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Biomedical subjects

M Noguchi

Publications and source records attributed to M Noguchi.

At least 181 records · Page 10Linked to original sources

Vasoactive effects of cimicifugic acids C and D, and fukinolic acid in cimicifuga rhizome.

Vasoactive effects of cimicifugic acids A-E, fukinolic acid and fukiic acid isolated from Cimicifuga plants were investigated using rat aortic strips. Cimicifugic acid D and fukinolic acid at 3x10(-4) M caused a sustained, slowly developing relaxation of aortic strips precontracted with norepinephrine (NE) in preparations with or without endothelium. Cimicifugic acid C inversely caused a weak contraction. Cimicifugic acids A, B and E and fukiic acid showed no vasoactivity at 3x10(-4) M. Cimicifugic acids A-E and fukinolic acid are esters between cinnamic acids and the hydroxyl group of benzyltartaric acids. For the manifestation of vasoactivity in the rat aorta, it is concluded that in the cinnamic acid moiety, a caffeoyl group might be necessary for the relaxation activity, and the p-coumaroyl group causes contraction. Concentration response curves for the Ca2+-induced contracture of depolarized aortic strips with isotonic high K+ were not affected by cimicifugic acid D or fukinolic acid. The Ca2+-induced contraction of aortic strips, preincubated with 10(-6) M NE in the presence of 10(-6) M nicardipine and 0.01 mM EGTA in Ca2+-free solution, were inhibited by cimicifugic acid D and fukinolic acid. These results indicated that the inhibition by cimicifugic acid D and fukinolic acid of the NE-induced contraction of rat aorta are attributable to the suppression of Ca2+ influx from the extracellular space enhanced by NE.

Animals↗

Characteristics of spontaneous erythema appeared in hairless rats.

The hairless rat (WBN/Kob-Ht), a dominant mutant rat derived from the Wistar strain, rarely develops spontaneous erythema of a progressive nature on its skin. Erythema was first observed at 8 weeks of age and the incidence at 20 weeks of age was about 4% in both males and females. Histopathologically, erythema was characterised by dermatitis induced by an immunological reaction. Areas of erythema in the skin were decreased by treatment with dexamethasone (1 mg/kg) or ciclosporin (25 or 50 mg/kg). These results suggested that erythema on the hairless rat could be used as an animal model of spontaneous dermatitis.

Animals↗

[Phase I study of TAT-59 (a new antiestrogen) in breast cancer. TAT-59 Study Group].

Phase I study of TAT-59 (Miproxifen), an antiestrogen developed in Japan for breast cancer, was conducted with the collaboration of 12 hospitals. A single dose of 1.25, 5, 10, 20, 40 and 80 mg, or 5 consecutive daily doses of 1.25, 5, 10, 20 and 40 mg/day, were given orally. After single dosing, no clinical adverse effects were found. Decrease of serum Na, Cl, Ca level and increase of serum LDH level were observed in one patient after a single dose of 5 mg of TAT. An increase in the serum LDH level was also observed in one patient after a single dose in the of 10 mg of TAT. An increase in the serum LDH level and total bilirubin, increase of eosinophil, K and milky serum were also observed in one patient after a single dose of 40 mg of TAT, respectively. All of these abnormal values returned to the normal level within 26 days after final administration of TAT. No adverse clinical findings nor abnormal laboratory findings were observed after consecutive administration of TAT. After postprandial single dosing, the time to reach the maximum serum concentration (Tmax) of DP-TAT, dephosphorylated metabolite of TAT, and its demethylated metabolite, DMDP, ranged from 5.0 to 7.3 hr and from 17.0 to 42.8 hr, respectively. The maximum serum concentration (Cmax) and AUC of DP and DMDP elevated in a dose-dependent manner. T1/2 of DP and DMDP ranged from 24.2 to 41.5, and from 91.9 to 214.7 hr, respectively. There were no significant differences between pharmacokinetics of TAT before and after food intake. Based on the above results, we concluded that a Phase II study should be conducted to evaluate the efficacy, safety and optimal dose of TAT.

