Japan bans pill through fear of HIV.
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Acquired Immunodeficiency Syndrome↗
Biomedical subjects
M Yamauchi
Publications and source records attributed to M Yamauchi.
Expression of MDR1 and glutathione S transferase-pi genes and chemosensitivities in human gastrointestinal cancer.
The relationship was analyzed between drug resistance and MDR1 (with MDR signifying multiple drug resistance) and glutathione S transferase-pi (GST-pi) gene expression in four stomach and four colon cancer cell lines. Northern blot analysis by pmdr1 probe showed that stomach cancer cell lines had no detectable level of MDR1 mRNA expression. By contrast, some levels of MDR1 mRNA expression were found in two colon cancer cell lines, indicating doxorubicin resistance. To examine the MDR1 mRNA in each cell level, in situ hybridization was used. It was found that all colon cell lines and two stomach cell lines had more silver grains per cell than KB cells (a human KB kidney epidermoid carcinoma cell line). However, the number of silver grains in each cell was heterogeneous in the colon and stomach cell lines. Low-level MDR1 mRNA expression could be detected even in cell lines without MDR1 mRNA expression by northern blot hybridization. These results suggest the possibility that all gastrointestinal cell lines can acquire multiple drug resistance. In addition, all examined gastrointestinal cell lines had high GST-pi mRNA expression. This GST-pi gene expression shows cisplatin resistance in the examined cell lines. Heterogeneity of GST-pi mRNA expression also was shown at the cellular level.
Adenocarcinoma↗
Cross-linking connectivity in bone collagen fibrils: the COOH-terminal locus of free aldehyde.
Quantitative analyses of the chemical state of the 16c residue of the alpha 1 chain of bone collagen were performed on samples from fetal (4-6-month embryo) and mature (2-3 year old) bovine animals. All of this residue could be accounted for in terms of three chemical states, in relative amounts which depended upon the age of the animal. Most of the residue was incorporated into either bifunctional or trifunctional cross-links. Some of it, however, was present as free aldehyde, and the content increased with maturation. This was established by isolating and characterizing the aldehyde-containing peptides generated by tryptic digestion of NaB3H4-reduced mature bone collagen. We have concluded that the connectivity of COOH-terminal cross-linking in bone collagen fibrils changes with maturation in the following way: at first, each 16c residue in each of the two alpha 1 chains of the collagen molecule is incorporated into a sheet-like pattern of intermolecular iminium cross-links, which stabilizes the young, nonmineralized fibril as a whole. In time, some of these labile cross-links maturate into pyridinoline while others dissociate back to their precursor form. The latter is likely due to changes in the molecular packing brought about by the mineralization of the collagen fibrils. The resultant reduction in cross-linking connectivity may provide a mechanism for enhancing certain mechanical characteristics of the skeleton of a mature animal.
Aldehydes↗
Collagen cross-linking of skin in patients with amyotrophic lateral sclerosis.
Collagen cross-links of skin tissue (left upper arm) from 11 patients with amyotrophic lateral sclerosis (ALS) and 9 age-matched control subjects were quantified. It was found that patients with ALS had a significant reduction in the content of an age-related, stable cross-link, histidinohydroxylysinonorleucine, that was negatively correlated with the duration of illness. The contents of sodium borohydride-reducible labile cross-links, dehydro-hydroxylysinonorleucine and dehydro-histidinohydroxymerodesmosine, were significantly increased and were positively associated with the duration of illness (r = 0.703, p less than 0.05 and r = 0.684, p less than 0.05, respectively). The results clearly indicate that during the course of ALS, the cross-linking pathway of skin collagen runs counter to its normal aging, resulting in a "rejuvenation" phenomenon of skin collagen. Thus, cross-linking of skin collagen is affected in ALS.
Aged↗
Rapid preparation of diagnostic probes for the fragile X syndrome by direct PCR amplification of human chromosomal DNA.
The fragile X syndrome is a common familial form of mental retardation and is associated with a rare fragile site at Xq27.3 (FRAXA). This disorder has recently been reported to correlate with length variations of restriction genomic DNA fragments which may due to the amplification of (CCG)n trinucleotide repeats located at the FRAXA locus. We described here a rapid preparation method of diagnostic DNA probes for the fragile X syndrome by direct enzymatic amplification of human chromosomal DNA. The PstI-assay, which is Southern blot analysis of DNA samples probed by PCR products, was shown to be sensitive method for diagnostic purposes to detect the size variations specific in the fragile X syndrome.
