Biomedical subjects

A Hamada

Publications and source records attributed to A Hamada.

At least 19 recordsLinked to original sources

PubMed2007

Variants in the SLCO1B3 gene: interethnic distribution and association with paclitaxel pharmacokinetics.

To explore retrospectively the relationships between paclitaxel pharmacokinetics and three known, non-synonymous single-nucleotide polymorphisms (SNPs) in SLCO1B3, the gene encoding organic anion transporting polypeptide (OATP)1B3. Accumulation of [(3)H]paclitaxel was studied in Xenopus laevis oocytes injected with cRNA of Oatp1b2, OATP1A2, OATP1B1, OATP1B3, OAT1, OAT3, OCT1, and NTCP. The 334T>G (Ser112Ala), 699G>A (Met233Ile), and 1564G>T (Gly522Cys) loci of SLCO1B3 were screened in 475 individuals from five ethnic groups and 90 European Caucasian cancer patients treated with paclitaxel. Only OATP1B3 was capable of transporting paclitaxel to a significant extent (P=0.003). The 334T>G and 699G>A SNPs were less common in the African-American and Ghanaian populations (P<0.000001). Paclitaxel pharmacokinetics were not associated with the studied SNPs or haplotypes (P>0.3). The studied SNPs in SLCO1B3 appear to play a limited role in the disposition of paclitaxel, although their clinical significance in other ethnic populations remains to be investigated.

Animals↗

PubMed2004

An experimental model for amoebic abscess production in the cheek pouch of the Syrian golden hamster, Mesocricetus auratus.

A new experimental model was developed in hamsters for amoebic abscess caused by Entamoeba histolytica. E. histolytica trophozoites were cultured in a liquid axenic medium, and then injected intradermally into the cheek pouch of the Syrian golden hamster, Mesocricetus auratus. Inoculation consistently resulted in abscess formation at the site in 20 of 22 (91%) study animals. The amoebic nature of the abscesses was confirmed by light microscopy and histopathologic examination. Abscess formation was maximal at day 12 post-inoculation. Potential applications of this simple and reliable model include further elucidation of the pathogenesis of invasive amoebiasis, studies of the host response to amoebae, and in vivo evaluation of chemotherapeutic agents that show in vitro efficacy against E. histolytica.

Amebiasis↗

PubMed2004

Efficacy of argon plasma coagulation in nonvariceal upper gastrointestinal bleeding.

BACKGROUND AND STUDY AIMS: Various methods of endoscopic hemostasis have been described. However, few reports have investigated the efficacy of argon plasma coagulation (APC) in the treatment of upper gastrointestinal bleeding. The aim of this study was to evaluate the efficacy of APC in various types of upper gastrointestinal bleeding. PATIENTS AND METHODS: The present study was designed as a prospective and observational study. A total of 254 consecutive patients with upper gastrointestinal bleeding (excluding variceal bleeding) were primarily treated using APC. If it was difficult to achieve complete hemostasis with APC alone, injection of a hypertonic saline-epinephrine solution and clipping were carried out. The initial hemostasis rate, rate of recurrent bleeding after APC, permanent hemostasis rate, and mean procedure time were evaluated. RESULTS: Initial hemostasis with APC alone was achieved in 193 of the 254 patients (75.9 %). With the assistance of other methods as well, initial hemostasis was achieved in 253 patients (99.6 %). Among the 193 patients treated with APC alone, recurrent bleeding was observed in 11 cases (11 of 193, 5.7 %). With one exception, these cases of recurrent bleeding were controlled with APC alone again; permanent hemostasis was thus ultimately achieved with APC alone in 192 of the 254 patients (75.5 %). The mean procedure time was 8 min. No complications (such as perforation) were observed with the APC treatment. CONCLUSIONS: These data indicate that APC is a safe, quick, and effective method of treating various types of nonvariceal upper gastrointestinal bleeding and that it can be a powerful tool for endoscopic hemostasis.

