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Biomedical subjects

S Fujimoto

Publications and source records attributed to S Fujimoto.

At least 505 records · Page 28Linked to original sources

Lipopolysaccharides from Campylobacter jejuni associated with Guillain-Barré syndrome patients mimic human gangliosides in structure.

Lipopolysaccharides extracted from Campylobacter jejuni serostrains (serotype reference strains) for serotypes O:4 and O:19 were found to have core oligosaccharides with terminal structures resembling human gangliosides GM1 and GD1a. High-molecular-weight molecules that reflected the presence of O chains were shown in immunoblots to be immunologically specific for each serostrain. The O:19 antiserum also reacted strongly with core oligosaccharides of two isolates from patients with Guillain-Barré syndrome (GBS), but the banding patterns and molecular structures were different from those of the O:19 serostrain. A neuraminobiose disaccharide unit is attached to the terminal Gal residue in one isolate, and the other isolate lacked terminal N-acetyl glucosamine and galactose with attached sialic acid so that the sialic acid residues were present in a neuraminobiose unit linked to the only remaining galactose. Analysis of the high-M(r) lipopolysaccharides of the O:19 serostrain and the two isolates from GBS patients revealed the presence of a hyaluronic acid-like polymer with disaccharide-repeating units consisting of beta-D-glucuronic acid amidated with 2-amino-2-deoxyglycerol and N-acetyl glucosamine. The results confirm a potential role for the core oligosaccharides in the etiology of GBS but also suggest that the O-chain polysaccharide may be a contributing factor.

Campylobacter jejuni↗

PCR-based restriction fragment length polymorphism typing of Helicobacter pylori.

We applied a molecular typing approach for Helicobacter pylori that uses restriction fragment length polymorphism (RFLP) analyses of an 820-bp PCR-amplified portion of the ureC gene in H. pylori. The PCR products were digested with restriction enzyme HhaI, MboI, or MseI, and the fragments generated were analyzed by agarose electrophoresis. Among 25 independent clinical isolates, each showed a different pattern when a combination of the three RFLP patterns was used. Using this method, we studied isolates from the antrum or the body of the stomach of 14 patients before and after antibiotic therapy. Before treatment, successful isolation of H. pylori from the two sites of the stomach was possible for 12 of the 14 patients. For 10 of these 12 patients, each pair of isolates had identical RFLP profiles. For the other two patients (16.7%), however, isolates from the antrum and the body of the stomach had different RFLP profiles. Treatment was successful for 6 of the 14 patients; of the 8 patients with treatment failures, 5 had identical isolate pairs. In each case, the isolates found posttreatment were the same as the pretreatment isolates. For one of the patients who was colonized with two different isolates pretreatment, one of the isolates was identified at both sites after unsuccessful treatment. We also studied six long-term follow-up patients who had sequential biopsies at intervals of up to 5 months. Each follow-up isolate from each patient had the same RFLP profile as the initial isolate. This typing method provides a reliable and reproducible typing scheme for the study of H. pylori infections and indicates that infection with more than one H. pylori isolate is not rare.

Bacterial Typing Techniques↗

Hypocarbia and cystic periventricular leukomalacia in premature infants.

One hundred sixty seven survivors among very low birthweight infants with a gestational age of less than 35 weeks have been studied prospectively. The purpose of this study was to clarify the relationship of severe prenatal and perinatal complications and hypocarbic alkalosis, defined as a carbon dioxide tension (PaCO2) of less than or equal to 2.67 kPa and a pH of 7.50 or greater during the first 24 hours of life, to cystic periventricular leukomalacia (PVL) depicted by serial cranial ultrasonographic examinations. Complications occurred in 16 infants, five of whom presented with PVL, while eight of 151 infants without complications had PVL. Twenty six of the infants had hypocarbic alkalosis, six with evidence of PVL, and seven of the 136 infants without hypocarbic alkalosis had PVL. These results suggest a significant relationship of complications and hypocarbic alkalosis to PVL. Mechanical ventilation should be managed carefully in premature infants to avoid PaCO2 of lower than 2.67 kPa.

