The mare as a model for luteinized unruptured follicle syndrome: intrafollicular endocrine milieu.

Luteinized unruptured follicle (LUF) syndrome is a recurrent anovulatory dysfunction that affects up to 23% of women with normal menstrual cycles and up to 73% with endometriosis. Mechanisms underlying the development of LUF syndrome in mares were studied to provide a potential model for human anovulation. The effect of extended increase in circulating LH achieved by administration of recombinant equine LH (reLH) or a short surge of LH and decrease in progesterone induced by prostaglandin F2α (PGF2α) on LUF formation (Experiment 1), identification of an optimal dose of COX-2 inhibitor (flunixin meglumine, FM; to block the effect of prostaglandins) for inducing LUFs (Experiment 2), and evaluation of intrafollicular endocrine milieu in LUFs (Experiment 3) were investigated. In Experiment 1, mares were treated with reLH from Day 7 to Day 15 (Day 0=ovulation), PGF2α on Day 7, or in combination. In Experiment 2, FM at doses of 2.0 or 3.0 mg/kg every 12 h and human chorionic gonadotropin (hCG) (1500 IU) were administered after a follicle ≥32 mm was detected. In Experiment 3, FM at a dose of 2.0 mg/kg every 12 h plus hCG was used to induce LUFs and investigate the intrafollicular endocrine milieu. No LUFs were induced by reLH or PGF2α treatment; however, LUFs were induced in 100% of mares using FM. Intrafollicular PGF2α metabolite, PGF2α, and PGE2 were lower and the ratio of PGE2:PGF2α was higher in the induced LUF group. Higher levels of intrafollicular E2 and total primary sex steroids were observed in the induced LUF group along with a tendency for higher levels of GH, cortisol, and T; however, LH, PRL, VEGF-A, and NO did not differ between groups. In conclusion, this study reveals part of the intrafollicular endocrine milieu and the association of prostaglandins in LUF formation, and indicates that the mare might be an appropriate model for studying the poorly understood LUF syndrome.

Isolation of novel mycobacteria contaminating an aquarium fish tank in a Japanese university hospital.

AIMS: To better understand nontuberculous mycobacteria (NTM) contamination in a hospital setting, six freshwater fish gut homogenates and water in an aquarium fish tank placed on the reception counter of a nursing station were cultured for mycobacteria. METHODS AND RESULTS: By direct sequencing of 16s rRNA, rpoB and hsp65, scotochromogenic and nonchromogenic Mycobacterium szulgai isolates containing hsp65 type II (GenBank accession nos. FJ384762 and FJ384764, respectively), Mycobacterium gordonae isolates containing rpoB clusters B and E (GenBank accession no. FJ384766), and Mycobacterium kansasii isolates containing hsp65 type VI were collected from the gut homogenates and water from the fish tank. However, no isolates were obtained from the tap water used to refill the fish tank. A randomly amplified polymorphic DNA (RAPD) analysis using a 10-mer primer (5'-TGGTCGCGGC) showed that some NTM from the fish tank water were identical to those obtained from the gut homogenates. CONCLUSIONS: Fish and water in the tank were contaminated by the novel NTM. SIGNIFICANCE AND IMPACT OF THE STUDY: These findings could help to elucidate infection routes and contamination sources of novel NTM from water sources.

Lunar global shape and polar topography derived from Kaguya-LALT laser altimetry.

A global lunar topographic map with a spatial resolution of finer than 0.5 degree has been derived using data from the laser altimeter (LALT) on board the Japanese lunar explorer Selenological and Engineering Explorer (SELENE or Kaguya). In comparison with the previous Unified Lunar Control Network (ULCN 2005) model, the new map reveals unbiased lunar topography for scales finer than a few hundred kilometers. Spherical harmonic analysis of global topographic data for the Moon, Earth, Mars, and Venus suggests that isostatic compensation is the prevailing lithospheric support mechanism at large scales. However, simple rigid support is suggested to dominate for the Moon, Venus, and Mars for smaller scales, which may indicate a drier lithosphere than on Earth, especially for the Moon and Venus.

Contaminated oral intubation equipment associated with an outbreak of carbapenem-resistant Pseudomonas in an intensive care unit.

