Biomedical subjects

A Hirai

Publications and source records attributed to A Hirai.

At least 55 records · Page 3Linked to original sources

PubMed2000

[Role of national insurance pharmacies in community complete home care networks--home TPN and home care supported by local national insurance pharmacies].

The reforms in the medical system and introduction of home care insurance have brought great changes to national health insurance pharmacies. In April 1998, Dr. Hirai became new director of the Chiba Togane Hospital. The development of a community complete medical system was included in a restructuring of the hospital, and various reforms were begun. A system covering all aspects of the medical/pharmaceutical field was started in August 1998. For its part, the Sanbu-gun Pharmacists Association began accepting prescriptions outside the hospital, and regular meetings for the exchange of knowledge were held with members of the physicians and pharmacists associations. After building a relationship of trust in this way, a community complete home treatment system was begun in July 1999 with Togane Hospital functioning as its backup support hospital. To date, home TPN terminal care has been provided in cases of terminal cancer, incurable neurological diseases, and for the very aged and patients with cerebrovascular impairments. Any general pharmacy in the region can participate in the program to fill prescriptions for TPN, provided that the pharmacist him or herself so wishes, establishes a clean bench at the pharmacy, and undergoes training at Togane Hospital on the preparation of i.v. medicines in order to function responsibly in this capacity. These pharmacies are called satellite pharmacies, and at present there are four of them located with a good balance within the region. These satellite pharmacies prepare liquid medications for TPN, including narcotics, and oral medicines following the prescriptions written by the physician from the hospital who is serving as the primary home treatment physician. The pharmacy also delivers the medicines to the home of the patient. The pharmacist checks the status of remaining TPN liquids and oral medicines and informs the primary home physician and support hospital by e-mail or fax, so that everyone shares the same information. The success or failure of home TPN from a general pharmacy depends on the formation of a digital network in order to share information using the Internet and a back-up system for unconditional support by the support hospital in times of patient emergency. In our region, these conditions have been fulfilled.

Community Networks↗

PubMed2000

[A case of terminal cancer patient whom the home staying terminal cares were provided with ease supported by the regional core hospital].

A physician who practices generally at his private clinic will be sometimes referred to a cancer patient staying at home. This referral is hardly acceptable without helps from other medical and paramedical specialities. He needs a support organization in which a supporting hospital is the most important. A case of home staying terminal cancer patient is reported here whom a private practician provided terminal cares with great difficulties at the beginning and afterwards with no significant difficulties organizing a care team for the home staying patient and assisted by a supporting hospital.

Aged↗

PubMed2000

[Home infusion therapy system from a resident's point of view].

We started a new home infusion therapy system in July 1999. The home infusion therapy system is made up of doctors, nursing stations, and pharmacies in the community. We coordinate these parties before patient discharge from our hospital and support them when the patient needs hospitalization (for example, he or she develops pneumonia). This report discusses past experiences and future issue.

Home Care Services, Hospital-Based↗

PubMed1999

A functional and quantitative mutational analysis of p53 mutations in yeast indicates strand biases and different roles of mutations in DMBA- and BBN-induced tumors in rats.

In order to analyze the mutational events and to understand the biological significance of the p53 gene in chemical carcinogenesis, we applied a new yeast-based p53 functional assay to ovarian tumors induced by 7, 12-dimethylbenz[a]anthracene (DMBA), as well as to transitional cell carcinomas of the urinary bladder induced by N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) in rats. The assay demonstrated that 15 of 19 DMBA induced tumors harbored clonal p53 mutations, which is consistent with the expectations of the "clonal expansion" hypothesis. The majority of the mutations were purine (AG) to pyrimidine (CT) transversions (12/19) on the non-transcribed (sense) strand (NTS), which is likely to be due to depurination created by DMBA adduct formation on the NTS. In contrast, we found no pyrimidine to purine [corrected] transversion on the NTS. After cessation of BBN treatment, BBN-induced multifocal lesions in the bladder contained heterogeneous p53 mutations at an early stage. In the later stage, however, clonal p53 mutations were identified in 4 out of 7 bladders analyzed, conforming with the concept of "field cancerization". The observed base substitutions were G-->A (1/6) or C -->T transitions (2/6), and mutations at T (3/6) on the NTS in clonal mutations, together with non-clonal mutations, showing a preference of C-->T to G-->A (17 vs. 0). Thus, preferential repair was found in the transcribed strand of the p53 gene, whether modified by DMBA or by BBN carcinogens. Very similar mutation patterns were observed between clonal and non-clonal mutations in the DMBA- and BBN-induced tumors, indicating that the rat yeast p53 functional assay can be a potential tool for the characterization of in vivo mutation patterns of p53, when modified by chemical carcinogens.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1999

A single nuclear transcript encoding mitochondrial RPS14 and SDHB of rice is processed by alternative splicing: common use of the same mitochondrial targeting signal for different proteins.

