Biomedical subjects

Hiroyuki Nakamura

Publications and source records attributed to Hiroyuki Nakamura.

At least 109 records · Page 6Linked to original sources

PubMed2003

Analysis of sepsis in allogeneic bone marrow transplant recipients: a single-center study.

We reviewed the records of 235 consecutive recipients of allogeneic bone marrow transplantation (allo-BMT) at our center between February 1983 and October 2000. Sepsis occurred in 25 patients (10.6%) at a median of 10 days (range, 1-280 days) after BMT. Five of the 25 patients (20%) died of sepsis. Pathogens isolated from blood culture were gram-positive cocci in 19 patients, gram-negative rods in 7, fungi in 2, and others in 1 patient. Two pathogens were detected concomitantly in 4 patients. Univariate analysis revealed that risk factors for sepsis were selective gut decontamination using lomefloxacin hydrochloride and nystatin, an unrelated donor, HLA mismatched BMT, and stomatitis. Multivariate logistic regression analysis revealed that an unrelated donor was the only significant independent risk factor, with a relative risk of 5.432. In 12 of 25 patients with sepsis, the pathogens of sepsis were sensitive to antibiotics used for gut decontamination. Selective gut decontamination significantly increased the incidence of sepsis, especially that with gram-positive cocci, but not the mortality rate of sepsis, compared with total gut decontamination using vancomycin. We also found a significant relationship between pathogens isolated from blood culture and those isolated from surveillance cultures of stool, urine, and gargled water in the period before sepsis occurred. The present study revealed an independent risk factor for sepsis (unrelated donor), the feasibility of selective gut decontamination, and the importance of surveillance culture.

Adolescent↗

PubMed2003

High contribution contrast between the genes of eosinophil peroxidase and IL-4 receptor alpha-chain in Japanese cedar pollinosis.

BACKGROUND: Japanese cedar pollinosis is the most common form of hayfever in Japan in spring and has remarkably increased since 1960. OBJECTIVE: We sought to clarify the candidate genes for cedar pollinosis using a case-control study. METHODS: After diagnosing 351 subjects on the basis of an intradermal test, nasal provocation test, and questionnaire regarding nasal and conjunctival symptoms, we determined the blood-specific IgE values and genotypes of eosinophil peroxidase (EPO) and interleukin-4 receptor alpha-chain (IL4RA) in 145 patients with pollinosis and 206 healthy subjects, including 75 healthy subjects with higher specific IgE values. RESULTS: We found significant differences in the frequencies of Pro358Leu in EPO and of Ile50Val and Glu375Ala in IL4RA between patients and healthy subjects. There was a significantly higher frequency of 358Leu in EPO in patients than in healthy subjects showing a higher specific IgE value. In contrast, we recognized significant changes in the prevalence of Ile50Val and Glu375Ala in IL4RA in healthy subjects with a normal IgE value compared with those in healthy subjects with a higher specific IgE value. The relationship between EPO polymorphisms and the onset of symptoms was exactly opposite that for IL4RA. CONCLUSIONS: These results suggest that Pro358Leu in EPO is strongly involved in the development of cedar pollinosis. Ile50Val and Glu375Ala in IL4RA seem to be related to cedar pollen sensitization. Subjects with Ile50 or Glu375 might develop cedar pollinosis with increased exposure to cedar pollen.

Adult↗

PubMed2003

Selective inhibition of cancer cell invasion by a geranylgeranyltransferase-I inhibitor.

A number of small GTPases are involved in cancer cell proliferation, migration and invasion. They need to be prenylated for full biological functions. We have recently reported that 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, which block the biosynthesis of farnesylpyrophosphate and geranylgeranylpyrophosphate, inhibit in vitro invasion of human pancreatic cancer cells. In the present study, we examined the effects of two selective inhibitors of prenylation, a farnesyltransferase inhibitor (FTI-277) and a geranylgeranyltransferase type I inhibitor (GGTI-298), on in vitro invasion of cancer cells in a modified Boyden chamber assay. The invasion of COLO 320DM human colon cancer cells was inhibited potently by HMG-CoA reductase inhibitor lovastatin and GGTI-298 but weakly by FTI-277. The treatment of cancer cells with GGTI-298 markedly caused RhoA to decrease in the membrane fraction and accumulate in the cytosolic fraction, whereas it had almost no effect on the translocation of Ras. FTI-277 markedly inhibited membrane localization of Ras, but its inhibitory effect on cancer cell invasion occurred only at doses that affected membrane localization of RhoA. FTI-277 and GGTI-298 decreased the growth potential of COLO 320DM cells, but the inhibitory effect of GGTI-298 was rather selective toward invasion in association with changes in cell morphology and RhoA localization. These results suggest that geranylgeranylation of RhoA by geranylgeranyltransferase type I is critical for cancer cell invasion, and inhibition of geranylgeranyltransferase type I activity should offer a novel approach to the treatment of invasion and metastasis of cancer cells resistant to farnesyltransferase inhibitors.