Alkalosis↗

Effect of bis (tributyl tin) oxide on permeability of the blood-brain barrier: a transient increase.

OBJECTIVES: To study the effect of bis (tributyl tin) oxide (TBTO) on permeability of the blood-brain barrier. METHODS: Electron microscopy and an x ray microanalyser with lanthanum chloride as a tracer were used, and blood tin concentrations were determined with an atomic absorption spectrophotometer. Adult male wistar rats received 0.05 ml/kg body weight of TBTO orally. RESULTS: A transient increase in paracellular permeability at the blood-brain barrier was found 2 h after the dose of TBTO. Electron dense lanthanum deposits penetrated tight junctions of the endothelia and permeated the subendothelial space. The x ray microprobe data showed an accumulation of TBTO at the tight junctions at 2 h. Leakage of tracer did not occur at 4 h, but oedematous changes in the surrounding glial cells were prominent between 4 and 8 h and had almost returned to normal by 24 h. By atomic absorption analysis, it was seen that blood tin concentrations rapidly increased at 1 h and rose to a maximum peak at 8 h, then gradually decreased to reach zero at 24 h. CONCLUSIONS: Accumulated TBTO at tight junctions could have caused the temporary replacement of calcium ion by tin, which induces a transient increase in paracellular permeability throughout the blood-brain barrier.

Animals↗

Alpha 1-adrenoceptor subtypes mediating contraction of the femoral artery in spontaneously hypertensive rats.

alpha 1-Adrenoceptors (ARs) were divided into alpha 1H and alpha 1L subtypes by their different affinities for bunazosin or prazosin. alpha 1H-ARs were further subdivided into alpha 1A, alpha 1B, and alpha 1C subtypes. Therefore, this study was undertaken to determine which alpha 1-AR subtypes were involved in the activation of femoral artery preparations by alpha 1-AR agonists in spontaneously hypertensive rats (SHR). For comparison, aortic strips were also incorporated in the present study. In the presence of propranolol, deoxycorticosterone, and desipramine, norepinephrine (NE) contracted the vascular strips in a dose-dependent manner. Negative log EC50 values and maximum responses of NE-induced contraction of the SHR femoral artery were unchanged and increased, respectively, compared with those of Sprague-Dawley and Wistar-Kyoto rats (WKY). Contractile responses of the SHR aortae to NE were similar to those of the normotensive tissues. Schild plot data for alpha 1-AR antagonists indicated that alpha 1-AR subtypes mediating contraction of the aorta were homogeneous and had high affinities for bunazosin (pA2 9.4, alpha 1H subtype) and WB 4101 (pA2 9.3) and a low affinity for 5-methylurapidil (pA2 7.7). In the femoral artery, because Schild plots for bunazosin had slopes of less than 1.0, there were alpha 1H and alpha 1L subtypes. Bunazosin, at 10(-9) M, which could mask the alpha 1H subtype, yielded a Schild plot for bunazosin with a slope not different from unity and decreased the pA2 value for bunazosin (pA2 9.4 vs. 8.5).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-1 Receptor Agonists↗

The differentiation of entero-endocrine cells of pre- and postnatal rats: light and electron microscopy and immunocytochemistry.

The differentiation of cholecystokinin/gastrin (CCK/GA)-, glucagon (GLU)- and somatostatin (SOM)-positive cells in the pre- and postnatal rat duodenum was investigated with a special emphasis on the relationship to that of the fibromuscular intestinal wall by light and electron microscopy and immunocytochemistry. Between prenatal days 16 and 21, contacts of mesenchymal cells with the epithelium are frequent, and the differentiation of the entero-endocrine cells which occasionally display a secretory function becomes advanced in close proximity to an extensive capillary network in the underlying connective tissue. CCK/GA-positive cells can be detected by immunocytochemistry in the intestinal epithelium at prenatal day 18. Other types of entero-endocrine cells are not detected until prenatal day 19. Quantitative analysis demonstrates that the volume density of CCK/GA-positive cells per 100 microns2 cytoplasmic area increases sharply at postnatal day 5 relative to earlier stages. This may be mainly due to suckling of the neonatal rat.