Base Sequence↗
Decreased heterotopic osteogenesis in vitamin-D-deficient, but normocalcemic guinea pigs.
The effect of vitamin D deficiency unhampered by hypocalcemia on de novo bone formation was studied in guinea pigs. Heterotopic induction of osteogenesis was evaluated 4 weeks after intramuscular transplantation of allogenic urinary bladder transitional epithelium from vitamin-D-repleted (+D) donors into +D and -D recipients. In -D recipients the frequency of osteogenesis and the amount of induced bone were significantly diminished; induced bone was less mature, scantly cellular woven bone poorly repopulated with bone marrow. No effect of vitamin D deficiency on orthotopic bone growth and on mineralization of orthotopic and heterotopically induced bone was observed. It is proposed that in addition to inducing factors (BMPs, growth factors) which may be responsible for transformation of mesenchymal cells to osteoprogenitor cells, normal concentrations of 1,25-(OH)2D3 may be required for proliferation and further differentiation of these cells into osteoblasts and for expression of genes engaged in extracellular matrix formation and maturation.
Alkaline Phosphatase↗
Prediction of doxorubicin resistance in gastrointestinal cancer by P-glycoprotein staining.
Feasibility of immunohistochemical staining of P-glycoprotein for the prediction of doxorubicin resistance in gastrointestinal cancers was examined. Among 10 cancer cell lines which consist of two gastric cancer cell lines and eight colon cancer cell lines, seven cell lines were stained positively by the monoclonal antibody to P-glycoprotein, C219. In consequence of the evaluation on the effect of doxorubicin on these tumour cells by means of succinic dehydrogenase inhibition test (SDI test), zero out of seven cell lines stained positively by C219 was sensitive to doxorubicin, but two out of three cell lines stained negatively were sensitive. Among 23 fresh surgical specimens of gastrointestinal cancers which consisted of 15 gastric cancers and eight colon cancers, seven tumour tissues were stained positively by C219. All P-glycoprotein positive tumours were resistant to doxorubicin. On the other hand, four of 16 P-glycoprotein tumours were sensitive to doxorubicin. These data indicate that positively stained cancer cells by C219 are resistant to doxorubicin.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Polyoxyethylene-modified superoxide dismutase reduces side effects of adriamycin and mitomycin C.
Polyoxyethylene-modified superoxide dismutase (SOD-POE) is a newly developed long-acting superoxide dismutase. Adriamycin (ADR) and mitomycin C (MMC) generate superoxide, which contributes to their cytocidal effects or side effects. We examined whether SOD-POE could prevent the side effects induced by superoxide generated by antitumor agents, and the following results were obtained. SOD-POE did not influence the antitumor effects of ADR and MMC either in vitro or in vivo, but prevented the toxic death of BALB/c, nu/nu male mice caused by overdoses of ADR or MMC. As for its effective sites, SOD-POE prevented a decrease in the specific activity of rotenone-sensitive NADH-ubiquinone oxido-reductase (complex I) in heart muscle mitochondrial respiratory chain function in BALB/c male mice administered 10 mg/kg ADR, and prevented damage to the sarcoplasmic reticulum and mitochondria of mouse heart muscle by ADR as observed by electron microscopy. Furthermore, SOD-POE prevented bone marrow suppression induced by MMC in Donryu rats. The above results suggest that combination chemotherapy with SOD-POE would make it possible to increase the maximum permissible doses of antitumor agents, improving the efficacy of these agents.
Animals↗
Endothelium-dependent and -independent relaxation by dopamine in the rabbit pulmonary artery.
1. The relaxing response of dopamine (DA) was studied in the rabbit pulmonary artery. DA caused concentration-related relaxation in helically cut strips of the artery contracted with prostaglandin F2 alpha in the presence of prazosin. 2. The DA-induced relaxation in endothelium-denuded strips was reduced to about 40% compared with that in endothelium-intact strips. 3. Methylene blue and haemoglobin, inhibitors of endothelium-dependent relaxation, reduced the DA-induced relaxations in endothelium-intact strips to the level of endothelium-denuded strips. These results indicate that the DA-induced relaxation is partially mediated or modified by the release of endothelium-derived relaxing factor (EDRF). 4. Apomorphine, as a DA agonist, caused concentration-dependent relaxation in endothelium-intact strips. Bromocriptine, a DA2 agonist, produced only a little relaxation at higher concentration. 5. In endothelium-intact strips, haloperidol, a DA antagonist, and the DA1 antagonists, fluphenazine and SCH 23390 inhibited DA-induced relaxations. On the other hand spiperone and domperidone, DA2 antagonists, were inactive. 6. In endothelium-denuded strips, fluphenazine and SCH 23390 inhibited DA-induced relaxations, but domperidone was inactive. 7. These results indicate that the DA-induced relaxation is mediated by DA receptors, and that DA1 receptors are involved in both endothelium-dependent and -independent relaxation in the rabbit pulmonary artery.
