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Biomedical subjects

M Hara

Publications and source records attributed to M Hara.

At least 595 records · Page 33Linked to original sources
PubMed1994

Hepatocellular carcinoma with splenic metastasis developing after 16 years of chemotherapy for chronic myelogenous leukemia: a case report.

A case of hepatocellular carcinoma (HCC), which developed during chemotherapy for chronic myelogenous leukemia (CML), is presented. A 55-year-old Japanese man, who had received an alkylating agent for 16 years, was diagnosed as having HCC with clinically evident splenic metastases. The patient died of the HCC rupture three months after diagnosis. The autopsy revealed the HCC to have developed from the non-cirrhotic liver. In the present case, DNA damage due to the long-term chemotherapy with the alkylating agent for CML may have endowed the HCC induced by post-transfusion hepatitis and alcohol abuse with an aggressive proliferative potential. This is the first report on HCC in association with CML.

Busulfan↗
PubMed1993

Identification of Ras farnesyltransferase inhibitors by microbial screening.

A microbial screen using a yeast strain with conditional deficiency in the GPA1 gene was carried out to search for inhibitors of protein farnesyltransferase (PFT). A strain of Streptomyces was found to produce active compounds named UCF1-A, UCF1-B, and UCF1-C. Structural determination of these compounds revealed that UCF1-C is identical to the known antibiotic, manumycin, whereas UCF1-A and UCF1-B are structurally related to manumycin. All three UCF1 compounds suppress the lethality of gpa1 disruption, with UCF1-C exhibiting the strongest activity. UCF1 inhibits yeast as well as rat brain PFT. Fifty percent inhibition of yeast PFT activity is observed with 5 microM UCF1-C. Kinetic analyses of the inhibition suggest that UCF1-C acts as a competitive inhibitor of PFT with respect to farnesyl pyrophosphate, exhibiting a Ki of 1.2 microM, whereas the same compound appears to act as a noncompetitive inhibitor of PFT with respect to the farnesyl acceptor, the Ras protein. UCF1-C shows significant activity to inhibit the growth of Ki-ras-transformed fibrosarcoma, raising the possibility of its use as an antitumor drug.

Alkyl and Aryl Transferases↗
PubMed1993

Interleukin 1 receptor on fibroblasts from systemic sclerosis patients induces excessive functional responses to interleukin 1 beta.

To determine if SSc fibroblasts are more sensitive to exogenous IL-1 than are normal fibroblasts, we studied the inductions of IL-6, prostaglandin E2 (PGE2), IL-1 beta mRNA production by IL-1-stimulated SSc and normal fibroblasts. The minimal IL-1 beta concentrations for stimulation of IL-6 and PGE2 production by SSc fibroblasts were 10-fold and 100-fold lower, respectively, than those for normal fibroblasts. The minimal IL-1 beta concentration for stimulation of IL-1 beta mRNA expression by SSc fibroblasts was also 10-fold lower than that for normal fibroblasts. These results suggest that the IL-1 signal transduction through IL-1R could be induced excessively in SSc fibroblasts. It is suggested that the IL-1 signal transduction plays an important role in the abnormal cytokine networks observed in the fibrosis of SSc.

Base Sequence↗
PubMed1993

Interaction of cutaneous stromal cells and gamma/delta T cell receptor (TcR)-positive cells. I. V gamma 5-gamma/delta TcR+ T cells migrating from organ-cultured murine skin proliferate by co-culture with cutaneous stromal cells in the presence of interleukin-2.