Alkyl and Aryl Transferases↗

PubMed2003

Enhancement of J-ST-segment elevation by the glucose and insulin test in Brugada syndrome.

The effects of glucose and insulin on J-ST-segment elevation were evaluated in seven men (mean age 45 +/- 10 years) with Brugada syndrome. Six patients had been reanimated from VF and one patient had experienced syncope. The effects of intavenous (1) pilsicainide 50 mg, (2) glucose 50 g, and (3) glucose 50 g plus regular insulin 10 IU on the precordial ECG leads were examined. Pilsicainide significantly enhanced J-ST elevation in all patients and induced VF in 1 patient. A significant accentuation of the abnormal J-ST configuration was observed in all patients at a mean of 51 +/- 40 minutes after glucose and insulin infusion. Changes in blood glucose and serum potassium concentration were 111 +/- 158 mg/dL and -0.30 +/- 0.48 mEq/L, respectively. These changes were not directly related to the ECG changes. Glucose infusion without insulin caused a subtle increase in J-ST elevation. In conclusion, the administration of glucose and insulin safely unmasked or accentuation the J-ST-segment elevation in Brugada syndrome. Blood glucose and insulin concentrations may be factors modulating the circadian or day-to-day ECG variations in this syndrome.

Adult↗

PubMed2003

Detection of Helicobacter pylori in nasal and maxillary sinus specimens from patients with chronic sinusitis.

OBJECTIVES: In patients with chronic sinusitis, the colonization of nasal and maxillary sinus tissues by Helicobacter pylori (HP) was investigated using polymerase chain reaction, urease test (CLO test), culture, and immunohistochemical analysis. STUDY DESIGN: A prospective clinical study. METHODS: The subjects were 11 patients aged 20 to 72 years with chronic sinusitis who had undergone sinus surgery under local anesthesia. In 7 of 11 patients, the HP status of the stomach was also studied. Nasal and maxillary sinus tissues were studied using polymerase chain reaction, urease test, culture, and immunohistochemical analysis. Helicobacter pylori infection of nasal and maxillary sinus tissues was defined by at least two positive results of different tests. RESULTS: Three (16%) of 19 nasal and maxillary sinus specimens from two patients were shown to be HP-positive (positive by polymerase chain reaction and immunohistochemical analysis and weakly positive by the CLO test). In one of these two patients, HP infection of the stomach was confirmed. In the other, a positive findings on immunohistochemical analysis suggested HP infection of the stomach. Immunoreactive structures were seen by immunohistochemical analysis in the nasal, maxillary sinus, and gastric specimens of these two patients but were partially degraded. CONCLUSION: Helicobacter pylori may exist in the nasal and maxillary sinus tissue specimens of some patients with chronic sinusitis with gastric HP infection.

Adult↗

PubMed2003

Global changes in Kaposi's sarcoma-associated virus gene expression patterns following expression of a tetracycline-inducible Rta transactivator.

An important step in the herpesvirus life cycle is the switch from latency to lytic reactivation. In order to study the life cycle of Kaposi's sarcoma-associated herpesvirus (KSHV), we developed a gene expression system in KSHV-infected primary effusion lymphoma cells. This system uses Flp-mediated efficient recombination and tetracycline-inducible expression. The Rta transcriptional activator, which acts as a molecular switch for lytic reactivation of KSHV, was efficiently integrated downstream of the Flp recombination target site, and its expression was tightly controlled by tetracycline. Like stimulation with tetradecanoyl phorbol acetate (TPA), the ectopic expression of Rta efficiently induced a complete cycle of viral replication, including a well-ordered program of KSHV gene expression and production of infectious viral progeny. A striking feature of Rta-mediated lytic gene expression was that Rta induced KSHV gene expression in a more powerful and efficient manner than TPA stimulation, indicating that Rta plays a central, leading role in KSHV lytic gene expression. Thus, our streamlined gene expression system provides a novel means not only to study the effects of viral gene products on overall KSHV gene expression and replication, but also to understand the natural viral reactivation process.