Administration, Oral↗

[Subarachnoid hemorrhage in 'Vital Statistics of Japan', 1993-1995: variability with age and sex].

The incidence and death rate of subarachnoid hemorrhage (SAH) varies with age and sex. Female preponderance in the incidence of SAH is a well-known fact. However, the degree varies with age. Autopsy data, records of natural history of unruptured aneurysms, epidemiological and clinical cooperative studies have provided a great amount of information regarding the statistics of subarachnoid hemorrhage. But, each individual study has its own limitation, such as a bias in case selection in autopsy or clinical studies, predominance of aged population in the epidemiological cohort studies, limited frequency in the detection of unruptured aneurysms in the entire population. These shortcomings are reflected in the variability in the statistical data of these studies. Death records in 'Vital Statistics of Japan', published annually by Ministry of Health and Welfare of Japan, exhibit the numbers of deaths by cause (according to ICD-9 or 10 code), sex and age. In this study, we calculated the death rates of SAH (per 100,000) in 1993-1995 for each age group of both sexes based on the published data. Deaths from breast cancers and automobile accidents (AMA) were assessed in the same manner and compared with the results of SAH. The annual death rate of SAH for all people in Japan is 10.7 per 100,000 population and the average age of death is 65.6 y.o. The death rate is 8.2 for men, and 13.1 for women. Average age at the death is 60.2 y.o. in men, and 68.8 y.o. in women (p < 0.001). The age-adjusted death rate to 1985 Japanese population was 7.3 for men and 9.2 for women. Below age 60, rate of death caused by SAH is higher for men than women, but the ratio reverses in the population over 60. For men, the death rates after the age of 40, 50, 60 and 70 were 16.4, 20.4, 24.1 and 29.2 respectively. For women, the rates were 25.0, 32.8, 44.1 and 62.4. The female-to-male ratio of the death rates increases with age. Female sex should be considered as a risk factor for death from SAH. Number of deaths from breast cancers was about 90% of those from SAH in women. There was a difference in the age distribution; deaths caused by breast cancer tend to occur in younger age than those caused by SAHs. Mean age of death was 59.3 for breast cancer and 68.8 for SAH. Deaths caused by SAH is 1.4 times more likely to occur than those by breast cancer for a 50 year-old woman for the rest of her life, 1.9 times for a 60 y.o. woman, and 2.7 times for a 70 y.o. woman. Regular examination to detect breast cancer is widely performed in Japan among elderly women. We believe that a similar screening effort should be targeted for unruptured aneurysms from the standpoint of the medico-social cost. Automobile accidents (AMA) victimize as many people as SAH in Japan, about 13,000 per year. For males over the age of forty, AMA victims are more than those from SAH. However, conversely females' deaths from SAH occur three times frequently as those from AMAs. The fact should be taken into consideration when screening for unruptured aneurysms.

Adult↗

[Intraarterial chemotherapy combined with radiation therapy for advanced cancer of the uterine cervix].

The results of intraarterial chemotherapy (IACT) combined with definitive radiation therapy for 23 advanced and bulky carcinomas of uterine cervix are reported. IA-CT with cisplatin 50 mg and doxorubicin 30 mg was administered by one shot method in bilateral internal iliac arteries. The protocol consisted of one to three treatment session every 3 weeks. Nine of eleven patients with clinical stage III achieved a complete local response (82%), and the 3- and 5-year survival in these cases were 72% and 72%, respectively. These results were superior to the response (58%), 3- and 5-year survivals (68%, 58%) obtained in 19 patients treated mainly with radiation therapy alone. The side effect of grade 2 and 3 for the intestine, such as ileus and hemorrhagic colitis, was noted in 3 patients (15%). In addition, 3 of 8 patients with radical surgery and postoperative radiation therapy after IA-CT developed insufficient fracture of pelvic bone. These complications accompanied by IA-CT combined with radiation therapy and/or surgery increased slightly, compared with that by the previous therapy without IA-CT, but were not critical. The results suggest that IA-CT following radiation therapy is effective to improve the prognosis of patients with Stage III cervical cancer.