It has been reported that Thy-1+CD3+CD4-CD8- cells as well as Langerhans cells migrate from organ-cultured murine skin into culture medium. We examined whether these Thy-1+ populations of migrating cells were derived from Thy-1+ dendritic epidermal T cells (Thy-1+ DEC) and found that they were Thy-1+CD3+CD4-CD8-gamma/delta TcR+ (gamma delta+T) cells but did not express V gamma 5TcR, which was used by a vast majority of Thy-1+ DEC. Recently, a unique interaction between stromal cells and lymphohemopoietic progenitors has been reported in bone marrow and thymus. In this study, we established fibroblastoid cutaneous stromal cell (CSC) lines and clones from murine skin and examined the interaction between CSC and gamma delta+T cells. When these gamma delta+T cells were co-cultured with CSC, a marked proliferation of small lymphoid cells was observed only in the presence of interleukin (IL)-2. Neither CSC alone nor IL-2 alone could induce a similar proliferation. Flow cytometry revealed that they were Thy-1+CD3+CD4-CD8-gamma/delta TcR+ but V gamma 5TcR-. Analysis of the major segments of their TcR by polymerase chain reaction demonstrated that V gamma 1, V gamma 2, V gamma 4 and all of the V delta chains from V delta 1 to V delta 7 were used without any predominant pattern. These data indicate the possible presence of gamma/delta+T cells other than V gamma 5TcR+Thy-1+ DEC in the murine skin and the unique capacity of the CSC to support the growth of these migrating gamma/delta+ T cells. The nomenclature of murine T cell receptor gamma chain is according to Reilly et al. (Nature 1986. 321:878). The relationship between the different nomenclature systems is summarized in Takagi et al. (J. Immunol. 1989. 141:2112).

Animals↗
PubMed1993

Monocyte chemoattractant protein-1 (MCP-1) in inflammatory joint diseases and its involvement in the cytokine network of rheumatoid synovium.

Macrophages infiltrated into synovium play an important role in joint destruction in inflammatory joint diseases. In this study we focused on the production of monocyte chemoattractant protein-1 (MCP-1), a recently identified monocyte chemotactic protein, by inflammatory synovium. Synovial fluid (SF) from rheumatoid arthritis (RA), osteoarthritis, gout, and traumatic arthritis contained MCP-1. MCP-1 was produced in the synovium of patients with RA and other inflammatory joint disease in in vitro culture systems; differences in the amounts produced were not significant. Synovial MCP-1 production in RA was further investigated. Levels of MCP-1 were significantly correlated with levels of IL-1 beta, IL-6, and IL-8 in the culture supernatants of synovia from RA. Using immunohistochemical techniques, MCP-1 was detected in the lining and sublining cells and in the vascular endothelial cells of rheumatoid synovia. Rheumatoid synovia with active inflammation were stained more intensely by anti-MCP-1 antibody than were those with weak or inactive inflammation. IL-1 beta and TNF-alpha stimulated the expression of MCP-1 mRNA and de novo MCP-1 synthesis by cultured synovial cells. These results suggest the production of MCP-1 by synovium of various inflammatory joint diseases. In rheumatoid synovium, a cytokine network involving MCP-1 and other proinflammatory cytokines (IL-1 beta, IL-6, IL-8, and TNF-alpha) contributes to the immunopathogenesis of RA.

Arthritis↗
PubMed1993

Kumacone II: an adapter to aid in the placement of a purse-string suture in very low anterior rectal resection.

We have designed an adapter called the "Kumacone II", being a bottle-shaped rubber device which greatly aids in placing a purse-string suture, even at the lowest level near the anorectal junction of the rectum. When this adapter is used, performing the anastomosis is much less time-consuming and not as much training is needed as for low anterior resection using conventional manual suturing. In a clinical study, the incidence of leakage and incontinence was nil in five out of five patients.

Anal Canal↗
PubMed1993

Age- and sex-dependent change in stratum corneum sphingolipids.

We measured six stratum corneum sphingolipid species (ceramides 1-6) in 26 males and 27 females, and found a significant change in their percentage composition only among female subjects of different age groups. There was a significant increase in ceramide 1 and 2 with a corresponding decrease in ceramide 3 and 6 from prepubertal age to adulthood. Thereafter the ratio of ceramide 2 to total sphingolipids decreased with age in contrast to ceramide 3 which showed an increase. Such a pattern of change in the aging population is different from that observed in scaly skin experimentally induced by tape stripping. The present results suggest a significant influence of female hormones on the composition of stratum corneum sphingolipids. Moreover, the different patterns of change in sphingolipid composition of stratum corneum lipids between scales from inflammatory skin and those from aged skin also suggest that epidermal biosynthesis of sphingolipids is influenced by epidermal proliferative activity.