The rice mitochondrial genome has a sequence homologous to the gene for ribosomal protein S14 (rps14), but the coding sequence is interrupted by internal stop codons. A functional rps14 gene was isolated from the rice nuclear genome, suggesting a gene-transfer event from the mitochondrion to the nucleus. The nuclear rps14 gene encodes a long N-terminal extension showing significant similarity to a part of mitochondrial succinate dehydrogenase subunit B (SDHB) protein from human and a malarial parasite (Plasmodium falciparum). Isolation of a functional rice sdhB cDNA and subsequent sequence comparison to the nuclear rps14 indicate that the 5' portions of the two cDNAs are identical. The sdhB genomic sequence shows that the SDHB-coding region is divided into two exons. Surprisingly, the RPS14-coding region is located between the two exons. DNA gel blot analysis indicates that both sdhB and rps14 are present at a single locus in the rice nucleus. These findings strongly suggest that the two gene transcripts result from a single mRNA precursor by alternative splicing. Protein blot analysis shows that the size of the mature RPS14 is 16.5 kDa, suggesting removal of the N-terminal 22.6-kDa peptide region. Considering that the rice mitochondrial genome lacks the sdhB gene but contains the rps14-related sequence, transfer of the sdhB gene seems to have occurred before the transfer of the rps14 gene. The migration of the mitochondrial rps14 sequence into the already existing sdhB gene could bestow the capacity for nuclear expression and mitochondrial targeting.

Alternative Splicing↗

PubMed1999

Down-regulation of p27(Kip1) by two mechanisms, ubiquitin-mediated degradation and proteolytic processing.

The intracellular level of p27(Kip1), a cyclin-dependent kinase (CDK) inhibitory protein, is rapidly reduced at the G1/S transition phase when the cell cycle pause ceases. In this study, we demonstrated that two posttranslational mechanisms were involved in p27(Kip1) breakdown: degradation via the ubiquitin (Ub)-proteasome pathway and proteolytic processing that rapidly eliminates the cyclin-binding domain. We confirmed that p27(Kip1) was ubiquitinated in vitro as well as in vivo. The p27(Kip1) -ubiquitination activity was higher at the G1/S boundary than during the G0/G1 phase, and p27(Kip1) ubiquitination was reduced significantly when the lysine residues at positions 134, 153, and 165 were replaced by arginine, suggesting that these lysine residues are the targets for Ub conjugation. In parallel with its Ub-dependent degradation, p27(Kip1) was processed rapidly at its N terminus, reducing its molecular mass from 27 to 22 kDa, by a ubiquitination-independent but adenosine triphosphate (ATP)-dependent mechanism with higher activity during the S than the G0/G1 phase. This 22-kDa intermediate had no cyclin-binding domain at its N terminus and virtually no CDK2 kinase inhibitory activity. These results suggest that p27(Kip1) is eliminated by two independent mechanisms, ubiquitin-mediated degradation and ubiquitin-independent processing, during progression from the G1 to S phase.

3T3 Cells↗

PubMed1999

A novel plant nuclear gene encoding chloroplast ribosomal protein S9 has a transit peptide related to that of rice chloroplast ribosomal protein L12.

We have cloned a novel nuclear gene for a ribosomal protein of rice and Arabidopsis that is like the bacterial ribosomal protein S9. To determine the subcellular localization of the gene product, we fused the N-terminal region and green fluorescent protein and expressed it transiently in rice seedlings. Localized fluorescence was detectable only in chloroplasts, indicating that this nuclear gene encodes chloroplast ribosomal protein S9. The N-terminal region of rice ribosomal protein S9 was found to have a high sequence similarity to the transit peptide region of the rice chloroplast ribosomal protein L12, suggesting that these transit peptides have a common lineage.

Amino Acid Sequence↗

PubMed1999

73-kDa heat shock cognate protein interacts directly with P27Kip1, a cyclin-dependent kinase inhibitor, during G1/S transition.

