Does increased superoxide dismutase activity really cause muscular dystrophy?
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Animals↗
Biomedical subjects
M Hirano
Publications and source records attributed to M Hirano.
Prospective study of interferon therapy for compensated cirrhotic patients with chronic hepatitis C by monitoring serum hepatitis C RNA.
Because interferon therapy exhibits low efficacy for cirrhotic patients infected with hepatitis C virus, this prospective study was conducted to determine effective interferon regimens tailored to treatment response by monitoring HCV RNA status. A total of 157 cirrhotic patients were enrolled to receive 9 million units (MU) of interferon three times a week. The HCV RNA values were drawn 8 weeks apart and the patients were randomized to a further 16 or 32 weeks of treatment after two sequential findings of negativity for HCV RNA. A total of 73 out of 157 patients (46%) proceeded to randomization to different durations of treatment, 37 short-course and 36 long-course (duration: 38 +/- 8 and 49 +/- 13 weeks; total amount of interferon: 940 +/- 240 and 1130 +/- 390 MU, respectively). The remaining 84 patients without two sequential negative serum HCV RNA determinations received 44.8 +/- 27.4 weeks of interferon (IFN) therapy with total amount of 993 +/- 633 MU. Of these 157 patients, sustained virological and biochemical response was shown in 32 (20%) and 37 patients (24%), respectively. Sustained virological and biochemical response rate in the randomized patients was significantly higher than in nonrandomized patients (41% vs. 2%, and 38% vs. 11%; each P <.01). Of the 73 randomized patients, the rate of sustained virological response in patients with long-course treatment (50%) was significantly higher than that of patients with short-course treatment (32%) (P =.026: log-rank test), and in patients with early disappearance of HCV RNA especially within 8 weeks, in patients with low virus load (</=10(6.3) copies/mL) and with HCV 2a. Multivariate analysis revealed that HCV RNA level and subtypes were the most important factors contributing to sustained virological response. Interferon is effective even in cirrhotic patients with low viral load and HCV 2a, but requires a longer course of administration.
Adult↗
Acute leukemia with the phenotype of a natural killer/T cell bipotential precursor.
An acute leukemia with an unusual immunophenotype developed in a 17-year-old girl. At the initial presentation, extramedullary involvement was not evident, but with advancing disease, massive splenomegaly and an osteolytic rib tumor developed. The disease was aggressive and refractory to intensive chemotherapeutic regimens for myeloid and lymphoid malignancies, and the patient died 3 months after the initial presentation. The leukemic cells were of irregular shape and variable size; they had deeply indented or bi-lobed nuclei and relatively fine, azurophilic granules in their cytoplasm. They were positive for acid phosphatase and beta-glucuronidase in granular staining, but they were negative for myeloperoxidase. The leukemic cells had a unique immunophenotype: it was positive for T-cell antigens (CD1a, CD2, cytoplasmic CD3, CD4), myeloid antigens (CD13 and CD33), NK-cell antigen (CD56), CD19 and CD30. DNA analysis revealed no gene rearrangement in the T-cell receptor beta, gamma and delta, or immunoglobulin heavy chain genes. The leukemic cells of our patient are thought to have arisen from the transformation of a putative precursor cell common to both the T- and NK-cell lineage in the bone marrow. The current literature on precursor NK-cell malignancy is reviewed, and its clinicopathological feature is discussed.
Acute Disease↗
Leber's hereditary optic neuropathy mitochondrial DNA mutations in familial multiple sclerosis.
Leber's hereditary optic neuropathy (LHON) can be difficult to distinguish from optic neuritis due to multiple sclerosis (MS). For several decades an association of LHON and MS has been suspected, and within the past 7 years the LHON nucleotide (nt)-3460 and nt-11778 mtDNA mutations have been identified in several patients with MS-like phenotypes. To further study this association, we tested 42 index patients with clinically definite, familial MS for the LHON mtDNA mutations at nt-3460, nt-11778, and nt-14484. No patients had a pathogenic LHON mtDNA mutation; however, two MS patients with unilateral optic neuritis harbored the nt-15257 mtDNA polymorphism that was reported originally as a pathogenic LHON mutation. Several investigators have shown evidence that the nt-15257 mtDNA mutation is not primarily pathogenic. Therefore, we conclude that pathogenic LHON mtDNA mutations are absent or rare in unselected patients with familial, clinically definite MS (95% confidence intervals for each of the negative mutations 0-7.0%).