Adolescent↗
PubMed1993

Relationships among residual beta cells, exocrine pancreas, and islet cell antibodies in insulin-dependent diabetes mellitus.

Quantitative analysis was performed using computerized morphometry on the relationships between residual beta cells, pancreatic exocrine glands, and islet cell antibodies (ICA) in 14 pancreata of insulin-dependent diabetic (IDDM) patients. Both pancreatic exocrine glands and beta cells were markedly reduced in weight in IDDM patients compared with non-insulin-dependent diabetic (NIDDM) patients or nondiabetic controls. beta cells were preserved in six cases and were completely abolished in eight cases. In nine IDDM pancreata weighed at autopsy, the weights of pancreatic exocrine glands in six patients with either no or virtually no residual beta cells (32.3 +/- 1.6 g) were greater than those in three patients with residual beta cells (23.1 +/- 2.5 g, P < .05). Infiltration of lymphocytes positive for leukocyte common antigen (LCA) around the islet was observed in only one case with ICA and residual beta cells. Infiltration of LCA-positive lymphocytes around pancreatic acinar cells was observed in 50% (six of 12) of patients examined. The weight of pancreatic exocrine glands in patients with LCA-positive lymphocyte infiltration (26.2 +/- 2.3 g) was lower than that in patients without this condition (33.2 +/- 2.4 g, P < .05). Pancreatic cytokeratin autoantibodies (PKA) were detected in four of 10 patients examined. In addition, all four ICA-positive patients had residual beta cells, while only one of seven ICA-negative patients had residual beta cells (P = .03).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

The expression of rat GAP-43 cDNA in transgenic carp.

To understand more about growth-associated protein-43 (GAP-43), we produced transgenic carp by introduction of a rat GAP-43 cDNA linked to the Rous sarcoma virus-long terminal repeat into fertilized eggs. Of 180 eggs microinjected with exogenous gene, 59 embryos hatched and 4 fish were found to contain the exogenous gene sequences in the genomic DNA. From a mature female transgenic carp, parthenogenetically, 126 progeny were derived and 52 of them survived for more than 90 days. The exogenous gene sequences were detected in 22 F1 progeny, and its messenger RNA was detected in all of 10 transgenic F1 carp examined. In serum-free medium, cultured retinal ganglion cells isolated from transgenic carp elongated their axons, while non-transgenic cells did not elongate axons.

Animals↗
PubMed1993

Direct visualization of polypeptide shell of ferritin molecule by atomic force microscopy.

The polypeptide shell of the ferritin molecule has been imaged in water by atomic force microscopy (AFM). The central dip and the quaternary structure could be observed on the surface of the ferritin molecule anchored inhomogeneously in two dimensions. These structures observed in the AFM images are quite similar to the electron density map near the top of the apoferritin viewed down from a 4-fold axis structure reported previously (S. H. Banyard, D. K. Stammers, and P. M. Harrison, 1978. Nature (Lond.). 271:282-284). It has been achieved by introducing a "self-screening effect" of the surface charges of the AFM sample (S. Ohnishi, M. Hara, T. Furuno, and H. Sasabe. 1992. Biophys. J. 63:1425-1431) and the specially sharpened stylus of AFM cantilever.

Animals↗
PubMed1993

Propofol activates GABAA receptor-chloride ionophore complex in dissociated hippocampal pyramidal neurons of the rat.

