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Biomedical subjects

T Morishima

Publications and source records attributed to T Morishima.

At least 91 records · Page 5Linked to original sources
PubMed1995

Ubiquitous, but variable, expression of two alternatively spliced mRNAs encoding mouse homologues of transcription factors E47 and E12.

Two basic helix-loop-helix (bHLH) transcription factors, E47 and E12, are involved in cell-specific gene expression as part of dimeric complexes which interact with the cis-acting motif E-box. Although both generated from a single gene (E2A) by means of alternative splicing, the structural difference in these bHLH regions between the two suggests that the two bHLH proteins may differ in some of their functions. As a step toward elucidating the individual implications of E47 and E12, we investigated the mRNA expression ratios of their homologues (A1 and kA1, respectively) in mouse tissues and cell lines. Both the A1 and kA1 mRNAs were ubiquitously expressed in all tissues examined. However, their ratios varied: e.g., skeletal muscle, 2.2 +/- 0.3 (mean +/- SE); spleen, 2.0 +/- 0.2; pancreatic islet cells, 1.2 +/- 0.2. The A1/kA1 ratios in the cell lines investigated were similar to those of their original tissues. In conclusion, the ubiquity in mRNA expression observed for both the E47 and E12 homologues in mouse provides support for their involvement in a broad range of transcriptional regulation. The variation in the A1/kA1 expression ratios, on the other hand, supports the idea that A1 (E47) and kA1 (E12) each have some unique roles in the functions of these E2A gene-encoded bHLH proteins.

Alternative Splicing↗
PubMed1995

Intact antigen presentation for Epstein-Barr virus (EBV)-specific CTL by a lymphoblastoid cell line established from a patient with severe chronic active EBV infection.

Severe chronic active Epstein-Barr virus (EBV) infection is a lymphoproliferative disease characterized by extremely high antibody titers to EBV, fever, lymphadenopathy, hepatosplenomegaly, and pancytopenia, without any prior immunological abnormality. A spontaneous lymphoblastoid cell line was established from a 4-year-old boy with severe chronic active EBV infection. Immunofluorescence and Western blotting analyses showed that the cell line was of B cell origin and expressed Epstein-Barr nuclear antigens 1, 2 3a, 3b and 3c, and latent membrane protein 1, which are reported to be targets for EBV-specific cytotoxic T lymphocytes (CTL). The cytotoxicity of peripheral blood mononuclear cells derived from the patient and his HLA-identical sister was assayed against the cell line. The cell line was recognized and killed by anti-EBV CTL derived from the HLA-identical sister, but the patient's peripheral blood mononuclear cells had no cytotoxicity. We conclude that antigen presentation in the EBV-infected cells from the patient is intact and sufficient for generation of an EBV-specific CTL response. These observations suggest that severe chronic active EBV infection may not be caused by impaired EBV-antigen presentation of the infected cells but by impaired cellular immune responses to the virus. Our results also suggest the therapeutic possibility that this disease may be treated by adoptive transfer of EBV-specific CTL or bone marrow transplantation from an HLA-matched donor whose immune response to EBV is intact.

Animals↗
PubMed1995

Influence of oral sulfonylurea agents on hepatic glucose uptake.

Although the metabolic derangement in the subjects with well-established NIDDM is characterized by both insulin resistance and diminished insulin secretion, the impaired sensitivity to insulin in the target tissues is assumed to represent the primary defect in most NIDDM individuals. Therefore, the therapeutic modality that can augment insulin-mediated glucose metabolism in the target tissues seems rational in the treatment of NIDDM. Glimepiride (HOE490), a newly developed sulfonylurea, has been reported to have a more potent hypoglycemic action than glibenclamide while its ability to stimulate insulin secretion is much weaker. Thus, part of the potent hypoglycemic action of HOE490 has been speculated as being due to an extrapancreatic effect. First we examined the effect of strict glycemic control on insulin resistance seen in NIDDM using euglycemic hyperinsulinemic clamp combined with oral glucose loading (Clamp-OGL) to 9 subjects with NIDDM. After 3 to 4 weeks of intensified insulin therapy, insulin-mediated glucose uptake by the liver significantly increased while peripheral glucose disposal did not change. Secondly we applied Clamp-OGL to 5 subjects with IDDM to study the acute metabolic effect of HOE490 on glucose handlings by the target tissues. Intravenous administration of HOE490 at a rate of 6.0 micrograms/min did not affect hepatic glucose uptake in these subjects. Thus we studied subacute metabolic effect of HOE490 on glucose handlings by the target tissues in 7 normal dogs using euglycemic clamp combined with hepatic venous catheterization technique.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1995

Growth and cytopathogenicity of herpes simplex virus in a macrophage cell line, RAW264: A good indicator of intraperitoneal pathogenicity.

