Biomedical subjects

T Kumamoto

Publications and source records attributed to T Kumamoto.

At least 73 records · Page 4Linked to original sources

PubMed1998

Localized muscle wasting as an initial symptom of skeletal muscle lymphoma.

A 25-year-old man who developed painless muscle wasting and weakness of only the right thigh, was eventually shown to have systemic lymphoma with muscle infiltration. The patient was initially misdiagnosed as focal inflammatory myopathy, and he had a partial response to steroid therapy. Immunohistochemical analysis of the biopsied muscle and the subcutaneous tumor revealed the infiltrating cells with a positive macrophage-associated marker (CD68) and negative T- or B-cell-associated antigens, leading to the final diagnosis of true histiocytic lymphoma. Although skeletal muscle lymphoma is extremely rare, it should be considered in the differential diagnosis of localized muscle wasting.

Adult↗

PubMed1998

CD4+ T-lymphocytopenia in long-term survivors following intensive chemotherapy in childhood cancers.

BACKGROUND: It is generally believed the effects of short intensive courses of therapy are rapidly reversible in childhood cancers, and immunologic function following years of maintenance treatment with chemotherapy usually returns to normal by 6 months or less when treatment is terminated. However, we previously demonstrated that dysregulation of immunoglobulins, especially IgD, was observed in long-term survivors following intensive chemotherapy in cancer patients. With regard to cellular immunity, investigators reported that antineoplastic chemotherapy significantly reduces the number of CD4+ T-lymphocytes, and production of newly developing CD4+ T-lymphocytes was inversely related to the patients' age. However, the incidence of CD4+ lymphocytopenia in long-term survivors of childhood cancers is not known. PROCEDURE: Here, we report the flow cytometric analysis of peripheral blood from long-term survivors who continue complete remission off chemotherapy for more than 5 years. RESULTS: Six out of 74 long-term survivors (8.1%), showed low CD4+ T-lymphocyte count (<300/mm3). Three of six patients showed continued CD4+ T-lymphocytopenia over a year. In spite of the persistent low levels of CD4+ T cells, these three patients were not susceptible to severe infections. COMMENT: Intriguingly, in patients with CD4+ T-lymphocytopenia there has been a tendency toward increased numbers of natural killer cells or gamma delta T cells that may be operating as a thymus-independent compensatory mechanism to defend the hosts.

Adolescent↗

PubMed1998

Single muscle fiber analysis of myoclonus epilepsy with ragged-red fibers.

We examined two muscle biopsy specimens from a proband and her mother with myoclonus epilepsy with ragged-red fibers (MERRF), both obtained at an interval of about 10 years, using histochemistry, in situ hybridization, and single-fiber polymerase chain reaction. Total (wild-type and mutant) mitochondrial DNAs (mtDNAs) were greatly increased in ragged-red fibers (RRF) over non-RRF in all muscle specimens analyzed. The proportion of mutant mtDNA was also significantly higher in RRF than in non-RRF. By comparing the first and second muscle biopsied specimens in each patient, we found that while the proportion of RRF, cytochrome coxidase deficient fibers, and mutant DNA in muscle changed over a 10-year period, the proportion of wild-type and mutant mtDNAs in RRF and in non-RRF was similar between the two specimens. These results suggest that the ratio of wild-type to mutant mtDNAs in RRF and non-RRF in MERRF is at a steady state level in each muscle fiber, without replicative advantage of mutant mtDNA.

Adult↗

PubMed1998

Effect of chloroquine-induced myopathy on rat soleus muscle sarcoplasm and expression of clathrin.

Clathrin-coated vesicles are involved in receptor-mediated intracellular transport pathways related to lysosomal proteolysis. Clathrin levels were significantly elevated in denervated soleus muscles from chloroquine- and saline-treated rats as compared with their contralateral, innervated muscles. No difference was found in the clathrin levels of the denervated muscles in both groups. The accumulation of autophagic vacuoles was marked only in chloroquine-treated muscles after denervation. These findings suggest that chloroquine does not inhibit intracellular trafficking of clathrin-coated vesicles during the overdevelopment of autophagic vacuoles.

