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Biomedical subjects

T Kamimura

Publications and source records attributed to T Kamimura.

At least 73 records · Page 4Linked to original sources
PubMed1997

Studies on 3'-quaternary ammonium cephalosporins--IV. Synthesis and antibacterial activity of 3'-(2-alkyl-3-aminopyrazolium) cephalosporins related to FK037.

The synthesis and in vitro antibacterial activity of 7 beta-[(Z)-2-(2-aminothiazol-4-yl)-2-methoxyiminoacetamido] cephalosporins bearing various 2-alkyl-3-aminopyrazolium groups at the 3-position are described. Antibacterial activity against MRSA was affected by the nature of the substituent at the 2-position on the 3'-aminopyrazolium groups. Among the cephalosporins prepared in this study, 7 beta-[(Z)-2-(2-aminothiazol-4-yl)-2-methoxyiminoacetamido]-3-[3-am ino-2-(2 -hydroxyethyl)-pyrazolio]methyl-3-cephem-4-carboxylate sulfate (23e, FK037) showed extremely potent broad-spectrum activity against both Gram-positive bacteria including MRSA, and Gram-negative bacteria including Pseudomonas aeruginosa. In particular, the in vivo activity against MRSA of FK037 was the highest of all the beta-lactam antibiotics tested.

Anti-Bacterial Agents↗
PubMed1997

Synthesis and antibacterial activity of novel 4-pyrrolidinylthio carbapenems--I. 2-Alkoxymethyl derivatives.

The synthesis and in vitro antibacterial activity of a novel series of 2-alkoxymethyl-4-pyrrolidinylthio-1 beta-methyl carbapenems are described. As a result of these studies, we discovered that FR27743 (19j) containing a novel 2-fluoroethoxymethyl substituent possesses a broad spectrum of antibacterial activity against both Gram-positive and Gram-negative organisms, including Pseudomonas aeruginosa. Furthermore, FR27743 exhibited excellent stability against renal dehydropeptidase-I (DHP-I), good urinary recovery, and superior in vivo activity compared to that for Meropenem against several systemic infections.

Animals↗
PubMed1997

Risk factors and the effect of interferon therapy in the development of hepatocellular carcinoma: a multivariate analysis in 343 patients.

The aims of the present study were to clarify the risk factors for the development of hepatocellular carcinoma (HCC) in chronic hepatitis C virus (HCV) infection and to investigate the effectiveness of interferon (IFN) therapy. We retrospectively studied 343 patients who had been admitted to our hospital; 161 with chronic hepatitis, 49 with liver cirrhosis, 42 with chronic hepatitis bearing HCC and 91 with liver cirrhosis bearing HCC. The mean (+/- SD) observation period was 41.6 +/- 31.1 months. The mean age of HCC and non-HCC patients was 63.5 +/- 7.6 and 56.9 +/- 12.5 years, respectively (P < 0.001). The HCV genotype II (1b) was the most prevalent genotype (92.5%) in HCC patients and the mean age was higher among patients with this genotype (63.6 +/- 7.7 years). Multivariate analysis identified age (P < 0.001), the male gender (P < 0.01), HCV genotype II (1b) (P < 0.05) and excessive alcohol intake (P < 0.05) as independent factors associated with the development of HCC. There was no relationship between the development of HCC and serum HCV levels as quantified by branched DNA assay or competitive reverse transcription polymerase chain reaction. The incidence of HCC in patients who had not received IFN therapy was 10.4/100 person-year, while that of patients who had received IFN therapy was 1.2/100 person-year (P < 0.01) by the person-year method. The low incidence of HCC in patients treated with IFN suggests that IFN may prevent the development of HCC.

Aged↗
PubMed1997

Rapid, sensitive and specific diagnosis of Bordetella pertussis using the polymerase chain reaction.

