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Biomedical subjects

T Kumamoto

Publications and source records attributed to T Kumamoto.

At least 127 records · Page 7Linked to original sources
PubMed1993

[Neoadjuvant chemotherapy effective for small cell lung cancer in a nephrectomized patient].

A 67-year-old man, who was nephrectomized due to renal cell cancer 4 years ago, was admitted to examine a mass shadow in the right middle lung field. He was diagnosed as small cell lung cancer with TBLB. Because of impaired renal function, he was treated with CBDCA (300 mg/m2, day 1), THP (30 mg/m2, day 1) and oral etoposide (25 mg/body, for 21 days) without any renal complications. After 3 courses of chemotherapy, the lung CT showed scar lesion despite the disappearance on the chest X-ray, and a right lower lobectomy was performed. Malignant cells remained in the scar lesion, but not in the lymph nodes. These findings suggested the effectiveness of neoadjuvant chemotherapy. This newly-designed chemotherapy procedure is necessary for patients with renal complications.

Aged↗
PubMed1992

A novel transthyretin mutation at position 30 (Leu for Val) associated with familial amyloidotic polyneuropathy.

A novel transthyretin (TTR) mutation associated with familial amyloidotic polyneuropathy was detected in a Japanese patient. Single-strand conformation polymorphism analysis and sequence analysis of polymerase chain reaction (PCR)-amplified exons of the patient's TTR gene revealed a point mutation resulting in a substitution of leucine for valine at position 30. As the mutation creates a Cfr13I site, it was confirmed by PCR and restriction analysis. Our finding indicates the importance of position 30 in TTR-derived amyloid fibril formation.

Amyloidosis↗
PubMed1992

Localization of the Ca(2+)-dependent proteinases and their inhibitor in normal, fasted, and denervated rat skeletal muscle.

Immunofluorescence and immunogold localization studies show that the two Ca(2+)-dependent proteinases (mu-calpain for the micromolar Ca(2+)-requiring proteinase and m-calpain for the millimolar Ca(2+)-requiring proteinase) and their protein inhibitor (calpastatin) are located exclusively intracellularly in normal rat soleus muscle. Quantitative immunogold studies indicate that binding of antibodies to both calpains and to calpastatin is approximately two times greater at the Z-disk of myofibrils than it is at the I-band or A-band regions. Mitochondria and nuclei in muscle cells contain both calpains and calpastatin at concentrations approximately one-tenth and one-fifth, respectively, of the concentration at the Z-disk, as estimated by antibody binding. Very little calpain or calpastatin was seen in the cytoplasmic intermyofibrillar spaces, and most of the calpain and calpastatin in muscle cells is associated with intracellular structures. Immunofluorescence results suggest that concentration of m-calpain but not mu-calpain or calpastatin is, in some instances, slightly higher near the intracellular surface of the plasma membrane than elsewhere in the muscle cell. Most m-calpain, however, is distributed throughout the interior of mature rat skeletal muscle cells. Denervation, or fasting and refeeding increases the concentration of the calpains and calpastatin in the muscle cell but does not change their distribution. Some mu- and m-calpain and calpastatin is found extracellularly in denervated soleus muscle or soleus muscle from fasting rats, but the extracellular calpains and calpastatin seem to originate from "leakage" of these proteins out of the cell because serum creatine kinase levels are much higher than normal in denervated or fasting rats.

Animals↗
PubMed1992

Circulating autoantibody to muscle protein in a patient with paraneoplastic myositis and colon cancer.

A muscle-specific autoantibody was found in a patient with paraneoplastic myositis and colon cancer. By immunoblotting, we found high titers of circulating antibody to a 34-kDa neutral protein in the soluble sarcoplasmic fraction of the rat skeletal muscle. The serum did not react at all with other tissue extracts including the central nervous tissue, liver, or kidney. The possible role of this muscle-specific autoantibody in the pathogenesis of paraneoplastic myositis is discussed.

Adenocarcinoma↗
PubMed1991

Analyses of T-cell differentiation from hemopoietic stem cells in the G0 phase by an in vitro method.

