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Biomedical subjects

T Taguchi

Publications and source records attributed to T Taguchi.

At least 559 records · Page 31Linked to original sources

Augmentation of beta adrenergic receptors in cardiomyopathic hamsters (BIO 14.6) with heart failure.

OBJECTIVE: The aim was to characterise the transmural distribution of beta adrenergic receptors in failing myocardium in cardiomyopathy. METHODS: Using a quantitative autoradiographic technique with 125I-cyanopindolol (ICYP), the density and transmural distribution of beta adrenergic receptors were compared between eight cardiomyopathic BIO 14.6 Syrian hamsters with heart failure and six normal age matched controls (BIO 14.6HAM). RESULTS: Binding of ICYP to transmural slices of hamster myocardium was rapid, saturable, stereoselective, and displaceable by antagonists. The binding isotherm showed a significant increase in the total tissue content of beta adrenergic receptors in the failing myocardium of cardiomyopathic hamsters: 15.3(SEM 1.6) fmol.mg-1 protein v 9.4(1.2) fmol.mg-1 protein in normal myocardium of control hamsters (p < 0.05). There was no difference in receptor affinity. Quantitative autoradiography showed regional heterogeneity of beta adrenergic receptors in cardiomyopathic hamsters, with an increase of beta adrenergic receptor density in the septal and subendocardial regions. In addition, the regions with increased interstitial fibrosis corresponded to the sites of increased beta adrenergic receptor density. CONCLUSIONS: The transmural distribution of beta adrenergic receptor is heterogeneous in the failing myocardium of cardiomyopathic hamsters and an increased beta adrenergic receptor density may be associated with the development of cardiomyopathy.

Animals↗

Selective induction of Th2 cells in murine Peyer's patches by oral immunization.

We have used three different methods to determine the T helper (Th) cell response, including Th1 and Th2 types, in murine Peyer's patches (PP) following oral immunization with sheep red blood cells (SRBC). These include: (i) use of cytokine-specific (IFN-gamma and IL-5), single cell assays to estimate the frequencies of Th1 and Th2 cells respectively, (ii) cytokine-specific mRNA--cDNA dot blot and Northern gel hybridizations to detect levels of specific mRNA, and (iii) T cell cloning techniques to determine the frequency of Th1 and Th2 clones. Mice were immunized with SRBC by either the oral or i.p. route. The PP and splenic (SP) CD3+ and CD3+ CD4+ T cell subsets were isolated and cultured with antigen, feeder cells, and IL-2, and were assessed at various intervals (days 0, 1, 3, and 6) for numbers of T cells producing either IFN-gamma or IL-5 by use of an enzyme-linked immunospot (ELISPOT) procedure. Cultures of T cells from PP or SP of mice given SRBC by the oral route had a high frequency of IL-5 spot forming cells (SFC), with lower numbers of IFN-gamma SFC. However, cultures of CD3+ T cells and CD3+ CD4+ Th cells from spleens of i.p. immunized mice exhibited predominantly IFN-gamma SFC, with smaller but significant numbers of IL-5 SFC. This distinct pattern of cytokine production was supported by mRNA analysis where high IL-5 specific mRNA levels were noted in PP T cell cultures of orally primed mice, while IFN-gamma mRNA was predominant in the SP CD3+ T cell and CD3+ CD4+ Th cell cultures from i.p. immunized mice. When the frequencies of IFN-gamma or IL-5 SFC were assessed among cloned Th cells from orally- or systemically-immunized mice, 74% of Th cell clones from PP of mice orally immunized with SRBC were IL-5 producers (Th2 type), while 67% of Th cell clones from SP of mice immunized by the i.p. route were IFN-gamma producers (Th1 type). Our studies show that higher frequencies of IFN-gamma producing Th1-type cells occur in SP of mice given antigen by the systemic route, while oral immunization results in predominantly IL-5 producing, Th2-type cells in PP.

