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Biomedical subjects

K Shimokata

Publications and source records attributed to K Shimokata.

At least 127 records · Page 7Linked to original sources
PubMed1994

Arginine residues in the extension peptide are required for cleavage of a precursor by mitochondrial processing peptidase. Demonstration using synthetic peptide as a substrate.

Mitochondrial processing peptidase (MPP) specifically recognizes a large variety of mitochondrial precursor proteins and correctly cleaves off the extension peptides. To determine the structure common to all the extension peptides that is required for specific recognition by MPP, we synthesized various oligopeptides of different chain lengths and amino acid sequences, based on the amino acid sequence of the extension peptide of pre-malate dehydrogenase, and determined kinetic parameters of the cleavage reactions. The minimal length of peptides for effective cleavage was 16 amino acid residues consisting of 11 and 5 residues from the cleavage site to the amino- and carboxyl-terminal sides, respectively. Two sets of basic amino acids in the peptide, the distal arginine residue at position -10 and the proximal ones at positions -3 and -2 relative to the cleavage site, were necessary for effective hydrolysis. Of these two, the residue at position -2 was more important for effective cleavage than the one at position -3 and could not be replaced by a lysine residue. The replacement of the distal arginine by lysine had no effect on the cleavage. Our study demonstrates that use of peptides with the proper length is essential for performing kinetic analyses on the cleavage reaction by MPP and that an arginine residue at position -2 to the cleavage site is necessary for the recognition and cleavage of the extension peptide.

Amino Acid Sequence↗
PubMed1994

Expression of fusion regulatory proteins (FRPs) on human peripheral blood monocytes. Induction of homotypic cell aggregation and formation of multinucleated giant cells by anti-FRP-1 monoclonal antibodies.

Fusion regulatory proteins (FRPs) are newly defined cell surface molecules that enhance and/or induce virus-mediated cell fusion. Anti-FRP-1 Abs reacted with all of the established cells derived from humans and monkeys, whereas FRPs were found to be selectively expressed on a fraction of monocytes in human PBMCs. Granulocytes expressed no FRP-1 molecules, but approximately 18% of granulocytes expressed FRP-2 molecules. Alveolar macrophages also expressed FRP-1 molecules. FRP-1 expression was enhanced by culture of monocytes, but CD14 expression was not influenced by cultivation. Anti-FRP-1 Abs induced homotypic cell aggregation and multinucleated giant cell formation of monocytes. Anti-beta 2 integrin Ab blocked anti-FRP-1 Ab-induced cell aggregation, and anti-beta 1 integrin Ab and fibronectin inhibited anti-FRP-1 Ab-induced polykaryocyte formation. There was no competitive binding to monocytes between anti-FRP-1 Ab and anti-beta 1 or anti-beta 2 integrin Ab or fibronectin. Furthermore, there was no enhancement of beta 1 and beta 2 integrin expression by anti-FRP-1 Ab on monocytes. These findings suggest that anti-FRP-1 Ab activated integrin systems, and that the functions of anti-FRP-1 Ab were demonstrated through the activated integrin systems. Furthermore, it is inferred that integrin systems are involved in polykaryocyte formation of monocytes.

Amino Acid Sequence↗
PubMed1994

Continuous infusion versus intermittent short infusion of metoclopramide for cisplatin-induced acute emesis.

