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Biomedical subjects

Y Yoshitake

Publications and source records attributed to Y Yoshitake.

71 records · Page 4Linked to original sources

[Role of growth factors in the autonomous growth of tumor cells].

Typical characteristic of tumor cells is a decreased dependence on the growth factors for promotion of their growth. Growth factor independence and autonomous growth of tumor cells has been thought to be due to the ability of the cells to produce growth factors. According to an autocrine hypothesis, growth factor can be secreted by tumor cells and then binds to its receptor on the same cells to create an uncontrolled growth stimulation. Although there has been much circumstantial evidence to support this hypothesis, an autocrine mechanism is still uncertain. We purified DSF (DNA synthesis factor) from an extract of rat Rhodamine fibrosarcoma. This factor with strong affinity for heparin-Sepharose was a basic protein with molecular weight of 17,000. These properties were similar to those of basic FGF (fibroblast growth factor). We found that primary cells from the sarcoma could grow in serum-free medium supplemented with the extract of the same sarcoma tissue. The extract was fractionated to purify proteins which supported the growth of primary cells. DSF, transferrin and albumin which localized in the tissue, not due to contamination of blood, were purified. When they were added to the serum-free medium, the cells grew at a similar rate to that in medium supplemented with serum. This finding suggests that the growth of sarcoma cells is stimulated by their own growth factor and by some environmental factors.

Animals↗

Suppressive effect of human natural killer cells on Epstein-Barr virus-induced immunoglobulin synthesis.

The suppressive effect of human natural killer (NK) cells on Epstein-Barr virus (EBV)-induced immunoglobulin (Ig) synthesis by autologous B cells was investigated. By Percoll discontinuous density gradient centrifugation, low-density fractions enriched for NK cells were isolated from human peripheral blood lymphocytes. These NK-enriched fractions were added to purified autologous B cells in the presence of EBV, were cultivated for 8 days, and were examined for their suppressive effect on Ig synthesis by an enzyme-linked immunosorbent assay. The fractions markedly suppressed both IgM and IgG synthesis induced by EBV. It was possible to reduce the suppressive effect of NK-enriched cells by complement-dependent lysis of NK cells and Leu-11, but not by OKT3 monoclonal antibody, indicating that NK cells may be responsible for the suppression of Ig synthesis. Upon close examination of interferon (IFN) activity, it was revealed that the co-cultures of NK-enriched cells and EBV-infected B cells generated production of IFN-alpha, which might be produced by NK cells in response to EBV-stimulated B cells. Addition of anti-IFN-alpha but not anti-IFN-gamma serum almost completely abrogated the suppressive effect of NK-enriched cells on Ig synthesis, indicating that IFN-alpha produced are required for the NK cell-mediated suppression of Ig synthesis. However, addition of IFN-alpha into purified B cells showed no direct suppressive effect on EBV-induced Ig synthesis by B cells in the absence of NK cells. Nevertheless, NK cells when previously incubated with IFN-alpha and added to B cells showed a suppressor activity on Ig synthesis to a level higher than that of untreated NK controls. These results strongly suggest the possibility that NK cells display an interaction with EBV-infected B cells and produce IFN-alpha, which in turn activates NK cells. These activated NK cells suppress the Ig synthesis by B cells, which undergo transformation induced by EBV.

Antibodies, Monoclonal↗

A human prostatic growth factor (hPGF): partial purification and characterization.

A growth factor capable of stimulating DNA synthesis of BALB/3T3 cells was purified about 1,000-fold from the cytosol of human benign hypertrophic prostates by heparin-Sepharose chromatography; the growth factor bound to the column in the presence of 0.5 M NaCl was eluted with 1.5-1.7 M NaCl. Its molecular weight and isoelectric point were estimated to be 11,000-13,000 and 10.5, respectively. It was sensitive to heat- and acid-treatments but resistant to disulfide-reducing agent. The final preparation was able to stimulate DNA synthesis at 10 ng/ml. The degree of stimulation was dependent on serum concentration in the assay system; the degree of maximum stimulation increased about 5 times as serum concentration increased from 0.2 to 2%.

Cytosol↗

Localization of prostatic basic protein ("probasin") in the rat prostates by use of monoclonal antibody.

Isolated nuclei of the rat prostates contain a unique androgen-dependent basic protein, "probasin". Despite that it was hardly detectable in the cytosol centrifugally prepared from the prostates, immunofluorescent histological analysis of whole tissues using monoclonal antibody, which was raised against probasin purified from the nuclei, revealed that probasin was abundantly localized in the lumen and acinal regions of the epithelium, but hardly in the nuclei. Previous extraction of secretory fluid from the prostates caused about 60% decrease in the probasin content of isolated nuclei. These suggest that probasin was originally a secretory component in the prostates, being redistributed from the secretory fluid and granule into nuclei during fractionation of subcellular components.

Androgen-Binding Protein↗

Production and properties of a monoclonal antibody against human epidermal growth factor.