Twenty intensive care patients were diagnosed as infected or colonized by Pseudomonas aeruginosa within a one-month period; a rate three to four times higher than the typical background frequency of this infection in the intensive care unit (ICU). Patients with positive respiratory specimens were mechanically ventilated, which included re-used disinfected bite blocks during intubation. Fourteen specimens from 20 positive patients originated in the respiratory tract. Seven clonal variants were isolated and identified as originating from the same strain by pulsed-field analysis. These isolates were also matched to the strain detected on the re-used bite blocks, which had been disinfected with 140ppm sodium hydrochloride. Notably, Staphylococcus aureus was also detected on bite blocks sterilized with ethylene dioxide, indicating incomplete disinfection. In immunocompromised patients, re-use of bite blocks during intubation must be prohibited. Single-use kits or intubation without the use of bite blocks is recommended.

Fatty acid metabolism assessed by 125I-iodophenyl 9-methylpentadecanoic acid (9MPA) and expression of fatty acid utilization enzymes in volume-overloaded hearts.

BACKGROUND: The peroxisome proliferator-activated receptor (PPAR) alpha is a member of the nuclear receptor superfamily and regulates gene expression of fatty acid utilization enzymes. In cardiac hypertrophy and heart failure by pressure-overload, myocardial energy utilization reverts to the fetal pattern, and metabolic substrate switches from fatty acid to glucose. However, myocardial metabolism in volume-overloaded hearts has not been rigorously studied. The aim of the present study was to examine fatty acid metabolism and protein expressions of PPARalpha and fatty acid oxidation enzymes in volume-overloaded rabbit hearts. METHODS: Volume-overload was induced by carotid-jugular shunt formation. Sham-operated rabbits were used as control. Chronic volume-overload increased left ventricular weight and ventricular cavity size, and relative wall thickness was decreased, indicating eccentric cardiac hypertrophy. (125)I-iodophenyl 9-methylpentadecanoic acid (9MPA) was intravenously administered, and animals were sacrificed at 5 min after injection. The 9MPA was rapidly metabolized to iodophenyl-3-methylnonanoic acid (3MNA) by beta-oxidation. Lipid extraction from the myocardium was performed by the Folch method, and radioactivity distribution of metabolites was assayed by thin-layer chromatography. The protein was extracted from the left ventricular myocardium, and levels of PPARalpha and fatty acid oxidation enzymes were examined by Western blotting. RESULTS: Myocardial distribution of 9MPA tended to be more heterogeneous in shunt than in sham rabbits (P = 0.06). In volume-overloaded hearts by shunt, the conversion from 9MPA to 3MNA by beta-oxidation was faster than the sham-control hearts (P < 0.05). However, protein levels of PPARalpha and fatty acid utilization enzymes were unchanged in shunt rabbits compared with sham rabbits. CONCLUSIONS: These data suggest that myocardial fatty acid metabolism is enhanced in eccentric cardiac hypertrophy by volume-overload without changes in protein expressions of PPARalpha and fatty acid utilization enzymes. Our data may provide a novel insight into the subcellular mechanisms for the pathological process of cardiac remodelling in response to mechanical stimuli.

[Evaluation of rapidly growing Mycobacteria isolates in a general hospital: reports from the hospital microbiology laboratory].

Forty isolates of rapidly growing Mycobacteria, Mycobacterium fortuitum group including M. fortuitum and M. peregrinum and M. chelonae group including M. chelonae subsp. chelonae and M. chelonae subsp. abscessus at Showa University Fujigaoka Hospital collected between February 1981 and December 1997 were investigated in this study. These isolates were from the patients who were not infected with HIV. The average age of fourteen patients, from whom M. fortuitum group was isolated, was 58 years, ranging from 17 to 80 years old. One patient (71-year-old) with chronic myelogenous leukemia and another (64-year-old) with chronic diabetes mellitus were diagnosed with skin abscesses of M. fortuitum group, which were located on the right site of the neck and in the scar after injecting insulin (injection abscess), respectively. The average age of twenty-six patients, from whom M. chelonae group was isolated, was 57 years, ranging from 32 to 84 years old. One patient (75-year-old) with articular rheumatism was diagnosed with a lung infection of mixed M. chelonae group and Pseudomonas aeruginosa, and another (74-year-old) with diabetes mellitus and kidney failure was strongly suspected of a lung infection. The isolates of the two mycobacteria from the remaining patients were due to colonization, while these patients had the following underlying diseases contributing to infections: pulmonary emphysema; diabetes mellitus; leukemia; collagen diseases; lung cancer; chronic kidney diseases; systemic lupus erythematosus; carcinomatous pleurisy; bronchiectasis; post-tuberculosis. Most isolates of the two mycobacteria were separated from the specimens of patients' respiratory tracts, but since M. chelonae group was a contaminant in the tap-water for diluting concentrated chlorhexidine, the organism happened to be isolated with the mucous membranes of the 6 patients' colons that were picked up while using the washed fiber-scope. These findings suggest that M. fortuitum and M. chelonae groups, in spite of the fact that they rarely cause infection, have a significant risk of infecting aged patients in general hospitals with various underlying diseases attributable to infections. As only a few colonies were isolated from patients' specimens in the majority of cases, it took time to carry out these clinical examinations, and to improve this "laboratory's delay", it is needed to make faster report to clinicians.