Administration, Oral↗

Evaluation of UW solution for preservation of small intestinal transplants in the rat.

Simple cold preservation was evaluated in the rat model of small intestinal transplantation. Lewis rats received a syngeneic heterotopic graft of the jejunum either immediately (SI) or after preservation for 24 hr in Euro-Collins (SPE24), for 48 hr in EC (SPE48), for 24 hr in University Wisconsin solution (SPW24), or for 48 hr in UW (SPW48). The survival rates of SI, SPE24, SPE48, SPW24, and SPW48 were 100%, 78%, 0%, 100%, and 33%, respectively. Physiologic and pharmacologic properties of the grafts and native intestine were evaluated in vitro between 8 and 12 days after transplantation. Smooth muscle in all specimens contracted in response to cholinergic agonists, phenylephrine, and substance P, and was relaxed by isoproterenol. Excitatory innervation was present in 100%, 100%, 100%, and 67% of SI, SPE24, SPW24, and SPW48, respectively, while inhibitory innervation in each group was 50%, 29%, 60%, and 0%. Thus, smooth muscle function was preserved in all groups, but neural activity was impaired by some of the storage conditions. Preservation was best in SPW24, which had physiologic responses similar to those of SI. The rat jejunum can, therefore, be preserved in good condition for up to 24 hr before transplantation using simple cold storage in UW solution.

Acetylcholine↗

The effect of breast self-examination on early detection and survival.

To investigate the effect of breast self-examination (BSE), we compared the stages, survival, and the risk of death for 355 patients with breast cancer detected by BSE with those for 1,327 patients with breast cancer detected by chance. The early stages of the disease were found to be more common among the symptomatic breast cancer patients detected by BSE than those by chance. The 5-year overall survival rate was 94.4% for the symptomatic patients detected by BSE, and was significantly higher by 8.7% than that (85.7%) for patients detected by chance (P less than 0.001). The 10-year survival rate was 81.6% for patients detected by BSE, and 76.6% for cases detected by chance (the difference was not significant). The overall difference between the two survival curves was statistically significant by the logrank test (P less than 0.01). A multivariate analysis using the Cox proportional hazards model showed that the risk of death for patients detected by BSE was smaller by 0.570 times than that for patients detected by chance, which was statistically significant (P less than 0.05). The effect of biases inherent to BSE in the survival analysis cannot be controlled completely even after conducting multivariate analysis. These results suggest that BSE may contribute to the reduction of the risk of death through early detection of breast cancer. However, further examination should be conducted by other methods to obtain conclusive evidence.

Breast Neoplasms↗

Enhancing effect of pokeweed mitogen on the proliferation and the cytotoxicity of lymphokine-activated killer cells.

In order to obtain more potent lymphokine-activated killer (LAK) cells for use in adoptive immunotherapy, pokeweed mitogen (PWM) was added to the culture medium for the initial 24-48 h of culturing. The proliferation rate of PWM-stimulated LAK cells reached about 1000-fold after 3-week culture. This rate was nearly the same as that of LAK cells stimulated by 10 ng/ml of OKT3, the mouse anti-CD3 monoclonal antibody. However, the cytotoxicity of PWM-stimulated LAK cells was significantly more potent than that of OKT3-stimulated LAK cells. Phenotypic analysis revealed that PWM-stimulated LAK cells were CD3+CD56(+)-dominant while OKT3-stimulated LAK cells were CD3+CD56(-)-dominant. About half of CD3+CD56+ PWM-stimulated LAK cells was CD8+. These results suggest that more efficient adoptive immunotherapy is possible by using high-dose PWM-stimulated LAK cells with more potent cytotoxicity. Interleukin-1 beta and tumor necrosis factor alpha were significantly increased in the culture media after 24-h incubation with 1 micrograms/ml of PWM. Secretion of interferon-gamma was not enhanced by this concentration of PWM within 24 h. Therefore, PWM is considered to activate monocytes or macrophages to produce these cytokines in advance, influencing the proliferation and the cytotoxicity of LAK cells.

