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Biomedical subjects

K Kitamura

Publications and source records attributed to K Kitamura.

At least 739 records · Page 41Linked to original sources
PubMed1992

Cytogenetic analysis of bone marrow from patients with primary myelodysplastic syndrome.

Of 34 patients with primary myelodysplastic syndrome (MDS), 26 (76.5%) were found to have chromosome defects using an improved bone marrow culture method and high-resolution G-banding technique induced by actinomycin D. The frequency of abnormalities varied among the subtypes: 1/2 in refractory anaemia with ringed sideroblasts; 18/24 in refractory anaemia; 5/6 in refractory anaemia with excess of blasts (RAEB); and 2/2 in refractory anaemia with excess of blasts in transformation. The most frequent abnormalities, either single, double or complex defects, were -5/5q-, -7, +8 and +21; 16q-/16p-, +19 and -X were also common. The percentage of aneuploid cells, in particular hypodiploid cells, was increased. The abnormalities were detected more frequently in complex aberrations associated with RAEB and RAEB in transformation. The presence of -5/5q- as a sole aberration was associated with longer mean survival time (greater than 18 months) but multiple (more than two) chromosomal abnormalities were associated with a poorer prognosis and a mean survival time of only 7.5 months. Chromosome follow-up studies indicated that patients with -7, +8, +21, -X and complex defects, increased hypodiploid cells and karyotpic evolution were likely to have a high risk of transformation to leukaemia or to a more severe subtype of MDS with a short overall mean survival time. These defects, mostly of the deleted type, are assumed to play a specific role in the pathogenesis of myelodysplasia. Repeated chromosomal analyses during the clinical course convey more accurate prognostic criteria for patients.

Adolescent↗
PubMed1992

Molecular design of potent inhibitor specific for cathepsin B based on the tertiary structure prediction.

To design a potent inhibitor specific for cathepsin B (rat liver), the tertiary structure was predicted based on the crystal structure of the papain complexed with (+)-(2S,3S)-3-(1-[N-(3-methylbutyl)amino]leucylcarbonyl)oxirane-2- carbolylic acid (E-64-c), a thiol protease inhibitor. Taking advantage of the structural characteristics of the predicted active site, seventeen inhibitors were chemically synthesized by molecular modeling, and one of them, N-(L-3-trans-propylcarbamoyloxirane-2-carbonyl)-L-isoleucyl-L-p rol ine (CA-074) was shown to be the first potent inhibitor specific for cathepsin B. The relationship between the structure and inhibitory activity is discussed based on the model structure of the cathepsin B-inhibitor complex.

Amino Acid Sequence↗
PubMed1992

Monoclonal antibody-drug conjugate therapy for the patients with colorectal cancer.

Monoclonal antibody drug conjugate A7 was prepared from a mouse splenocyte immunized against human colon cancer. A7 reacted with 80 percent of colorectal cancer and pancreatic cancer. A7 was bound covalently to neocarzinostatin (NCS) to form A7-NCS. A7-NCS had strong cytotoxic activity in vivo and in vitro study. A total of 77 patients with colorectal cancer, including the patients with liver, lung and peritoneal metastasis, were treated with A7-NCS. There were some tumor reduction of liver metastasis on CT scan and pain relief. Follow up study of colorectal cancer patients treated with monoclonal antibody drug conjugate A7-NCS was carried out, with comparing to those treated conventional chemotherapy. Survival rate of the patients with postoperative liver metastasis treated with A7-NCS was slightly higher than that of the patients treated with conventional intraarterial infusion chemotherapy. There was no difference between the group treated with A7-NCS and that treated with conventional chemotherapy in the overall postoperative survival. Patients given a higher dose of the conjugate had a higher survival rate. There were no serious adverse effects in the patients given A7-NCS. Human anti-mouse antibody (HAMA) was detected in all A7-NCS treated patients.

Antibodies, Monoclonal↗
PubMed1992

Ultrastructural findings in the inner ear of Jackson shaker mice.

