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Biomedical subjects

T Murakami

Publications and source records attributed to T Murakami.

At least 883 records · Page 49Linked to original sources
PubMed1994

Comparison of actin-filament bundles in myoid cells and Sertoli cells of the rat, golden hamster and mouse.

Testes of adult rats, golden hamsters and mice were fixed with paraformaldehyde. Seminiferous tubules were then isolated by collagenase dissociation, stained with fluorescent phallotoxin, and viewed in a confocal laser microscope to observe actin filaments. Bundles of actin filaments in the myoid cells, especially in the rat, were arranged at right angles to each other in relation to the longitudinal axis of the tubule. In the hamster, circumferentially directed bundles were more frequent than longitudinally directed bundles. The actin bundles in the mouse were thinner than those in the rat and hamster, and their lattice network was less prominent. Nuclei of the myoid cells were elliptical and their short diameters were parallel to the long axis of the seminiferous tubules in the animals examined. Areas of myoid cells and of basal junctional portions of Sertoli cells were measured and compared in all animals studied. There were significant differences in the areas among the three species. The golden hamster showed the largest value for myoid-cell area, and the mean value for Sertoli-cell area was highest in the mouse.

Actins↗
PubMed1994

New development of transarterial immunoembolization (TIE) for therapy of hepatocellular carcinoma with intrahepatic metastases.

The prognosis of patients with multiple hepatocellular carcinoma (HCC) remains disappointing. In this study, we devised a new therapeutic modality for HCC consisting of transarterial immunoembolization (TIE) using OK-432 and fibrinogen and then analyzed the preliminary results. In the first series, we applied the treatment to 19 patients with advanced HCC who had proved to be insensitive to several previous conventional treatments. In all, 14 patients (74%) with unresected HCC have currently survived for between 2 and 16 months after TIE. The remaining 5 patients died at 17, 14, 8, 7, and 4 months after TIE. The serum levels of tumor markers decreased in all of the patients, and a marked reduction in tumor size was observed in six patients after TIE. A high fever occurred in all cases, and abdominal pain and loss of appetite were also observed after TIE. However, deterioration of liver function was negligible. After confirmation of the safety of this method, we started a second study series in which this TIE treatment was selected as the first choice. Six patients have been treated to date. All patients in this group underwent hepatic resection at 6-48 days following TIE. Histological examination of the resected specimens following TIE showed massive infiltration of mononuclear cells around tumor cell nests and lytic necrosis as well as coagulation necrosis of the main tumor and the intrahepatic metastases. In conclusion, our results indicate that TIE may be a safe and promising therapy for patients with HCC.

Adult↗
PubMed1994

Five-year survival after transcatheter chemoembolization for hepatocellular carcinoma.

The 5-year cumulative survival rate of 443 patients who underwent transcatheter chemoembolization (TCE) for non-resectable hepatocellular carcinoma (HCC) before December 1986 was 8.0%, and 29 patients survived for 5 years or more. Of these 29 patients, 25 were men and 4 were women; their mean age was 63.9 years. Macroscopic classification showed lesions of the single nodular type in 16 cases, the multiple nodular type in 10 cases, and the massive type in 3 cases; 12 of the single nodular lesions measured 5 cm or less in size. The TNM classification showed lesions of stage I in 3 cases, stage II in 14 cases, stage III in 6 cases, and stage IV in 6 cases. Lesions classified as Child A were found in 23 patients, and they were thus much more common than Child B lesions (2 patients) and Child C lesions (1 patient). The response was analyzed in relation to the use of iodized oil (Lipiodol). It was used in 215 of the patients, and the 5-year cumulative survival rate of those patients was 12.9% (23 of them survived for 5 years or more). Lipiodol was not used in 228 patients, and they showed a 5-year cumulative survival rate of 3.4%, with 6 patients surviving for 5 years or more. The 6 patients with stage III disease and the 6 with stage IV disease received Lipiodol. TCE with Lipiodol thus contributed greatly in prolonging the survival of patients with HCC complicated by intrahepatic metastases or intraportal tumor thrombi.

Adult↗
PubMed1994

Systemic amyloidosis in transgenic mice carrying the human mutant transthyretin (Met 30) gene. Pathological and immunohistochemical similarity to human familial amyloidotic polyneuropathy, type I.