Animals↗

Doppler echocardiographic assessment of left ventricular diastolic function in patients with systemic lupus erythematosus.

Thirty patients with clinically inactive systemic lupus erythematosus (SLE) were examined by Doppler echocardiography to investigate the diastolic properties of the left ventricle. Twelve age-matched healthy women were also examined as controls. The pulsed wave transmitral Doppler flow velocity curves were digitized and curves of their first derivatives were obtained. Isovolumic relaxation time (IRT), acceleration and deceleration half-time of the rapid filling wave (E) and atrial contraction wave (A) (AHTe, DHTe, AHTa, DHTa), A/E, peak dE/dt, -peak dE/dt, peak dA/dt, -peak dA/dt were measured. In the SLE group, IRT and DHTe were prolonged, A, A/E, peak dA/dt and -peak dA/dt were increased compared with the control group. We conclude that patients with SLE have abnormal left ventricular diastolic function, even though their disease is clinically inactive.

Adult↗

Effect of radical scavengers on the inactivation of papain by ascorbic acid in the presence of cupric ions.

Incubation of papain (EC 3.4.22.2) with ascorbic acid (AsA) and Cu2+ in acetate buffer (pH 5.6) results in an irreversible loss of enzyme activity by site-specific generation of free radicals [H. Kanazawa, S. Fujimoto, A. Ohara, Biol. Pharm.Bull., 16, 11 (1993)]. In this study, the effect of some compounds, known free radical scavengers, on the relationship between the inactivation of papain by the Cu(2+)-AsA system and the oxidation of AsA was investigated. Catalase completely protected the enzyme from inactivation by the Cu(2+)-AsA system, although hydrogen peroxide (H2O2) by itself, known to be generated during the autoxidation of AsA, did not inactivate the enzyme. The oxidation of AsA was unaffected by catalase. Both thiourea and sodium thiocyanate completely protected the enzyme from inactivation, while AsA was partially oxidized only in the initial stage. In the presence of potassium iodide, both the inactivation of the enzyme and the oxidation of AsA were characterized by a rapid initial phase followed by a stable phase where no reaction took place and, subsequently, a slower phase. Histidine partially prevented the inactivation of the enzyme and the oxidation of AsA. The present results suggest that H2O2 serves as a source of secondary, highly reactive species, probably hydroxyl radicals, which are responsible for the inactivation, and that the protection from inactivation by some radical scavengers, such as thiourea, sodium thiocyanate, potassium iodide, and histidine, is based on the removal of metal ions (Cu2+ or Cu+) at the specific site of inactivation.

Ascorbic Acid↗

Hydroxylation of phenylalanine and salicylate by stimulated polymorphonuclear leukocytes and the accelerating effect of glutathione on their hydroxylation.

Incubation of phorbol-myristate acetate-stimulated human polymorphonuclear leukocytes (PMNs) with phenylalanine and salicylate induced significant levels of formation of o- and m-tyrosines, and 2,3- and 2,5-dihydroxybenzoates (DHBAs), respectively, dependent on reaction time. Aromatic hydroxylation reactions were not inhibited by desferrioxamine, nor were they affected by the removal of trace ion contamination from the buffer solution used by treatment with conalbumin. Hydroxylation reactions were largely blocked by superoxide dismutase and hydroxyl radical (OH.) scavengers. The results of the present study suggest that the generation of OH. by human PMNs occurs during the respiratory burst. Hydroxylation of both phenylalanine and salicylate by stimulated human PMNs were significantly accelerated by incubation in the presence of the reduced form of glutathione (GSH). Hydroxylation of phenylalanine by stimulated guinea pig PMNs in the presence of GSH was significantly inhibited by desferrioxamine, although the same hydroxylation in the absence of GSH was not affected. Hydroxylation of phenylalanine by the hypoxanthine (HX)-xanthine oxidase (XO) system by intact PMNs was significantly accelerated by the addition of GSH, although that in the absence of PMNs was largely inhibited. Desferrioxamine showed an inhibitory effect on hydroxylation by the HX-XO system in the presence, but not in the absence, of intact PMNs. The results suggest that the formation of OH. by stimulated PMNs is accelerated by GSH, based on the occurrence of the Harber-Weiss reaction catalyzed by transition metal ions liberated and reduced by GSH from PMNs, and by the effective accumulation of H2O2 by the GSH-induced inhibition of catalase.