Base Sequence↗

PubMed2003

Poly(ADP-ribose) polymerase 1 and Ste20-like kinase hKFC act as transcriptional repressors for gamma-2 herpesvirus lytic replication.

The replication and transcription activator (RTA) of gamma-2 herpesvirus is sufficient to drive the entire virus lytic cycle. Hence, the control of RTA activity should play an important role in the maintenance of viral latency. Here, we demonstrate that cellular poly(ADP-ribose) polymerase 1 (PARP-1) and Ste20-like kinase hKFC interact with the serine/threonine-rich region of gamma-2 herpesvirus RTA and that these interactions efficiently transfer poly(ADP-ribose) and phosphate units to RTA. Consequently, these modifications strongly repressed RTA-mediated transcriptional activation by inhibiting its recruitment onto the promoters of virus lytic genes. Conversely, the genetic ablation of PARP-1 and hKFC interaction or the knockout of the PARP-1 gene and activity considerably enhanced gamma-2 herpesvirus lytic replication. Thus, this is the first demonstration that cellular PARP-1 and hKFC act as molecular sensors to regulate RTA activity and thereby, herpesvirus latency.

Cell Line↗

PubMed2003

Principal role of TRAP/mediator and SWI/SNF complexes in Kaposi's sarcoma-associated herpesvirus RTA-mediated lytic reactivation.

An important step in the herpesvirus life cycle is the switch from latency to lytic reactivation. The RTA transcription activator of Kaposi's sarcoma-associated herpesvirus (KSHV) acts as a molecular switch for lytic reactivation. Here we demonstrate that KSHV RTA recruits CBP, the SWI/SNF chromatin remodeling complex, and the TRAP/Mediator coactivator into viral promoters through interactions with a short acidic sequence in the carboxyl region and that this recruitment is essential for RTA-dependent viral gene expression. The Brg1 subunit of SWI/SNF and the TRAP230 subunit of TRAP/Mediator were shown to interact directly with RTA. Consequently, genetic ablation of these interactions abolished KSHV lytic replication. These results demonstrate that the recruitment of CBP, SWI/SNF, and TRAP/Mediator complexes by RTA is the principal mechanism to direct well-controlled viral gene expression and thereby viral lytic reactivation.

Amino Acid Sequence↗

PubMed2003

Enhancement of a sense of coherence and natural killer cell activity which occurred in subjects who improved their exercise habits through health education in the workplace.

We have previously demonstrated that a sense of coherence (SOC), a candidate for a mediating stress factor, is involved in natural killer cell activity (NKCA) reduced in smokers, whereas the relationship among exercise, NKCA and SOC is unclear. To clarify the effects of exercise on SOC and NKCA, we examined the changes in SOC and NKCA before and after health education to encourage exercise. Of one-hundred and one male office workers who received the health education for one year, 27 improved, 65 were unchanged and 9 had deteriorated exercise habits. The repeated measures analysis of variance showed that SOC in workers with improvement in the exercise habit were increased more significantly by the health education than those in workers without improvement (p<0.05). Although the change in NKCA produced by health education was recognized to be significantly different in those who had never smoked from that in current smokers (p<0.05), multiple regression analysis demonstrated that improvement in health practice significantly contributed to increases in both SOC (p<0.01) and NKCA (p<0.05) in never smokers, independently of other psychological factors. These results suggest that subjects with improvement in exercise enhance NKCA through increased SOC in never smokers.

Adult↗

PubMed2003

Chest CT findings and clinical features in mild Legionella pneumonia.

OBJECTIVE: To evaluate mild Legionella pneumonia (LP) by chest CT, and clinical features. PATIENTS: In June 2000, an outbreak of LP occurred in Japan. Eight patients with mild LP (seven men, one woman; mean age 55.9 years) had fevers of more than 38 degrees C, but respiratory symptoms were observed only in four. Chest CT was performed before starting an appropriate treatment. MEASUREMENT: CT images were assessed by the distribution of ground-glass opacity (GGO), consolidation, and the existence of pleural effusion. RESULTS: Chest CT findings: multiple segments were affected in all of the patients, (pleural effusion in three, peripheral lung consolidation in seven, and GGO in seven). GGO was located around the consolidation in six patients. CONCLUSION: Mild LP may present as fever without respiratory symptoms. Chest CT findings of mild LP are bilateral, multiple affected segments and peripheral lung consolidation with GGO.

