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Biomedical subjects

T Morishima

Publications and source records attributed to T Morishima.

At least 73 records · Page 4Linked to original sources

Augmentation of hepatic glucose uptake by a positive glucose gradient between hepatoportal and central nervous systems.

To determine the role of the glucose gradient between the hepatoportal system (HPS) and the central nervous system (CNS) in regulating hepatic glucose uptake, experiments were conducted with seven conscious dogs using a hepatic venous catheterization technique. With the infusion of somatostatin (0.8 microg x kg(-1) x min(-1)), glucagon (0.65 ng x kg(-1) x min(-1)), and insulin (27 pmol x kg(-1) x min(-1)), arterial glucose levels could be maintained at 8 mmol/l by adjusting the intravenous glucose infusion (G(inf)) according to the following three periods: 1) peripheral glucose infusion period (PE), G(inf) alone; 2) portal glucose infusion period (PO), G(inf) plus constant glucose infusion into the portal vein (GIR(PV), 55.6 micromol x kg(-1) x min(-1)); 3) portal and brain glucose infusion period (PO+CNS), G(inf) and GIR(PV) plus additional glucose infusion into the unilateral carotid and vertebral arteries to abolish the positive glucose gradient between HPS and CNS. Arterial plasma glucose levels were clamped during the three periods (8.1 +/- 0.1, PE; 8.2 +/- 0.1, PO; 8.2 +/- 0.1 mmol/l, PO+CNS). During PO, when a positive glucose gradient was promoted between HPS and CNS, the net hepatic glucose balance (NHGB) determined by the difference between hepatic glucose inflow and outflow was significantly lower than that of PE (-41.5 +/- 5.3, PO vs. -7.5 +/- 3.4 micromol x kg(-1) x min(-1), PE; P < 0.01). However, this decrease in the NHGB significantly increased during PO+CNS, when the glucose gradient between HPS and CNS was minimized, compared with PO (-21.7 +/- 3.2 micromol x kg(-1) x min(-1), P < 0.05). We conclude that a positive glucose gradient between HPS and CNS is an important regulatory factor of hepatic glucose uptake, but other factors also play important roles because minimizing the glucose gradient between HPS and CNS diminished the net hepatic glucose uptake by 50%.

Animals↗

Symptomatic porphyria secondary to hepatocellular carcinoma.

A 58-year-old woman gave a 6-month history of porphyria-like photosensitivity. Fractioned porphyrin analysis by high performance liquid chromatography revealed elevated concentrations of all urinary porphyrins and faecal protoporphyrin. Hepatocellular carcinoma had developed in an otherwise normal liver. Tumour tissue fluoresced strongly under fluorescence microscopy, exhibiting elevated activity of three haem-biosynthetic enzymes, delta-aminolevulinic acid (ALA) synthase. ALA dehydratase and porphobilinogen deaminase. This patient did not satisfy any of the criteria for inherited porphyria. The patient's symptoms were relieved after excision of the liver tumour. This strongly suggests that excessive porphyrin synthesis originated from the tumour tissue. Primary porphyria-like photosensitivity occurs as a paraneoplastic phenomenon, secondary to hepatocellular carcinoma.

Carcinoma, Hepatocellular↗

[Adoptive immune therapy using EBV-specific CTL].

The Epstein-Barr virus (EBV) has been implicated in the etiology of many lymphoid and other malignancies. Understanding of the immune control of the virus appears to be very important to establish strategy to overcome those disease. Recent advance of T cell biology and the culture technic have made it possible to apply adoptive immune transfer of EBV-specific cytotoxic T lymphocytes (CTL) in clinical settings. This review summarizes immunotherapy using EBV-specific CTL for the treatment of EBV-associated lymphoproliferative disorders in patients receiving bone marrow transplantation and for a patient with severe chronic active EBV infection. Its future application is discussed.

Herpesviridae Infections↗

Analysis of mother-to-infant transmission of hepatitis C virus: quasispecies nature and buoyant densities of maternal virus populations.

