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Biomedical subjects

Y Hata

Publications and source records attributed to Y Hata.

At least 73 records · Page 4Linked to original sources

Identification of functional elements that regulate the glucoamylase-encoding gene (glaB) expressed in solid-state culture of Aspergillus oryzae.

Aspergillus oryzae has-two glucoamylase-encoding genes, glaA and glaB, whose expressions are distinguished by the type of culture used. The glaB gene is markedly expressed in solid-state culture but is little expressed in submerged culture. In solid-state culture, glaB expression at the transcriptional level is enhanced by low-Aw (water activity), high-temperature, and physical barriers to hyphal extension, as well as by starch. To determine the cis-acting factors in the glaB promoter, deletion analysis of the promoter was done with GUS (beta-glucuronidase) as the reporter. Deletion of the 27 bp from -350 to -324 (Region A) in 1.1 kb of the glaB promoter completely abolished starch, low-Aw, and high-temperature induction. Substitution of the 12-bp GC-rich motif from -335 to -324 (GC-box) resulted in significant loss of starch and low-Aw inductivities. These findings suggest that the GC-box is a cis-element essential for the high-level expression of glaB in solid-state culture.

Aspergillus oryzae↗

Production of the entire extracellular domain of BP180 (type XVII collagen) by baculovirus expression.

Bullous pemphigoid (BP) is an acquired autoimmune skin disease, and its target antigens are a 230 kDa plaque protein (BP230) and a 180 kDa transmembrane protein with interrupted collagenous domains (BP180, type XVII collagen), which localize at the hemidesmosome. In this study we have attempted to express the entire extracellular domain of BP180 (rBP180EC) as a secreted protein by baculovirus expression. Seventy out of 83 BP sera (84.4%) showed positive reactivity against rBP180EC by immunoblot analysis, and 56 out of 83 BP sera (67.5%) were positive against rBP180EC by ELISA. These figures were comparable with those when a bacterial recombinant protein encoding the NC16a domain of BP180 (rNC16a) was used as an antigen source. Reactivity of BP sera against rBP180EC by ELISA was completely abolished or significantly reduced by immunocompetition with rNC16a in 11 out of 14 BP sera tested, while the reactivity was not altered in the rest of the three sera. These findings indicate that the NC16a domain represents the major epitopes on the extracellular domain of BP180, although there are some other minor epitopes outside of NC16a which are uniquely expressed by rBP180EC. rBP180EC will be useful to develop a diagnostic tool for BP as well as to dissect a molecular role for BP180 in interactions of keratinocytes with epidermal basement membrane.

Autoantigens↗

Association of synapse-associated protein 90/ postsynaptic density-95-associated protein (SAPAP) with neurofilaments.

BACKGROUND: Synapse-associated protein (SAP) 90/Postsynaptic density (PSD)-95-associated protein (SAPAP) (also called Guanylate kinase-associated protein/hDLG-associated protein) interacts with the guanylate kinase domains of PSD-95 and synaptic scaffolding molecule (S-SCAM) via the middle region containing 5 repeats of 14 amino acids. SAPAP also binds the recently identified proteins, nArgBP2 and synamon (also called Shank 1a), via the proline-rich region and the C-terminus, respectively. SAPAP is highly enriched in the Triton X-100-insoluble PSD fraction, and recruits PSD-95 into the Triton X-100-insoluble fraction in transfected cells. We have further characterized here the Triton X-100-insolubility of SAPAP and tried to identify the Triton X-100-insoluble structures which SAPAP interacts with. RESULTS: N-Methyl-D-aspartate receptors were recruited into the Triton X-100-insoluble fraction with PSD-95 by SAPAP. The N-terminal region of SAPAP was Triton X-100-insoluble, whereas the middle and C-terminal regions were Triton X-100-soluble. We identified proteins interacting with 35S-methionine-labelled SAPAP in the overlay assay, determined their amino acid sequences, and found them to be neurofilaments. SAPAP interacted with neurofilaments via the N-terminal region, was co-immunoprecipitated with neurofilaments from the rat brain, and co-localized with neurofilaments in transfected cells. CONCLUSION: SAPAP associates with neurofilaments via the N-terminal region and may link various components of the PSD to neurofilaments.

Actin Cytoskeleton↗

Angiogenesis and its regulation: roles of vascular endothelial cell growth factor.

