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Biomedical subjects

T Nakayama

Publications and source records attributed to T Nakayama.

At least 19 recordsLinked to original sources
PubMed1992

[Hyperresponsiveness of TSH and prolactin and impaired responsiveness of GH in Japanese patients with isolated ACTH deficiency].

Two hundred and forty-one cases of isolated ACTH deficiency have been reported in Japan since 1969. Pituitary hormone responsiveness to stimulation tests before and after hydrocortisone supplementation was investigated in these cases. Plasma ACTH level showed no or little change in response to lysine vasopressin, metyrapone, CRF or insulin-induced hypoglycemia in 97.3-100% of the cases. Serum GH level changed little or not at all in response to GRF, insulin-induced hypoglycemia, glucagon, 1-dopa and arginine in 26.9, 29.3, 40.0, 50.0 and 56.1%, respectively. Serum TSH and prolactin (PRL) levels showed hyperresponse to TRH in 34.7 and 35.6%, respectively. After hydrocortisone therapy, GH secretion was more responsive than before therapy in 78.9% of the cases. After supplementation, TSH level was less responsive to TRH stimulation than before therapy in 59.3% of the cases. After hydrocortisone supplementation, TSH response to TRH decreased in 75% of ACTH-deficient patients without primary hypothyroidism but did not decrease in more than half of those with primary hypothyroidism. TSH response to TRH decreased after supplementation in 76.5% of the patients with TSH hyperresponsiveness before therapy, and increased after therapy in 66.7% of those with normal TSH responses before therapy. After supplementation, PRL response to TRH was less than that before therapy in 43.5% of ACTH--deficient patients, and greater than that before therapy in 30.4%. PRL response to TRH decreased after therapy in 66.7% of the patients with PRL hyperresponsiveness before therapy, and increased in 63.6% of those with normal PRL response before therapy. Primary hypothyroidism and Hashimoto's thyroiditis were complicated in 21.6 and 11.6%, respectively, of the 241 patients with isolated ACTH deficiency. In patients who had TSH hyperresponsiveness and/or high basal TSH levels and PRL hyperresponsiveness and/or high basal PRL levels, primary hypothyroidism was complicated in 58.4 and 42.3%, respectively. Hashimoto's thyroiditis was complicated in 29.8 and 20.5%, respectively, of these patients. Pituitary cell antibody (PCA) was detected in 36.6% of ACTH-deficient patients who were examined. Pituitary cell surface antibody (PCSA) to AtT-20 cells and GH3 cells was detected in 50.0 and 28.0% of the examined cases, respectively. The prevalence of PCA and PCSA did not differ between TSH-hyperresponsive patients and those with normal TSH basal levels and response, whereas PCA and PCSA were significantly more prevalent in PRL-hyperresponsive patients than in those with normal PRL levels and response. An empty sella was found in 30.2% of the examined case.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenocorticotropic Hormone↗
PubMed1992

[Pregnancy in Cushing's syndrome].

Pregnancy in cases of Cushing's syndrome is rare. A pregnant patient with Cushing's syndrome due to an adrenal adenoma who was diagnosed in the third trimester is described. She underwent conservative treatment for Cushing's syndrome and delivered a normal infant by Caesarean section. Currently, 121 pregnancies in 97 patients have been reported, but a principle for the treatment of the mother and fetus has not yet been established. We reviewed pregnancy in Cushing's syndrome based on the world literature and evaluated the choice of treatment to take. In the first trimester of pregnancy, therapeutic abortion or surgical treatment, such as adrenalectomy or resection of the pituitary tumor in Cushing's syndrome, is recommended for patients with severe hypercorticism (plasma cortisol > or = 30 micrograms/dl, urinary 17-OHCS > or = 15 mg/day, urinary free cortisol > or = 1000 micrograms/day), while conservative treatment is recommended for patients with mild hypercorticism (plasma cortisol < 30 micrograms/dl, urinary 17-OHCS < 15 mg/day, urinary free cortisol < 1000 micrograms/day). In the second trimester of pregnancy, surgical treatment is recommended for patients with severe hypercorticism, while conservative treatment is recommended for patients with mild hypercorticism. In the third trimester of pregnancy, Caesarean section is recommended for most cases. Drug treatments such as with metyrapone should be limited to patients showing severe hypercorticism or a maternal high risk who have contraindications to surgical treatment.

Adenoma↗
PubMed1992

Expression in human hepatocellular carcinoma of nucleoside diphosphate kinase, a homologue of the nm23 gene product.

