Biomedical subjects

K Arai

Publications and source records attributed to K Arai.

At least 199 records · Page 11Linked to original sources

PubMed1999

alpha1- and alpha2-adrenoceptors in BPH.

The dynamic obstruction of the bladder outlet secondary to benign prostatic hyperplasia (BPH), and the contractile properties of the human prostate are mediated primarily by alpha1-adrenoceptors. There are now at least three subtypes (A, B, and D) of alpha1-adrenoceptors, and recent work revealed that alpha1A-adrenoceptor and alpha1B-adrenoceptor may have a prime role for prostatic obstruction, and contraction of artery, respectively. Very recently, the presence of a low affinity alpha1-adrenoceptor for prazosin, named alpha1L, in the human BPH tissue has been determined. Because the DNA sequence of alpha1L-adrenoceptor has not yet been cloned, the alpha1L-adrenoceptor may be another form of the alpha1A-adrenoceptor, or another pharmacologically distinct alpha1-adrenoceptor which mediates the norepinephrine-induced contraction of the prostatic smooth muscle. Furthermore, the contribution of alpha1-adrenoceptors in the prostate to symptoms (not only obstructive, but irritative symptoms) which are elicited by prostatic obstruction remains to be determined.

Adrenergic alpha-Antagonists↗

PubMed1999

Polymorphisms of amiloride-sensitive sodium channel subunits in five sporadic cases of pseudohypoaldosteronism: do they have pathologic potential?

Pseudohypoaldosteronism (PHA) is characterized by congenital resistance of the kidney and/or other mineralocorticoid target tissues to aldosterone, resulting in excessive salt wasting. Mineralocorticoid receptor (MR) and postreceptor defects in the aldosterone-responsive amiloride-sensitive sodium channel (ENaC) subunits have been suggested as potential loci of the defect in this disease, whereas recently defects in MR and ENaC subunits were reported in familial PHA cases. Here we studied the ENaC subunit alpha, beta, and gamma complementary DNAs (cDNAs) in a series of five sporadic cases of PHA, whose MR cDNA contained nonconservative homozygous (C944-->T944, Ala241-->Val241) and/or a conservative heterozygous substitutions (A760-->G760, Ileu180-->Val180), which, however, were also present at high frequencies in a control population with apparently normal salt conservation. We found a nonconservative substitution (A2086-->G2086, Thr663-->Ala663) in the alphaENaC in all five of our patients, two of whom were homozygous and three of whom were heterozygous for this alteration, which was also present in the homozygous and heterozygous form in 31% and 64% of control subjects, respectively. We also found a nonconservative homozygous substitution (C1006-->G1006, Pro336-->Ara336) in the betaENaC and three nonconservative and conservative homozygous substitutions (T554-->A554, Trp178-->Arg178; C1526-->G1526, Pro501-->Ala501; T1862-->G1862, Ser614-->Ala614) in the gammaENaC of all five of our patients and in a substantial proportion of control subjects. Interestingly, when the patient group was compared to controls, a significantly increased concurrence of the MR and alphaENaC polymorphisms was found in the patients (P<0.025). We conclude that the changes identified in the cDNA of the three ENaC subunits in the patients with sporadic PHA are polymorphisms, which on their own have no apparent pathophysiological significance. We hypothesize, however, that these polymorphisms might influence salt conservation negatively if they are present concurrently with other genetic defects of the MR or other proteins that participate in sodium homeostasis. The latter would be compatible with a sporadic presentation and digenic or multigenic expression and heredity in PHA.

Adolescent↗

PubMed1999

Characterization of the mouse alpha1D-adrenergic receptor gene.

Alpha1-adrenergic receptors (alpha1-ARs) play critical roles in the regulation of a variety of physiological processes. Increasing evidence suggests that multiple receptor subtypes of alpha1-ARs regulate these physiological processes. Molecular cloning has identified three distinct cDNAs encoding alpha1-AR subtypes (alpha1A, alpha1B and alpha1D) that are structurally homologous. Among the alpha1-AR subtypes, the function of the alpha1D-AR remains unclear. In order to examine the physiological role of alpha1D-AR, we cloned and characterized a gene for the mouse alpha1D-AR. Using a mouse alpha1D-AR cDNA as a probe, we isolated the gene for the mouse alpha1D-AR from a mouse genomic library. The alpha1D-AR consists of two exons and an intron that interrupts the coding region of the putative sixth transmembrane domain. The 5'-flanking region of exon 1 contains neither a TATA box nor a CAAT box but is high in GC content and contains several Sp1 binding sites (GC boxes). This pattern is similar to promoters described for other members of alpha1-ARs. The untranslated region also contains putative cyclic AMP response elements. Isolation of this gene will allow further investigation, via gene knock-outs and deletion mutants, of the mechanisms of transcriptional regulation and a greater understanding of the physiological role of alpha1D-AR.

