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Biomedical subjects

Y Ohtsuka

Publications and source records attributed to Y Ohtsuka.

At least 73 records · Page 4Linked to original sources

[Recent advances in tetrodotoxin research].

One century has passed since fugu toxin was named tetrodotoxin (TTX) by Tahara. Chemical problems such as crystallization of tetrodotoxin and subsequent structure determination were solved by research groups headed by Tsuda, Hirata, Woodward, and Mosher. The International Symposium on the Chemistry of Natural Products in Kyoto (1964) was well known as symposium which the structure of TTX was internationally clarified. Since the first isolation of toxin from taricha torosa (imori) as natural source except for fugu fishes, distribution of toxin in nature has been widely investigated. And, it was proved that toxin is not produced by fugu fishes, but rather is formed by sea bacteria (30 sp.) such as Alteromonas sp, Vibrio sp, Shewanella. However, it seems to be difficult to explain the tetrodotoxin accumulation at high concentration in fugu by only toxin production by bacteria. TTX analogues were isolated from natural origins such as crabs, fish, annelids, and algae. Based on the structure of these toxin analogues, the biosynthesis of toxin and the structure-activity relationship (Na+ channel) were proposed by Yasumoto-Yamashita. The findings of wide distribution of toxin in nature may be attributed to development of highly sensitive detection method for toxin. The interesting proposal for the biosynthesis and the structure activity, and the detection method for toxin are outlined in this review.

Alteromonas↗

Serum KL-6 concentrations in dairy farmers.

STUDY OBJECTIVES: Serum KL-6 (Krebs von den Lungen-6) has been recognized to be a marker for the activity of diffuse interstitial lung diseases. The purpose of the study is to evaluate serum KL-6 measurement as a marker for farmer's lung disease (FLD). DESIGN: A cross-sectional survey of a cohort of dairy farmers. Retrospective measurement of KL-6 stored serum samples from those dairy farmers previously screened for FLD. SETTING: University hospital screening project for FLD within a dairy-farming community in Japan. PARTICIPANTS: Four hundred seventy-two dairy farmers were invited to attend a local clinic. MEASUREMENTS AND RESULTS: We examined serum KL-6 concentrations in 272 farmers. Subjects were classified into three groups: (1) 5 farmers with FLD, (2) 30 farmers with positive serum precipitating antibodies to Saccharopolyspora rectivirgula and/or Thermoactinomyces vulgaris without FLD (Ab(+)), and (3) 237 farmers without these antibodies (Ab(-)). Serum KL-6 concentrations in the FLD group were significantly higher than those in the Ab(+) and the Ab(-) groups (1,263 +/- 288 [SEM], 328 +/- 57, and 207 +/- 6 U/mL, respectively, p < 0.001). Serum KL-6 concentrations in those with FLD were significantly higher than KL-6 concentrations from stored screening samples from the same individual when FLD was not diagnosed (1,263 +/- 288 and 419 +/- 209 U/mL, respectively, p < 0.05). Serum KL-6 concentrations of the Ab(+) group were significantly higher than those of the Ab(-) group (p < 0.001). In the Ab(+) group, farmers with high serum KL-6 concentrations had lower permeability coefficients than farmers with normal serum KL-6 concentrations (p < 0.05). These results may suggest that subclinical FLD can be detected in farmers with high KL-6 concentrations and precipitating antibodies. CONCLUSION: Serum KL-6 concentration can be a useful marker for assessing the activity of FLD and may be able to be used to detect subclinical disease.

Actinomycetales↗

PF1163A and B, new antifungal antibiotics produced by Penicillium sp. II. Physico-chemical properties and structure elucidation.

The structures of new antifungal antibiotics, PF1163A and B, were elucidated by spectroscopic analyses of the degradation products and by X-ray crystallography of the de-2-hydroxyethyl derivative of PF1163B. Both antibiotics consist of a 13-membered macrocyclic structure containing a derivative of N-methyl tyrosine and a hydroxy fatty acid. PF1163A differs from PF 1163B by having an additional hydroxyl group on the side chain.