Metoclopramide is an active antiemetic against cisplatin-induced acute emesis. However, the optimal administration method (continuous infusion versus intermittent short infusion) for metoclopramide has not yet been clearly defined. We have conducted a randomized crossover study to compare the antiemetic efficacy of continuous infusion of metoclopramide with that of intermittent short infusion of metoclopramide in 54 evaluable patients. Patients were stratified according to sex and were randomized to receive either a continuous-infusion regimen (regimen A) or an intermittent-short infusion regimen (regimen B). Patients were switched to the alternate therapy in the second course. In regimen A, metoclopramide at 3 mg/kg i.v. was given before cisplatin, and then metoclopramide at 4 mg/kg was infused intravenously over 7.5 hours. In regimen B, metoclopramide at 3 mg/kg i.v. was followed by 2 mg/kg i.v. for two doses. Dexamethasone and diphenhydramine were given intravenously in both regimens. There was no significant difference between two regimens in their ability to prevent emesis. Complete protection (no episode of emesis) and major protection (< or = 2 episodes of emesis), respectively, were obtained by 67% (95% confidence interval: 53-79%) and 85% (95% confidence interval: 73-93%) of all patients given regimen A and by 59% (95% confidence interval: 45-72%) and 81% (95% confidence interval: 68-91%) of those given regimen B. The two regimens were also equally effective in controlling nausea. However, male patients showed better control of nausea and vomiting than did female patients, regardless of treatment regimen. Toxicity was mild in both regimens and was well tolerated. Our findings indicate that both continuous-infusion metoclopramide and intermittent-short infusion metoclopramide are effective in controlling cisplatin-induced acute nausea and vomiting.

Acute Disease↗
PubMed1994

Rapid degradation of the heavy chain of class I major histocompatibility complex antigens in the endoplasmic reticulum of human cytomegalovirus-infected cells.

Human cytomegalovirus (HCMV) infection results in a marked reduction in the surface expression of class I major histocompatibility complex antigens on the host cells, which is thought to be one of the means for HCMV to evade the host immune system. To clarify the precise mechanism(s) of this phenomenon, we investigated the fate of the heavy chain of class I major histocompatibility complex antigens in HCMV-infected human embryonic lung fibroblasts (HEL) by pulse-chase analysis and immunocytochemical techniques. In HCMV-infected HEL, the heavy chain was synthesized at an increasing rate. However, instead of being transported to the cell surface through the Golgi apparatus, it was retained in the endoplasmic reticulum (ER) without acquisition of a complex-type N-linked oligosaccharide. In addition, it was rapidly degraded, with a half time of 20 min, and the amount of the heavy chain remaining at the end of 3 h of chase was 10% (or less) of that initially synthesized. ER degradation of host glycoproteins in HCMV-infected HEL was selective for the heavy chain, since the posttranslational processing of the transferrin receptor in these cells was not affected. The heavy chain degradation in infected cells was resistant to inhibitors of a lysosomal proteolytic pathway and to metabolic poisons. These observations suggest the presence of an energy-dependent nonlysosomal proteolytic pathway in the ER.

1-Deoxynojirimycin↗
PubMed1994

Sendai virus pneumonia: evidence for the early recruitment of gamma delta T cells during the disease course.

We previously reported that gamma delta T cells appeared and could play a protective role early in infections with intracellular bacteria such as Listeria monocytogenes, Mycobacterium bovis BCG, and Salmonella choleraesuis. To extend these findings to virus infection, we examined the developmental sequence of gamma delta T cells in bronchoalveolar lavage during the course of Sendai virus infection in C57BL/6 mice. To produce a natural but nonlethal infection course as far as possible, we used a sublethal dose of a wild-type virus which had not been subjected to serial passages in a chicken embryo, hence retaining full virulence for mice. Virus titers in lungs reached a peak on day 6 and then decreased to an undetectable level by day 10. This time course of virus reproduction was immediately and coincidentally followed by the developmental course of gamma delta T cells, in which the cell number peaked on day 7 and then decreased to a marginal level by day 10. On the other hand, the alpha beta T-cell number continued to increase until day 10 and remained at a high level thereafter. The early-appearing gamma delta T cells were CD4-, CD8-, IL-2R alpha- beta+, CD44+, Mel-14-, and LFA-1 alpha/beta+ in phenotype and used V gamma 1/2 and V gamma 4 and V delta 3, V delta 4, V delta 5, and V delta 6. The gamma delta T cells were responding to macrophages from infected mice when the cells were cultured in vitro. Furthermore, the expression of endogenous heat shock protein (hsp) was infection specific, and its level appeared to correlate with the gamma delta T-cell development. These results suggest that the early recruitment of gamma delta T cells, which proliferate in response to endogenous hsp+ cells, is also characteristic of this virus infection, although this view appears to be contradictory to earlier reports.