Adult↗
Binding of human secretory leukocyte protease inhibitor in uterine cervical mucus to immunoglobulins: pathophysiology in immunologic infertility and local immune defense.
OBJECTIVE: To identify an Fc receptor-like molecule in human cervical mucus. DESIGN: Controlled experimental laboratory study. SETTING: Department of Obstetrics and Gynecology, School of Medicine, University of Tokushima. PATIENT(S): Women undergoing treatment for infertility. INTERVENTION(S): Sodium dodecyl sulfate-polyacrylimide gel electrophoresis and Western blot were used for analysis. MAIN OUTCOME MEASURE(S): A water-insoluble protein with immunoglobulin-binding activity was purified from human cervical mucus by ammonium sulfate fractionation. The initial 21 amino acids of the N-terminus of the immunoglobulin-binding protein were determined and analyzed in a computer search for homology. RESULT(S): The purified fraction contained a 15-kd protein that binds immunoglobulin A, immunoglobulin M, and all subclasses of human immunoglobulin G as determined by Western blot analysis. The amino acid sequence of the N-terminus is identical to that of secretory leukocyte protease inhibitor. The capacity of secretory leukocyte protease inhibitor to bind immunoglobulins was confirmed by Western blot analysis. CONCLUSION(S): A component in human cervical mucus capable of binding immunoglobulins was identified as secretory leukocyte protease inhibitor. The capacity to bind immunoglobulins is a unique property of the protein, providing additional support for the contention that it plays an important physiologic role in local tissue defense mechanisms. It also is involved in the pathogenesis of immunologic infertility by trapping sperm in the cervical mucus.
Amino Acid Sequence↗
Neonatal presentations of mitochondrial metabolic disorders.
Because of the high energy requirements of the growing neonate, disorders of mitochondrial metabolism caused by defects in fatty acid oxidation, pyruvate metabolism, and the respiratory chain may often present in the neonatal period. Common neonatal presentations are hypotonia, lethargy, feeding and respiratory difficulties, failure to thrive, psychomotor delay, seizures, and vomiting. Laboratory clues include alterations in the levels of lactate, pyruvate (and the lactate/pyruvate ratio), glucose, and ketone bodies. Diagnosis usually depends on specific enzyme assays or on molecular genetic analysis. Without treatment, most infants die in the first few days or months of life. In the last decade, there have been significant advances in the understanding of the molecular basis of these disorders. This review discusses the major subgroups of mitochondrial disorders, focusing on defects of pyruvate oxidation, the Krebs cycle, and the respiratory chain. Disorders caused by respiratory chain defects may involve nuclear DNA, mitochondrial DNA, or intergenomic signaling. Recognition and early diagnosis of these conditions are important in the genetic counseling of these families.
DNA, Mitochondrial↗
Characterization of Ribes rubrum callus cultured under low temperature.
Ribes rubrum callus was cultured at the temperature of 15 degrees C for 28 d. The contents of proteins and lipids in the callus cultured at 15 degrees C in a 28 d culture was significantly increased, being 1.1- and 1.2-fold, respectively, of those in callus cultured at 25 degrees C. Comparisons of the contents of monogalactosyldiacylglycerol (MGDG), digalactosyldiacylglycerol (DGDG), sulfoquinovosyldiacylglycerol (SQDG) and phosphatidyldiacylglycerol (PG) revealed that in the callus cultured at 25 degrees C, the content of MGDG was significantly decreased and those of the others significantly increased compared to those in callus cultured at 15 degrees C, in a 7 d culture. But, in a 28 d culture, the contents of these lipids in callus at 15 degrees C became the same as those in callus cultured at 25 degrees C. In regard to the protein composition, the contents of proteins 30 KDa or less in callus cultured at 15 degrees C in a 28 d culture were significantly higher than those in callus cultured at 25 degrees C. These consequences reflect that not only increase in the polyunsaturated fatty acid (PUFA) ratio of total fatty acid (TFA) with cold treatment reported by us previously [Hirano, M., J. Ferment. Bioeng., 83, 608-611 (1997)], but also an increase in low-molecular-weight protein content might be responsible for the cold-tolerance of R. rubrum callus.