Animals↗

On the mechanism of inactivation of active papain by ascorbic acid in the presence of cupric ions.

An inactivation mechanism of active papain (EC 3.4.22.2) by the Cu(2+)-ascorbic acid (AsA) system was examined. Incubation of active papain, which contains an active sulfhydryl (SH) group, with the Cu(2+)-AsA system under aerobic conditions resulted in an irreversible loss of enzyme activity. The enzyme was not inactivated at a molar ratio of enzyme to Cu2+ of 1:< 1, whereas at a molar ratio of 1:1-2, the extent of inactivation showed the same dependence on the extent of oxidation of AsA. Saturation kinetics were observed with respect to the concentration of AsA. The degree of inactivation was dependent on the decrease in SH content of the enzyme. Catalase at a low concentration partially protected the enzyme from inactivation, but did not affect the oxidation of AsA. In addition, catalase at a high concentration completely protected both the enzyme from inactivation and AsA from oxidation. The present results suggest that an additional function of H2O2, besides producing hydroxyl radicals (.OH), is to promote the conversion of Cu+ into Cu2+, and that an active SH group of papain is site-specifically modified by the .OH, resulting in inactivation of the enzyme.

Amino Acids↗

Effects of beta 1- and beta 2-adrenoceptor agonists applied into the hypothalamic paraventricular nuclei of spontaneously hypertensive rats on urine production.

We investigated effects of beta-adrenoceptor agonists (beta 1-selective: T-1583 and dobutamine, beta 2-selective: fenoterol, non-selective: isoproterenol) on urine outflow rate, blood pressure, heart rate, respiratory rate and rectal temperature. The drugs were applied into the paraventricular nuclei (PVN) of spontaneously hypertensive (SHR), Wistar-Kyoto (WKY) and Wistar rats. Fenoterol and isoproterenol markedly decreased the urine outflow rate, compared with T-1583 and dobutamine in the rats. There was no marked difference among the three strains in responsiveness to fenoterol and isoproterenol. The antidiuretic effects of fenoterol were inhibited by a beta 2-selective antagonist, butoxamine, more markedly than a beta 1-selective antagonist, atenolol, in SHR; and the inhibitory effects of these drugs were partial in WKY. In Wistar rats, the effect of fenoterol was inhibited by a non-selective beta-antagonist, timolol, but not by atenolol or butoxamine. A vasopressin antagonist (i.v.) did not diminish the antidiuretic effect of fenoterol. Fenoterol reduced the blood pressure in SHR and WKY, but not in Wistar rats. It was suggested that there were predominantly beta 2-adrenoceptors mediating antidiuresis in SHR. In WKY and Wistar rats, however, the beta-adrenoceptor subtypes mediating antidiuresis have yet to be determined. The ability of beta-adrenoceptor agonists to decrease urine outflow rates in SHR was not altered as compared to that in the control rats. beta-Adrenoceptor-mediated antidiuresis was not due to vasopressin release.

Adrenergic beta-Agonists↗

Toxic effects of bis (tributyltin) oxide on the synthesis and secretion of zymogen granules in the rat exocrine pancreas.

