Biomedical subjects

Y Yamada

Publications and source records attributed to Y Yamada.

At least 271 records · Page 15Linked to original sources

PubMed2001

[Analysis of 5-HT3 receptor antagonist, ramosetron hydrochloride, based on receptor occupancy considering its active metabolite].

Severe nausea and vomiting induced by antineoplastics diminish the patient's quality of life and the ability to tolerate further chemotherapy. Ramosetron hydrochloride is a 5-HT3 receptor antagonist, which has an active metabolite (M-1), expected to be useful in the inhibition of chemotherapy-induced nausea and vomiting. In the present study, in order to analyze the pharmacological effect of ramosetron hydrochloride in a comprehensive manner, we estimated the 5-HT3 receptor occupancy after intravenous administration of ramosetron hydrochloride using pharmacokinetic parameters and the dissociation constants for the 5-HT3 receptor. The average total receptor occupancy after intravenous administration of 0.3 mg of ramosetron hydrochloride to human was calculated to be 82.9% (ramosetron, 77.8%; M-1, 5.1%), thus exhibiting a significant antiemetic activity. Furthermore, the estimated time course of 5-HT3 receptor occupancies after intravenous administration of 0.3 mg of ramosetron hydrochloride suggested a substantial impact of the active metabolite (M-1). It suggested that M-1 contributed to the long duration of binding on the 5-HT3 receptor. The present analysis method should be useful for designing the rational dosage regimen of ramosetron hydrochloride and predicting the duration of its antiemetic activity in a quantitative manner.

Benzimidazoles↗

PubMed2001

[Development of an inspection-supporting system using drug images for unit dose packages].

When inspecting unit-dose packaged drugs, there would be some possibility of inspection errors and ultimately dispensing errors due to pharmacist's incorrect memory of drug identification. Therefore, this study was aimed to establish a computer-aided system for inspecting drugs of unit dose packages more accurately and efficiently. First, we analyzed the identifiability of 5846 tablets and capsules using drug codes, in order to define an identification problem for unit dose-packaged drugs. It was shown that as much as 36% of the drugs do not have any codes, 4.0% of the code-marked drugs have identical codes with others, and that 9.7% of the drugs with codes on both sides of the surface share the same code with other drugs. Thus, it was clearly shown that in many cases it is impossible to identify pharmaceuticals exactly using drug codes only. On the other hand, it was indicated that approximately 80% of the drugs which were not identified with drug codes only, could be identified when additional information on drugs' color, size, form, and splitting line was provided. Therefore, in this study, we designed an inspection-supporting system to present promptly all the information necessary for the drug identification by displaying real drug images as linked with prescribing information on the monitor. Retrieval of prescription data from the order entry host was automatically performed by entering patient's ID number or by selecting a patient from the name list of patients at the inspection terminal computer. Moreover, the system was equipped with abilities to automatically check drug interactions and duplicate prescriptions, to provide various information of prescribed drugs and to monitor patients' drug history. We used the developed system and evaluated that it is a useful tool for accurate and efficient inspection of unit dose-packaged drugs. In addition, the quality of drug inspection increased by utilizing system functions such as checking drug interactions and providing drug information.

Clinical Pharmacy Information Systems↗

PubMed2001

[Glimepiride (Amaryl): a review of its pharmacological and clinical profile].

In Type 2 diabetes, it is considered that the lowered insulin secretion and the lowered insulin sensitivity cause hyperglycemia. Sulfonylureas have strong blood-glucose lowering effect by stimulating insulin secretion and have been widely used in the treatment of Type 2 diabetes. However, the use of sulfonylurea has several problematic issues (weight gain, hypoglycemia, second failure and so on), which would due to stimulation of strong insulin secretion. Glimepiride, a new sulfonylurea, has a blood-glucose lowering effect as strong as those of existing sulfonylureas, but only induces mild insulin secretion. The sulfonylurea receptor has a weaker affinity for glimepiride than glibenclamide. The association and dissociation to the sulfonylurea receptor of glimepiride are faster than those of glibenclamide. Additionally, it is confirmed by basic studies that part of the glimepiride effect is attributable to improving insulin sensitivity. Glimepiride has already been used in more than 60 countries in the world. Outside of Japan, several clinical studies have demonstrated that glimepiride shows less hypoglycemia and no weight gain. Glimepiride is expected to be a new efficient agent for the treatment of Type 2 diabetes.

Animals↗

PubMed2001

Production of menaquinone (vitamin K2)-7 by Bacillus subtilis.