Adult↗

PubMed2001

Inhibitory effect of JTV-803, a new cyclic guanidine derivative, on factor Xa in vitro and in vivo.

JTV-803, 4-[(2-amidino-1,2,3,4-tetrahydroisoquinolin-7-yloxy)methyl]-1-(4-pyridinyl)piperidine-4-carboxylic acid monomethanesulfonate trihydrate showed a competitive inhibitory effect on human factor Xa, with a K(i) value of 0.019 microM. This compound was 100 times more selective in inhibiting human factor Xa as compared to its inhibitory activity against thrombin, plasmin, and trypsin. JTV-803 was also examined for its inhibitory effect on activated factor Xa obtained from plasma of various animal species. JTV-803 exerted a potent inhibitory effect on human factor Xa (IC(50): 0.081 microM). JTV-803 prolonged activated partial thromboplastin time and prothrombin time in a dose-dependent manner. Oral anticoagulant efficacy of JTV-803 was examined ex vivo for its inhibition of human factor Xa in cynomolgus monkeys. JTV-803 produced more than 20% inhibition of human factor Xa for 8 h. Taken together, the results indicate JTV-803 is a long-acting oral anticoagulant which exerts its effect via specific inhibition of human factor Xa.

Administration, Oral↗

PubMed2001

High-performance liquid chromatographic assay for the simultaneous determination of lansoprazole enantiomers and metabolites in human liver microsomes.

In this study, a simple, sensitive and enantioselective HPLC method was developed for the simultaneous determination of lansoprazole enantiomers: a proton pump inhibitor, and its major metabolites: 5-hydroxylansoprazole and lansoprazole sulfone in human liver microsomes. After extraction from the microsomal incubation mixture with a diethyl etherdichloromethane (7:3, v/v) mixture, analytes were measured by reversed-phase HPLC on a Chiralcel OD-R column. Detection was made using an ultraviolet absorbance detector set at a wavelength of 285 nm. The mobile phase consisted of a methanol-water (75:25, v/v) mixture. At a flow-rate of 0.5 ml/min, the total run time was 35 min. The limit of quantification for both lansoprazole enantiomers was 0.25 microM and for the metabolites 0.13 microM. The method is suitable for the analysis of lansoprazole enantiomers and its metabolites from human microsomal liver incubations.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed2001

Flow cytometric analysis of hemetopoietic progenitor cells in peripheral blood stem cell harvest from patients with CD34 positive acute leukemia.

We analyzed CD34 positive cells in peripheral blood stem cell harvest (PBSCH) using flow cytometry. PBSCH from CD34 positive acute myelogeous leukemia (AML-M2) patient contained 1.87% CD34 positive cells, of which 1.21% was represented by MRD.PBSCH from CD34 positive acute lymphoblast leukemia (ALL) patient contained 3.14% CD34 positive cells, of which 0.11% was accounted for by minimal residual disease (MRD). If PBSCH from CD34 positive acute leukemia patient is analyzed for CD34 monoclonal antibody alone, the presence of CD34 positive MRD may escape attention so that CD34 positive hematopoietic progenitor cells may be overestimated. To avoid this risk, it is necessary to analyze PBSCH using both CD34 monoclonal antibody and characteristic markers of leukemia cells that were found pre-treatment.

Antigens, CD34↗

PubMed2001

Role of CYP3A4 and CYP2C19 in the stereoselective metabolism of lansoprazole by human liver microsomes.