Using differential radiation sensitivity of components of mouse embryonal thymus, an in vitro method for studying T-cell differentiation from hemopoietic stem cells (HSCs) in the G0 phase was established. Intrathymic T-cell precursors present in embryonal thymus were found to be quite radioresistant (up to 20 Gy), and consequently 25-Gy-irradiated embryonal thymic lobes were used. Thymic lobes (25-Gy irradiated) taken from mouse fetuses (gestation day 15) were placed in Millipore-HA culture plates supported on squares of gelatin foam sponge in 24-well culture plates in which neonatal thymus stromal cells were cultured. HSCs (10(5) cells per well) in the G0 phase were added to these thymic lobes and cocultured at 37 degrees C in a 5% CO2/95% air incubator. Half the culture medium was changed every week. After 3 weeks, a large number of colonies had formed. Immunohistochemical studies and fluorescence-activated cell sorter analyses revealed that the colonizing cells regularly develop and exhibit surface markers characteristic of T cells (Thy-1, IL-2R, L3T4, Lyt-2, etc.). In situ hybridization analyses revealed that mRNA expression for T-cell receptor (TCR) beta chains occurred within colonizing cells. Using a monoclonal antibody (F23.1), expression of TCR beta-chain variable domain (V beta 8) on the surface of these developing T cells was demonstrated. These cells responded to interleukin 2 and/or anti-CD3 monoclonal antibody, indicating functional T cells. This method will be useful in studying T-cell differentiation pathways from pluripotent HSCs and in clarifying the mechanisms involved in negative and positive selection of T cells within the thymus.

Animals↗
PubMed1991

Distinct mechanisms of neonatal tolerance induced by dendritic cells and thymic B cells.

To assess the role of different types of antigen-presenting cells (APC) in the induction of tolerance, we isolated B cells, macrophages, and dendritic cells from thymus and spleen, and injected these into neonatal BALB/c mice across an Mls-1 antigenic barrier. One week after injection of APC from Mls-1-incompatible mice or from control syngeneic mice, we measured the number of thymic, Mls-1a-reactive, V beta 6+ T cells and the capacity of thymocytes to induce a graft-vs.-host (GVH) reaction in popliteal lymph nodes of Mls-1a mice. Injection of thymic but not spleen B cells deleted thymic, Mls-1a-reactive V beta 6+ T cells and induced tolerance in the GVH assay. The thymic B cells were primarily of the CD5+ type, and fluorescence-activated cell sorter-purified CD5+ thymic B cells were active. Injection of dendritic cells from spleen or thymus also induced tolerance, but the V beta 6 cells were anergized rather than deleted. Macrophages from thymus did not induce tolerance. Dendritic cells and thymic B cells were also effective in inducing tolerance even when injected into Mls-, major histocompatibility complex-incompatible, I-E- mice, but only thymic B cells depleted V beta 6-expressing T cells. Therefore, different types of bone marrow-derived APC have different capacities for inducing tolerance, and the active cell types (dendritic cells and CD5+ thymic B cells) can act by distinct mechanisms.

Animals↗
PubMed1991

Ontogeny of thymic B cells in normal mice.

Ontogeny of thymic B cells and their surface characteristics were analyzed using monoclonal antibodies (mAbs) against B220 molecules (CD45, CD45R). A small number of B cells were detected in fetal thymus on Gestation Day 14 (approximately 3.5% of the low-density fraction). Similarly, the percentage of B cells in the low-density fraction was 3.2% on Gestation Day 18, and 3.5% on Day 1 after birth. These were the same level as that of adult mice. CD5+ B cells, which form the major population of thymic B cells, were also found in the fetal life (0.5% on Day 14 and 2.2% on Day 16 in the low-density cells). The percentage of CD5+ B cells in B cell-enriched fraction was about 65% on Day 1 after birth, which is the same level as that in adult mice. These results indicate that a small number of B cells or cells in the B-cell lineage are present in the fetal thymus and also suggest the importance of these thymic B cells in the negative selection of T cells during early developmental stages.

Animals↗
PubMed1991

Intracellular calcium of longitudinal muscles isolated from pregnant rat myometrium.