Cine viewing of abdominal CT.

A few studies have been reported that CT cine viewing on the CRT is superior to film-based viewing of CT images (Seltzer et al., Radiology 197 (1994) 119; Bonaldi et al., Am. J. Roentgenol. 170 (1998) 373; Tillich et al., Am. J. Roentgenol. 169 (1997) 1611). The purpose of our study is to know how to use cine viewing of abdominal CT. Thirty CT studies on the abdomen with both precontrast and postcontrast images were examined. The suitable rate of cine viewing ranged from 1 to 6 frames per second according to the size, the contrast and the complexity of the anatomical structures, and the slice thickness. For small or complex structures, checking each image might be required to know the full detail of them. Positional sorting among multiphase images, which is followed by consecutive display of a precontrast image, postcontrast early and late phase images at one position and so on, is useful to see the dynamic pattern of enhancement of the anatomical structures. However, there was no significant difference between cine viewing and film-based viewing concerning both the detectability of the anatomical structures and the conspicuity of enhancement of the liver and the pancreas, so that cine viewing might be an alternative to film-based viewing for CT diagnosis of the abdomen.

KRH-594, a new angiotensin AT1 receptor antagonist, prevents end-organ damage in stroke-prone spontaneously hypertensive/Izm rats.

1. In the present study, we examined whether KRH-594, a new angiotensin AT1 receptor antagonist, would stop the progression of renal failure and end-organ damage and improve the survival rate in salt-loaded stroke-prone spontaneously hypertensive rats (SHRSP/Izm). 2. Oral administration of KRH-594 (3 and 10 mg/kg per day) for 11 weeks significantly reduced systolic blood pressure, urinary total protein, blood urea nitrogen, serum creatinine and urinary N-acetyl glucosaminidase and increased creatinine clearance in SHRSP/Izm. 3. In a histological study, KRH-594 (3 and 10 mg/kg per day) significantly improved the glomerulosclerosis, basophilic change and hyalin cast of tubules, proliferation of afferent arterioles and interlobular artery wall scores of the kidney and the cardiac fibrosis scores of the heart in SHRSP/Izm. KRH-594 (3 and 10 mg/kg per day) also significantly inhibited cardiac hypertrophy. 4. KRH-594 (3 and 10 mg/kg per day) prevented death in SHRSP/Izm during the examination period. 5. These results suggest that KRH-594 improves hypertensive complications, such as renal failure, cardiac hypertrophy and thickening of the artery wall, and prevents death in salt-loaded SHRSP/Izm.

Cloning and expression of mouse deafness dystonia peptide 1 cDNA.

Complementary DNA of mouse deafness dystonia peptide 1 (DDP1) was isolated from adipocyte cDNA library and expressed in mammalian cells. The sequence shares homology of 92 and 97% on the nucleic acid and the amino acid levels with human DDP1. In comparison to mouse Bruton's tyrosine kinase (Btk) locus, the coding region spans 2 exons and the splice point is the same as human DDP1. Northern blot analysis suggests that mouse DDP1 expresses ubiquitously. In vitro transcription/translation study showed that the cDNA of mouse DDP1 codes about 11 kDa peptide. DDP1 tagged with FLAG localized in mitochondria and cytoplasm of COS7 cells. P19 embryonal carcinoma cells transfected with anti sense DDP1 cDNA were frequently dead after subculture and all the survivals expressed endogenous DDP1 mRNA. Therefore, mouse DDP1 may play an important role to survive in contrast to Tim8p, a yeast homologue, which was unnecessary in yeast.