Neovascularization is well known to occur in human atherosclerotic plaques, proliferative retinopathies, and malignant neoplasias. However, its pathophysiologic roles and mechanisms still remain unclear. In this study, histochemical examination of atherosclerotic plaques showed that vascular endothelial cell growth factor (VEGF) was expressed by the smooth muscle cells and foamy macrophages in the atherosclerotic intimas. The number of VEGF-positive cells was positively correlated with the number of intimal blood vessels. Moreover, VEGF gene transfer into rabbit carotid arteries using the hemagglutinating virus of Japan (HVJ)-liposomes showed that VEGF overexpression could induce the angiomatoid proliferation. In diabetic rats, VEGF was overexpressed in diabetic retinas, and thus the local overexpression of VEGF seemed to play an important role in the development of blood-retinal barrier breakdown in simple diabetic retinopathy. These results indicated that the VEGF can act as a local and endogenous regulator of endothelial cell functions and that VEGF induces the neovascularization under pathophysiologic conditions. On the other hand, the transfer of a decoy for the cis-element in the promoter region of the angiogenic factors would be an effective method for regulating angiogenesis, because other angiogenic factors' expression promoted by such cis-element could be simultaneously suppressed. Therefore, this method may supply a useful therapeutic tool for the regulation of pathologic angiogenesis.

Animals↗

Acute production of vascular superoxide by angiotensin II but not by catecholamines.

OBJECTIVE: To determine whether vascular superoxide is rapidly released by angiotensin II and is involved in vascular contraction. DESIGN: The effect of superoxide dismutase (SOD) on angiotensin II induced elevation of mean arterial blood pressure was measured. Subsequently, acute production of vascular superoxide by angiotensin II and its effect on isometric tension were measured in rat aortic rings. The effects of catecholamines were concomitantly measured. METHODS AND RESULTS: The acute pressor effects of angiotensin II were significantly reduced when rats were pretreated intravenously with SOD. When angiotensin II was added on aortic segments in the presence of Cypridina luciferin analog, immediate elevations of chemiluminescence were observed which were inhibited by SOD. Furthermore, angiotensin II-induced elevations of isometric tension in aortic rings were significantly reduced by SOD. The effects of epinephrine and norepinephrine were concomitantly measured and were not significant CONCLUSIONS: The acute superoxide producing effect is likely to be specific to angiotensin II, because such a significant modification of the effects was not observed for catecholamines. Our results suggest that angiotensin II causes acute vascular superoxide production, which may be involved in the acute pressor effects.

Angiotensin II↗

Toxic shock syndrome after suction lipectomy.

We present a case of toxic shock syndrome with necrotizing fasciitis after suction lipectomy. The patient underwent aesthetic suction lipectomy of the abdomen, buttocks, and thighs during an office procedure by a cosmetic surgeon. On postoperative day 2, the patient was referred to the emergency department of our hospital because of pain. On admission, the patient was in toxic shock. She required intensive medical treatment for about 1 month, along with psychiatric help to adapt after the illness. Although toxic shock syndrome is a rare postoperative complication, every plastic surgeon should be acquainted with it. A combination of early recognition, diagnosis, and aggressive supportive therapy is the only successful treatment.

Adult↗

Retinal expression, regulation, and functional bioactivity of prostacyclin-stimulating factor.

Prostacyclin-stimulating factor (PSF) acts on vascular endothelial cells to stimulate the synthesis of the vasodilatory molecule prostacyclin (PGI2). We have examined the expression, regulation, and hemodynamic bioactivity of PSF both in whole retina and in cultured cells derived from this tissue. PSF was expressed in all retinal cell types examined in vitro, but immunohistochemical analysis revealed PSF mainly associated with retinal vessels. PSF expression was constitutive in retinal pericytes (RPCs) but could be modulated in bovine retinal capillary endothelial cells (RECs) by cell confluency, hypoxia, serum starvation, high glucose concentrations, or inversely by soluble factors present in early vs. late retinopathy, such as TGF-beta, VEGF, or bFGF. In addition, RPC-conditioned media dramatically increased REC PGI2 production, a response inhibited by blocking PSF with a specific antisense oligodeoxynucleotide (ODN). In vivo, PGI2 increased retinal blood flow (RBF) in control and diabetic animals. Furthermore, the early drop in RBF during the initial weeks after inducing diabetes in rats, as well as the later increase in RBF, both correlated with levels of retinal PSF. RBF also responded to treatment with RPC-conditioned media, and this effect could be partially blocked using the antisense PSF ODN. We conclude that PSF expressed by ocular cells can induce PGI2, retinal vascular dilation, and increased retinal blood flow, and that alterations in retinal PSF expression may explain the biphasic changes in RBF observed in diabetes.

