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Biomedical subjects

K Kishimoto

Publications and source records attributed to K Kishimoto.

At least 19 recordsLinked to original sources

The effects of new platelet inhibitory drug E-5510 on platelet deposition on aortic bifurcation grafts: assessment by indium-111-oxime labeled platelet imaging.

The effects of a recently synthesized anti-platelet aggregation drug (E-5510) on platelet deposition in a knitted Dacron aortic graft underwent preliminary evaluation by In-111 oxime labeled platelet imaging. Seven patients undergoing aortofemoral bypass using this graft for occlusive disease were randomized into two groups: those receiving E-5510 and those receiving no medication. This agent was administered for 17 days postoperatively, and on the 14th day In-111 platelets were injected and images were acquired at 24, 48, and 72 hours. Platelet deposits in the grafts were assessed by the ratios of graft radioactivity to that of the adjacent native iliac arteries. Platelet deposition at the sites of anastomosis and deposition along the entire graft were normalized by initial deposition at 24 hours, and had significantly decreased at 72 hours in the three treated patients, while the normalized deposition increased progressively over time in the remaining four nonmedicated patients. E-5510 seems to have the potential to inhibit excessive platelet deposition on recently implanted grafts.

Aged

Compensation for D-glutamate auxotrophy of Escherichia coli WM335 by D-amino acid aminotransferase gene and regulation of murI expression.

D-glutamate, an indispensable component of peptidoglycans of bacteria, is provided by glutamate racemase in E. coli cells. Compensation for D-glutamate auxotrophy of E. coli WM335 cells lacking the glutamate racemase gene, murI, with the D-amino acid aminotransferase gene suggests that presence of a threshold concentration for the D-glutamate required by E. coli cells, as well as a regulation system for murI expression.

Alanine Transaminase

[Long-term survival in terms of DNA-RNA contents in breast cancer].

Fifty-nine primary breast cancers were analyzed by flow cytometric cellular DNa-RNA contents stained by acridine orange simultaneous DNA-RNA double staining. Forty-three cases (72.9%) out of 59 had abnormal stemlines (DNA aneuploidy), and 16 normal ones (DNA diploidy). RNA indices widely ranged from 1.41 to 9.02 (2.99). There was no correlation between DNA indices and RNA indices. The patients with DNA diploidy had a better prognosis than those with DNA aneuploidy, but the differences were not significant. The patients with a high RNA index of more than 4.0 had a significantly poorer prognosis than those with an index of less than 4.0. Those results suggest that RNA contents, and DNA contents are independent prognostic factors, and especially RNA contents may be a good prognostic factor in long-term survival in breast cancer.

Breast Neoplasms

Mutation of arginine 98, which serves as a substrate-recognition site of D-amino acid aminotransferase, can be partly compensated for by mutation of tyrosine 88 to an arginyl residue.

D-Amino acid aminotransferase is the only aminotransferase that catalyzes the transamination of D-amino acids. We studied the role of the binding site for the alpha-carboxyl group of substrates, which is presumably crucial for the unique stereospecificity of the enzyme. The site-directed mutagenesis of Arg98, which is the putative carboxyl-binding site, as judged on the basis of X-ray crystallographic studies [Sugio, S., Petsko, G.A., Manning, J.M., Soda, K., and Ringe, D. (1995) Biochemistry 34, 9661-9669], by replacement with methionine and lysine, resulted in decreases in the kmax values and increases in the Kd values for both amino donors and amino acceptors. The introduction of another mutation, that of Tyr88, which is located near Arg98 in the spacial structure, by replacement with arginine, in addition to the above Arg98 mutation, resulted in increases in the kmax values but little change in the Kd values. These results suggest that Arg98 constitutes the carboxyl-binding site for the substrate, efficient catalysis by the enzyme being facilitated upon binding. The mutant enzymes are also relieved from inhibition by high concentrations of alpha-ketoglutarate, which is an inherent character of the wild-type enzyme. Therefore, Arg98 is also responsible for the inhibition by alpha-ketoglutarate.

Arginine

[Idiopathic plasmacytic lymphadenopathy with polyclonal hyperimmunoglobulinemia in a patient who died of progressive peripheral polyneuritis and cerebral dysfunction].

