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Biomedical subjects

M Koike

Publications and source records attributed to M Koike.

At least 307 records · Page 17Linked to original sources

Human chorionic gonadotropin alpha-subunit in endocrine cells of fibrotic and neoplastic lung. Its mode of localization and the size profile of granules.

To investigate the nature of various endocrine cells immunoreactive for human chorionic gonadotropin (hCG alpha) in the lung, immunoelectron microscopic study was performed on fibrotic adult lungs and endocrine neoplasms of the lung. The mode of localization of hCG alpha and the size profile of hCG alpha granules were different among endocrine cells under various proliferative conditions. The population of hCG alpha granules in the grouped type of endocrine cells was more variable with a shift to smaller size (mean area: 1.395 x 10(-2) microns 2, mean maximum diameter: 149.8 nm), than that in solitary ones (1.493 x 10(-2) microns 2, 155.4 nm). Tumorlet endocrine cells had larger hCG alpha granules (1.800 x 10(-2) microns 2, 171.3 nm) without change of SD of size parameters. In carcinoid tumors, the size profile of hCG alpha granules was considerably different from that in the three types described above. Moreover, hCG alpha granules were significantly smaller in size in carcinoid tumors without lymph node metastasis (2.295 x 10(-2) microns 2, 189.8 nm) than those in malignant carcinoid tumors with metastasis (3.368 x 10(-2) microns 2, 230.5 nm). The population of hCG alpha granules in atypical endocrine tumor was the parallel shift to a larger scale (6.251 x 10(-2) microns 2, 307.5 nm) from that of malignant carcinoids and the distribution pattern was different from that in benign carcinoids. In small cell carcinoma of the lung, hCG alpha immunoreaction was preferentially present in perinuclear space and dilated rough endoplasmic reticulum. The mode of localization of hCG alpha and the size profile of hCG alpha granules, representing specific features of intracellular processing of hCG alpha, may be closely related with some qualitative changes in the neoplastic process of pulmonary endocrine cells.

Carcinoid Tumor↗

[Esophageal carcinoma with hypercalcemia that appeared to be caused by prostaglandin E2 produced by the tumor cells].

Discussed is the case of a 50-year-old man with a well advanced esophageal carcinoma who, during his final clinical course, suddenly developed hypercalcemia (max: 15.0 mg/ml). His serum parathyroid hormone level, however, remained within normal limits. On autopsy, an extensive metastasis to many organs and lymph nodes was noted but no evidence of a bone metastasis. Nude mice bearing the same tumoral tissue were found, on autopsy, to have similarly developed hypercalcemia and cells that were cultured were found to produce an excessive amount of Prostaglandin E2 (PGE2). These findings suggest that this humoral hypercalcemia of malignancy (HHM) was caused by excessive PGE2 produced by the tumor cells, although other possible factors should be investigated.

Animals↗

Human chorionic gonadotropin in the thymus. An immunocytochemical study on discordant expression of subunits.

To demonstrate discordant expression of human chorionic gonadotropin (hCG) subunits in the human thymus and thymic tumors, immunocytochemical studies were performed with immunoelectron microscopy. In the fetus, hCG beta-positive cells were identified in excess of hCG alpha-positive cells (hCG alpha: 1.38 +/- 0.18/mm2, hCG beta: 4.50 +/- 1.13/mm2). They were usually different populations in serial sections. There were 0.18 +/- 0.03/mm2 synchronously positive cells using the double immunostaining method, comprising approximately 3% of the total positive cells. The immunoreactive material for both subunits was present at the rough endoplasmic reticulum (RER), perinuclear space, and vesicular structures with protruding microvilli in the lumens. hCG alpha was expressed preferentially in the endocrine tumors of the thymus and non-germ-cell tumor, with rare positivity for beta-subunits of glycoprotein hormones. The hCG alpha-immunoreactive material also was present in the granules as well as in RER of the neoplastic cells. In four teratomas of the thymus, hCG alpha-positivity only was present in endocrinelike cells. The subunit profile of hCG was unbalanced in the thymus and isolated hCG alpha-expression in the fetal thymus may represent the endocrine cell with a primitive storage mechanism. The discordant expression of hCG subunits may be common in nontrophoblastic tissues.

Adult↗

Establishment of a human malignant meningioma cell line with amplified c-myc oncogene.

A new cell line (KT21-MG1) has been established from a human malignant meningioma transplanted into nude mice. The cultured cells showed epithelial cell-like morphology and were positive immunohistochemically for vimentin as the original tumor. They have been grown continuously in vitro for more than 2 years. The population doubling time was about 24 hours at the 30th passage. The cells are capable of proliferating in soft agar medium and produced tumors in nude mice, the histologies of which were similar to the original patient-derived tumor. Analysis of cellular oncogenes showed that myc and fps were amplified approximately tenfold and threefold, respectively, in this cell line, whereas N-myc, L-myc, N-ras, K-ras, H-ras, abl, erbB2, Blym, src, raf-1, myb, and sis were not changed significantly. The amplification of myc was accompanied by an enhanced expression. Chromosome studies of cultured cells showed the monosomy of chromosome 22 that has been reported to be a specific abnormality in meningiomas.