Adult↗

PubMed2003

A large outbreak of Legionnaires' disease due to an inadequate circulating and filtration system for bath water--epidemiologic manifestations.

OBJECTIVE: To study the epidemiologic manifestations of a large outbreak of Legionnaires' disease due to an inadequate circulating and filtration system for bath water. PATIENTS: In June 2000 at Ishioka City, Ibaraki Prefecture, a large outbreak of Legionnaire's disease occurred, as a result of an inadequate circulating and filtration system for communal bath water. This outbreak was the worst ever experienced in Japan, involving a total of 34 patients (20 confirmed, 14 probable), 3 of whom died. MEASUREMENTS AND RESULTS: Legionella pneumophila serogroup 1 was isolated from sputum culture in two patients. Bacteriological culture of the public bath water subsequently yielded large numbers of Legionella species. Cleavage of genomic DNA showed that restriction fragment patterns coming from clinical and environmental isolates of L. pneumophila serogroup 1 were closely related, focusing the inquiry to a public bathhouse where a circulating filtration system was suspected as the source of infection. CONCLUSIONS: It was later concluded that the circulating filtration system adopted for bath water was marred by a serious design flaw that subsequently caused the mass outbreak. Specifically, a line of the bath water was being returned to the bath without undergoing heat exchange or sterilization by chlorine; and the Legionella species that had proliferated in the filter and the bright stone filtration unit were allowed to return to the bath, eventually culminating in a mass infection.

Adult↗

PubMed2003

Synthesis of chemotactic peptide analogs with a photoaffinity cross-linker as new probes for analysis of receptor-ligand interaction.

Formylpeptide receptors are well-characterized receptors which participate in host defense responses of neutrophils. We designed and synthesized chemotactic peptide analog with p-benzoylphenylalanine (Bpa) and biotin to probe structural and mechanistic aspects of peptide-receptor interaction. These peptides possess biological activities which were dependent upon spacer residue length of and Bpa position. The covalent photoaffinity label was detected by Streptavidine-blot, which was inhibited by the parent peptide.

Biotin↗

PubMed2003

Cyclic phosphatidic acid inhibits RhoA-mediated autophosphorylation of FAK at Tyr-397 and subsequent tumor-cell invasion.

We demonstrated previously that rat ascites hepatoma MM1 cells require both lysophosphatidic acid (LPA) and fibronectin (FN) for phagokinetic motility and transcellular migration and that these events are regulated through the RhoA-ROCK pathway and tyrosine phosphorylation of proteins including focal adhesion kinase (FAK). Moreover, we reported that palmitoyl-cyclic phosphatidic acid (Pal-cPA), a structural analogue of LPA, inhibits LPA-induced migration of MM1 cells and experimental metastasis of B16 murine melanoma cells. However, the molecular mechanisms of action of Pal-cPA remains to be clarified. To examine this, total cellular lysates after stimulation with LPA or FN were subjected to time-course immunoblot analysis with anti-phophotyrosine and anti-pY397-FAK antibodies. Tyrosine-phosphorylation of FAK especially at Tyr-397 was obviously persistent after stimulation with LPA + FN compared to after stimulation with LPA alone. This persistent phosphorylation was necessary for MM1 cell migration and inhibited by Pal-cPA as by C3 exoenzyme Rho inhibitor. RhoA activity (GTP-bound RhoA) was also measured by the pull down assay using the Rho binding domain of Rhotekin. LPA-induced RhoA-activation of MM1 cells was completely inhibited by Pal-cPA. Moreover, we demonstrated that autophosphorylation of FAK at Tyr-397, downstream of RhoA, contributed to formation of focal adhesions and was critical in LPA-induced MM1 cell migration by developing autophosphorylation-deficient (Y397F) FAK-transfectants. Collectively, Pal-cPA hampered LPA-induced morphological changes and transcellular migration of MM1 cells through downregulating active RhoA and inhibiting its downstream events including autophosphorylation of FAK. Pal-cPA also inhibited endogenous (LPA-independent) activation of RhoA in human fibrosarcoma HT-1080 cells. Pal-cPA may potentially provide a new therapy for the treatment of cancer invasion and metastasis.

