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Biomedical subjects

M Nakazawa

Publications and source records attributed to M Nakazawa.

At least 271 records · Page 15Linked to original sources

Production of cytolethal distending toxin (CLDT) by Campylobacter fetus subsp. fetus isolated from calves.

Cytolethal distending toxin (CLDT) production by Campylobacter fetus subsp. fetus isolated from calves was examined using CHO cells. Twenty-five of the 26 strains tested were positive for CLDT with titer of ranging 1:8 to 1:2,048. CLDT positive strains were divided into low and high cytotoxin titer groups. Isolates from diarrhea cases tended to produce a significant amount of CLDT compared with isolates from liver. CLDT produced by C. fetus showed no effect on Y-1 cells and was heat-labile and trypsin-sensitive.

Animals↗

The epidemiological studies of Streptococcus suis infections in Japan from 1987 to 1991.

The epidemiological studies of S. suis infections in Japan were carried out between 1987 to 1991. A total of 380 S. suis strains isolated from pigs, cattle and a horse were serotyped by using antisera against S. suis types 1 to 22. A total of 318 (83.7%) of S. suis isolates were serologically typable. Serotype 2 was the most prevalent with 28.2%, followed by type 7 (10.8%), 1/2 (8.4%), 3 (7.4%) and 4 (5.5%). Of twenty S. suis strains isolated from cattle, eight were type 9, one was type 10, five were type 18, one was type 20 and five were untypable. One out of all the strains was also isolated from a racing horse with pneumonia. The majority of the isolates were originated from meningitis (38.2%), followed by from pneumonia (33.4%) and endocarditis (9.2%). Of all of the S. suis isolates, 333 isolates (87.6%) were identified correctly by API STREP 20 system.

Animals↗

Combined assessment with myocardial contractility and an index related to ventricular afterload in patients with isolated severe mitral regurgitation undergoing valve replacement. A retrospective study.

The afterload to the left ventricle increases following valve replacement in chronic mitral regurgitation (MR), yet there has been no study taking into account left ventricular (LV) afterload. In 43 patients with isolated chronic MR undergoing mitral valve replacement (MVR), we calculated LV wall stress using preoperative LV end-diastolic dimensions and diastolic aortic pressure (predictive LV wall stress = pWS). This value would represent LV wall stress at the instant of aortic valve opening immediately after MVR, assuming that LV end-diastolic dimensions and the aortic pressure did not change after operation. We also calculated end-systolic wall stress/volume index (ESS/ESVI) ratio, an index of myocardial function. None of 15 patients with the ESS/ESVI ratio > 1.6 had postoperative mortality or morbidity, whereas among the 26 patients with the ESS/ESVI ratio < 1.6, 12 patients had mortality (3 patients) and/or morbidity requiring intraaortic balloon pumping or prolonged catecholamine support. Three patients who died had pWS > 200 kdynes/cm2. Including these 3, all 5 patients whose pWS > 200 had mortality or severe morbidity immediately after surgery. In contrast, among the 38 patients with lower pWS, none died and only 7 patients (18%) had morbidity. Thus, patients who had a low contractility index and a high predictive afterload value had high mortality and morbidity. We conclude that the prediction of postoperative mortality and morbidity is improved by combined assessment of myocardial function and the hypothetical postoperative LV afterload.

Catecholamines↗

[Thirteen-week repeated dose toxicity by oral administration of trandolapril (RU44570) with 4-week recovery test in beagles].

Trandolapril (RU44570) was orally administered to dogs at a daily dose of 2.5, 25 or 250 mg/kg for 13 weeks. After the administration period, 25 and 250 mg/kg groups were observed for recovery for 4 weeks. The results obtained are as follows: 1. One male in the 250 mg/kg group showed decrease of food consumption and body weight, stomatitis, hematemesis, decumbence, hypothermia, and finally loss of reactivity to stimuli. This animal was killed because of these severe changes on the 39th day of administration. Among the surviving animals, a temporary loss of body weight was observed in a few animals of the 25 and 250 mg/kg groups, and a decreased food consumption was sporadically seen in a few animals of the 250 mg/kg group during the administration period. No abnormal changes were found in the clinical observation and water intake in the surviving animals. 2. The changes attributable to the pharmacological effect of RU44570 were a decreased activity of the angiotensin-converting enzyme, increases in plasma renin activity and urine volume, and decreases in specific gravity and concentrations of Na, K and Cl in the urine of every administration group. A decrease in blood pressure and an increase in the PAS and Bowie positive granules in the juxtaglomerular cells were also found in the 25 and 250 mg/kg groups. In addition, thickening of the afferent arteriolar wall of the glomeruli, a basophilic change of the renal tubular epithelial cells, and localized atrophy and hypertrophy of the renal tubules were observed in the 25 and 250 mg/kg groups, and increases in BUN, ALP and creatinine, and a slight dilation of the renal tubules were seen in the 250 mg/kg group. These observations indicated that RU44570 affected renal structure at a dose of 25 mg/kg or more renal function at a dose of 250 mg/kg. The animal killed in a moribund state showed nephrosis which consisted mainly of a moderate dilation of the renal tubules and vacuolation of the renal tubular epithelial cells, stomatitis, severe hemorrhage and necrosis with neutrophil infiltration in the fundus of the glandular stomach, atrophy of the hemopoietic system, and ectopic calcification in the heart, kidneys, stomach, trachea and alveolar wall. Changes in the kidneys similar to those observed in other animals were also detected. These changes suggested that this animal lapsed into a moribund state due to renal dysfunction and the resultant uremia.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Oral↗

