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Biomedical subjects

N Matsui

Publications and source records attributed to N Matsui.

At least 181 records · Page 10Linked to original sources

Expression of low density lipoprotein receptor gene in human placenta during pregnancy.

Mammalian cells require cholesterol as a structural component of plasma membranes. It is also required for placental steroid synthesis. De novo synthesis of cholesterol is limited in human placenta and cholesterol is obtained mainly from plasma low density lipoprotein (LDL). Cholesterol delivery from LDL is mediated by receptor-mediated uptake and the receptor amount is the most important factor for cellular delivery. Thus, the regulation of receptor synthesis is important for placental development and function. Since the regulation of LDL receptor gene expression has not been studied in human placenta, LDL receptor mRNA was measured in placentae of 5-40 weeks of gestation by hybridization of RNA with 32P-labeled cDNA for human LDL receptor. Two mRNA species for LDL receptor were demonstrated by Northern blot analysis. The longer mRNA [5.3 kilobases (kb)] was much more abundant than the shorter mRNA (3.7 kb). The amount of 5.3 kb mRNA was highest early in gestation and decreased during pregnancy. However, the amount of 3.7 kb mRNA did not change appreciably during gestation. Dot blot analysis of 26 placental mRNAs obtained from various stages of gestation revealed a negative correlation between LDL receptor mRNA and gestation (r = -0.76, P less than 0.001). Considering the rapid growth of the trophoblast during gestation, especially in the first and the second trimester, increased expression of the LDL receptor gene and subsequent translation are expected for efficient cholesterol uptake to provide a sufficient substrate for cell growth. Possible mechanisms for the appearance of two mRNA species for LDL receptor are also discussed.

Actins↗

Regulation of prolactin gene expression during early pregnancy in rats.

We have shown that administration of estrogen which increases prolactin (PRL) synthesis in the rat may be mediated by an increase in poly [adenosine diphosphate ribose (ADP-ribose)] synthesis. Present investigation was attempted to study whether poly (ADP-ribose) synthesis is involved in rat PRL gene expression during early pregnancy. Anterior pituitaries were obtained on days 0, 2, 4, 6, 8, 10 and 12 of pregnancy (group C). Another group of pregnant rats was given nicotinamide, an inhibitor of poly (ADP-ribose) synthesis twice a day intra-peritoneally from day 0 to the day of sacrifice (group N). Serum estradiol (E2) concentration was determined by radioimmunoassay. PRL mRNA was measured by cytoplasmic dot hybridization using 32P-labeled cDNA. Poly (ADP-ribose) synthesis was assessed by incubating purified nuclei with 14C-nicotinamide adenine dinucleotide. The serum concentration of E2 increased between days 2 and 4, and on day 6 it decreased to the level of day 0. It remained low until day 12. No difference in the serum E2 level was observed in groups C and N. In group C, PRL mRNA increased from day 2 and remained high until day 8. In group C, poly (ADP-ribose) synthesis increased between days 2 and 4, decreased on day 6 to the level of day 0, and thereafter gradually increased until day 10. Administration of nicotinamide abolished the increase in poly (ADP-ribose) synthesis observed in group C during early pregnancy. In group N, the increase in PRL mRNA was completely suppressed. It is suggested that the increase in PRL mRNA in early pregnancy may be mediated by increased poly (ADP-ribose) synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Plasma thyroxine-binding proteins and thyroid hormone levels in primate species; is callithricidae thyroid hormone resistant?

Thyroxine(T4)-binding to serum proteins in primates; catarrhini, prosimiae, and platyrrhini were studied by polyacrylamide gel electrophoresis T4 binding analysis. From the electrophoretic analysis, it was shown that thyroxine-binding proteins similar to human thyroxine-binding globulin (TBG) and thyroxine-binding prealbumin (TBPA) were present in catarrhini and prosimiae species, but not in platyrrhini (callithricidae and cebidae). T4-binding analysis also revealed that catarrhini and prosimiae have a high affinity T4-binding protein similar to human TBG. The association constant (Ka) for T4 of the plasma proteins in these species was approximately 2.0 X 10(10) M-1. On the other hand, it was unable to demonstrate a high affinity binding site for T4 in the plasma of platyrrhini species. Both the total and free thyroid hormone concentrations in catarrhini and prosimiae were similar to those in human. Total T4 in cebidae, one of the platyrrhini species, was extremely low. Among 8 animals examined, T4 in 6 was undetectable by radioimmunoassay and the mean T4 of the other two was 2.8 micrograms/dl. However, free thyroid hormone concentrations were similar to those in human. In callithricidae, another platyrrhini species, T4 in plasma was 6.90 +/- 2.11, which is comparable to the level in normal human subjects. However, in this species, high-affinity T4-binding protein was lacking and free thyroid hormone concentrations were extremely high (most were higher than the assay limit). Although the thyroid function of callithricidae remains to be studied, it will be interesting if callithricidae is resistant to thyroid hormone action.