Antigens, CD↗

Endogenous calcitonin gene-related peptide mediates nonadrenergic noncholinergic depressor response to spinal cord stimulation in the pithed rat.

The role of endogenous calcitonin gene-related peptide (CGRP) in the nonadrenergic noncholinergic depressor response to spinal cord stimulation was studied in the pithed rat in vivo. Pithed rats were given hexamethonium (2 mg/kg per minute i.v.) to block autonomic outflow, and mean blood pressure was artificially maintained at approximately 100 mm Hg with methoxamine (10-15 micrograms/kg per minute i.v.). Electrical stimulation of the spinal cord at the level of the lower thoracic vertebra (T9-12) caused a fall in blood pressure in a frequency-dependent (0.5-10 Hz), voltage-dependent (2.5-50 V), and pulse duration-dependent (0.25-8 msec) manner. The heart rate did not change during the depressor response. The depressor response was long lasting, and the maximum response was elicited by stimulation at 4-6 Hz. The neurotoxin tetrodotoxin (100 micrograms/kg i.v.) abolished the depressor response to spinal cord stimulation, whereas treatment with propranolol (0.5 mg/kg per minute i.v.), atropine (0.05 mg/kg per minute i.v.), or a combination of pyrilamine (0.5 mg/kg per minute i.v.) and cimetidine (0.5 mg/kg per minute i.v.) did not affect the response. In pithed rats treated with capsaicin (total dose of 500 mg/kg s.c.), spinal cord stimulation caused a slight depressor response. Exogenous CGRP, but not acetylcholine, isoproterenol, histamine, or substance P, caused a sustained fall in blood pressure that mimicked the spinal cord stimulation-induced depressor response. Continuous infusion of CGRP[8-37] (60 nmol/kg per minute i.v.), a CGRP receptor antagonist, markedly inhibited the depressor responses not only to spinal cord stimulation but also to exogenous CGRP.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Sustained damage to energy metabolism of brain regions after microsphere embolism in rats.

BACKGROUND AND PURPOSE: Information on sustained damage to cerebral function and metabolism after cerebral ischemia is useful for prophylaxis and therapeutics of cerebral infarction. The purpose of the present study was to induce sustained damage to brain regions after cerebral ischemia in experimental animals. For this purpose, we examined animal behavior and cerebral energy metabolism following microsphere embolism in rats. METHODS: We injected 900 microspheres (48 microns in diameter) into the right internal carotid artery of 110 rats and determined the time course of changes in the rats' behavior and the energy metabolism of the cortex, striatum, and hippocampus of both hemispheres. We injected the same volume of vehicle, without microspheres, into 28 sham-operated rats; there were 14 nonoperated control rats. RESULTS: Peak increase in lactate content and decrease in adenosine triphosphate and creatine phosphate of these brain regions of the right hemisphere were seen on the first day after microsphere embolism, whereas peak increases in glucose and glycogen contents of these regions were observed on the third day. Most of the metabolic alterations in all these regions continued for up to 28 days after operation, although they recovered toward control levels with time after the operation. The extent and trend of metabolite changes of the right hemisphere after microsphere embolism were similar in the three brain regions. In the left hemisphere, similar metabolic changes were observed, but to a lesser degree. The time course of changes in behavioral scores following microsphere embolism revealed marked stroke-like symptoms on the first day and relatively rapid disappearance of the symptoms with time after embolism. CONCLUSIONS: Microsphere embolism is capable of inducing widespread, sustained damage to energy metabolism of brain regions.

Adenosine Triphosphate↗

Alterations in DNA synthesis and cellular constituents in mouse lung following bleomycin injections.

