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Biomedical subjects

S Takai

Publications and source records attributed to S Takai.

At least 127 records · Page 7Linked to original sources
PubMed1998

High proportion of missense mutations of the BRCA1 and BRCA2 genes in Japanese breast cancer families.

Mutations in either of two recently identified genes, BRCA1 and BRCA2, are thought to be responsible for approximately two-thirds of all cases of autosomal-dominantly inherited breast cancer. To examine the nature and frequency of BRCA1 and BRCA2 mutations in Japanese families exhibiting a high incidence of breast cancer, we screened 78 unrelated families in this category for mutations of these two genes. Examining the entire coding sequences as well as exon-intron boundaries of both genes by polymerase chain reaction (PCR) single-strand conformation polymorphism (SSCP) and multiplex-SSCP analysis, we identified possible disease-causing alterations in BRCA1 among affected members of 15 families and in BRCA2 in another 14 families. In 15 of those 29 families, the affected individuals carried missense mutations, although most germline mutations reported worldwide have been deletions or nonsense mutations. Our results, indicating that missense mutations of BRCA1 and BRCA2 tend to predominate over frameshifts or nonsense mutations in Japanese breast cancer families, will contribute significantly to an understanding of mammary tumorigenesis in Japan, and will be of vital importance for future genetic testing.

BRCA2 Protein↗
PubMed1998

Induction of angiotensin converting enzyme and angiotensin II receptors in the atherosclerotic aorta of high-cholesterol fed Cynomolgus monkeys.

Antiatherogenic effects of imidapril and involvement of renin angiotensin system were examined in experimental atherosclerosis induced by feeding a high-cholesterol diet to Cynomolgus monkeys. Eighteen male monkeys were divided into three groups and placed under (1) normal diet (normal group), (2) high-cholesterol diet (control group), (3) high-cholesterol diet with imidapril (20 mg/kg body wt/day, orally) treatment (imidapril group). At the end of the experiment, the normal group showed no apparent atherosclerosis in their aorta evaluated by oil red-O staining, while the control group exhibited marked atherosclerotic involvement of the intimal surface of the aorta (58.4 +/- 9.3%, P < 0.01). Imidapril reduced systolic blood pressure and atherosclerotic involvement (24.1 +/- 5.5%, P < 0.05). Total cholesterol content of the descending thoracic aorta was also significantly reduced in the imidapril group. In the atherosclerotic vessels, angiotensin converting enzyme (ACE) activity evaluated by quantitative in vitro autoradiography was significantly increased in the intimal lesion. Further evaluation revealed angiotensin II (Ang II) type I (AT1) receptor density was significantly increased in the medial lesion and type II (AT2) receptor density in the adventitia. When the progression of atherosclerosis was impeded by imidapril treatment, the ACE activity level as well as the AT1 and AT2 receptor density remained at normal. Expression of mRNA for fibronectin, TGF-beta1, types I and III collagen was studied by Northern blot analysis. No significant differences in types I and III collagen mRNA levels were found between the control and imidapril group. On the other hand, mRNA expression for fibronectin and TGF-beta1 were much lower in the imidapril group than in the control group. These results suggest that increased production of Ang II and activated receptors may be involved in atherosclerotic process in this model and also antiatherogenic effect of imidapril may be derived from reduction of local Ang II production as well as its hypotensive action.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1998

Pathogenicity of Rhodococcus equi strains possessing virulence-associated 15- to 17-kDa and 20-kDa antigens: experimental and natural cases in pigs.