Animals↗
PubMed1994

Clinical and epidemiologic investigations of nosocomial pulmonary infections caused by methicillin-resistant Staphylococcus aureus.

We evaluated the clinical features of 32 patients with pulmonary infections caused by methicillin-resistant Staphylococcus aureus (MRSA). Most of the patients were elderly, postoperative, and had severe underlying diseases. Chest radiograph typically showed bilateral and multilobar involvement. Empyema was not common and no abscess was identified. Mortality rate was 38 percent. We also performed an epidemiologic study of MRSA infections by chromosomal DNA analysis using pulsed-field gel electrophoresis. Thirty-two strains were classified into 20 different types by chromosomal DNA pattern, and 5 epidemic strains were observed. These strains were considered to be transmitted among patients by hospital personnel.

Cross Infection↗
PubMed1994

Interbronchoscopist variability in the diagnosis of lung cancer by flexible bronchoscopy.

STUDY OBJECTIVE: We evaluated the interbronchoscopist variability in the diagnosis of lung cancer by flexible bronchoscopy. DESIGN AND SETTING: A retrospective review of the bronchoscopic records and clinical charts of patients at a university-affiliated hospital. PATIENTS AND MEASUREMENTS: All records of flexible bronchoscopic procedures performed for the diagnosis of lung cancer were retrospectively reviewed, and procedures that obtained histologic or cytologic evidence of malignancy were considered positive. Rates of positivity were compared according to the following factors: operator, operator experience, bronchoscopic findings, tumor location, and tumor laterality. Factors that affected the positivity rate were evaluated using logistic regression analysis. RESULTS: Of 384 bronchoscopic procedures performed in 353 patients, 275 (72 percent) were positive. The positivity rate differed significantly depending on the operator (p = 0.003) and the bronchoscopic findings (p < 0.001). A difference between operators was noted in technically difficult cases without epithelial or subepithelial findings and when tumors were located in the upper lobe or the superior segment of the lower lobe. The bronchoscopic findings and the operator also emerged as factors significantly affecting the positivity rate in the logistic analysis. CONCLUSIONS: The diagnostic yield of bronchoscopy for lung cancer is dependent on both the type of bronchial lesion present and the bronchoscopist.

Bronchoscopy↗
PubMed1994

[Clinical efficacy of arbekacin on MRSA infections].

Clinical efficacy of arbekacin (ABK) was examined on patients with MRSA infection during hospitalization in Nagoya University Hospital. A total of 15 analysed cases of 5 sepsis, 3 pneumonias, 6 wound infections and one abdominal abscess. ABK was administered intravenously by drip infusion of 200 mg per day divided into 2 doses with or without other antibiotics. Overall clinical efficacy rate was 76.9%, and eradication rate for the MRSA was 54.5%. Adverse effects were noted in 3 cases (one each case of urticaria, disorder of liver function, and renal disorder). The renal disorder was found in the case where ABK was used in combination with vancomycin.

Adolescent↗
PubMed1994

Predominantly tumor-limited expression of a mutant allele in a Japanese family carrying a germline p53 mutation.

Germline mutations of p53 have been implicated as a cause of cancer susceptibility in the Li-Fraumeni syndrome. Since inactivation of p53 has been suggested to play an important causative role in lung cancer, the present study of the prevalence of germline mutations in 148 patients with this neoplasm was performed. None of 138 randomly chosen patients were found to carry such mutations, while a single patient had a nonsense mutation at codon 213 among 10 patients selected for early onset and/or occurrence of multiple primary cancers. In contrast to the previous report of biallelic expression of p53 in a case with a germline missense mutation, preferential expression of the wild-type allele was observed in the heterozygous state in both normal lung and peripheral blood lymphocytes of our case, whereas expression of mutant mRNA was readily detectable in her lung cancer in the absence of the remaining wild-type allele. Interestingly, the family history of the proband showed a mild aggregation of adulthood cancers and a high prevalence of stomach cancer, a rare component in American families affected by the syndrome. These observations suggest the presence of heterogeneity with regard to molecular and clinical features of germline p53 mutations.