Menaquinone-7 (MK-7) is a highly bioactive homologue of vitamin K. We obtained a diphenylamine-resistant mutant strain D200-41 from Bacillus subtilis strain MH-1 which was isolated from fermented soybeans, natto. The mutant strain exhibited decreased production of MK-6. Using strain D200-41, efficient production of MK-7 was achieved. We found that, compared with an agitated and aerated culture, production of MK-7 was increased by static culture. The sporulation of the cells progressed more slowly in a static culture than in an agitated culture. The maximum concentration of MK reached about 60 mg/l in a medium containing 10% soybean extract, 5% glycerol, 0.5% yeast extract and 0.05% K2HPO4 (pH 7.3) when D200-41 cells as well as MH-1 cells were statically cultured at 45 degrees C for 5 d after being cultured with shaking at 37 degrees C for 1 d.

Journal Article↗

PubMed2001

Designing potent derivatives of ovokinin(2-7), an anti-hypertensive peptide derived from ovalbumin.

We obtained a potent anti-hypertensive peptide, RPFHPF, by replacing the amino acid residues of ovokinin(2-7) (RADHPF), an orally active anti-hypertensive peptide derived from ovalbumin. After intravenous administration in anesthetized Wistar rats, the designed peptide [Pro2, Phe3]-ovokinin(2-7) had a long-lasting hypotensive activity at a dose of 10 mg/kg, while that of ovokinin(2-7) was only transient even at a dose of 100 mg/kg. After oral administration in conscious spontaneously hypertensive rats (SHRs), [Pro2, Phe3]-ovokinin(2-7) significantly lowered the systolic blood pressure in a dose-dependent manner. It is noteworthy that the minimum effective dose of [Pro2, Phe3]-ovokinin(2-7) was 0.3 mg/kg, about one-thirtieth of that of ovokinin(2-7). On the other hand, orally administered [Pro2, Phe3]-ovokinin(2-7) did not show any significant hypotensive effect in normotensive Wistar-Kyoto rats (WKYs) even at a dose of 3 mg/kg. Taken together, [Pro2, Phe3]-ovokinin(2-7) proved to be an ideal, potent anti-hypertensive peptide with little effect on normal blood pressure when given orally.

Animals↗

PubMed2001

A natural history of adrenocorticotropin-independent bilateral adrenal macronodular hyperplasia (AIMAH) from preclinical to clinically overt Cushing's syndrome.

A 49-year-old man was referred to our hospital for the treatment of gallstones in 1993. Bilateral adrenal nodular masses were detected incidentally by abdominal computed tomography. He had no clinical signs of Cushing's syndrome such as central obesity, striae of skin and diabetes mellitus. We performed cholecystectomy and partial adrenalectomy of right adrenal gland as a biopsy, and diagnosed him as preclinical Cushing's syndrome due to adrenocorticotropin-independent bilateral adrenal macronodular hyperplasia (AIMAH) based on endocrinological and histological examinations. We followed him up for 7 years. During the observation period, the sizes of both adrenal glands increased gradually, and finally serum cortisol level increased beyond normal range, and he showed a Cushingoid appearance such as moon face and central obesity. His skin became atrophic and very fragile, and the bone mineral density of his lumbar spine was extremely low. Serum cortisol level was elevated, and plasma ACTH level was always suppressed. Urinary excretion of 17-hydroxycorticosteroid and free cortisol were increased. Diurnal rhythm of cortisol and ACTH was completely lost and high dose (8 mg/day) dexamethasone did not suppress urinary 17-hydroxycorticosteroid excretion. He became clinically overt Cushing's syndrome. We recommended total adrenalectomy, but he refused it. It is important to know the natural history of preclinical Cushing's syndrome due to AIMAH when choosing an adequate treatment.

17-Hydroxycorticosteroids↗

PubMed2001

Dexamethasone enhances SOX9 expression in chondrocytes.

SOX9 is a transcription factor that activates type II procollagen (Col2a1) gene expression during chondrocyte differentiation. Glucocorticoids are also known to promote chondrocyte differentiation via unknown molecular mechanisms. We therefore investigated the effects of a synthetic glucocorticoid, dexamethasone (DEX), on Sox9 gene expression in chondrocytes prepared from rib cartilage of newborn mice. Sox9 mRNA was expressed at high levels in these chondrocytes. Treatment with DEX enhanced Sox9 mRNA expression within 24 h and this effect was observed at least up to 48 h. The effect of DEX was dose dependent, starting at 0.1 nM and maximal at 10 nM. The half life of Sox9 mRNA was approximately 45 min in the presence or absence of DEX. Western blot analysis revealed that DEX also enhanced the levels of SOX9 protein expression. Treatment with DEX enhanced Col2a1 mRNA expression in these chondrocytes and furthermore, DEX enhanced the activity of Col2-CAT (chloramphenicol acetyltransferase) construct containing a 1.6 kb intron fragment where chondrocyte-specific Sry/Sox- consensus sequence is located. The enhancing effect of DEX was specific to SOX9, as DEX did not alter the levels of Sox6 mRNA expression. These data suggest that DEX promotes chondrocyte differentiation through enhancement of SOX9.