To analyze the pathologic processes of amyloid deposition in type I familial amyloidotic polyneuropathy (FAP), mice were made transgenic by introducing the human mutant transthyretin (TTR) gene(MT-hMet 30). An inbred strain of mouse, C57 BL/6, was chosen. Transgenic mice were killed using ether anesthesia at 3-mo intervals up to 24 mo after birth. In these transgenic mice, amyloid deposition started in the gastrointestinal tract, cardiovascular system, and kidneys and extended to various other organs and tissues with advancing age. The pattern of amyloid deposition was similar to that observed in human autopsy cases of FAP, except for its absence in the choroid plexus and in the peripheral and autonomic nervous systems. We extracted the amyloid fibrils from kidneys of these mice with a human mutant TTR gene and analyzed them immunochemically and electronmicroscopically. Deposited amyloid was shown to be composed of human mutant TTR and mouse serum amyloid P component. Amyloid fibril from transgenic mice was morphologically and immunohistochemically similar to that of human FAP. The most striking pathologic feature of the transgenic mice was the absence of amyloid deposition in the peripheral and autonomic nervous tissues. Thus, other intrinsic factors may be involved in amyloid deposition in the nervous tissues of human FAP.

Age Factors↗
PubMed1994

Exonic trinucleotide repeats and expression of androgen receptor gene in spinal cord from X-linked spinal and bulbar muscular atrophy.

We studied exonic trinucleotide repeats and expression of androgen receptor (AR) gene in the spinal cord from an autopsied patient with X-linked spinal and bulbar muscular atrophy (SBMA). Forty-nine CAG triplet repeats were found in tissues from the spinal cord, cerebrum, cerebellum, cardiac muscle and bladder, while there were 20-24 CAG repeats in these tissues from control subjects, consisting of three patients with amyotrophic lateral sclerosis (ALS) and three patients with lung cancer. Thus, mitotic instability of the AR gene in SBMA may not occur at the level of somatic cells. To determine whether expression of the AR gene in the spinal cord of SBMA differs from that in control subjects, we used quantitative reverse transcriptase (RT)-PCR and Western blot. AR mRNA and protein were detected in the spinal cord from the patient with SBMA, but the levels of both AR mRNA and protein were less than those from the patients with ALS in whom the loss of motor neurons was similar to findings in the patient with SBMA. These findings suggest that structural alteration plus a reduced level of AR in the spinal cord are involved in the pathogenesis of SBMA, resulting in degeneration of motor neurons.

Adult↗
PubMed1994

Cytogenetic and immunogenotypic alterations of blast crisis cells in chronic myelogenous leukemia independently linked to immunophenotypic expression.

Chronic myelogenous leukemia (CML) is a disease of the hematopoietic stem cells, which can differentiate into either B-lymphoid or myeloid cells, because most of them develop either lymphoid or myeloid blast crisis. Immunophenotypic, genotypic, and cytogenetic analyses of 22 patients (24 episodes) with Philadelphia (Ph) positive CML in blast crisis were performed to determine the genetic alterations of the blast crisis cells. In B-lymphoid blast crisis, all the five patients had immunoglobulin heavy-chain (IgH) rearrangements and most of them showed normal karyotypes. Among the five patients, T-cell receptor (TCR) genes were rearranged at the following occurrence rates: 20% in TCR-beta, 60% in TCR-gamma, and 40% in TCR-delta chain genes. A high incidence of additional chromosome changes was noted in patients with B-lymphoid/myeloid-mixed blast crisis, but about 80% of them had rearranged IgH and about 40% had TCR rearrangements. In contrast, most of the patients with non-lymphoid blast crisis showed further chromosomal abnormalities, including +8, +19, i(17q), and double Ph, and most of them had germline configurations of IgH and TCR-gamma chain genes. Notably, only one patient (dual lymphoid and myelomegakaryoblast crisis) in this group exhibited IgH rearrangement, and TCR-beta and TCR-delta rearrangements were also rarely noted. Rearrangement of the IgH gene in CML blast crisis might be linked to expression of lymphoid markers, especially CD19.

Antibodies, Monoclonal↗
PubMed1994

Normalization of hair growth in sparse fur-abnormal skin and hair (SPF-ASH) mice by introduction of the rat ornithine transcarbamylase (OTC) gene.