BACKGROUND: Expression of nucleoside diphosphate (NDP) kinase, which is highly homologous to the nm23 gene product in a variety of species, has been found to be inversely associated with metastatic potential in human breast cancer. PURPOSE: The present study was conducted to clarify the association of NDP kinase expression with metastatic potential in human hepatocellular carcinoma. METHODS: The immunohistochemical expression of NDP kinase was analyzed in 30 patients with histopathologically proven hepatocellular carcinoma. These patients included nine with distant metastases and 21 without distant metastases. Tissue specimens were reacted with rabbit anti-rat NDP kinase antibody and stained by the biotin-streptavidin complex method. The relative staining intensities were evaluated by comparing primary tumor sites with adjacent nontumorous liver tissue or with metastatic sites, RESULTS: The expression of NDP kinase in primary sites in patients with distant metastases was significantly less intense than that in patients without distant metastases (P = .018). NDP kinase was expressed significantly less intensely in metastatic sites than in primary sites (P = .005). The intensity of NDP kinase expression did not statistically correlate with tumor size or number of lesions in the liver, histopathological classification of tumor, associated liver diseases, hepatitis virus markers, or tumor markers. CONCLUSION: These results suggest that the reduced expression of NDP kinase is closely associated with distant metastatic potential in hepatocellular carcinoma. IMPLICATIONS: It is possible that both NDP kinase and the nm23 gene product may be active in the progression and differentiation of tumor cells and that their reduced expression induces a high metastatic potential in tumor cells. Studies using Northern blotting or in situ hybridization should be planned to confirm our findings.

Adult↗
PubMed1992

In vivo calcium elevations in thymocytes with T cell receptors that are specific for self ligands.

Selection of the T cell receptor (TCR) repertoire in the thymus probably involves TCR-mediated signals transduced in developing thymocytes after interaction with thymic stromal cells bearing self ligands. TCR-transduced signals should have identifiable consequences that would distinguish thymocytes whose TCRs have been engaged by self ligands from those whose TCRs have not. Among thymocytes expressing a transgenic TCR of defined specificity, a large number had elevated intracellular calcium concentrations but only when resident in a negatively selecting thymus in which their self ligand was expressed. Thus, developing thymocytes are stimulated by endogenous ligands in vivo to mobilize intracellular calcium, and increased intracellular calcium concentrations may reflect the consequences of intrathymic signaling associated with thymic negative selection.

Animals↗
PubMed1992

Presence of distinct transcriptional regulatory elements in the 5'-flanking region shared by the chicken H3 histone gene homopair.

The chicken H3 histone gene family contains nine members belonging to two major histone gene clusters. Six of these genes have been sequenced and shown to encode two different H3 protein variants. Five H3 genes (H3-I, -II, -IV, -V, and -VI) encode the same amino acid sequence (class I) and another H3 gene (H3-III) differs from class I in a single amino acid (IIe113-Met) (class II). H3-II and H3-III have inverted orientations and share a 5' intergenic region of about 900 bp. To understand the regulation of expression of these two genes, we fused the 5'-flanking region to the CAT gene in inverted orientations to generate two chimeric plasmids, pH3-II-900 and pH3-III-900. Transient CAT assays using these constructs indicated that the promoter of H3-III is more active than that of H3-II. CAT assays with deletion mutants showed that H3-II and H3-III each possess a particular transcription regulatory sequence 5' adjacent to their coding sequence. In addition, the functional sequences of H3-II have no effect on expression of H3-III and vice versa. These results suggest that the regulations of expression of the two H3 genes are distinct.

3T3 Cells↗
PubMed1992

Evidence for possible structural changes of particular H3 and H2B histone genes in different chicken tissues (cells).

The two chicken histone gene families H3 and H2B contain nine and eight members, respectively. To clarify whether the structures of these genes differ in different tissues (and cells), we analyzed DNAs from chicken lung, kidney, oviduct, and sperm. An H3-specific probe (probe 1.3SS) hybridized with a 10 kb EcoRI fragment carrying two H3 genes (H3-II and H3-III) from the lung, kidney, and oviduct with intensities of about one quarter of that of the fragment from the sperm. On the other hand, the intensities of hybridization of the H2B-specific probes (probes H2B-Ia, H2B-IIb, and H2B-III) with a 12 kb EcoRI fragment carrying two H2B genes (H2B-IV and H2B-V) from the oviduct, lung, and sperm were about a quarter of the intensity of hybridization with this fragment from the kidney. These findings, together with those reported previously, suggest that these particular histone genes H3 and H2B possess inherent abilities to form either a tight or loose structure, and that they exist in a loose form in the sperm and kidney but in a tight form in the other tissues tested.

