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Biomedical subjects

T Tamura

Publications and source records attributed to T Tamura.

At least 937 records · Page 52Linked to original sources

[Clinical cytogenetic studies on patients with cleft lip and/or cleft palate--2. Chromosome analysis of twins].

Development of DNA diagnosis on the monocular level for patients with cleft lip and/or palate may be expected in the near future. The necessary condition for this is to confirm the heredity, elucidate the mode of inheritance and decide on the regional mapping etc. The authors tried a chromosome analysis on a pair of monozygotic twins with cleft lip and palate by using high-resolution banding techniques (about 700 bands). However, chromosome aberration was not confirmed. Therefore, the relation between this congenital anomaly and the chromosome aberration could not be confirmed. In this paper the authors discussed about this problem.

Chromosome Aberrations↗

cdc2/pp56-62 are in vitro substrates for the tyrosine kinase encoded by the v-fms oncogene.

In eukaryotic cells, the serine-threonine-specific kinase cdc2 induces entry into mitosis by phosphorylation of several proteins including cyclin (pp62) with which it forms a tight complex. We show here that cdc2 and several phosphoproteins in the range of 56 to 62 kilodaltons (kDa), associated with cdc2, serve as in vitro substrates for the v-fms-specific tyrosine kinase. This is the first demonstration of in vitro phosphorylation of a physiologically relevant substrate through the v-fms specific kinase. In addition, cdc2 phosphorylated the v-fms polypeptides in serine and threonine residues. The biological significance of the mutual phosphorylations is discussed.

CDC2 Protein Kinase↗

[Molecular cloning and expression of Mycobacterium tuberculosis Aoyama B peptide antigen genes in Escherichia coli--a gene encoding 60 kD antigen (AT201) and immunological activity of recombinant peptides (15 and 60 kD)].

To obtain recombinant peptides related to PPDs, we constructed a genomic library from the DNA of Mycobacterium tuberculosis Aoyama B, a standard strain in Japan to manufacture PPDs, using plasmid vectors pUC18 series. Seven clones reacting the anti-PPDs-rabbit-serum on immunoblotting were obtained, and restriction map was analysed. A nucleotide sequence and a putative open reading frame (ORF) of pAT01, encoding 15kD peptide, as well as the mode of expression was reported previously). In this study, nucleotide sequence of 60 kD peptide gene was determined, and the comparative database analysis (GENBANK) revealed a striking level of homology to so called mycobacterial heat shock protein. The expression mode of pAT201 encoding 60 kD, as well as pAT01 encoding 15 kD peptide, indicated that these peptides were not hybrid proteins with the lacZ gene product, but they were consisted of peptides only mycobacterial source. Therefore, 15 kD and 60 kD directly were subjected to immunological studies. The peptides were extracted from E. coli, carrying pAT01 or pAT201, purified through series of DEAE chromatography and followed by Detoxi-Gel to remove LPS. 15 kD peptide behaved almost similar to PPDs both in the DTH skin reaction and the lymphocyte proliferation response on guinea pigs or rats in respect to sensitivity. However, 60 kD was unique in that, and it behaved like a general mitogen. We discussed role of 60 kD peptide, comparing with the common antigen, generally found in most species of bacteria as the heat shock protein.

Antigens, Bacterial↗

[Mental disorders of Japanese people in western Europe].

As the number of Japanese going abroad has increased in recent years, so has there been an increase in the number of Japanese who seek for help at the Consulate of Japan due to problems relating to mental disorders. Three Consulates in Europe (London, Madrid, Paris), that had experience dealing with mental disorder cases, which had been brought for various reasons, were visited in order to investigate the state of the situation among Japanese with mental disorders in Europe. The following findings were obtained: 1. The number of mental disorder cases treated by the Consulates of Japan in Europe from April 1988 to March 1989 was 37 out of the total 147 in the whole world or 25%. 2. Among them were 7 cases in Great Britain (London), 5 cases in Spain (Madrid), and 11 cases in France (Paris), all of which required tremendous effort to resolve. 3. Among possible additional measures that are needed are support by local Japanese Organizations, development of a system of medical care manned by Japanese physicians on a rotation basis, a medical escort system for returning patients to Japan, overseas insurance and telephone counseling as well as measures to prevent manifestation of mental disorders overseas.