Animals↗

Ultrastructural identification and clinical significance of light microscopic giant mitochondria in alcoholic liver injuries.

The identification and clinical significance of light microscopic giant mitochondria (GM) were investigated in liver biopsy specimens of 60 alcoholics. By light microscopic examinations using the same section and neighboring sections, we suggest that light microscopic GM correspond to the crystalloid bodies (CB) detected on ultrastructural observation. The reasons are as follows: (1) difference in stainability between eosinophilic light microscopic GM and acidbasophilic mitochondria; (2) similarity in morphological features and density of the round- and cigar-shaped types at the light microscopic level to those of CB at the electron microscopic level; (3) similarity of the area occupied in the hepatic cytoplasm at both light and electron microscopic levels; (4) the crystalline structure of CB in compatible with the subtype of Mallory body (MB); (5) a description of CB has been made at the electron microscopic level, although not yet at the light microscopic level. Moreover, we clinically observed that light microscopic GM seldom appeared either in early fatty liver of cases aged 35 or less or the late macronodular liver cirrhosis stage of alcoholic liver injuries while they were frequently recognized during the acute aggravation phase of the chronic stage (GPT: p less than 0.05). Furthermore, if one was to assume that MB is a change accompanying necrosis of the liver cells, the light microscopic GM might be a change accompanying degeneration of the cytoplasmic organelles.

Fatty Liver, Alcoholic↗

High level expression of a synthetic gene coding for IgG-binding domain B of Staphylococcal protein A.

A gene coding for one of the IgG-binding domains of Staphylococcal protein A, designated domain B, was chemically synthesized. This gene was tandemly repeated to give dimeric and tetrameric domain B genes by the use of two restriction enzymes which gave blunt ends. The genes were highly expressed in Escherichia coli to afford a large amount of dimeric and tetrameric domain B proteins. The single domain B protein was efficiently produced as a fusion protein with a salmon growth hormone fragment. The fusion protein was converted to monomeric domain B by cyanogen bromide cleavage. The CD spectra of the monomeric, dimeric and tetrameric domain B proteins were essentially the same as that of native form protein A, showing that their secondary structures were very similar. The dimeric and tetrameric domain B proteins formed precipitates with IgG as protein A. This system permits the efficient production of mutated single and multiple IgG-binding domains which can be used to study structural changes and protein A-immunoglobulin interactions.

Amino Acid Sequence↗

Incorporation of human chorionic gonadotropin alpha-subunit into different types of granule in stomach endocrine cells. An immunoelectron microscopic study.

In order to demonstrate the ultrastructural localization of the alpha-subunit of human chorionic gonadotropin (hCG) in the stomach mucosa, an immunoelectron microscopic study was performed using formalin-fixed specimens. In pyloric glands, alpha hCG-positive granules were irregular in outline, with a mean area and maximum diameter of 2,857 x 10(4) nm2 and 218.4 nm, respectively. In fundic glands, the granules had a smoother outline and were larger in both area and maximum diameter (3,943 x 10(4) nm2, 246.8 nm) than those of pyloric glands (p less than 0.001). In the atrophic fundic glands of non-antral gastritis, the alpha hCG granules showed a difference in shape; more elliptical granules appeared to be increased, as indicated by the higher value of the axial ratio (1,452) and lower value of D (1,862) (log10 area alpha D.log10 perimeter) compared with those in pyloric (1,231, 1,968) and fundic glands (1,148, 1,979) (p less than 0.001). The alpha-subunit of hCG is thus incorporated into different types of endocrine cell in pyloric and fundic glands, and the granule morphology appears to differ in hyperplastic alpha hCG cells of non-antral gastritis.

Adult↗

Prevention of vertical transmission of hepatitis B virus by yeast recombinant hepatitis B vaccine.

In order to prevent vertical transmission of hepatitis B virus (HBV), yeast recombinant HB vaccine at a dose of either 5 mcg or 10 mcg was administered to 185 infants born to mothers who were positive for HBs antigen (HBsAg). All of them developed antibody to HBsAg (anti-HBs) after three vaccinations. Generally, the cut-off index (COI) of anti-HBs by radioimmunoassay (RIA) was higher in the 10 mcg dosage group than in the 5 mcg dosage group. The geometric mean titer (GMT) of anti-HBs, as measured by quantitative RIA, in the former group was 2.4 times that in the latter one month after the third vaccination. The incidence of clinical reactions was only 4% in a total of 561 injections, and none of the reactions were severe. It is concluded that recombinant HB vaccine is safe and has excellent immunogenicity for infants requiring prevention of HBV vertical transmission. It is also suggested that 10 mcg doses of the recombinant HB vaccine can provide more solid protection to high-risk infants without serious adverse reactions.