A monoclonal antibody against human epidermal growth factor (hEGF) was obtained from a mouse hybridoma cell line. The purified monoclonal antibody from the ascites fluid of a mouse injected with one of the cell lines was specific for hEGF and did not cross-react with mouse EGF (mEGF). Its Kd value for hEGF was 1.4 X 10(-9) M. This monoclonal antibody inhibited the biological activities of hEGF, including its binding to the receptor of BALB/3T3 cells and its stimulation of DNA synthesis in the cells, but did not affect the activities of mEGF. The monoclonal antibody completely inhibited DNA synthesis stimulated by human urine from a patient without a tumor, but only partially inhibited the stimulatory activity in urine from a tumor-bearing patient.

Animals↗

Enhanced glycogen repletion in liver and skeletal muscle with citrate orally fed after exhaustive treadmill running and swimming.

A possibility whether an oral feeding of citrate, which has been reported to inhibit phosphofructokinase in vitro, following exercise to exhaustion could increase the rate of glycogen repletion in liver and soleus muscle was tested in treadmill running trained (experiments 1 and 2) and swimming trained rats (experiment 3). An exhaustive running or swimming was loaded at the end of the experiments, resulting in a significant reduction in liver and soleus muscle glycogen stores. The feeding of 1.0 and 0.5 g of citrate per kg of body weight just after the exhaustive running could significantly increase the liver glycogen repletion during a 2-hr recovery period, but this was not observed in soleus muscle (experiment 1). As compared with a single feeding of 3.3 g of glucose per kg of body weight, a mixed feeding of 0.5 g of citrate and 3.0 g of glucose after an exhaustive running (experiment 2) and swimming (experiment 3) could significantly enhance the repletion of glycogen stores in both liver and soleus muscle. These results clearly indicate that the postexercise feeding of citrate can stimulate the glycogen repletion in liver and skeletal muscle during an early period of recovery.

Administration, Oral↗

HLA antigens as immunogenetic markers of alcoholism and alcoholic liver disease.

HLA antigens were studied among 94 chronic alcoholics. Concerning A and B-loci, there was no significant change of phenotype frequency (PF) in the HLA typing between the patients and controls (80 healthy subjects). However, there was a significant difference in the PF of CW3 between chronic alcoholics and controls (58.5% in alcoholics vs 30.0% in controls). The corrected p value was less than 0.05 with relative risk value being 3.29 HLA-DR loci were also detected in 26 patients, but there was no significant difference between the patients and controls. All alcoholics were subdivided according to the hepatic morphology, and the PF of HLA was examined. A significant high frequency of HLA CW3 was found in patients with hepatitis (64%) compared to controls (30%). There was also an increased PF of CW3 in the liver cirrhosis group (59% in cirrhosis group vs 30% in controls). In conclusion, chronic alcoholics have a significantly higher PF of HLA-CW3 as compared to controls. This characteristic feature becomes even more distinct in alcoholics with severe hepatic lesions.

Adult↗

Influence of heart rate and age on Q-Korotkoff sound intervals.

The Korotkoff sound appearance time (QK intervals) was measured in 224 normal subjects of both sexes between the age of 6 and 79 years. The sex difference was not obvious except for the diastolic values of the intervals (QKd) in the sixth decade. Although the QK intervals remained almost unchanged between the third and the fifth decade, both the systolic (QKs) and the diastolic values were significantly smaller in the young subjects under the age of 20. On the other hand, QKs was significantly decreased and QKd and the difference between the systolic and diastolic values (QKs-d) were significantly increased in the elderly subjects. The short QK interval in the young subjects was considered to be mainly attributable to the short preejection period, while the increased pulse wave velocity was postulated to be the main responsible factor for the shortening of QKd in the elderly subjects. A statistically significant negative correlation was demonstrated between QKd and the heart rate in both sexes, while QKs and QKs-d were not significantly correlated with the heart rate.

Adolescent↗

Functionally atrialized parchment-like right ventricle with extensive myocardial fibrosis of left ventricle.

A 18-year-old female with unusual type of parchment-like right ventricle died of intractable congestive heart failure was reported. A catheter study revealed the absence of systolic contraction of the right ventricle. The pressure tracing curve in the right ventricle was virtually the same as in the right atrium. At autopsy, there was an extensive myocardial fibrosis of the left ventricle in addition to the almost total absence of the myocardium of the right ventricle. The case was considered to be a unique type of idiopathic cardiomyopathy.

Adolescent↗

Different antitumor activities of anti-bFGF neutralizing antibodies: heparin-binding domain provides an inefficient epitope for neutralization in vivo.

Basic fibroblast growth factor (bFGF) plays an important role in tumor growth and angiogenesis. To elucidate the efficient recognition sites by anti-bFGF neutralizing antibodies, we generated two anti-bFGF neutralizing monoclonal IgG1 antibodies (mAbs), 2G11 and 1E6, recognizing different sites, and estimated as binding to the heparin-binding and the receptor-binding regions of bFGF, respectively, both of which have been shown to be important for its receptor interaction. Despite their high in vitro anti-bFGF activity in the absence of heparin, 2G11, with in vitro activity in competition with heparin, failed to inhibit the in vivo tumor growth of bFGF-producing RPMI4788 cells, though 1E6, showing non-competition with heparin, exhibited a significant antitumor effect. These results show that the heparin-binding domain of bFGF provides an inefficient epitope for in vivo neutralization of anti-bFGF mAb, and anti-bFGF neutralizing mAbs without competition against heparin have the potential to show in vivo antitumor effects.

Animals↗