Adult↗

[Idiopathic enlargement of the right atrium with persistent superior vena cava].

A 69-year-old male, who had been found (during a routine roentgenogram of the chest at an annual check-up) to have cardiomegaly, had been asymptomatic until 63 years of age, when DOE and swelling of the legs appeared. He visited our hospital because these symptoms has become more severe. Physical examination revealed JVD, third heart sound and a grade 3 holosystolic murmur, hepatomegaly and edema in the lower legs. His ECG showed atrial fibrillation. His chest X-P showed marked cardiomegaly and rt pleural effusion. His echocardiography and MRI revealed a marked enlargement of the right atrium and a slight enlargement of the right ventricle. The latter also showed persistent left superior vena cava. The cardiac catheterization, angiocardiography and intracavitary electrocardiography revealed no organic cardiac disease which induced enlargement of the right atrium. The idiopathic enlargement of the right atrium is a rare disease. Patients suffering from this disease are asymptomatic in most cases. We reported the idiopathic enlargement of the right atrium with persistent left superior vena cava in this paper.

Aged↗

Negative phase II study of 5-fluorouracil with high-dose leucovorin in non-small cell lung cancer.

Fourteen patients with inoperable or recurrent non-small cell lung cancer (NSCLC) were treated with 5-fluorouracil (5-FU) plus high-dose leucovorin (LV). The administration schedule was 2 h infusion of LV at a dose of 500 mg/m2 and 30 min infusion of 5-FU at a dose of 600 mg/m2 given 1 h after the start of the LV infusion. This regimen was followed weekly, six times. No objective (complete or partial) response was seen in any of the patients. Ten patients showed no change and there were four with progressive disease. One patient experienced grade 3 leukopenia after two courses of treatment. Another experienced grade 2 leukopenia. One patient experienced grade 2 vomiting and six, skin pigmentation. Other myelosuppressive effects and non-hematologic toxicities, including diarrhea and mucositis, were mild. It was concluded that the schedule of 5-FU with high-dose LV therapy employed could not be expected to produce a response rate greater than or equal to 20% against NSCLC. 5-FU plus high-dose LV therapy was, therefore, considered to be ineffective against NSCLC with the schedule of administration followed.

Adult↗

[A case of herpes simplex encephalitis with cerebral white matter lesion after acyclovir administration].

Herpes simplex virus (HSV) is regarded as an agent that selectively affects temporal and frontal lobes with necrosis and hemorrhage, and no case of herpes simplex encephalitis (HSE) with white matter lesion in a diffuse fashion has previously been reported. A 2-year-old boy developed high fever, right hemi-convulsions and lethargy. Computed tomography (CT) showed wedge-shaped areas of high density in the left frontal region, whereas, cerebral angiography disclosed no vascular abnormality. T1-weighted magnetic resonance imaging (MRI) demonstrated cortical changes which were similar to those illustrated by CT. However, T2-weighted images depicted further spread high intensities of the lesion. The patient's symptoms spontaneously disappeared before an antiviral drug, acyclovir, was administered. After the significant increase of HSV antibody titers in serum and cerebro-spinal fluid (CSF) established a definite diagnosis, acyclovir was intravenously given at a daily dosage of 30 mg/kg for a period of 6 days in order to prevent the recurrence of HSE. Two months later, T2-weighted MRI visualized a diffuse lesion of increased signal intensities involving the white matter of both hemispheres, while both CSF protein and myelin basic protein were significantly elevated. Despite of these changes of the white matter, our patient developed a few symptoms such as mild speech disturbance, slight weakness of the right upper limb and sialorrhea. Although the mechanism of these changes in the white matter remains obscure, it is postulated that a direct invasion of HSV to the white matter, an immunological disorder following HSV infection and a side effect of acyclovir could have triggered a reversible process of demyelination of the cerebral white matter.

Acyclovir↗

Activity staining of acylphosphatase after gel electrophoresis.