KRH-594, a new angiotensin AT1 receptor antagonist, ameliorates nephropathy and hyperlipidaemia in diabetic spontaneously hypertensive rats.

1. We examined whether KRH-594, a new angiotensin AT1 receptor antagonist, ameliorates the progression of diabetic nephropathy and hyperlipidaemia in streptozotocin (STZ)-induced diabetic unilateral nephrectomized spontaneously hypertensive rats (DM-1K-SHR) or not. 2. The oral administration of KRH-594 (3 and 10 mg/kg per day) and candesartan cilexetil (1 mg/kg per day) for 16 weeks significantly reduced systolic blood pressure, urinary albumin and urinary total protein in DM-1K-SHR. 3. In a histological study, KRH-594 (3 and 10mg/kg per day) and candesartan cilexetil (0.3 and 1 mg/kg per day) dose-dependently improved glomerulosclerosis and the hyalin cast of tubules in DM-1K-SHR kidneys. Both KRH-594 (10 mg/kg per day) and candesartan cilexetil (0.3 and 1 mg/kg per day) dose-dependently inhibited cardiac hypertrophy. 4. KRH-594 (3 and 10 mg/kg per day), but not candesartan cilexetil, dose-dependently reduced the levels of triglyceride, total cholesterol and phospholipids in DM-1K-SHR. 5. These results suggest that KRH-594 improves diabetic complications, such as nephropathy and hyperlipidaemia, with hypertension.

Heterogeneous cardiac sympathetic innervation in heart failure after myocardial infarction of rats.

We examined cardiac neuronal function and beta-receptor with a dual-tracer method of [(131)I]meta-iodobenzylguanidine (MIBG) and [(125)I]iodocyanopindolol (ICYP) in rat heart failure after myocardial infarction (MI). In rats with MI, left ventricular (LV) systolic function decreased, and LV dimension and right ventricular (RV) mass increased gradually. MIBG accumulations of the noninfarcted LV (remote region) and RV decreased by 15% at 1 wk compared with sham-operated rats, and these accumulations were restored by 71% and 56%, respectively, at 24 wk compared with age-matched sham rats despite sustained depletion of myocardial norepinephrine contents in these regions. ICYP accumulation of the remote region and of the RV did not decrease at any stages. Myocardial MIBG distribution was heterogeneous at 1 wk when it was lower in the peri-infarcted region than in the remote region, associated with reduced ICYP accumulation in the peri-infarcted region. The heterogeneous distribution of both isotopes disappeared at 12 wk. Thus cardiac sympathetic neuronal alteration was coupled with downregulation of beta-receptors in rat heart failure after MI. The abnormal adrenergic signaling occurred heterogeneously in terms of ventricular distribution and time course after MI.

Effect of ozagrel on locomotor and motor coordination after transient cerebral ischemia in experimental animal models.

The effect of ozagrel, a selective thromboxane A(2) (TXA(2)) synthetase inhibitor, on the obstruction after cerebral ischemia-reperfusion was studied in experimental animal models. The reduced spontaneously locomotor activity and the obstruction of motor coordination were improved by the administration of ozagrel in the conscious cerebral ischemia-reperfusion mouse model. Ozagrel suppressed the decrease in specific gravity of the brain tissue induced by the occlusion-reperfusion in the conscious cerebral ischemia-reperfusion SHR model, and recovered the postischemic decrease in cortical PO(2) after middle cerebral artery occlusion-reperfusion in cats. The level of TXB(2), a metabolite of TXA(2), in the brain increased after the cerebral ischemia-reperfusion, and ozagrel prevented this increase. Additionally, ozagrel also increased the level of 6-keto-PGF(1alpha), a metabolite of prostaglandin I(2) (PGI(2)), in the brain tissue after cerebral ischemia-reperfusion, and the administration of PGI(2) improved the reduced spontaneous locomotor activity in the conscious cerebral ischemia-reperfusion mouse model. Our data suggest that ozagrel suppressed the obstruction following cerebral ischemia-reperfusion by preserving the cerebral blood flow via preventing the increase in TXA(2) and causing an increase in the PGI(2) level.

Washout of I-123 meta-iodobenzylguanidine for assessing cardiac sympathetic activity with progression of hypertension in Dahl salt-sensitive rats.