The sparse fur-abnormal skin and hair (SPF-ASH) mouse is a model for the human X-linked hereditary disease, ornithine transcarbamylase (OTC) deficiency. This condition is characterized by abnormal skin and delayed hair growth, hyperammonemia, orotic aciduria and low levels of serum citrulline and arginine. Murakami et al. [1] established a line of transgenic mice, by introducing the recombinant rat OTC (rOTC) gene into fertilized C57BL mouse eggs. We introduced the rOTC gene into SPF-ASH mice by mating SPF-ASH heterozygotes and transgenic mice, which carried this gene. The hemizygous SPF-ASH mice bearing the rOTC gene showed normal hair growth without sparse fur, normal urinary orotic acid excretion and normal serum citrulline and arginine levels. These mice showed OTC activities 2 and 6 times higher in the liver and small intestine, respectively, than the SPF-ASH mice but about 12% and 27% those of the controls [2].

Animals↗
PubMed1994

Pharmacokinetic analysis of the absorption enhancing action of decanoic acid and its derivatives in rats.

The enhancing action of decanoic acid (C10) and its derivatives on mucosal absorption of phenolsulfonphthalein (PSP) in the jejunum or colon was analyzed using pharmacokinetics in rats. After administration of a solution containing PSP and an enhancer [C10, 2-hydroxydecanoic acid (2-OHC10), or 3-hydroxydecanoic acid (3-OHC10)] into the jejunal or colonic loop, the amounts of PSP and enhancer remaining in the loop and/or plasma PSP concentration were determined periodically. 2-OHC10 exhibited a greater absorption enhancing potency than C10, while 3-OHC10 was less effective. Disappearance of residual PSP from the loop ceased after complete absorption of the enhancer. The enhancer-induced disappearance rate constant of PSP correlated well with the product of the enhancer disappearance rate and its capacity to sequester calcium ions. In conclusion, the enhancement of PSP mucosal absorption by C10 and its derivatives is consistent with a pharmacokinetic model, assuming that the enhanced membrane permeability of PSP depends on the enhancer disappearance kinetics from the loop and its calcium ion sequestration capacity.

Animals↗
PubMed1994

Decanoic acid induced enhancement of rectal absorption of hydrophilic compounds in rats.

The enhancing effect of decanoic acid (C10) on the rectal absorption of phenolsulfonphtalein (PSP) was analyzed with a pharmacokinetic model. The transfer index of PSP from the rectal lumen to the epithelial layer in the presence of C10 was proportional to the product of the C10 disappearance rate from the rectal lumen and its calcium ion sequestration capacity. The enhancement of rectal PSP absorption by different doses of C10 was also predictable by using a permeability index, Pa, of PSP, which was defined as a proportionality constant relating transfer index and the product value described above. The Pa values of various hydrophilic compounds with different molecular weights were also estimated from their rectal bioavailability in the presence of C10. A linear relationship was observed between Pa values and reciprocal values of the square root of individual molecular weight. These findings suggest that the Pa index is related to the permeant's diffusion coefficient through paracellular aqueous openings formed by C10.

Animals↗
PubMed1994

Transforming growth factor beta 1 secreted from scirrhous gastric cancer cells is associated with excess collagen deposition in the tissue.

To explore the mechanism of increased collagen deposition in scirrhous carcinoma of the stomach, an attempt was made to define the role of transforming growth factor beta 1 (TGF-beta 1), secreted from tumour cells, as a possible humoral factor which functions in a paracrine manner to stimulate the production of collagen in regional fibroblasts. Immunohistochemical staining revealed that tumour cells in scirrhous carcinomas were generally stained more intensively than those in other types of carcinomas. On Northern blot analysis the tumour cells established from scirrhous carcinoma (KATO-III, OCUM-1 and HSC-39) exhibited relatively strong signals compared with those from non-scirrhous carcinoma (MKN-28 and MKN-45). In the culture media of scirrhous carcinoma cells, the active form of TGF-beta 1 was detected, while in those of the non-scirrhous carcinoma cells the latent form was demonstrated by both colony and radioreceptor assays. The culture medium from KATO-III showed strong stimulating activity of collagen synthesis in fibroblasts, and this activity was partially neutralised by an anti-TGF-beta 1 antibody. These results suggest that tumour cells in scirrhous carcinoma produce more active-form TGF-beta 1 than does non-scirrhous carcinoma and thus is partially responsible for the observed enhanced collagen deposition in the region.