The ultrastructural characteristics of the inner ear of Jackson shaker mice were analyzed. We used 12 Jackson shaker mutants (js/js) with ages ranging from 10 to 47 days and 10 heterozygotes of the Jackson shaker (js/+) with ages ranging from 10 to 30 days. The most striking findings observed were incomplete differentiation of the stereocilia of the outer hair cells and the maculae, although outer and macular hair cell cytoplasm, including the nerve terminals, became fully developed. Most outer hair cells did not show regular W-shaped configuration of the stereocilia throughout the entire turns of the cochlea except for a few hair cells. In many hair cells of the utricular and saccular maculae, the classical pipe organ configuration of the stereocilia was not observed. The Jackson shaker mice have been reported to have a gene abnormality on chromosome 11, and its gene locus was close to that of our new-mutant mice which showed deranged stereocilia of the outer and macular hair cells. Therefore, future studies can provide additional information on the cytodifferentiation of the stereocilia as a function of the gene on chromosome 11.

Animals↗
PubMed1992

Hyperthermo-chemo-radiotherapy as a definitive treatment for patients with early esophageal carcinoma.

Ten patients with early stage esophageal carcinoma were treated with hyperthermo-chemo-radiotherapy (HCR) without surgery. The reasons for the inoperability of these patients included medically inoperable unresectable cancers, advanced age, and/or refusal to undergo surgery. The diagnosis of early esophageal carcinoma was determined by esophagograms, endoscopy, and ultrasonography. Squamous cell carcinoma was histopathologically confirmed in each case. Each patient underwent four to nine sessions of hyperthermic treatment combined with external irradiation and chemotherapy using bleomycin; eight of these patients received additional radiation, and two terminated treatment after the HCR therapy. The tumors in all patients showed either a complete response (CR) or a partial response (PR) after HCR therapy; in two patients viable cancer cells remained, but later disappeared after additional radiation. Five patients experienced no local recurrence for 12 to 70 months and are now alive and doing well, three died of other medical conditions without any evidence of esophageal cancer, and two died of recurrent esophageal cancer 20 to 27 months after initial admission. All ten patients tolerated the HCR well without any systemic side effects. However, in two patients, esophageal erosion was recognized endoscopically. HCR therapy therefore deserves serious consideration when treating patients with small malignant lesions of the esophagus who, for various reasons, are unable to undergo surgery.

Aged↗
PubMed1992

Platelet neuropeptide Y in spontaneously hypertensive rats.

OBJECTIVE: To investigate the pathological role of platelet neuropeptide Y (NPY) in genetically hypertensive rats, we measured the platelet content and plasma concentration of immunoreactive (ir)-NPY in hypertensive and normotensive rats and examined the aggregating ability of rat platelets and the NPY releasing reaction in each of these rat types. In addition, we purified platelet NPY and determined its amino acid sequence. DESIGN AND METHODS: To characterize immunoreactive NPY in rat platelets, rat platelet NPY was purified to homogeneity and the purified peptide was analysed by gas-phase sequencer. Platelet content and plasma concentration of NPY was measured by a sensitive radioimmunoassay for NPY. Aggregating ability was examined by a turbidimetric method; aggregation was recorded for 5 min and the maximum aggregation was read. RESULTS: Rat platelet NPY was purified and the amino acid sequence was determined to be YPSKPDNPGEDAPAEDMARYYSALRHYINLITRQRY. The platelet content of ir-NPY in 5-, 10-, and 15-week-old spontaneously hypertensive rats (SHR) was higher than that in Wistar-Kyoto (WKY) rats of the same age. The platelet content of ir-NPY in 10-week-old stroke prone-SHR was also higher than that in 10-week-old WKY rats. No differences were observed between any of the pairs in any WKY rats, SHR or stroke-prone SHR group with regard to the plasma concentration of ir-NPY. Ir-NPY was not released from rat platelets when adenosine diphosphate was used for aggregation. However, NPY was released from the platelets when they were aggregated by collagen and, furthermore, in this case the amount of NPY released from platelets was greater in SHR than in WKY rats. CONCLUSION: That the platelet content of NPY in SHR (and stroke-prone SHR) was higher than that in WKY rats seems to be an important genetic characteristic of SHR. As NPY is a potent vasoconstrictor, it may be involved in the progression of vascular lesions.

Amino Acid Sequence↗
PubMed1992

[A case of verrucous carcinoma showing a good partial response by C.P.E. (CDDP, PEP, etoposide) chemotherapy].