We reported a 59-year-old woman who received a diagnosis of psoriasis vulgaris at the age of 35 and had been under medical treatment. She was admitted to our department on August 16, 1993 because of lymphadenopathy, arthralgia and neuralgia. We observed cervical and axillar lymphadenopathy 1-3 cm in diameter, anemia and leukothrombocytosis. Elevated levels of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and immunoglobulin G (IgG), but not M-protein were observed by immunological analysis of the serum. Bone marrow aspiration biopsy revealed hypercellularity with myeloid hyperplasia and slight increase in plasma cells. Elevated levels of serum interleukin-6 (IL-6) and granulocyte colony-stimulating factor (G-CSF) were detected; IL-6 was 62.1 pg/ml and G-CSF was 66 pg/ml, but IL-1 alpha, IL-1 beta and TNF-alpha were within the normal range. Idiopathic plasmacytic lymphadenopathy (IPL) with polyclonal hyperimmunoglobulinemia was diagnosed by lymph-node biopsy and the patient received following treatment with prednisolone and hydroxyurea. Leukocytes, platelets and skin eruptions increased again when the steroid dose was tapered, so we changed treatments to MP (melphalan, prednisolone) therapy. In addition, various neurological abnormalities such as convulsions, loss of consciousness and peripheral polyneuritis were observed. Despite treatment her condition deteriorated and she finally died. Very few reports show these neurological abnormalities in IPL or Castleman's disease therefore we think this is a very rare case.

Brain Diseases

Effect of ferrous ion on amino acid metabolism in mildiomycin production by Streptoverticillium rimofaciens.

The physiological features of the mildiomycin production by Streptoverticillium rimofaciens were examined in iron-sufficient and -deficient media. Activities of NADP-linked glutamate dehydrogenase (GDH) and aspartate aminotransferase (AAT) were markedly enhanced by the addition of 10 micrograms/ml of ferrous ion into culture. Ammonium nitrogen assimilation increased with the increase in mildiomycin production. These indicate that ferrous ion contributes the supply of amino acids as a precursor of mildiomycin production. In the iron-sufficient medium, glutamate, aspartate, serine and arginine in cells were 2 to 10-fold to those in the iron-deficient medium. The major amino acid excreted from cells was arginine in the iron-sufficient culture, while in the iron-deficient culture, valine. Change in the amino acid profile by addition of ferrous ion was useful for mildiomycin biosynthesis, in which ferrous ion played a leading role in amino acid metabolism.

Alanine Dehydrogenase

Effect of ferrous ion on amino acid metabolism in mildiomycin production by Streptoverticillium rimofaciens

The physiological features of the mildiomycin production by Streptoverticillium rimofaciens were examined in iron-sufficient and -deficient media. Activities of NADP-linked glutamate dehydrogenase (GDH) and aspartate aminotransferase (AAT) were markedly enhanced by the addition of 10 micrograms/ml of ferrous ion into culture. Ammonium nitrogen assimilation increased with the increase in mildiomycin production. These indicate that ferrous ion contributes the supply of amino acids as a precursor of mildiomycin production. In the iron-sufficient medium, glutamate, aspartate, serine and arginine in cells were 2 to 10-fold to those in the iron-deficient medium. The major amino acid excreted from cells was arginine in the iron-sufficient culture, while in the iron-deficient culture, valine. Change in the amino acid profile by addition of ferrous ion was useful for mildiomycin biosynthesis, in which ferrous ion played a leading role in amino acid metabolism.

Journal Article

SFA-2, a novel bZIP transcription factor induced by human T-cell leukemia virus type I, is highly expressed in mature lymphocytes.

A novel cellular gene, SFA-2, was isolated by differential hybridization of a cDNA library, using probes obtained from an adult T-cell leukemia cell line in comparison with normal CD4+ T cells and MOLT-4 cell line. The mRNA of the SFA-2 gene is approximately 0.9-kb in size and encodes a protein of 125 amino acids, containing a basic region-leucine zipper DNA-binding domain. The N-terminal region of SFA-2 is rich in serine and contains a consensus sequence for casein kinase II phosphorylation. The SFA-2 gene was strongly expressed in mature T and B lymphocytes, and was up-regulated after transformation by human T-cell leukemia virus type I. The SFA-2 did not homodimerize efficiently but formed heterodimer preferentially with c-Jun. The SFA-2/c-Jun heterodimer bound preferentially to the AP-1 and CRE sites.

Amino Acid Sequence

Suicide inactivation of porcine leukocyte 12-lipoxygenase associated with its incorporation of 15-hydroperoxy-5,8,11,13-eicosatetraenoic acid derivative.