Animals↗

Office blood pressure variability as a predictor of brain infarction in elderly hypertensive patients.

Large 24-h blood pressure (BP) variability and an excessive drop in BP during nighttime are associated with a higher risk of cardiovascular events. Data are lacking regarding the prognostic significance of variability in BP measured during office visits. We analyzed the relationship between office BP variability and the risk of brain infarction in elderly patients receiving antihypertensive therapy. Patients who experienced their first-ever stroke at the age of 60 years or over were registered in the study. At least 2 sex- and age-matched control patients were registered for each case patient. Office BP at each clinic visit and known cardiovascular risk factors were recorded. The BP variability was defined as the variation coefficient (VC) of office BP. In this report, we analyze the data of brain infarction patients. The VC of both systolic and diastolic BPs was significantly higher in the brain infarction patients than in the control patients. Higher office BP variability was associated with a higher risk of brain infarction after adjustment for BP level and other confounding factors. Regarding diastolic BP, the association of brain infarction with the maximal value for the difference of office BPs taken at any consecutive two visits (Max-deltaBP) or the difference between the highest and lowest values of office BP (BP-range) recorded during a 1-year period prior to the event was also significant. In conclusion, a retrospective case-control study suggested that office BP variability was an independent predictor of brain infarction. Either the Max-deltaBP or the BP-range may be surrogate indices of diastolic BP variability.

Aged↗

[Two cases of Trichophyton mentagrophytes infection contracted from a hamster and a chinchilla].

We report two cases of Trichophyton mentagrophytes infection. Case 1: A 10-year-old girl visited Tokyo Electric Power Hospital in June 1994 for evaluation of an erythematous lesion on her head. Three months of topical steroid therapy exacerbated the lesion with pustular formation. Histopathological and mycological examination revealed that the patient had tinea capitis caused by T. mentagrophytes. T. mentagrophytes was also isolated from her pet, a hamster. Case 2: A-14-year-old girl was referred to Shonan Clinic in January 1996 with scaly erythema on her face. She had been treated with neticonazole hydrochloride at another clinic, but the lesion became worse. Direct microscopic examination of the scale was negative at that time, so treatment with topical steroid was started. After 10 days, the lesion was almost cured, but one month later it recurred with an annular distribution. KOH preparation of the scale revealed mycelia and T. mentagrophytes was isolated on culture. T. mentagrophytes was also isolated from her pet, a chinchilla. In both cases, the oral administration of itraconazole at 50 mg/day was effective. The isolated pathogen was identified as Arthroderma vanbreuseghemii with species-specific primers of chitin synthase 1 gene. T. mentagrophytes is one of the most common dermatophytes isolated from man and animals. Rodents like the hamster and the chinchilla have recently become popular as pets in Japan. We should be aware that rodents may carry this kind of fungal pathogen as they become even more popular as pets.

Adolescent↗

[A case of fixed sporotrichosis with recurred in a child following itraconazole treatment].

We report a case of fixed sporotrichosis in a 2-year-old girl who showed a reddish nodule on her left cheek for 1 year without trauma. Fungi flora-Y staining showed fungal elements from the exudate onthe erosion of this nodule. Sporothrix schenckii was isolated from a culture of the fungus taken from the biopsy specimen. Treatment with itraconazole 4.5 mg/kg/day for 16 weeks resulted in an atrophic scar after 2.1 mg/kg/day for 8 weeks without side effects. Six months later, her eruption recurred and wastreated with potassium iodide for 21 weeks with complete resolution. During the 1 year follow up period, there was no recurrence. Six cases of sporotrichosis in children including ours have been reported in Japan. Each case showed complete resolution and no recurrence. However, careful follow-up is believed to be necessary based on our case.

Antifungal Agents↗

Life-style and serum lipids and lipoproteins.

