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Biomedical subjects

T Otani

Publications and source records attributed to T Otani.

At least 181 records · Page 10Linked to original sources

An investigation of Japanese subjects maps susceptibility to type 1 (insulin-dependent) diabetes mellitus close to the DQA1 gene.

Insulin-dependent diabetic and control subjects of Japanese origin were HLA-DRB1, -DQB1, and -DQA1 typed using restriction fragment length polymorphism analysis and sequence-specific oligonucleotide gene probing. The DQA1 allele DQA1*0301 was positively associated with the disease [48/52 (92%) diabetic patients versus 44/64 (69%) control subjects, Pc less than 0.03, RR = 4.97]. Alleles of the DRB1 and DQB1 genes showed no significant association with the disease. The frequency of DQB1 genotypes encoding the amino acid aspartic acid at position 57 of the DQ beta chain did not differ significantly between subjects with insulin-dependent diabetes mellitus (IDDM) and controls. These findings suggest that a susceptibility allele for IDDM in the Japanese is more closely associated with the DQA1 gene than the DQB1 gene.

Alleles↗

Diagnostic validity of fecal occult blood tests for detecting gastroenterological cancers.

In order to estimate the diagnostic validity of chemical fecal occult blood tests, i.e. orthotolidine (Shionogi A) and guajac (Shionogi B) slides for detecting cancers of the esophagus, stomach and colorectum, the authors followed up all the examinees (n = 3,449) of comprehensive medical check-ups at the Center for Adult Diseases, Osaka, by means of record linkage to the Osaka Cancer Registry's files. Then, diagnostic validity was calculated based on the results of two years' follow-up. Sensitivity for the respective cancers was 20.0%, 11.8% and 62.5% for Shionogi A, and 20.0%, 5.9% and 43.8% for Shionogi B slides. Likelihood ratio for the respective cancers was 1.4, 0.8 and 4.5 for Shionogi A, and 3.3, 1.0 and 7.5 for Shionogi B. Specificity was analogous among the three cancer sites, being 86% for Shionogi A and 94% for Shionogi B. These results suggest that the diagnostic validity of chemical occult blood tests for detecting cancers of the esophagus and the stomach is very poor, and therefore imply that close examinations of these sites for screening positives is unnecessary in mass screenings for colorectal cancer.

Adult↗

Synergistic effect of romurtide with ampicillin against pneumococcal pneumonia in mice.

The anti-infective activity of romurtide, a synthetic muramyl dipeptide (MDP) derivative, was evaluated in experimental pneumococcal pneumonia in mice deficient in the third component of complement (C3). The compound was found to be effective against the pneumonia in combination with subcutaneous ampicillin (ABPC). This synergistic effect of romurtide with ABPC was most pronounced when the compound was administered subcutaneously 1 day before infection. Romurtide alone, however, was not effective, irrespective of its treatment timing. Similarly, consecutive treatment with ABPC alone failed to kill pneumococci in the lungs completely, and resultant regrowth of the organisms provoked purulent pneumonia. In contrast, the combination treatment of romurtide with ABPC successfully prevented most of the mice from the purulent pneumonia: the initial infiltration of resident alveolar macrophages and subsequent accumulation of macrophages were observed in the pneumonic foci. In accordance with the occurrence of these cellular responses in the lungs, pneumococci were successfully eliminated from the lungs in mice treated with romurtide in combination with ABPC. Thus, romurtide was suggested to promote recovery of the mice with pneumococcal pneumonia by activating resident and accumulated macrophages in the pneumonic foci to eliminate pneumococci from the lung.

Acetylmuramyl-Alanyl-Isoglutamine↗

Cloning and nucleotide sequencing of the antitumor antibiotic C-1027 apoprotein gene.