BACKGROUND: To evaluate cardiac sympathetic activity, a simple method should be developed to replace such complex methods as the spillover rate of tritiated norepinephrine (3H-norepinephrine) or microneurography of sympathetic nerve activity. The goal of this study is to evaluate cardiac sympathetic activities by analyzing the washout of I-123 meta-iodobenzylguanidine (123I-MIBG), a radiolabeled norepinephrine analogue, in Dahl salt-sensitive (DS) rats as it relates to the progression of hypertension. METHODS AND RESULTS: Dahl salt-resistant (DR) rats and DS rats were fed an 8 % salt diet starting at age 5 weeks. Marked hypertension and cardiac hypertrophy developed in the DS rats, whereas DR rats remained normotensive. Then the time-activity curves of 123I-MIBG from 15 to 200 minutes were obtained from both DS and DR strains at ages 8, 11, and 13 weeks using dynamic scintigraphic analysis. We also examined the nonneuronal washout of 123I-MIBG using dynamic scintigraphic studies in desipramine pretreated normal rats. In the preliminary study with desipramine pretreatment, the majority of the nonneuronal 123I-MIBG washout occurred by 90 minutes after injection. Therefore the late-phase washout in the control rats was found to reflect the neuronal washout. We then applied exponential curve fitting to the time activity curves acquired in the 90- to 200-minute period after 123I-MIBG injection in both DR and DS rats. When we compared the coefficients of these washout curves in the DS and DR rats as an index of cardiac sympathetic activities, the coefficient values remained high during all stages in DS rats, whereas they decreased with age in DR rats. CONCLUSION: Measurement of late-phase 123I-MIBG washout may be a useful tool for assessing the change in sympathetic activity in the progression of hypertension without the influence of extraneuronal washout of 123I-MIBG and left ventricular hypertrophy.

Tranilast inhibits the proliferation of human coronary smooth muscle cell through the activation of p21waf1.

Restenosis after percutaneous transluminal coronary angioplasty (PTCA) occurs due to vascular smooth muscle cell proliferation and migration. Recently, tranilast, an anti-allergic drug, has been used for the prevention of restenosis after PTCA. To determine the molecular mechanism involved, the effect of tranilast on the proliferation of human coronary smooth muscle cells (SMCs) was investigated. Tranilast arrested the proliferation of human coronary SMCs at the G0/G1 phase of the cell cycle. In association with this inhibitory effect, tranilast increased p21waf1 and p53 tumor suppressor factor, and decreased cyclin-dependent kinase 2 (CDK2) activity. These results suggest that tranilast inhibits the proliferation of human coronary SMCs during restenosis after PTCA via an induction of p21waf1 and p53. Tranilast may thus allow us to prevent restenosis after PTCA by interfering with this mechanism.

[Evaluation of Mycobacterium kansasii isolates from a clinical laboratory in a city hospital].

Fifteen isolates of Mycobacterium kansasii in Showa University Fujigaoka Hospital between 1982 and 1995 were investigated. Comparing by gender, 13 were isolated from male patients and only two were isolated from female patients. The average of cases was 48 years old and 14 out of 15 cases (93%) were isolated from respiratory tract specimens. The rate of the smear- and culture-positives was 64%, which was significantly higher than that (26%) of M. avium complex (p < 0.01 by chi 2 test). All 4 isolates were susceptible to rifampicin (10 micrograms/ml) by drug susceptibility testing using Ogawa egg medium, and only 1 was resistant to ethambutol (2.5 micrograms/ml). Seven out of 10 patients whose medical record was available were diagnosed as pulmonary infection with M. kansasii. Two out of 4 patients with primary infection type had underlying diseases such as diabetes mellitus and leukemia, while the remaining two patients did not have any underlying disease. Two out of 3 patients with secondary infection type had a medical history of tuberculosis and the remaining 1 patient had infected pulmonary cyst. Such as Pseudomonas aeruginosa, Enterobacter aerogenes and Flavobacterium spp., and Branhamella catarrhalis, associated with M. kansasii, bacteria more than 10(7) cfu/ml were isolated from the sputa of 3 patients with leukemia, infected pulmonary cyst and post-tuberculosis, respectively. M. kansasii, Stenotrophomonas maltophilia (10(7) cfu/ml) and Candida albicans were detected from the sputum of 1 patient with nephrosis, for which steroid (predonin) and antibiotics (piperacillin and latamoxef) were administrated, however, this patient was not diagnosed as a case of M. kansasii infection. These findings suggest the fact that M. kansasii inhabits among compromised hosts of a city hospital.