Use of a repetitive DNA sequence of Bordetella pertussis allowed successful detection of the organism by the polymerase chain reaction (PCR). The method was highly sensitive, being able to detect B. pertussis in specimens containing only a few cells. It was also highly specific, with no amplification of specimens containing other organisms, for example Haemophilus influenzae or Neisseria, being observed. A diagnosis could be made within 1 day. The PCR assay was also evaluated in clinical specimens. Among 47 nasopharyngeal specimens obtained from 24 patients with laboratory-confirmed pertussis, 27 were positive by PCR and 19 by culture. In particular, all three bronchial aspirates from one patient with pertussis were positive by PCR, but only one showed positive on culture. Eleven specimens from parapertussis patients and 65 specimens from patients without pertussis tested negative. It was concluded that this newly developed PCR method for the diagnosis of pertussis was more rapid and sensitive than the usual culture method. Polymerase chain reaction could have a major impact on the treatment and control of this infection and would be a useful tool for studying the pathogenesis of B. pertussis infection.

Bacteriological Techniques↗
PubMed1996

Neuronal and muscular functions as parameters of graft viability in small bowel transplantation.

The physiological properties of neurons and smooth muscles were studied after cold preservation of a rat small intestinal graft, in order to evaluate the graft viability before reperfusion. A 25-cm jejunal graft was harvested from a Lewis rat and stored in University of Wisconsin solution for 0, 12, 24, 48, and 72 hr at 4 degrees C (n = 8, each group). The intestinal samples were physiologically studied at the end of cold preservation. The positive rates of the specimens showing both biphasic nervous activities and spontaneous rhythmic activities were 100, 100, 88, 25, and 0% in 0-, 12-, 48-, and 72-hr preservation groups, respectively. The maximal contractions produced by acethylcholine chloride were 1.12 +/- 0.32, 0.63 +/- 0.22, 0.43 +/- 0.15, 0.52 +/- 0.32, and 0.27 +/- 0.13g for the 0-, 12-, 24-, 48-, and 72-hr preservation groups, respectively. The graft survivals after syngeneic transplantation (n = 6, each group) were 6 out of 6 (100%), 5 out of 6 (83%), 5 out of 6 (83%), 1 out of 6 (17%), and 0 out of 6 (0%) for the 0-, 12-, 24-, 48-, and 72-hr preservation groups, respectively. The graft survival correlated closely with the positive sample rates of the specimens, showing both biphasic nervous activities and spontaneous rhythmic activities. It only took about 1 hr and 20 min to complete the physiological examination of the graft, and thus, such an examination of the graft is considered to be both a simple and a reliable method for predicting graft viability before transplantation.

Animals↗
PubMed1996

Cardiac oxygenation by extracorporeal membrane oxygenation in exteriorized fetal lambs.

OBJECTIVE: The purpose of this study was to determine the degree of cardiac oxygenation produced by different routes of extracorporeal membrane oxygenation in fetal lambs submerged in warm saline solution. STUDY DESIGN: Seven fetal lambs ranging in age from 113 to 133 days of gestation were delivered by cesarean section and oxygenated with extracorporeal membrane oxygenation. To maintain the patency of the ductus arteriosus, prostaglandin E1 was continuously infused intravenously to the fetus. Initially the extracorporeal membrane oxygenation route was from the right atrium to the carotid artery. Then the extracorporeal membrane oxygenation route was changed to flow from the right atrium to the umbilical vein. The fetus was kept in a warm saline solution bath, and the fetal circulation was maintained. Extracorporeal membrane oxygenation flow ranged between 100 and 200 ml/min throughout the experiment. Simultaneous blood samples were taken during both types of extracorporeal membrane oxygenation from the following points in the fetal circulation: premembrane (least oxygenated blood leaving the fetus from the right atrium), postmembrane (oxygenated blood returning to the fetus), the carotid artery, and the left ventricle. The respiratory gases and pH of each sample were measured. Six fetuses received nonradioactive colored microspheres injected into the oxygenated blood returning to the fetus flow before returning to the fetuses during both types of extracorporeal membrane oxygenation. After the animals were killed, microspheres were counted in the myocardium separately taken from the right and left atria and the right and left ventricles to determine cardiac blood flow. RESULTS: During right atrium to carotid artery extracorporeal membrane oxygenation, left ventricle PO2 remained low as postmembrane PO2 increased; these values were not significantly correlated (r = 0.234, p = 0.61). During right atrium to umbilical vein extracorporeal membrane oxygenation, left ventricle and postmembrane PO2 exhibited a significant positive correlation (r = 0.855, p = 0.014). When the extracorporeal membrane oxygenation route was switched from the right atrium to carotid artery to the right atrium to umbilical vein, there was a significant increase in left ventricle PO2 and a decrease in left ventricle PCO2, whereas the respiratory gases and pH remained unchanged at other sites in the circulation. Microsphere counts were consistently higher during right atrium to umbilical vein extracorporeal membrane oxygenation than during right atrium to carotid artery extracorporeal membrane oxygenation in all four samples from different parts of myocardium (p < 0.001 by paired t test). CONCLUSION: More effective cardiac oxygenation is provided by right atrium to umbilical vein extracorporeal membrane oxygenation than by right atrium to carotid artery extracorporeal membrane oxygenation.

