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Biomedical subjects

Y Koga

Publications and source records attributed to Y Koga.

At least 487 records · Page 27Linked to original sources

Pharmacological profiles of a potential LTB4-antagonist, SM-9064.

Antagonistic activity against leukotriene B4 (LTB4) and other pharmacological activities of SM-9064 were studied in vitro and in vivo. It inhibited the chemotaxis of rat polymorphonuclear leukocytes (PMNLs) induced by LTB4 (IC50 = 1.3 X 10(-7) M, not by other chemoattractants. Its agonistic activity was much less than that of LTB4. It suppressed the Arthus reaction-induced inflammation in mice with the dose of 5 mg/kg, i.p. or 10 mg/kg, p.o. These results suggest that SM-9064 is a candidate of LTB4 antagonists, which is effective in some type of inflammation.

Animals↗

Augmentation of B16 melanoma lung colony formation in C57BL/6 mice having marked granulocytosis.

The effect that polymorphonuclear leukocytes (PMN) may have on the metastatic colonization of tumor cells is controversial: some laboratories have reported that PMN can inhibit metastasis whereas others have shown an augmentation effect. We have exploited our finding that a particular fibrosarcoma (BMT-11) transplanted subcutaneously into syngeneic C57BL/6 mice induces a progressive increase in the number of circulating PMN, to re-examine this question. We used such "granulocytosis-positive" mice as recipients of B16 melanoma cells to examine the influence of significant granulocytosis on the level of lung tumor colonies. The number of B16 melanoma lung colonies detected after intravenous (i.v.) injection was significantly higher in BMT-11 tumor-bearing mice with granulocytosis than in control (non-tumor-bearing) mice. Retention of 125IUdR-labelled B16 cells 24 hr after the i.v. injection was 3 to 10 times greater in mice with granulocytosis than in controls. Either simultaneous injection, or preinjection of PMN with B16 cells, increased the lung-colonizing capacity of B16 melanoma cells. These results suggest that abnormally increased numbers of PMN in the peripheral blood, particularly in the lung circulation, can enhance the ability of tumor cells to colonize or metastasize.

Animals↗

Malignant potentiality of squamous cell carcinoma of the esophagus predictable by DNA analysis.

Cell nuclear deoxyribonucleic acid (DNA) content was microspectrophotometrically determined in biopsy specimens from 75 patients with squamous cell carcinoma of the esophagus. The relationships among DNA distribution patterns, pathohistologic features, and prognosis were investigated. In patients with a high hyperploid DNA content (type IV), there was a high frequency of lymph node metastasis and lymphatic invasion, as compared with those exhibiting the near diploid DNA content (type II). In the type IV group, 22 of 23 patients died within 2 years, whereas patients with type II had a good clinical course and the 5-year survival rate was 60%. The DNA distribution pattern, determined by a multivariate Cox model analysis, was one of independent and significant prognostic variables. As these findings suggest that the DNA distribution pattern reflects the malignant potentiality of the tumor, the preoperative determinations of the DNA pattern in biopsy specimens of the esophageal carcinoma should provide a valuable parameter for predicting the prognosis.

Adult↗

A human T cell-specific cDNA clone (YT16) encodes a protein with extensive homology to a family of protein-tyrosine kinases.

We report here the isolation of a human T cell-specific cDNA clone (YT16) that encodes a protein with extensive homology to a family of transformation and proliferation-related protein-tyrosine kinases (PTK). The message size of YT16 is 2.2 kb and it encodes a protein of 507 amino acids with a mol. mass of 57,136 Daltons. The deduced protein sequence has an overall homology of about 50% to the viral oncogene products of src and yes. Around the PTK catalytic domain, the homologies increase to 70-80% between the deduced protein sequence of YT16 and those of the PTK viral oncogenes. Of special interest is the extensive homology between the deduced protein sequence of YT16 and that of a recently reported murine B and T lymphocyte-specific PTK, lskT. It is possible that YT16 either encodes the human homologue of this murine gene, or a protein with similar function(s) in T cells.

Amino Acid Sequence↗

T cell recruitment from the thymus to the spleen in tumor-bearing mice. I. Analysis of recruited cells by surface markers.

After inoculation of tumor cells (methylcholanthrene-induced sarcoma), the number of Thy 1+ cells and PNA (peanut agglutinin) binding cells, which were shown to be different subpopulations were increased in the spleen of thymus-intact mice, in contrast this increase was not observed in adult thymectomized mice. In experiments performed concurrently with splenic cell analysis, we found that the plasma PGE2 levels declined in parallel with the tumor growth. Prevention of such a decline of plasma PGE2 level by replenishment with exogenous PGE2 inhibited the splenic cell increase in tumor bearers. In the tumor-bearing mice, cell traffic systems from the thymus to the periphery was ascertained by injecting fluorescein diacetate (FDA) into the thymus and observing fluorescein positive cells in the periphery. We suggest that increased recruitment of thymic cells to the periphery may be mediated by PGE2 in the presence of a tumor.