OBJECTIVE: The aim of this investigation was to clarify the stereoselective properties in lansoprazole metabolism by monitoring the metabolic consumption for each enantiomer and the formation of the main metabolites, lansoprazole sulfone and 5-hydroxylansoprazole, in the presence of human liver microsomal enzymes. METHODS: Human liver microsomes or recombinant cytochrome P450 (CYP) enzymes were incubated with either (+/- )-, (+)-, or (-)-lansoprazole in the presence of reduced nicotinamide adenine dinucleotide phosphate. The metabolic consumption of lansoprazole enantiomers was estimated from the amounts of enantiomers consumed by microsomal enzymes after incubation at 37 degrees C for 60 min. Metabolites of lansoprazole, lansoprazole sulfone, and 5-hydroxylansoprazole were determined after incubation at 37 degrees C for 20 min, and kinetic parameters [Michaelis constant (Km) and maximum velocity (Vmax)] were obtained using Eadie-Hofstee plots. RESULTS: (-)-Lansoprazole was metabolized more preferentially than (+)-lansoprazole in human liver microsomes. Stereoselective sulfoxidation and hydroxylation [(+) > (-)] were observed in human liver microsomes. Strikingly, in sulfoxidation, a significantly higher intrinsic clearance (Vmax,l/Km,l) of (-)-lansoprazole (0.023 +/- 0.001 ml/min/mg) than (+)-lansoprazole (0.006 +/- 0.000 ml/min/mg) was observed. Consequently, sulfoxidation is likely to play an important role in the stereoselective metabolism of lansoprazole enantiomers. P450-isoform specificity for each enantiomer was evident. CYP3A4, which mainly catalyzed sulfoxidation, was more active toward (-)-lansoprazole in either a chiral or racemic drug as a substrate. CYP2C19, which catalyzed hydroxylation, preferentially metabolized (+)-lansoprazole. The consumption of (+)-lansoprazole was markedly inhibited by (-)-lansoprazole, indicating a metabolic enantiomer/enantiomer interaction. However, this alteration of recombinant CYP2C19 specificity for (+)-lansoprazole did not appear in metabolism in human liver microsomes. CONCLUSIONS: Stereoselective metabolism was observed in human liver microsomes, and this stereoselectivity was mainly based on CYP3A4 specificity for preferable metabolism of (-)-lansoprazole.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed2001

Combined treatment with interferon-alpha and ribavirin for subacute sclerosing panencephalitis.

Two patients with subacute sclerosing panencephalitis (SSPE) are described. They were diagnosed on admission to the hospital with SSPE, as judged on cerebrospinal fluid examination involving reverse transcription followed by polymerase chain reaction, at the second stage of Jabbour's classification. They first were treated with intraventricular interferon-alpha monotherapy; however, the combination of interferon-alpha and IV ribavirin was started at 8 and 5 months after beginning the interferon-alpha monotherapy, respectively. Although slow progressive brain atrophy was observed in Patient 1 on brain magnetic resonance imaging before the ribavirin therapy, no further progression was noted 11 months after starting combination therapy with ribavirin. The event-related potential study results and audiography of the right ear improved in Patient 1 after the combination therapy was initiated. In Patient 2 the hypertonicity, neurobladder incontinence, and dysphagia improved 3 months after starting the combination treatment. Although this group of patients is small, these results suggest treatment with intrathecal high-dose interferon-alpha and IV ribavirin is effective in the treatment of SSPE. Early administration of intrathecal high-dose interferon-alpha and IV ribavirin should be considered as a possible therapy for SSPE patients, especially interferon-nonresponding ones.

Adolescent↗

PubMed2001

Isolation and characterization of a Na+/H+ antiporter gene from the halophyte Atriplex gmelini.

With a homologous gene region we successfully isolated a Na+/H+ antiporter gene from a halophytic plant, Atriplex gmelini, and named it AgNHX1. The isolated cDNA is 2607 bp in length and contains one open reading frame, which comprises 555 amino acid residues with a predicted molecular mass of 61.9 kDa. The amino acid sequence of the AgNHX1 gene showed more than 75% identity with those of the previously isolated NHX1 genes from glycophytes, Arabidopsis thaliana and Oryza sativa. The migration pattern of AgNHX1 was shown to correlate with H+-pyrophosphatase and not with P-type H+-ATPase, suggesting the localization of AgNHX1 in a vacuolar membrane. Induction of the AgNHX1 gene was observed by salt stress at both mRNA and protein levels. The expression of the AgNHX1 gene in the yeast mutant, which lacks the vacuolar-type Na+/H+ antiporter gene (NHX1) and has poor viability under the high-salt conditions, showed partial complementation of the NHX1 functions. These results suggest the important role of the AgNHX1 products for salt tolerance.