Animals↗
PubMed1996

Oxygenation in fetal lambs supported by extrauterine right atrium to artery extracorporeal membrane oxygenation.

OBJECTIVE: Our purpose was to determine the adequacy of oxygenation, particularly cranial and cardiac oxygenation, in exteriorized fetal lambs on right atrium to artery extracorporeal membrane oxygenation. STUDY DESIGN: Thirteen fetal lambs were placed on right atrium to artery extracorporeal membrane oxygenation between the gestational ages of 113 and 133 days. Various PO2 and oxygen saturation (SO2) values were obtained by varying the oxygen concentrations at the oxygenator membrane. Blood gases, pH, and SO2 were observed on samples taken before and after membrane oxygenation from the left ventricle and through the cranial carotid arterial catheter. These were compared with control values obtained before the cessation of umbilical circulation. Fetal coronary oxygenation was represented by left ventricle PO2 and SO2 and cranial oxygen by carotid artery PO2 and SO2. RESULTS: We classified oxygen saturation as low, medium, and high on the basis of the level of postmembrane SO2. Carotid artery cranial oxygenation in the low SO2 group was equivalent to control values, but that in the medium and high SO2 groups was significantly higher than in the control group. Left ventricle oxygenation was consistently lower than cranial oxygenation in any SO2 group. In the low group left ventricle oxygenation was significantly lower than the control values. CONCLUSIONS: Right atrium to artery extracorporeal membrane oxygenation appears sufficient to oxygenate the fetal cranial circulation but may be inadequate for the efficient distribution of oxygenated blood into the left ventricle and thus the coronary circulation.

Animals↗
PubMed1996

Efficient production of the C-terminal domain of secretory leukoprotease inhibitor as a thrombin-cleavable fusion protein in Escherichia coli.

We have developed a high-level production system for the C-terminal domain of secretory leukoprotease inhibitor (SLPI) to investigate its pharmacological activities. A gene for the C-terminal domain of SLPI, (Asn55-Ala 107)SLPI, was constructed from chemically synthesized deoxyoligonucleotides. It was fused to a gene for the N-terminal portion of human growth hormone via a DNA sequence encoding Leu-Val-Pro-Arg, which can be cleaved by thrombin. The fused gene was expressed in Escherichia coli under the control of a trp promoter, and the fusion protein was obtained as an inclusion body. After sulfonation of the cysteine residues, the sulfonated fusion protein was cleaved at the desired site by thrombin. Sulfonated (Asn55-Ala107) SLPI was refolded in Tris buffer containing reduced and oxidized glutathione. The resulting (Asn55-Ala107) SLPI was purified by cation-exchange chromatography and reverse-phase high performance liquid chromatography. The final yield was 50 mg/I culture. (Asn55-Ala107) SLPI was as active against elastase as, but had less trypsin inhibitory activity than, native SLPI. This system is suitable for the large-scale production of the C-terminal domain of SLPI, which is an elastase-specific inhibitor.

Amino Acid Sequence↗
PubMed1996

Maternal and fetal catecholamine responses to acute hypoxemia in Japanese Saanen goats.