Antineoplastic Combined Chemotherapy Protocols↗

Coronary revascularization and abdominal aortic aneurysm repair in a patient with Behçet's diseases.

Behçet's disease is a systemic disease characterized by oral aphta, genital ulcer, and ocular lesion. Arterial involvement is an uncommon complication of Behçet's disease, and it most frequently affects the abdominal aorta followed by the femoral artery and the pulmonary artery. Coronary lesions in Behçet's disease have been little reported in the literature. In this communication, we present a case with coronary artery stenosis and with subsequently developed supra-renal abdominal aortic aneurysm. The coronary lesions were revasculized with gastroepiploic artery, right internal mammary artery, and saphenous vein graft. Abdominal aortic repair was performed with partial cardiopulmonary stand by, because of the risk of coronary ischemia during the cross clamp including the celiac artery. To our knowledge, this is the first report of successful repair of combined lesions of the coronary and the abdominal aorta in a patient with Behçet's disease.

Aortic Aneurysm, Abdominal↗

The Role of Axillary Lymph Node Dissection in Breast Cancer Management.

Although it is generally accepted that axillary dissection provides no survival advantage in patients with breast cancer, it is commonly regarded as a reliable method of assessing nodal status and treating regional disease. However, it is time to consider eliminating routine axillary dissection in patients who are clinically node-negative. A sentinel lymph node biopsy may assess axillary nodal status while obviating a full axillary dissection. At present, axillary dissection remains the standard approach for the surgical management of all patients with invasive carcinoma of the breast, regardless of tumor size or patient age, though it is unnecessary for patients with small intraductal carcinomas.

Journal Article↗

Functional cleavage of the common cytokine receptor gamma chain (gammac) by calpain.

The small subunit of calpain, a calcium-dependent cysteine protease, was found to interact with the cytoplasmic domain of the common cytokine receptor gamma chain (gammac) in a yeast two-hybrid interaction trap assay. This interaction was functional as demonstrated by the ability of calpain to cleave in vitro-translated wild-type gammac, but not gammac containing a mutation in the PEST (proline, glutamate, serine, and threonine) sequence in its cytoplasmic domain, as well as by the ability of endogenous calpain to mediate cleavage of gammac in a calcium-dependent fashion. In T cell receptor-stimulated murine thymocytes, calpain inhibitors decreased cleavage of gammac. Moreover, in single positive CD4(+) thymocytes, not only did a calpain inhibitor augment CD3-induced proliferation, but antibodies to gammac blocked this effect. Finally, treatment of cells with ionomycin could inhibit interleukin 2-induced STAT protein activation, but this inhibition could be reversed by calpain inhibitors. Together, these data suggest that calpain-mediated cleavage of gammac represents a mechanism by which gammac-dependent signaling can be controlled.

Amino Acid Sequence↗

Expression and tissue localization of membrane-types 1, 2, and 3 matrix metalloproteinases in human invasive breast carcinomas.

Activation of the zymogen of matrix metalloproteinase 2 (proMMP-2, progelatinase A) possibly is one of the key steps in invasion and metastasis of various human carcinomas. Three different membrane-type MMPs (MT-MMPs), MT1-, MT2-, and MT3-MMPs are thought to be activators of proMMP-2 in the tissues. MT4-MMP is structurally different from the other three enzymes, and its function as proMMP-2 activator is uncertain. In the present study of human invasive breast carcinomas, we examined a correlation between the expression of MT1-, MT2-, and MT3-MMPs, immunolocalization of MT1- and MT2-MMPs, and proMMP-2 activation. Northern blot analysis demonstrated the predominant expression of MT1-MMP mRNA in carcinoma tissues (20 of 20 cases), whereas MT2-MMP was detected in only 25% of the cases (5 of 20 cases), and no detectable expression of MT3-MMP was observed. The expression levels of MT1-MMP but not MT2-MMP correlated well with the presence of lymph node and distant metastases, clinical stages, and size of tumors. Immunohistochemically, MT1-MMP was localized predominantly in the carcinoma cells in all of the samples (32 of 32 cases). Immunostaining of MT2-MMP in the carcinoma cells was observed in only 38% of the cases (12 of 32 cases). Immunoblot analysis of tumor homogenates confirmed the presence of these MT-MMPs. Activation of proMMP-2 was significantly higher in the carcinoma samples with lymph node or distant metastasis compared to carcinoma without metastasis, normal control, or fibrocystic disease (P < 0.05). An increase in the activation ratio of proMMP-2 correlated directly with the expression of MT1-MMP but not MT2-MMP, as measured by either Northern blot analysis or immunostaining. These results suggest that MT1-MMP may play a key role in human breast carcinoma invasion and metastasis by being predominantly responsible for activation of proMMP-2.