Animals↗

PubMed1998

[Right ventricular myxoma in a 71-year-old female].

Right ventricular myxoma in elderly is very rare and this is the 36th case report of right ventricular myxoma in Japan. A healthy 71-year-old female with no symptoms or constitutional signs except heart murmur was hospitalized. Findings of transthoracic echocardiogram, CT scan, MRI and angiocardiogram demonstrated a mobile tumor in the right ventricular outflow tract. Transesophageal echocardiogram clearly revealed that the stalk was arising from the right ventricular free wall. Under cardiac arrest, right atriotomy was made and a gelatinous tumor (4.5 x 2 x 2 cm in size, 7.3 g in weight) was excised with 5 mm of surrounding endocardium and a few millimeters of underlying myocardium through the tricuspid valve. Histopathologically, the tumor was diagnosed as a myxoma. Her postoperative course was uneventful.

Aged↗

PubMed1998

Immunohistochemical study of clathrin in distal myopathy with rimmed vacuoles.

Clathrin-coated vesicles are involved in three receptor-mediated intracellular transport pathways: export from the Golgi apparatus, transfer of lysosomal enzymes from the Golgi apparatus to lysosomes, and endocytosis at the plasma membrane. Seeking evidence of transport abnormalities in distal myopathy with rimmed vacuoles (DMRV), we performed immunohistochemistry for clathrin in muscle biopsy specimens from patients with this disorder or other neuromuscular disorders, and also in control muscle samples resected in orthopedic procedures. While most myofibers from control muscle did not stain for clathrin, some fibers revealed finely granular sarcoplasmic staining. In specimens from patients with Duchenne and Becker muscular dystrophy, amyotrophic lateral sclerosis, peripheral neuropathy, and DMRV, numerous clathrin-positive granules were often scattered through the sarcoplasm and seen to a lesser extent in subsarcolemmal regions. Quantitative immunohistochemical assessment showed more reactivity for clathrin in DMRV than in controls and other diseased muscles, particularly in atrophic fibers and type 2 fibers. Not all strongly clathrin-positive muscle fibers contained rimmed vacuoles, although most fibers with vacuoles were clathrin positive. The result suggests that the lysosome system is activated and receptor-mediated intracellular transport pathways function appropriately in the muscles of DMRV patients.

Adolescent↗

PubMed1998

Comparative effects of alpha- and gamma-linolenic acids on rat liver fatty acid oxidation.