The pathogenic role of Rhodococcus equi in pigs remains controversial. Small numbers of pigs were inoculated intravenously (i.v.), or intramuscularly (i.m.) around the mouth, with a virulent, an intermediately virulent, or an avirulent strain of R. equi and killed 14 days later. None showed clinical signs other than transient fever and weight loss. The virulent and intermediately virulent strains were recovered in culture from various organs and lymph nodes of pigs inoculated i.v., but only from the mandibular lymph nodes of pigs inoculated i.m. The avirulent strain was not recovered from any site. None of the pigs developed macroscopically visible lesions, but they showed reactive hyperplasia of the mandibular lymph nodes. The latter contained scattered phagocytic cells, which were labelled immunohistochemically for virulence-associated antigens (15- to 17-kDa antigens or 20-kDa antigen). Intermediately virulent and virulent strains of R. equi were isolated from mandibular lymph nodes of 5.5% of apparently healthy abattoir pigs (n = 1615). Virulence-associated antigens were detected in phagocytic cells of culture-positive nodes, but the latter showed no lesions other than reactive lymphoid hyperplasia. The results would seem to question the pathogenic role of R. equi in pigs, and it is speculated that the organism survives in the lymph nodes without causing pathognomonic lesions.

Actinomycetales Infections↗
PubMed1998

Prolonged decreases in plasma nitrate levels at early postoperative phase after hepato-pancreato-biliary surgery.

Nitric oxide (.NO) is known to influence circulatory, neural, immunologic, and metabolic alterations. To evaluate the clinical significance of .NO production under surgical stress, serial measurements of plasma nitrite plus nitrate levels were performed in 45 surgical patients. Group A included 19 patients who underwent major surgery with uneventful postoperative courses. Group B included 18 patients who underwent laparoscopic cholecystectomy. Group C included 8 patients whose surgery was complicated by intra-abdominal abscesses. Eight healthy volunteers served as controls. Plasma nitrate levels were determined with a redox chemiluminescence .NO analyzer and coincided with measurements made by high-performance liquid chromatography (r = 0.868, p < 0.0001, 58 samples). During laparotomy, arterial nitrate levels correlated well with peripheral, portal, and hepatic venous nitrate levels (r = 0.966, 0.938, and 0.949, respectively; p < 0.0001). A significant decrease in nitrate from preoperative levels in groups A (postoperative day (POD) 1 and 3; p < 0.0005) and B (POD 1, p < 0.0001) was observed; nitrate levels in group C did not decrease for 14 days after surgery. Plasma nitrate levels in groups A and B were significantly different (POD 1 through 6, p < 0.05) and at POD 3 were significantly lower in group A (p < 0.005). Plasma nitrate levels measured before and after fasting or food intake were not significantly different. These results suggest that surgical stress leads to a decrease in the end product of .NO in the whole body, and that the greater the surgical stress the longer the duration of decreased .NO production.

Adult↗
PubMed1998

Arthroscopic treatment of voluntary superior dislocation of the patella.

The patient, a 45-year-old woman who complained of crepitation and locking of her patella, had a voluntary superior dislocation of the patella and was arthroscopically treated. Radiography showed patella alta and osteoarthrosis in the patellofemoral joint. Fluoroscopy showed that, during active contraction of the quadriceps muscle, the tip of the osteophyte on the inferior edge of the patella was positioned at the same level as the osteophyte on the superior margin of the articular surface of the medial femoral condyle. The inferior edge of the patella could be made to catch on the femoral osteophyte by application of slight pressure to the patella. Arthroscopic resection of the osteophte was performed, and the postoperative course was uneventful. The patient reported no difficulty when she was last seen 1 year after the operation.

Arthroscopy↗
PubMed1998

Antitumor effect of medium-chain triglyceride and its influence on the self-defense system of the body.

Medium-chain triglyceride (MCT), long-chain triglyceride (LCT), and their mixture were compared in reference to both cytotoxic effect against human tumor cells and influence on the immune system. MCT showed more potent cytotoxicity than LCT. Continuous contact with MCT also inhibited the cytotoxic effect of lymphokine-activated killer (LAK) cells much more strongly than LCT. However, there is a discrepancy between the concentration of MCT, or the mixture, that could suppress the growth of tumor cells and the concentration that inhibited the cytotoxicity of LAK cells. Moreover, no damage was observed in PBL or LAK cells or in their cytotoxicity when the cells were incubated with TG for 2 h a day. Thus, short-term contact with TG could inhibit tumor growth while immune system was maintained within normal range. Clinically fine control of the concentration of injected triglycerides, especially MCT, can be expected to provide potent antitumor effect and maintenance of normal immune system.