Toxic effects of bis (tributyltin) oxide (TBTO) on the rat exocrine pancreas were studied with an electron microscope and X-ray microanalyzer. To measure tin concentrations in the blood, atomic absorption spectrophotometry was carried out. Adult male Wistar rats received an intramuscular injection of TBTO (0.5 ml/kg). At 2 h after injection, a marked swelling of mitochondria and an enlargement of the cisterns of the rough endoplasmic reticulum appeared in the pancreatic acinar cells. Using X-ray microanalysis, tin peaks were preferentially obtained from the swollen mitochondria. Heterogeneous zymogen granules with an electron dense core and a pale central zone increased in number in the acinar cells between 4 and 8 h after TBTO treatment. By 24 h after TBTO injection, the acinar cells had been ultrastructurally restored. Atomic absorption analyses showed that blood tin concentrations peaked at approximately 1 h after TBTO injection and then progressively declined, reaching the zero level at 12 h after injection. The effects of TBTO on the synthesis and secretion of zymogen granules were investigated with and without caerulein as a stimulant of secretion. Data obtained from these experiments indicated that TBTO inhibited both the synthesis and secretion of zymogen granules. The inhibition of the protein synthesis and secretion might be caused partly by mitochondrial dysfunctions due to the toxic effects of TBTO.

Animals↗

[Influence of physical responses due to controlled frequency breathing during exercise].

The purpose of this study was to examine the influence of respiratory responses due to controlled frequency breathing (CFB) during steady state cycle ergometric exercise (50% of Peak VO2, 60rpm) and to compare their responses between long distance (L), badminton (B), Swimming (S) and untrained (C; Control) group. Twenty-two (n = 6; L, B, C.n = 4; S) female university students were forced to take CFB for 1 min every 3 min during 20 min exercise. The breathing frequencies (BR) were 10, 12, 15, 20 and 30 frequencies in a minute. They were represented by CFB10, CFB12, CFB15, CFB20 and CFB30 respectively. In addition, CFB5, and 40 were given in a separate series. Ventiratory volume (VE) decreased significantly, (P < 0.05) when BR decreased less than about 50% of normal breathing (NB), CFB15 in (B) and (C). It showed to be less than CFB12 in (S), and CFB10 in (L). According to the decrease of VE, tidal volume and O2 pulse increased during CFB10 and 15 in all groups to maintain a constant O2 consumption for a given workload. End tidal partial pressure of O2 (PETO2) significantly decreased during less than CFB15 in (B) and (C), during CFB10 in (L). PETCO2 increased during less than CFB15 in (B), less than CFB12 in (L) and (C). However in (S) during every CFB, neither PETO2 nor PETCO2 changed significantly. Talking about the main differences shown between the four groups, (S) and (L) significantly exceeded (C) in maintaining of VE during CFB. However, in consideration of a ratio of the frequency of CFB to that of NB, (L) could maintain VE against more strictly controlled of breathing than other groups. (B) showed similar tendencies as (C) about some responses. It is considered that these differences in respiratory responses to CFB may result from difference of the duration and the level of breathing control that were forced during their daily training rather than whether their breathing frequency during each exercise is high or low.

Adult↗

[13-week oral toxicity study of lactitol (NS-4) in rats followed by 5-week recovery test].

Twenty male and 20 female Slc : SD rats were orally given lactitol, a hepatic encephalopathy drug, for 13 weeks at doses of 0, 0.625, 2.5 or 10 g/kg/day. A 5 week recovery test was conducted after the discontinuation of the drug treatment. Soft stool and decreased food consumption were seen in the 2.5 and 10 g/kg groups. In the 10 g/kg group, there were diarrhea, soiled fur, abdominal distention, salivation, piloerection, decreased body weight gain and increased water consumption. Urinalysis showed decreased urine volume and K+ excretion in the 10 g/kg group. In this dose group, biochemical examination showed decreased ALP, total cholesterol, triglyceride, glucose, Ca, Na+, Cl- and total protein. In the pathological examination, the cecum weight was increased in all dose groups. In the 2.5 and 10 g/kg groups, cecum distention with mucosal hyperplasia was observed. The adrenal weight was increased in the 10 g/kg group and hypertrophy of zona fasciculata of adrenal gland were seen in the 2.5 and 10 g/kg groups. The thymic weight was decreased in the 10 g/kg group. Ophthalmoscopic and hematologic examinations failed to reveal any drug induced changes. The increased cecum weight in the 0.625 g/kg group was regarded as toxicologically insignificant because of the failure of the association with any clinical or morphological findings. The above mentioned changes were satisfactorily reversible except for those in the cecum. Based on the results obtained, the NOAEL of this study was suggested to be 0.625 g/kg/day.