It has been reported that both n-3 and n-6 octadecatrienoic acids can increase hepatic fatty acid oxidation activity. It remains unclear, however, whether different enzymes in fatty acid oxidation show a similar response to n-3 and n-6 octadecatrienoic acids. The activity of hepatic fatty acid oxidation enzymes in rats fed an oil mixture rich in alpha-linolenic acid (18:3n-3) and borage oil rich in gamma-linolenic acid (18:3n-6) was therefore compared to that in rats fed an oil mixture rich in linoleic acid (18:2n-6) and a saturated fat (palm oil) in this study. Linseed oil served as the source of 18:3n-3 for the oil mixture rich in this octadecatrienoic acid and contained 30.6% 18:3n-3 but not 18:3n-6. Borage oil contained 25.7% 18:3n-6 and 4.5% 18:3n-3. Groups of seven rats each were fed diets containing 15% various fats for 15 d. The oxidation rate of palmitoyl-CoA in the peroxisomes was higher in rats fed a fat mixture rich in 18:3n-3 (3.03 nmol/min/mg protein) and borage oil (2.89 nmol/min/mg protein) than in rats fed palm oil (2.08 nmol/min/mg protein) and a fat mixture rich in 18:2n-6 (2.15 nmol/min/mg protein). The mitochondrial palmitoyl-CoA oxidation rate was highest in rats fed a fat mixture rich in 18:3n-3 (1.93 nmol/min/mg protein), but no significant differences in this parameter were seen among the other groups (1.25-1.46 nmol/min/mg protein). Compared to palm oil and fat mixtures rich in 18:2n-6, a fat mixture rich in 18:3n-3 and borage oil significantly increased the hepatic activity of carnitine palmitoyltransferase and acyl-CoA oxidase. Compared to palm oil and a fat mixture rich in 18:2n-6, a fat mixture rich in 18:3n-3, but not fats rich in 18:3n-6, significantly decreased 3-hydroxyacyl-CoA dehydrogenase activity. Compared to palm oil and a fat mixture rich in 18:2n-6, borage oil profoundly decreased mitochondrial acyl-CoA dehydrogenase activity, but a fat mixture rich in 18:3n-3 increased it. 2,4-Dienoyl-CoA reductase activity was significantly lower in rats fed palm oil than in other groups. Compared to other fats, borage oil significantly increased delt3,delta2-enoyl-CoA isomerase activity. Activity was also significantly higher in rats fed 18:2n-6 oil than in those fed palm oil. It was confirmed that both dietary 18:3n-6 and 18:3n-3 increased fatty acid oxidation activity in the liver. These two dietary octadecatrienoic acids differ considerably, however, in how they affect individual fatty acid oxidation enzymes.

Animals↗

PubMed1998

Suppression of alloreactivity with gamma delta T-cells: relevance to increased gamma delta T-cells following bone marrow transplantation.

Several reports have shown that an increase in T-cell receptor gamma/delta-positive T-cells (gamma delta T-cells) have been observed following bone marrow transplantation. gamma delta T-cells expanded from peripheral blood mononuclear cells from normal volunteers were used to investigate the function of gamma delta T-cells in vitro. Peripheral blood mononuclear cells were cultured with synthetic ligand of gamma delta T-cells, monoethyl phosphates (MEP), for 7 days. MEP specifically expanded gamma delta T-cells. Expanded gamma delta T-cells from subject "B" were added to an A anti-B or A anti-C mixed lymphocyte culture (MLC) containing responder cells from subject "A" and irradiated stimulator cells from subjects "B" or "C". The cultures were harvested on day 6 and tested for cytotoxicity against stimulator-type Con A blasts. gamma delta T-cells from subject "B" specifically inhibit generation of allospecific cytotoxic T lymphocytes (CTL) in A anti-B MLC. The results indicate that gamma delta T-cells exhibit veto-type suppression of alloreaction. If the current experiments are also applicable in vivo, gamma delta T-cells originating from the donor after bone marrow transplantation may inhibit graft rejection by suppressing recipient anti-donor reactivity. gamma delta T-cells may be involved in the suppression of allogeneic reaction in vivo following allogeneic bone marrow transplantation.

Bone Marrow Transplantation↗

PubMed1998

Late-onset unilateral renal dysfunction combined with non-insulin-dependent diabetes mellitus and bronchial asthma following allogeneic bone marrow transplantation for acute lymphoblastic leukemia in a child.

We report a child with T cell acute lymphoblastic leukemia who developed late-onset multiple complications after allogeneic bone marrow transplantation from an HLA-matched sibling. The preparative regimen consisted of total body irradiation (TBI, 12 Gy), splenic irradiation (6 Gy) and cytosine arabinoside (3 g/m2 x 10). Splenic irradiation was added because of persistent splenomegaly in spite of intensive chemotherapy. He developed bronchial asthma 1 1/2 years post transplant. He presented with microhematuria and proteinuria 4 1/2 years post-transplant, which were due to unilateral left renal dysfunction. He developed type II, non-insulin-dependent diabetes mellitus 8 years post-transplant. A biopsy from the left kidney was not compatible with diabetic nephropathy. All these complications appear to be independently related to BMT, particularly TBI and/or splenic irradiation.