Mother-to-infant transmission of hepatitis C virus (HCV) was analyzed by sequencing of viral RNA and semiquantitative polymerase chain reaction following ultracentrifugation of maternal sera. In two mother-infant pairs, the hypervariable region 1 (HVR1) and carboxyl terminus of envelope 1 (E1) were sequenced. Both viral sequences in the infants were less diverse than those of their mothers. Although the E1 sequences were almost identical in each mother-infant pair, the HVR1 sequences of the infants were related, but not identical, to those of the mothers. Serial examinations of one infant revealed that the HVR1 nucleotide sequence did not change from 10 days to 3 months of age. In six mothers with uninfected infants, all of the dense fractions of sera contained significant amounts of HCV RNA, whereas in six mothers with infected infants, only two of those fractions contained significant amounts of HCV RNA. These results indicate that the strains of HCV detected in the infants were not dominant in the mothers, but were still transmissible to the infants. As dense fractions are known to contain antibody-bound HCV particles, maternal antibodies against HCV may inhibit viral transmission.

Amino Acid Sequence↗

[A case of infiltration of scar of sarcoidosis after blepharoplasty].

A case of a 28-year-old woman with infiltration of sarcoidosis scar tissue after blepharoplasty is reported. Nodules developed two times in her right upper eyelid about 1 and 2 years after blepharoplasty of both eyes and they were resected each time, but eruption recurred. Ophthalmic examination revealed aqueous flare and cells, snowball vitreous opacities, and retinal periphlebitis. A chest X-ray disclosed bilateral hilar lymphadenopathy (BHL). Laboratory studies showed an elevation of the serum angiotensin converting enzyme (ACE). Light microscopy revealed epithelioid granuloma with no caseation necrosis in a biopsy specimen, Viewing through polarized light demonstrated crystalline-like foreign bodies with bi-refringence in the epithelioid granuloma. Electron microscopic X-ray microanalysis confirmed these foreign bodies to be composed of Si, Mg, and O. These findings indicate that this skin lesion was caused by an infiltration of sarcoidosis scar tissue.

Adult↗

Epidemiology of bacterial meningitis in children: Aichi Prefecture, Japan, 1984-1993.

The details of 328 patients with bacterial meningitis, admitted from 1984 through 1993, were obtained from 46 departments of pediatrics of large hospitals through questionnaires. The incidence rate per 100,000 child-years was 2.32, being higher in children aged 0-4 years (rate, 7.22) than 5-15 years (rate, 0.49). The disease in the 274 (84%) etiologically diagnosed patients was due to Haemophilus influenzae (95), Streptococcus pneumoniae (56), Group B streptococci (GBS) (41), Escherichia coli (27), and other agents (55), including 7 patients with Mycobacterium tuberculosis infection. The short-term outcome (mean length of follow-up, 2 years, 11 months) of meningitis was death in 26 patients (8.2%) and sequelae in 49 (16.0%), including 26 children with multiple residual impairment. Tuberculous, pneumococcal, and GBS meningitis with a poor outcome increased during the late period (1989-1993) of the 10-year study. The annual infant mortality rate for purulent meningitis decreased from 3.7 to 1.4 per 100,000 population between 1984 and 1993. The incidence of a poor outcome (death and sequelae) in newborns decreased by half during the late period.

Adolescent↗

Portal insulin delivery is superior to peripheral delivery in handling of portally delivered glucose.