Antineoplastic Agents↗
PubMed1998

Roles of vascular angiotensin converting enzyme and chymase in two-kidney, one clip hypertensive hamsters.

BACKGROUND: A chymase-dependent angiotensin II-forming pathway is present in human vascular tissues; however, the role, if it plays any, of chymase in the pathogenesis of hypertension is not known. When investigating the role of chymase, it is important to recognize marked differences in vascular angiotensin II-forming systems among species. We found recently that hamsters, like humans, possess the dual angiotensin II-forming system. OBJECTIVE: To analyze the potential involvement of angiotensin converting enzyme and chymase in the pathogenesis of hypertension, and to further characterize the efficiency of angiotensin converting enzyme inhibitors and angiotensin II receptor antagonists for the treatment of hypertension. METHODS AND RESULTS: The mean arterial pressure in the two-kidney, one clip hamster model had increased significantly 2 weeks after clipping (acute stage), reached a peak after 4 weeks, and was sustained at the high level until 32 weeks after clipping (chronic stage). Plasma renin activity increased markedly during the acute stage, but returned to the normal level during the chronic stage. Vascular angiotensin converting enzyme activity during 4-32 weeks after clipping was significantly higher than that in the control hamsters. By contrast, vascular chymase was not activated throughout the experimental period. Administrations of an angiotensin converting enzyme inhibitor, trandolapril, and an angiotensin II receptor antagonist, CV-11974, equally lowered the mean arterial pressure during the acute and chronic stages. CONCLUSIONS: Vascular angiotensin converting enzyme plays a predominant role in the maintenance of two-kidney, one clip hypertension in hamsters, which, like humans, possess a dual system of formation of angiotensin II. Vascular chymase was not involved in the pathogenesis of two-kidney, one clip hypertension in the hamster.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1998

Functional role of chymase in angiotensin II formation in human vascular tissue.

Recent reports suggested that human heart chymase contributed little to angiotensin (Ang) II formation in the presence of natural protease inhibitors such as alpha-antitrypsin. We studied whether chymase could contribute to Ang II formation in the presence of natural protease inhibitors in the homogenate, the extract, and slices of human vascular tissue, and whether these inhibitors affect Ang I-induced vasocontractile responses due to chymase. In the homogenate, lisinopril, chymostatin, and alpha-antitrypsin inhibited the formation of Ang II by 14, 92, and 74%, respectively. In the extract, the inhibition of Ang II formation by lisinopril, chymostatin, and alpha-antitrypsin was 18, 94, and 93%, respectively. In the slices, lisinopril and chymostatin inhibited Ang II formation by 5 and 90%, respectively. However, unlike the homogenate and the extract experiments, only 8% of the Ang II formation was suppressed by alpha-antitrypsin. In isolated human gastroepiploic artery, 30% of Ang I-induced vasoconstriction was blocked by lisinopril, and the rest was completely eliminated by a combination of lisinopril and chymostatin. On the other hand, alpha-antitrypsin was ineffective in blocking Ang I-induced vasoconstriction in the presence of lisinopril, which demonstrates that Ang II formation is dependent on chymase. These findings suggest that chymase in human vascular tissue plays a functional role in Ang II formation in the presence of natural protease inhibitors such as alpha-antitrypsin.

Angiotensin I↗
PubMed1998

Cutaneous malakoplakia in pigs inoculated with Rhodococcus equi.