Adenocarcinoma, Scirrhous↗
PubMed1994

Centrally induced vasopressor and sympathetic responses to a novel endogenous peptide, adrenomedullin, in anesthetized rats.

Possible central actions of adrenomedullin were explored and compared with the peripheral effects by injecting it into the lateral ventricle, cisterna magna, and femoral vein in urethane-anesthetized rats. Adrenomedullin, 1.0 to 3.0 nmol/kg, injected intravenously (i.v.), caused a transient vasodepression of about 10 to 30 mm Hg, dose dependently, which lasted for < 15 min. On the other hand, intracerebroventricular (ICV) and intracisternal (IC) injections of adrenomedullin elicited sustained elevations of arterial pressure of gradual onset, dose dependently; the arterial pressure started to rise at about 3 min after the injection, and gained peak response after > 20 min. The pressor response lasted for > 2 h. Heart rate was not significantly influenced by these doses of adrenomedullin. The abdominal sympathetic outflow was markedly increased in relation to the blood pressure elevation. The time-course of the responses was quite similar with both ICV and IC injections. Hypotensive effects of i.v. injected adrenomedullin was partially attenuated, and the centrally induced vasopressor responses were abolished by the pretreatment with human calcitonin gene-related peptide (hCGRP)-receptor antagonist, hCGRP(8-37). These findings indicate that the receptors for adrenomedullin exist in the brain, and that the receptor site may be anatomically far from the surface of the brain and the ventricular system because the onset of the pressor response was delayed. Or, CGRP and adrenomedullin may share the same receptors, particularly in the brain.

Adrenomedullin↗
PubMed1994

Characterization of multiple molecular forms of Mg(2+)-dependent protein phosphatase from Saccharomyces cerevisiae.

Three molecular species of Mg(2+)-dependent protein phosphatase (MPPs-1, -2, and -3) were isolated by DEAE cellulose column chromatography and gel filtration from an extract of Saccharomyces cerevisiae. MPP-1 was further purified 150-fold by chromatography using thio-phosphorylated myosin light chain-agarose. MPPs-1, -2, and -3 were distinct from the major acid and alkaline phosphatases, and their activities were not affected by okadaic acid, microcystin-LR or Ca2+, and calmodulin, resembling the enzymatic properties of type 2C protein phosphatase of mammalian cells. The apparent molecular masses of MPPs-1, -2, and -3 on gel filtration were 53, 112, and 128 kDa, respectively. It was demonstrated that MPP-1 is a globular protein of 53-55 kDa and that MPPs-2 and -3 are oligomeric proteins that dissociate upon sucrose density gradient centrifugation, generating catalytic proteins of about 50 kDa. Since the substrate specificities of MPPs-1, -2, and -3 differed from each other both before and after sucrose density gradient centrifugation, it was suggested that the catalytic proteins of these three enzymes are distinct molecular species.

Chromatography, DEAE-Cellulose↗
PubMed1994

Transthoracic percutaneous ethanol injection into the liver.

RATIONALE AND OBJECTIVES: The feasibility of the new transthoracic approach of percutaneous ethanol injection through the lower lung to the subphrenic region of the liver was evaluated in normal rats. METHODS: Fourteen normal rats received percutaneous ethanol injection. A 22-gauge fine needle was inserted into the liver via the thoracic cage and through the lower lung parenchyma under computed tomographic (CT) guidance. After ethanol (0.1-0.2 mL) was injected, three follow-up CT scans were performed: immediately after, 1 day after, and 1 week after the initial injection. All animals were killed 1 week after injection to evaluate macroscopic changes of the diaphragm and pleura. RESULTS: No major complications were observed. Minor complications were observed in six rats; these included one pneumothorax (7%) and five band-like and streaky shadows (presumably pulmonary hemorrhages) (35%) on the CT scan obtained immediately after the procedure. However, all complications had disappeared spontaneously in the follow-up CT scan obtained 1 day after the procedure. At autopsy, no pleural changes were seen. CONCLUSIONS: This study demonstrates that percutaneous ethanol injection through the lower lung parenchyma is achievable. Although this study was performed only in normal rats, the transthoracic approach can be a complementary method of ultrasound-guided percutaneous ethanol injection for tumors in the subphrenic region of the liver. Further study will be needed in abnormal livers and then in human subjects to verify the safety and efficacy of this procedure.

Animals↗