Longitudinal muscle cells were successfully isolated from pregnant rat myometrium (21 days of gestation) with more than a 95% survival rate. The approximate size of relaxed cells was 232.2 +/- 74 microns in length and 16.2 +/- 7.0 microns in width. Using the fluorescent indicator Fura-2, the concentration of intracellular free calcium ([Ca2+]i) in resting state cells was calculated to be 116 +/- 18.5 nM. The isolated cells responded well to K+, acetylcholine and oxytocin in terms of contraction as well as the increase in [Ca2+]i. The increase in [Ca2+]i induced by acetylcholine and K+ appeared to be mainly due to an influx of extracellular Ca2+. On the other hand, the oxytocin-induced increase in [Ca2+]i was mainly due to a release of Ca2+ from intracellular storage sites in the isolated cells. Isolated longitudinal muscle cells can serve as a useful tool in establishing the relationship between [Ca2+]i and regulation of the uterine contraction at the final stage of pregnancy.

Acetylcholine↗
PubMed1991

Characterization of B cells in human thymus.

The surface characteristics of B cells present in the human thymus were investigated. Cytofluorometrical and immunohistological studies, using anti-human IgM or anti-B cell monoclonal antibodies (mAbs; anti-Leu 12Ab, anti-Leu 16Ab, or L26), revealed that a small number of B cells are present in the human thymus. The thymic B cells were detected only in a low-density cell population, whereas in a high-density cell fraction, only T cells were found. In 15 cases, all of which the thymi were histologically normal, the percentages of B cells in the low-density fraction were 0.28% to 50% (6.8% in average), and Leu 1+ (CD5+) B cells in the low-density fraction were 0.1% to 26% (3.5% in average); approximately 50% of the thymic B cells were Leu 1+ B cells. These results indicate that B cells, especially Leu 1 (CD5)+ B cells, are also present in the human thymus, as suggested from our previous reports on mice.

Adolescent↗
PubMed1991

Progressive myoclonus epilepsy: dentato-rubro-pallido-luysian atrophy (DRPLA) in childhood.

A 22-year-old female with progressive myoclonus epilepsy (PME) considered to be due to hereditary dentato-rubro-pallido-luysian atrophy (DRPLA) was reported. Some of her family members showed progressive myoclonus, seizures, dementia, ataxia and choreoathetosis, with variation of onset from childhood to adult life, which suggested that they had been suffering from DRPLA. CT scan and MRI studies, including some on family members, revealed cerebral and cerebellar atrophy accompanied by dilatation of the fourth ventricle, compatible with the findings in DRPLA reported previously. We emphasize that a detailed family history may be essential in dealing with a PME patient and that DRPLA should be considered in the differential diagnosis of the PME syndrome with onset in childhood, in Japan.

Adolescent↗
PubMed1991

An improved ELISA system for the measurement of IgG antibodies against pertussis toxin (PT) and filamentous hemagglutinin (FHA) in human sera.

We have developed a modified assay method for the measurement of antibodies against PT and FHA. Polystyrene balls coated with purified PT and FHA were incubated with standard or test sera, washed, incubated with goat anti-human IgG F(ab')2 conjugated with horseradish peroxidase and then washed again. Peroxidase activity was then measured by color development using o-phenylenediamine. The anti-PT and anti-FHA IgG titers were determined using calibration curves. The assay standard curves for anti-PT and anti-FHA were both linear from 1 to 100 ELISA units per milliliter (EU ml-1), and the assay sensitivity was calculated to be 1 EU ml-1 in both cases. Intra- and inter-assay CVs were both less than 10%. Inter-laboratory assay CVs calculated from the results from four different facilities were 3.3-34.6% (average 14.5%) and 2.1-30.3% (average 13.6%) for anti-PT and anti-FHA IgG, respectively, and the correlation coefficient between the Chinese hamster ovary (CHO) cell assay and the anti-PT PS-ball ELISA assay was 0.959. Using this assay method we obtained in a highly sensitive and reproducible measurement of IgG antibodies against PT and FHA in human sera. This assay should be especially useful for the determination of low concentrations of these antibodies.

Adhesins, Bacterial↗
PubMed1991

[A case of adult-onset tethered cord syndrome accompanied with slowly progressive muscular atrophy in the lower limbs].

A 70-year-old man developed slowly progressive muscular atrophy in the lower limbs from age 28, followed by urinary disturbance from age 40. Neurological examination revealed bilateral severe muscular atrophy in the lower limbs with hypesthesia and hypalgesia, mild muscle wasting of both hands, urinary incontinence, and constipation. A sacral dimple was also recognized. A diagnosis of tethered cord syndrome with thick filum terminale was made by spinal magnetic resonance imaging (MRI). After the operation for untethering, urinary disturbance has been slightly improved. Although the adult-onset tethered cord syndrome with the thick filum terminale was extremely rare, the presence of congenital dermal abnormality and segmental distribution of the muscular involvement is often helpful for the clinical diagnosis of this disease. Spinal MRI is one of the most diagnostic method for this disease.