In reviewing the trends and influences of life-style in this country on health and disease in the latter half of 20th century, we focused our attention on 4 major habits of smoking, drinking, exercise and diets, and collected data on the Japanese to conduct a meta-analysis of their relationship with serum lipids and lipoproteins, which are the metabolic risk factors most closely related to atherosclerosis. 1) The percentage of smokers was 54.0% in adult males and 14.5% in adult females in 1999. In the data of 7,256 subjects (mean age 47 years) in 16 papers, smoking increased triglycerides by 13 mg/dl (0.15 mmol/L) or in 559 non-drinkers with a mean age of 49 years in 3 papers by 18 mg/dl (0.20 mmol/L), and decreased HDL-cholesterol by 3.5 mg/dl (0.09 mmol/L) with every 20 cigarettes smoked according to the regression equation. 2) As for drinking, the annual ethanol consumption per adult was 8.5L in 1996. The effects of alcohol on serum lipids were analyzed in 27,035 males (mean age 47 years) in 24 studies. Drinking elevated triglycerides by a mean of 10 mg/dl (0.11 mmol/L), and also HDL-cholesterol by 2.5 mg/dl (0.06 mmol/L) per 23 g of alcohol intake (corresponding to 1 go of sake or 1 large bottle of beer). 3) Concerning exercise habit, 25% of males and 21% of females (mean age 47 years) regularly performed exercise such as jogging, swimming, aerobics, and tennis. However, walking was regarded as an easy exercise to be practiced by subjects of all ages. The effects of walking on serum lipids were studied in a total of 46,074 subjects (mean age 47 years) in 8 populations. Triglycerides were significantly lower by 10 mg/dl (0.11 mol/L), and HDL-cholesterol higher by 3 mg/dl (0.08 mmol/L) in those who walked 6,000 or more steps/day than in those who walked less than 2,000 steps/day. The effects of harder exercise like jogging or swimming were analyzed in 2,242 subjects in 14 papers (mean age 44 years). Triglycerides decreased by 10 mg/dl (0.11 mmol/L), and HDL-cholesterol elevated by 5 mg/dl (0.13 mmol/L) with an increase in the exercise intensity by one level of about 300 kcal. In exercise therapy, triglycerides were decreased by a mean of 20 mg/dl (0.23 mmol/L), and HDL cholesterol increased by a mean of 10 mg/dl (0.26 mmol/L) by exercise at a mean heart rate of about 135 bpm, which is equivalent to 50% VO2max for 30 minutes x 3 times/week. 4) In nutritional trends, the mean energy intake in 52 postwar years averaged 2,116+/-84 kcal with no marked changes according to nutritional surveys. However, the percentage of fat in total energy intake was lowest at 7% in 1946, increased thereafter until it exceeded 20% in 1973, and surpassed 25% in 1988. The mean total cholesterol level of the Japanese increased by 28 mg/dl (0.72 mmol/L) in the past 30 years and reached 204 mg/dl (5.28 mmol/L) in a survey in 1990. 5) Concerning dietary habits, total cholesterol was lower by a mean of 13 mg/dl (0.34 mmol/L), triglycerides lower by 40 mg/dl (0.45 mmol/L), and HDL-cholesterol higher by 5 mg/dl (0.13 mmol/L) in the group who ate 7 or more Japanese-style meals in the 9 meals during 3 days than in the group who ate 3 or less Japanese-style meals in the 9 meals. When serum lipids were compared among individuals living in cities (8 groups; 3,613 subjects; mean age 51 years), agricultural villages (13 groups; 5,364 subjects; mean age 51 years), and fishing villages (9 groups; 1,071 subjects; mean age 52 years). Total cholesterol was lower by a mean of 10 mg/dl (0.26 mmol/L) in fishing villages than in cities, and triglycerides lower by a mean of 15 mg/dl (0.17 mmol/L) in fishing villages than in cities and agricultural villages. HDL-cholesterol was 5 mg/dl (0.13 mmol/L) higher in agricultural villages and 3 mg/dl (0.08 mmol/L) higher in fishing villages than in cities. 6) The effects of dietary therapy or guidance were evaluated in 585 subjects (mean age, 53 years) in 12 papers. Total cholesterol was reduced by 20 mg/dl (0.52 mmol/L), triglycerides by a mean of 40 mg/dl (0.45 mmol/L), and HDL-cholesterol was increased by 5 mg/dl (0.13 mmol/L) by restriction of fat intake or restriction of the intake of saturated fat and dietary cholesterol. The results of these meta-analyses are considered to indicate the extent to which abnormalities of serum lipids are caused by a distorted life-style and the extent to which they are improved by correction of the life-style and exercise or dietary therapy. Correction of the life-style as a non-drug therapy may clearly improve hyperlipidemias or hypo-HDL-cholesterolemia so that this approach should be aggressively employed as part of the prevention and treatment for hyperlipidemias.

Alcohol Drinking↗

The effects of pantethine on fatty liver and fat distribution.