BACKGROUND: The molecular mechanism of propofol anesthesia has been related to facilitation of the inhibitory neurotransmission mediated by gamma-aminobutyric acid (GABA). In the current study, the authors examined the direct actions of propofol on the acutely dissociated mammalian central neurons. METHODS: Hippocampal pyramidal neurons were dissociated after enzymatic treatment of the brain slices of the rat. Single neurons were voltage-clamped using the whole cell configuration of the patch clamp technique, and drugs were applied with a rapid drug-application system. RESULTS: In the pyramidal neurons voltage-clamped at -60 mV, propofol evoked a transmembrane inward current, which desensitized at high concentrations of the anesthetic. The peak amplitude of the current increased sigmoidally with increasing doses of propofol applied. A least-squares fitting gave a dissociation constant of 1.2 x 10(-5) M and a Hill coefficient of 1.8, thereby indicating that clinical concentrations of propofol evoke the current, and that the anesthetic cooperatively activates the channel. The threshold concentration was less than 10(-6) M. The reversal potential for the current shifted according to the chloride equilibrium potential predicted by the Nernst equation, indicating that the current was carried by chloride ions. Bicuculline and strychnine suppressed the current in a concentration-dependent manner, in which the former was almost 40-fold more potent than the latter. The propofol-induced current cross-desensitized with the GABA-induced current, but no such interaction was observed with the glycine-induced current. Ro15-1788 (10(-6) M), an allosteric benzodiazepine antagonist, had no effect on the response. Diazepam (10(-6) M) enhanced the propofol-induced current, but pentobarbital (10(-6) M and 3 x 10(-5) M) did not affect the current. CONCLUSIONS: Propofol at clinically relevant concentrations directly activates the GABAA receptor-chloride ionophore complex in the mammalian central neurons and, hence, increases the chloride conductance, which may contribute to anesthesia produced by the agent. The desensitization of the GABAA receptor in the presence of high concentrations of propofol may result in a suppression of the GABAA inhibitory system.

Animals↗
PubMed1993

Assessment of body composition measured by bioelectrical impedance in children.

Bioelectrical impedance methods have been found to be a valid and reliable way of estimating per cent body fat (%BF) in adults. We applied them to healthy children and compared them with conventional anthropometry methods. One thousand two hundred and sixteen children participated in this study. Impedance and skinfold thickness were measured, and %BF was estimated using these values. Bodyweight and height were measured, and per cent obesity (%OB) and body mass index (BMI) were obtained. The values of %BF by the bioelectrical impedance method (%BFi) were 8.6 +/- 4.0% in the junior male group, 14.2 +/- 2.8% in the junior female group, 7.9 +/- 4.7% in the senior male group and 16.1 +/- 2.9% in the senior female group. The %BFi correlated strongly with skinfold thickness, %OB and BMI. Thus %BFi correlated strongly with variables from conventional methods. It was concluded that it is a reliable way of assessing lipid storage in children.

Adolescent↗
PubMed1993

Enhancing effect of protein A on the interaction between opsonized corneocytes and neutrophils in staphylococcal infection.

Formation of subcorneal pustules characterizes skin lesions infected by Staphylococcus aureus. To elucidate the mechanism underlying the subcorneal pustule formation as well as that of anti-bacterial host defence, we studied the effect of staphylococcal protein A on the interaction between the stratum corneum (SC) and neutrophils. We found that protein A significantly promoted opsonized SC-induced chemiluminescence (CL) in neutrophils. This was specific to SC because no enhancement was observed with opsonized zymosan. It took place even with the serum obtained from a patient with agammaglobulinemia, ruling out the possibility of the involvement of Fc-receptors of neutrophils in this phenomenon. Microscopic observation of such SC revealed an increase in the number of neutrophils adhering to the surface of the protein A-coated corneocytes. Ultrastructural observation showed a distinct deformation of the neutrophils adhering to the surface of the corneocytes, suggesting that they are in an activated state. Such an enhanced interaction between protein A-attached SC and neutrophils seems to play an important role in the host defence mechanism against the invading S. aureus and in the production of the characteristic pustules by the neutrophil-mediated damage of the surrounding epidermal tissue.

Cell Communication↗
PubMed1993

[Studies on hemolytic streptococcal infection: 1). Outbreak of group C hemolytic streptococcal infection in Formosan squirrels].