It is still controversial as to whether physiological portal insulin delivery has metabolic advantages over peripheral insulin delivery. To clarify this issue, glycemic regulation during intravenous (IVGTT) and oral (OGTT) glucose tolerance tests and hyperglycemic clamp studies with either peripheral or portal glucose infusion was investigated in left-segmentally pancreatectomized dogs with portal ([PPx] n = 7) or systemic ([Tx] n = 7) venous drainage of the remaining pancreas. In Tx dogs, systemic diversion of pancreatic venous effluent was accomplished by gastroduodenal-caval shunt. Data obtained were compared with those in normal control dogs ([NC] n = 7). The loss of pancreatic beta-cell mass in PPx dogs decreased insulin responses to peripheral and portal glucose loads. In contrast, Tx dogs showed insulin responses comparable to those of NC dogs to glucose loads via both routes. Against peripheral glucose loads (IVGTT and hyperglycemic clamp with peripheral glucose infusion), PPx and Tx dogs showed deteriorated glucose handling. Against portal glucose loads (OGTT and hyperglycemic clamp with portal glucose infusion), deteriorated glucose handling was observed in Tx dogs, but not in PPx dogs. Deterioration in glycemic regulation against portal glucose loads in left-segmentally pancreatectomized dogs with peripheral insulin delivery but not in pancreatectomized dogs with portal delivery indicates that intraportal hyperglycemia and hyperinsulinemia are essential for promoting hepatic glucose handling.

Animals↗

CD4 expression is important but not essential for infection with exogenous mouse mammary tumor virus.

We studied local events in the popliteal lymph nodes of CD4-deficient mice following foot pad injection with an MMTV strain which carries the gene for a V beta 14-specific superantigen. Injection of the V beta 14-specific MMTV induced vigorous expansion of V beta 14+ CD4+ T cells and B cells in their lymph nodes of CD4+/- heterozygous control mice. On the other hand, CD4-/- mice injected with the MMTV showed a proliferation of V beta 14+ T cells among the population of TCR alpha beta + CD4-CD8- T cells, although to a lesser extent. This phenomenon was not accompanied by vigorous B cell expansion. A PCR assay revelated that the MMTV definitely infected the lymph nodes cells of the CD4-/- mouse. However, the infectivity of the MMTV in CD4-/- mice was approximately 20 times lower than that in CD4+/- mice. These findings indicate that, in MMTV infection of CD4-deficient mice, the superantigen-reactive T cells among the population of TCR alpha beta +CD4-CD8- T cells substitute for the superantigen-reactive CD4- T cells of normal mice, and that the absence of CD4 molecules decreased the infectivity of MMTV because of insufficient expansion of the superantigen-reactive T cells.

Animals↗

Probable BCG osteomyelitis of the hard palate: a case report.

A 4-year-old child with probable multifocal BCG osteomyelitis is reported. The lesions in the skull, clavicula, humerus, ribs, fibula, calcaneus, metatarsus, and hard palate were mainly osteolytic and healed rapidly with antituberculotic therapy. This is the first time that involvement of the hard palate has been described.

Antibiotics, Antitubercular↗

Establishment of anti-Epstein-Barr virus (EBV) cellular immunity by adoptive transfer of virus-specific cytotoxic T lymphocytes from an HLA-matched sibling to a patient with severe chronic active EBV infection.

We describe an experience of a specific immune transfer treatment in a patient with chronic active EBV infection. The patient had low anti-EBV T cell-mediated cytotoxic activity in his peripheral blood mononuclear cells (PBMC), which may have been the primary cause of the disease. An EBV-specific cytotoxic T lymphocyte (CTL) line was established from PBMC obtained from the patient's sister whose human leucocyte antigens (HLA) are identical to patient's. The patient received three courses of intravenously administered CTL at 3-week intervals. The number of the cells was increased with each course of treatment. After infusion of the T cell line, anti-EBV CTL activity was detected in the patient's PBMC. CTL activity increased markedly after the second course of immune transfer therapy. The amount of EBV DNA in the patient's plasma showed transient but repeated decreases. Serum levels of tumour necrosis factor-alpha (TNF-alpha), which had elevated before treatment, began to decrease after initiation of treatment. No adverse effects were directly associated with CTL infusions. Despite having previously received a pneumococcal vaccine and prophylactic antibiotics, the patient died of infection caused by Streptococcus pneumoniae bacteraemia 27 days after the third infusion. Although the long-term efficacy and safety of this therapy remains to be established, our findings suggest that adoptive transfer of CTL specific for EBV obtained from an HLA-matched donor might be a promising treatment for patients with chronic active EBV infection.

