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Biomedical subjects

K Ohsumi

Publications and source records attributed to K Ohsumi.

At least 73 records · Page 4Linked to original sources
PubMed1992

Urinary excretion of parathyroid hormone-related protein as a predictor of hypercalcemia in patients with adult T-cell leukemia.

Hypercalcemia with adult T-cell leukemia (ATL) is chiefly caused by an excessive production by tumor cells of parathyroid hormone-related protein (PTHrP). We have previously reported hypercalcemic patients with solid tumors to excrete a large amount of the C-terminal fragments of PTHrP (C-PTHrP) into their urine. To elucidate whether PTHrP production correlates with or predicts the development of hypercalcemia, we studied the urinary excretion of C-PTHrP in 36 ATL patients. The urinary excretion of C-PTHrP was in the normal range (< 0.40 nmol equivalent to PTHrP (109-141)/g creatinine) in HTLV-1-positive carriers (n 3), ATL patients in complete remission (n 2) and chronic type ATL patients (n 2). It was marginally increased in seven patients in partial remission, and gradually increased as the disease progressed. In 20 patients who died without or with hypercalcemia, it was increased to 1.98 +/- 0.69 (n 9) and 7.6 +/- 2.1 nmol/g creatinine (mean +/- SD, n 11, P < 0.01), respectively. Urinary C-PTHrP excretion was significantly correlated with serum calcium and LDH levels as well as with CD25-positive cells in the peripheral blood. In four patients whose urinary excretion had been serially determined, it increased prior to the development of hypercalcemia. The findings suggest the urinary excretion of C-PTHrP to be of use as a predictor of the development of hypercalcemia in ATL patients. In ATL patients whose urinary excretion of C-PTHrP is progressively increasing, the serum calcium concentration should be carefully monitored to prevent hypercalcemic crisis.

Adult↗
PubMed1992

[Intrapleural treatment of breast cancer patients with pleural effusions: an analysis of 13 institutes in Kyoto and Shiga Prefectures. Kyoto and Shiga Breast Cancer Study Group].

Sixty-seven breast cancer patients with malignant pleural effusions underwent their first thoracentesis between 1980 and 1990 at 13 institutes in Kyoto and Shiga Prefectures. They received various intracavitary treatments including OK-432 and cultured effusion lymphocytes (n = 29, group A), OK-432 alone (n = 12), chemotherapeutic agents alone (n = 9), OK-432 and chemotherapy (n = 16) or other (n = 1, lentinan and tetracycline) therapy. Response rate and median survival time were 90%, 12 months for group A, respectively and 40% and 3 months for other treatments (group B, n = 38), resulting in significant differences. Multivariate analysis using Cox's proportional hazard model showed that the immunotherapy using cultured lymphocytes was the most important factor prolonging survival among several significant prognostic factors such as concomitant liver metastasis, disease-free period and laterality of effusion.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Characterization of the ooplasmic factor inducing decondensation of and protamine removal from toad sperm nuclei: involvement of nucleoplasmin.

Immunohistochemical studies with antiserum against the protamines of the toad, Bufo japonicus, revealed that the sperm nucleus loses protamines within 5 min after entry into the egg. Likewise, lysolecithin-permeabilized sperm incubated with the egg extract lose the protamines within 1 min, accompanied by nuclear decondensation. The activities that induce both protamine removal and decondensation in sperm nuclei were found in extracts from growing and mature oocytes and pregastrula embryos, but not in postneurula embryos or adult tissues. SDS-PAGE analyses revealed that the egg extract removed not only protamines from the Bufo sperm, but also selectively the sperm-specific basic proteins from sperm nuclei of Xenopus laevis. The protamine-removing activity (PRA) was partially purified from egg extracts as negatively charged macromolecules by anion-exchange chromatography and gel filtration. The PRA was heat-stable (100 degrees C, 10 min) and sensitive to proteinase K, but not to RNase A and DNase I. Immunoblot analysis of the supernatant after incubation of Bufo sperm in the fraction with the PRA revealed that protamines derived from sperm nuclei were associated with a major protein of the fraction. This protein exhibited mobilities of 140 and 36 kDa on native- and SDS-PAGE, respectively, with the isoelectric points in the range 4.2 to 4.5 and possessed an amino acid composition quite similar to that reported for Xenopus nucleoplasmin. We propose that in fertilized eggs the protamines are removed from sperm nuclei by nucleoplasmin by binding to but not by enzymatic degradation of the protamine.

Amino Acids↗
PubMed1991

Occurrence of H1 subtypes specific to pronuclei and cleavage-stage cell nuclei of anuran amphibians.