Animals↗

PubMed2001

Elevated level of soluble HLA class I antigens in serum and bronchoalveolar lavage fluid in patients with sarcoidosis.

OBJECTIVE: Soluble HLA class I antigens (sHLAs) in human serum have been reported to be associated with allografts and autoimmune disease and could modify immunological reactions induced by membrane type HLAs. To investigate the clinical significance of sHLAs in sarcoidosis, we assessed concentrations of sHLAs in both serum and bronchoalveolar lavage fluid (BALF) and also examined their production by peripheral blood mononuclear cells (PBMCs) and BALF cells. METHODS: Concentrations of sHLAs were determined by enzyme-linked immunosorbent assay, using a monoclonal antibody against HLA class I (W6/32) and an enzyme-labeled polyclonal antibody to human beta2-microglobulin. PBMCs and BALF cells were cultured in the presence or absence of either LPS or PHA. PATIENTS: Serum levels of sHLAs were assessed in 96 patients with sarcoidosis and in 32 healthy control subjects. sHLAs concentrations in BALF were also investigated in 17 active sarcoidosis patients and in 13 control subjects. RESULTS: sHLAs levels in both serum and BALF were higher in sarcoidosis cases than in control subjects (p<0.05, in both). In the patients, values were significantly higher in active than in inactive stages (p<0.001) and significantly correlated with angiotensin-converting enzyme (ACE) levels. Both PBMCs and BALF cells produced enhanced amounts of sHLAs in patients with active sarcoidosis compared with those in control subjects. CONCLUSION: These results demonstrated that the level of sHLAs in serum is a useful index of disease activity of sarcoidosis, partly reflecting production by PBMCs and BALF cells.

Adult↗

PubMed2001

Anorexia nervosa with ischemic necrosis of the segmental ileum and cecum.

A 41-year-old woman with long-standing anorexia nervosa showed paralytic ileus and serum creatine kinase elevation. Surgical treatment showed necrosis of the segmental ileum and cecum with perforation. She died of septic shock 3 days after the operation. Postmortem examination revealed no occlusion of the superior mesenteric artery or its main branches, and no arteriosclerotic changes. Histological examinations confirmed non-occlusive mesenteric infarction. This case suggested that necrosis of bowels might have been caused by poor blood supply due to severe malnutrition and dehydration for many years, which could be one of the fatal complications of anorexia nervosa.

Adult↗

PubMed2001

Human TSC-22 gene: no association with type 2 diabetes.

OBJECTIVE: In order to elucidate whether or not genetic variations of TSC-22 (TGF [transforming growth factor]-beta-stimulated clone 22), which was originally identified as a TGF-beta-responsive leucine zipper protein in murine osteoblastic cells, are associated with type 2 diabetes, the genomic organization of the human TSC-22 gene was determined and the association between its polymorphisms and type 2 diabetes was examined. RESULTS: The human TSC-22 gene spans approximately 5 kilobase pairs and is encoded in three exons. Two single nucleotide polymorphisms (SNPs) were identified in the coding region of the first exon, two other SNPs in the first intron, and one SNP in the putative promoter region. There were, however, no significant differences in the frequency of these polymorphisms between patients with type 2 diabetes and non-diabetic control subjects. CONCLUSION: It is unlikely that the TSC-22 gene is a locus responsible for type 2 diabetes.

Aged↗

PubMed2001

Substrate phage as a tool to identify novel substrate sequences of proteases.

Combinatorial phage peptide libraries have been used to identify the ligands for specific target molecules. These libraries are also useful for identification of the specific substrates of various proteases. A substrate phage library has a random peptide sequence at the N-terminus of the phage coat protein and an additional tag sequence that enables attachment of the phage to an immobile phase. When these libraries are incubated with a specific enzyme, such as a protease, the uncleaved phage is excluded from the solution with tag-binding macromolecules. This provides a novel approach to define substrate specificity. The aim of this review is to summarize recent progress on the application of the substrate phage technique to identify specific substrates of proteolytic enzymes. As an example, some of our own experimental data on the selection and characterization of substrate sequences for thrombin, a serine protease, and membrane type-1 matrix metalloproteinase (MT1-MMP) will be presented. Using this approach, the canonical consensus substrate sequence for thrombin was deduced from the selected clones. As expected from the collagenolytic activity of MT1-MMP, a collagen-like sequence was identified in the case of MT1-MMP. A more selective substrate sequence for MT1-MMP was identified during a substrate phage screen. The delineation of the substrate specificity of proteases will help to elucidate the enzymatic properties and the physiological roles of these enzymes. Comprehensive screening of very large numbers of potential substrate sequences is possible with substrate phage libraries. Thus, this approach allows novel substrate sequences and previously unknown target molecules to be defined.