Child↗

Immunohistochemical studies on the transneuronal spread of virulent herpes simplex virus type 2 and its US3 protein kinase-deficient mutant after ocular inoculation.

The transneuronal spread of a virulent wild-type herpes simplex virus type 2 (HSV-2) and its US3 protein kinase-deficient (US3 PK-) mutant was immunohistochemically studied in mice after inoculations into the cornea, anterior chamber, tongue, and masseter muscle. After corneal inoculation, the wild-type virus was demonstrated in various brain stem areas including the trigeminal tract and nucleus, the reticular formation, and cerebellar nucleus group. Viral antigen-positive neurons were strictly confined to the ipsilateral spinal trigeminal nucleus in mice corneally infected with the US3 PK- mutant. No viral antigens were detected in the central nervous system (CNS) after inoculation with the mutant into the tongue and masseter muscle. However, when mice were immunosuppressed by treatment with cyclophosphamide, both the corneally infected mutant and wild-type virus could invade the CNS. The results suggest that the US3 PK- mutant principally retains the capacity to spread in the CNS.

Animals↗

Long-term administration of natural interferon-alpha in patients with chronic hepatitis C: relationship to serum RNA concentration, HCV-RNA genotypes, histological changes and hepatitis C virus.

To virologically assess the efficacy of interferon therapy in chronic hepatitis C, either 5 or 10 MU/day natural interferon-alpha (IFN alpha) was administered to 57 patients with chronic hepatitis C for 38 weeks. A complete and sustained response (CR-SR), as evidenced by the absence of serum hepatitis C virus (HCV)-RNA during the administration period and at 6 months after the final administration of IFN alpha and normal GPT level at 6 months after final administration, occurred in 42.6% (23/54) of subjects. Liver tissue was histologically evaluated using the histological activity index (HAI) score before and after the administration period. In CR-SR cases, significant improvements (P < 0.01) occurred in periportal necrosis, intralobular necrosis, portal inflammation and total score. A comparison, by HCV genotypes, revealed that CR-SR occurred in 60% (9/15) of subjects with type 2a and 30.3% (10/33) of subjects with type 1b. A comparison by virus concentration revealed that CR-SR occurred in 71.4% (15/21) of those subjects having a virus concentration of < 10(5) copies/mL, but in only 24.2% (8/33) of those having a virus concentration of > 10(5) copies/mL. Analysis by a multiple logistic model revealed a strong correlation between the therapeutic effect of interferon therapy and the pre-administration virus concentration (P = 0.0061) and genotype (P = 0.0015). These results suggest that the pre-administration virus concentration and genotype are both key factors affecting the therapeutic effect of interferon therapy in chronic hepatitis C and that the therapeutic effect of interferon is satisfactorily high, irrespective of virus concentration, in subjects with type 2a HCV, but varies depending on virus concentration in subjects with type 1b.

Aged↗

Modification of cultured Madin-Darby canine kidney cells with dietary unsaturated fatty acids and regulation of arachidonate cascade reaction.