Changes in the DNA synthesis and cellular constituents of mouse lung following repeated bleomycin (BLM) injections were studied. ICR mice were administered BLM subdermally for 10 days. Wet lung weight was increased 1.36 times on day 5 after the final administration compared with control mice receiving an identical volume of saline only for 10 days. The total number of cells in the bronchoalveolar lavage fluid of the BLM group reached a maximum on day 14, and histologic investigation of the lungs revealed marked cellular infiltrations. The labeling index obtained by the antibromodeoxyuridine monoclonal antibody method for cells was increased from days 5 to 14 in the BLM group. By day 28, these inflammatory changes had subsided and fibrotic remodeling had occurred. DNA polymerase activity in the lung tissue reached its maximal level on day 5 and remained unchanged until day 14. This phenomenon occurred in parallel with increases in DNA content and synthesis. During this period, an increase in DNA polymerase-beta activity and new induction of DNA polymerase-alpha activity were observed by phosphocellulose column chromatography. From these observations, it is concluded that: (1) repeated injections of BLM cause DNA injury in lung cells; (2) there is a subsequent increase in the DNA repair function as supported by the finding of an increase in DNA polymerase-beta activity; and (3) these lead further to cell proliferation as supported by the increase in both DNA polymerase-alpha activity and DNA content. Thus, a close relationship between morphologic changes and altered DNA synthesis was observed in the lungs of mice after BLM injections.

Animals↗

The blood vascular bed of the human pancreas, with special reference to the insulo-acinar portal system. Scanning electron microscopy of corrosion casts.

Microdissection and scanning electron microscopy of corrosion casts showed the structures of the vascular bed of the human pancreas to consist mainly of the capillary plexuses of the exocrine lobules, extralobular ducts and endocrine islets. A considerable number of the exocrine lobules were found to contain one to four marked endocrine islets larger than 30 microns in diameter. These intralobular islets received one or more arterioles (afferent vessels) and emitted conspicuous insulo-acinar portal vessels which continued into the lobular capillaries, suggesting insular control over the functions of the exocrine acini of the pancreas. Direct drainage of the intralobular islets into the veins was never reproduced. Not excluding the possibility that some lobules might contain smaller, unidentifiable islets, there nonetheless were many lobules which directly received arterioles. These lobules are free of control by an islet. Rarely, an islet was located in the interlobular tissue space or along an extralobular duct. Such an extralobular islet issued no portal vessels, and drained into the interlobular or periductal veins. The surface of this type of islet comprised a thin network of fine capillaries. A possibility was suggested that this cortical network might be homologous with the lobular capillaries. No portal route was observed between the islets and extralobular ducts. Few connections were noted between the capillary plexuses of the lobules and ducts.

Adult↗

Coronary artery disease in patients with arteriosclerosis obliterans of the lower extremities or aortic aneurysm.

Routine coronary angiography was performed in order to determine the incidence and clinical condition of coronary artery disease in 37 patients with arteriosclerosis obliterans or aortic aneurysm. Coronary angiography demonstrated significant stenosis in 12 (57%) of 21 patients with arteriosclerosis obliterans and in 7 (44%) of 16 patients with aortic aneurysm. The prevalence of risk factors for arteriosclerosis was similar for patients with arteriosclerosis obliterans and those with aortic aneurysm, and similar for patients with and without coronary artery stenosis. But coronary artery disease is often silent in patients with arteriosclerosis obliterans.

Aged↗

DNA synthesis and related enzymes altered in compensatory lung growth in rats.