Animals↗

Primary malignant thymoma in a 6-year-old boy.

Although not uncommon in adults, thymomas are the least common mediastinal tumors in children. The behavior of these tumors in children is partially distinct with a much more rapid course and a poor prognosis. A symptom-free 6-year-old boy was treated for malignant thymoma detected incidentally on a chest X-ray in a school mass examination. At operation, the tumor was found to have already invaded the surrounding tissue. Complete removal at the base of the invasive tumor is the treatment of choice.

Child↗

Primary liposarcoma of the mediastinum--a case report and review of the literature.

Liposarcoma of the mediastinum is a rare disease. A 59 year old woman was seen with the complaint of dizziness. A chest radiogram taken during the course of investigation for hypertension revealed a large mass shadow 24 X 18.5 X 12 cm located in the anterior mediastinum. The tumor of the mediastinum was diagnosed as a benign lipoma when it was first resected, but subsequently proved to be a liposarcoma when it re-appeared 2 years and 10 month later. Based on the WHO classification, the mixed type of liposarcoma was diagnosed. The salient and pathological features of mediastinal liposarcoma are reviewed and compared with those nine cases reported in Japan and fifty in North America and European countries. Treatment by simple enucleation or shelling out of the tumor should be discouraged, since this seems to be the main cause of local recurrence. Surgical wide en bloc excision is the treatment of choice.

Female↗

Prostaglandin modulation of the postnatal development of T and B lymphocytes in the spleens of newborn mice.

The effects of prostaglandin E2 (PGE2) on postnatal development of the T and B cells in the spleen were studied to investigate the relationship between in vivo PG concentration and immunological development of peripheral lymph organs after birth. The development of the T and B cells were suppressed by the PGE2 injection, while augmented by the indomethacin injection. Especially in the T cells, cellular immigration from the thymus to the spleen was suppressed by the PG injection. Therefore, in vivo PG concentration in postnatal period might have some affect on the development of peripheral lymph organs, and the cellular traffic from central to peripheral lymph organs.

Animals↗

Indomethacin-induced sialic acid-mediated changes in surface markers from "cortical type" to "medullary type" in murine thymoma line EL-4.

The effect of indomethacin (INDO), a specific inhibitor of prostaglandin (PG) synthesis, on the expression of markers during thymocyte differentiation such as Thy-1, H-2K, and peanut agglutinin (PNA) receptor was examined by immunofluorescence, using poorly differentiated thymoma, EL-4, as the indicator cells. EL-4 cells grown in the culture medium in the presence of INDO exhibited lower levels of Thy-1 and PNA, and a higher level of H-2K, compared with the EL-4 cells grown in medium without INDO. The decrease in PNA level by INDO was attributed to an increased density of sialic acid bound to PNA receptors on the cell surface, because treatment with neuraminidase (Nase) released more sialic acid from such cells, as compared with control cells, and markedly increased the detectable amounts of PNA receptors. On the other hand, a decrease of Thy-1 or an increase of H-2K may be ascribed to the decrease of Nase-resistant sialic acid on the cell surface, determined by analyses with FITC-LPA, sialic acid-specific lectin, and by metabolic labeling of surface sialic acid. These results suggest that the PG-system modulates the metabolism of sialic acid located on the thymocyte surface and alters the expression of surface markers of thymocytes.

Animals↗

Quantitative evaluation of regional myocardial blood flow by videodensitometric analysis of digital subtraction coronary arteriography in humans.

Videodensitometric analysis of digital subtraction coronary arteriography, a new approach for calculating contrast disappearance half-life (T1/2), was assessed in determining regional myocardial blood flow quantitatively. Forty-one patients with coronary artery disease and 12 with angiographically normal coronary arteries underwent digital subtraction coronary arteriography by manual injection of contrast medium into the left main coronary artery. The T1/2 was calculated from a time-density curve generated in the four sectors of the myocardium perfused by the left anterior descending coronary artery. The mean T1/2 value of the four sectors correlated inversely with the great cardiac vein flow measured by the thermodilution method (r = -0.89), and appeared to be a reliable index of myocardial blood flow. The relation of mean T1/2 with percent stenosis of the left anterior descending coronary artery was curvilinear (r = 0.88) and an abnormally high T1/2 occurred in patients with coronary stenosis greater than 75%. In patients with comparable stenosis of the left anterior descending artery, the apical T1/2 was significantly increased in those with impaired apical wall motion, while it was significantly decreased in those with coronary collateral vessels. These findings suggest that regional myocardial blood flow begins to decrease in vessels with greater than 75% stenosis, and that myocardial contraction and collateral flow are additional factors that modify regional myocardial blood flow. Thus, the contrast disappearance half-life (T1/2) derived by computerized washout analysis of digital subtraction coronary arteriograms proved useful as an index for quantitative evaluation of regional myocardial blood flow.