Cutaneous malakoplakia was observed in pigs inoculated intramuscularly with Rhodococcus equi strains of intermediate virulence. Macroscopically, the inoculation sites showed the indurated swelling of the skin. Histopathologically, abscess formation with histiocytic granulomatous reaction was observed. Many macrophages contained target or owl-eye shaped hematoxyphil intracytoplasmic inclusions or calcosherites (Michaelis-Gutmann bodies) of various sizes. The Michaelis-Gutmann bodies were also seen outside of the macrophages. Histochemically, most Michaelis-Gutmann bodies stained positively with the von Kossa silver method and periodic acid Schiff. Immunohistochemically, some of Michaelis-Gutmann bodies were stained by two rabbit polyclonal antibodies (rabbit anti-A5 serum and rabbit anti-ATCC 33701 serum) and a mouse monoclonal antibody (anti-20-kDa antigen monoclonal antibody). This is the first report of cutaneous malakoplakia in domestic animals, which also revealed the relationship between R. equi infection and malakoplakia immunohistochemically. This experimental swine model is useful to investigate the morphogenesis of Michaelis-Gutmann bodies in malakoplakia through chronological skin biopsies.

Actinomycetales Infections↗
PubMed1998

Delayed aseptic swelling after fixation of talar neck fracture with a biodegradable poly-L-lactide rod: case reports.

A 63-year-old woman complained of acute swelling and pain in her ankle at 15 months, after fixation of a talar neck fracture with poly-L-lactide rods. Roentgenographic and laboratory data revealed no abnormalities, but T1-weighted magnetic resonance imaging showed a diffuse area of low intensity in the talus. After nonweightbearing for 1 month, local findings had disappeared and the area of low intensity shown by magnetic resonance imaging had decreased without surgical treatment. Although there have been some reports of aseptic swelling or synovitis after fixation of a fracture with polyglycolide rods or screws, there has been no report of such cases with poly-L-lactide rods or screws.

Acute Disease↗
PubMed1998

Improved electroporation of Rhodococcus equi.

The condition of an electroporation method was re-evaluated for the introduction of foreign plasmid DNA into Rhodococcus equi. The method is based on an electroporation of the bacteria made competent by culturing in a broth containing glycine and by heat shock at 50 degrees C. Transformation of R. equi could be achieved with a chloramphenicol-resistant shuttle vector originating from Rhodococcus fascians at an efficiency of about 10(4) transformants/microgram DNA. The bacteria were also shown to become competent when they were incubated with a chemical transformation buffer prior to washing with an electroporation buffer.

Culture Media↗
PubMed1998

Familial isolated hyperparathyroidism caused by single adenoma: a distinct entity different from multiple endocrine neoplasia.

Familial hyperparathyroidism (FHPT) is a hereditary disease where hyperparathyroidism (HPT) is transmitted in an autosomal dominant fashion. FHPT consists of a variety of diseases such as multiple endocrine neoplasia type1 (MEN 1) and type2 (MEN 2), familial isolated hyperparathyroidism (FIHPT) with single adenoma and with multiple adenomas (or hyperplasia), and FHPT with jaw-tumor (FHPT-JT). Isolation of the genes responsible for MEN1, and 2, i.e. MEN1 and RET, respectively, makes it possible to examine the relations among disorders constituting FHPT. We studied germ-line mutations in these 2 genes in a family of FHPT with single parathyroid adenoma. The disorder in this family was proved to be an entity different from MEN1 because no germ-line mutations in MEN1 gene were found in the affected members. The loss of heterozygosity (LOH) at MEN1 gene and PYGM were not found in the abnormal parathyroid in this family, supporting the above conclusion. No mutations in exons 10, and 11 of RET proto-oncogene was found in germ-line DNA of the affected member of the family, suggesting no relation to MEN2A. Linkage study excluded the possibility of FHPT-JT syndrome. PRAD1 was not overexpressed in the parathyroid tumors in this family. The relation of this disorder to FIHPT with multiple enlarged parathyroid glands remains to be clarified. A search for the gene(s) predisposing to FIHPT is needed.

Adenoma↗
PubMed1998

Prognostic impact of urokinase-type plasminogen activator (PA), PA inhibitor type-1, and tissue-type PA antigen levels in node-negative breast cancer: a prospective study on multicenter basis.