Antifungal Agents↗

[Utility of Ringer's acetate solution as an intraoperative fluid during cardiovascular surgery with cardiopulmonary bypass].

This study aimed to clarify the difference in the effects of Ringer's acetate (AR) and Ringer's lactate (LR) administration during cardiovascular surgery with cardiopulmonary bypass. We evaluated their effects on intra and postoperative metabolism, liver functions, blood gas and hemodynamic states. Twenty patients were divided into two groups; AR group (n = 10) and LR group (n = 10). Intraoperative serum D-lactate levels in LR group were significantly higher than those in AR group from the beginning of the operation to awakening. Serum acetate levels showed no increase in both groups. The arterial ketone body ratio (AKBR) in AR group was higher than that in LR group, but the difference was not significant. Serum glutamic pyruvic transaminase (GPT) and alkaline phosphatase (ALP) levels in LR group were significantly higher than those in AR group from the induction of the anesthesia. It has been reported that acetate has a greater vasodialatory effect than lactate. However, our findings indicate no significant difference in hemodynamics between the two groups. These results suggest that AR may be more useful than LR during cardiovascular surgery with cardiopulmonary bypass.

Adult↗

Enhanced expression of N-myc messenger RNA in neuroblastomas found by mass screening.

A substantial fraction of neuroblastomas found by mass screening have been suggested to regress spontaneously because of the high incidence of infantile neuroblastomas in the screening population. In this study, 70 neuroblastomas were analyzed for expression of proto-oncogenes related to neuronal differentiation to clarify the biological significance of proto-oncogene expression in the screening-positive and -negative tumors. The tumors consisted of 39 neuroblastomas found by screening (group 1), 16 non-N-myc-amplified neuroblastomas found by clinical symptom(s) (group 2), and 15 N-myc-amplified neuroblastomas found by clinical symptom(s) (group 3). The expression of c-src, trk A, and N-myc in tumor tissues was analyzed by quantitative RNA PCR. Neuronal c-srcN2 expression varied significantly in the following order: group 1 > group 2 > group 3. The level of expression of trk A was markedly reduced in group 3 but did not differ in groups 1 and 2. Most tumors in group 3 overexpressed N-myc. However, N-myc expression in group 1 was significantly higher than that in group 2. Thus, the characteristics of proto-oncogene expression in screening-positive tumors included enhanced expression of c-srcN2 and N-myc mRNA, regardless of nonamplification of N-myc. Our results suggest that the role of N-myc differs in neuroblastomas detected by screening and in N-myc-amplified tumors.

Disease-Free Survival↗

The development of normal feeding and swallowing: Showa University study of the feeding function.

Since the 1980s the Department of Hygiene and Oral Health at the Showa University School of Dentistry has focused its research efforts on the development of feeding function and disorders. In addition, we have treated dysphagic children and dysphagic elderly using our feeding training program approach. The developmental course of the feeding function includes the following steps: 1) Suckle feeding and prefeeding period; 2) Acquiring the ability to swallow with lips closed; 3) Acquiring the ability to take food with lips closed; 4) Acquiring the ability to push mashed food with the tongue and anterior hard palate; 5) Acquiring the ability to perform mastication; 6) Beginning self-feeding; 7) Beginning finger feeding; 8) Beginning using table ware.

Child Development↗

Expression of extended polyglutamine sequentially activates initiator and effector caspases.