Journal Article↗
Expression of 5-HT2A and 5-HT1B receptor mRNA in blood vessels.
Expression of two subtypes of 5-hydroxytryptamine (5-HT) receptors, 5-HT1B and 5-HT2A, was investigated in normal rat arteries (abdominal aorta) and veins (inferior vena cava) by the quantitative reverse transcription-polymerase chain reaction (RT-PCR). The arterial 5-HT2A receptor mRNA level in artery was 25-fold (p < 0.01) higher than the venous level, and the arterial 5-HT1B receptor mRNA level was at least 7000-fold (p < 0.005) higher the venous level.
Animals↗
Expression of PDGF-beta receptor, EGF receptor, and receptor adaptor protein Shc in rat osteoblasts during spaceflight.
A number of studies have indicated that microgravity induces osteopenia and modulates functions of mammalian cells. However, the molecular mechanisms underlying these effects of microgravity are still unknown. Rat osteoblasts were cultured for 4 and 5 days during Shuttle-Spacelab flight, and fixed by guanidine isothiocyanate solution on board after treatment with 1alpha, 25 (OH)2 vitamin D3. The mRNA levels for platelet-derived growth factor (PDGF)-beta receptor, epidermal growth factor (EGF) receptor, the growth factor receptor adaptor protein Shc, and c-fos were determined using the method of quantitative reverse transcription-polymerase chain reaction. The mRNA levels for EGF receptor were not altered by microgravity. However, the mRNA levels for PDGF-beta receptor, Shc, and c-fos were decreased to 62, 55 and 25% on the 4th day of flight, and 47, 40, and 43% on the 5th day, respectively, as compared to the corresponding ground controls. Expression of the growth factor receptor and the receptor adaptor protein was modulated in rat osteoblasts during spaceflight. Data suggest that signal transduction via growth factor receptors in rat osteoblasts is impaired by microgravity. Dysfunction of osteoblasts might be involved in spaceflight-induced osteopenia.
Animals↗
Sulfamethizole capsules containing contrast medium for assessment of gastric emptying in functional dyspepsia patients.
The usefulness of sulfamethizole capsules containing contrast medium in gastric emptying tests for functional dyspepsia was evaluated in five healthy volunteers and nine patients with dysmotility-like symptoms. Each subject swallowed 15 capsules with a liquid, food, and at 0, 15, 30, 45, 60, 90, and 120 min, the capsule position and size were monitored fluoroscopically for 30 sec and radiograms were obtained. Blood sulfamethizole concentrations were also measured at the same time. Visualized capsule movement from the proximal to distal stomach up to 60 min was faster in the patients, whereas in the later digestion period, proximal stomach emptying in the patients was delayed significantly (P < 0.05), and the number of capsules remaining in the distal stomach at 120 min was significantly larger in the patients (P < 0.05). This test method was evaluated as being useful in monitoring solid emptying in normal and pathophysiologic conditions.
Adult↗
Fatal infantile cardioencephalomyopathy with COX deficiency and mutations in SCO2, a COX assembly gene.
Mammalian cytochrome c oxidase (COX) catalyses the transfer of reducing equivalents from cytochrome c to molecular oxygen and pumps protons across the inner mitochondrial membrane. Mitochondrial DNA (mtDNA) encodes three COX subunits (I-III) and nuclear DNA (nDNA) encodes ten. In addition, ancillary proteins are required for the correct assembly and function of COX (refs 2, 3, 4, 5, 6). Although pathogenic mutations in mtDNA-encoded COX subunits have been described, no mutations in the nDNA-encoded subunits have been uncovered in any mendelian-inherited COX deficiency disorder. In yeast, two related COX assembly genes, SCO1 and SCO2 (for synthesis of cytochrome c oxidase), enable subunits I and II to be incorporated into the holoprotein. Here we have identified mutations in the human homologue, SCO2, in three unrelated infants with a newly recognized fatal cardioencephalomyopathy and COX deficiency. Immunohistochemical studies implied that the enzymatic deficiency, which was most severe in cardiac and skeletal muscle, was due to the loss of mtDNA-encoded COX subunits. The clinical phenotype caused by mutations in human SCO2 differs from that caused by mutations in SURF1, the only other known COX assembly gene associated with a human disease, Leigh syndrome.