Macrophages are known to play a critical role in host resistance to herpes simplex virus (HSV). In this study, we investigate the interaction between various HSV strains with different virulence and a murine macrophage cell line, RAW264. Highly attenuated strains replicated poorly in RAW264 cells and were cleared from the cultures. For the eleven viruses tested, there was good correlation between intraperitoneal pathogenicity for adult mice and replication in RAW264 cells. It was also shown that interferon alpha/beta was involved in restricted replication of some strains.

Animals↗
PubMed1995

A female infant successfully treated by ganciclovir for congenital cytomegalovirus infection.

An 11 month old female infant, diagnosed as having congenital cytomegalovirus (CMV) infection and suffering from pneumonia and intractable diarrhea, was treated with 9-(1,3-dihydroxy-2-propoxymethyl) guanine (DHPG), intravenously for 8 weeks. Watery diarrhea ceased and pneumonia associated with massive endotracheal aspirates was reduced. No leukopenia, thrombocytopenia or other side effects were observed during the therapy. The clinical findings suggest that DHPG might be an effective and safe agent for the treatment of both intestinal and lower respiratory CMV infection in young infants.

Cytomegalovirus Infections↗
PubMed1995

Chronic active Epstein-Barr virus infection in children in Japan.

The patients with chronic active Epstein-Barr virus infection (CAEBV) in childhood in Japan are described. Among 39 registered cases, 20 patients were males and 19 were females. Unlike the X-linked lymphoproliferative syndrome, there was no hereditary background. The incidence of hypersensitivity to mosquito bites was high (31.3%) as a past history. Most patients exhibited hepatomegaly (92.3%), splenomegaly (87.2%) and fever (84.6%). The incidence of absent anti-EB virus nuclear antigen titres was unexpectedly low (17.1%). Lymphoreticular disorders and cardiovascular diseases were major complications. Twenty-four (61.5%) patients died 6 months to 8 years after the onset, mainly of hepatic failure (eight cases), cardiac failure (five cases), virus-associated haemophagocytic syndrome (three cases) and haematological malignancies (two cases). This study reveals the CAEBV in Japan has several clinical features and should be informative for the pathogenesis of EB virus.

Antibodies, Viral↗
PubMed1995

Low humoral responses to hepatitis C virus among pediatric renal transplant recipients.

Immunosuppressed patients infected with hepatitis C virus (HCV) are known to have a low prevalence of antibodies to the virus. We examined 12 HCV-infected renal transplant recipients and 18 immunocompetent patients in terms of viral markers. The renal patients had a lower prevalence of anti-C100-3 antibodies and lower titers of anti-p22 than the immunocompetents. Low titers of the antibodies seemed to be characteristic of HCV, because titers of anti-mumps and anti-cytomegalovirus antibodies were the same or even increased. Quantitation of HCV RNA showed approximately 200-fold more copies of mean HCV RNA in the sera of the kidney patients than in the immunocompetents. This indicates that the low humoral responsiveness to HCV is not due to the lower concentration of the virus. Immunosuppressive conditions seemed to suppress anti-HCV production with greater magnitude than other viral antibodies.

Adolescent↗
PubMed1995

Detection and quantification of virus DNA in plasma of patients with Epstein-Barr virus-associated diseases.