To date, eight neurodegenerative disorders, including Huntington's disease and dentatorubral-pallidoluysian atrophy, have been identified to be caused by expansion of a CAG repeat coding for a polyglutamine (polyQ) stretch. It is, however, unclear how polyQ expansion mediates neuronal cell death observed in these disorders. Here, we have established a tetracycline-regulated expression system producing 19 and 56 repeats of glutamine fused with green fluorescent protein. Induced expression of the 56 polyQ, but not of the 19 polyQ stretch caused marked nuclear aggregation and apoptotic morphological changes of the nucleus. In vitro enzyme assays and Western blotting showed that polyQ56 expression sequentially activated initiator and effector caspases, such as caspase-8 or -9, and caspase-3, respectively. Furthermore, using cell-permeable fluorogenic substrate, the activation of caspase-3-like proteases was demonstrated in intact cells with aggregated polyQ. This is the first direct evidence that the expression of extended polyQ activates caspases and together with the previous findings that some of the products of genes responsible for CAG repeat diseases are substrates of caspase-3 indicates an important role of caspases in the pathogenesis of these diseases.

Amino Acid Chloromethyl Ketones↗

Nonoperative management of blunt pancreatic injury in childhood.

PURPOSE: Nonoperative management for blunt pancreatic injury in children was performed between 1977 and 1998. The efficiency and safety of nonoperative management was examined. METHODS: Pancreatic injury was diagnosed in 20 children. The surgical indication was determined by hemodynamic instability and the management of associated injuries. Children without surgical indications were treated initially by nonoperative management. RESULTS: Nineteen of 20 children were treated initially nonoperatively, and 18 of the 19 survived. Surgical exploration was performed in only 1 child with perforation of the duodenum and bile duct. One child died of complications of total parenteral nutrition. Ultrasound scan and computed tomography scan showed pancreatic contusion in 9, laceration in 6, and injury of the main pancreatic duct (MPD) in 5. Pseudocysts were detected in 10 (5 laceration and 5 MPD injury). Pseudocysts smaller than 10 cm disappeared after nonoperative management, and those larger than 10 cm required operative management. Rupture of pseudocysts occurred in 2 children by rotating the upper torso. CONCLUSIONS: Nonoperative management of pancreatic injuries is effective in children, although careful management is required to avoid complications. Pseudocysts smaller than 10 cm were treated successfully by nonoperative management, and those larger than 10 cm required surgical management.

Child↗

Electroclinical characteristics of hemimegalencephaly.

Presented here are two long-term follow-up patients with hemimegalencephaly. Patient 1 had Ohtahara's syndrome, which evolved into West's syndrome. Patient 2 had localization-related epilepsy, which demonstrated epilepsia partialis continua throughout the clinical course. The patients' interictal electroencephalograms revealed asymmetric suppression-burst patterns sometime during the clinical course: only during early infancy in patient 1 and until the last follow-up (at 30 years of age) in patient 2. Both patients had moderate mental and motor disturbances with persistence of seizures. Hemiplegia was progressive during early childhood. Aggravation of hemiplegia might be related to frequent seizures and persistent electroencephalographic abnormalities during early childhood. Although asymmetric suppression-burst patterns are considered characteristic electroencephalographic findings in these cases, the duration of their appearance did not have definite prognostic significance.

Adolescent↗

Coronary artery bypass grafting in patients with systemic lupus erythematosus.