Animals↗
PubMed1992

Chemical modification of cysteinyl, lysyl and histidyl residues of mouse liver 17 beta-hydroxysteroid dehydrogenase.

Monomeric 17 beta-hydroxysteroid dehydrogenase from mouse liver was rapidly inactivated by 5,5'-dithiobis(2-nitrobenzoic acid) and 2,4,6-trinitrobenzene-1-sulfonate, and the absorption spectra of the inactivated enzymes indicated that cysteine and lysine residues were modified. The kinetics of inactivation and spectrophotometric quantification of the modified residues suggested that complete inactivation was caused by modification of two cysteine residues or one lysine residue per active site. The inactivation by the two reagents was protected by NADP+ and some coenzyme analogs, but not by a steroid substrate, testosterone. Moreover, chemical modification by diethyl pyrocarbonate also produced inactivation of the enzyme, and showed a difference spectrum with a peak at 242 nm characteristic of N-carbethoxyhistidine residues, which decreased with the addition of hydroxylamine. The inactivation by this reagent, following pseudo-first-order kinetics, was protected partially by either NADP+ or testosterone and completely in the presence of both the coenzyme and substrate. The results suggest the presence of essential cysteine and lysine residues at or near the coenzyme-binding site and that of essential histidine residue(s) in the catalytic region of the active site of mouse liver 17 beta-hydroxysteroid dehydrogenase.

17-Hydroxysteroid Dehydrogenases↗
PubMed1992

Enhanced DNA synthesis in rat hepatoma cells by conditioned media from Kupffer cells incubated with supernatants of tumor necrosis factor-alpha-pretreated hepatocytes.

The effects of tumor necrosis factor-alpha (TNF-alpha) on DNA synthesis in AH66 rat hepatoma cells and rat hepatocytes were analysed by means of [3H]thymidine incorporation. DNA synthesis in AH66 cells was suppressed when AH66 cells were directly incubated with TNF-alpha. When primary culture of rat Kupffer cells was incubated with hepatocyte conditioned media pretreated with TNF-alpha (0-200 U/ml), and AH66 cells were then treated with these hepatocyte/Kupffer cell-conditioned media, TNF-alpha used in the pretreatment caused a dose-dependent increase in DNA synthesis in AH66 cells with a maximum effect amounting to a more than 10-fold increase. In contrast, DNA synthesis in primary culture of rat hepatocytes was not stimulated by the TNF-alpha-pretreated hepatocyte/Kupffer cell conditioned media. These results suggest that TNF-alpha-mediated hepatocyte-Kupffer cell interaction selectively promotes proliferation of rat hepatoma cells.

Animals↗
PubMed1992

Highly conserved hexamer, octamer and nonamer motifs are positive cis-regulatory elements of the wheat histone H3 gene.

Base substitution mutations were introduced into the promoter region of the wheat histone H3 gene, and promoter activity was assayed in stably transformed sunflower calli or in wheat protoplasts transfected transiently. At least four positive regulatory elements, a hexamer motif (ACGTCA), two octamer(-like) motifs of a direct (CcCGGATC) and a reverse (aATCCGCG) form, and a nonamer motif (CATCCAACG) were identified within the -185 region of the H3 promoter. Analyses of the type I element (CCACGTCACCaATCCGCG) consisting of the hexamer and reverse-oriented octamer motifs, and which is conserved in other plant histone genes as well, predicted the presence of an octamer-binding protein(s).

Base Sequence↗
PubMed1992

Structural change of a particular H2B histone gene possibly results in differences in its transcriptional regulation in different chicken tissues.

The chicken H2B histone gene family consists of eight highly homologous members (H2B-I to H2B-VIII) belonging to two major histone gene clusters. Seven of these genes have been sequenced and shown to encode three different H2B protein variants. Northern analysis with a probe, which mainly consists of the 5'-flanking region containing the sequence for the mRNA leader of H2B-V encoding a particular H2B protein variant, revealed that the mRNA level transcribed from this particular gene was higher in the kidney than in the oviduct and lung. To elucidate whether the structure of the H2B gene differs in the three different tissues, we analyzed DNAs from the oviduct, lung, and kidney. On Southern analysis, various H2B gene-specific probes hybridized with two particular H2B genes (H2B-IV and H2B-V), which are located in close proximity within a 12 kb EcoRI fragment, from the oviduct and lung with an intensity of about one quarter of that from the kidney. These findings suggest that some difference of DNA structure of the H2B-V gene may result in its relatively higher expression in the kidney.

Animals↗
PubMed1992

Selective irreversible inhibitors of aldose reductase.