Epstein-Barr virus (EBV) causes various diseases, such as infectious mononucleosis (IM), fatal IM, EBV-associated hemophagocytic syndrome (EBVAHS), and chronic active EBV infection (CAEBV). In the present study, cell-free EBV DNA was detected in the plasma of patients with EBV-associated diseases by PCR assay. The patients included 20 patients with IM, 2 patients with fatal IM, 4 patients with EBVAHS, 4 patients with CAEBV, and 38 healthy children (20 EBV seropositive and 18 EBV seronegative). In patients with IM, plasma samples were positive for EBV DNA in all patients (100%) in the acute phase and in 44% of the patients in the convalescent phase, but plasma samples from the 38 healthy control children were negative (0%) for EBV DNA. Quantitative PCR assay revealed that plasma from patients with IM contained the highest amount of virus DNA within 7 days following the onset of disease (mean, 6 x 10(4) copies per ml). The EBV DNA concentration decreased thereafter as the patients recovered. Plasma from patients with fatal IM contained more than 100 times more copies of EBV DNA (3 x 10(7) copies per ml) than plasma from patients with IM. Plasma from patients with the acute phase of EBVAHS contained 10 times more copies of EBV DNA (5 x 10(5) copies per ml) than plasma from IM, and then patients with the number of copies decreased similarly in both groups of patients in the convalescent phase (2 x 10(4) copies per ml). The amount of virus DNA in patients with CAEBV (6 x 10(4) copies per ml) was similar to that noted in patients with IM; however, it became higher (1 x 10(6) copies per ml) when the patients' clinical status deteriorated. These data suggest that the presence of cell-free EBV DNA in plasma is a common phenomenon in patients with EBV-associated diseases. The concentration of EBV DNA in plasma seems to be higher in patients with the more severe clinical categories of EBV diseases.

Acute Disease↗
PubMed1995

A case of non-insulin dependent diabetes mellitus with antiinsulin antibody: effect of subcutaneous injection of human recombinant insulin-like growth factor-I.

We saw a 57-yr-old female non-insulin dependent diabetes mellitus (NIDDM) patient with antiinsulin antibody, in whom insulin-like growth factor-I (IGF-I) was shown to be effective as a blood glucose-lowering agent. Due to the presence of the antibody, the patient suffered from postprandial hyperglycemia and frequent hypoglycemia, which were uncontrollable even by multiple insulin injection therapy. In contrast to insulin injection (0.24 IU/kg body wt) which showed a delayed glucose-lowering effect, subcutaneous injection of recombinant human IGF-I (0.05-0.1 mg/kg body wt) caused a quick fall in plasma glucose levels. Prolongation of the glucose-lowering effect of "rapid-acting" insulin frequently caused subsequent hypoglycemia in this patient, but the effect of IGF-I seemed to have disappeared within the first three hours.

Diabetes Mellitus, Type 2↗
PubMed1995

Recurrent Cushing's disease associated with nephrotic syndrome.

A case of recurrent Cushing's disease with nephrotic syndrome due to membranoproliferative glomerulonephritis (MPGN) is presented. Functional pituitary adenoma recurred 6 years after transsphenoidal pituitary adenomectomy. Due to infiltration into the surrounding tissues, transcranial surgery was performed. However, this failed to induce a remission and thus gamma knife therapy was applied. Histopathological evaluation revealed that the glomerular lesions had progressed to a rather advanced stage of MPGN. Although this association could be coincidental, the recurrence of pituitary macroadenoma might be induced by the cessation of steroid treatment for the nephrotic syndrome.

Adult↗
PubMed1995

1,5-Anhydro-D-glucitol evaluates daily glycemic excursions in well-controlled NIDDM.

