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Biomedical subjects

Y Koga

Publications and source records attributed to Y Koga.

At least 523 records · Page 29Linked to original sources

Activation of natural resistance against lung metastasis of an adenocarcinoma in T-cell depressed spontaneously hypertensive rats by infection with Listeria monocytogenes.

We report here our study of the role of natural host defense mechanisms mediated by macrophages and natural killer (NK) cells in an experimental model of spontaneous pulmonary metastases of a mammary adenocarcinoma SST-2 in spontaneously hypertensive rats (SHR) with congenital T-cell depression. To activate macrophages and NK cells, Listeria monocytogenes (LM) was injected IV into SHR which had received a transplantation of SST-2. To assess the antimetastatic responses induced by LM, the number of lung nodules and the lung weight in SHR were evaluated 30 days after tumor inoculation. The growth of lung metastases, though not of primary tumors, was significantly reduced if 10(7) LM were injected IV into SHR 2, 10 and 20 days after the SC transplantation of 5 X 10(4) or 5 X 10(5) SST-2. An inhibitory effect of LM on pulmonary metastases was also observed in tumor-excised rats, in which the number of lung metastases and the lung weight were enhanced as compared with those in tumor-bearing rats which had not undergone surgery. Peritoneal resident cells which were harvested from rats injected with LM showed a significant augmentation of tumoricidal activity against SST-2 cells as measured by in vitro cytotoxicity. Similarly, the NK activity of spleen cells of SHR injected with LM increased significantly when compared with untreated SHR. These data suggest that the inhibition of metastatic growth, though not of primary tumor growth, was accomplished by the, possibly T-cell independent, activation of macrophages and NK cells.

Adenocarcinoma↗

Further comparative studies on chemical properties of carcinoembryonic antigen in tumor tissues and closely related antigens in adult feces and meconium.

The chemical structure of carcinoembryonic antigen (CEA) and two closely related antigens, normal fecal antigen-2 (NFA-2) in normal adult feces and nonspecific cross-reacting antigen-2 (NCA-2) in the meconium, were further analyzed comparatively. The NH2-terminal amino acid sequence of NCA-2 was newly determined to position 18 and found to be identical to that so far determined for CEA- and NFA-2. After proteolytic digestion with chymotrypsin or protease V8, the digests of these antigens showed two groups of fragments upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis. One consisted of the sharply banded fragments which were identical in all antigens and stained only with Coomassie brilliant blue (CBB) (five bands in the range 2500-10,000 daltons for chymotrypsin and 11 bands in the range 8000-35,000 daltons for protease V8, respectively), and the other consisted of the dispersed fragments which had variable mol. wts in the range 10,000-100,000 and were stainable with both CBB and periodic acid-Schiff reagent. Elution profiles of CEA, NFA-2, and NCA-2 from lectin columns, especially from concanavalin A-Sepharose columns, suggested some differences in oligosaccharide chains between them. These results indicate that the fundamental chemical structure of these antigens seems to be very similar to one another and is divided into two parts; an homologous portion(s) which is common to all three antigens and contains no sialylated sugar components, and a heterogeneous portion(s) which is variable among these antigens and contains sialylated sugar components.

Adult↗

Thymus cell migration in a prostaglandin-mediated system.

Prostaglandin (PG)-mediated T cell traffic and the nature of these emigrant T cells were analyzed by using a fluorescent activated cell sorter. Administration of indomethacin (INDO), an inhibitor of PG synthesis, increased the number of splenic T cells in normal mice but not in adult-thymectomized mice. An increase in thymus cell migrants in peripheral blood lymphocyte and splenic cell populations of mice pretreated with INDO were detected, using the method of in situ labelling of thymocytes with fluorescein diacetate. These results indicate that the increase in the T cell population in the spleen by INDO treatment results from the increase in thymus cell migration to the spleen. Such recent emigrants in the spleen were thought to have been derived from the thymus cortex, judging from the response to phytohemagglutinin and intracellular terminal deoxynucleotidyl transferase activity; however, they expressed a Thy-1 level similar to that found on peripheral T cells. These results suggested that a cortical thymocyte population was recruited from the thymus to the spleen by a PG-mediated system, but its Thy-1 level rapidly changed to that found on the peripheral T cell population.