OBJECTIVE: Few reports exist on the results of coronary artery bypass grafting (CABG) in patients with systemic lupus erythematosus (SLE). METHODS: We retrospectively reviewed eight CABG in seven SLE patients. In early and late postoperative angiography, all grafts were evaluated for occlusion, development of string sign, or presence of significant stenosis. The early and late results were compared. The pathological studies were performed on the segments of the internal thoracic artery (ITA) and saphenous vein collected from each patient. Atherosclerosis of the ITA was analyzed using the subjective evaluation proposed by Kay et al. (Kay HR, Korns ME, Flemma RJ, Tector AJ, Lepley D. Atherosclerosis of the internal mammary artery. Ann Thorac Surg 21;1976:504-507) scale 0-4 (0 = normal, 1 = minimal disease, 2 = less than 25% luminal narrowing, 3 = 25-50% narrowing, and 4 = greater than 50% narrowing). RESULTS: The patients consisted of three men and four women with a mean age of 59.8 years. Co-morbid diseases were frequent and there were three patients (37.5%) with renal failure (two dialysis patients, one with renal dysfunction) and two patients with severe atherosclerosis of the aorta. The ITA was used in four patients. Saphenous vein graft was used in seven patients. Concomitant procedures included aortic valve replacement and mitral annuloplasty, mitral valvuloplasty and tricuspid annuloplasty, mitral valve replacement and tricuspid annuloplasty (TAP). There was one hospital death (12.5%). Early patency rates were 87.5% (21/24). No other atherosclerotic changes or stenosis suggesting vasculitis were noted. In pathological studies, there was no significant atherosclerosis in the six ITA specimens from four patients, although three patients had degree two atherosclerosis. No vasculitis was found in ITA or saphenous vein grafts. During the mean follow-up period of 35.3 months (range, 5-91 months), there was one non-cardiac late death. Late restudy (in three patients, 12, 57 and 64 months later respectively) revealed no deterioration in either ITA or vein grafts. Overall prognosis after the operation in SLE patients appears to be good. No other cardiac events were observed, and patients demonstrated marked clinical improvement. CONCLUSIONS: CABG in SLE patients can be performed with acceptable morbidity and mortality. Our data so far reveals no evidence to preclude the use of ITA and vein grafts in SLE patients.

Adult↗

Ethanol distribution in the brain of a victim autopsied after acute subdural hemorrhage.

We examined ethanol distribution in the brain of a 62-year-old male, who had died of acute subdural hemorrhage 4 days after injury. His blood ethanol concentration was 2.70 mg/g on admission. Blood pressure suddenly decreased and spontaneous respiration ceased 7 h after admission. He was artificially ventilated and died 4 days later. Ethanol was detected in the subdural hematoma, cerebellum, medulla oblongata and all cerebral lobes. Ethanol level in the right parietal lobe was highest; the levels in the right hemisphere of the cerebrum were higher than those in the left. Ethanol levels in the right parietal lobe were almost the same as the blood level calculated 7 h after admission; while the levels in the left parietal lobe and cerebellum were much lower. Thus, it was judged that cerebral blood flow first ceased in the right parietal lobe at 7 h after admission and completely ceased in other regions 11-12 h after. Assessment of ethanol distribution in multiple brain regions seems useful for estimating the time and progression profile of brain death.

Journal Article↗

Long-term follow-up of an individual with vitamin B6-dependent seizures.

We report on a 31-year-old female with vitamin B6-dependent seizures whose seizure onset was in the neonatal period. Her elder brother had the same disorder and died in infancy. Administration of vitamin B6 was initiated in the postnatal period. At the age of 12 years 1 month, 2 months after withdrawal of vitamin B6, visual seizures began to occur frequently. Myoclonic seizures and occasional generalized convulsive seizures were also observed. At the same time, photoparoxysmal response and spontaneous diffuse spike-wave bursts were seen on her EEG. Myoclonic seizures were provoked by intermittent photic stimulation during the EEG. It is distinctive that visual seizures were one of the main seizure types in this patient, that her clinical course was relatively benign, and that she has normal intellectual outcome.

Adult↗

Nonconvulsive status epilepticus in childhood localization-related epilepsy.

PURPOSE: To report on three children with localization-related epilepsy who exhibited minor seizures (atypical absences, brief atonic, and myoclonic) and nonconvulsive status epilepticus (NCSE) consisting of these minor seizures, and to elucidate their significance. METHODS: We studied the electroclinical characteristics of these children. Ictal electroencephalograms (EEGs) of NCSE were evaluated by using simultaneous video-EEG-electromyogram (EMG) polygraphic recordings. RESULTS: All patients began to have partial seizures between the ages of 6 months and 2 years 7 months, with minor seizures appearing later, between the ages of 1 year 11 months and 6 years 6 months. These minor seizures evolved into NCSE. Complex partial seizures remained after suppression of the minor seizures. Interictal EEGs taken when the minor seizures appeared showed excessive diffuse epileptic discharges in addition to multifocal spike-waves. Before and after suppression of the minor seizures, focal epileptic discharges predominated on the EEGs. On ictal EEGs of brief atonic and myoclonic seizures, diffuse spike-wave and polyspike-wave bursts were detected. Ictal EEGs of the atypical absences revealed diffuse spike-wave bursts mixed with irregular high-voltage slow waves, often interspersed with brief atonic and myoclonic seizures. When atypical absences lasted for a long time, patients manifested NCSE. Polytherapy might be related to the occurrence of minor seizures and NCSE, because all patients were treated with polytherapy at their appearance, and simplification of antiepileptic drug (AED) therapy seemed to be effective. CONCLUSIONS: We concluded that this NCSE is a type of atypical absence status which is an age-dependent, transient, electroclinical condition. The mechanism of occurrence of these minor seizures might be related to secondary bilateral synchrony.