Administration, Oral↗

Intrapulmonary lymph nodes.

We report two cases of intrapulmonary lymph nodes detected by a chest roentgenogram or CT scan. The first patient was a 61-year-old fisherman referred complaining of cough and hemosputum. Chest roentgenogram showed a subpleural small nodular shadow at the superior segment of the right lower lobe. Thoracotomy showed a small anthracotic lymph node. The other case was a 68-year-old female patient admitted for further examination of a subpleural small nodular shadow at the latero-basal segment of the left lower lobe detected on a chest CT scan. Thoracoscopic surgery revealed that the black nodule was an anthracotic lymph node. The appearance of an intrapulmonary lymph node on radiological examination is rare, however, it should be considered in the differential diagnosis of a solitary or multiple peripheral pulmonary nodules in adults. A small nodular shadow should be resected if malignancy is suspected though not proven. Subpleural intrapulmonary lymph node warrants thoracoscopic surgery.

Aged↗

Immunohistochemical localization of interferon-gamma in normal human ovary.

There is increasing evidence that cytokines are important intraovarian non-steroidal regulators. The aim of the present study was to evaluate the presence in the human ovary of interferon (IFN)-gamma, a cytokine produced by T lymphocytes after mitogenic or antigenic stimulation. Very low levels of IFN-gamma (0.025-0.057 IU/ml) were found in follicular fluid of large spontaneously maturing follicles, in the ovarian vein (< 0.01-0.079 IU/ml) or peripheral blood (< 0.01-0.06 IU/ml). The avidin-biotin immunocytochemical technique, with appropriate monoclonal antibodies, was used to localize IFN-gamma-positive cells, human leukocyte antigen (HLA)-DR molecules, activated T cells, T helper/inducer cells and T cytotoxic/suppressor cells. IFN-gamma-positive cells were only detected in preovulatory follicles, associated with the follicular basal lamina, thecal vessels and interstitial tissue. In the same large follicles very few T helper/inducer cells were detected, but a high proportion of T lymphocytes expressed the CD8 phenotype in the theca, interstitial tissue and follicular cavity. No IFN-gamma-positive cells were observed in preantral and small antral follicles. The results indicate that the human ovary contains immunoreactive IFN-gamma, suggesting that the cytokine plays a paracrine role in human ovarian function.

Adult↗

[HTLV-I and retinal antigen recognized by T cells].

MT-2 immune but not naive murine (B10.BR) spleen cells responded not only to HTLV-I-infected cell lines but also to retinal antigens of various species by antigen-induced cell proliferation. The phenotype of the responding cells against HTLV-I-infected cell lines as well as retinal antigens was Thy-1.2+, CD4+ and CD8-. The antigen-induced cell proliferation against both HTLV-I-infected cell lines and retinal antigens was clearly inhibited by monoclonal antibodies to CD3, CD4, and MHC class II (I-AK). These data indicate that an epitope of HTLV-I-infected cell lines recognized by the CD4+ T cell is crossreactive to that of retinal antigens.

Animals↗

[Factors contributing to exercise-induced hypoxemia in patients with chronic lung diseases].

Arterial oxygen tension (PaO2) was found to decrease linealy during incremental exercise in patients with chronic lung diseases. The slopes of PaO2 during increasing workload (delta PaO2/delta VO2) in patients with COPD were closely and negatively correlated with diffusing capacity of the lung (DLco). In patients with IPF, the values of delta PaO2/delta VO2 were much higher, and were more strongly correlated with DLco than those in patients with COPD. Therefore, exercise-induced hypoxemia (EIH) was found to be related to three factors: PaO2 at rest, PaO2 slope predicted from %DLco, and exercise workload. The most important factor in EIH in patients with COPD was the decrease in PvO2 during exercise, which was caused by right heart failure and venous admixture. In patients with IPF, EIH was caused by abnormal O2 diffusion during exercise, decreased PvO2, and venous admixture. In conclusion, the factors contributing to EIH depend on the workload, so exercise testing is needed to decide on exercise therapy and O2 therapy in patients with chronic lung diseases.

Aged↗