Adolescent↗

PubMed1998

Cytokine-enhanced mixed lymphocyte reaction (MLR) in cord blood.

Although in cord blood (CB) transplantation graft-versus-host disease (GVHD) is reported to be less severe, GVHD may occur even in patients with HLA-identical sibling donors. This result shows that HLA typing can not entirely predict GVHD. The standard MLR with CB cells was either normal or slightly reduced compared with adult peripheral blood (PB) cells. We used two manipulations to increase the responses of CB cells to allo-antigens. The first was to treat the stimulator cells with cytokines, and the second to amplify weak proliferative responses by adding exogenous cytokines to MLR cultures (modified MLR). The stimulator cells were treated with both interferon-gamma (IFN-gamma) and IL-4. The responder cells were treated with both IL-2 and tumour necrosis factor-alpha (TNF-alpha). It is still to be determined whether or not this cytokine-enhanced MLR could be a possible predictor of GVHD. However, using these cytokines, 90% of CB could recognize allo-antigens, even if the standard MLR was negative.

Adult↗

PubMed1998

Clinical and genetic studies of spinocerebellar ataxia type 2 in Japanese kindreds.

OBJECTIVES: We report the results of clinical and genetic studies from 2 related Japanese kindreds with spinocerebellar ataxia type 2 (SCA2). MATERIAL AND METHODS: Family A showed 19 patients through 4 generations, while family B showed 6 patients, including dizygotic twin brothers, through 3 generations. We performed clinical, radiological, neurophysiological, and genetic analyses in the family members. RESULTS: Neurologic analysis of 13 affected patients revealed a mean age at onset of 43.5 years. The most common neurologic finding was cerebellar ataxia with deep sensory disturbance. Slow saccades was found only in the younger patients below age 35 years. Nerve conduction studies revealed subclinical sensory neuropathy. Brain MRI showed the presence of pontocerebellar atrophy. Genetic study using PCR revealed that all affected patients had an expanded CAG allele in the ataxin-2 gene, which led to a final diagnosis of SCA2. CONCLUSION: SCA2 may be more clinically heterogeneous than previously thought. PCR is useful in differentiating SCA2 from other types of inherited ataxia.

Adult↗

PubMed1998

Proteasomes in distal myopathy with rimmed vacuoles.

In a previous report we suggested that muscle fibers in distal myopathy with rimmed vacuoles (DMRV) were degraded by both lysosomal proteolysis (cathepsins) and Ca2+-dependent, nonlysosomal proteolysis (calpain). Given recent evidence of abnormal ubiquitin accumulation in rimmed vacuoles, we examined the role of the ATP-ubiquitin-dependent proteolytic pathway (proteasomes) in myofiber degradation in this myopathy. Immunohistochemically, proteasomes (26S) were located in the cytoplasm in normal human muscle, but the staining intensity was weak. Quantitative analysis showed more reactivity for proteasomes in DMRV muscles and, to a lesser extent, in muscles from muscular dystrophy, polymyositis, and amyotrophic lateral sclerosis patients. In DMRV, proteasomes often were located within or on the rim of rimmed vacuoles, and in the cytoplasm of atrophic fibers. Ubiquitin accumulation was marked within rimmed vacuoles and was seen less extensively in the cytoplasm of atrophic fibers. The latter proteins colocalized well. In other diseased muscles, proteasomes and ubiquitin showed a positive reaction in the atrophic or necrotic fibers. The results indicate increased proteasome and ubiquitin in these muscle fibers as well as in other diseased muscle fibers. We suggest that the ATP-ubiquitin-proteasome proteolytic pathway as well as the nonlysosomal calpain and the lysosomal proteolytic pathway may participate in the muscle fiber degradation in DMRV.