Amino Acid Sequence↗

PubMed2001

Effects of guided bone regeneration with non-resorbable and bioabsorbable barrier membranes on osseointegration around hydroxyapatite-coated and uncoated threaded titanium dental implants placed into a surgically-created dehiscence type defect in rabbit tibia: a pilot study.

The purpose of this study was to evaluate the effects of guided bone regeneration (GBR) with either a non-resorbable (ePTFE) or bioabsorbable barrier membrane (RSLT) on osseointegration and extent of bone formation around hydroxyapatite-coated (HA) and uncoated threaded titanium (Ti) dental implants placed into surgically-created dehiscence type defects in rabbit tibia. A dehiscence type bone defect, approximately 3 mm in width and height was surgically created on the outer surface of the bone in each tibia of 9 rabbits. For the conventional group, either a HA or a Ti implant was then placed at this site. After the same procedure was performed as in the conventional group, the implant site of the GBR group was covered with either an ePTFE or a RSLT. After 4 months, the rabbits were sacrificed. Specimens were prepared and examined histometrically. It was found that the mean percentage of osseointegration tended to increase in HA compared to Ti implants, both with and without membranes. There was a tendency that the extent of newly regenerated bone was higher in the GBR group than that in the conventional group.

Absorbable Implants↗

PubMed2001

Antiatherogenic mitochondrial genotype in patients with type 2 diabetes.

OBJECTIVE: To evaluate the significance of a longevity-associated mitochondrial genotype (Mt5178A) derived from a C --> A transversion at nucleotide position 5178 of mitochondrial DNA, which causes a Leu-to-Met substitution within the NADH dehydrogenase subunit 2 gene, in type 2 diabetic subjects. RESEARCH DESIGN AND METHODS: Mt5178 typing was done by polymerase chain reaction-restriction fragment-length polymorphism with the restriction enzyme AluI in 1,148 type 2 diabetic Japanese subjects, and the results were compared with the clinical characteristics. Then, the association of Mt5178 type with early atherosclerotic changes of the bilateral carotid arteries on ultrasonography was assessed in 412 diabetic subjects randomly selected from the original 1,148 type 2 diabetic subjects, while maintaining the same frequency of Mt5178A and Mt5178C. RESULTS: The frequency of Mt5178A in the type 2 diabetic subjects (454 of 1,148; 40%) was not different from that previously found in healthy blood donors (114 of 252; 45%). Clinical characteristics regarding diabetes were not significantly different between the Mt5178A group (n = 454) and the Mt5178C group (n = 694). However, the mean intima-media thickness (IMT) at six sites in the bilateral carotid arteries was significantly smaller in the Mrt5178A group than in the Mt5178C group (0.906 +/- 0.018 vs. 0.995 +/- 0.021 mm, mean +/- SEM, P = 0.022), and the Mt5178 type was significantly correlated with both the mean IMT and the presence of plaque on multiple regression analysis and discriminant analysis. CONCLUSIONS: The Mt5178A genotype may be unrelated to the etiology of type 2 diabetes. However, Mt5178A seems to have an antiatherogenic effect, at least in type 2 diabetic individuals.

Adult↗

PubMed2001

Soluble Fas (APO-1/CD95) isoform in adult T-cell leukemia.

Fas (APO-1/CD95) consists mainly of 2 isoforms, membrane-anchored (mFas) and soluble (sFas), both of which can mediate apoptosis through the Fas-signalling process, not only in normal but also in leukemia T-cells. This suggests that aberrant expression of either mFas or sFas may affect the natural history of T-cell neoplasms, such as adult T-cell leukemia (ATL). For studying the tumor biology related to Fas-mediated apoptosis, ATL cells with up-regulated Fas proteins and its mRNAs are convenient and useful for understanding apoptotic oncology as it occurs in nature. Most attention, so far, has been focused on mFas, and little is known about neoplasms from the viewpoint of sFas. Accordingly, we herein review and discuss the biological and clinical implications of sFas in ATL.