Adult↗
PubMed1993

Higher expression of topoisomerase II in lung cancers than normal lung tissues: different expression pattern from topoisomerase I.

To examine the expression of topoisomerase I and topoisomerase II in primary lung cancer specimens at mRNA level, we carried out Northern blot analysis. As for topoisomerase I expression, there was no remarkable difference between lung cancer specimens and non-cancerous lung tissues. On the other hand, we could detect topoisomerase II mRNA in almost all lung cancer specimens, but not in non-cancerous tissues. By Southern blot analysis, we could not detect large deletion nor rearrangement in DNA level. These results suggest that the expression of topoisomerase II is highly increased in lung cancer at mRNA level and drugs against topoisomerase II might be more tumor-specific than those against topoisomerase I.

Adenocarcinoma↗
PubMed1993

Recombinant human stem cell factor mediates chemotaxis of small-cell lung cancer cell lines aberrantly expressing the c-kit protooncogene.

Accumulating evidence suggests that c-kit and its ligand, stem cell factor (SCF), play an important role in the regulation of at least three lineages of stem cell growth and possibly in leukemogenesis, while only limited data are available that suggest possible involvement of c-kit/SCF in the development of human solid tumors such as lung cancer. We have recently reported that c-kit is aberrantly expressed almost exclusively in small-cell lung cancer (SCLC) among various types of solid tumors. The present study revealed that c-kit protein ectopically expressed in SCLC is indistinguishable from that in leukemia cell lines with megakaryocytic characteristics with respect to amount, molecular size, and autophosphorylation status in response to recombinant human SCF. Furthermore, significant chemotactic response as well as moderate in vitro cell growth was induced in SCLC cell lines by the addition of recombinant human SCF, suggesting that c-kit/SCF may play an important biological role in the development of SCLC. Our extensive search for activating mutations naturally occurring in the c-kit gene revealed an amino acid substitution in the transmembrane domain of an SCLC cell line, although the functional consequences of this variant allele are yet to be determined.

Carcinoma, Small Cell↗
PubMed1993

Prognostic significance of p53 mutations and 3p deletions in primary resected non-small cell lung cancer.

We evaluated the prognostic significance of p53 mutations and an allelic loss of chromosome 3p in 71 patients with non-small cell lung cancer who underwent potentially curative resection. p53 mutations were detected in 35 cases (49%), while 3p deletions were observed in 34 of 70 informative cases (49%). The presence of the p53 mutation was associated with a shortened survival in all patients (P = 0.014 by log rank test), including those in early stages of the disease (stage I or II, n = 48) (P = 0.016 by log rank test). Multivariate analysis by the Cox proportional hazards model also revealed that p53 mutation was an independent yet unfavorable prognostic factor (P = 0.013). Patients with 3p deletion tended to have a poorer prognosis, but not to a statistically significant extent.

Aged↗
PubMed1993

Down-regulation of the surface expression of class I MHC antigens by human cytomegalovirus.

Class I major histocompatibility complex (MHC) antigens of higher eukaryotes play a crucial role in the recognition of human cytomegalovirus (HCMV)-infected cells by cytotoxic T lymphocytes. In the present study, we have demonstrated that HCMV infection resulted in a marked reduction in the surface expression of class I MHC antigens on human embryonic lung fibroblasts (HEL). Even when HCMV-infected HEL were cultured in the presence of 9-(1,3-dihydroxy-2-propoxymethyl)-guanine (DHPG), the reduction was observed to the same extent, indicating that HCMV DNA synthesis was not required for this phenomenon. However, immunoprecipitation studies have shown that there was no significant reduction in the synthesis of either the heavy chain or the light chain of class I MHC antigens after HCMV infection. In addition, Western blotting studies have revealed that the total amount of the antigens was almost unaltered after HCMV infection. These results suggest that the reduction in the cell surface expression of class I MHC antigens is due to some defect occurring post-translationally, most likely at the level of the correct complex formation and/or the intracellular transport of class I MHC antigens.

Blotting, Western↗