Although heat shock proteins (HSPs) were discovered as inducible proteins by the physical stress to protect cells, recent evidence has suggested that HSPs are likely involved in cell cycle control under normal conditions without stress. In the present study, we demonstrated that 73hsc (heat shock cognate protein), which belongs to the HSP70 family of molecular chaperones, interacts with P27Kip1, an inhibitor of cyclin-dependent kinase, during G1/S transition. 73hsc was detected in the immunoprecipitates with anti-P27Kip1 antibody and, vice versa, P27Kip1 was present in the immunoprecipitates with anti-73hsc antibody by Western blotting using growth-stimulated rat thyroid FRTL-5 cells. This complex formation of 73hsc and P27Kip1 was cell cycle dependent and its maximum formation was observed at G1/S transition where the level of P27Kip1 dramatically decreased. ATP dissociated this complex formation in a dose-dependent manner. These data indicated that 73hsc might be involved in the cell cycle progression through the regulation of cell cycle regulators such as P27Kip1.

Adenosine Diphosphate↗

PubMed1999

Eicosapentaenoic acid and docosahexaenoic acid inhibit vascular smooth muscle cell proliferation by inhibiting phosphorylation of Cdk2-cyclinE complex.

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in the form of triacylglycerol (TG) were dose dependently incorporated into phospholipid fraction of vascular smooth muscle cells (VSMC) and suppressed the proliferation of VSMC. Flow cytometric analysis demonstrated both EPA and DHA inhibited G1/S progression. EPA and DHA inhibited the phosphorylation of Cdk2 protein and Cdk2 kinase activity without altering the amount of cyclin E and p27(kip1) proteins and cyclin dependent kinase activating kinase activity by growth stimulation. This mechanisms remained to be clarified but this is the first report of a novel mechanisms of inhibition of DNA synthesis by EPA and DHA.

Animals↗

PubMed1999

Oxidative DNA damage in diabetes mellitus: its association with diabetic complications.

AIMS/HYPOTHESIS: Augmented oxidative stress induced by hyperglycaemia possibly contributes to the pathogenesis of diabetic complications. Oxidative stress is known to increase the conversion of deoxyguanosine to 8-oxo, 2'-deoxyguanosine in DNA. To investigate the possible contribution of oxidative DNA damage to the pathogenesis of diabetic complications, we measured the content of 8-oxo, 2'-deoxyguanosine in the urine and the blood mononuclear cells of Type II (non-insulin-dependent) diabetic patients. METHODS: We studied 53 Type II diabetic patients and 39 age-matched healthy control subjects. We assayed 8-oxo, 2'-deoxyguanosine by HPLC-electrochemical detection method. RESULTS: The content of 8-oxo, 2'-deoxyguanosine in the urine and the mononuclear cells of the Type II diabetic patients was much higher than that of the control subjects. Urinary 8-oxo, 2'-deoxyguanosine excretion and the 8-oxo, 2'-deoxyguanosine content in the mononuclear cells from the diabetic patients with complications were higher than those from the diabetic patients without complications. Urinary excretion of 8-oxo, 2'-deoxyguanosine was significantly correlated with the 8-oxo, 2'-deoxyguanosine content in the mononuclear cells. The 8-oxo, 2'-deoxyguanosine content in the urine and mononuclear cells was correlated with the haemoglobin A1c value. CONCLUSIONS/INTERPRETATION: This is the first report of a direct association between oxidative DNA damage and the complications of diabetes. The augmented oxidative DNA damage in diabetes is speculated to contribute to the pathogenesis of diabetic complications.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed1999

Idiopathic small-fiber sensory neuropathy in childhood: A diagnosis based on objective findings on punch skin biopsy specimens.

Idiopathic small-fiber sensory neuropathy (SFSN) has not previously been reported in children. Although affected patients complain of neuropathic pain, this condition is often difficult to diagnose because of the few objective physical signs and normal nerve conduction studies. We report a girl with idiopathic SFSN in whom the results of a sural nerve biopsy were normal, but punch skin biopsy revealed reduced intraepidermal nerve fiber density and established the diagnosis. Idiopathic SFSN should be considered in the differential diagnosis of children who have burning limb pain with no routine electrophysiologic or pathologic abnormalities.

Child↗

PubMed1999

Oxidative damage to mitochondrial DNA and its relationship to diabetic complications.