Carrier State↗

Molecular cloning of cDNAs for alpha and beta subunits of human pyruvate dehydrogenase.

The cDNAs encoding human PDH alpha and PDH beta were isolated from a HeLa cell cDNA library in the lambda gt11 expression vector by immunoscreening, followed by colony hybridization from a human foreskin fibroblast cDNA library. Nucleotide sequence analyses of the positive plasmid clones (pHPDA and pHPDB) revealed an insert of 1.36 kilobases (kb) for PDH alpha and one of 1.69 kb for PDH beta, respectively, allowing us to predict the complete amino acid sequences of the precursor and mature proteins of these two subunits. The amino acid sequences of the amino-terminal regions of the two subunits of human PDH were highly homologous with those of mature porcine PDH. The amino acid sequences of phosphorylation sites determined in PDH alpha of the bovine and porcine enzymes were also conserved in the human PDH alpha. Blot analysis of HeLa cell poly(A)+ RNA and the transcriptional product of the two cDNAs showed a single mRNA of 1.8 kb for PDH alpha and one of 1.7 kb for PDH beta. The precursor proteins of PDH alpha and PDH beta were detected by immunoprecipitation from an 35S-labeled, cell-free translation system. Our sequence of PDH alpha cDNA was compared with those of two other origins. The differences among these three PDH alpha cDNAs have been discussed.

Amino Acid Sequence↗

Intracellular topography of glycine-extended pro-gastrin-processing intermediates in human antral mucosa: an electron-microscopic immunocytochemical study.

To identify and characterize the subcellular topography of glycine-extended pro-gastrin-processing intermediates (G-Gly) in human antral mucosa, we performed an electron microscopic immunocytochemical study using region-specific antisera generated against the synthetic peptide, Tyr-Gly-Trp-Met-Asp-Phe-Gly (GL7), and C-terminal-specific anti-gastrin antisera. As has been previously reported, G-cells contained both electron-dense and electron-lucent granules, with a range of intermediate forms. Gastrin immunoreactivity was demonstrated in almost all granules of each type, whereas anti-GL7 antisera immunostained chiefly electron-dense granules. The relative ratio of GL7/gastrin granules varied among different cells but was approximately 1:10 on average. Other cytoplasmic organelles were devoid of specific labeling for GL7 or gastrin. As we have assumed that G-Gly serves as the immediate precursor for each molecular form of gastrin, electron-dense granules with high labeling for GL7 are regarded as the principal site for conversion of G-Gly to gastrin. This speculation supports many previous reports that electron-dense granules are immature and that the granules become less electron-dense with maturation.

Adult↗

Effect of yohimbine on urethane-induced hyperglycemia in rats.

Urethane is a widely used anesthetic and yohimbine is a well-known alpha 2-adrenergic antagonist. In fasted Wistar rats urethane at an anesthetic dose (1.25 g/kg, i.p.) caused an increase in plasma glucose, while pentobarbital at an anesthetic dose (40 mg/kg, i.p.) did not. Urethane caused no change in plasma glucose in adrenalectomized rats. The hyperglycemic effect of urethane was not inhibited by pretreatment with propranolol (1 mg/kg, p.o.) or prazosin (10 mg/kg, p.o.), but was reduced by pretreatment with phentolamine (10 mg/kg, p.o.) or yohimbine (10 mg/kg, p.o.). Urethane caused an elevation of plasma adrenaline, and yohimbine reduced the elevation. In addition, the pretreatment of yohimbine potentiated the urethane-induced increase in plasma insulin. These results indicate that yohimbine may inhibit the urethane-induced hyperglycemia that is mediated by the central and peripheral alpha 2-adrenergic systems.

Animals↗

Curve patterns in idiopathic scoliosis. A clinical and radiographic study.

We have developed a simple technique for demonstrating the sagittal profile of each rotated level of a scoliotic spine and used it to determine the patterns of lordosis and kyphosis in each of six clinical types of idiopathic scoliosis. The currently accepted classification of scoliosis is inaccurate and a modification is proposed. The three main types of scoliosis were shown to have sagittal profiles distinctly different from each other and from normal. Single structural curves had short lordotic sections at their apices, limited above and below by kyphosis. Double curves showed longer lordotic sections limited only by one area of kyphosis. Lordosis throughout the thoracic and lumbar spine was associated with triple curve patterns. The biomechanical effects of the abnormal sagittal profiles provide a simple explanation for the genesis and progression of the different types of scoliosis, and the recognition of the pattern of the sagittal abnormalities permits treatment to be designed on a sound anatomical basis for individual cases.