Angiotensin II type 1 receptor blockade prevents up-regulation of angiotensin II type 1A receptors in rat injured artery.

We investigated the effects of the angiotensin II (Ang II) type 1 receptor (AT1) antagonist KRH-594 on levels of the mRNAs for AT1A, AT1B, platelet-derived growth factor-receptor beta (PDGF-Rbeta), and extracellular matrix (ECM)-related genes using the competitive reverse transcription-polymerase chain reaction (RT-PCR) method and on neointimal formation in the balloon-injured rat carotid artery. The mRNA levels for AT1A and PDGF-Rbeta, but not for AT1B, increased from day 3 after injury to day 14. KRH-594 administered orally at 3 and 10 mg/kg/day significantly suppressed these increases. KRH-594 (10 mg/kg/day) also suppressed the injury-induced gene expressions for transforming growth factor-beta1 and fibronectin and reduced collagen alpha1(I) and alpha1(III) mRNA levels for the first 7 days after injury. KRH-594 (10 and 30 mg/kg/day) significantly and dose-dependently reduced the neointimal area in cross sections of the artery 14 days after injury. Another AT1 antagonist, TCV-116 (candesartan cilexetil; 1 and 3 mg/kg/day p.o.), had similar effects on the morphological change and AT1A mRNA level, whereas a smooth muscle relaxant, hydralazine (10 mg/kg/day p.o.), did not. These results indicate that up-regulation of AT1A, PDGF-Rbeta, and ECM-related genes in the balloon-injured carotid artery is in part an AT1-mediated phenomenon and that prevention of receptor up-regulation may contribute to the attenuating effects of AT1 antagonists on neointimal formation after injury.

[The Clinical Significance of Plasma]

(1 --> 3)- beta - D -Glucan ( beta -glucan), a fungal cell wall component existing in plasma was measured by the kinetic turbidimetric limulus test. Here 3 reported cases have proven the clinical usefulness of plasma beta -glucan. Case 1: A 46-year-old female with non-Hodgkin's lymphoma was admitted for severe hepatitis type B in June 1997. During hospitalization, the fever rose with no response to antibiotics and with a negative blood culture. Although the plasma beta -glucan concentration was high, the patient was administered with antimycotics (fluconazole; FLCZ) and she showed some signs of improvement. Case 2: A 52-year-old male with jaundice was hospitalized in November 1997. The third day following the operation on the pancreas head carcinoma, the body temperature rose higher with a negative blood culture. The fourth day, the plasma beta -glucan concentration was positive with negative endotoxin. As some improvements were obserbed from taking FLCZ, he was discharged in January 1998. Case 3: A 19-year-old male with epilepsy was hospitalized for ARDS in August 1997. A butterfly-like shadow was observed in the chest roentgenogram (suspected malignant lymphoma). The high titer of beta -glucan has continued and endotoxin was detected. The symptoms showed some signs of improvement and the titer of beta -glucan reduced with FLCZ. Although a high level of beta -glucan still remained, the patient was discharged, but has to under go regular follow-up examinations. The measurment of beta -glucan proved very useful not only as a diagnosis for the screening of deep mycosis but also as monitoring for therapies.

Effects of the new angiotensin receptor antagonist dipotassium (Z)-2-[[5-ethyl-3-[2'-(1H-tetrazol-5-yl)biphenyl-4-yl] methyl-1,3,4-thiadiazoline-2-ylidene]aminocarbonyl]-1-cy clopentencarbox ylate on experimental cardiac hypertrophy and acute left ventricular failure.

