[Morphological studies of hormone-secreting tumors of the endocrine pancreas].
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Biomedical subjects
Publications and source records attributed to S Kishimoto.
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A genealogical survey of familial amyloid polyneuropathy in the Arao district of Japan was undertaken, and the data were analysed statistically. The survey revealed 92 patients (46 males and 46 females) in 9 families. Thirty-one of the patients (16 males and 15 females) are alive. For 44 patients, the mean age of onset was 34.1 years (range 20-46 years). The penetrance corrected for late onset was 83.5% by Morton's method. The segregation ratio of 18 sibships in which one of the parents was affected was 36 +/- 6% for single ascertainment and 46 +/- 5% for complete ascertainment; the corresponding figures of 14 sibships in which neither parent was affected was 30 +/- 7% for single ascertainment and 40 +/- 6% for complete ascertainment. The results of the analysis were consistent with the assumption of an autosomal dominant mode of inheritance.
An assay system for the measurement of human BCGF was established by employing anti-id-stimulated B-CLL cells, anti-mu-stimulated normal B cells, or a transformed B cell line. PHA-Sup from PHA-stimulated T cells induced proliferation of anti-lg-stimulated B cells or augmented proliferation of a B cell line, and the activity was dose-dependent. BCGF, IL 2, and BCDF activities in PHA-Sup were eluted in a 17K fraction by gel filtration in 0.5 M NaCl. BCDF activity (pl 5.8) was isolated by chromatofocusing, but BCGF and IL 2 activities (pl 6.5 and 6.9) were not separated. Absorption with an IL 2-dependent T cell line or anti-id-stimulated B-CLL cells showed BCGF and IL 2 were distinct molecules. An IL 2-dependent helper T cell clone, d4, secreted BCGF with the m.w. of 50K. The 50K-BCGF fraction had no IL 2 activity and was eluted in a 19K fraction by gel filtration in 4 M urea and 1 M NaCl. PMA stimulation of normal T cells induced 50K-BCGF, the m.w. of which was reduced to 19K in 4 M urea and 1 M NaCl. 50K-BCGF from d4 cells and 17K-BCGF from PHA-Sup showed a synergistic effect on the proliferation of anti-lg-stimulated B cells. The results show the existence of two distinct kinds of BCGF and the presence of the synergism between them.
In order to evaluate the clinical benefit of Nocardia rubra cell wall skeleton (N-CWS), a randomized controlled study was performed with inoperable lung cancer patients entered in 5 institutions from October 1978 to June 1981. Patients without pleural effusions were treated initially with conventional therapies such as chemotherapy and/or radiotherapy, according to common protocol, and then patients in performance statuses 0 to 3 were randomized into control and N-CWS groups with stratification into 16 categories according to 4 histological types and 4 clinical stages In the N-CWS group, 400 micrograms N-CWS were initially injected once or twice into the bronchial tumor using a fiberoptic bronchoscope, and subsequently 200 micrograms of N-CWS were injected at monthly intervals into the skin from the shoulders to upper arms. Of 309 patients, 118 patients in the N-CWS group and 108 patients in the control group were eligible for statistical analysis. There was statistically no significant difference in survival rate between the control and the N-CWS groups. According to histological type, significant prolongation of the survival period was observed in patients with small-cell carcinoma. The 97 patients with pleural effusions were initially randomized into control and N-CWS groups. In the control group, local chemotherapy with Adriamycin was performed and, in the N-CWS group, local administrations and monthly intracutaneous injections of N-CWS were given. Tube thoracostomy was performed in both groups. The local response rate was statistically greater in the N-CWS group than in the control group, and survival period was also prolonged significantly in the N-CWS group. The main adverse reactions to N-CWS were skin lesions in the injected sites and fever, but these were temporary and not serious.
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A cell line, designated OKK, has been established from a human maxillary carcinoma in a Japanese man. The cultured cells were inoculated into nude mice, with the subsequent establishment of tumors. Alkaline phosphatases were extracted from these tumors and partially purified by chromatography. The electrophoretically fastest moving isoenzyme, designated tentatively as OKK T isoenzyme, was biochemically and immunologically investigated by comparing it with the Kasahara isoenzyme purified partially from the tumor, which originated from FL cells inoculated into a nude mouse. The properties of the OKK T isoenzyme were identical to those of the Kasahara isoenzyme. Thus, the enzymes showed a similar inhibition by amino acids (L-phenylalanine and L-leucine), the same behavior with respect to other properties, including heat stability, immunological character and molecular weight. The genetic phenotype of the glucose-6-phosphate dehydrogenase of this established cell line was proved not to be identical to that of a HeLa cell line.
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An estrogen-responsive mouse Leydig cell tumor line (Tumor 124958) has been shown to contain only a low-affinity binder for estradiol in the cytosol fraction. This differed from the putative estrogen receptor in terms of its hormone-binding specificity as well as affinity. In addition, the possibility that an estrogen receptor-like molecule exists in the nuclei even without hormonal stimuli was examined using purified nuclei. Scatchard plot analyses showed that these nuclei possessed a large amount of estrogen binder having a high affinity for estradiol and diethylstilbestrol. The content of this nuclear binding component was not diminished by using molybdate, a potent inhibitor for receptor activation, and in vitro incubation of collagenase-dispersed cells with estradiol did not cause significant increase in the number of nuclear binding sites when compared with the values obtained by direct incubation of isolated nuclei with estradiol. These results support the view that this nuclear estrogen binder is not due to artificial migration of the cytosol receptor into nuclei during homogenization. The characterization of this nuclear binding component under cell-free conditions revealed that its affinity for estradiol in Mg2+-containing buffer was temperature dependent (Kd 3 nM at 30 degrees and 12 nM at 0 degrees) without significant alteration in the number of maximum binding sites. Introduction of a chelating agent (ethylenediaminetetraacetate) into the buffer system abolished the temperature effect on the affinity, resulting in high affinity for estradiol at both low and high temperatures. These Mg2+ and temperature effects were reversible. In addition, when compared with putative nuclear estrogen receptors, this nuclear binding was observed to be relatively resistant to high salt or micrococcal nuclease treatments in relation to solubilization from nuclei. However, trypsin digestion was found to result in a marked decrease in the nuclear binding sites, indicating that this unique nuclear binding component contains a protein unit(s). These results suggest the possibility that this tumor line contains a unique unoccupied nuclear estrogen binder which might be able to transmit estrogen signals to tumor cell nuclei with regard to tumor growth.