Comparative metabolic study between two selective estrogen receptor modulators, toremifene and tamoxifen, in human liver microsomes.

Toremifene (TOR) and Tamoxifen (TAM) are widely used as endocrine therapy for estrogen receptor positive breast cancer. Poor metabolizers of TAM are likely to have worse clinical outcomes than patients who exhibit normal TAM metabolism due to lower plasma level of its active metabolite, 4-hydroxy-N-desmethyl (4OH-NDM) tamoxifen (endoxifen). In this study, we examined the role of individual cytochrome P450 (CYP) isoforms in the metabolism of TOR to N-desmethyl (NDM), 4-hydroxy (4OH) and 4OH-NDM metabolites in comparison with TAM using human liver microsomes (HLMs) with selective chemical inhibitors for each CYP isoform and recombinant CYP proteins.

Preclinical anticancer effects and toxicologic assessment of hepatic artery infusion of fine-powder cisplatin with lipiodol in vivo.

We conducted an in vivo study to evaluate the anticancer effect and toxicity of fine-powder cisplatin suspended in lipiodol (fCDDP/LPD suspension) after a single administration of three different doses to rats via the intrahepatic artery after transplantation of rat ascites hepatoma cells. The toxicity of the fCDDP/LPD suspension was also assessed in the same protocol in noncancer-bearing rats and the observed toxicologic changes were compared among groups administered saline (Sal), an aqueous solution of fCDDP (fCDDP/Sal solution), and LPD alone. In parallel with the toxicity test, plasma CDDP concentrations were compared between the fCDDP/LPD suspension and fCDDP/Sal solution.

Sensitive measurement of vinorelbine in dog plasma by liquid chromatography-electrospray ionization tandem mass spectrometry utilizing transitions from double-charged precursor ions.

A sensitive high-performance liquid chromatography/tandem mass spectrometry (LC/MS/MS) method for measuring vinorelbine was developed. A 100 µL aliquot of plasma was spiked with deuterium-labeled internal standard and subjected to solid-phase extraction using an Oasis HLB μ-elution plate. Two microliters of the extracted samples was directly injected into LC/MS/MS.

[Applicability of atmospheric pressure photoionization mass spectrometry to trace analysis of hydrophilic drugs].

Applicability of atmospheric pressure photoionization mass spectrometry (APPI-MS) to the analysis of hydrophilic drugs was investigated. Model compounds with moderate to high hydrophilicity was tested, and most compounds showed good signal response with APPI-MS, but some compounds with high molecular polarity like folic acid derivatives, glycoside and some nucleic acid derivatives showed very weak signal responses. By observing relationship between the compounds' physicochemical properties and APPI response, compounds with higher lipophilicity and less polar surface area were considered to be advantageous for APPI-MS.

Effects of long-term low-dose oxygen supplementation on the epithelial function, collagen metabolism and interstitial fibrogenesis in the guinea pig lung.

Background: The patient population receiving long-term oxygen therapy has increased with the rising morbidity of COPD. Although high-dose oxygen induces pulmonary edema and interstitial fibrosis, potential lung injury caused by long-term exposure to low-dose oxygen has not been fully analyzed. This study was designed to clarify the effects of long-term low-dose oxygen inhalation on pulmonary epithelial function, edema formation, collagen metabolism, and alveolar fibrosis.

[Comparative study of bactec MGIT 960 AST and conventional proportion method using Ogawa medium for the drug susceptibility testing of Mycobacterium tuberculosis to isoniazid].

Objective: To evaluate the accuracy of drug susceptibility testing to isoniazid with BACTEC MGIT 960 (MGIT AST) comparing with the standard proportion method using Ogawa medium.

Method: A total of 1109 M. tuberculosis strains, which were selected from the collection of RYOKEN drug resistance survey in 2002, were selected and subjected to the susceptibility testing to isoniazid using MGIT AST and 1% Ogawa standard methods.

[Clinical analysis of patients with sequelae of pulmonary tuberculosis undergoing home oxygen therapy].

Purpose: To clarify the clinical characteristics of patients with sequelae of pulmonary tuberculosis undergoing home oxygen therapy.

Objects And Methods: We conducted a cross-sectional survey of those with newly-introduced home oxygen therapy for the sequelae of pulmonary tuberculosis from 1998 through 2001, using national hospital network of respiratory diseases.

Results: The study subjects were 402 in total (271 men and 131 women), who started the home oxygen therapy at the age ranging between 33 and 100 years (72.

[Evaluation of respiratory failure due to sequelae of tuberculosis].

Though the mortality of tuberculosis in Japan has been extremely rapidly depressed from about 150 deaths per 100,000 in 1950 down to about 4 in 1985 during the period of a couple of decades after the World War II. However, the declining trend of the mortality and the morbidity seem to be leveling off now and the morbidity of the tuberculosis remain on the almost same level which are much higher than that of the developed countries. We have to make the progress in the field of the new diagnostic technique and the creation of the new drugs applying the most frontier science and the social system supporting the completion of the treatment for every patient.

Functional characterization of single nucleotide polymorphisms with amino acid substitution in CYP1A2, CYP2A6, and CYP2B6 found in the Japanese population.

As a part of the studies conducted by the Pharma SNPs Consortium (PSC), the enzyme activities of CYP1A2, CYP2A6 and CYP2B6 variants with altered amino acids as a result of single nucleotide polymorphisms (SNPs) found among the Japanese population were analyzed under a unified protocol using the same lots of reagents by the laboratories participating in the PSC. Mutations in CYP1A2, CYP2A6 and CYP2B6 were introduced by site-directed mutagenesis and the wild type and mutated CYP molecules were expressed in Escherichia coli. The expressed cytochrome P450s were purified and the enzyme activities were measured in reconstitution systems.