A series of 5-substituted-1,3-dioxo-1H-benz[de]isoquinoline-2(3H)-acetic acid analogues have been examined as irreversible inhibitors of aldose reductase. The 5-alpha-bromoacetamide and 5-alpha-iodoacetamide analogues 5 and 6 gave irreversible inhibition of aldose reductase while the 5-alpha-chloroacetamide analogue 3 did not show this type of inhibition. Protection studies indicate that irreversible inhibitions are occurring at the inhibitor binding site. Comparative irreversible inhibition studies with rat lens aldose reductase (RLAR) and rat kidney aldehyde reductase (RKALR) indicate that 5-alpha-haloacetamide analogues 5 and 6 are much more effective inhibitors of RLAR.

Aldehyde Reductase↗
PubMed1992

Structural and functional comparison of two human liver dihydrodiol dehydrogenases associated with 3 alpha-hydroxysteroid dehydrogenase activity.

Two monomeric dihydrodiol dehydrogenases with pI values of 5.4 and 7.6 were co-purified with androsterone dehydrogenase activity to homogeneity from human liver. The two enzymes differed from each other on peptide mapping and in their heat-stabilities; with respect to the latter the dihydrodiol dehydrogenase and 3 alpha-hydroxysteroid dehydrogenase activities of the respective enzymes were similarly inactivated. The pI 5.4 enzyme was equally active towards trans- and cis-benzene dihydrodiols, and towards (S)- and (R)-forms of indan-1-ol and 1,2,3,4-tetrahydronaphth-1-ol and oxidized the 3 alpha-hydroxy group of C19-, C21- and C24-steroids, whereas the pI 7.6 enzyme showed high specificity for trans-benzene dihydrodiol, (S)-forms of the alicyclic alcohols and C19- and C21-steroids. Although the two enzymes reduced various xenobiotic carbonyl compounds and the 3-oxo group of C19- and C21-steroids, and were A-specific in the hydrogen transfer from NADPH, only the pI 5.4 enzyme showed reductase activity towards 7 alpha-hydroxy-5 beta-cholestan-3-one and dehydrolithocholic acid. The affinity of the two enzymes for the steroidal substrates was higher than that for the xenobiotic substrates. The two enzymes also showed different susceptibilities to the inhibition by anti-inflammatory drugs and bile acids. Whereas the pI-5.4 enzyme was highly sensitive to anti-inflammatory steroids, showing mixed-type inhibitions with respect to indan-1-ol and androsterone, the pI 7.6 enzyme was inhibited more potently by non-steroidal anti-inflammatory drugs and bile acids than by the steroidal drugs, and the inhibitions were all competitive. These structural and functional differences suggest that the two enzymes are 3 alpha-hydroxysteroid dehydrogenase isoenzymes.

3-Hydroxysteroid Dehydrogenases↗
PubMed1992

Purification and characterization of pig lung carbonyl reductase.

A pyrazole-sensitive carbonyl reductase from pig lung was purified to homogeneity by electrophoretic criteria. Chemical cross-linking study suggested that the native enzyme is a tetramer with a Mr of 103,000, consisting of apparent identical subunits of Mr 24,000. The enzyme reduced aliphatic and aromatic carbonyl compounds with NADPH as a preferable cofactor to NADH and catalyzed the oxidation of secondary alcohols and the aldehyde dismutation in the presence of NAD(P)+. Immunohistochemical study with the antibodies against the enzyme revealed that the enzyme was localized in the ciliated cells, nonciliated bronchiolar cells, Type II alveolar pneumocytes, and the epithelial cells of the ducts of the bronchial glands in the pig lung. In addition to the properties and distribution, the pig lung enzyme was immunochemically similar to the pulmonary enzymes in the guinea pig and mouse. However, the pig enzyme showed the following unusual features. (1) The enzyme exhibited an equatorial specificity in the reduction of 3-ketosteroids; the 4-pro-S hydrogen of NADPH was transferred to the carbonyl carbon atom of 5 alpha- and 5 beta-androstanes, and the respective reduced products were identified as 3 beta- and 3 alpha-hydroxysteroids. (2) Although the NADPH-linked reduction of carbonyl compounds apparently obeyed the Michaelis-Menten kinetics at pH 6.0, the double-reciprocal plots of the velocity vs concentrations of the carbonyl substrates were convex at pH higher than 6.5. The Hill coefficients and [S]0.5 values for the substrates decreased as the pH for reaction increased. The results suggest that the pig enzyme exhibits negative cooperativity with respect to the carbonyl substrates and that the hydrogen ion acts as an allosteric effector abolishing the negative interaction.

Alcohol Dehydrogenase↗
PubMed1992

Activation of carbonyl reductase from pig lung by fatty acids.