Male pronuclei were induced in vitro by incubating the lysolecithin-permeabilized sperm nuclei of anuran amphibians Bufo japonicus and Xenopus laevis with the extracts from homologous eggs, and nuclear basic proteins were analyzed by two-dimensional gel electrophoresis. By 5 min after the incubation, the sperm nuclei had completely lost sperm-specific proteins but possessed a whole set of nucleosomal core histones, except that H2A was mostly replaced by a putative H2A.X. The pronuclei did not possess any H1 histone subtypes found in differentiated somatic cell nuclei, but instead possessed components showing electrophoretic mobilities distinct from other H1 histones. This protein, designated as H1X, was regarded as an H1 subtype on the basis of its solubility in acids or salt and its lysine-rich amino acid composition. Peptide mapping using V8 protease further indicated that H1X is not a post-transcriptionally modified form of other somatic type H1 histones. By the time of chromosome condensation, pronuclear histones comprised H1X, H2A.X, H2B, H3, and H4. During embryonic development, H1X persisted in the nuclei up to the blastula stage, but mostly disappeared at the gastrula stage concomitant with the appearance of H1 subtypes of differentiated cells and the replacement of H2A.X by H2A. We conclude that H1X represents a maternally stored histone variant specific to nuclei of cleaving embryos.

Amino Acids↗
PubMed1991

Plasma immunoreactive endothelin, but not thrombomodulin, is increased in patients with essential hypertension and ischemic heart disease.

To ascertain an involvement of vascular endothelial cells in cardiovascular disease, we have determined plasma levels of two endothelium-derived substances, endothelin (ET) and thrombomodulin (TM), in essential hypertension (EH) and ischemic heart disease. Plasma ET was determined by radioimmunoassay (RIA) after extraction. Plasma TM levels were determined by enzymunoimmunoassay. Plasma ET levels were significantly elevated in patients with EH involving target organ damage, vasospastic angina pectoris (VSA), and acute myocardial infarction (AMI), especially in those associated with cardiogenic shock. There was a weak but significant correlation between plasma ET levels and serum creatinine concentration in patients with EH. Plasma ET levels were elevated even before the coronary spasm in patients with VSA, whereas they did not show any further increase during the spasm. In contrast, plasma TM levels in patients with EH and VSA did not show a significant difference from that in normal subjects. These results suggest that ET plays an important role in the pathophysiology of EH and ischemic heart disease, and also that increases in plasma ET cannot be simply attributed to a leakage of the peptide from the injured endothelial cells.

Angina Pectoris↗
PubMed1991

Is big endothelin converted to endothelin-1 in circulating blood?

Although evidence has been accumulating to support an intracellular processing of big endothelin-1 (big ET-1) to ET-1, molecular conversion in the circulating blood remains to be elucidated. The present study was undertaken to investigate whether big ET-1 was converted to ET-1 in human blood. In the first experiment, normal serum with synthetic big ET-1 exogenously added or serum from patients with chronic renal failure was incubated in vitro at 37 degrees C for 1 h. In the second experiment, synthetic big ET-1 was incubated in the whole blood at 37 degrees C for 1 h. In the third experiment, synthetic big ET-1 was administered intravenously in anesthetized rat and a plasma sample was obtained before and after 15 min and 1 h. After respective incubation, molecular forms of ET were determined by a combination of reverse-phase high-performance liquid chromatography and radioimmunoassay. There was no significant conversion of big ET-1 to ET-1 in the serum obtained from normal and CRF patients. However, there was a slight but significant increase of ET-1 after incubation of big ET-1 in the whole blood or after administration of big ET-1 in anesthetized rat. The conversion in the whole blood was inhibited by 5 mM EDTA. These results suggest that circulating blood may not be a major site of molecular conversion from big ET-1 to ET-1, although conversion does occur in the circulation by blood cell-mediated process.

Animals↗
PubMed1991

Molecular form of immunoreactive endothelin in plasma and urine of normal subjects and patients with various disease states.

To elucidate the pathophysiologic significance of the family of endothelin (ET) peptides, we have investigated plasma and urinary immunoreactive (ir-) ET levels and its molecular forms in normal and pathological conditions. Plasma and urine ET were extracted with an Amprep C2 column. The molecular form of ET was determined by a combination of radioimmunoassay and reverse-phase high-performance liquid chromatography. Although plasma ir-ET was composed mainly of big ET and endothelin-1 (ET-1) in normal subjects, that in acute myocardial infarction, chronic renal failure (CRF), essential hypertension, and vasospastic angina pectoris was characterized by an increase of high molecular ir-ET in addition to increases in big ET and ET-1. Urinary ir-ET in both normal subjects and patients with CRF was composed mainly of a high molecular form in addition to big ET and ET-1. These results suggest that the biosynthetic and/or degradation process of ET under pathological conditions appears to be different from that under normal conditions.