Amino Acid Sequence↗

PubMed1999

Some characteristics of bacteria found in a bioreactor to treat trichloroethylene-contaminated groundwater.

A mixture of bacteria, having a methane-utilizing ability, was separated from a bioreactor supplied with air and methane gas. The bioreactor was operated to treat trichloroethylene (TCE)-contaminated groundwater. The mixture was composed of an obligate methane-utilizing bacterium and a heterotroph, identified as Methylomonas methanica and Pseudomonas sp., respectively. The mixed culture of these two strains removed TCE. In addition, it appeared that a cooperative metabolic interaction of these strains enabled Meth.methanica to maintain the TCE degradation ability.

Bioreactors↗

PubMed1999

Bioremediation of trichloroethylene and cis-1,2-dichloroethylene-contaminated groundwater by methane-utilizing bacteria.

Experimental studies on the bioremediation of groundwater contaminated with low concentration trichloroethylene (TCE) and cis1,2-dichloroethylene (DCE) were performed with two sets of bioreactors. Reactors No. 1 and No. 2 were operated without and with methane supplement, respectively. No inoculum was used. The concentrations of TCE and DCE in the effluent and the off gas from reactor No. 2 were much lower than those from reactor No. 1. When air and an H2O2 solution were supplied to reactor No. 2, concentrations of TCE and DCE in the effluent and the off gas were lower than the lowest detectable limit. The population of methane-utilizing bacteria in reactor No. 2 was 1,000 times higher than that in groundwater or in the effluent from reactor No. 1. These methane-utilizing bacteria were apparently attributable to the treatment of TCE.

Biodegradation, Environmental↗

PubMed1999

Preventing effect of anti-ICAM-1 and anti-LFA-1 monoclonal antibodies on murine islet allograft rejection.

Immunosuppressive potentials of the blockade of intercellular adhesion molecule-1 (ICAM)-1/leukocyte function-associated antigen 1 (LFA-1) were examined in a murine islet allotransplantation model by using blocking monoclonal antibodies (MAbs) against these molecules. Isolated islets from ICR mice were transplanted into the renal subcapsular space of streptozotocin-induced diabetic C57BL/6 mice. Antibodies were administered immediately after transplantation at a dose of 100 micrograms/mouse/d for 3 or 7 d. In non-treated mice, islet grafts were rejected within 16 d, but the treatment with an anti-ICAM-1 MAb (KAT-1) alone, with anti-LFA-1 MAb (KBA) alone, or with both MAbs significantly prolonged the graft survival. In particular, the combination of KAT-1 and KBA in a 7-d course produced a marked prolongation and induced indefinite graft survivals over 100 d in 88% of recipients. Expression of cytokine transcripts within the islet allografts was analyzed by reverse transcriptase polymerase chain reaction (RT-PCR). In the mice treated with KAT-1 and KBA, the transcripts for Th1 cytokines (interleukin 2 [IL-2] and interferon gamma [IFN-gamma]) were not detected, but the expression of Th2 cytokines (IL-4 and IL-10) was enhanced and persisted over 140 d. In contrast, Th1 cytokines were dominantly expressed in the grafts from untreated mice. These results indicate that administration of anti-ICAM-1 and/or anti-LFA-1 MAbs prolongs murine islet allograft survival potentially by indicating a Th2 deviation.

Animals↗

PubMed1999

Secretion of inhibin A, inhibin B and inhibin pro-alphaC during the oestrous cycle of the golden hamster (Mesocricetus auratus).