Two isozymes of arachidonate 12-lipoxygenase, platelet-type and leukocyte-type, which were distinguished by their substrate specificities and primary structures, were investigated with reference to 'suicide' inactivation. Upon reaction with arachidonic acid the leukocyte-type enzyme was inactivated rapidly during the catalysis, whereas the platelet-type enzyme did not show such a rapid inactivation. The two 12-lipoxygenase isozymes were incubated with various hydroperoxy and hydroxy products from arachidonic acid. (15S)-Hydroperoxy-5,8,11,13-eicosatetraenoic acid (15-HPETE) was found to be a unique substrate of the leukocyte-type 12-lipoxygenase as follows. (1) 15-HPETE was an active substrate for porcine leukocyte 12-lipoxygenase, and converted anaerobically to a 14,15-epoxy compound (14,15-leukotriene A4). (2) A rapid inactivation of the enzyme was observed within 2 min upon aerobic and anaerobic incubations with 15-HPETE. (3) 15-HPETE was rapidly incorporated into the enzyme in a nearly equimolar amount under both aerobic and anaerobic conditions. (4) Several findings suggested a covalent binding of 15-HPETE or its derivative to the enzyme. (5) Such a rapid and stoichiometric incorporation of 15-HPETE was not observed with the platelet-type 12-lipoxygenase. On the basis of these findings we presumed that 15-HPETE was transformed to 14,15-leukotriene A4, which was covalently bound to the leukocyte-type 12-lipoxygenase leading to the suicide inactivation of the enzyme.

Animals

Serum levels of soluble interleukin-2 receptor in patients with perennial allergic rhinitis before and after immunotherapy.

BACKGROUND: Interleukin-2 receptor (IL-2R) exists in soluble form in sera, and the rate of release of the soluble form of IL-2R (soluble IL-2R) reflects T cell activation in vivo. Since T lymphocytes play a central role in respiratory allergic disorders, the measurement of serum levels of soluble IL-2R may be useful in analyzing the disease state of allergic disorders. OBJECTIVE: To investigate the serum concentrations of soluble IL-2R in 48 patients with perennial allergic rhinitis and 14 nonatopic healthy controls, with special reference to the possible changes following long-term immunotherapy. METHODS: This retrospective study included 48 patients who had had variable periods of long-term immunotherapy with Dermatophagoides farinae extracts. The duration of immunotherapy ranged from 5 to 15 years. Serum samples were collected twice from each patient, before the initiation of immunotherapy and at the time of clinical assessment of immunotherapy. All the serum samples were simultaneously used for determination of soluble IL-2R concentrations, by the use of an enzyme-linked immunosorbent assay. To serve as controls, 14 nonallergic subjects of the same age range and sex were chosen. RESULTS: Patients with allergic rhinitis before immunotherapy had significantly higher serum levels of soluble IL-2R than nonatopic subjects. Elevated serum levels of soluble IL-2R decreased significantly following immunotherapy and the serum levels of soluble IL-2R in patients with allergic rhinitis after immunotherapy were not statistically different from those of nonatopic subjects. In addition, the percent decrease in serum soluble IL-2R correlated significantly with the duration of immunotherapy. CONCLUSIONS: Hyperactivity of helper T cells of atopic patients is altered after long-term immunotherapy, and such immunoregulatory changes could be theoretically involved in the mechanisms of immunotherapy.

Adolescent

Serum level of interleukin-4 in patients with perennial allergic rhinitis during allergen-specific immunotherapy.

Interleukin-4 (IL-4) may play a central role in the IgE synthesis system, the development of Th-2-like cells, and co-ordination as well as the persistence of airway inflammatory process in allergic disorders. Therefore, IL-4 plays a key role in airway allergic disorders. This study aimed at investigating the serum concentrations of IL-4 in patients with perennial allergic rhinitis, with special reference to the possible changes and the clinical relevance following long-term immunotherapy. The study has demonstrated that the serum level of IL-4 in allergic rhinitis patients before immunotherapy is significantly higher than that in non-atopic individuals. However, the serum IL-4 level in allergic rhinitis patients did not decrease following anti-allergic medications but significantly decreased following immunotherapy. The percentage decrease in IL-4 was correlated significantly with the percentage decrease in specific IgE antibodies following long-term immunotherapy. Immunotherapy also significantly decreased specific IgE anti-bodies, but this reduction in specific IgE antibodies was not significantly correlated with the clinical improvement. In contrast, the percentage decrease in serum IL-4 was significantly correlated with the percentage decrease in symptomatic scores. The authors interpret these data to mean that immunotherapy alters T-cell cytokine profiles in the long-term, and a decline of IL-4 following immunotherapy could modulate not only production of specific IgE antibodies but also inflammatory cellular events, leading to symptomatic relief in allergic rhinitis.

Adolescent

SFA-1, a novel cellular gene induced by human T-cell leukemia virus type 1, is a member of the transmembrane 4 superfamily.