OBJECTIVE: To evaluate the usefulness of plasma 1,5-anhydro-D-glucitol (1,5-AG) as a possible marker for daily glycemic excursion, we measured plasma 1,5-AG, HbA1c, fasting plasma glucose (FPG) level, and daily excursion of glycemia, from which the M-value (after Schlichtkrull) was calculated as an index of daily glycemic excursion. RESEARCH DESIGN AND METHODS: The subjects were 76 patients with well-controlled non-insulin-dependent diabetes mellitus (NIDDM) treated with diet therapy only (diet, n = 17), oral hypoglycemic agents (OHA, n = 28), conventional insulin therapy (CIT, n = 16), or multiple insulin injection therapy (MIT, n = 15). RESULTS: HbA1c values were similar among all the groups (diet, 6.9 +/- 0.6; OHA, 7.2 +/- 0.5; CIT, 7.1 +/- 0.6; MIT, 7.2 +/- 0.5%). The MIT group showed a significantly higher 1,5-AG concentration (11.5 +/- 5.3 micrograms/ml), a significantly lower M-value (9.2 +/- 5.2), and little risk of hypoglycemia ( < 4 mmol/l) and hyperglycemia ( > 10 mmol/l) (1.3 +/- 1.1 times/24 h) compared with the CIT group (6.9 +/- 3.3 micrograms/ml, 15.7 +/- 8.9, 2.2 +/- 1.6 times/24 h, respectively). Insulin doses (22.4 +/- 4.5 vs. 22.0 +/- 8.9 U/day), FPG (6.6 +/- 2.2 vs. 7.4 +/- 2.4 mmol/l), and HbA1c concentrations were not significantly different between the CIT and MIT groups. M-values significantly correlated with 1,5-AG concentrations (r = 0.414, P < 0.05), but not with HbA1c concentrations. CONCLUSIONS: The findings suggest that the plasma 1,5-AG concentration can be a useful index of the daily excursion of blood glucose, especially in patients with well-controlled NIDDM.

Biomarkers↗
PubMed1994

Estrogen regulation of the insulin-like growth factor I gene transcription involves an AP-1 enhancer.

As a step toward elucidating the physiological role of insulin-like growth factor-I (IGF-I) in mediating estrogen action, we sought to determine the molecular basis of the phenomenon. In HepG2 cells expressing exogenous estrogen receptors (ER), a reporter gene plasmid containing 600 base pairs of the chicken IGF-I promoter enhanced expression of luciferase 8.6-fold in response to 10(-6) M 17 beta-estradiol, indicating that the IGF-I promoter is a target of estrogen regulation. Although no conventional estrogen-responsive element was identified within the promoter fragment, the AP-1 motif located therein was shown to be essential; the estrogen-responsive enhancement of the Fos-Jun binding to the AP-1 motif, which takes place by means of post-translational modification, mediates the estrogen action. A direct or indirect interaction between the estrogen-ER complex and the Fos-Jun complex seems to facilitate the Fos-Jun binding to the target DNA. Although ER binding to the target DNA was not considered to be involved in the signaling pathway, the DNA binding domain-deficient ER did not mediate the phenomenon, providing support for the existence of a unique function of the DNA binding domain of ER in facilitating some protein-protein interaction. In conclusion, our present observations demonstrate that the chicken IGF-I gene promoter is controlled by estrogen through a unique pathway involving Fos, Jun, and the DNA binding domain of ER.

Animals↗
PubMed1994

Identification of amino-acid polymorphism within the leucine zipper motif of mouse transcription factor A1.

Mouse transcription factor A1 (A1) is a mouse homologue of human E47, a ubiquitously expressed DNA-binding protein which contains a basic region, helix-loop-helix (HLH) and leucine zipper (LZ) motifs [Walker et al., Nucleic Acids Res. 18 (1990) 1159-1166]. Analyses of the nucleotide (nt) sequences of A1 cDNAs isolated from various mouse strains revealed amino acid (aa) polymorphism in the highly conserved region within the LZ motif. Interestingly, the location and pattern of aa deletions are identical to those previously described for the aa polymorphism within the human counterpart, E47 (E12) [Kamps et al., Cell 60 (1990) 547-555].

Amino Acid Sequence↗
PubMed1994

Aberrant androgen action and increased size of tandem CAG repeat in androgen receptor gene in X-linked recessive bulbospinal neuronopathy.

Plasma levels of testosterone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) after 3 or 6 days of administration of the synthetic androgenic hormone fluoxymesterone (10 mg/day) were measured in 26 patients with X-linked recessive bulbospinal neuronopathy (X-BSNP) and 22 age-matched male controls. The testosterone, LH and FSH levels in the controls were markedly suppressed after administration, but in the patients with X-BSNP, they were suppressed significantly less. The level of suppression varied considerably with the patients, and those of plasma testosterone and FSH were significantly correlated with the number of CAG repeats in the androgen receptor gene. These findings suggest that the androgen action was aberrantly transduced in the target organs in the patients with X-BSNP and which is related to the elongated CAG repeat in the androgen receptor gene.