Between mid-October to mid-November 1992, of 500 freely-ranging Formosan and striped squirrels kept at Garden Y in the suburbs of Kanagawa Prefecture, 414 (82.8%) suddenly died one after another by bleeding from the nasal and oral cavities after developing a mild facial swelling. Isolation of microbes including viruses were carried out from the Formosan squirrels that had suddenly died. Various organs from these animals were histologically examined. 1. In bacteriological tests, beta-hemolytic streptococcal strains were isolated in a pure culture from 5 (83.3%) of 6 Formosan squirrels that had died suddenly. By serological analysis, 14 isolated strains were serotyped as group C according to the classification of Lancefield. From their biochemical characteristics, these were identified as Streptococcus equi subsp. zooepidemicus. A drug sensitivity test revealed that ABPC, PCG, SBPC, CMX and CPZ are highly sensitive against the isolates. 2. In the virological test, the viral isolation was applied for three blind passages by primary cultured kidney cells of Formosan squirrels, but no evidence of CPE was obtained. 3. At autopsy, a pathological change was detected mainly in the lungs. Histopathological examinations revealed severe hypertrophic changes of the alveolar wall in the entire pulmonary lobe. Severe congestion, hemorrhagic pneumonia, neutrophils and macrophages infiltration were observed in the hypertrophic alveolar wall. In the other cases, thrombi were observed in the branches of the pulmonary artery. Other organs demonstrated no remarkable histopathological changes. 4. Streptococcal strains were not isolated from the pharynx in all of the employees working at this garden.

Animals↗
PubMed1993

Experimental immunoglobulin A nephropathy induced by gram-negative bacteria.

A study was conducted to determine whether intraperitoneal and oral administration of formalin-fixed gram-negative bacteria induced immunohistologically and ultrastructurally evident glomerular deposition of IgA and C3 in C3H/HeN mice. Separate treatments with strains of Pseudomonas aeruginosa, Escherichia coli, Haemophilus influenzae, Klebsiella pneumoniae, and two kinds of lipopolysaccharide (LPS) were used. Two mice in each treatment group were sacrificed at 10, 20 and 30 weeks of age to examine sequential glomerular changes. In addition to the intraperitoneal administration (IP) groups receiving whole formalin-fixed bacterial cells, cell precipitate and supernatant fractions of each bacterial strain after sonication were injected intraperitoneally once a week, and the mice were sacrificed at 30 weeks of age. Sequential quantitation or IgG, IgA or IgM in serum and the isotypes specific for each of the bacterial strains or LPS administered was performed by ELISA. The incidence of immunofluorescence positivity for glomerular IgA and C3 was 37-71 and 37-66.7%, respectively, in the IP groups that had received bacterial cells of each strain, which was significantly higher than that in the IP groups given LPS or in the controls. These results suggest that cell wall components common among gram-negative bacteria, other than LPS, play a major role in the glomerular deposition of IgA and C3. This is the first use of gram-negative bacteria to establish an active model of IgA nephropathy.

Administration, Oral↗
PubMed1993

Morphology of the membrana limitans.

The morphology of the membrana limitans (ML) was studied by light and electron microscopy to further understand its functional significance. The ML is a porous shield composed of a few to several layers of tightly packed fibrocytes that separate the perilymphatic space of the cochlea and saccule from that of the utricle and canal system. These fibrocytes are thinner on the side of the vestibule. They show many desmosomes and gap junctions and are interspersed with fibrils. The 3-dimensional reconstruction from celloidin sections shows that the ML, as it is viewed from the anterior side, is rectangular in shape, with various surface curvatures and an invagination toward the internal aperture of the vestibular aqueduct. Horseradish peroxidase, a tracer substance, placed on either side of the ML fails to pass to the opposite side. The ML and trabecular meshwork may be a factor contributing to differential sensitivity of cochlear and vestibular sensory cells in the presence of noxious substances.

Animals↗