Adult↗

Ectopic Breast Caner: Two Case Reports and Review of the Japanese Literature.

Two cases of carcinoma involving ectopic breast tissue are reported, along with a review of the Japanese literature. A total of 65 cases of ectopic breast cancer have been reported; 59 of which occurred in the axilla. Total mastectomy with axillary dissection was performed in 29 cases, and tumor excision with or without nodal dissection was done in 30 cases. Outcome was known in 33 cases, and 5 cases had recurred at the time of this writing. Although the prognosis of ectopic breast cancer was difficult to establish with the limited follow-up data, all the 5 cases in our series with recurrence had axillary lymph node metastases at the time of surgery. Therefore, the complete excision of ectopic breast tissue with nodal dissection, and subsequent chemoendocrine therapy, especially in node-positive patients, is recommended as the treatment of choice.

Journal Article↗

The common cytokine receptor gamma chain plays an essential role in regulating lymphoid homeostasis.

In the immune system, there is a careful regulation not only of lymphoid development and proliferation, but also of the fate of activated and proliferating cells. Although the manner in which these diverse events are coordinated is incompletely understood, cytokines are known to play major roles. Whereas IL-7 is essential for lymphoid development, IL-2 and IL-4 are vital for lymphocyte proliferation. The receptors for each of these cytokines contain the common cytokine receptor gamma chain (gammac), and it was previously shown that gammac-deficient mice exhibit severely compromised development and responsiveness to IL-2, IL-4, and IL-7. Nevertheless, these mice exhibit an age-dependent accumulation of splenic CD4+ T cells, the majority of which have a phenotype typical of memory/activated cells. When gammac-deficient mice were mated to DO11.10 T cell receptor (TCR) transgenic mice, only the T cells bearing endogenous TCRs had this phenotype, suggesting that its acquisition was TCR dependent. Not only do the CD4+ T cells from gammac-deficient mice exhibit an activated phenotype and greatly enhanced incorporation of bromodeoxyuridine but, consistent with the lack of gammac-dependent survival signals, they also exhibit an augmented rate of apoptosis. However, because the CD4+ T cells accumulate, it is clear that the rate of proliferation exceeds the rate of cell death. Thus, surprisingly, although gammac-independent signals are sufficient to mediate expansion of CD4+ T cells in these mice, gammac-dependent signals are required to regulate the fate of activated CD4+ T cells, underscoring the importance of gammac-dependent signals in controlling lymphoid homeo-stasis.

Animals↗

Extended lymph node dissection in gastrointestinal cancer.

We reviewed the literature concerning the effect of extended lymph node dissection on survival in patients with gastrointestinal cancer. Most retrospective and/or prospective nonrandomized comparative studies have claimed that extended lymph node dissection significantly improves survival rate in patients with esophageal cancer, gastric cancer, and colorectal cancer. However, it is difficult to interpret these results since specialized care provided in trials may itself improve survival. In gastric cancer, several prospective randomized trials have failed to demonstrate a survival advantage of extended dissection, while there are few well-done prospective randomized trials in esophageal or colorectal cancer. Therefore, the therapeutic value of extended lymph node dissection remains to be determined in gastrointestinal cancer. Randomized prospective studies within the bounds of the ethical treatment of patients can and should be done.

Clinical Trials as Topic↗