Adult↗
PubMed1994

Effect of strict metabolic control on glucose handling by the liver and peripheral tissues in non-insulin-dependent diabetes mellitus.

To examine the effect of strict glycemic control on the insulin resistance of non-insulin-dependent diabetes mellitus (NIDDM), we applied euglycemic hyperinsulinemic clamp combined with an oral glucose load (OGL) to nine non-obese subjects with NIDDM and quantitated insulin-mediated glucose uptake by the liver (HGU) and peripheral tissues (PGU) simultaneously before and after 3 to 4 weeks of intimate glycemic control by preprandial regular insulin injections 3 times a day. The glucose infusion rate (GIR) required to maintain euglycemia during the clamp before OGL was considered as PGU. After OGL, the fraction of ingested glucose that is not extracted by the liver enters the systemic circulation and reduces the GIR required for the clamp. HGU was calculated from the difference between the amount of OGL and the cumulative decrements in GIR after OGL and was expressed as the ratio to the amount of OGL (%). Three to 4 weeks after initiation of strict metabolic control, FPG and HbA1c levels significantly improved (9.1 +/- 0.5 vs. 6.4 +/- 0.4 mmol/l, and 11.2 +/- 0.8 vs. 8.3 +/- 0.3%, P < 0.05). HGU significantly increased to 33.1 +/- 9.5 from 14.5 +/- 4.8%, while PGU did not change (38.2 +/- 5.2 vs. 37.4 +/- 3.9 mumol/kg.min). These data suggest that short-term strict metabolic control ameliorates insulin resistance in NIDDM mainly at the hepatic level.

Adult↗
PubMed1994

[Clinical evaluation of aciclovir granules in the treatment of chickenpox in otherwise healthy children].

The efficacy and safety of aciclovir granules (containing 40% w/w aciclovir) were evaluated in the treatment of chickenpox in otherwise healthy children. Patients presenting with chickenpox received aciclovir granules at a dose of 20 mg/kg four times daily for five to seven days. Overall 51 children received treatment with aciclovir. A further 53 patients receiving conventional symptomatic therapy acted as a control. In the aciclovir group the overall efficacy rate was 92.2%. There were reductions in the numbers of lesions, fever, itching and the duration of symptoms. No adverse experiences were reported. Overall this formulation of aciclovir appears to be a safe and effective treatment for chickenpox in this patient population. However the need for anti-viral therapy in otherwise healthy children is still the subject of debate and it might be appropriate to identify sub-groups for whom such therapy is justified.

Acyclovir↗
PubMed1994

Atherosclerosis in carotid artery of young IDDM patients monitored by ultrasound high-resolution B-mode imaging.

Ultrasound high-resolution B-mode imaging was used to assess the carotid arteries in 105 patients with insulin-dependent diabetes mellitus (IDDM), 4-25 years of age, with duration of diabetes ranging from 0.5-17 years, 529 patients with non-insulin-dependent diabetes (NIDDM), 31-86 years of age, with duration of diabetes ranging from 0.5-49 years, and 104 nondiabetic healthy subjects, 7-76 years of age, to determine the intimal plus medial thickness (IMT) of the arterial wall. The IMT values for IDDM patients 10-19 years of age (0.525 +/- 0.123 mm, n = 68) or 20-25 years of age (0.696 +/- 0.124 mm, n = 14) were significantly greater than those in age-matched nondiabetic subjects (0.444 +/- 0.057 mm, n = 12, P = 0.01169; 0.538 +/- 0.098 mm, n = 34, P < 0.00006). NIDDM patients showed IMT values equivalent to those in normal adults > or = 20 years of age. Multiple regression analysis showed that IMT in IDDM patients was positively related to the duration of diabetes (P = 0.00061) as well as to age (P = 0.00046). No other possible risk factors, such as serum total cholesterol level, serum high-density lipoprotein (HDL)-cholesterol level, serum low-density lipoprotein-cholesterol level, serum triglycerides, serum lipoprotein(a) level, or systolic or diastolic blood pressure, have shown significant correlations with IMT in IDDM patients. However, non-HDL-cholesterol, smoking, and systolic hypertension were independently responsible for increases in IMT values of NIDDM patients as well as age and duration of diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