[A molecular biological study on retinitis pigmentosa].

Retinitis pigmentosa was investigated with molecular genetic techniques, to identify gene abnormalities and to obtain a better understanding of the mechanism of retinal degeneration. First, a search for candidate genes was performed focusing on rhodopsin, peripherin/RDS, and phosducin genes, using non-radioisotopic SSCP and genomic DNA samples obtained from 387 Japanese patients with retinitis pigmentosa, including 56 families of the autosomal dominant type (ADRP). One ADRP family with rhodopsin Pro-347-Leu mutation and another with peripherin/RDS Asn-244-Lys mutation were identified. The genotype and phenotype correlation of each ADRP family was then analysed. Ocular findings associated with the rhodopsin Pro-347-Leu in the Japanese family were similar to those reported in Caucasian families, indicating that the same mutation can produce the common phenotype even among different ethnic populations. The phenotype associated with the peripherin/RDS Asn-244-Lys showed typical findings of retinitis pigmentosa associated with bull's-eye maculopathy. Finally, glutamate was immunohistochemically quantified in the photoreceptor inner segment of rds/rds mice using anti-Glu antibody. The results showed that glutamate was accumulated in the rds/rds mouse photoreceptor inner segment, suggesting that glutamate may play a role in the process of retinal degeneration caused by the peripherin/RDS gene abnormality, although the precise mechanism is currently unknown.

Animals↗

Identification of surface-exposed parts of red-light- and far-red-light-absorbing forms of native pea phytochrome by limited proteolysis.

Peptide fragments were obtained by limited proteolysis with trypsin and Staphylococcus aureus V 8 protease from either the PR or the PFR form of 121-kDa phytochrome purified from etiolated pea (Pisum sativum L.) shoots. Patterns of bands after polyacrylamide gel electrophoresis in the presence of SDS of the digests were different, with some bands appearing preferentially when the digestions were carried out with the PR or the PFR form. Amino-terminal sequences of the fragments were analyzed to determine the exact locations of the amino-termini of the fragments within the amino acid sequence of the apoprotein of pea phytochrome. The amino acid compositions of some of the sequenced fragments were determined in order to confirm the carboxy-terminal amino acids. Three cleavage regions were identified as kinetically favored sites of cleavage of PFR (Arg-746 to Lys-752, around Glu-877 and around Arg-1010), whereas only one was identified for PR (Glu-38 to Arg-62). Regions of Glu-255, Arg-383, Arg-583 to Glu-620 and Lys-1093 to Glu-1115 were also identified as potential sites of proteolytic cleavage in both forms of the phytochrome. Other cleavage sites, the specificities of which have not yet been determined, are Glu-404, Glu-695 and Lys-1045. Surface-exposed parts of phytochrome in the PR and PFR forms are discussed.

Amino Acid Sequence↗

[Cognitive function and its evaluation methods in Parkinson's disease--a study including RCPM and ERP].

In order to investigate features of cognitive impairment in idiopathic Parkinson's disease (PD) and suitable methods for the cognitive evaluation of patients with PD, 23 PD patients and 15 normal control subjects were studied using neuropsychological tests and auditory event-related potential (ERP). The two groups did not differ from each other in age or education. Clinical severity of the patients based on Hoehn & Yahr's staging ranged from stage I to IV: 7 patients at stage I, 8 at stage II, 7 at stage III and 1 at stage IV. All patients achieved the Mini-Mental State test (MMS) scores of 24 or greater, and none of the patients showed middle or serious grade of dementia based on the Diagnostic and Statistical Manual of Mental Disorders-Third edition-Revised (DSM-III-R). All patients and controls underwent MMS, the Hasegawa's Dementia Screening Scale (HDS), the Wechsler Adult Intelligence Scale-Revised (WAIS-R), the Raven's coloured progressive matrices (RCPM), The Wisconsin Card Sorting Test (WCST) and the Benton Visual Retention Test (BVRT). Auditory ERPs by standard oddball paradigm (two-choice reaction time task) were elicited (band-pass 0.1-50 Hz) from Cz electrode sites on all subjects with a random series of binaural 1,000 (standard; 80%) or 2,000 (target; 20%) Hz tones presented every 2 sec at 70 dB SPL. In RCPM, N100 peak latencies of ERP (target and standard), performance-IQ of WAIS-R (especially block design and digit symbol subtests) and in error scores of BVRT there were striking differences between the two groups (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

In vitro maturation and fertilization of preovulatory dog oocytes.