Adult↗

T-cell recruitment from the thymus to the spleen in tumor-bearing mice. II. Functional characteristics of recruited T-cells.

The effect of prostaglandin E2 (PGE2) on characteristics of splenic T-cells in tumor-bearing mice (TBM) was studied from the viewpoint of PGE2-mediated cell-recruitment system from the thymus to the spleen. The splenic T-cells of TBM enhanced tumor growth. In the TBM, the total number of thymocytes decreased, and the number of splenic T-cells concurrently increased. In adult thymectomized tumor bearers, these tumor growth-enhancing T-cells were absent in the spleen, and the number of splenic T-cells remained unchanged. Such suppressor T-cells in the spleens of TBM may relate to recruitment of immature T-cells from the thymus. The levels of PGE2 in the plasma were depressed in the TBM. Replenishment by exogenous PGE2 prevented both an increase in splenic T-cell population and an augmented generation of T-cells that had an enhancing effect on tumor growth. Our findings show that a low level of PGE2 induced the T-cell recruitment from the thymus to the spleen and that such recruited cells led to an acceleration of tumor growth.

Animals↗

Thymus-dependent increase in splenic T cell population in postpartum mice.

Cell dynamics in the thymus and spleen of mice during the first allogeneic pregnancy and during postpartum were investigated. A considerable decrease in the number of thymocytes occurred at midpregnancy and was sustained until postpartum. There was an increase in the number of splenic T cells on the third postpartum day. These splenic T cells were shown to have the Lyt-1+ 2-phenotype, as determined by multiparameter analysis, and their responsiveness to Con A was increased compared with splenic T cells of virgin mice. Since such T cells were not observed in the postpartum spleen of adult thymectomized mice, they may have derived from the thymus. The response to Con A by normal virgin spleen cells was depressed when spleen cells from 3-day postpartum mice were added to the culture as the third party cells. Thus, the increased number of splenic T cells may act as inducer cells in the suppressor circuit during postpartum.

Animals↗

Clinical study of objective pulse diagnosis.

The recording of the objective pulse diagnosis was performed and the meridian points were selected from this recording. The proper meridian points (five element points) according to the five element theory and the improper points (non-five element points) were stimulated. Pain threshold was elevated by the stimulation of five element points and not raised by non-five element points in a patient who had nasal polypectomy under acupuncture analgesia and also in 6 of 9 healthy volunteers. Naloxone reversal of elevated pain threshold was also observed in volunteers.

Acupuncture Therapy↗

Effects of propranolol and nifedipine on exercise-induced attack in patients variant angina: assessment by exercise thallium-201 myocardial scintigraphy with quantitative rotational tomography.

To examine the effects of propranolol and nifedipine on exercise-induced attack in patients with variant angina, exercise 201Tl myocardial scintigraphy with quantitative analysis by emission-computed tomography was performed in 20 patients with variant angina after oral propranolol (80 mg), nifedipine (20 mg), and placebo. Exercise-induced attack occurred in 11 patients on placebo, in 14 on propranolol, and in none on nifedipine. The exercise duration was significantly shorter in those on propranolol (p less than .05), but significantly longer in patients on nifedipine (p less than .05) than in those on placebo. The peak rate-pressure product was significantly lower in patients on propranolol (p less than .01), but did not change in those on nifedipine, as compared with that in patients on placebo. The size of the perfusion defect as measured by 201Tl tomography was significantly greater in patients on propranolol (p less than .05), but significantly less in those on nifedipine (p less than .01) than in those on placebo. In conclusion, propranolol does not suppress but rather may aggravate exercise-induced attack in patients with variant angina, while nifedipine suppresses it. This unfavorable effect of propranolol on exercise-induced attack in patients with variant angina is likely to be due to a reduction of regional myocardial blood flow.

Adult↗

Relationship of exercise or pacing induced ST segment depression and myocardial lactate metabolism in patients with hypertrophic cardiomyopathy.

To elucidate a mechanism and clinical implications of chest pain and ST segment depression during exercise in patients with hypertrophic cardiomyopathy (HCM), we investigated myocardial lactate metabolism during atrial pacing in 18 patients with HCM and 7 control subjects with normal coronary arteriograms. At an average peak pacing rate of 146 beats/min, 11 patients with HCM showed the lactate extraction ratio decreasing to less than 5%, and 6 of them produced lactate, suggesting the development of myocardial ischemia. These 11 patients with abnormal lactate metabolism demonstrated ST segment depression (82%) and chest pain (73%) during pacing and also presented abnormal results (55%) on an exercise stress test. These abnormal findings were not observed in the other 7 patients who had ratios of 5% or more at peak pacing. These observations suggest that ST segment depression and chest pain are manifestations of myocardial ischemia even in patients with HCM who have normal coronary arteriograms, and that patients with pacing induced abnormal lactate metabolism are at an increased risk of developing myocardial ischemia during exercise.

Adolescent↗