The apoprotein gene for a chromoprotein antitumor antibiotic, C-1027, was cloned from the producer strain, Streptomyces globisporus C-1027, and sequenced. The process verified that; (1) the sequence included the entire structural gene directing a precursor of the apoprotein (pre-apoprotein having Met1---Ala33 leader peptide ahead of the apoprotein) and flanking regions, (2) the amino acid sequence of the apoprotein deduced from the base sequence perfectly matched the one based on protein analysis, (3) 3rd letters of the codons were 88% G or C, while the 1st plus the 2nd letters were 63% G or C, (4) the structural gene had 57% homology with that of macromomycin apoprotein (mcmA) while the flanking regions had little homology with the corresponding ones of mcmA, except some homology at the -10th and -35th promoter regions, and (5) the gene was transcribed as a monocistronic mRNA in an early growth phase, independent of chromophore production.

Amino Acid Sequence↗

Increase in the expression of thyroid hormone receptors in porcine granulosa cells early in follicular maturation.

Thyroid hormone has been demonstrated to synergize with FSH to exert stimulatory effects on the differentiation of porcine granulosa cells. In order to further characterize the nature of thyroid hormone action on granulosa cells, the presence of triiodothyronine (T3) receptors in the nuclei of porcine granulosa cells was examined, and qualitatively and quantitatively compared during follicular maturation. Then, comparative abilities of granulosa cells from varying follicle stages to respond to T3 were assessed in terms of FSH-induced LH/hCG receptor formation and progesterone secretion. Furthermore, the expression of erb-A was analyzed using Northern blot hybridization of porcine granulosa cell RNA with a v-erb-A probe. Binding experiments with [125I]T3 showed that granulosa cell nuclei obtained from small follicles had a greater ability to bind [125I]T3 compared to those from large follicles. Scatchard analysis revealed the presence of nuclear T3 receptors with a single class of binding sites. There was little difference in the affinity of the T3 receptors during follicular maturation. By contrast, the number of the T3 receptors was higher in small follicle granulosa cells compared to that in large follicle granulosa cells. Thus, the increased T3 binding to small follicle granulosa cells relative to large follicle granulosa cells appears to be attributable to the increased number of the nuclear T3 receptors rather than to a change in the affinity. The magnitude of the stimulatory effects of T3 on granulosa cell functions was maximal in small follicle granulosa cells, but negligible in large follicle granulosa cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Aminopeptidase activity of an antitumor antibiotic, C-1027.

An antitumor antibiotic C-1027, a complex protein consisting of an apoprotein and a non-covalently bound chromophore, showed some aminopeptidase activity, 1/15 (on the basis of activity per mg protein) that of porcine kidney enzyme [E.C. 3.4.11.2] by use of L-phenylalanyl 4-methyl-coumaryl-7-amide as the substrate. Neither the apoprotein alone nor the chromophore alone were active. Amastatin and bestatin but not leupeptin inhibited the activity. The enzyme activity of the holo-antibiotic, as opposed to that of the porcine kidney enzyme, was readily lost by UV irradiation, indicating that the intact structure of the chromophore was needed to maintain the native conformation of the holo-antibiotic. The cytotoxicity of the holo-antibiotic, but not that of the chromophore, to Ehrlich carcinoma cells in vitro was reduced to 1/5 by 1 microgram/ml of amastatin which alone had no effect on cell growth. The porcine aminopeptidase was not cytotoxic at all even at higher concentrations (higher enzyme activities/ml). Amastatin possibly occupied the catalytic domain of the holo-antibiotic, interfering with the binding of the holo-antibiotic with some cell-surface protein(s). Amastatin did not inhibit the holo-antibiotic to cleave isolated DNA.

Aminoglycosides↗

[Molecular biological studies on expression of placental CRF gene and its product].

Corticotropin releasing factor, a neuropeptide secreted by the hypothalamus, was recently found to be also secreted by the placenta. However, the biological role of placental CRF is obscure. In this study, we performed Northern blots and in situ hybridizations to determine the time course and site of placental CRF production. Then we measured maternal and fetal CRF, ACTH, cortisol and DHAS levels during the course of pregnancy. The results of these studies indicated that placental CRF mRNA is 1.5 kb in size and its expression increases dramatically near term. It was shown that placental CRF is transcribed in the cytotrophoblast layer. Both maternal and fetal CRF, ACTH and cortisol increased near term. The DHAS level was significantly higher on the fetal side than in the maternal plasma. It was assumed that on the maternal side, placental CRF activates the basal level of the pituitary-adrenal axis to produce more corticosteroids. The increased corticosteroids may compete with progesterone receptors and cause the removal of a progesterone block of uterine muscle contraction. On the fetal side, placental CRF activates the pituitary-adrenal axis to produce corticosteroids and DHAS. The increased corticosteroids may again compete with progesterone receptors. The increased DHAS directly affects the uterine cervix to cause ripening of it.