Amino Acid Sequence↗

PubMed2001

Lack of association between the hKCa3 gene and Japanese schizophrenia patients.

Several researchers have suggested an association between large numbers of CAG repeats in the hKCa3 gene and schizophrenia. However, these reports remain inconclusive and require further investigation. We tried to replicate these results in 112 Japanese schizophrenia patients and 102 control subjects of highly matched age and sex by applying an allele dichotomization model. No association was found. The overall distributions of allele frequencies were not significantly different between schizophrenic patients and normal control subjects. In addition, we tested the association between the size of the CAG repeats and the scores on three dimensions (positive and negative symptoms, and disorganization), but no significant results were obtained. Our results do not support the involvement of the hKCa3 gene in schizophrenia, at least in the Japanese population.

Adult↗

PubMed2001

Na+/H+ antiporter from Synechocystis species PCC 6803, homologous to SOS1, contains an aspartic residue and long C-terminal tail important for the carrier activity.

A putative Na(+)/H(+) antiporter gene whose deduced amino acid sequence was highly homologous to the NhaP antiporter from Pseudomonas aeruginosa and SOS1 antiporter from Arabidopsis was isolated from Synechocystis sp. PCC 6803. The Synechocystis NhaP antiporter (SynNhaP) was expressed in Escherichia coli mutant cells, which were deficient in Na(+)/H(+) antiporters. It was found that the SynNhaP complemented the salt-sensitive phenotype of the E. coli mutant. Membrane vesicles prepared from the E. coli mutant transformed with the SynNhaP exhibited the Na(+)/H(+) and Li(+)/H(+) antiporter activities, and their activities were insensitive to amiloride. Moreover, its activity was very high between pH 5 and 9. The replacement of aspartate-138 in SynNhaP with glutamate or tyrosine inactivated the SynNhaP antiporter activity. The deletion of a part of the long C-terminal hydrophilic tail significantly inhibited the antiporter activity. A topological model suggests that aspartate-138 in SynNhaP is conserved in NhaP, SOS1, and AtNHX1 and is involved in the exchange activity. Thus, it appeared that the SynNhaP would provide a model system for the study of structural and functional properties of eucaryotic Na(+)/H(+) antiporters.

Amino Acid Sequence↗

PubMed2001

The role of AIDS volunteers in developing community-based care for people with AIDS in Thailand.

The present study analyses the effectiveness of AIDS volunteers in mitigating the stigma attached to People With AIDS (PWAs) within the context of developing community-based care (CBC) in Thailand. A total of 86 trained village health volunteers (T-VHVs) and 99 non-trained village health volunteers (N-VHVs) were enrolled in the study. In addition, 58 villagers in the T-VHV's intervention area and 72 villagers in the non-intervention area were also enrolled. Both T-VHVs and N-VHVs as well as villagers were assessed to determine their level of knowledge with respect to HIV/AIDS and attitudes toward PWAs. Furthermore, we also determined the village health volunteers' level of activity in distributing knowledge of HIV/AIDS in order to prevent and reduce stigma in the community. Although T-VHVs showed a greater depth of knowledge of HIV/AIDS than N-VHVs (p < 0.05), positive attitudes toward PWAs and the level of practice of village health volunteers did not differ significantly between T-VHVs and N-VHVs. While the level of health knowledge of villagers did not differ significantly between the T-VHV's intervention and control areas, a significant difference was observed between the two areas in terms of the villagers' attitudes towards PWAs (p < 0.01). Villagers in the intervention area attached less stigma to PWAs; therefore, T-VHVs played a role in providing basic information on AIDS to the villagers and in mitigating the stigma attached to PWAs. However, these volunteers need to undergo further training through a well-organized training programme in order to obtain a greater depth of knowledge. This is essential for the development of community-based care for PWAs.