Increased oxidative stress induced by hyperglycemia may contribute to the pathogenesis of diabetic complications. Oxidative stress is known to increase the conversion of deoxyguanosine (dG) to 8-hydroxydeoxyguanosine (8-OHdG) in DNA, which is linked to increased mitochondrial DNA (mtDNA) deletions. We investigated mtDNA deletions and 8-OHdG in the muscle DNA of non-insulin-dependent diabetes mellitus (NIDDM) patients. mtDNA deletion of 4977 bp (delta mtDNA4977) and the content of 8-OHdG in the muscle DNA of the NIDDM patients were much higher than those of the control subjects. There was a significant correlation between delta mtDNA4977 and the 8-OHdG content (P < 0.0001). Both delta mtDNA4977 and the 8-OHdG content were also correlated with the duration of diabetes. Delta mtDNA4977 and the 8-OHdG content in muscle DNA increased in proportion to the severity of diabetic nephropathy and retinopathy. This is the first report that an increase in delta mtDNA4977 and 8-OHdG is proportional to the severity of diabetic complications. Oxidative mtDNA damage is speculated to contribute to the pathogenesis of diabetic complications though a defect in mitochondrial oxidative phosphorylation or other mechanisms. 8-OHdG and delta mtDNA4977 are useful markers to evaluate oxidative mtDNA damage in the diabetic patients.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed1999

Collagen secretion and growth of mesangial cells require geranylgeranylpyrophosphate.

BACKGROUND: The mevalonate pathway is important for the biosynthesis of isoprenoids such as geranylgeranylpyrophosphate (GGPP) and farnesylpyrophosphate, as well as cholesterol. It has been reported that treatment with 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor ameliorates glomerular injury in several experimental models of progressive glomerular disease. However, the effect of HMG-CoA reductase inhibitor on mesangial cell function has not been fully understood. This investigation was performed to elucidate the role of a mevalonate metabolite(s) in mesangial cell proliferation and extracellular matrix accumulation. METHODS: Cycling or quiescent human mesangial cells were incubated in RPMI 1640 containing 10% heat-inactivated fetal calf serum (FCS) in the absence or presence of pravastatin, an inhibitor of HMG-CoA reductase, and mevalonate metabolites. Type IV collagen secretion, mRNA expression, and [3H]thymidine incorporation were measured. Cell cycle phases were monitored by flow cytometry. RESULTS: Pravastatin inhibited FCS-stimulated type IV collagen secretion (IC50 = 210 microM) and mRNA expression. Pravastatin also inhibited FCS-stimulated [3H]thymidine incorporation (IC50 = 430 microM). Analysis with flow cytometry revealed that pravastatin inhibited the G1 to S phase transition of FCS-stimulated mesangial cells. Mevalonate reversed these inhibitory effects of pravastatin completely. Among two major metabolites of mevalonate, GGPP and farnesylpyrophosphate, only GGPP reversed pravastatin-induced inhibition of type IV collagen secretion, DNA synthesis, and the G1 to S phase progression. CONCLUSIONS: These results suggest that GGPP plays critical roles for the type IV collagen secretion and G1 to S phase transition in FCS-stimulated human mesangial cells.

Animals↗

PubMed1999

Effect of pravastatin on type IV collagen secretion and mesangial cell proliferation.

BACKGROUND: The mevalonate pathway is important for the biosynthesis of isoprenoids such as geranylgeranylpyrophosphate (GGPP) and farnesylpyrophosphate (FPP) as well as cholesterol. It has been reported that treatment with 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor ameliorates glomerular injury in several experimental models of progressive glomerular disease. The present investigation was performed to elucidate the role of mevalonate metabolites in mesangial cell proliferation and extracellular matrix accumulation. METHOD: Cycling or quiescent human mesangial cells were incubated in RPMI1640 containing 10% heat-inactivated fetal calf serum (FCS) in the absence or presence of pravastatin, an inhibitor of HMG-CoA reductase, and mevalonate metabolites. Type IV collagen secretion and mRNA expression, [3H]-thymidine incorporation was measured. Cell cycle phases were monitored by flow cytometry. RESULTS: Pravastatin inhibited FCS-stimulated type IV collagen secretion (IC50 = 210 microM) and mRNA expression. Pravastatin also inhibited FCS-stimulated [3H]-thymidine incorporation (IC50 = 430 microM). Analysis with flow cytometry revealed that pravastatin inhibited G1 to S phase transition of FCS-stimulated mesangial cells. Mevalonate reversed these inhibitory effects of pravastatin completely. Among two major metabolities of mevalonate, GGPP and FPP, only GGPP reversed pravastatin-induced inhibition of type IV collagen secretion, DNA synthesis and G1 to S phase progression. CONCLUSION: The present results suggest that GGPP plays a critical role in the type IV collagen secretion and G1 to S phase transition in FCS-stimulated human mesangial cells.