Angina Pectoris↗
PubMed1991

Effects of glucocorticoids and calcitonin on parathyroid hormone-related protein (PTHrP) gene expression and PTHrP release in human cancer cells causing humoral hypercalcemia.

Glucocorticoids are widely used for the treatment of malignancy-associated hypercalcemia to delay the occurrence of an escape phenomenon inherent in calcitonin therapy. Using parathyroid hormone-related protein (PTHrP)-producing squamous carcinoma cells (T3M-1 and EC-GI) established in our laboratory, we investigated the in vitro effects of glucocorticoids and calcitonin on PTHrP mRNA expression in the cells and release of PTHrP into the culture medium. The PTHrP gene was constitutively expressed in the logarithmic growth phase in both squamous carcinoma cell lines. When these cells became superconfluent, PTHrP mRNA expression was greatly diminished in T3M-1 cells but was not distinctly diminished in EC-GI cells. Hydrocortisone inhibited the PTHrP mRNA expression in T3M-1 cells and EC-GI cells in a dose-dependent manner. In accordance with the decreased expression of PTHrP mRNA, the release of immunoreactive as well as bioactive PTHrP also decreased in the conditioned medium of glucocorticoid-treated cells. The minimal effective concentration of prednisolone was about 10(-7) M, which is readily attainable in the serum of patients treated with the agent. Calcitonin and indomethacin did not affect the PTHrP mRNA expression or PTHrP release into the medium. Calcitonin did not modulate the hydrocortisone-induced inhibition of PTHrP production. These in vitro findings suggest that the combined use of glucocorticoids and calcitonin plays a beneficial role in the treatment of malignancy-associated hypercalcemia, since the steroid hormone can suppress PTHrP mRNA expression and release of bioactive PTHrP in certain PTHrP-producing tumors.

Aged↗
PubMed1991

[The effects of prostaglandin E1 on myeloperoxidase and alpha 1-protease inhibitor in head-neck surgery].

To investigate whether prostaglandin E1 (PGE1) 30 ng.kg-1.min-1 inhibits the release of lysosomal enzyme from granulocytes by surgical stimuli, we measured myeloperoxidase and alpha 1-protease inhibitor (alpha 1-PI) in 32 patients for head neck surgery. The patients were divided into two groups; no PGE1 infusion group (C group) and PGE1 30 ng.kg-1.min-1 infusion group (P group). PGE1 was infused intravenously using a syringe pump during operation. MPO and alpha 1-PI were measured at 4 points: before induction of anesthesia, before surgery, 4 hours after the start of surgery or the infusion of PGE1, and on the first postoperative day. MPO was maintained at significantly higher levels during and after surgery in both groups. alpha 1-PI decreased significantly during operation and increased for 10% in the first postoperative day in both groups. There were no significant differences between groups in MPO and alpha 1-PI levels. We conclude that the infusion of PGE1 30 ng.kg-1.min-1 did not completely inhibit the release of lysosomal enzyme from granulocytes by surgical stimuli.

Aged↗
PubMed1988

Human sperm nuclei can transform into condensed chromosomes in Xenopus egg extracts.

The conditions necessary for inducing pronucleus formation and chromosome condensation of human sperm nuclei were studied using Xenopus egg extracts. When lysolecithin (LC)-and dithiothreitol (DTT)-treated spermatozoa were incubated with egg extract prepared with an extraction medium containing 10 mM EGTA, sperm nuclei transformed into chromosomes, bypassing the pronuclear stage. On the contrary, LC-DTT-treated spermatozoa incubated in egg extract without EGTA mimicked LC-permeabilized Xenopus spermatozoa in that they underwent pronucleus formation accompanied by DNA synthesis and subsequent chromosome condensation in the correct chronological order. These observations suggest the importance of intracellular calcium for regulating the states of nuclear chromatin. LC-permeabilized human spermatozoa were not responsive to the egg extract without any additives, but formed pronuclei when incubated with the egg extract supplemented with 5-10 mM DTT. However, subsequent chromosome condensation of sperm nucleus did not occur in the DTT extract. This suggests that disulfide-reducing agent blocks transformation of sperm pronuclei into condensed chromosomes.

Animals↗
PubMed1986

Development of pronuclei from human spermatozoa injected microsurgically into frog (Xenopus) eggs.