Acquired Immunodeficiency Syndrome↗

PubMed2001

Pharmacokinetic differences between lansoprazole enantiomers and contribution of cytochrome P450 isoforms to enantioselective metabolism of lansoprazole in dogs.

The purpose of this study was to evaluate the pharmacokinetics of lansoprazole enantiomers and contribution of cytochrome P450 enzymes to enantioselective metabolism in dogs. The mean Cmax and area under the curve (AUC) values of (+)-lansoprazole were 4-5 times greater than those of (-)-lansoprazole following oral administration of 30-mg racemic lansoprazole to dogs. The CLtot/F values of (+)-lansoprazole were significantly smaller than those of (-)-lansoprazole (p<0.05). The mean unbound fraction of (-)-lansoprazole was significantly greater than that of the (+)-lansoprazole. The amount of (+)-lansoprazole remaining was significantly greater than that of the (-)-lansoprazole after incubation of racemic lansoprazole in dog liver microsomes. When the effects of ticlopidine or ketoconazole on the metabolism of lansoprazole were studied using dog liver microsomes, ticlopidine significantly inhibited the formation of 5-hydroxylansoprazole, but not another metabolite, lansoprazole sulfone; however ketoconazole significantly inhibited formation of both metabolites. When the amount of (+)- and (-)-enantiomers remaining was measured in the presence and absence of ticlopidine, the amount of (+)-lansoprazole was significantly greater than that of the (-)-lansoprazole. On the other hand, there was no significant difference between the amount of (+)- and (-)-enantiomers remaining in combination with ketoconazole. These results suggest that the enantioselective pharmacokinetics of lansoprazole enantiomers are probably ascribable to their enantioselective protein binding and/or metabolism, and among the cytochrome P450 enzymes, CYP3A contributed to the enantioselective metabolism of lansoprazole.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed2001

Increase in doxorubicin cytotoxicity by inhibition of P-glycoprotein activity with lomerizine.

Acquired resistance to chemotherapy is a major problem during cancer treatment. One mechanism for drug resistance is overexpression of the MDR (multidrug resistance)1 gene encoding the transmembrane efflux pump, P-glycoprotein (P-gp). Calcium channel blockers such as verapamil, nifedipine and nicardipine have been shown to reverse cellular drug resistance by inhibiting P-gp drug efflux. This study evaluated whether a new calcium channel blocker, lomerizine, influenced doxorubicin (Dox) cytotoxicity and P-gp activity in a P-gp-expressing cell line compared to a non-expressing subline. Verapamil, and even more markedly, lomerizine, increased cellular uptake of calcein transported by P-gp in a P-gp-expressing erythroleukemia cell line, K562-Dox. Ten microM of lomerizine reduced the IC50 of doxorubicin in the K562-Dox from 60000 ng/ml to 800 ng/ml, whereas the IC50 of doxorubicin in the K562 subline was only marginally affected by these drugs. Lomerizine showed greater reduction in P-gp efflux than verapamil at an equimolar concentration. These results suggest that lomerizine has the clinical potential to reverse tumor MDR involving the efflux protein P-gp.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2000

Evaluation of pelvic descent disorders by dynamic contrast roentgenography.