A 60-year-old woman was admitted to our hospital with a complaint of rough feeling on the oral mucosa and diagnosed as verrucous carcinoma with histopathological examination. She was treated with CPE chemotherapy, and showed a good response and improvement of clinical symptoms. Toxicities were leukopenia, alopecia and anorexia. However, these were slight side effects. The patient is currently healthy with no recurrence after two years and 3 months. CPE chemotherapy is considered to be effective for a patient with verrucous carcinoma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

[Mode of origin of esophageal squamous cell carcinoma--serial histopathologic and immunohistochemical studies].

I. Serial histopathologic study of esophageal squamous cell carcinoma. A review of 335 cases of squamous cell carcinoma disclosed 55 cases (16.4%) with glandular components in addition to the ordinary component of squamous cell carcinoma, suggesting that this type of esophageal tumor had originated not only from the covering squamous epithelium but from esophageal gland or ductal epithelium. Intra-epithelial carcinoma concomitant with squamous cell carcinoma was seen in 95 cases (28.4%). The incidences of coexistence in such lesion were higher in the groups of early stage esophageal cancer. These observations support the concept of field carcinogenesis of esophageal cancer. II. Histopathologic study of squamous epithelial dysplasia. Among 91 cases without preoperative treatment, there were 40 dysplastic lesions in 23 cases (25.3%). The continuity of dysplasia to the carcinoma was 48.3% and it was often encountered in severe dysplasia rather than in moderate or mild dysplasia, suggesting some relationship between the severity of dysplasia and carcinoma. III. Immunohistochemical study of EGF and c-myc. Among 27 cases, EGF was positive in 10 (37.0%). c-myc was positive in 18 (66.7%) not only cancer but normal epithelium suggesting that some change of products of oncogene occurred also in the normal epithelium of the patients of esophageal cancer.

Carcinoma, Squamous Cell↗
PubMed1992

Rapid induction of atherosclerosis in rabbits.

Japanese white rabbits fed a restricted amount (100 g/head/day) of an atherogenic diet (AD) containing 0.2% cholesterol and 6% peanut oil showed mild and persistent hypercholesterolemia (338 +/- 79 mg/dl). They developed atherosclerotic lesions 4 weeks after deendothelialization of aorta carried out at the 4th week of AD-feeding. This rabbit model of atherosclerosis has such advantages as being able to be produced in a short period and having similar biochemical and pathological characteristics with those in human atherosclerosis.

Animals↗
PubMed1992

[Treatment of pericardial cyst under thoracoscopy].

Thoracoscopic therapy was carried out on two cases of pericardial cyst. The first patient was a 24-year-old male. An abnormal shadow on a chest X-ray was pointed out at a regular checkup. Thoracoscopy was carried out under the local anesthesia and a thin-walled cyst was discovered. The cyst was punctured and serous fluid was aspirated. Then, several biopsy specimens were obtained from the cyst wall, a pathological diagnosis of the cyst was made as a pericardial cyst. One year after the thoracoscopy, no abnormal shadow is observed on chest X-ray. The second patient was a 26-year-old male. It was also discovered that he had an abnormal shadow on a chest X-ray at a regular medical checkup. Since a solid mass couldn't be completely denied, thoracoscopy was carried out in preparing for thoracotomy under the general anesthesia. The cyst observed between SVC and the azygos vein, and serous fluid was aspirated form the cyst. Following this, the cyst wall was biopsied and opened. Since no cases of malignant pericardial cysts have been reported, an operation is not usually required for these patients. We suggest that thoracoscopy is very useful tool for the final diagnosis and therapy of pericardial cyst because this method is easily carried out under local anesthesia.

Adult↗
PubMed1992

Lack of association of Ca(2+)-calmodulin with the beta gamma-subunits of the photo-receptor G protein (transducin).