Animals↗

Thymus-dependent increase in number of T cells in parathymic lymph nodes induced by the biscoclaurine alkaloid, cepharanthine.

In mice treated with cepharanthine (Cepha), a biscoclaurine alkaloid, the number of T cells was increased in the parathymic lymph nodes (PtLNs) which are considered to be the specialized lymph nodes in local differentiation of T cells. Such PtLN cells exhibited augmented proliferative responses to T cell mitogens and exogenous interleukin 2 (IL 2) and showed a great ability to produce IL2, which suggests an increase in mature T cells in the PtLN. However, such increases in the number of T cells and in the mitogen response were not observed in adult thymectomized mice. A low level of plasma prostaglandin E2 (PGE2) was observed in Cepha-treated mice. Replenishment of the PGE2 in such mice with exogenous PGE2 prevented the increase in T cells in the PtLN. These results suggest that the migration of mature T cells from the thymus to PtLN is increased by Cepha and that Cepha is able to regulate their traffic by a prostaglandin-mediated system.

Alkaloids↗

Effect of implanted ethylene-vinyl alcohol copolymer matrices containing 5-fluorouracil on Ehrlich ascites carcinoma.

The antitumour activity of ethylene-vinyl alcohol (EVAl) copolymer matrices containing 5-fluorouracil (5-FU) was evaluated against Ehrlich ascites carcinoma in mice. A prolongation of the life-span of tumour-bearing mice following intraperitoneal implantation of therapeutic matrices was noted. These results indicated that EVAl matrices containing 5-FU may be effective in cancer chemotherapy. Matrices composed of EVAl copolymer could be useful vehicles for implanted, inserted, or surface-applied delivery systems for anticancer agents.

Animals↗

Medical management of infective endocarditis; limitations and indication for surgery.

Problems and limitations of medical management for infective endocarditis were studied and surgical indications were discussed based on the retrospective analysis of 55 episodes. Since perioperative complications still occur during highly active infection, antibiotic treatment was suggested as the primary management. Intractable or progressing heart failure appeared to be a definite indication for emergency surgery, but medical therapy was recommended for mild to moderate heart failure. For uncontrolled infection of more than one month duration despite the best available antibiotics, surgical debridement of the infected tissue was indicated. Occurrence of peripheral or fatal emboli was difficult to predict from clinical features and echocardiogram and therefore presented a therapeutic dilemma. Since major or fatal emboli frequently occurred during highly active infection, early initiation of effective antibiotic therapy was considered to be of primary importance. Demonstration of vegetation by echocardiography alone did not seem to justify urgent surgery. In addition, disseminated intravascular coagulation appeared to be a serious complication and thus sedimentation rate should be followed carefully. In the healed stage, prophylactic surgery seemed unnecessary for prevention of recurrent infection or embolization, as they were relatively rare.

Adult↗

An impedance cardiographic study of the mechanism of blood pressure fall after moderate dietary sodium restriction.

Impedance cardiography was performed on 13 free-living subjects to determine the mechanism which ties modest sodium restriction to a reduction in blood pressure. During salt restriction intervention, significant decreases in systolic and diastolic blood pressure (6 and 7 mmHg) were observed associated with mild reduction in urinary sodium excretion from 176 to 85 mmol/day. The impedance cardiogram demonstrated a significant decrease in stroke volume (12 ml), which was related to a fall in diastolic pressure (r = 0.59, p less than 0.05). In the further analysis of individual parameters in Kubicek's formula calculating stroke volume, thoracic impedance (Zo/L) showed a significant increase during salt restriction and a change (delta) in ln L/Zo related significantly to delta ln diastolic pressure in linear multiple regression analysis. As thoracic impedance has been reported to reflect intrathoracic fluid content, a decrease in extracellular fluid volume was suggested as a possible mechanism of the fall in blood pressure even with modest sodium restriction.

Adult↗

Increased cardiovascular response to epinephrine in hypertrophic cardiomyopathy.