Our purposes were to investigate the effects of acute hypoxemia on maternal and fetal physiological and biochemical responses in Japanese Saanen goat and to compare these responses to those obtained in other species in the previous studies. Five pregnant Japanese Saanen goats at about 120 days of gestation were operated to make fetal chronic preparation models. After a minimum of 4 days of postoperation, hypoxemia was induced by having the ewe breathe a hypoxic gas mixture (10% O2, 3% CO2, in N2) for 30 min. Maternal PO2 decreased from 84 to 40 mmHg, and fetal PO2 decreased from 22 to 16 mmHg. Only the fetal pH was significantly decreased by hypoxemia. Maternal heart rate increased with increases in arterial pressures. On the other hand, fetal heart rate showed bradycardia with a transient increase in blood pressure. During hypoxemia, maternal catecholamines minimally increased, while fetal plasma concentrations of epinephrine and norepinephrine were significantly increased. These changes in Japanese Saanen goats were first revealed by the current study and were compatible with the previous reports with sheep and monkeys. These observations suggest that the Japanese Saanen goats may be an adequate animal model for investigation of fetal physiology.

Animals↗
PubMed1996

Effects of inhaled nitric oxide on hypoxic pulmonary vasoconstriction in dogs and a case report of venae cavae syndrome.

We investigated the effect of inhaled nitric oxide (NO) on hypoxic pulmonary vasoconstriction (HPV) in dogs, by treating a dog suffering from venae cavea syndrome (VCS) and pulmonary hypertension (PH) with NO inhalation. The increasing mean pulmonary arterial pressure (mPAP) induced by hypoxia was lessened significantly by NO inhalation. High PAP in VCS also declined as a result of NO inhalation. These results suggested that inhaled NO can reverse HPV in dogs and prevent worsening PH during surgical extraction of heartworm in VCS.

Administration, Inhalation↗
PubMed1996

Evaluation of pulmonary vasodilatory capacity with inhaled nitric oxide in a dog with patent ductus arteriosus.

A female Maltese dog with patent ductus arteriosus (PDA) showing left congestive heart failure and moderate pulmonary hypertension was evaluated for pulmonary vasodilatory capacity using low concentrations of inhaled nitric oxide (NO) in comparison with oxygen during preoperative cardiac catheterization. Increasing the inspired oxygen concentration (FiO2) to 1.0 without adding NO did not reduce the mean pulmonary arterial pressure (mPAP). However, inhalation of NO at FiO2 1.0 reduced mPAP rapidly without changing other hemodynamic and gas exchange parameters. From these results, inhaled NO caused selective pulmonary vasodilation without producing systemic vasodilation, which may provide a safe and effective mean of evaluating the pulmonary vasodilatory capacity of dogs with PDA.

Administration, Inhalation↗
PubMed1996

[A case of common bile duct cancer responding to MMC leucovorin, 5-FU, and UFT combination chemotherapy and radiation].

A case of unresectable common bile duct cancer involving the portal vein and with Virchow lymph node metastasis was treated with MMC, Leucovorin, 5-FU and UFT combination chemotherapy as well as radiation. The case was a 71-year-old female who was admitted to the hospital with vomiting and anorexia. Abdominal US study showed obstructive jaundice. The PTCD tube was pierced to dilate the intrahepatic bile duct. Bile juice cytology was class V. Abdominal CT showed paraaortic lymph node metastasis. Angiography revealed portal vein invasion, and the diagnosis was unresectable common bile duct cancer. We started anticancer therapy and radiation. The anticancer therapy selected was MMC, LEUCOVORIN, 5-FU and UFT combination chemotherapy. After 2 cycles of the treatment, Virchow lymph node completely disappeared and the symptoms diminished. These combination therapies were effective for common bile duct cancer.

Aged↗
PubMed1995

Epidemiologic survey and genetic analysis of endemic hepatitis C virus infection in a Japanese town with a high prevalence of hepatitis B virus carriers.

Mass screening for hepatitis C virus antibody was carried out in 875 inhabitants (313 men and 562 women) of a town in Japan with a high rate of hepatitis B virus infection. The overall rate of positivity for anti-HCV was 8.8% (6.4% in men and 10.1% in women). The rate of positivity for hepatitis B virus surface antigen was 11.2%. Five subjects (0.6%) were positive for both markers. HCV-RNA was detected in 65 (88.4%) of 77 individuals who were positive for anti-HCV and in 1 (1.5%) of 60 individuals negative for anti-HCV. The genotype of the HCV genome was determined by PCR analysis using type-specific primers in 60 individuals. HCV type 1b was detected in 51 subjects (85%), type 2a in 3 subjects (5%), and type 2b in 6 subjects (10%). None of the individuals was infected with more than one genotype. The nucleotide sequences of the partial nonstructural 5 region of HCV type 1b genotype obtained from 6 individuals showed at least 92.0% homology in the nucleotide sequence, and 94.8% homology in the amino acid sequence. Homology among these clones was greater than their homology with previously described type 1b sequences. The findings suggest that there was a specific local origin of HCV infection, although it was not possible to identify any single source of HCV infection. The results also indicate that presence of asymptomatic HCV carriers.