Amino Acid Sequence↗
Evaluation with three-dimensional computed tomography after anterior skull base reconstruction using two musculopericranial flaps and a grafted bone.
Postoperative evaluation by three-dimensional (3D) computed tomography (CT) was performed in 15 patients who underwent anterior skull base reconstruction using two musculopericranial flaps and a grafted bone sandwiched between the two flaps. Especially in the case of large bone grafts (4 x 4 cm or more), the graft was positioned with the convex side facing upward into the cranial cavity to avoid creating an intracranial dead space. The extent of the absorption and changes in the contour of the grafted bone were evaluated. Imaging was done at a CT level of 150 using a Proceed 3-D CT scanner (Yokogawa Medical Co., Tokyo, Japan). Donor bone for grafting to the skull base was harvested the cranium in 10 patients and the ilium in 5 others. Patients ranged in age from 7 to 76 years (mean, 47); there were 10 men and 5 women. The grafted bone ranged in size from 1 x 2 cm to 5 x 8 cm (1 x 2 cm to about 4 x 3 cm: 10 patients; 4 x 4 to about 5 x 8 cm: 5 patients).No marked absorption of grafted bone was seen in these 15 patients, and no brain hernia occurred. In patients with large bone grafts (4 x 4 cm to about 5 x 8 cm), a graft that had been positioned with the convex side facing upward into cranial cavity at the time of transplant was subsequently observed to be transformed into a downward convex contour of normal skull base. Fostoperative infection did not occur because of the dead space nor were there any symptom of pressure on the brain because of the upward convexity of the grafted bone.The present reconstructive method is not only a minimum invasive but also a safe and reliable method for anterior skull base surgery.
Journal Article↗
Fibroblasts in human vocal fold mucosa.
Fibroblasts in two portions of the vocal fold mucosa, the macula flava (MF) and Reinke's space (RS), were investigated by means of transmission electron microscopy. Five adult and five newborn larynges from autopsy cases were subjected to study. Both in adults and newborns, fibroblasts in the MF tended to be stellate in shape, to have a small nucleus/cytoplasm (N/C) ratio, and to have a well developed rough endoplasmic reticulum (rER) and Golgi apparatus (GA). They were active in producing collagenous and elastic fibres. Most fibroblasts in RS were oval in newborns and spindle-shaped in adults. They had a large N/C ratio and less developed rER and GA, indicating that they were inactive in producing fibres. We postulate that many fibroblasts in the newborn and infant MF contribute to the development of the vocal ligament, many of those in the adult MF participate in the metabolism of the vocal ligament, and many of those in RS of both age groups are activated when the vocal fold tissue is injured.
Adult↗
Maternally inherited cardiomyopathy: an atypical presentation of the mtDNA 12S rRNA gene A1555G mutation.
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Adult↗
Alternating combination chemotherapy COP (cyclophosphamide, vincristine, prednisone) and MP (melphalan, prednisone) in multiple myeloma: a multicenter phase II study (JCOG8906). Lymphoma Study Group of the Japan Clinical Oncology Group.
BACKGROUND: The main form of cytotoxic treatment for multiple myeloma (MM) is conventional dose chemotherapy at present. METHOD: Between November 1989 and December 1991, a multicenter phase II study of alternating conventional dose combination chemotherapy (CCT) with COP (cyclophosphamide, vincristine, prednisone) and MP (melphalan and prednisone) to evaluate its clinical usefulness for overt MM patients was conducted by the Lymphoma Study Group of the Japan Clinical Oncology Group (JCOG). RESULTS: Eighty-one previously untreated patients were enrolled in the study. For 69 eligible patients, the response rate was 50.7% [95% confidence interval (CI) 38.4-63.0%]. The median survival time was 38.5 (95% CI 32.0-44.4) months. The survival rate at 3 and 5 years was 50.7 and 27.3%, respectively. Grade 4 toxicity by the criteria of the World Health Organization consisted of anemia in eight patients, leucocytopenia in three, cardiac in one and hepatic in two, but there was no treatment-related death. CONCLUSION: The COP-MP regimen for overt MM is thought to be one of the effective CCTs according to the results of the present phase II study.