Adenosine Triphosphate↗

PubMed1998

Clinicopathologic characteristics of the lungs of patients with human T cell lymphotropic virus type 1-associated myelopathy.

Lung autopsy specimens were evaluated histologically in the six patients with human T cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy (HAM). The results revealed two histologic changes. First, lymphoid infiltrates were distributed widely in peribronchiolar and perivascular regions, subpleural regions, and the alveolus. Lymphoid infiltrates were also observed in bronchial mucosal glands in relatively large bronchi, in which the acinar epithelium was sometimes degenerated. Second, chronic inflammatory changes, such as smooth muscle hypertrophy, fibrosis, or squamous cell metaplasia, were increased significantly in the membranous bronchioles of HAM patients compared with specimens from lung cancer control patients. Such histologic changes were subclinical in most cases, but one case had an abnormal chest shadow, and two cases had recurrent pneumonia. In HAM patients, high levels of HTLV-1-specific cytotoxic T lymphocytes are believed to attack the HTLV-1-bearing cells in the lung, resulting in inflammatory reactions.

Aged↗

PubMed1998

Pyomyositis associated with Bacteroides fragilis in a patient with multiple myeloma.

Pyomyositis is an infection of the skeletal muscle that is usually caused by Staphylococcus aureus. We report a 68-year-old Japanese woman who developed pyomyositis caused by Bacteroides fragilis following treatment for multiple myeloma. There are only two cases of pyomyositis associated with multiple myeloma in the literature. After receiving melphalan and prednisolone for five days, she developed multiple abscesses in the muscles of the right arm and thigh. Purulent exudate was aspirated from the abscess, and B. fragilis was identified. This is the first case of B. fragilis pyomyositis. Magnetic resonance imaging aided the diagnosis. Treatment consisted of surgical incision and drainage, with antibiotic administration. The immunosuppression caused by the myeloma and/or the chemotherapy presented a risk factor for the unusual infection observed in this patient.

Abscess↗

PubMed1998

[Effects of various Ringer's solutions on acid-base balance in rats in hemorrhagic shock and with hepatic dysfunction].

We investigated the effects of bicarbonated Ringer's solution (BR) on arterial blood acid-base balance, and compared these with the effects of lactated Ringer's solution (LR) and acetated Ringer's solution (AR) in rats in hemorrhagic shock. Rats underwent 70% reduction of hepatic blood flow and blood shedding of 1.5% of body weight. Each solution was infused through the femoral vein at a rate of shed blood volume x 8.hr-1 for 30 min under urethane anaesthesia. After the blood shedding, arterial blood pH and HCO3-decreased but plasma lactate concentration increased. These parameters improved significantly in the BR group compared with those in the LR group. However, the LR group showed the lowest blood pH and the highest plasma lactate concentration among the groups. These results suggest that BR has superior effects on the arterial blood acid-base balance and glucose metabolism in rats in hemorrhagic shock and with hepatic dysfunction.

Acid-Base Equilibrium↗

PubMed1998

[A case of chronic progressive external ophthalmoplegia presenting as inflammatory myopathy].

A 64-year-old female had slowly progressive bilateral external ophthalmoplegia, blepharoptosis and muscle weakness of the extremities since age 30. Laboratory examination showed an elevation of serum CK level. Biopsied specimens from the left biceps and the left orbicularis oculi muscles revealed myopathic change with infiltration of mononuclear cells. In addition, some ragged-red fibers and a few cytochrome c oxidase-negative fibers, which are characteristic of mitochondrial myopathy, were observed. Polymerase chain reaction analysis of mtDNA in the muscles showed multiple mtDNA deletions. On administration of prednisolone (initial dose, 60 mg/day), blepharoptosis and muscular strength improved transiently and serum CK level was normalized but external ophthalmoplegia was not improved. We diagnosed our case as chronic progressive external ophthalmoplegia (CPEO). This is the first report of CPEO presenting as inflammatory myopathy.

