groups. Cluster analysis showed that the RS fingerprints were correlated with the nif and hup genotypes. We found multiple bands of RS-specific hybridization for two isolates that differed from the patterns of the other isolates. These results suggest that RS fingerprinting is a valuable tool for evaluating the genetic structure of indigenous B. japonicum populations.

Bacterial Typing Techniques↗
PubMed1992

Lack of cell density-dependent changes in gangliosides of rat primary culture neurons.

Cell density-dependent changes in neuronal gangliosides, primarily relating to neurite outgrowth under dense to sparse conditions, were examined at cell seeding densities over an 8-fold range. During the first 24 h of incubation, the dissociated fetal rat neurons showed characteristic protrusion of neurites as a function of cell density. Ganglioside and protein contents per the same cell numbers were higher in dense cultures than sparse ones. However, the ganglioside pattern was essentially unchanged from dense to sparse culture, showing a predominance of GD3 and GT1b. The biosynthetic activity of gangliosides, as estimated by the incorporation of 3H-labeled N-acetyl-D-mannosamine, a precursor of sialic acid, was similar at various cell densities, with the labeling of b-series gangliosides predominating. The expression of neuronal gangliosides was monitored by indirect immunofluorescence using anti-GM1 antibody, but was found to be poor. A2B5 antigen, which was mainly identified as GT1b, appeared to be readily expressed on cell surfaces in sparse cultures. In contrast, the highly polysialylated form of the neural cell adhesion molecule (NCAM-H) was fully expressed on both the neurites and cell soma at various cell densities. The results suggest that the polysialic acids in NCAM have more important roles in neurite outgrowth than gangliosides, since the composition and synthesis of gangliosides are not affected by cell seeding density.

Animals↗
PubMed1992

Prodrugs of 2',3'-dideoxyinosine (DDI): improved oral bioavailability via hydrophobic esters.

Five ester prodrugs of 2'3'-dideoxyinosine (DDI) were synthesized for the purpose of improving oral bioavailability. The prodrugs, acetate (C2-DDI), octanoate (C8-DDI), stearate (C18-DDI), benzoate (Bz-DDI), and hemisuccinate (Suc-DDI) were proved to quantitatively regenerate their parent drug by enzymatic hydrolysis. Though the chemical stability of the prodrugs under acidic conditions was not improved, their solubility in water was significantly decreased by esterification, except for Suc-DDI. Bioavailability was evaluated by oral administration to rats. Two hydrophobic prodrugs (C8-DDI and Bz-DDI) showed higher absolute bioavailability (23.5% and 31.0%, respectively) than did DDI (15.2%), though that of C2-DDI (11.5%) and Suc-DDI (4.5%) was poor.

Administration, Oral↗
PubMed1992

Effects of diethofencarb on thyroid function and hepatic UDP-glucuronyltransferase activity in rats.

To examine the mechanism and toxicological significance of thyroidal tumor observed slightly in a long-term rat study with diethofencarb (isopropyl 3,4-diethoxycarbanilate), male Sprague-Dawley rats were fed diethofencarb in diets at concentrations of 0, 5,000 or 20,000 ppm for 3 months. Examinations mainly for thyroid functions including thyroid uptake of 125I, serum thyroid hormone and thyroid stimulating hormone (TSH) level, hepatic UDP-glucuronyltransferase (UDP-GT) activity and histopathological examination in thyroid were performed at week 13. Decreases of body weights and food consumptions were observed at and above 5,000 ppm. Under these conditions, decrease of serum free T4 and increase of serum TSH level were observed only at 20,000 ppm, concurrently with liver weight increase at and above 5,000 ppm and increase of hepatic UDP-GT activity at 20,000 ppm. However, no compound related effects were noted in thyroid weight, thyroid uptake of 125I and gross or histopathological examination in thyroid. These results indicate that the administration of diethofencarb leads to an increase in UDP-GT activity and acceleration of thyroid hormone excretion from the liver. The acceleration causes a decrease in serum free T4 level, triggering the feedback mechanism of the pituitary gland, promotion of TSH release and consequently an increase in serum TSH level. Thus, the slightly higher incidence of thyroid follicular cell tumors observed in the chronic and oncogenicity study with non-genotoxic diethofencarb is considered to be caused by these weak pituitary-thyroid hormonal imbalances. The toxicological significance in humans is extremely low according to the well established facts that the chronic TSH stimulating would not induce thyroid tumors in humans and humans may be less sensitive than rats in regard to the response to goitrogenic stimuli.

Animals↗
PubMed1992

[A fifty two-week oral repeated dose toxicity study of suplatast tosilate (IPD-1151T) in dogs].

A 52-week oral repeated dose toxicity study of suplatast tosilate (IPD-1151T), a newly developed anti-allergic agent, was carried out in beagles by oral administration of 30, 90, 270 and 810 mg/kg/day for 52 weeks. The recovery study was carried out by the withdrawal for 5 weeks using control and the 810 mg/kg groups. The results are as follows: 1. Observation of general conditions revealed soft feces, mucous feces, and diarrhea in both sexes of the 270 and 810 mg/kg groups during the administration period, and these findings disappeared during the withdrawal period. One female of the 810 mg/kg group exhibited tremors in the legs and neck, staggering, a decrease of spontaneous motor activity, and clonic convulsions in Week 17 of administration and died on Day 118. One male of the same group exhibited whole body tremors and staggering from Week 32 to Week 52. 2. Body weight gain tended to be inhibited in males of the 810 mg/kg group during the administration period. The body weight of the female that died decreased rapidly after the appearance of neurological symptoms. The body weight of the male that exhibited neurological symptoms decreased after their appearance but later increased. 3. There were no abnormal changes in food consumption in all of the sacrificed dogs. The female that died did not eat at all after the appearance of neurological symptoms. The male that exhibited neurological symptoms did not eat at all for 1 week after their appearance, but the food consumption returned to normal thereafter. 4. Prothrombin times were prolonged in males of the 270 and 810 mg/kg groups at Week 26, and activated partial thromboplastin times were prolonged in males of the 810 mg/kg group at Week 52. 5. Plasma levels of alkaline phosphatase, GPT and LDH were elevated in some males and females of the 810 mg/kg groups. 6. No abnormalities due to IPD-1151T administration were found in urinalysis, opthalmological examination, electrocardiography, and fecal occult blood examination, or organ weights. 7. Autopsies including histopathological and electron microscopic examinations on the sacrificed dogs revealed no abnormalities. Subserosal hemorrhage in the base of the heart, congestion in the lungs, congestion and vacuolation in the liver and slight cell infiltration around vessels of the brain were found in the female that died.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Oral↗