To study the role of catecholamines in the pathogenesis of hypertrophic cardiomyopathy (HCM), hemodynamic responses to low and high dose infusions of epinephrine (0.037 and 0.074 micrograms/Kg/min) were compared between 21 patients with nonobstructive HCM and 21 healthy controls, matched for age and sex. During low dose infusion, patients with HCM showed significantly greater responses (p less than 0.05) than controls in echocardiographic left ventricular (LV) end-systolic dimension (-8 +/- 1% vs -4 +/- 1%, mean +/- SEM), fractional shortening (12 +/- 2% vs 7 +/- 1%) and peak systolic velocity of the LV posterior wall (32 +/- 5% vs 15 +/- 4%), but the differences disappeared during high dose infusion. Thus, patients with HCM started to respond to epinephrine earlier than controls and seemed to have an increased sensitivity of beta-adrenergic receptors in the cardiovascular system. As the augmented responses were more evident in younger patients (less than 35 years) who manifested frequent familial occurrences of HCM, the increased sensitivity to catecholamine was postulated to be genetically determined and to be related to the abnormal myocardial hypertrophy of HCM.

Adolescent↗

The effect of thymectomy on the development of hypertension in spontaneously hypertensive rats.

We studied the effect of thymectomy on the development of hypertension in spontaneously hypertensive rats (SHR). There were no significant differences between thymectomized and sham thymectomized SHR during either the initial or chronic phase of spontaneous hypertension. Similarly, administration of anti-Thyl. 1 or anti-T sera did not influence the blood pressure in SHR during the chronic phase. The results suggest that the thymus does not play a direct role in the development and maintenance of blood pressure in SHR.

Animals↗

An advanced form of familial hypertrophic cardiomyopathy showing massive myocardial fibrosis with intramural small arterial thickening. An autopsy case.

An autopsy case of an advanced form of hypertrophic cardiomyopathy (HCM) showing marked fibrosis with intramural small arterial abnormalities is presented in this report. A 52-year-old woman, who had a positive family history of HCM, was admitted because of palpitations. The chest roentgenogram showed a mildly enlarged cardiac silhouette and the electrocardiogram revealed abnormal Q waves and R wave and T wave abnormalities. The echocardiogram revealed hypokinesis with thinning of the interventricular septum and the anterior wall of the left ventricle. Percutaneous right ventricular endomyocardial biopsies demonstrated moderate interstitial fibrosis with small arterial thickening. At necropsy, the anterior and posterior walls of the left ventricle and the interventricular septum were markedly thinned and showed a massive transmural fibrosis. Moreover, the intramural small arteries, 50-300 microns in diameter, showed marked intimal and medial hypertrophy with proliferation of elastic fibers and smooth muscle cells. From these findings, it is suggested that this was originally a case of HCM which progressed to a decompensated stage because of the abnormal intramural small arteries. The significance of small arterial lesions in HCM is discussed.

Cardiomyopathy, Hypertrophic↗

[Left ventricular peak filling velocity and its relevant factors in hypertrophic hearts].

To evaluate the relevant factors of left ventricular peak filling velocity, M-mode echocardiograms showing the left ventricular cavity were recorded and digitized for 81 patients with hypertrophic hearts (HTH) due to hypertensive heart disease (HHD, n = 30), hypertrophic cardiomyopathy (HCM, n = 25), aortic valve stenosis (AS, n = 9), and HHD and HCM with congestive heart failure (HHD and HCM with CHF, n = 17). Peak rates of increase or decrease in dimension (Vf and Ve, respectively) and peak values of instantaneous circumferential fiber lengthening and shortening velocities (Vf/D and Ve/D, respectively) were determined by computer analysis of left ventricular internal dimensions. Systolic excursion (SE), percent fractional shortening (%FS), mean circumferential fiber shortening velocity (mVcf), thickness of the interventricular septum and posterior wall at end-diastole and the sum of them (WThivs, WThpw, and WThivs + pw, respectively) were also calculated. Their variables were compared with those of normal subjects (n = 24). The results obtained were as follows: Systolic functions in HTH without CHF were similar to those of the normal subjects, but Vf and Vf/D were significantly decreased. Differences in Vf and Vf/D between various HTH without CHF were not significant. In AS and HTH with CHF, Vf and Vf/D were significantly decreased together with systolic function. Vf correlated significantly with WThivs + pw, SE, Ve, and WThivs, and Vf/D with %FS, SE, Ve/D, and Ve.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