Child↗

Induction of anaphylaxis in mouse intestine by orally administered antigen and its prevention with soluble high affinity receptor for IgE.

Early symptoms of food allergy, including diarrhea, are caused by IgE-mediated anaphylactic reactions. To clarify the mechanisms of IgE-mediated anaphylactic reactions in the intestine induced by orally administered antigen, a mouse model was established by s.c. implantation of a murine hybridoma capable of producing monoclonal anti-trinitrophenyl IgE antibody. Morphologic and immunologic changes in the intestine, as well as the effect of the soluble high affinity IgE receptor alpha chain, were investigated after oral challenge with antigen in this mouse model. Diarrhea, a decrease in s.c. blood flow, an increase in vascular permeability, a substantial increase in serum histamine levels, and noticeable infiltration of mast cells and IgE-bearing cells into the lamina propria were observed around 30 min after antigen challenge. However, these changes were efficiently prevented by pretreatment of the mice with the soluble high affinity IgE receptor alpha chain. These findings suggested that oral administration of antigen actually induced anaphylactic shock in our mouse model. This reaction was most likely to be mediated by mast cell activation, in response to the IgE-antigen complex, and a soluble form of the high-affinity IgE receptor efficiently prevented this IgE-mediated anaphylactic reaction by trapping free IgE.

Administration, Oral↗

Polaprezinc down-regulates proinflammatory cytokine-induced nuclear factor-kappaB activiation and interleukin-8 expression in gastric epithelial cells.

Gastric epithelial chemokine response is a primary factor in the induction of gastric inflammation associated with Helicobacter pylori infection. Because sustained inflammation is a risk for gastric mucosal damage, agents that down-regulate inflammatory responses may be of therapeutic significance. We examined the effect of polaprezinc, a potent antiulcer agent, on proinflammatory cytokine-induced interleukin (IL)-8 expression in gastric epithelial cells. Because IL-8 expression is regulated by the transcription factor nuclear factor-kappaB (NF-kappaB), we also examined the effect of polaprezinc on NF-kappaB activity. MKN28 cells were used as a model of gastric epithelial cells. Secreted IL-8 was quantified by IL-8 specific enzyme-linked immunosorbent assay, and IL-8 mRNA expression was examined by Northern blot analysis. NF-kappaB activity was analyzed by electrophoretic mobility shift assay. Western blot analysis with anti-phospho-IkappaB-alpha antibody was performed to assess IkappaB-alpha phosphorylation. Polaprezinc-suppressed IL-8 secretion induced by tumor necrosis factor alpha (TNF-alpha) or IL-1beta in a dose-dependent manner. IL-8 mRNA expression also was inhibited by polaprezinc. NF-kappaB activation in response to TNF-alpha, IL-1beta, phorbol ester, and H(2)O(2) was down-regulated by polaprezinc. Western blot analysis showed inhibition of TNF-alpha-induced IkappaB-alpha phosphorylation in the presence of polaprezinc. Collectively, these results suggest that polaprezinc is a novel type of anti-inflammatory agent that down-regulates inflammatory responses of gastric mucosal cells.

Anti-Ulcer Agents↗