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Biomedical subjects

H Murakami

Publications and source records attributed to H Murakami.

At least 397 records · Page 22Linked to original sources
PubMed1995

Effects of transforming growth factor alpha (TGF-alpha) on DNA synthesis and thyrotropin-induced iodine metabolism in cultured porcine thyroid cells.

Transforming growth factor alpha (TGF-alpha) is a potent mitogen that is similar structurally to epidermal growth factor (EGF). As EGF is a potent growth stimulator and an inhibitor of iodine metabolism in cultured thyroid cells of several species, we studied whether TGF-alpha has similar effects using porcine thyroid cells in culture. Recombinant human TGF-alpha dose-dependently stimulated DNA synthesis of thyroid cells, with maximal stimulation (eight- to ninefold above basal) occurring at 2 nmol/l. The potency was approximately 50% that of mouse EGF and correlated with the ability to compete with EGF for receptor binding, suggesting that the action of TGF-alpha is mediated by interaction with EGF receptors. When thyroid cells were cultured for 3 days with thyrotropin (TSH) in the presence of TGF-alpha, TSH-induced iodide uptake was inhibited in a dose-dependent manner. The potency of TGF-alpha again was approximately 50% that of EGF. Transforming growth factor alpha did not inhibit TSH-stimulated cAMP production. Moreover, iodide uptake stimulated by either forskolin or 8-bromo-cAMP also was inhibited by TGF-alpha. Thus, we conclude that TGF-alpha inhibits TSH-induced iodine metabolism largely by acting at the steps distal to cAMP production. Northern blot analysis revealed expression of TGF-alpha mRNA in porcine thyroid cells. These observations suggest that TGF-alpha acts as an autocrine modulator of growth and differentiated functions in porcine thyroid cells.

Animals↗
PubMed1995

A modified bioassay for energy utilization in newly hatched chicks. 2. Determination of feed input and procedures to estimate endogenous energy loss.

Two experiments were conducted to develop a modified bioassay system to determine bioavailability of dietary energy in newly hatched chicks based on the TME assay system. Broiler chicks aged 0, 1, 3, 7, and 14 d old were force-fed or consumed feed ad libitum following 24 h of feed withdrawal to determine the optimum level for feed input. In the second experiment, 7-d-old chicks were force-fed various diets and feedstuffs at three levels following 24 h of feed deprivation. Linear regressions (P < .01) between energy input (X) and excreted energy (Y) were demonstrated irrespective of diets and feedstuffs at any age in Experiments 1 and 2. Endogenous energy loss (EEL), estimated by the regression method and approximated over a small range was lower than EEL estimated using feed-deprived chicks. The TME and TMEn values of diets and feedstuffs calculated using EEL estimated by the regression method were not modulated by the feed input level, whereas those estimated by feed-deprived chicks tended to increase with decreases in the level of feed input. Thus, a modified method for determination of energy utilization in newly hatched chicks based on TME assay is proposed, which seems to have proper physiological and chemical bases.

Age Factors↗
PubMed1995

[A case of advanced gastric cancer successfully treated with combination chemotherapy using THP, 5'-DFUR and CDDP, followed by surgical resection].

We reported a patient with advanced gastric cancer and a liver metastasis, who responded remarkably to combination chemotherapy using THP, 5'-DFUR and CDDP. The patient was administered four courses of THP (15 mg/m2/day, on day 1, iv), 5'-DFUR (1400 mg/m2/day, on days 1-4 and 15-18, orally), and CDDP (80 mg/m2/day, on day 5, iv) every 4 weeks. As a result, both the primary and metastatic tumors decreased remarkably in size at more than 19 weeks (PR) and we performed curative total resection of the stomach and partial resection of the liver. Histologically, the effects of chemotherapy on gastric focus were evaluated as grade 1a and the liver metastasis completely disappeared. This combination therapy proved useful to treat advanced gastric cancer in this patient.

Adenocarcinoma↗
PubMed1995

[Porphyrias and drugs].

The porphyrias are a metabolic disorders of heme biosynthesis characterized by the excessive production and excretion of porphyrins and porphyrin precursors. They are caused by defects in specific enzyme activities and classified into 7 subtypes. Some of them present with photosensitivity of skin and intermittent acute attacks related to nervous system disturbance. Especially in acute intermittent porphyria, patients have recurrent acute attacks of abdominal, neurologic, and psychiatric symptoms. Some precipitating factors; including drugs, hormonal factors, starvation, and stress; induces acute attacks. In this article, pathophysiology of the neurologic symptoms and relation between precipitating factors, especially focused in drugs, and acute attacks may be reviewed.

Carbamazepine↗
PubMed1995

[The effectiveness of perfluorotributylamine/pluronic F-68 stem-emulsion (FC43se) against xenograft rejection in the guinea pig-to-rat model].