Adolescent↗

[Biochemical investigation on periodontal tissue of abutment teeth. Analysis of proteins in gingival crevicular fluid by high performance liquid chromatography].

Inflammatory responses in periodontal tissues cause breakdown of normal protein metabolism. The biochemical analysis of the protein components in gingival crevicular fluid (GCF) which is exudate from periodontal tissues offers a sensitive means of determining periodontal disease activity of abutment teeth. GCF proteins were applied to the high performance liquid chromatography (HPLC) analysis with following conditions: (1) column: an anion exchanger, (2) starting buffer: 20 mM tris HCl pH 8.5, (3) elution buffer: 20 mM tris HCl with 1 M NaCl pH 8.5, (4) gradient of NaCl concentration: 0-0.5 M = 20 min., 0.5-1 M = 5 min., (5) flow rate: 1 ml/min.. 12-15 peaks were observed in HPLC chromatograms, they were then divided to 6 fractions and were qualitatively analysed with agarose IEF, IEP and 2 DPAGE. Determined main protein components in each peak were IgG (peak 1), transferrin and hemopexin (peak 2), C'3 and IgA (peak 3), Albumin, C'3, IgA, IgM, Haptoglobin, alpha 2-macroglobulin and alpha 1-antitrypsin (peak 4), respectively. Those protein components were thought to be closely related to periodontal inflammation. It was suggested that the activity of periodontal disease was evidenced by observation of HPLC chromatogram on GCF proteins.

Chromatography, High Pressure Liquid↗

[Clinico-pathological study of solid poorly differentiated carcinoma of the stomach].

We have studied the clinico-pathological features of 42 autopsied cases involving solid, poorly differentiated carcinomas that histologically revealed a medullary growth pattern but none showing a tubular formation. Ninety percent of these 42 cases were male, and the 42 carcinomas were of 5 histological types as listed below: 1) small cell carcinoma-atypical carcinoid type (15 cases); 2) AFP-producing type (so-called "hepatoid carcinoma") (4 cases); 3) acinar type (8 cases); 4) signet ring cell-medullary type (2 cases); and, 5) large cell type (13 cases) The small cell carcinoma-atypical carcinoid type, the AFP-producing type, and the large cell type showed a severe hematogenous metastasis. In contrast, the acinar type had a lymphogenous metastasis the signet ring cell-medullary type, showed a lymphogenous and peritoneal metastasis. Each histological type well corresponded to the typical biological characteristics of each of these carcinomas of the stomach.

Adenocarcinoma, Mucinous↗

Human chorionic gonadotropin alpha-subunit in rectal carcinoids. Its mode of presence and the change of granule morphology.

To investigate the nature of endocrine cells immunoreactive for human chorionic gonadotropin alpha-subunit (hCG alpha), rectal carcinoid tumors were studied with immunohistochemistry and immunoelectron microscopy. There were two types of rectal carcinoids: Type A (n = 5) was diffusely argyrophilic and immunoreactive for serotonin with many hCG alpha-positive cells (16.7%-91.1%). Type B (n = 5) was dispersedly argyrophilic and contained, at most, 5% positive cells for pancreatic polypeptide (PP) with hCG alpha cells in 1.4% to 9.7%. By double immunostaining, 55.0% to 89.7% of hCG alpha cells were synchronously immunoreactive for serotonin in Type A and 3.2% to 11.8% of hCG alpha cells showed PP-positivity in Type B. HCG alpha-positive granules had a constant relationship between perimeter (P) and area (A), log10 A approximately D log10 P, in each case (n = 5). The inverse correlation was found between the value of D and the frequency of hCG alpha in the tumor or in the neoplastic cells (P less than 0.05). HCG alpha may represent the quantitative difference of rectal carcinoids and its expression may have some relation with granule morphology in neoplastic endocrine cells of the rectum.

Carcinoid Tumor↗

[Adult T cell leukemia with CD4- and CD8-].

A 53-year-old woman born in Kamo village of Shizuoka prefecture was admitted to Juntendo Izunagaoka hospital complaining cough and appetite loss. On physical examinations, general lymphadenopathy and hepatosplenomegaly were recognized. And also dry rales and wet rales were heard in the bilateral lungs. On hematological examinations, leukocytes has counted 74,900/microliters, of which 61% atypical lymphocytes, and there were HTLV-I infection and positive anti-ATLA antibody. By the above results, she was diagnosed as adult T cell leukemia (ATL). T cell subset analysis was (CD4-, CD8-, CD3-), which is rare in ATL. Three months after the admission, she was died of disturbances of respiratory function in spite of VEPA therapy. Surface marker changed from CD3- to CD3+ in the course. To illuminate this mechanism will be a key step for the future study.

Antigens, Differentiation, T-Lymphocyte↗