Adult↗
PubMed1995

A retrospective study of hepatitis C virus carriers in a local endemic town in Japan. A possible presence of asymptomatic carrier.

Chronic hepatitis, cirrhosis, and hepatocellular carcinoma are the accepted sequelae of chronic hepatitis C virus (HCV) infection. However, the real natural history of HCV infection is not still well understood. To approach this problem, we investigated 91 individuals positive for antibodies against HCV (anti-HCV), who have received annual liver function examination in a local town known to have had high carrier rates of hepatitis B virus (HBV) and HCV. Among the 91 anti-HCV-positive individuals, 63 had undertaken the annual examination more than five times in the past 14 years. We analyzed retrospectively the past liver function test results of these 63 subjects and evaluated their present virological status by determining HCV genotypes and estimating quantity of HCV RNA in the sera. Among the 63 subjects, 50 (79.4%) had HCV RNA in the serum and 40 (80%) of the 50 subjects with HCV RNA had abnormal alanine aminotransferase or aspartate aminotransferase level more than once in their records. However, the other 10 (20%) had no abnormal levels during the period examined. Six of 50 (12%) had ultrasonographic findings suggestive of cirrhosis. Thus, HCV-infected individuals in this area did not seem to have progressive liver diseases. Considering the advanced ages of the individuals examined (mean 64 years old), we may have observed a stage in the natural history of HCV infection in which viremia persists in most individuals and the tendency to progress to serious chronic liver disease is mild.

Base Sequence↗
PubMed1995

Pharmacological activity of the C-terminal and N-terminal domains of secretory leukoprotease inhibitor in vitro.

1. In order to characterize the physiological functions of the domain structure of secretory leukoprotease inhibitor (SLPI), the biological capacities of half-length SLPIs, (Ser1-Pro54)SLPI and (Asn55-Ala107)SLPI, were investigated and compared with those of full-length SLPI. 2. The activities of these inhibitors against several serine proteases were determined using synthetic chromogenic substrates. The inhibitory capacity of the C-terminal domain, (Asn55-Ala107)SLPI, was as strong as that of full-length SLPI against human neutrophil elastase (NE), cathepsin G and chymotrypsin. It possessed less trypsin inhibitory activity than intact SLPI. For the N-terminal domain of SLPI, (Ser1-Pro54)SLPI, no inhibitory activity could be detected against the serine proteases tested in this study. 3. The inhibitory activity of (Asn55-Ala107)SLPI against the proteolysis of the natural substrates elastin and collagen by NE was comparable with that of full-SLPI (elastin, IC50 = 907 +/- 31 nM for SLPI, 767 +/- 33 nM for (Asn55-Ala107)SLPI; collagen, IC50 = 862 +/- 36 nM for SLPI, 727 +/- 47 nM for (Asn55-Ala107)SLPI). 4. The binding affinities of full- and half-length SLPIs for heparin were measured by affinity column chromatography. Full-length SLPI showed high affinity for heparin while the binding capacities of both half-length SLPIs were lower. (Concentration of NaCl for elution, 0.45 M for SLPI, 0.24 M for (Ser1-Pro54)SLPI, 0.27 M for (Asn55-Ala107)SLPI). 5. The effects of full-SLPI and (Asn55-Ala107)SLPI on blood coagulation were measured using the activated partial thromboplastin time (APTT). Full-length SLPI prolonged clotting time dose dependently(1.25, 2.5 and 5.0 microM), whereas (Asn55-AlalO7)SLPI had no effect even at the highest concentration.6. In conclusion, the C-terminal domain of SLPI is a promising candidate for the treatment of inflammatory diseases in which participation of neutrophil proteases has been suggested.

Animals↗