The administration of perfluorotributylamine/pluronic F-68 stem-emulsion (FC43se), a fluorine compound emulsion, to a rodent discordant xeno-transplantation (dXT) model led to the discovery of the inhibitory effect of this compound against hyperacute rejection (HAR). When a guinea pig heart was transplanted to a rat administered with FC43se (10 microliters/g body weight), rhythmic beating was maintained for 1110 +/- 111.1 min (mean +/- SD; n = 8) whereas the untreated heart continued to beat for 15.5 +/- 6.6 min (mean +/- SD; n = 8). After 720 min of re-beating; pathologic changes observed in the untreated group, such as multiple thrombosis in the coronary vessels, were not observed in the FC43se-administered group by light and electron microscopic examination, and endothelial cells were well preserved. On the other hand, scattered necroses of the myocardium were observed and lymphocytic infiltration was demonstrated in the interstitium. We concluded that FC43se possessed a HAR inhibitory effect by inhibiting thrombus formation in the xeno-graft heart. Using this model, we speculated that action in the vessels of the graft heart (intravascular HAR) caused thrombus formation in the vessels. On the other hand, extravascular HAR causes myocardial necrosis more slowly, not resulting in cardiac arrest in the short term.

Acute Disease↗
PubMed1995

Central cord syndrome secondary to hyperflexion injury of the cervical spine in a child.

A 10-year-old girl sustained hyperflexion injury to the midcervical spine, i.e., wedge compression fractures of the C3, C4, and C5 vertebral bodies, when hit by an automobile, subsequently manifesting central cord syndrome below the C4 spinal cord level. Serial magnetic resonance imaging helped identify the spinal cord lesion at the corresponding levels. Conservative management combined with corticosteroid administration resulted in nearly full neurologic recovery approximately 3 months after the trauma, although a cystic lesion remained present within the spinal cord 11 months after trauma.

Cervical Vertebrae↗
PubMed1995

Histamine excess symptoms in basophilic crisis of chronic myelogenous leukemia.

We encountered a patient with chronic myelogenous leukemia in basophilic crisis accompanied with histamine excess symptoms including bronchial asthma and gastric ulcer. The concentrations of histamine and histidine decarboxylase in leukemic cells containing granules typical for basophils were similar to those in mature basophils. His histamine excess symptoms rapidly disappeared concomitant with the reduction of blast cells after chemotherapy. We speculate that his histamine excess symptoms were induced by the leukemic cells.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Effects of ET antagonists (PD143296 and PD145065) on contractions in guinea pig hilar bronchus induced by endothelin-1 and its related peptide.

ETs-induced contractions were resistant to ET(A)-selective antagonists and believed to be mediated by activation of ETB receptors in guinea pig bronchus. In the present study, the effects of the ET antagonists, PD143296 (Ac-D-Phe-L-Leu-L-Phe-L-Ile-L-Ile-L-Trp.2Na) and PD145065 (Ac-[(R)-2-10, 11-dihydro-5H-dibenzo[a, d]cyclohepten-5-yl]Gly)-L-Leu-L-Asp-L-Ile-L-Ile- L-Trp.2Na), on contractions induced by ET-1, ET-3, sarafotoxin S6c (STXc), and IRL1620 in the isolated hilar bronchus of the guinea pig were investigated. An ETA/B nonselective antagonist, PD145065 antagonized contractions induced by ET-1, ET-3, STXc, and IRL1620. Its antagonistic activity against ET-1, with pKB of 5.77 +/- 0.02 (n = 16, 3-10 microM), was significantly lower than that against ET-3, with pKB of 6.18 +/- 0.02 (n = 12, 3-10 microM), STXc, with pKB of 5.97 +/- 0.01 (n = 14, 3-10 microM), and IRL1620, with pKB of 6.80 +/- 0.04 (n = 14, 0.3-1 microM). Conversely, although a putative ETB-selective antagonist, PD143296 (10 microM) slightly but significantly antagonized the concentration-response curve of IRL1620 (pKB = 5.28 +/- 0.14, n = 6), it had no effect on ET-1-,ET-3-, or STXc-induced contractions. These results suggest that ETs possibly activate ETB2 or an atypical ETB receptor subtype in guinea pig hilar bronchus.

Animals↗
PubMed1995

[The role of interstitial hyaluronan in acute lung injury].

The pulmonary interstitium may affect the movement of water, macromolecules, and inflammatory cells between capillaries and lymphatics. Hyaluronan (hyaluronic acid), a glycosaminoglycan of the interstitial matrix, helps to retain water in the lung interstitium and to exclude proteins. Marked reduction of interstitial hyaluronan by infusion of hyaluronidase decreased the resistance to fluid transport and decreased water retention in the interstitium, and thus accelerated lymphatic removal of fluid filtered across capillary walls. However, reduction of hyaluronan increased the accumulation of neutrophils in the lung and exacerbated acute lung injury caused by pancreatic elastase. Interstitial hyaluronan may protect against acute inflammatory changes in elastase-induced lung injury.