Plasma concentrations of inhibin pro-alphaC, inhibin A and inhibin B were determined by enzyme-linked immunosorbent assay at 6 h intervals throughout the 4-day oestrous cycle of the golden hamster. Plasma concentrations of follicle-stimulating hormone (FSH) and oestradiol-17beta were also measured by radioimmunoassay during the oestrous cycle. Plasma concentrations of inhibin A increased from the early morning of day 1 (day 1=day of ovulation) and reached plateau levels at 0500 h on day 2. An abrupt increase in plasma concentrations of inhibin A was found at 1700 h on day 4, when the preovulatory FSH surge was observed. An increase in plasma concentrations of inhibin B occurred on day 1 and reached plateau levels at 1700 h on day 1. The levels remained elevated until 0500 h on day 4 and declined gradually by 2300 h on day 4. Plasma concentrations of inhibin pro-alphaC gradually increased with some fluctuation from day 1 to 1700 h on day 4 and then declined. Significant negative relationships were noted between plasma FSH and both dimeric forms of inhibin from day 1 to day 3. Significant positive relationships were found between plasma oestradiol-17beta and inhibin A or inhibin pro-alphaC throughout the oestrous cycle. In contrast, no significant relationship was found between plasma oestradiol-17beta and inhibin B. These findings suggest that both dimeric forms of inhibin play a role in the regulation of FSH secretion during follicular development. These findings also suggest that inhibin pro-alphaC could be secreted primarily by large follicles, and early atretic follicles could also be responsible for inhibin pro-alphaC secretion. On the other hand, the secretory pattern of dimeric inhibins might shift from inhibin B to inhibin A with follicular development.

Animals↗

PubMed1999

Evidence for beta3-adrenoceptor subtypes in relaxation of the human urinary bladder detrusor: analysis by molecular biological and pharmacological methods.

The purpose of the present study was to confirm the presence of beta3-adrenoceptor subtype in the relaxation of human urinary bladder detrusor tissue by reverse transcription-polymerase chain reaction (PCR); direct sequencing of the PCR product, in situ hybridization; and isometric contraction. Using reverse transcription-PCR, the mRNAs of three receptor subtypes (beta1, beta2, and beta3) were expressed in the human urinary bladder detrusor tissue. Direct sequencing of the PCR product of the above beta3-adrenoceptor revealed no mutation in the amplified regions. In situ hybridization with digoxygenin-labeled oligonucleotide probe revealed the presence of the mRNA of beta3-adrenoceptor subtype in the smooth muscle of the urinary bladder. The relaxant effects of isoproterenol (a nonselective beta-adrenoceptor agonist); ZD7114, BRL37344, and CGP12177A (putative selective beta3-adrenoceptor agonists); and SR59230A (a putative selective beta3-adrenoceptor antagonist) were tested using an isometric contraction technique. Isoproterenol in either the presence or absence of both atenolol (a beta1-adrenoceptor-selective antagonist) and butoxamine (a beta2-adrenoceptor-selective antagonist) revealed a relaxant effect on the carbachol-induced contraction of the human urinary bladder detrusor. Both BRL37344 and CGP12177A also revealed relaxant effects on the human urinary bladder detrusor, but ZD7114 did not elicit any relaxation. These results suggest that beta3-adrenoceptor may have some role in urine storage in the human urinary bladder.

Adrenergic beta-Agonists↗

PubMed1999

Pharmacological and molecular biological evidence for ETA endothelin receptor subtype mediating mechanical responses in the detrusor smooth muscle of the human urinary bladder.

The aim of this study was to characterize endothelin receptor subtypes of the detrusor muscle of the human urinary bladder. The receptor subtypes mediating endothelin (ET)-1-induced activity in the human detrusor smooth muscles have been characterized using isometric contraction and reverse transcription-polymerase chain reaction (RT-PCR). ET-1 (a non-selective ET receptor agonist; 10(-10) M to 10(-6) M) exhibited concentration-dependent contractions in human urinary bladder with a plateau at concentrations above 3x10(-7) M. Neither IRL1620 nor sarafotoxin S6c (both ETB-selective agonists; 10(-10) M to 10(-6) M) elicited contractile activity in the human urinary bladder detrusor smooth muscle. FR139317 (an ETA-selective antagonist; 10(-7) M to 10(-5) M) produced a marked shift to the right of the ET-1 concentration-response curve in human urinary bladder detrusor smooth muscle (from the Schild plot TpA2=7.96; slope=0.95). In contrast, RES701-1 (an ETB-selective antagonist; 10(-7) M to 10(-5) M) had no effect on the ET-1 concentration-response curve. RT-PCR revealed positive amplification of ETA receptor mRNA fragment, but not ETB. These results indicate that the ET-1-induced contractile effects of urinary bladder detrusor smooth muscle seem to be mediated mainly by the ETA receptor, not by the ETB receptor.