Adrenocorticotropic Hormone↗

[Effect of cyclic AMP and adenosine on hCG transcription by trophoblast cells].

It is well established that cAMP stimulates secretion of both alpha and beta subunits of hCG by trophoblasts. However, the molecular mechanism behind this phenomenon, especially that of beta subunit stimulation is still obscure. Moreover, while adenosine is known to play a pivotal role in the message transduction system of various cells, its effect on trophoblasts is not known. We therefore tried to answer these questions and found that cAMP stimulates hCG beta secretion by increasing transcription of its mRNA. However, no discrete cAMP responsive element like that seen in the hCG alpha gene seemed to be present in hCG beta transcriptional regulatory elements. It was assumed that hCG beta transcription is augmented indirectly by numerous trans acting elements which respond to cAMP. We have also shown that adenosine is a potent stimulator of hCG production. Its effect was synergistic with cAMP. It was therefore assumed that adenosine and cAMP are likely to act through different pathways.

Adenosine↗

Investigation of the mode of inheritance of insulin-dependent diabetes mellitus in Japanese subjects.

Previous studies have shown that insulin-dependent diabetes mellitus is positively associated with HLA-DR4 and HLA-DR9 in Japanese populations. It was proposed that susceptibility to the disease is determined by a single HLA allele associated with both DR4 and DR9. DR genotypes in a Japanese population with insulin-dependent diabetes mellitus were determined by DRB/DQB RFLP analysis. A single disease-susceptibility-allele model was tested by the antigen-genotype-frequency-among-patients method. Recessive and additive inheritance of a single susceptibility allele were rejected. The DR9-associated disease-susceptibility allele in Japanese subjects is distinct from both the DR3- and DR4-associated susceptibility alleles in white Caucasians. The data suggest further complexity in the inheritance of HLA-associated susceptibility to insulin-dependent diabetes mellitus.

Adult↗

[Experimental study on the stability of cementless porous coated endoprosthesis].

This study investigated cementless fixation of titanium porous coated endoprosthesis using canine weight-bearing model. Though immature and thin, ingrown trabeculae reached the deepest region of porous coating four weeks after implantation, and gradually matured and thickened thereafter. Pull-out tests of the porous stem at eight weeks showed excellent fixation with average ultimate pull-out force of 142 kgf and average ultimate shear strength of 2.6 GPa. Bone ingrowth rate gradually increased at the proximal and distal region of the stem and, conversely, it gradually decreased at the middle level, suggesting the dependence of bone ingrowth upon the distribution of the amount of stress transferred from implant to the femur. Severe bone remodeling was found on some specimens in which stress transfer was not physiological. Porous coated femoral stems achieve excellent fixation by bone ingrowth, but require physiological stress transfer in order to avoid significant bone remodeling after implantation.

Animals↗

[Surgical and non-surgical treatments of gallstones].

Comparisons were made of therapeutic modalities for gallstones. Four-hundred thirty-five patients with gallstones were operated on with the mortality rate of 0.7%. Extracorporeal shock-wave lithotripsy (ESWL) was performed in 84 patients with gallbladder stones. Complete stone disappearance rate at 1 year was 31% in patients with one to three radio-lucent stones not larger than 3cm in diameter and 57% in solitary stones up to 2cm with the US pattern of Ia or Ib. There was no major complication. Endoscopic sphincterotomy (EST) was performed in 131 patients with common bile duct stones. The success rate was for stone extraction, was 97%. Immediate complications occurred in 8% cases, yielding the mortality rate of 0.8%. Common bile duct stones recurred in 2 of 113 patients (3%). Acute cholecystitis was experienced in 2 of 43 patients with the gallbladder left in situ; 2 of 12 with and none of 31 without gallbladder stones. In conclusion, ESWL is a safe and effective treatment in selected patients. EST can be the first-choice modality in the treatment of not only the post-cholecystectomy cases but also the patients with the gallbladder without stones.