Madin-Darby canine kidney (MDCK) cells were modified with dietary unsaturated fatty acids. The effects on the fatty acid composition in each phospholipid class and the formation of prostanoids upon stimulation were studied, from which the specificity of metabolism of individual unsaturated fatty acids and the regulation of arachidonate cascades in the modified cells were discussed. C18 unsaturated fatty acids were preferentially incorporated into phosphatidylcholine (PC) over phosphatidylethanolamine (PE), but arachidonic acid (20:4(n-6)) derived from gamma-linolenic acid (18:3(n-6)) was much more predominant in PE than PC. The fatty acid level in PE ranged from about 26-28% when the cells were modified with 20:4(n-6) or 5,8,11,14,17-eicosapentaenoic acid (20:5(n-3)), indicating the limitation of the storage of the eicosapolyenoic acids. The extra amounts appeared to be stored in PC. 18:3(n-6) was comparable to 20:4(n-6) to raise the level of 20:4(n-6) in PE, but not in PC which had half of 20:4(n-6) in PE. The supplementation of linoleic acid (18:2(n-6)). 18:3(n-6), and 20:4(n-6) caused significant increases in the synthesis of prostaglandin (PG)E2 up to almost the same levels when the modified cells were stimulated with 50 nM PMA and 100 nM A23187 for 24h. The cultured cells modified with eicosapolyenoic acids including 20:3(n-6), 20:4(n-6), and 20:5(n-3) were found to be inhibitory for the induction of PGE2 synthetic activity involving de nova synthesis of PG endoperoxide synthase, suggesting negative feedback regulation of the modified cells.

Animals↗

Morphogenesis of degenerative changes predisposing dogs to rupture of the cranial cruciate ligament.

The cranial cruciate ligaments (CCL) of 13 dogs with clinical signs of CCL rupture and those of 22 clinically healthy young beagle dogs for laboratory use were examined histopathologically and immunohistopathologically. The most constant changes at an early stage of degenerating ligament tissue in affected dogs were nuclear enlargement and perinuclear halo formation of fibrocytes followed by chondroid metaplasia. These changes were also frequent in apparently healthy young beagles kept under laboratory conditions. PAS and alcian blue positive substance accumulated around activated fibrocytes and within perinuclear halos. S-100 protein was also positive in these cells preceding the morphological change of chondroid metaplasia. Increased mitotic figures and Ki-67 positive cells showed the proliferating nature of these cells at a later stage. Alteration of extracellular matrices from dense collagen fiber type to those of cartilage tissue seemed to predispose dogs to rupture of the CCL along with a degradation in collagen fiber of the primary bundles. Collagen fiber bundles with a parallel fibrillar array never formed in the CCL with degraded primary bundles, whereas activated fibrocytes constantly underwent chondroid metaplasia. The pathogenic mechanism underlying chondroid metaplasia was thought to be nonspecific and attributable to an essential property of activated fibrocytes in the mature tendon tissue.

Animals↗

[Mal de Meleda].

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Heart Diseases↗

Concomitant infection with exogenous mouse mammary tumor virus encoding I-E-dependent superantigen in I-E-negative mouse strain.

We found that milk from II TES mice contained two species of exogenous mouse mammary tumor viruses (MMTV). Sequence analysis of the open reading frame (ORF) in the MMTV 3' long terminal repeat indicated that the two MMTV, MMTV (II TES2) and MMTV (II TES14), encode superantigens specific for V beta 2+ T cells and V beta 14+ T cells, respectively. In an experiment of subcutaneous injection of II TES milk, both T cells bearing TCR V beta 2 and V beta 14 proliferated vigorously in the draining lymph node from BALB/c mice (H-2d I-E+), whereas only V beta 14+ T cells showed significant proliferation in C57BL/6 mouse (B6 H-2b I-E-) lymph nodes. These findings indicated that the superantigen encoded by MMTV (II TES2) required MHC class II I-E molecules exclusively for Ag presentation, but MMTV (II TES14) stimulated V beta 14+ T cells even in the absence of I-E molecules. Semiquantitative analysis of MMTV proviruses using PCR revealed that B6 mice were not infected with MMTV (II TES2) by injection of this MMTV alone. However, injection of II TES milk containing both MMTV (II TES14) and MMTV (II TES2) induced infection of B6 mice with MMTV (II TES2) besides MMTV (II TES14), in spite of no expansion of V beta 2+ T cells in this mouse strain. These results suggested that I-E-negative mice were concomitantly infected with MMTV (II TES2) with the help of I-E independent T cell activation mediated by MMTV (II TES14).

Amino Acid Sequence↗