Aged↗

PubMed1999

[The effect of propofol as an anticonvulsant].

We observed that propofol was very effective for the refractory general convulsion after surgical operation of cerebral aneurysmal clipping in two patients. The first patient had suffered from asthma. Standard regimens except for thiopental were ineffective for the refractory general convulsion after the operation. So, we administered propofol to the patient, at the dosage of 1 mg.kg-1 intravenously and then, 1 mg.kg-1.hr-1 continuously i.v. Propofol suppressed the general convulsions completely. On the EEG, there were no convulsive spikes. Furthermore, patient's consciousness became clearer during the administration of propofol. The convulsion in the second patient not suffering from asthma, was intractable, too and diazepam, phenytoin, and phenobalbital were not effective. Then, we tried propofol in the same way, and good effect was obtained. Propofol may be an effective medicine for the refractory general convulsion.

Anticonvulsants↗

PubMed1999

[A case of type 4 gastric cancer with peritoneal dissemination treated with intra-aortic chemotherapy].

A 45-year-old woman was admitted to our hospital because of lower abdominal pain and anorexia. A barium gastrography and gastroscopy showed a type 4 gastric cancer in the upper gastric body. Histologic study on biopsy specimens from the tumor revealed poorly differentiated adenocarcinoma. Computed tomography revealed bilateral hydronephrosis, and barium enema showed diffuse stenosis of the sigmoid colon because of peritoneal dissemination. This patient was treated by intra-aortic infusion therapy with sequential MTX and 5-FU. After five courses of the administration, barium enema revealed reexpansion of the lumen of sigmoid colon with normalization of the tumor markers. The patient was discharged without symptoms. Intra-aortic infusion therapy with sequential MTX and 5-FU was considered an effective treatment for unresectable gastric cancer.

Adenocarcinoma↗

PubMed1999

Interleukin-4 adenoviral gene therapy reduces production of inflammatory cytokines and prostaglandin E2 by rheumatoid arthritis synovium ex vivo.

BACKGROUND: The rheumatoid arthritis (RA) joint is characterized by an inflammatory synovial pannus which mediates tissue destruction. Interleukin (IL)-4 reduces the production of many proinflammatory cytokines, particularly by activated macrophages. Therefore, we examined the ability of adenovirally delivered IL-4 for the treatment of human RA to reduce the secretion of proinflammatory molecules. METHODS: Adenoviral vectors encoding the genes for human IL-4 (AxCAIL-4) and bacterial beta-galactosidase (AxCAlacZ) were generated and examined for appropriate production and biological activity. RA synovial tissue (ST) explants or fibroblasts were infected with AxCAIL-4 or a beta-galactosidase producing vector, as a control, and conditioned medium (CM) was collected for ELISA analysis. RESULTS: AxCAIL-4 decreased the production of the inflammatory cytokines IL-1 beta and tumor necrosis factor-alpha in RA ST explant CM. IL-8 levels were significantly reduced by 71%, 88%, and 82% at 24, 48, and 72 hours, respectively, in RA ST explant CM. In the same CM, monocyte chemotactic protein-1 (MCP-1) levels decreased 60% at 48 hours. In contrast, RA synovial fibroblast CM levels of MCP-1 were increased by AxCAIL-4. Epithelial neutrophil activating peptide-78 levels produced by RA ST explants were significantly decreased by AxCAIL-4 by 88%, 92%, and 93% at 24, 48, and 72 hours, respectively. Growth related gene product-alpha levels were likewise decreased in RA ST explant CM. In ST explants as well as RA synovial fibroblasts, IL-4 treatment decreased prostaglandin E2 (PGE2) production. CONCLUSIONS: Increased expression of IL-4 via gene therapy may decrease RA-associated inflammation by reducing proinflammatory cytokines and PGE2.

Adenoviridae↗

PubMed1999

[A case of liver metastases from gastric cancer responding to induced hypertensive chemotherapy with angiotensin II].

A 69-year-old man, who had undergone distal gastrectomy for Borrmann type 3 gastric cancer two years ago, experienced a recurrence of multiple liver metastases. Then intra-arterial hepatic cannulation connecting to a subcutaneously implanted port system was indwelt via left subclavial artery. Mitomycin C (20 mg) was injected through out the induced hypertension (1.5 times of his median blood pressure) with intravenously-administered angiotensin II (Delivert), and 5-FU (250 mg/day) was continuously followed for 5 days. He received a total of five courses of this treatment every 4 to 7 weeks. The liver metastases disappeared on CT scan after 4 courses, and a complete response (CR) has been maintained with no use of other chemotherapy. The patient has obtained good quality of life for 32 months after the start of this chemotherapy. Induced hypertensive chemotherapy could be one of the effective treatments for liver metastases from gastric cancer.