Left pneumonectomy was performed on 4 week-old male Fischer-344 rats. Changes in DNA biosynthesis and the activities of related enzymes were studied in the contralateral lungs of the pneumonectomized animals (n = 55) and compared with sham-operated (n = 55) and untreated control animals (n = 40) The wet weight of the contralateral lung of the pneumonectomized rats reached that of both lungs of the untreated and sham-operated rats 14 days after the operation. The activities of thymidine kinase and DNA polymerase from the regenerating lungs were elevated on Days 1 and 7. To determine the molecular forms of DNA polymerase in the crude extract, phosphocellulose column chromatography was performed. The type of DNA polymerase with the highest activity was alpha in regenerating lung on Days 1, 3, and 7. These results suggest that DNA replication for cellular proliferation was elevated in the remaining lung after pneumonectomy. In addition, an interlobar difference in DNA biosynthesis was observed in the remaining lung. The increase was especially marked in the cardiac lobe, followed by increases in the DNA content of the remaining lobes on Day 7. From these observations we conclude (1) that increased activity of DNA polymerase alpha is likely to be an initial change in compensatory lung growth, and may be caused by some unknown stimulator in lung tissue, and (2) that DNA biosynthesis may differ among the lobes of the lung, at least until 3 days post-pneumonectomy.

Animals↗

Pokeweed mitogen induces p55 interleukin-2 receptor expression on human monocytes and its effect on interleukin-2 activated monocyte cytotoxicity.

Activation of human peripheral blood monocytes by pokeweed mitogen (PWM) results in the expression of interleukin 2 receptor(IL-2R) p55 chains, which are absent on resting monocytes. By dual-fluorescence flow cytometry, we found PWM induced detectable numbers of IL-2R+ cell which were further identified as LeuM3+ monocytes (22.91% of the LeuM3+ cells were IL-2R+ within 24h, and 32.17% in 48h). In addition, LPS can also induce IL-2R on 15.39% of LeuM3+ cells. On the contrary, other mitogens such as PHA or Con A, and cytokines as IFN-gamma, IL-2, M-CSF, TNF-alpha and IL-1 beta showed no influence on the IL-2R expression on monocytes. It was also noticed that PWM itself had no direct effect on HLA-DR antigen expression on LeuM3+ cells. The addition of IL-2 to PWM-pretreated IL-2R positive monocytes significantly augmented their tumoricidal activity. Thus monocytes when activated underwent a series of phenotypic and functional changes including the expression of IL-2R which may provide an important immunoregulatory pathway.

Cytotoxicity, Immunologic↗

[Co-operative clinical evaluation of 5'-DFUR tablets for breast cancer at 31 institutions].

A phase II study of 5'-deoxy-5-fluorouridine (5'-DFUR) tablets for breast cancer was done at 31 institutions in Japan. Forty-five patients were registered and 44 of them were eligible for the study. Of the 40 patients whose results could be evaluated, 11 (28%) responded (four complete responses and seven partial responses). Side effects, such as diarrhea, anorexia, leukocytopenia, and liver dysfunction were observed in 24 of the 44 patients. The side effects were mild and transient. 5'-DFUR is a promising drug for breast cancer treatment, and its tablet form makes chemotherapy easier for the patient.

Administration, Oral↗

[Combination therapy of doxifluridine (5'-DFUR) + cyclophosphamide (CPA) + tamoxifen (TAM) for advanced or recurrent breast cancer. Joint Research Group in the Osaka Area for Combination Therapy of 5'-DFUR with Other Drugs].

Outpatients with advanced and recurrent breast cancer were treated by a combination therapy of the following drugs: doxifluridine (5'-DFUR) orally administered at a dose of 1200 mg/day; cyclophosphamide (CPA) orally given at dose of 100 mg/day; and tamoxifen (TAM) orally given at dose of 20 mg daily. 5'-DFUR and CPA were administered on consecutive days 1-14, then discontinued for 14 days. The response rate was 44.8% including five CR and eight PR out of 29 complete cases. As for response cases in terms of the subject lesions, corresponding cases were chiefly found in soft tissue and the lung. As for the response rate with or without pretreatment, cases previously treated showed a higher response rate such as 42.9% indicating that the present therapy was effective in pretreatment cases. The main side effect was leukopenia, but not so severe. Few cases with diarrhea were found. Based on the above findings, the present treatment is conceivably a highly useful therapy, on an outpatient basis, for advanced and recurrent breast cancer, especially metastatic lesions of soft tissue and the lung.

Administration, Oral↗