[Pulmonary infection in immunocompromised hosts].

While typical pulmonary infections can be cured with antimicrobial agents, three types require surgical lung resection: those in immunocompromised patients; those with acquired resistance to medication; and those caused by microorganisms against which there are no effective drugs. We discuss these three types from the viewpoint of physicians. With the development of chemotherapy for malignant disease, patients with leukemia can be cured with bone marrow transplantation.

[A clinical study on tuberculosis among young adults in Japan: analysis on patients admitted to national hospitals in Kanto- and Kinki-areas in the year 2000].

Considering the high social activity, the trend of tuberculosis among young adults appears to be one of the key factors that influence the future morbidity rate of tuberculosis in Japan. To investigate its current characteristics, we analyzed new cases of tuberculosis aged 20 to 29 who were admitted to 7 national hospitals in Kanto- and Kinki-areas during the period of January 1st to December 31st, 2000. Data on the following items were compiled: sex, age, body height and weight, nationality; background factors such as life style, complications; course of the disease before the diagnosis; result of PPD skin test; severity of the disease estimated by the amount of M.

[Trends in drug-resistant tuberculosis in National Higashisaitama Hospital, 1994-2001].

To know the prevalence of resistance to four first-line anti-tuberculosis drugs, we reviewed the results of drug-susceptibility tests of patients with tuberculosis who were admitted to our hospital from 1994 to 2001. Among patients with no prior chemotherapy against tuberculosis, the complete resistance rate was 1.9% for INH, 0.

[Superior sensitivity of MGIT method in identification of specimens culture-positive for acid-fast bacilli (AFB) and individuals with positive AFB cultures].

To investigate the superiority of the Mycobacteria Growth Indicator Tube (MGIT) over Ogawa medium in the detection of acid-fast bacilli (AFB), we surveyed all specimens for AFB culture using Ogawa medium in 1999 and MGIT in 2000. The MGIT method increased the culture-positive rate from 23.1% (Ogawa medium) to 34.

[Tuberculosis of the elderly (above the age of 75) in national hospitals].

In Japan tuberculosis is becoming rapidly the disease of the elderly. We studied the background, the type and level of hospital cares needed, and the outcome of patients with pulmonary tuberculosis (sputum smear and/or culture positive) above the age of 75 who were admitted to 8 national hospitals during the period from January 1 to December 31, 1997. The study included 150 patients (male: 109, female: 41, mean age: 81.

[Proposal for a new method for evaluation of physical exercise capacity in patients with chronic respiratory disease].

We developed a new method of evaluating the tolerance for physical exercise in patients with chronic respiratory disease. Using a newly developed portable pulse oxymeter, with which we could measure kinetic energy (physical activity), calculated from the vertical acceleration involved in physical movements in the patient's daily life, we considered the correlation between the characteristics of the distribution of oxygen saturation (SpO2) and the degree of physical activity. The characteristics of SpO2 distribution in normal healthy subjects are uniform at all degrees of physical activity.

A study on the metabolism of etoposide and possible interactions with antitumor or supporting agents by human liver microsomes.

The metabolism of etoposide was investigated by using human liver microsomes and nine recombinant human cytochrome P450 (CYP) isoforms to identify the CYP isoform(s) involved in the major metabolic pathway (3'-demethylation) of etoposide as well as to evaluate the possible metabolic interactions with several antitumor or supporting agents. The 3'-demethylation of etoposide followed a Michaelis-Menten one-enzyme kinetic behavior in six human liver microsomal samples. The relationships were assessed with six different human liver microsomes between the 3'-demethylation of etoposide and metabolic activities for substrate probes of the respective CYP isoforms, showing a significant correlation (r = 0.

Mutual inhibition between quinine and etoposide by human liver microsomes. Evidence for cytochrome P4503A4 involvement in their major metabolic pathways.

The mutual inhibition between quinine and etoposide with their major metabolic pathways (i.e. quinine 3-hydroxylation and etoposide 3'-demethylation) was examined in vitro by human liver microsomes.

[Difference of new mutation rates in dystrophin gene between deletion and duplication mutation in Duchenne and Becker muscular dystrophy].

To clarify new mutational rates in the dystrophin gene between deletion and duplication mutations, carrier diagnosis was performed on 123 mothers of probands suffered from Duchenne (DMD) and Becker (BMD) muscular dystrophy. Quantitative Southern blot analysis with cDNA probes was applied in this study. Out of 108 mothers of DMD/BMD patients with deletion mutation in dystrophin gene, 69 were carriers and 39 were non-carriers.

[Serodiagnosis of tuberculosis by detection of antituberculous glycolipid antigen (TBGL antigen) antibodies in serum using enzyme-linked immunosorbent assay: clinical evaluation of anti-TBGL antibodies assay kit].

Kyowa Medex Co., Ltd. developed the kit for the sero-diagnosis of tuberculosis, which detects IgG antibodies against tuberculous glycolipids antigen containing cord factor (TBGL antigen) prepared from M.

[Two cases of pulmonary disease caused by Mycobacterium chelonae subsp. abscessus].

We encountered two-cases of pulmonary disease caused by M. chelonae subsp. abscessus, [Case 1] A 72-year-old man was admitted to the hospital because of fever.

[Home oxygen therapy (HOT) in patients with pulmonary tuberculosis sequelae--comparison between patients medically treated and those surgically treated].

In Japan there are about 40,000 patients under home oxygen therapy (HOT), of whom about 30 to 40% are pulmonary tuberculosis sequelae (TBS). These patients can be divided into three groups depending on the treatments they had, Group 1: those who had medical treatments only, Group 2: those who had artificial pneumothorax, and Group 3: those who had thoracoplasties or other surgical treatments. The purpose of this study was to observe the distributions and possible differences in the survival rates among these groups.