Animals↗

PubMed2003

[A major outbreak of Legionnaire's disease due to a public bathhouse: clinical examination].

The largest epidemic outbreak of legionnaires' disease occurred in Japan, where there were 45 cases, including three deaths. There was a high degree of homology at the genetic level between Legionella pneumophila sero-group 1 isolated from two patients and water samples collected from a public bath, and this highlighted the public bath visited by the patients as the source of the infection. We report our clinical observations of 34 cases with a pneumonia type (20 definite and 14 probable) of the 42 cases for whom a diagnosis was made and follow-up care was subsequently provided at our hospital or hospital-affiliated facilities, out of the initial total of 45 cases. Twenty-one cases had underlying diseases, but the disease was mild in all patients. Three cases showed different neuropsychiatric symptoms such as reduced capacity for memorization, somnolence or delirium. Diarrhea was found in three cases, and relative bradycardia in ten. Clinical laboratory test results indicated that a severe inflammatory reaction, renal or hepatic dysfunction, an electrolyte abnormality and abnormal urinalysis were common in the 34 cases. Chest radiography showed a shadow suggestive of infection of the pulmonary parenchyma with multilobar involvement in most cases and pleural effusion in nine cases.

Baths↗

PubMed2003

[Specific notch in early expiration region of a flow-volume curve in a case of Mounier-Kuhn syndrome].

A 75-year-old man presented at our hospital for evaluation of a chronic cough and sputa. Radiographic examination showed enlargement of the trachea and main bronchi. On chest radiography, the transverse diameter of the trachea was 39 mm at the level of the third thoracic spine. On bronchoscopy, the trachea and main bronchi were dilated on inspiration and were completely collapsed on expiration. A 3-D CT examination showed the trachea and main bronchi dilated, and the cartilage of the trachea and bronchi distorted. In pulmonary function testing, this disorder is characterized by the appearance of a specific notch in the early phase of expiration on the flow-volume curve.

Aged↗

PubMed2003

Inhibition of lysophosphatidic acid-induced RhoA activation and tumor cell invasion by 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors.

The mevalonate metabolic pathway is necessary for the isoprenylation of a number of small GTPases. We have previously presented that Rho plays a pivotal role in 1-oleoyl-lysophosphatidic acid (LPA)-induced invasion of rat ascites hepatoma MM1 cells. Herein we report the effect of HMG-CoA reductase inhibitors, fluvastatin and lovastatin, on the in vitro invasion of MM1 cells. Fluvastatin and lovastatin inhibited LPA-induced MM1 cell invasion in a dose-dependent manner. Fluvastatin inhibited LPA-induced translocation of RhoA protein from the cytosol to the membrane and RhoA activation which was measured by pull-down assay for GTP-bound RhoA. Fluvastatin also inhibited the translocation of both endogenous and dominant-active RhoA from the cytosol to the membrane, actin stress fiber assembly and in vitro invasion of the cells expressing dominant-active RhoA (Val14-RhoA). These results indicate that HMG-CoA reductase inhibitors have the potential to reduce RhoA activation and cancer cell invasion by targeting the Rho protein isoprenylation.

Actins↗

PubMed2002

Preparation of CdSe nanocrystals in a micro-flow-reactor.

A micro-reactor was utilized for continuous and controlled CdSe nanocrystal preparation. Effects of reaction conditions on optical properties of the nanocrystals were investigated; in this current system, rapid and exact temperature control of the micro-reactor was beneficial for controlling particle diameter and reproducible preparation of particles; additional effort was made towards narrower particle-size distributions.

Journal Article↗

PubMed2002

Phase-vanishing reactions that use fluorous media as a phase screen. Facile, controlled bromination of alkenes by dibromine and dealkylation of aromatic ethers by boron tribromide.

In fluorous triphasic reactions, such as bromination of alkenes by dibromine and dealkylation of aromatic ethers by boron tribromide, the middle fluorous phase acts as a liquid membrane permitting passive transport of the reagents at the bottom to the top layer involving the substrates, thereby regulating the reactions.

Alkenes↗