The NADPH-linked reductase activity of pig lung carbonyl reductase was activated two- to fivefold by fatty acids with a carbon chain length greater than nine at pH 7.0. cis-Unsaturated fatty acids of C:18 and C:20 were potent activators, showing Ka values of 2-14 microM which were lower than the values of 21-125 microM for saturated fatty acids (C:9 to C:16). Of the fatty acids arachidonic acid (C20:4) gave the highest activation. No significant stimulatory effect was observed with acyl CoAs, fatty alcohols, phospholipids, and nonionic detergents. Anionic detergents (sodium dodecyl sulfate and sarkosyl) stimulated the enzyme activity more than ninefold, but the Ka values for them were much higher than those for the cis-unsaturated fatty acids. Although no change in molecular weight or in subunit composition was observed in the enzyme activated by C20:4, the activation led to a decrease in thermal stability of the enzyme. The binding of C20:4 to the enzyme was instantaneous and reversible, shifted the pH optimum of the activity from 5.8 to 6.5, and changed the inhibitor sensitivity. In addition, C20:4 acted as an allosteric effector abolishing the negative interaction of the enzyme with carbonyl substrates which was seen without the fatty acid, but the activation increased both Vmax and [S]0.5 values for the substrates. Kinetic analysis with respect to NADPH concentration, in which no cooperativity was detected with or without C20:4, indicated that C20:4 was a nonessential activator of mixed type showing a binding constant of 10 microM. These results suggest that cis-unsaturated fatty acids may be potential modulators of pulmonary carbonyl reductase.

Alcohol Oxidoreductases↗
PubMed1992

[Relationship between types of hypertension and patterns of urinary catecholamine excretion in Sipple's syndrome].

We report here a case of Sipple's syndrome, and we also analyze the relationship between the type of hypertension and urinary excretion of catecholamines in Sipple's syndrome based on the literature in Japan. One hundred and fourteen cases of Sipple's syndrome have been reported in Japan. The hypertension of patients with Sipple's syndrome shows a ratio of fitfull hypertension to continual hypertension of 6 to 1, whereas the ratio is 1 to 1.5 in patients whose pheochromocytoma is not accompanied by Sipple's syndrome. The patients with Sipple's syndrome, being pheochromocytoma can be classified into the adrenaline (U-AD) dominant type and noradrenaline (U-NA) dominant type based on the catecholamine excretion in the urine. The U-AD predominant (U-AD/U-NA greater than 0.4) patients mostly reveal fitfull hypertension, while patients with continual hypertension hardly show U-AD predominant.

Adrenal Gland Neoplasms↗
PubMed1992

Inhibition of T-cell receptor beta-chain gene rearrangement by overexpression of the non-receptor protein tyrosine kinase p56lck.

The variable region genes of the T cell receptor (TCR) alpha and beta chains are assembled by somatic recombination of separate germline elements. During thymocyte development, gene rearrangements display both an ordered progression, with beta chain formation preceding alpha chain, and allelic exclusion, with each cell containing a single functional beta chain rearrangement. Although considerable evidence supports the view that the individual loci are regulated independently, signaling molecules that may participate in controlling TCR gene recombination remain unidentified. Here we report that the lymphocyte-specific protein tyrosine kinase p56lck, when overexpressed in developing thymocytes, provokes a reduction in V beta--D beta rearrangement while permitting normal juxtaposition of other TCR gene segments. Our data support a model in which p56lck activity impinges upon a signaling process that ordinarily permits allelic exclusion at the beta-chain locus.

Animals↗
PubMed1992

Combination of interleukin-2 and irradiation in therapy of murine tumors.

Experiments were designed to investigate the therapeutic efficacy of interleukin-2 (IL-2) combined with radiotherapy. The effect of IL-2 and local thoracic irradiation (LTI) was determined on 4-day-old lung micrometastases, generated by i.v. injection of tumor cells into mice. IL-2 alone reduced the number of lung nodules more effectively when given from 1 to 4 than 4 to 7 days after tumor cell injection. The combination of IL-2 and LTI reduced the number of lung nodules more than did the individual treatments alone. When IL-2 therapy was combined with local irradiation of 8-mm leg tumors, there was no change in the TCD50 (radiation dose yielding 50% local tumor control). However, the combination of IL-2 treatment on days 1-4 with irradiation of tumor-bearing legs on day 1 after inoculation of tumor cells reduced the TCD50 by a factor of 1.3. These results show that IL-2 improves tumor radiotherapy, but that the improvement depends on anatomic localization and tumor size at the time of treatment.

Animals↗