Cell Cycle↗

PubMed1999

AtUCP2: a novel isoform of the mitochondrial uncoupling protein of Arabidopsis thaliana.

Mitochondrial uncoupling proteins (UCPs) play a central role in adaptive thermogenesis in mammals. The UCPs dissipate the proton gradient formed through respiration without ATP synthesis, and the freed energy is readily converted to heat, helping the animals to maintain their body temperature in cold environments. Recently, it was found that UCPs also function in plant mitochondria. Subsequently, a cDNA clone encoding a UCP in potato was isolated. Whereas the UCP gene constitutes a multigene family in mammals, only a single cDNA sequence has been reported so far for the potato UCP. Moreover, it has been recently suggested that Arabidopsis has only a single nuclear gene for UCP. Here we report the existence of another UCP gene in the Arabidopsis genome, showing for the first time the occurrence of a multigene family for the protein in higher plants. A cDNA analysis of this gene showed that the novel isoform possesses all typical features reported for known UCPs. However, the new gene, unlike the other gene in Arabidopsis and the gene in potato, did not appear to respond to low temperature.

Amino Acid Sequence↗

PubMed1999

High malignant transformation rate of widespread multiple oral leukoplakias.

OBJECTIVE: This study was undertaken in order to investigate clinicopathologic characteristics and malignant potential of widespread multiple oral leukoplakias. PATIENTS AND METHODS: The present study includes 12 patients with widespread multiple leukoplakias (widespread patients) and 99 with localized lesions (localized patients), and all patients were followed for more than 6 months with the mean follow-up period of 4 years. RESULTS: Gingiva and tongue were the major affected sites of leukoplakias in the localized patients, whereas gingiva and buccal mucosa were predominantly affected in the widespread patients. The rate of developing carcinoma was significantly (P < 0.02) higher in the widespread patients (3/12) than in the localized patients (5/99), although there was no significant difference in the rate of dysplastic lesions between these groups. CONCLUSION: These results indicate that the widespread leukoplakias have a higher potential for the development of carcinoma than do the localized lesions.

Adult↗

PubMed1999

Identification of cDNA encoding cytochrome c oxidase subunit 5c (COX5c) from rice: comparison of its expression with nuclear-encoded and mitochondrial-encoded COX genes.

Little is presently known about the nuclear-encoded genes for cytochrome c oxidase (COX) in higher plants. In rice, only the nuclear-encoded COX5b gene has been reported. To understand the relationship between the expression of nuclear-encoded and mitochondrial-encoded COX genes in rice, we first characterized a cDNA encoding one of the other nuclear COX genes, COX5c, which encodes 63 amino acids. The deduced amino acid sequence of COX5c from rice was highly homologous to that from sweet potato. Genomic Southern hybridization indicated that the rice COX5c subunit is encoded by a single copy of the COX5c gene. Furthermore, we compared the expression patterns of the nuclear-encoded COX5c and COX5b genes with the expression pattern of the mitochondrial-encoded COX1 gene among several organs by Northern blot analysis. The results suggested that regulatory systems of expression between the nuclear-encoded and the mitochondrial-encoded COX genes are different among different organs in rice.

Amino Acid Sequence↗

PubMed1999

Bilateral pleuritis caused by Legionella micdadei.

A 58-year-old woman was hospitalized because of progressive respiratory distress. She had a history of myasthenia gravis and invasive thymoma. After thymectomy, she had been administered oral prednisolone and intrathoracic anti-cancer drugs postoperatively. Her chest radiograph revealed bilateral pleural effusions. Legionella micdadei (L. micdadei) was isolated from the pleural effusions, and she was diagnosed as pleuritis caused by L. micdadei. She died despite intensive therapy with mechanical ventilation, drainage tube in the chest and intravenous erythromycin. Although only two cases of Legionellosis caused by L. micdadei have been reported in Japan, clinicians should be aware of L. micdadei as one of the candidates for infection in immunosuppressed hosts.

Combined Modality Therapy↗