Human spermatozoa were demembranated with Triton X-100 (TX) and injected into the mature eggs of Xenopus laevis. The nuclei of these spermatozoa decondensed and developed into pronuclei. Chromosomes did not appear in the eggs until the end of a 5-hr incubation period. When the demembranated human spermatozoa were further treated with dithiothreitol (DTT) before they were injected into the eggs, the sperm nuclear decondensation and pronuclear development took place considerably faster than in spermatozoa treated with the detergent alone. By the end of the 5-hr incubation period, decondensed chromatin threads or chromosome-like structures appeared, but none of the eggs cleaved. When human spermatozoa were injected into full-grown ovarian oocytes with intact germinal vesicle (GV) or oocytes which had matured without GV, the nuclei of a proportion of TX-treated and all TX-DTT-treated sperm decondensed but showed no sign of developing into pronuclei. Sperm nuclei injected into maturing oocytes formed condensed chromatin fragments as long as the oocytes were not activated, but they transformed into pronuclei when the oocytes were stimulated with electric shock. These results indicate that the cytoplasmic factors responsible for the decondensation of human sperm nuclei are present in egg cytoplasm independent of GV-materials. We also suggest that the factors controlling development of decondensed sperm nuclei into pronuclei are dependent on GV materials.

Animals↗
PubMed1986

Periodic changes in the rigidity of activated anuran eggs depend on germinal vesicle materials.

The eggs of Xenopus laevis and Bufo bufo japonicus matured in vitro by progesterone were denuded and activated by electrical shock or pricking, and their diameters were determined periodically until the postactivation time equivalent to the 8- to 16-cell stage. Normally matured eggs showed a quick rounding-up and flattening immediately after activation (activation response), followed by a periodic flattening and rounding-up (postactivation response) corresponding to the intervals of early cleavage cycles. When denuded eggs that were induced to mature after removal of the germinal vesicle (GV) were activated, they showed a normal activation response, but retained the rounded-up state without exhibiting the periodic postactivation changes. Injection of GV materials back into enucleated Bufo oocytes and determination of the postactivation flattening 120 min after activation revealed that the extent of flattening correlated well with the amount of GV materials injected, provided injection was made before the first polar body was emitted. Thus, postactivation flattening, but not activation flattening, is an active property of eggs established under the influence of the GV and is linked to the periodical changes of rigidity during early cleavage cycles.

Animals↗
PubMed1983

Do the substance P-ergic vagus afferents in cats reinnervate the deafferented superior cervical ganglion?

By ligating specific nerves in the cat, the central processes of the nodose ganglion (NG) cells containing substance P-like immunoreactive materials were shown, immunohistochemically, to run through the cross-anastomosis made between the cranial end of the NG and the caudal end of the superior cervical ganglion (SCG), and to reach the portions cranial to the SCG without making synaptic contacts with the SCG cells.

Afferent Pathways↗
PubMed1982

Effect of spinal ganglionectomy on substance P-like immunoreactivity in the gastroduodenal tract of cats.

Bilateral ligation of the splanchnic nerves and spinal ganglionectomy from T5 to L2 both produced a profound decrease of substance P (SP)-like immunoreactivity in Auerbach's plexuses of the duodenum and the antrum of the stomach in the cats. As unilateral dorsal rhizotomy from T5 to L2 produced no such changes, SP is probably synthesized in the spinal ganglion and transported through the splanchnic nerve to the gastroduodenal wall.

Animals↗
PubMed1982

Immunohistochemical studies on enteric substance P of extrinsic origin in the cat.

The origin of substance P (SP)-like immunoreactivity in the Auerbach's plexuses of the esophagus, stomach duodenum was examined in the cat. The intensity of the fluorescence and the area of distribution of SP-like immunoreactivity in the Auerbach's plexuses of the cardiac part of the esophagus and the corpus of the stomach were markedly reduced by bilateral ligation of the abdominal vagus nerve, while little change occurred in the antrum of the stomach and the duodenum. After splanchnic nerve ligation or celiac ganglionectomy, the SP-like immunoreactivity in the Auerbach's plexuses of the antrum of the stomach and the duodenum was markedly reduced, whereas that in the esophagus and the corpus of the stomach was only slightly attenuated. Intense SP-like immunoreactivity was observed in the portions of the abdominal vagus and splanchnic nerve cranial to the ligation. This the Auerbach's plexuses of the esophagus, stomach and duodenum were considered to contain SP transported through the vagus and splanchnic nerve. It was also indicated experimentally that the SP-like immunoreactive fibers in the auerbach's plexus arose from the nodose and spinal ganglia as well as from the dorsal vagus nucleus in the medulla oblongata.

Animals↗