Adult↗

[Clinical evaluation of usefulness of cefixime (200 mg administered once daily) in the treatment of acute uncomplicated cystitis].

A comparative study of cefixime (CFIX), a new oral cephem antibiotic, was carried out at the Department of Urology, Nagoya University Hospital and its four affiliated hospitals to evaluate the clinical efficacy and safety of two dosage regimens of CFIX, given either in twice daily doses (BID group) or once daily dose (UID group), in the treatment of acute uncomplicated cystitis. Forty six female patients (BID group) were administered the daily dose of 200 mg in two divided doses for 3 days, 30 female patients (UID group) were administered 200 mg once daily for 3 days. The clinical efficacy was evaluated in 33 cases from the BID group and in 22 cases from the UID group, respectively, according to the criteria recommended by the Japan UTI Committee. In the BID group, the clinical efficacy was evaluated as excellent in 18 cases, moderate in 13 and poor in 2, with an overall clinical effectiveness rate of 94%. In the UID group, it was evaluated as excellent in 9 cases, moderate in 12 and poor in 1, with an overall clinical effectiveness rate of 96%. Safety was monitored in 71 patients, and only one case of stomatitis was seen in the UID group. This findings suggest that 200 mg once daily dosing regimen of cefixime is as effective as 100 mg twice daily dosing regimen in treatment of acute uncomplicated cystitis, and is well tolerated in terms of safety.

Acute Disease↗

Failure of cementless fixation of the femoral component in total hip arthroplasty.

The basic concepts involved in cementless fixation of the total hip arthroplasty femoral component have been controversial. Some clinicians advocate fixation only of the proximal portion of the stem so that weight-bearing loads will be transferred proximally, and proximal stress shielding will be avoided. Others advocate distal fixation to ensure rigidity of fixation but concede that it will lead to proximal stress shielding and bone loss. However, clinical evidence suggests that the design of the implant is one important factor in determining stress shielding. When the stem is smooth and cylindrical distally, proximal stress relief does not occur, even when the stem is fixed tightly distally. Because femoral component loosening is the most common clinical problem with cementless total hip arthroplasty, every effort should be made to achieve fixation of the implant. Proximal and distal fixation can be achieved with most of the available implants. For tight proximal fixation, a good proximal implant design and a precise line-to-line preparation technique are critical, but aggressive broaching and interference-fit techniques result in a high rate of proximal femoral fracture during preparation and implantation. When the conditions are good for excellent proximal fixation, a flexible stem should be selected to apply a large amount of stress proximally. The stress transferred through distal fixation will be small in this situation, and the reaming technique of the femoral diaphysis does not need to be very aggressive. Approximately 10 to 20 mm of tight distal fit combined with the 0.5-mm underreaming technique provides sufficient distal fixation, and the chance of distal femoral fracture during insertion of the stem is minimum with this technique. When conditions are unfavorable for excellent proximal fixation, such as in revision hip arthroplasty, or when a proximal deformity or osteoporosis is present, a relatively rigid stem should be selected to avoid overloading proximal fixation and, thus, generating large proximal micromotion. The stress transferred through distal fixation will be large in this situation, and a relatively aggressive but well-controlled reaming technique of the diaphysis is required. Approximately 20 to 40 mm of tight distal fit combined with a 0.5-mm underreaming technique is adequate to obtain sufficient distal fixation and still avoid distal femoral fracture. Implant design features that improve proximal fixation and instrumentation features that improve bone preparation and decrease the risk of failure will broaden the indications for cementless fixation. As fixation and instrumentation improve, more flexible implants can be developed to improve bone preservation and avoid proximal stress relief.(ABSTRACT TRUNCATED AT 400 WORDS)

Biomechanical Phenomena↗

[Control of house dust mites and mite allergens by special mite-preventive futon].