Aged↗

PubMed1999

[Keloids].

The treatment of keloids has always been a formidable task and no definitive treatment method has yet been established. We have thus studied the histopathological findings to develop a new and effective treatment for keloid scars. In this article, we first describe the morphological and histopathological analysis of keloid lesions and then secondly keloid treatment methods with a mast cell degranulation suppressant that we developed and a modified enucleation method to remove keloid-forming cells and suppress the herniation-like phenomenon. We further summarize other currently available keloid treatment methods.

Humans↗

PubMed1999

Effects of forced walking stress on formalin-induced paw licking in mice.

This study examined the effects of exposing mice to forced walking stress on formalin-induced paw licking. At each observation period (0.5-6 h) after exposure to forced walking stress, a significant antinociceptive effect (stress-induced analgesia, SIA) was observed only in the second phase (from 10 to 30 min), but not in the first phase (from 0 to 10 min) of formalin-induced paw licking in mice. The present data showed that SIA induced by exposure to forced walking stress was dependent on duration of the stress (0.5-4 h). SIA was dose-dependently antagonized by the NMDA receptor antagonist dizocilipine (0.01-0.04 mg/kg) but not by naloxone (10 mg/kg). Thus, the present results suggest that exposure to forced walking stress could cause SIA which may be involved in the nonopioid system via NMDA receptors.

Analgesia↗

PubMed1999

[Efficacy and problems of hepatic arterial chemotherapy with angiotensin II for liver metastasis from gastric cancer].

Hepatic arterial chemotherapy with angiotensin II was performed on 11 patients with liver metastases from gastric cancer. Mitomycin C was injected for 10 minutes via implanted port, whose tip was located in the hepatic artery, when the mean systolic blood pressure rose to 50 percent above the level in the untreated state by intravenous administration of angiotensin II. After this procedure, 5-fluorouracil at 250 mg/day was continuously infused for 5-days. The response could be measured in 6 of all 11 cases (response rate, 55%). CR was found in 3 patients, PR in 3, NC in 1 and PD in 4. The fifty-percent survival period of responders was 362 days, against 239 days in non-responders. Even if the liver metastases completely disappeared, a recurrence could develop in the liver, bone, lung, peritoneum and lymph nodes. We concluded that this mode of chemotherapy effectively controlled liver metastases from gastric cancer, but it was necessary to follow up with second-line therapy for the recurrence of liver and the other organs.

Aged↗

PubMed1999

[Repeated intraperitoneal chemotherapy for peritoneal dissemination from gastric carcinoma].

Repeated intraperitoneal chemotherapy (RIC) via i.p. port was carried out in 16 patients with peritoneal dissemination P(+) and 8 with positive washing cytology P0.cy (+). CDDP with/without MMC soluted by physiological saline was periodically administered via i.p. port. The average administration was 5.6 times (2-16, median: 6) and the average dose was 288.0 mg. As the results, negative change of washing cytology after RIC was found in 71%, with a high rate especially in P0.cy (+) cases. Also, median survival time (MST) of responders was statistically longer than that of non-responders (777 days vs 254 days). Although diarrhea and anorexia of grade 3 developed once in each one patient, serious toxicities were not found. In conclusion, RIC is effective for peritoneal dissemination, especially P0.cy (+) cases, from gastric carcinoma.

Adult↗

PubMed1999

[Preoperative laparoscopy by local anesthesia for advanced gastric cancer].

Preoperative laparoscopy by local anesthesia was performed in 8 patients with advanced gastric cancer, whose lesions had been diagnosed to be more than T3 or suspected to have peritoneal seeding, and its usefulness was assessed. After insertion of the trocars, the abdominal cavity was inspected, and biopsy and/or abdominal lavage sampling was performed. Three patients out of 8 were diagnosed as P3, and 5 patients were diagnosed as P0 and CY0. Based on these results, 6 patients underwent operation. The accuracy rate of diagnosis was 83% in P category, and 100% in CY category. In conclusion, it is considered that laparoscopy by local anesthesia is a useful preoperative examination for advanced gastric cancer.

Aged↗