We previously reported that the beta gamma-subunit of transducin (T beta gamma) is composed of two components, T beta gamma-1 and T beta gamma-2 with distinctive gamma-subunits, T gamma-1 and T gamma-2, respectively. T beta gamma-2 enhances GTP binding to the alpha-subunit of transducin (T alpha) in the presence of a photobleaching intermediate of rhodopsin, while T beta gamma-1 is an inactive component with little enhancement ability (Fukada, Y., Ohguro, H., Saito, T., Yoshizawa, T., and Akino, T. (1989) J. Biol. Chem. 264: 5937-5943). To further elucidate the functional differences between T beta gamma-1 and T beta gamma-2, we examined the association of T beta gamma s with Ca(2+)-calmodulin, and the effect of Ca2+ on binding of GTP to T alpha in the presence of either T beta gamma-1 or T beta gamma-2. Ca2+ had no effect on the GTP binding activity of transducin and T beta gamma s could not associate with Ca(2+)-calmodulin, indicating that the relationship of T beta gamma with Ca(2+)-calmodulin of is different from that of the brain G protein.

Animals↗
PubMed1991

Proline residues responsible for thermostability occur with high frequency in the loop regions of an extremely thermostable oligo-1,6-glucosidase from Bacillus thermoglucosidasius KP1006.

The gene encoding for an extremely thermostable oligo-1,6-glucosidase from Bacillus thermoglucosidasius KP1006 (DSM2542, obligate thermophile) was sequenced. The amino acid sequence deduced from the nucleotide sequence of the gene (1686 base pairs) corresponded to a protein of 562 amino acid residues with a Mr of 66,502. Its predicted amino acid composition, Mr, and N-terminal sequence of 12 residues were consistent with those determined for B. thermoglucosidasius oligo-1,6-glucosidase. The deduced sequence of the enzyme was 72% homologous to that of a thermolabile oligo-1,6-glucosidase (558 residues) from Bacillus cereus ATCC7064 (mesophile). B. cereus oligo-1,6-glucosidase contained 19 prolines. Eighteen of these were conserved at the equivalent positions of B. thermoglucosidasius oligo-1,6-glucosidase. This enzyme contained 14 extra prolines besides the conservative prolines. The majority of extra prolines was replaced by polar or charged residues (Glu, Thr, or Lys) in B. cereus oligo-1,6-glucosidase. The extra prolines were responsible for the difference in thermostability between these two enzymes. We suggested that 11 of the extra prolines in B. thermoglucosidasius oligo-1,6-glucosidase occur in beta-turns or in coils within the loops binding adjacent secondary structures.

Amino Acid Sequence↗
PubMed1991

Inhibition by lipoxygenase-3 of n-hexanal generation in soybeans.

Soybean seeds contain three lipoxygenase isozymes. The functions of these lipoxygenase isozymes in n-hexanal generation were investigated by using mutant lines which lack two or three isozymes. In the presence of linoleic acid, the level of n-hexanal produced was highest in the lipoxygenase-1, -3 double deficient line, followed by the lipoxygenase-2, -3 double deficient, wild type, and lipoxygenase-1, -2, -3 triple deficient lines in that order, and lowest in the lipoxygenase-1, -2 double deficient line. This suggests that lipoxygenase-3 itself cannot produce the n-hexanal precursor and inhibits the n-hexanal generation through other pathways.

Aldehydes↗
PubMed1991

The novel gene trs1 encodes an essential protein for the transition from mitotic cell cycle to resting state in Schizosaccharomyces pombe.

A novel gene trs1 in the fission yeast Schizosaccharomyces pombe has been genetically defined. The trs1 mutant showed several intriguing phenotypes. Cells were sensitive to starvation and rapidly lost viability in the stationary phase; cells in the stationary phase were sensitive to heat shock. Some heat-shock proteins were not induced and the heat-shock response in log-phase cells was defective. These mutant phenotypes strongly suggest a vital function of the trs1 gene product for transition from the G1 to G0 phase on starvation and for the normal heat-shock response.

Cell Cycle↗
PubMed1991

Overproduction, purification and crystallization of Bacillus cereus oligo-1,6-glucosidase.

The gene coding for oligo-1,6-glucosidase from Bacillus cereus ATCC7064 has been overexpressed in Escherichia coli MV1184 cells under the control of the lac promoter in the genetically engineered plasmid pBCE4-2. Oligo-1,6-glucosidase was purified in large quantities and was crystallized at 25 degrees C by using a hanging drop vapor diffusion method with 53% saturated ammonium sulfate. The crystals have the shape of hexagonal bipyramids and belong to the space group P6(2) or P6(4) with lattice constants of a = b = 106.1 A, c = 120.0 A and gamma = 120 degrees.

Bacillus cereus↗