Mature beagle bitches were injected with exogenous gonadotrophins to induce superovulation. Preovulatory oocytes were collected at 72 h after intravenous injection of human chorionic gonadotrophin and cultured for 72 h in a modified Krebs-Ringer bicarbonate solution containing 10% fetal calf serum and 30 mg gentamicin sulfate l-1. Control oocytes were collected from ovaries of anoestrous bitches and cultured for 72 h. All oocytes were at the germinal vesicle stage when collected. At 72 h of culture, a significantly larger population (31.9%) of preovulatory oocytes reached metaphase II, compared with the control group (12.1%). Ejaculated beagle spermatozoa were washed and preincubated for 4 h, then capacitated spermatozoa were added to the oocytes. The kinetics of sperm penetration into the ooplasm did not differ between the two groups of oocytes, but the development of male and female pronuclei was observed more frequently in oocytes collected from preovulatory follicles. These results suggest that preovulatory maturation is required for the normal development of canine oocytes, although they are ovulated at the germinal vesicle stage.

Animals↗

Putative, selective inhibitors of sarcoplasmic reticulum Ca+(+)-pump ATPase inhibit relaxation by nitroglycerin and atrial natriuretic factor of the rabbit aorta contracted by phenylephrine.

Using three putative, selective inhibitors of the Ca+(+)-pump ATPase of sarcoplasmic reticulum (SR), cyclopiazonic acid, thapsigargin and 2,5-di-(tert-butyl)-1,4-benzohydroquinone, the mechanisms of relaxation of the arterial smooth muscle by cyclic GMP-generating vasodilators were studied in the ring preparations of the rabbit aorta. Nitroglycerin (NTG) and atrial natriuretic factor (ANF) were used as representative cyclic GMP-generating vasodilators. When the above three inhibitors of SR Ca+(+)-pump ATPase were present during the period of reloading of intracellular store sites with Ca++, the phasic contractions induced by phenylephrine or caffeine in the succeeding period in Ca+(+)-free media containing 2 mM EGTA were inhibited in a concentration-dependent manner. With 3 x 10(-5) M of cyclopiazonic acid the inhibition was almost complete for both agonists. NTG and ANF relaxed the aorta contracted by phenylephrine (10(-6) M) and produced an increase in cyclic GMP content. All the three SR Ca+(+)-pump ATPase inhibitors produced a concentration-dependent inhibition of the relaxation by NTG and ANF without affecting the increment of cyclic GMP content. These results indicate that the proper functioning of SR Ca+(+)-pump ATPase is necessary for elicitation of relaxation by NTG and ANF. Enhanced sequestration of Ca++ by SR may be an important mechanism by which these compounds induce relaxation in this type of smooth muscle.

Adenosine Triphosphatases↗

IgE and IgG2a antibody responses are induced by different antigen groups of the nematode Nippostrongylus brasiliensis in rats.

The differences were examined between IgE, IgG1 and IgG2a antibody responses against two kinds of nematode antigens in rats infected with Nippostrongylus brasiliensis. With ELISA studies, remarkable IgE and IgG1 antibody responses were observed against antigens in excretory/secretory products (ES) of N. brasiliensis, whereas the IgG2a antibody response against ES was negligible. On the other hand, antibody response to antigens in an extract of homogenized adult worm (AW) was observed mainly in IgG2a, with little response in IgE or IgG1. Immunohistochemical studies showed that IgE- and IgG1-binding antigens were localized almost exclusively in the subventral glands, a secretory apparatus in N. brasiliensis, while IgG2a-binding antigens were found mainly in the nematode wall along the body cavity. Immunoblot analysis revealed that the major IgE- and IgG1-binding molecules in ES were identical. On the other hand, some, but not all, of the major IgG2a-binding molecules in AW were different from the IgE/IgG1-binding molecules in ES. The findings suggest that the IgE/IgG1 and IgG2a antibody responses in N. brasiliensis-infected rats are induced by different groups of nematode antigens. Thus, it is presumed that the production of each class of antibody might be dependent, at least in part, on the nature of the antigen or antigen-linked molecules.