Animals↗

Elevation of plasma atrial natriuretic peptide in a neurosurgical patient with the syndrome of inappropriate secretion of antidiuretic hormone--case report.

The authors describe a case of subarachnoid hemorrhage with hyponatremia accompanied by elevation of plasma atrial natriuretic peptide (ANP). The early phase of hyponatremia was classified as the syndrome of inappropriate secretion of antidiuretic hormone (ADH) due to subarachnoid hemorrhage. However, in the later phase, hyponatremia and natriuresis were accompanied by suppression of ADH while plasma ANP remained elevated. The patient was effectively treated with demeclocycline and hypertonic saline. The significance of ANP in the pathophysiology of increased natriuresis is discussed.

Aged↗

[Assessment of plasma inactive renin by trypsin and thermolysin treatment during open heart surgery].

Plasma inactive renin (IRA) were assayed through open heart surgery by trypsin treatment in twenty-two patients. Postoperatively plasma renin activities and IRA increased, remarkably in IRA, however total renin activities were lesser than plasma renin activities during extracorporeal circulation. From the results of addition of 125I-angiotensin I before trypsin treatment, the presence of unknown enzyme was assumed, which was activated by trypsin and catalyzed angiotensin I in extracorporeal circulation. Bacterial enzyme, thermolysin, also activated plasma inactive renin, more stably until 60 min at 0-37 degrees C than trypsin. By trypsin, activities were in peaks at 1 min and gradually decreased thereafter. Conclusively we could assess the superiority of thermolysin treatment over trypsin treatment.

Adult↗

[Hyperthermia in malignant tumors of the extremities--experimental heating by a radiofrequency applicator and its clinical significance].

We studied hyperthermia for malignant tumors of the extremities, and obtained the following findings. In osteosarcoma cultured cells from OST (Human) and Dunn (Mouse), proliferation was clearly inhibited on being heated to 42 approximately 43 degrees C. On heat-treating the femurs of pigs, a rise in temperature to 42.5 degrees C or above was observed so that an antitumor effect could be anticipated. Moreover, no abnormal rise in temperature in the tissues surrounding the bone and light microscopy revealed no particular abnormalities. Clinically, a rise in temperature above 42.5 degrees C was observed in the majority of the malignant bone tumors (4 cases of osteosarcoma and 1 case of chordoma) and soft tissue tumors (1 case of epithelioid sarcoma, malignant fibrous histiocytoma, rhabdomyosarcoma, malignant melanoma and osteosarcoma) of which 2 cases were metastatic tumors. Before administration, 7 patients complained of pain, 4 of whom (57%) experienced an alleviation following treatment. Also in 5 (50%) out of 10 cases a shrinking of the tumor was observed and especially, in the case of soft tissue tumors a tendency towards a softening of tumor texture was seen.

Animals↗

[Arthroscopic findings of cartilage changes in knees with rheumatoid arthritis].

We evaluated 28 cases (45 knee joints) with rheumatoid arthritis as our subjects using simple X-rays of the knee joints according to their Larsen grade and also measured the femoro-tibial angle (FTA). Moreover, using an arthroscope we observed 6 regions, namely, the medial femoral condyle, medial tibial plateau, medial meniscus, lateral femoral condyle, lateral tibial plateau, and lateral meniscus, and evaluated the degree of cartilage degeneration according to a 5-point grade classification of our own devising. We studied the relationship between the simple X-ray findings and the arthroscopic findings of cartilage degeneration and reached the following conclusions. Even when simple X-ray findings are slight as in Larsen grade I, various degrees of cartilage degeneration are observed and moreover, as the stage of the disease progresses, cartilage degeneration becomes more severe. The progression of cartilage degeneration up to Larsen grade III is not uniform but degenerative changes in the lateral meniscus progress. Also, a correlation was observed between the nature of the cartilage destruction and the FTA.

Aged↗

Combined 17 alpha-hydroxylase/17,20-lyase deficiency due to a stop codon in the N-terminal region of 17 alpha-hydroxylase cytochrome P-450.