The cardiovascular effects of dipotassium (Z)-2-[[5-ethyl-3-[2'-(1H-tetrazol-5-yl)biphenyl-4-yl] methyl-1,3,4-thiadiazoline-2-ylidene]aminocarbonyl]-1-cyc lopentencarboxylate CAS 169328-25-0, KRH-594), a new angiotensin II type 1 (AT1) receptor antagonist, on pressure-overload cardiac hypertrophy in rats and on acute left ventricular failure in dogs were investigated. In rats with a 2-week abdominal aorta constriction, left ventricular weight (LVW) and systolic blood pressure (SBP) were significantly greater than in sham-operated rats. Oral administration of KRH-594 (10 or 30 mg/kg/day for 2 weeks) reduced the increases in both LVW and SBP. Another AT1 receptor antagonist, candesartan cilexetil (1 or 3 mg/kg/day for 2 weeks), also prevented this type of cardiac hypertrophy. In anesthetized dogs with a 60-min coronary ligation, left ventricular end-diastolic pressure (LVEDP) and total peripheral resistance (TPR) were raised, whereas the maximum first derivative of left ventricular pressure and cardiac output were both decreased. Intravenous administration of KRH-594 (3 mg/kg) significantly attenuated the increases in both LVEDP and TPR after coronary ligation. These results suggest that KRH-594, by reducing the cardiac afterload, may ameliorate pressure-overload cardiac hypertrophy in rats and produce an improvement in the hemodynamic status of dogs with acute left ventricular failure.

[Epidemiological evaluation of mycobacteria isolates in one city hospital: reports from the hospital microbiology laboratory].

The frequency of mycobacteria isolated from patient's specimens at Showa University Fujigaoka Hospital was investigated. By fitting a polynominal curve (degree = 3) of the annual frequency of culture-positive Mycobacterium tuberculosis (1977 through 1995), it was noted that the frequency had not changed since 1977. The patients in the 40s or older and 60s or older comprised 74 and 38%, respectively. Of 104 patients diagnosed as tuberculosis (between 1993 and 1995), 43 (41%) were compromised hosts with the following underlying diseases: kidney disease; diabetes mellitus; malignant tumor; respiratory disease; Behçet's disease; ophthalmosarcoidosis; multiple arthritis; Hashimoto's disease. This suggested that these compromised hosts are at high risk of onset and relapse of tuberculosis, and occasionally the doctor's or patient's delay was seen during the diagnostic process. By fitting a polynominal curve (degree = 3) of the annual frequency of culture-positive atypical mycobacteria (1977 through 1995), it was noted that the frequency had increased since 1981. The patients in the 40s or older and 60s or older comprised 88 and 60%, respectively. Between 1982 and 1994, we encountered 46 cases of atypical mycobacteriosis of the lung: 37 M. avium complex (MAX) diseases; 7 M. kansasii diseases; one M. chelonae disease; one unidentified disease involving Runyon Group II mycobacterium. Eight involved patients with bronchiectasia (5 cases), diabetes mellitus (2 cases), or leukaemia (one case). Haemophilus influenzae, Pseudomonas aeruginosa, and Moraxella catarrhalis at more than 10(7) CFU per ml of sputum were isolated from 6 patients diagnosed with MAC or M. kansasii lung diseases, suggesting the possibility of mixed infections. M. tuberculosis and atypical mycobacterium (15 cases), and two different atypical mycobacteria (16 cases) were isolated from the same or different specimens of the same patients at the same or different times. However, the pathogenicity of these mycobacteria remained unknown, because atypical mycobacteria are non-pathogenic in many cases. The above findings suggested that the environment fit for the mycobacteria growth in human body has gradually been formed associating with aging, lung-lesion, and decline of immune capacity.

[Antimicrobial activities of roxithromycin against recently obtained clinical isolates].

The purpose of our investigation was to monitor current trends in the susceptibility patterns of clinical bacterial isolates to roxithromycin (RXM). We measured the MICs of macrolide antibiotics, such as RXM, erythromycin (EM), clarithromycin (CAM), rokitamycin (RKM) and midecamycin (MDM), and other classes of antibacterial compounds against various clinical isolates at seven institutions between October and December in 1994 and 1995. RXM had excellent antibacterial activities for S. pyogenes, S. agalactiae, M. (B.) catarrhalis and methicillin sensitive S. aureus. Against methicillin sensitive S. epidermidis, RXM activity was fairly good but about 20% of the strains had MIC > or = 128 micrograms/ml. The activity against S. pneumoniae was not so potent and similar to activities of EM, CAM, MDM, and clindamycin. The vast majority of methicillin resistant S. aureus and S. epidermidis were also resistant to macrolide antibiotics and other classes of compounds tested. In conclusion, RXM is an unique macrolide antibiotic by retaining potent activity against S. pyogenes, S. agalactiae, S. aureus except MRSA, M. (B.) catarrhalis and M. pneumoniae.