Animals↗
Glutamate and aspartate are decreased in the skin in amyotrophic lateral sclerosis.
We measured the levels of amino acids in biopsied skin from eight patients with amyotrophic lateral sclerosis (ALS) and seven controls. The most conspicuous changes in ALS patients were as follows. First, the contents of the acidic amino acids glutamate and aspartate were significantly decreased in ALS, and were negatively and significantly associated with the duration of illness. Second, the levels of the collagen-associated amino acids hydroxyproline, proline, glycine, alanine, and hydroxylysine were significantly decreased in ALS, and correlated inversely with the duration of illness. These results suggest that there are abnormalities of acidic amino acids and collagen-associated amino acids in the skin of patients with ALS. These changes may underlie the pathogenesis of ALS.
Aged↗
Induction of a BrdU-enhanceable fragile site-like lesion and sister chromatid exchanges at 11q23.1 in EBV-transformed lymphoblastoid cell lines.
We examined the expression of a fragile site-like lesion and induction of sister chromatid exchanges (SCEs) at 11q23.1 in EBV-transformed lymphoblastoid cell lines derived from carriers of distamycin A-inducible fragile sites and ataxia telangiectasia patients. The fragile site-like lesion at 11q23.1 was found to be BrdU-enhanceable in all cell lines examined, and the expression frequencies increased linearly with the rates of BrdU substitution in replicated DNA. In addition, an increased frequency of SCEs was observed at 11q23.1 on the expressed chromosome. Thus, the BrdU-enhanceable fragile site-like lesion at 11q23.1 is a "hot spot" for the formation of SCEs, as has been reported for other rare and common fragile sites.
Bromodeoxyuridine↗
Amyotrophic lateral sclerosis: increased solubility of skin collagen.
We studied the solubility of skin collagen from six patients with amyotrophic lateral sclerosis (ALS) and six controls. The amount of collagen extracted with neutral salt solution was significantly greater in patients with ALS than in controls. In addition, there was a statistically significant increase in the proportion of collagen extracted from ALS patients with increased duration of illness. The collagen solubilized by pepsin and cyanogen bromide treatments was significantly higher in ALS patients than in controls, and its proportion was positively and significantly associated with duration of illness in ALS patients. These results indicate that the metabolism of skin collagen may be affected in the disease process of ALS, causing an increase in immature soluble collagen in the tissue, which is the opposite to that which occurs in the normal aging process.
Amyotrophic Lateral Sclerosis↗
Tactile sensibility of sapphire endosseous dental implants.
Experiments are described in which the tactile thresholds of sapphire (bioceram) endosseous implants were measured and compared with those of natural teeth. The effects of local anaesthesia were determined in an attempt to localize the mechanoreceptors involved. The thresholds of the implants were higher than those of natural teeth but lower than those of another type of implant (alumina tubingen) examined in another study. The results of local anaesthesia testing indicated that the sensory receptors involved were located in the connective tissues around the implant.
Adult↗
[A case of hCG-producing large cell carcinoma of the lung--clinical utility of serum hCG levels].
We describe a case of hCG-producing large cell carcinoma of the lung in a 73-year-old man who had gynecomastia associated with high serum concentration of hCG. Serum hCG levels fluctuated in parallel with the response of the cancer to surgery, chemotherapy, and radiotherapy. The patient was admitted to our hospital with a huge mass shadow in the right lung filed on chest X-ray film on July 31, 1989. Physical examination revealed bilateral gynecomastia. Serum hCG and beta-hCG were 1108.0 mIU/ml (Normal less than 2.0) and 31.9 ng/ml (Normal less than 1.0), respectively. Clinical staging was T2N1M0, determined by radioisotope scanning of bone, and CT scans of the chest, brain and upper abdomen. Right upper and middle lobectomy with mediastinal lymph node dissection was performed on August 18, 1989. The tumor, 6 x 6 x 8 cm in size, was located in the middle lobe and was histologically confirmed to be large cell carcinoma of the lung. A few of small nodules found on the surface of the middle lobe at thoracotomy were histologically proved to be pleural dissemination. Metastatic involvement was present in the hilar and mediastinal lymph nodes. The pathological stage was concluded to be T4N2M0. Immunohistochemistry showed positive staining reaction for hCG within some of the tumor cells. Three weeks after the operation, serum hCG had decreased rapidly but did not reach the normal range. Two courses of DDP, VDS, and MMC were given at four week intervals. Following chemotherapy, serum hCG decreased to the normal range. He was discharged from our hospital on November 29, 1989.2+ useful parameter for the evaluation of treatment and the prediction of prognosis.