PURPOSE: For precise diagnosis and rational treatment of the increasing number of patients with descent of intrapelvic organ(s) and anatomic plane(s), dynamic contrast roentgenography of multiple intrapelvic organs and planes is described. METHODS: Sixty-six patients, consisting of 11 males, with a mean age (+/- standard deviation) of 65.6+/-14.2 years and with chief complaints of intrapelvic organ and perineal descent or defecation problems, were examined in this study. Dynamic contrast roentgenography was obtained by opacifying the ileum, urinary bladder, vagina, rectum, and the perineum. Films were taken at both squeeze and strain phases. On the films the lowest points of each organ and plane were plotted, and the distances from the standard line drawn at the upper surface of the sacrum were measured. The values were corrected to percentages according to the height of the sacrococcygeal bone of each patient. From these corrected values, organ or plane descents at strain and squeeze were diagnosed and graphically demonstrated as a descentgram in each patient. RESULTS: Among 17 cases with subjective symptoms of bladder descent, 9 cases (52.9 percent) showed roentgenographic descent. By the same token, among the cases with subjective feeling of descent of the vagina, uterus, peritoneum, perineum, rectum, and anus, roentgenographic descent was confirmed in 15 of 20 (75 percent), 7 of 9 (77.8 percent), 6 of 16 (37.5 percent), 33 of 33 (100 percent), 25 of 37 (67.6 percent), and 22 of 36 (61.6 percent), respectively. The descentgrams were divided into three patterns: anorectal descent type, female genital descent type, and total organ descent type. CONCLUSIONS: Dynamic contrast roentgenography and successive descentgraphy of multiple intrapelvic organs and planes are useful for objective diagnosis and rational treatment of patients with descent disorders of the intrapelvic organ(s) and plane(s).

Aged↗

PubMed2000

Disorder of salivary secretion in inbred polydipsic mouse.

To find mechanisms of an extreme polydipsia in an inbred strain of mice, STR/N, this study was undertaken using Institute of Cancer Research (ICR) mice as a control. During food deprivation, daily water intake of both strains decreased. The decrement in the STR/N mice was larger than that in the ICR mice. During dehydration, daily food intake of the STR/N mice was smaller than that of the ICR mice. These data indicate that prandial drinking was more severely affected for the STR/N mice. Under anesthesia, the stimulated salivary secretion by pilocarpine of the STR/N mice was significantly smaller than that of the ICR mice. The submandibular gland of the STR/N mice was lighter and harder than that of the ICR mice. After desalivation from the major three salivary glands, the ICR mice drank as much as the STR/N mice. Young STR/N mice with undeveloped polydipsia did not show different salivary secretion stimulated by pilocarpine from the young ICR mice. These findings indicate a dysfunction with age in the salivary glands of the STR/N mice, and they suggest that the decreased saliva induces thirst and triggers extraordinary drinking in the polydipsic mice.

Age Factors↗

PubMed2000

A new light on the community health fund--effective political support for a community essential drug project in Vietnam.

This report sheds new light on the development of a community health fund through the implementation of a community essential drug project, and its impact on the improvement of primary health care at the community level. The experience of community drug funds in Vietnam, supported by a strong government commitment, in which full delegation of authority on the management of drugs and finances is given to the community along with a measure for tax exemptions for drug fund revenues, provides a significant example of an autonomous community with active participation of people and effective resource mobilization, that is leading to the improvement of community health.

Community Health Services↗

PubMed2000

Inhibitory effect of human immunodeficiency virus protease inhibitors on multidrug resistance transporter P-glycoproteins.

The objective of this study was to determine whether human immunodeficiency virus (HIV) protease inhibitors (saquinavir, ritonavir and nelfinavir) interact with other HIV protease inhibitors and/or HIV reverse transcriptase inhibitors (zidovudine, didanosine, lamivudine, zalcitabine and sanilvudine). We measured transport of nelfinavir, an HIV protease inhibitor which is known as a substrate for the multidrug resistance transporter P-glycoprotein (P-gp), in an epithelial monolayer model and Ki for P-gp of some drugs by a calcein flux assay. Transport in a basal to apical direction was 2-fold greater than apical to basal flux for nelfinavir, Ki for P-gp of a potent P-gp inhibitor cyclosporin A was 1.09 microM and those of ritonavir and nelfinavir were 111 microM and 28.6 microM, whereas all HIV reverse transcriptase inhibitors gave high K1 values. These data show that nelfinavir, which is a substrate for P-gp, inhibits a P-gp function as a drug efflux pump and that HIV reverse transcriptase inhibitors do not inhibit P-gp.

ATP Binding Cassette Transporter, Subfamily B, Mem↗