A novel cellular gene termed SFA-1 was isolated by differential hybridization of a cDNA library, using probes obtained from an adult T-cell leukemia cell line in comparison with probes obtained from normal CD4+ T cells and the MOLT-4 cell line. The mRNA of the SFA-1 gene is approximately 1.6 kb in size and encodes a protein of 253 amino acids, containing four putative transmembrane domains, a number of cysteine residues, and one potential N-glycosylation site in a major hydrophilic region between the third and fourth transmembrane domains. Expression of the SFA-1 gene was either absent or present at a low level in lymphoid cells but was up-regulated after transformation by human T-cell leukemia virus type 1 and transactivated by Tax. SFA-1 was broadly expressed in many human cell types and conserved in different species. Computer-aided comparison showed that SFA-1 had significant sequence homology and common structural features with members of the transmembrane 4 superfamily. SFA-1 antigen was detected as a 29-kDa membrane protein by immunoblotting, using anti-SFA-1 monoclonal antibody.

3T3 Cells

Effect of ferrous ion on mildiomycin production by Streptoverticillium rimofaciens.

A specific regulatory effect of ferrous ion on a biosynthesis of mildiomycin by Streptoverticillium rimofaciens was investigated. The minimal concentration of ferrous ion necessary for the maximal production of mildiomycin was about 8 micrograms/ml. The physiological effects of ferrous ion on the mildiomycin production were examined in the media with and without the ferrous ion. Addition of ferrous ion to the culture medium increased both the mildiomycin production (10 times) and an assimilation of ammonium-nitrogen, activities of peptidase and protease.

Antifungal Agents

Effect of phosphate ion on mildiomycin production by Streptoverticillium rimofaciens.

Effect of inorganic phosphate and ammonium nitrogen on mildiomycin production by Streptoverticillium rimofaciens was investigated in culture with and without addition of ferrous ion. In the presence of ferrous ion, the suitable supply of inorganic phosphate increased the intracellular ATP, but that was not observed without ferrous ion addition. The intracellular ATP remarkably affected ammonium nitrogen assimilation and mildiomycin production, and its concentration in the ferrous-sufficient culture was about 2 approximately 3 times higher than that in the ferrous-deficient culture. The low concentration of intracellular ATP in the ferrous-deficient culture resulted in the reduction of ammonium nitrogen assimilation and mildiomycin biosynthesis. This phosphate ion effect on the intracellular ATP concentration was demonstrated only when ferrous ion was added into the medium. These suggest that mildiomycin biosynthesis is regulated through the concentration of intracellular ATP related to the ammonium nitrogen assimilation.

Adenosine Triphosphate

[A case of penile cancer treated with combination of chemotherapy, radiation and radical operation].

A 60-year-old [correction of 68] male was referred to our hospital because of a penile tumor with necrosis. Pathological examination of the penile tumor and superficial inguinal lymph nodes in biopsy revealed well differentiated squamous cell carcinoma (SCC) and the SCC tumor marker was elevated. TNM classification was T2, N2, M0 according to findings obtained by computed tomography (CT) and magnetic resonance imaging (MRI). We diagnosed the tumor inoperable radically and administered 10 mg peplomycin once a week for 10 weeks intravenously. The SCC marker level was not reduced and the tumor was not changed on MRI. Then, we performed combined pirarubicin treatment and radiotherapy. The patient received linac radiotherapy between 40 Gy/4 weeks/20 fractions. Pirarubicin, 10 mg/m2, was administered once a week for 4 weeks during irradiation intravenously. After the combined therapy, the SCC marked level was reduced to the normal range and the tumor was reduced. We performed radical operation. Pathological diagnosis revealed no viable tumor cells. The patient was alive with no evidence of disease a year later. This combined therapy is suggested to be useful.

Antibiotics, Antineoplastic

[Spontaneous rupture of renal parenchyma caused by renal pelvic and ureteral cancer: a case report].

Two cases of spontaneous rupture of the renal parenchyma caused by the renal pelvic and the ureteral cancer are reported. Case 1 was in a 53-year-old male who had left flank pain 2 weeks before admission to the hospital. In retrograde pyelography, the left upper ureter was visualized irregularly, but the left pelvis was not visualized. Computed tomography (CT) and magnetic resonance imaging (MRI) showed perirenal hematoma. Left nephroureterectomy with bladder cuff was performed under diagnosis of left renal pelvic and ureteral cancer. The rupture of the left renal parenchyma with extracapsular hematoma was identified. Pathological diagnosis was transitional cell carcinoma, grade 2 and pT1 of the left renal pelvis and the left ureter. Case 2 was in a 57-year-old male who had left flank pain 2 hours after he had enhanced CT study. MRI showed the left pelvic and the ureteral cancer with perirenal hematoma after 4 days. Left nephrourererctomy and partial cystectomy were performed. The rupture of the renal parenchyma with subcapsular hematoma was identified. Pathological diagnosis was transitional cell carcinoma, grade 2 and pT1 of the left renal pelvis and the left ureter.

Carcinoma, Transitional Cell