Aged↗
[The incidence of alcoholic liver disease in Japan].
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Adult↗
Elastin content, cross-links, and mRNA in normal and aneurysmal human aorta.
Although elastin depletion is thought to be an etiologic factor in abdominal aortic aneurysm, little is known about its transcription and posttranslational modification in normal and diseased human aorta. Our objectives were to quantify total elastin and elastin cross-links (desmosine/isodesmosine [DID]) and to determine if elastin mRNA was detectable in the disease-prone infrarenal aorta from patients with abdominal aortic aneurysm and a comparative group with no aneurysmal diseases. After preliminary extraction and thermolysin digestion, content of DID and the elastin tetrapeptide, valine-alanine-proline-glycine (VAPG), were determined by high-performance liquid chromatography. Tissue mRNA was studied by Northern blot analysis. Mean values (+/- SE) were compared by Student's t test. The proportion of insoluble elastin was markedly decreased in abdominal aortic aneurysm tissue (1.3% +/- 0.04% vs 12% +/- -2.8%; p less than 0.001). There was no difference in the small percentage of elastin solubilized during extraction in abdominal aortic aneurysm (5.3% +/- 1%) and no aneurysmal disease (6.0% +/- 1.2%; p = 0.71) tissues. The DID concentration of insoluble elastin was not different for abdominal aortic aneurysm and no aneurysmal disease tissue (0.18% +/- 0.07 vs 0.18 +/- 0.05 nm DID/nm VAPG; p = 0.97). On the basis of VAPG content, only 26% +/- 4% of the sodium hydroxide insoluble residue from abdominal aortic aneurysm was elastin; the predominate protein(s) was high in polar amino acids. Elastin mRNA was detectable in all tissues.(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗
[Large volume intraperitoneal chemotherapy as treatment for the peritoneal carcinomatosis from gastric cancer].
Gastric cancer sometimes spread to peritoneal surfaces in the absence of lymphatic or hematogenous metastases. For the treatment of peritoneal carcinomatosis, we applied large volume intraperitoneal chemotherapy (L.V.I.C.). In L.V.I.C., drugs were administered with large volume of saline through the reservoir buried in the subcutaneous tissue of the abdominal wall. We used mitomycin C (MMC), 5-fluorouracil (5-FU) and CDDP and examined the pharmacokinetics of these drugs when they were administered by this method to the patients of peritoneal carcinomatosis. A marked pharmacokinetic advantage was observed when 5-FU and CDDP were administered. AUC of these drugs were much larger than that of MMC. In vitro sensitivity test (SDI test) was useful for the selection of adequate drugs for each patient. On this method, drugs were distributed widely in the abdominal cavity and the patients could be taken this treatment repeatedly as out-patient. L.V.I.C. seems to fulfill the need for a safe, effective and acceptable delivery system of intraperitoneal chemotherapy.
Antineoplastic Combined Chemotherapy Protocols↗
[A case of limited form of Wegener's granulomatosis associated with persistent high titer of serum antineutrophil cytoplasmic antibodies].
A thirty-six year-old male was admitted to our hospital because of a two year history of orbital mass. He had experienced inflammatory tumor of right lung six years before admission. Both the lung tumor and orbital mass were revealed as chronic panarteritis with diffuse necrotizing lesions. He was treated with low dose prednisolone, but the orbital mass gradually enlarged. We detected fluorescent cytoplasmic pattern of antineutrophil cytoplasma antibodies (ANCA) by the indirect immunofluorescence method (IF). We ascertained this case to be a limited form of Wegener's granulomatosis (WG) by histopathological finding and positive ANCA. The value of ANCA, estimated by enzyme linked immunosorbent assay (ELISA) was rather higher than that of generalized form of WG in other reports. There was no reduction of the size of orbital mass and the value of ANCA despite strong immunosuppressive therapy. In this case, the value of ANCA didn't represented disease activity. The presence of histopathological findings such as those observed in the present patient, i.e., abnormally high ANCA levels not associated with disease severity or progression, which are not in accordance with those conventionally reported, was considered very interesting in terms of the prevailing beliefs concerning involvement of ANCA in the mechanism of onset of WG.
Adult↗