Steroid 17 alpha-hydroxylase (cytochrome P-450(17)alpha) mediates both 17 alpha-hydroxylase and 17,20-lyase activities. A relatively rare disease, 17 alpha-hydroxylase deficiency is characterized by defects in either or both of these activities. The molecular basis for variability of the defect is not well understood. We have determined the exonic sequence of the mutant P-450(17)alpha gene from one Japanese patient with combined 17 alpha-hydroxylase/17,20-lyase deficiencies. A stop codon (TGA) due to a single point mutation was found at the position of amino acid 17 in exon 1 of the P-450(17)alpha gene. The presence of a stop codon in the N-terminal region of this gene leads to the absence of a functional P-450(17)alpha protein in adrenal cortex and ovary, and consequently hypertension, primary amenorrhea and osteoporosis in this patient.

Adrenal Cortex↗

Temporal lobe epilepsy with ictal ecstatic state and interictal behavior of hypergraphia.

The authors describe an epileptic patient with ictal ecstatic experiences and an interictal behavioral change of hypergraphia. The patient had a temporal lobe EEG spike focus in the dominant hemisphere. The ecstatic states can be considered true epileptic auras, i.e., simple partial seizures originating in the temporal lobe or the nearby structures. Hypergraphia in this patient seemed to be related to temporal lobe ictal focus in the dominant hemisphere.

Epilepsy, Temporal Lobe↗

Cloning of a complementary deoxyribonucleic acid coding for human thyroxine-binding globulin (TBG): existence of two TBG messenger ribonucleic acid species possessing different 3'-untranslated regions.

An adult human liver cDNA library constructed in expression vector, bacteriophage lambda gt11, was screened with polyclonal antibody directed against human T4-binding globulin (TBG). TBG cDNA cloned in the present study was 944 nucleotides in length. It contained approximately 70% of the coding region and complete 3'-untranslated region. When the sequence was compared with that of TBG cDNA recently cloned by I. L. Flint, T. J. Bailey, T. A., Gustafson, B. E. Markham, and E. Morkin, the 3'-untranslated region of our cDNA was 231 nucleotides shorter than their cDNA. These results indicated that two TBG mRNAs with different length of 3'-untranslated regions may exist in human liver. Indeed, Northern blot analysis revealed that two TBG mRNAs differing in the length approximately 200 base pairs were present in normal human liver as well as in human hepatoma cell line (HepG2). It was demonstrated that this size difference was due to the length of 3'-untranslated region by hybridization with a probe specific to the longer 3'-end. Together with the sequence data, it was suggested that these two TBG mRNA species may be produced by alternative processing and polyadenylation at two different sites.

Bacteriophage lambda↗

Effect of ovarian steroids on cyclic adenosine 3':5'-monophosphate production stimulated by arginine vasopressin in rat renal monolayer cultured cells.

Renal resistance to antidiuretic hormone (ADH) has been speculated to be a mechanism of transient nephrogenic diabetes insipidus occurring during late pregnancy. In order to study possible involvement of ovarian steroids in this mechanism, their effect on cyclic adenosine 3':5'-monophosphate (cAMP) response to arginine vasopressin (AVP) was examined utilizing rat and human renal medullary cells in monolayer culture. In both rat and human cells, estradiol significantly reduced cAMP response to AVP; estradiol at 1.84 x 10(-8) M, 1.84 x 10(-7) M and 1.84 x 10(-6) M decreased cAMP production stimulated by 10(-8) M AVP to 78 +/- 5%, 67 +/- 2% (P less than 0.05) and 52 +/- 1% (P less than 0.001) of the control in rat renal cells, respectively, and in human renal cells the effect of estradiol was comparable to that in rat cells. In rat renal cells, progesterone also reduced cAMP response to AVP dose-dependently; progesterone at 1.59 x 10(-7) M, 1.59 x 10(-6) M and 1.59 x 10(-5) M decreased cAMP production stimulated by 10(-8) M AVP to 87 +/- 1%, 72 +/- 5% (P less than 0.001) and 37 +/- 5% (P less than 0.001) of the control, respectively. On the other hand, corticosterone and dexamethasone at concentrations ranging from 10(-8) M to 10(-5) M and aldosterone at concentrations ranging from 10(-9) M to 10(-5) M did not alter cAMP response to AVP significantly. The suppressive effect of estradiol increased with time until six hours and thereafter it reached a plateau.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Studies of structure-function relationship of human parathyroid hormone using rat and human renal cortical cells in culture.