Animals↗

[Biventricular repair with a modified Glenn shunt for the hypoplastic right ventricle].

Between 1982 and 1990, 14 patients with small right ventricle underwent biventricular repair with a modified Glenn shunt. The patients consisted of 8 cases of pulmonary atresia and intact ventricular septum, 2 with pulmonary stenosis and intact ventricular septum, 3 with tetralogy of Fallot, 1 with pulmonary atresia and straddling tricuspid valve. Nine patients had one or more prior preliminary palliative procedures. Repairs consisted of a modified Glenn shunt and closure of the intracardiac and extracardiac shunt, with right ventricular outflow reconstruction in 13, and pulmonary valvotomy in 1. In nine patients superior vena cava was not ligated. There was one operative death (7%). Preoperative RVEDV ranged from 19 to 70% of normal with a mean of 36.1% of normal. Preoperative pulmonary resistance ranged from 1.6 to 5.3 unit with a mean of 2.8 unit. Preoperative PA index ranged from 102 to 444 mm2/m2 with a mean of 234.3 mm2/m2. No patients died later. Follow-up 2 to 9 year after operation showed that 9 patients were in the New York Heart Association class I and 4 were in class II. Our experience shows that this procedure can be safely done for patients, who have hypoplastic right ventricle smaller than 40% of normal and are not candidate for Fontan procedure because of high pulmonary vascular resistance and inadequate size of pulmonary artery. In this procedure a modified Glenn shunt without ligation of SVC may effectively reduce the volume overload on the right ventricle.

Adolescent↗

Evidence that [3H]glutamate binding sites are masked by biologically relevant endogenous factor on cell membranes of frog spinal cord.

We identified the possible endogenous factor effective to modulate the binding of [3H]-labeled excitatory amino acid agonists and antagonists in the 100,000 x g supernatant of Triton X-100 (0.01%)-treated cell membranes from frog spinal cords. The factor inhibited the binding of [3H]glutamate to Triton X-100-treated cell membranes, to which the binding capacity of [3H]glutamate increased much more than that to intact cell membranes. The binding capacities of [3H]AMPA (an AMPA type agonist) and [3H]CPP (an NMDA type antagonist) to cell membranes remained low by Triton treatment, but they were enhanced significantly by the addition of the factor. The effect of the factor on the [3H]kainate binding was hardly observable. The factor may provide key information on receptor structures and the classification of receptor types concerning excitatory amino acids in the mammalian central nervous system.

Animals↗

Transient patterns of serotonergic innervation in the rat visual cortex: normal development and effects of neonatal enucleation.

The transient aggregation of serotonin (5-HT)-containing fibers in the early development of rat visual cortex was examined immunohistochemically. The aggregation of 5-HT immunoreactive (IR) fibers consisted of three stages which were classified according to the course of time and degree of space occupied. The primary aggregation appeared in the subplate and moved upward along the development of the cortex. The aggregation proceeded to the secondary stage in presumptive layer IV. The fibers extended in a column-like structure following the secondary aggregation and formed the tertiary aggregation. The upper edge of the tertiary aggregation formed a lattice-like pattern in layer I and its structure was recognized to be similar to the structure of a 'blob' which characterizes the primary visual cortex in monkey. This transient aggregation of 5-HT-IR fibers began in the subplate of the anterior visual cortex on postnatal day 2 (PND 2) and progressed towards the posterior. On PND 11, the secondary and tertiary aggregations were completed in the entire region. No further aggregation of 5-HT-IR fibers was observed on PND 15. The anterior-to-posterior axis in the aggregation process corresponds to the direction of differentiation in the layer structure of cortex. In order to investigate the relationship between the transient aggregation of 5-HT-IR fibers and the development of the visual pathway, the secondary and tertiary aggregation on PND 11 were observed after postnatal monocular or binocular enucleation. Enucleation of eye balls did not affect either the area occupied by the 5-HT-IR fibers in the secondary aggregation or the number of column structures in the tertiary aggregation. However, the contralateral and ipsilateral cortices of monocularly enucleated cases were irregularly shaped in the secondary aggregation. The distribution of 5-HT-IR fiber terminals in the binocular area (Oc1B) increased in density on the contralateral side in the monocular enucleation, while that of both sides in the binocular enucleation was of non-homogeneous density and were shaped irregularly. The above results suggest that the transient aggregation of 5-HT-IR fibers observed in the early stage of development of visual cortex is regulated primarily by the intrinsic factors, and that extrinsic factors, such as visual pathway input, affect the aggregation within the boundary of such intrinsic factors. That is, the visual pathway input and the input balance from both eyes affect the distribution density of 5-HT-IR fibers and the shape of the visual cortex, respectively.

Animals↗