DNA, Mitochondrial↗

PubMed1998

Effects of BX661A, a new therapeutic agent for ulcerative colitis, on reactive oxygen species in comparison with salazosulfapyridine and its metabolite sulfapyridine.

5-[4-(2-Carboxyethylcarbamoyl)phenylazo]salicylic acid disodium salt dihydrate (CAS 80573-04-2, BX661A) is developed as a therapeutic agent for ulcerative colitis. To clarify its mechanism of action, the effects of BX661A and its metabolites 5-aminosalicylic acid (5-ASA) and 4-aminobenzoyl-beta-alanine (4-ABA) on reactive oxygen species: superoxide radicals (O2-) generated by hypoxanthine and xanthine oxidase, hydrogen peroxide (H2O2), hypochlorite radicals (OCl-) and hydroxyl radicals (OH.), were investigated and compared with the effects of 2-hydroxy-5-[[4-[(2-pyridinylamino)sulfonyl]phenyl]azo]-benzoic acid (CAS 599-79-1, salazosulfapyridine, SASP) and its metabolite 4-amino-N-2-pyridinyl-benzenesulfonamide (CAS 144-83-2, sulfapyridine, SP). 1. BX661A, SASP and 5-ASA inhibited O2- radical production in a concentration-dependent manner (IC50 = 0.14, 0.13 and 0.19 mmol/l, respectively). The effects of 4-ABA and SP on O2- radical production were weak (IC50 = > 10 and > 3 mmol/l, respectively). In contrast, superoxide dismutase inhibited O2- radical production in a concentration-dependent manner (IC50 = 1.7 U/ml). 2. BX661A, SASP, 4-ABA and SP had no H2O2 scavenging effects. 5-ASA scavenged H2O2, but its maximal scavenging action was 51.3%. In contrast, catalase scavenged H2O2 in a concentration-dependent manner (IC50 = 0.47 U/ml). 3. BX661A, SASP and 5-ASA scavenged OCl- radicals in a concentration-dependent manner (IC50 = 69.5, 73.8 and 21.7 mumol/l, respectively). 4-ABA and SP had no OCl- radical scavenging effects. In contrast, nordihydroguaiaretic acid (NDGA) scavenged OCl- radicals in a concentration-dependent manner (IC50 = 8.7 mumol/l). 4. BX661A and SASP scavenged OH. radicals in a concentration-dependent manner; the maximal scavenging values were 39.5 (10 mmol/l) and 48.6% (3 mmol/l), respectively. 4-ABA and SP had no OH. radical scavenging effects. In contrast, 5-ASA scavenged OH. radical in a concentration-dependent manner (IC50 = 1.46 mmol/l). These results suggest that BX661A has O2- and OCl- radical scavenging effects and that 5-ASA has O2-, OCl- and OH. radical scavenging effects. Therefore, these effects may be partially involved in the therapeutic effects of BX661A on ulcerative colitis.

Aminosalicylic Acids↗

PubMed1997

Fluorescence polarization study of a salt bridge between a single-chain Fv and its antigen ribonuclease A.

The interaction between a single-chain Fv (sFv) of the monoclonal antibody 3A21 and its antigen, bovine pancreatic ribonuclease A (RNase A), was studied by site-directed mutagenesis of the hypervariable regions and fluorescence polarization analysis. The affinity constants of wild-type sFv and a mutant sFv D31A (Asp31 of heavy chain was replaced by Ala) for RNase A were found to be 2.7 x 10(7) and 4.7 x 10(6) M-1 in PBS at pH 7.2 and 37 degrees C, respectively. While the affinity constant of D31A is not affected by NaCl concentration, that of wild-type sFv is almost the same as that of D31A in the presence of more than 1 M NaCl. These results demonstrate that Asp31 of the heavy chain interacts electrostatically with a positively charged amino acid residue of RNase A.

Alanine↗