The structure-function relationship of human PTH was studied by testing the effects of its synthetic analogues on cAMP production in cultures of rat and human renal cortical cells. The human cell system was by two orders more sensitive to an agonist, hPTH1-34, than the rat cell system. In both culture systems, Tyr34hPTH3-34NH2, which by itself had no influence on adenylate cyclase, caused approximately 90% inhibition of the hPTH 1-34-induced cAMP production at a molar ratio of 1000:1. On the other hand, Tyr34hPTH5-34NH2, Tyr34hPTH7-34NH2, Tyr34hPTH8-34NH2 and Tyr34hPTH9-34NH2 had weak but distinct agonist activity. When these four analogues were tested in the presence of hPTH1-34, they acted as antagonists in the human cell system, whereas they still showed agonist activity in the rat cell system which was additive to that of hPTH1-34. These data indicate that the amino acids at positions 1 and 2 of hPTH are important for its biological activity and that those in the sequence 9-34 also participate in the activation of adenylate cyclase. The higher sensitivity to hPTH1-34 and the different response to some of the analogues of human renal cortical cells compared with rat renal cortical cells emphasize the importance of employing human cell systems in evaluating the structure-function relationship of hPTH.

Animals↗

Characterization of neuroectodermal antigen by a monoclonal antibody and its application in CSF diagnosis of human glioma.

Monoclonal antibodies were produced by immunization of the human glioma cell line SK-MG-4. One of the antibodies, designated G-22, reacted with 18 of 20 glioma cell lines, two melanoma cell lines, and three lung cancer cell lines, but not with 39 cell lines derived from sarcoma, carcinoma, or hematopoietic tumors. The antigen was expressed in the brain of human fetuses in early gestation (9 weeks) but not in late gestation (8 months) or in normal adult brain, suggesting that the antibody recognizes neural differentiation antigens expressed by neuroectodermal origin. A high incidence of positive antigens has been observed in gliomas but not in the other neural tumors, such as ependymomas, meningiomas, and neuroblastomas. Thus, the antigen defined by the G-22 monoclonal antibody could be defined as glioma-associated antigen. Pulse-labeling with tritiated leucine and subsequent immunoprecipitation of the solubilized cell membrane revealed that the antigen recognized by this antibody had a molecular weight of 67 kD on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). It was shown by dot-blot enzyme-linked immunospecific assay (ELISA) that the antigen could be detected in the cerebrospinal fluid (CSF) from patients with gliomas. From analysis of affinity chromatography and SDS-PAGE, the antigen present in the CSF had a molecular weight similar to that of a 1% Nonidet P-40 (NP-40) extract from a glioma cell line. When the antigen in CSF was quantitatively assayed by ELISA, the mean antigen level (expressed as optical density at 450 nm) in the CSF of seven patients was 0.8 +/- 0.28 (mean +/- standard deviation), which was significantly higher than the 0.38 +/- 0.14 level observed in the CSF of 15 patients with nonglioma brain tumors and the 0.23 +/- 0.09 level in the CSF of four patients without brain tumors. These results indicate that the monoclonal antibody G-22 is useful for the diagnosis of glioma.

Antibodies, Monoclonal↗

Detection of mRNA of prolactin and ACTH in clinically nonfunctioning pituitary adenomas.

Clinically nonfunctioning pituitary adenomas have been thought to synthesize some pituitary hormones as shown by studies involving cell culture, immunocytochemistry, or measurement of hormone levels in tumor homogenates. Nevertheless, they are not associated with hypersecretion of pituitary hormones. To further clarify hormone synthesis in such pituitary adenomas, the presence of messenger ribonucleic acid (mRNA) of prolactin (PRL) growth hormone, and adrenocorticotropic hormone (ACTH) in the cytoplasm of 16 nonfunctioning adenomas was determined by means of a hybridization technique, and compared to the immunocytochemical findings. In three adenomas (19%) PRL mRNA was detected and in one case (6%) ACTH mRNA was detected. The hybridization technique appears to be more sensitive than immunohistochemistry for detection of specific mRNA's in assigning the hormone synthesis potential to clinically nonfunctioning tumors. The results suggest that PRL and ACTH are synthesized in some cases of clinically nonfunctioning pituitary adenomas and that hybridization techniques are useful to investigate hormone synthesis in pituitary adenomas. The ability to demonstrate PRL mRNA in tumor tissues allowed differentiation between hyperprolactinemia caused by synthesis of PRL in the tumor and that due to hypersecretion from the adjacent normal pituitary.

Adenoma↗