Aged↗
PubMed1990

Elevated soluble interleukin-2 receptor levels in patients with active multiple sclerosis.

The level of soluble interleukin-2 receptor (sIL-2R) was quantitated with enzyme-linked immunosorbent assay in serum and cerebrospinal fluid obtained from 24 patients with multiple sclerosis and 10 patients with other neurological disorders in whom immunological mechanisms are unlikely to participate. The sIL-2R level in the serum and cerebrospinal fluid of patients with multiple sclerosis in relapse was significantly higher compared with patients with multiple sclerosis in remission and with controls. The sIL-2R level, especially in the cerebrospinal fluid, showed higher sensitivity and specificity than other clinical parameters including the cerebrospinal fluid IgG ratio, peripheral lymphocyte CD4/CD8 ratio, cerebrospinal fluid myelin basic protein and oligoclonal bands. Our data suggest that measurement of the sIL-2R level may be useful in evaluating disease activity in patients with multiple sclerosis.

Adult↗
PubMed1990

Effect of 2,4-dihydro-3H-1,2,4-triazole-3-thiones and thiosemicarbazones on iodide uptake by the mouse thyroid: the relationship between their structure and anti-thyroid activity.

Antithyroid activity of 2,4-dihydro-3H-1,2,4-triazole-3-thiones and thiosemicarbazones was tested by measuring the uptake ratio of thyroid: serum (T/S) of 125I through the mouse thyroid. Substitution with an alkyl group at the 5-position of the triazole nucleus remarkably increased the activity but substitution at the N-2 and/or N-4 positions caused a significant decrease in the activity, indicating the necessity of unsubstituted thioureylene moiety for the antithyroid activity. Thiosemicarbazone derivatives which are an open ring structure of triazoles showed comparable antithyroid activities to those in a ring form, but one thiosemicarbazone showed a much higher toxicity than the corresponding ring form compound. This suggests that the ring structure is not essential for the activity but is necessary to reduce toxic effect. Of fourteen compounds tested, 5-methyl-2,4-dihydro-3H-1,2,4-triazole-3-thione was the most potent antithyroid compound with low toxicity, with a potency tenfold that of propylthiouracil, a drug currently used.

Animals↗
PubMed1990

[Oculopharyngeal muscular dystrophy in a Japanese family].

The first instance of familial oculopharyngeal muscular dystrophy (OPMD) affecting a Japanese family is reported. Three patients (a 62-year-old female, her sisters 66-year-old and 53-year-old) were described with suspicious other 2 cases. A 62-year-old woman (case 1) developed bilateral blepharoptosis at the age of 52. Then she became aware of difficulty in swallowing solid foods, had developed a nasal voice and aspiration of liquids. On admission, neurological examination revealed moderate bilateral blepharoptosis, nasal voice, dysphagia and hyporeflexia of the pharynx. There was mild weakness of the muscles of the temporalis, masseter, face, neck and proximal portions of the upper limbs. The levels of serum creatine phosphokinase, lactic acid and pyruvic acid were normal. Tensilon test was negative. The needle EMG showed a myogenic pattern with no waning phenomenon. Nasopharyngeal fiberscopy, laryngoscopy, esophageal fluoroscopy and hydrodynamic examination showed dyskinesis of the soft palate, retention of saliva in recessus piriformis and streaming into the larynx. Cricopharyngeal myotomy was performed for the purpose of relieving the dysphagia. The muscles were obtained from cricopharyngeus of both sides during surgery, and right deltoid muscle in biopsy. The muscles of sternohyoideus and deltoideus showed myogenic changes, and some fibers with rimmed vacuoles especially in small angulated fibers under the light microscope. Whereas the crycopharyngeus showed dystrophic change, which was apparent in the right side. There were also nemaline rods found in a few fibers undergoing necrosis. ATPase preparations revealed type 1 predominant in cricopharyngeus and type 2 predominant in sternohyoideus. Most atrophic fibers were in type 1 fibers.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