Acylphosphatase is an ubiquitous enzyme found in a variety of mammalian and avian tissues. Two isozymes of different amino acid sequence have been found in human, chicken, pig, and horse. To survey the distribution of the acylphosphatase isozymes among animal species and tissues, we have developed an activity staining procedure for the enzyme after electrophoresis on a polyacrylamide gel. Tissue extracts of pigs were subjected to electrophoresis, then the gel was stained for acylphosphatase activity in a solution containing acetyl phosphate and lead nitrate. Three activity bands were observed: the slowest moving one, which coincided with that of purified testis acylphosphatase, was widely distributed in testis, muscle, brain, heart, spleen, kidney, liver, and erythrocyte; the other two bands, which coincided with monomer and dimer of purified muscle acylphosphatase, were relatively localized in skeletal muscle.

Acid Anhydride Hydrolases↗

Stabilization of the superoxide-generating respiratory burst oxidase of human neutrophil plasma membrane by crosslinking with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide.

The superoxide-generating respiratory burst oxidase (NADPH-oxidase) of neutrophil plasma membranes is known to be highly unstable. In an attempt to stabilize the enzyme, we investigated the effect of crosslinking with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC). The stability of superoxide-generating activity of plasma membrane was significantly enhanced by crosslinking. The half-life (t1/2) of the activity at 37 degrees C in the absence of crosslinker was about 2 min. Crosslinking extended the t1/2 significantly. Crosslinked material exhibited a biphasic loss of activity: about half was lost in each phase with respective t1/2 values of 20 and 240 min. The lifetime of the crosslinked material at 37 degrees C was further extended (about sixfold) with 30% glycerol, and the crosslinked material was completely stable for more than 2 weeks if stored on ice. Crosslinking also stabilized the activity to the effects of high salt and detergent, both of which have inactivating effects on the oxidase. In addition, crosslinking stabilizes not only the Vm but also the Km of the enzyme, which was noted to increase upon storage in the absence of crosslinking. Unlike the native material, the crosslinked oxidase failed to be stimulated (and in fact was inhibited) by phosphatidylserine, recently reported to be an activator of the oxidase (Tamura et al. (1988) J. Biol. Chem. 263, 17,621-17,626). The crosslinked plasma membrane provides a useful stabilized system for kinetic studies. When the activated plasma membrane was treated with EDC, the stabilized oxidase could not be solubilized effectively using detergents, since greater than 95% of the activity remained with the pellet following centrifugation, perhaps due to crosslinking to the cytoskeleton. However, when the activity was first detergent-solubilized, the soluble activity was also stabilized by EDC. This solubilized, crosslinked material may provide useful starting material for subsequent isolation and characterization of a stabilized active NADPH-oxidase.

Carbodiimides↗

Separation of yeast proteasome subunits. Immunoreactivity with antibodies against ATP-dependent protease Ti from Escherichia coli.

On two-dimensional gel electrophoresis, proteasomes (multicatalytic proteinase complexes) from the yeast Saccharomyces cerevisiae were separated into a characteristic set of approximately 20 components with molecular weights of 21,000 to 31,000 and isoelectric points of 3.5 to 7.5. The main components were isolated by reverse-phase high performance liquid chromatography on a TSK gel phenyl-5PW RP column and named YC1 to YC11, in order of their elution. Immuno-blot analysis showed that two components (YC1-alpha and YC1-beta) with molecular weights of 30,800 and 28,300 strongly cross-reacted with antibody against the P-component of ATP-dependent protease Ti from Escherichia coli, but no components were found to react with antibodies against the A-component of protease Ti or another ATP-dependent protease La (the Ion gene product) of Escherichia coli. These results indicate a structural relationship between eukaryotic proteasomes and bacterial ATP-dependent protease Ti.

Adenosine Triphosphatases↗

Dose escalation study of recombinant human granulocyte-colony-stimulating factor (KRN8601) in patients with advanced malignancy.