We studied the effect of a recently-developed special mite-preventive futon (bedding) on mite population and mite allergen contents (Der I and Der II) in asthmatic children and their families (23 sets) for 2 years. 1. The number of mites (vacuumed samples) in the 124 sets of futon for 2 years was 6.4 (SD +/- 8.8) in average in the mite-preventive futon which was significantly smaller than the number (about 1/10) in the control futon: 70.0 (SD +/- 99) (p less than 0.001). 2. Follow-up studies were made on the mite population about 2 years (3, 6, 9 12 and 27 months afterwards). The numbers of mites in all the mite-preventive futon was always 1/10 or less than that of in the control futon (p less than 0.01). 3. The mite allergens (Der I and Der II) were measured in the cotton stuffing of the futon used for 2 years. The mite allergen counts in the mite-preventive futon averaged about 1/24 of those in the control futon. 4. Airborne mite allergens (Der I and Der II) obtained by beating the futon were measured. The ratio of the mite allergen count in the mite-preventive futon to the control futon was found to be 1:22-264. These results indicate that the special mite-preventive futon always inhibit mite infestation at least 1/10 of that in the ordinary (control) futon and that the count of mite allergens in the cotton stuffing and in the airborne particles was even lower in the mite-preventive futon.

Adult↗

[Development of ligament-bone junction in anterior cruciate ligament reconstruction with the scaffold type polyester artificial ligament (Leeds-Keio) in the dog].

The anterior cruciate ligament (ACL) was reconstructed in sixty mongrel dogs with artificial ligament (Leeds-Keio). The tibial ligament-bone junction was completely removed before the reconstruction in order to investigate the remodelling process of the junction. The dogs were divided into five groups. In all of these the artificial ligament was taut when implanted except for one group which had deliberately a slack reconstruction. In three groups the reconstructions included the use of a strip of infrapatellar synovium alone or with a strip of fascia lata within or outside the artificial ligament. After two, four, twelve and twenty-four weeks, the tibial junction was investigated macroscopically, histologically and by means of microangiography. Newly formed fibrocartilage and functionally aligned collagen were observed in the junction 12 weeks after the initial surgery in all groups, but not in the group with a slack reconstruction. From the results of this study, it was concluded that infrapatellar synovial transfer improved tissue induction in the early stages, and further, the additional use of the fascia speeded up the remodelling process.

Animals↗

Modulation of methotrexate cytotoxicity with natural interferon upon human leukemia cell line HL-60.

The effect of alpha- and gamma-interferon on methotrexate cytotoxicity against human promyelocytic cell line HL-60 has been evaluated. Synergistic inhibition of proliferation is observed with the combination of methotrexate and gamma-interferon. Enhanced cytotoxic effect of methotrexate with alpha- or gamma-interferon is removed by adding thymidine to the growth medium. The depletion of folate pools caused by methotrexate is enhanced in presence of interferons, this depletion is also removed by adding thymidine to the growth media. Synchronization of HL-60 cells in 'S' phase of cell cycle caused by methotrexate is enhanced in the presence of interferons. These results suggest that specially gamma-interferon changes the cellular environment of HL-60 cells in such a way as to make methotrexate more potent cytotoxic agent to HL-60 cells causing cell death. This study also clearly indicates the biochemical role of thymidine in modulating the activity of methotrexate in combination with interferons.

Biological Transport↗

Purification and primary structure of C-1027-AG, a selective antagonist of antitumor antibiotic C-1027, from Streptomyces globisporus.

C-1027-AG, a selective antagonist of antitumor antibiotic C-1027, was isolated by column chromatography on DEAE-cellulose, butyl-Toyopearl and Sephadex G-50 from a culture filtrate of Streptomyces globisporus. The amino acid sequence of purified C-1027-AG was determined with a protein sequencer on the basis of fragment peptides obtained by enzymatic hydrolysis with lysylendopeptidase, V8 protease, endopeptidase AspN and chymotrypsin, after performic acid oxidation. C-1027-AG is shown to consist of a single polypeptide chain cross-linked by two disulfide bonds, and to contain a total of 110 amino acid residues with alanine and glycine as its amino- and carboxyl-termini, respectively; its molecular weight was calculated to be 10,500 daltons. The primary structure of C-1027-AG is indicated to be identical to the protein moiety of C-1027, and is highly homologous to the sequences of antitumor proteins obtained from other Streptomyces species.

Amino Acid Sequence↗