Urokinase-type plasminogen activator (u-PA) is a key protease in cancer invasion and metastasis. Recent studies demonstrated that u-PA, plasminogen activator inhibitor type-1 (PAI-1), and tissue-type plasminogen activator (t-PA) are prognostic factors in breast cancer. However, there have been no prospective studies of node-negative breast cancer on a multicenter basis. On the other hand, some patients, even those with node-negative breast cancer, developed recurrence, and only tumor size is available as a predicting factor in this group. Therefore, it is necessary to find other prognostic factors in node-negative breast cancer to determine suitable adjuvant therapies. Tissue samples in this prospective study were obtained from 130 patients with node-negative invasive breast cancer who underwent radical operation at four hospitals. The median follow-up was 52.6 months. u-PA, PAI-1, and t-PA antigen levels were assayed by ELISA kits using the cytosolic fractions of tumors. Patients with high u-PA, high PAI-1, or low t-PA had significantly higher relapse rates than did those with low u-PA, low PAI-1, or high t-PA, respectively, by the Kaplan-Meier method (P = 0.006, 0.032, and 0.028, respectively). Analyses of the combinations of both u-PA and PAI-1 or both u-PA and t-PA showed that the differences in relapse rate between the high- and low-risk groups were statistically very significant. In the univariate analysis, u-PA, PAI-1, t-PA, progesterone receptor, and tumor size (T3 versus T1) were significantly correlated with relapse. However, the multivariate analysis revealed that only u-PA (P = 0.023) was an independent prognostic factor. This study showed that u-PA was a new significant independent prognostic factor in node-negative breast cancer.

Adult↗
PubMed1998

[Characteristics of screening-detected breast cancer and trends in its therapy].

Recently breast cancer has become one of the most common malignancies and one of the major causes of cancer death in Japan. In order to detect earlier stage breast cancer and to stop the increasing mortality, there is a greater need for mass screening. Mass screening performed by physical examination has a history of about thirty years in Japan, but it has had no effect in reducing breast cancer mortality. A new modality, mammography, is effective to detect non-palpable lesions, so it is expected to improve the accuracy of screening and reduce the mortality of breast cancer. Randomized trials in western countries have demonstrated that screening with mammography is effective for breast cancers in women aged 50 -69. In Japan, limited studies reported that effectiveness of screening was improved when mammography was combined with physical examination for detecting early breast cancer, but it is still unknown whether screening reduces breast cancer mortality. Since indications of breast conservation therapy have been rapidly extended it follows that breast conservation surgery for screening-detected cancer has increased. In Japan, because of its medical system, it seems impossible to conduct randomized trials for evaluating the efficacy of screening. Thus, it is important to interpret the screening data in western countries and to compare data with those from screening trials of Japan in the future.

Adult↗
PubMed1998

[Results of clinical study with epirubicin hydrochloride injectable solution and cyclophosphamide in breast cancer].

A 10-center cooperative clinical study with a new formulation of epirubicin hydrochloride injectable solution (Epirubicin-RTU) was conducted in patients with breast cancer. One course of treatment consisted of one intravenous administration of Epirubicin-RTU at the dose of 60 mg/m2 followed by a 3-week drug-free interval and concomitant daily administration of oral cyclophosphamide at 100 mg/day during the period between Days 1 through 14. At least, two courses of treatment were given. Among 20 registered cases, all 20 cases were eligible and 16 cases completed the whole course of the study. In 16 completers, PR was observed in 5 cases, indicating the efficacy rate of 31.3% (5/16).. No local irritation was observed at the injection sites. Adverse reactions frequently observed were leukopenia, neutropenia, anorexia, alopecia, and nausea/vomiting, which were all reversible and tolerable. From the above results, Adverse reactions both locally and systemically were tolerable. Intravenous administration of Epirubicin-RTU was considered to be useful for the treatment of breast cancer.

Administration, Oral↗