Although the prognosis of fatty liver depends on its causes, we feel from our clinical experience that fatty liver with hypertriglyceridemia has a good prognosis and responds well to treatment. In this study, 600 mg/day of pantethine was administered to 16 outpatients with fatty liver and hypertriglyceridemia for six months or longer to examine whether the drug improved fatty liver using abdominal plain computed tomography (CT). Nine of the 16-pantethine patients were no longer diagnosed as having fatty liver after the study period. An chi2 test indicated the significant disappearance of fatty liver. At the same time, the visceral fat calculated from the CT image passing the umbilical region was also significantly reduced. On the contrary, the subcutaneous fat area tended to increase, so the ratio of the visceral-to-subcutaneous fat area was reduced significantly. This indicates triglycerides may be pooled in the body as hepato-visceral fat and subcutaneous fat, and that pantethine may transfer fat from the liver and viscera to the subcutaneous tissue. This suggests that visceral fat deposition and fatty liver occurring with hypertriglyceridemia may have a common basis, probably excessive matrixes, and that pantethine may simultaneously improve the two conditions.

Abdomen↗

Gene transfer of a soluble receptor of VEGF inhibits the growth of experimental eyelid malignant melanoma.

PURPOSE: To determine the effect of adenovirus-mediated gene transfer of a soluble receptor of vascular endothelial growth factor (VEGF) on the growth of experimental eyelid malignant melanoma. METHODS: An adenovirus vector encoding a soluble VEGF receptor/flt-1 (Adflt-ExR) was constructed. The bovine retinal endothelial cells (ECs) were incubated in a culture medium of 293E1 cells infected by means of an adenovirus vector or uninfected (control), which contained human recombinant VEGF, and the [3H]thymidine uptake was tested. The experimental eyelid malignant melanoma was induced by the injection of B16 melanoma cells (4 x 10(6) cells) into the right upper eyelid of BALB/c nu/nu mice, and the size of the tumor was recorded for 3 weeks after tumor cell injection. The effect of Adflt-ExR was examined in three ways. Model 1: B16 cells were infected by Adflt-ExR beforehand (at a multiplicity of infection [MOI] of 10) and injected into the eyelid. Model 2: Adflt-ExR was injected into pre-established B16 cell-induced eyelid malignant melanoma. Model 3: Adflt-ExR was injected into the femoral muscle of mice before B16 cell injection into the eyelid, and the remote effect was evaluated. An adenovirus vector bearing the LacZ gene (AdLacZ) or phosphate-buffered saline was used as a control. The amount of VEGF and the flt-ExR protein was measured by sandwich enzyme-linked immunosorbent assay (ELISA). Vascularization was evaluated by counting the number and the size of the vessels. RESULTS: The supernatant of Adflt-ExR-transfected cells clearly inhibited VEGF-induced bovine retinal EC proliferation in vitro. In models 1 and 2, the tumor growth in Adflt-ExR-treated mice was significantly lower than that of controls (P < 0.05). In model 3, no significant difference was found (P = 0.14). The molar ratio of VEGF/flt-ExR protein was clearly low in the tumors of Adflt-ExR-treated mice in models 1 and 2 (P < 0.01) but not in model 3 (P > 0.05). In vessel density, the tumors in Adflt-ExR-treated mice had fewer vessels than tumors in control animals in models 1 and 2 (P < 0.05). CONCLUSIONS: Adenovirus-mediated gene transfer of a soluble form of VEGF receptor (flt-1) gene inhibited the growth of the experimental eyelid malignant melanoma. This method may be useful as an antiangiogenic therapy for eyelid malignant melanoma.

Adenoviridae↗

[Surgical removal of renal cell carcinoma after partial splenic embolization in a patient with liver cirrhosis: a case report].

Partial splenic embolization is used to treat patients with liver cirrhosis accompanied by hypersplenism for improving thrombocytopenia and leukopenia. We report a case in which partial splenic embolization was used before nephrectomy because both renal cell carcinoma and liver cirrhosis were present. A 75-year-old woman visited our hospital complaining of abdominal distension. Computed tomography revealed a 5.5 cm left renal tumor. Liver cirrhosis, ascitis, splenomegaly was observed. Blood tests revealed pancytopenia; platelet count was 2.9 x 10(4)/mm3. The patient was treated by partial splenic embolization in an attempt to ensure a safe nephrectomy. After the embolization, her platelet count increased immediately to 19.2 x 10(4)/mm3, and left nephrectomy was performed successfully.

Aged↗