Acute Disease↗
PubMed1994

Heterogeneous expression of human antibody lambda chains by concanavalin A-resistant hybridomas lead to changed antigen binding.

Human HB4C5 hybridoma cells produce a lung cancer-specific human monoclonal antibody that possesses a lambda light chain on which a N-linked carbohydrate chain is attached at the first complementary determining region. Up to six light chains of various sizes are secreted by the original and concanavalin A (ConA)-resistant HB4C5 clones. Two of these six light chains are derived directly from the HB4C5 original and are 30 and 32 kDa in size. The structural difference between these two light chains has been shown to be a N-linked carbohydrate located at a single site. The other four variants, which are derived from ConA-resistant variants, have light chain sizes ranging from about 26 to 29 kDa. No changes in the secretory forms were observed when glycosylation was inhibited by the addition of tunicamycin, indicating that the heterogeneous light chain forms produced by these ConA-resistant variants resulted from the size differences of core polypeptides and not from N-glycosylation. Sequence analysis from one of the variant light chains revealed that its V lambda gene segment differs markedly from identified human V lambda gene segments (at most, 60% homology with known human V lambda subgroups) and, furthermore, the variant light chain shares 80% homology with the rabbit V lambda gene. In addition, the antigen binding ability of these variant antibodies changed significantly in both specificity and affinity. These results suggest that heterogeneous light chains expression by ConA-resistant variants may provide a new way for developing an antigen-specific human monoclonal antibody repertoire.

Amino Acid Sequence↗
PubMed1994

Spatial precision of a catalytic carboxylate of F1-ATPase beta subunit probed by introducing different carboxylate-containing side chains.

Combining mutation and chemical modification, we have introduced Asp, Gln, Cys, S-carboxymethylcysteine (Cax) and S-carbamoylmethylcysteine (Cam) into the positions of Glu190 and Glu201 of the beta subunit of F1-ATPase from the thermophilic Bacillus PS3. The steady-state ATPase activities of alpha 3 beta 3 gamma complexes containing these changed beta subunits were 12% (E190Cax), 7% (E190D), 3% (E190Cam), < 1% (E190C), < 1% (E190Q), and 73% (E201D), 40% (E201Cax), 25% (E201C), 20% (E201Q), 4% (E201Cam), of that of that of the wild-type alpha 3 beta 3 gamma complex. For the complexes containing E190C or E190Q, even the ability of single-site catalysis was lost. Thus, the presence of a carboxylate at 190 (but not at 201) is absolutely required for catalysis and its spatial precision is very strict. Analysis of inactivation of the complexes by dicyclohexylcarbodiimide suggests that Glu190 and Glu201 are interacting in the F1-ATPase.

Amides↗
PubMed1994

Changes in parathyroid hormone receptors during chondrocyte cytodifferentiation.

The purpose of this study was to investigate the relationship between changes in parathyroid hormone (PTH) receptor levels and chondrocyte maturation during endochondral ossification. Chondrocytes were isolated from the growth plate of rabbit ribs and maintained in the presence of 10% serum in mass cultures. Treatment with PTH-(1-84) and a PTH-(1-34) fragment suppressed the increases in alkaline phosphatase activity and in type X collagen and 1 alpha,25-dihydroxyvitamin D3 receptor levels and abolished 45Ca incorporation into mineral, all of which occurred in parallel untreated cultures in the hypertrophic (terminal) stage. These effects of PTH were observed at low concentrations (10(-10) to 10(-9) M) and within 24-48 h of treatment. PTH-(1-84) and PTH-(1-34) also increased [35S]sulfate incorporation into newly synthesized proteoglycans. In contrast, the middle and carboxyl-terminal fragments of PTH tested had little effect on proteoglycan synthesis or terminal differentiation. The binding of 125I-PTH-(1-34) to cells in the growth plate was greater than that to cells in liver, skin, muscle, brain, or kidney. When the correlation between binding levels and stage of maturation was examined, we found that 125I-PTH-(1-34) binding to its 72-kDa receptor was low in resting and proliferating chondrocytes, increased 10-fold in matrix-forming chondrocytes, and thereafter decreased in hypertrophic chondrocytes both in vitro and in situ. Scatchard analysis revealed that the changes in PTH binding were due to changes in the number, and not in the affinity, of the receptor. The changes in PTH-(1-34) binding paralleled those in [35S]sulfate incorporation into proteoglycans. These findings suggest that stage-dependent increases in PTH/PTH-related peptide receptor levels localize the hormone stimulation of proteoglycan synthesis and inhibition of precocious hypertrophy in the matrix-forming zone of growth plates.

Alkaline Phosphatase↗