Apoptosis↗

PubMed2001

[Antigenicity and phototoxicity of water-soluble extract from Salacia reticulata (Celastraceae)].

The antigenicity and phototoxicity of water-soluble extract from Salacia reticulata (SRE) were examined in guinea pigs. In a study of active systemic anaphylaxis reaction, neither the oral administration group (64 or 320 mg/kg, 5 times/week, 3 weeks) nor the subcutaneous administration group (64 mg/kg, 1 time/week, 3 weeks) exhibited any anaphylactic reaction. Moreover, sensitization with serum obtained from these animals did not induce passive cutaneous anaphylaxis reaction in normal animals. In a phototoxicity study, oral administration of SRE (320 mg/kg) induced neither erythema nor edema. These results suggest that SRE is not antigenic or phototoxic.

Anaphylaxis↗

PubMed2001

Excessive fatigue and weight gain among cleanroom workers after changing from an 8-hour to a 12-hour shift.

OBJECTIVES: This study attempted to clarify the health effects of implementing a 12-hour shift in place of the traditional 8-hour shift in work in a clean room in an electronic parts producing factory. METHODS: Health-check records during a year or longer before and after the shift change were reviewed regarding subjective symptoms, height, body weight, and blood pressure for 189 male workers who had moved to a 12-hour shift and for 16 male workers who remained on an 8-hour shift. RESULTS: The workers changing to a 12-hour shift showed significant increases in subjective symptoms, particularly psychological symptoms defined as related to fatigue and bodyweight gain, 1 kg on average, in the year after the shift change. Increased symptoms and body weight remained high even another year later. The workers remaining in the 8-hour shift did not show significant changes in symptoms or body weight during the observation. No changes in blood pressure were observed in relation to the shift move. CONCLUSIONS: The results suggested that implementing a 12-hour shift caused marked psychological fatigue and unhealthy weight gain among some cleanroom workers and that the adaptation to the new work shift did not seem easy for these workers. Working in a clean room can be considered a job in which special caution is needed regarding increased fatigue when a compressed working schedule is implemented. Attention should also be paid to possible weight gain among persons working 12-hour shifts.

Adult↗

PubMed2001

[Acute ultraviolet B induced lens epithelial cell photo-damage and its repair process].

PURPOSE: To clarify the process of acute lens epithelial cell photo-damage induced by ultraviolet B (UV-B) exposure and its repair. METHODS: Pigmented rabbits were exposed to UV-B (300 mJ/cm2). The time course of lens epithelial cell photo-damage was evaluated by light microscopy of lens epithelial cell flat mounts. The flat mounted lens epithelial cells were stained with Mayer's hematoxylin or by immunohistochemistry with anti-proliferating cell nuclear antigen (PCNA) monoclonal antibodies. RESULTS: The lens epithelial cells were irregularly arranged and there were debris and pycnotic nuclei, small nuclei, existence of large cells, and phagocytosis of neighboring cells in the pupillary area. A repair process was seen in the injured areas within a week after UV-B exposure. PCNA positive cells were seen and it was confirmed that the healing of the photo-injured part was due to epithelial cell proliferation. CONCLUSIONS: The acute lens epithelial cell photo-damage induced by UV-B exposure was repaired within a week by cell proliferation.

Animals↗

PubMed2001

[Sentinel node detection of patients with breast cancer by radionuclide method: consideration of radiation safety].

Sentinel node was detected by 99mTc labeled nanocolloid in five patients with breast cancer. Surgery of breast cancer was done at 16 hours after the administration of 74 MBq of 99mTc labeled nanocolloid. Sentinel node was searched by scintigraphy prior to surgery and by gamma-probe during surgery. Radioactivity of injected site, sentinel nodes, blood contaminated gauze, and other garbage was measured by GM detector. Radiation to medical staffs was monitored by a pocket radiation detector and film batches. Sentinel nodes were successfully detected both by scintigraphy and gamma-detector. More than 70% of radioactivity remained in the administered site at 16 hours. Small amount of radioactivity was detectable in the sentinel node. Almost no radioactivity was detectable in blood-contaminated gauze and other garbage. Radiation dose to the main surgeon was 4 to 6 microSv per surgery by a pocket radiation detector. Radiation dose to the assistant surgeon was 2 microSv per surgery. Radiation dose by labeling or injection was 0 to 1 microSv per procedure. No detectable radiation was measured by film batches. It is concluded that the detection of sentinel node by 99mTc labeled nanocolloid is a safe procedure from the point of radiation safety consideration.

Breast Neoplasms↗