To evaluate the toxicity and efficacy of recombinant human granulocyte-colony-stimulating factor (rh G-CSF) administered with intensive chemotherapy, 39 patients with advanced pulmonary cancers were enrolled in a dose escalation trial of rh G-CSF. Three days after initiation of chemotherapy rh G-CSF was administered i.v. for 14 consecutive days at five dose levels (50-800 micrograms/m2). Absolute neutrophil counts showed a dose-dependent increase with an increasing dose of rh G-CSF and the durations of neutropenia (less than 1000/mm3) shortened significantly at doses of 200, 400, and 800 micrograms/m2 compared to those at 50 micrograms/m2 (P less than 0.01). The duration of neutropenia was shortened significantly at all five dose levels following treatment with rh G-CSF compared to treatment without rh G-CSF (P less than 0.05). Adverse side effects associated with rh G-CSF administration were fever higher than 38 degrees C (21%), chest pain, and low back pain (13%). No intolerable side effects were experienced. It can be concluded that rh G-CSF is effective in shortening the duration of neutropenia following intensive chemotherapy at a dose level of 100 to 200 micrograms/m2 i.v. a 400-micrograms/m2 dose of rh G-CSF is recommended in patients with prior treatment because of the possibility of a lower bone marrow response.

Adult↗

Okadaic acid and dinophysistoxin-1, non-TPA-type tumor promoters, stimulate prostaglandin E2 production in rat peritoneal macrophages.

Okadaic acid and dinophysistoxin-1 isolated from a black sponge, Halichondria okadai are non-12-O-tetrade-canoylphorbol 13-acetate (non-TPA)-type tumor promoters of mouse skin. Okadaic acid at concentrations of 10-100 ng/ml stimulated prostaglandin E2 production in rat peritoneal macrophages. Dinophysistoxin-1 (35-methylokadaic acid) stimulated prostaglandin E2 production as strong as okadaic acid, but okadaic acid tetramethyl ether, an inactive compound as a tumor promoter, did not. Okadaic acid at 10 ng/ml (12.4 nM) stimulated prostaglandin E2 production as strongly as TPA at 10 ng/ml (16.2 nM) 20 h after incubation. Unlike TPA-type tumor promoters, okadaic acid required a lag phase before stimulation. The duration of this lag phase was dependent on the concentration of okadaic acid. Indomethacin inhibited okadaic acid-induced preostaglandin E2 production in a dose-dependent manner, and its inhibition was more strongly observed in okadaic acid-induced prostaglandin E2 production. Cycloheximide inhibited okadaic acid-induced release of radioactivity from [3H]arachidonic acid-labeled macrophages and prostaglandin E2 production dose dependently, suggesting that protein synthesis is a prerequisite for the stimulation of arachidonic acid metabolism. These results support our idea that tumor promoters, at very low concentrations, are able to stimulate arachidonic acid metabolism in rat peritoneal macrophages.

Animals↗

Light adaptation in cat retinal rods.

It has long been an open question whether individual rod receptors in the mammalian retina show any light adaptation. The prevailing evidence so far has suggested that these cells, unlike those in lower vertebrates, adapt little if at all. The experiments on cat rods reported here, however, indicate that this is not really true. Since the cone system in the cat retina has a fairly high light threshold, the rods also need to adapt so that they do not saturate with light before the cones fully take over vision at higher light intensities. In similar experiments, adaptation was found in rods of other mammalian species, including primates.

Adaptation, Ocular↗

Spontaneous chromosome fragility in band 3q21, 11p11, or 11q13 of cultured bone marrow cells from two patients with hematologic disorders.

Chromatid gaps and breaks clustering to band 3q21, 11p11, or 11q13 were observed prior to chemotherapy in short-term cultured bone marrow cells from two patients with hematologic disorders, one with acute monoblastic leukemia having +8 as the sole karyotypic abnormality and the other with pernicious anemia having no chromosome abnormality. The mitogen-stimulated peripheral blood lymphocytes of both patients, however, yielded a negligible frequency of chromosome aberrations. Because of no notable history of clastogen exposure in these patients, the observed chromosome fragility is most probably spontaneous, which might be correlated with the patients' physiologic condition at examination, i.e., an unusually low level of folic acid or vitamin B12, both being involved in DNA synthesis. Although band 11q13 is known to contain a common fragile site, chromosome fragility in bands 3q21 and 11p11 has not yet been reported in either normal or neoplastic cells. The present findings appear to favor the in vivo expression of chromosome fragility.

Aged↗