Adult↗
Complex hprt deletion events are recovered after exposure of human lymphoblastoid cells to high-LET carbon and neon ion beams.
Hypoxanthine phosphoribosyltransferase gene (hprt) mutations were induced in human TK-6 lymphoblastoid cells by irradiation at a linear energy transfer (LET) of 250 or 310 keV/micron for carbon and neon ions, respectively. At such a high level of LET, ions will lose most of their total energy and stop shortly after passing through the cell. The hprt mutations were analyzed by multiplex PCR, long-PCR and DNA sequencing of both genomic and cDNA. Over half of the C ion-induced hprt mutations (10 of 19) were point mutations, in contrast to 15% of the mutations induced by Ne ions (three of 20). The remaining 47 and 85% of the C and Ne ion-induced mutants, respectively, are deletion events. The latter events include three complex losses of multiple non-contiguous exon regions in both ion irradiation collections. We note that mutations involving the exon 6 region are frequent in the Ne ion collection: all three of the complex events retained the exon 6 region with flanking deletion of sequence and three other mutants involved deletion of this region. It may be concluded that these high-LET C and Ne ion irradiations produce different mutational spectra.
Carbon↗
Involvement of two plasmids in the degradation of carbaryl by Arthrobacter sp. strain RC100.
A bacterium capable of utilizing carbaryl (1-naphthyl N-methylcarbamate) as the sole carbon source was isolated from carbaryl-treated soil. This bacterium was characterized taxonomically as Arthrobacter and was designated strain RC100. RC100 hydrolyzes the N-methylcarbamate linkage to 1-naphthol, which was further metabolized via salicylate and gentisate. Strain RC100 harbored three plasmids (designated pRC1, pRC2, and pRC3). Mutants unable to degrade carbaryl arose at a high frequency after treating the culture with mitomycin C. All carbaryl-hydrolysis-deficient mutants (Cah-) lacked pRC1, and all 1-naphthol-utilization-deficient mutants (Nat-) lacked pRC2. The plasmid-free strain RC107 grew on gentisate as a carbon source. These two plasmids could be transferred to Cah- mutants or Nat- mutants by conjugation, resulting in the restoration of the Cah and Nah phenotypes.
Arthrobacter↗
Ca2+ sensitization of smooth muscle contractility induced by ruthenium red.
The effects of ruthenium red (RuR) on contractility were examined in skinned fibers of guinea pig smooth muscles, where sarcoplasmic reticulum function was destroyed by treatment with A-23187. Contractions of skinned fibers of the urinary bladder were enhanced by RuR in a concentration-dependent manner (EC50 = 60 microM at pCa 6.0). The magnitude of contraction at pCa 6.0 was increased to 320% of control by 100 microM RuR. Qualitatively, the same results were obtained in skinned fibers prepared from the ileal longitudinal smooth muscle layer and mesenteric artery. The maximal contraction induced by pCa 4.5 was not affected significantly by RuR. The enhanced contraction by RuR was not reversed by the addition of guanosine 5'-O-(2-thiodiphosphate) or a peptide inhibitor of protein kinase C [PKC-(19-31)]. The application of microcystin, a potent protein phosphatase inhibitor, induced a tonic contraction of skinned smooth muscle at low Ca2+ concentration ([Ca2+]; pCa > 8.0). RuR had a dual effect on the microcystin-induced contraction-to- enhancement ratio at low concentrations and suppression at high concentrations. The relaxation following the decrease in [Ca2+] from pCa 5.0 to >8.0 was significantly slowed down by an addition of RuR. Phosphorylation of the myosin light chain at pCa 6.3 was significantly increased by RuR in skinned fibers of the guinea pig ileum. These results indicate that RuR markedly increases the Ca2+ sensitivity of the contractile system, at least in part via inhibition of myosin light chain phosphatase.
Animals↗