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Biomedical subjects

Y Kasai

Publications and source records attributed to Y Kasai.

At least 19 recordsLinked to original sources
PubMed1995

Stretch-induced enhancement of contractions in uterine smooth muscle of rats.

1. We studied the effect of servo-controlled stretch of smooth muscle strips from rat uterus on tension and intracellular Ca2+ concentration ([Ca2+]i, using fura-2 as an indicator) at 30 degrees C. 2. When quiescent uterine muscle strips were stretched at a ramp time of 0.5 s by multiples of 5% of the resting muscle length (L0) up to 40%, forty-two out of sixty muscle strips responded with a transient active contraction and a [Ca2+]i increase. The minimum excursion of stretch required for contraction was 26.3 +/- 7.5% of L0 (mean +/- S.D.). The peak response had an all-or-none property and was almost independent of the duration of stretch. 3. Stretches of 30 or 35% of L0 induced contraction in most cases when rapidly applied in 0.2-0.5 s, but slowly applied stretch (ramp duration of 5-10 s) rarely induced contraction. 4. The stretch-induced response was inhibited by the removal of extracellular Ca2+ or by the addition of 10 nM nicardipine. However, it was unaffected by 1 microM tetrodotoxin, 1 microM atropine or by 10 microM cyclopiazonic acid, an inhibitor of Ca2+-ATPase in intracellular Ca2+ stores. 5. When a stretch of 15-35% of L0 was applied during the relaxation phase of 10 nM oxytocin-induced rhythmic contractions, the first contraction after the stretch occurred earlier than that expected from the control rhythm. However, the frequency of the subsequent rhythm returned to almost the control level even during continued application of stretch, although the half-width of rhythmic contractions was increased during stretch. 6. The present study demonstrates that stretch of uterine muscle induces a transient contraction due to Ca2+ influx, which is myogenic and dependent on the excursion and velocity of stretch. The all-or-none property of the stretch-induced contractions suggests initiation of Ca2+ spikes. Furthermore, stretch modulates the oxytocin-induced rhythmic contractions.

Animals↗
PubMed1995

Detection of hepatic micrometastasis in pancreatic adenocarcinoma patients by two-stage polymerase chain reaction/restriction fragment length polymorphism analysis.

Hepatic metastasis and retroperitoneal recurrence generally are considered to be the two primary modes of recurrence in pancreatic cancer. The goal of this study was to determine if patients with pancreatic adenocarcinoma have hepatic and peritoneal micrometastasis at operation. Pancreatic adenocarcinomas are known to have a high incidence of K-ras gene mutations. Liver tissue specimens were obtained from 30 patients (17 with pancreatic adenocarcinoma and 13 with other diseases) with a biopsy needle at operation. Peritoneal washings were obtained during operation from 20 patients with pancreatic adenocarcinoma. Two-stage polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis were used to detect K-ras oncogene mutation at codon 12. Thirteen of 17 pancreatic adenocarcinoma patients had K-ras gene mutations in the liver, whereas all 13 patients with other diseases did not. However, only two of 20 pancreatic adenocarcinoma patients revealed K-ras gene mutation in peritoneal lavage fluids. These results indicate the feasibility of detecting hepatic micrometastasis in patients with pancreatic adenocarcinoma, and imply that PCR/RFLP analysis may be of value in the diagnosis, treatment and follow-up of hepatic metastasis of pancreatic adenocarcinoma.

Adenocarcinoma↗
PubMed1995

Protective effects of kampo medicines and baicalin against intestinal toxicity of a new anticancer camptothecin derivative, irinotecan hydrochloride (CPT-11), in rats.

In clinical use, irinotecan hydrochloride (CPT-11; 7-ethyl-10-[4-(piperidino)-1-piperidino]carbonyloxycamptothecin), a novel antitumor agent, causes a relatively high incidence of severe forms of diarrhea. We investigated whether baicalin, an inhibitor of beta-glucuronidase, which deconjugates the glucuronide of the active metabolite of CPT-11, SN-38 (7-ethyl-10-hydorxycamptothecin), and Japanese herbal medicines (Kampo medicines) which contain baicalin can ameliorate CPT-11-induced intestinal toxicity in rats. CPT-11 (60 mg/kg i.v. once daily for 4 consecutive days) induced intestinal toxicity characterized by diarrhea, loss of body weight, anorexia and disruption of intestinal epithelium. Treatment with baicalin (25 mg/kg p.o. twice daily) or Kampo medicines (TJ-14 and TJ-114; 1 g/kg p.o. twice daily) from the day before to 4 or 10 days after the start of CPT-11 administration resulted in significantly decreased weight loss, improved anorexia and delayed onset of diarrheal symptoms. Histological examination revealed that Kampo medicine-treated animals had less damage to the intestinal epithelium and that damage was repaired more rapidly than in control rats. These results suggest that the prophylactic use of Kampo medicines (TJ-14 and TJ-114) may be of value against CPT-11-induced intestinal toxicity.

Animals↗
PubMed1995

[Study on the mechanisms of diarrhea induced by a new anticancer camptothecin derivative, irinotecan hydrochloride (CPT-11), in rats].

We investigated the mechanisms of CPT-11-induced diarrhea. 1) CPT-11 (80 mg/kg, i.v.) induced watery diarrhea within 1 hr after dosing in saline-loaded (10 ml/kg, p.o.) rats. This was partially inhibited by subcutaneous injection of atropine (1 mg/kg) or ondansetron (1 mg/kg) and almost completely inhibited by a combination of atropine and ondansetron or by clonidine (0.3 mg/kg) or morphine (10 mg/kg) alone. 2) CPT-11 at the same dose reduced intestinal fluid absorption, which was blocked by the anti-diarrheal agents mentioned above. Intraluminal injection of CPT-11 (20 mg/2 ml) inhibited fluid absorption and induced fluid secretion. 3) CPT-11, 60 mg/kg, by single intravenous injection induced fewer enzymological and histological changes in the small intestine than 5-FU at 270 mg/kg, while 4 consecutive dosings of CPT-11 induced delayed diarrhea (days 5-7) associated with disruption of intestinal integrity. Co-administration with anti-diarrheal agents, except for ondansetron, protected against watery diarrhea appearing within 1 hr after CPT-11 on days 3 and 4, but worsened delayed diarrhea. These results suggest that single injection of higher doses of CPT-11 causes watery diarrhea at an acute phase at least partly by reducing fluid absorption or increasing secretion, and that while conventional anti-diarrheal agents protect against watery diarrhea, their co-administration in repeated CPT-11 administration has no ameliorative effect on CPT-11-induced delayed diarrhea.

Animals↗
PubMed1995

[General pharmacological study of iodixanol, a new non-ionic isotonic contrast medium].

The general pharmacological study of iodixanol, a non-ionic isotonic contrast medium, was conducted. 1) Iodixanol administered intravenously over a dose range of 320 to 3,200 mgI/kg had little or no effect on the general behavior, spontaneous locomotor activity, hexobarbital sleeping time, pain response, electroshock- or pentylenetetrazol-induced convulsion (mouse), EEG or body temperature (rabbit), gastrointestinal propulsion (mouse) or skeletal muscle contraction (rabbit). Iodixanol had no specific interaction with acetylcholine, histamine, serotonin, nicotin, BaCl2 (ileum), methacholine (trachea), isoprenaline (atrium) or oxytocin (pregnant uterus), nor had any effect on spontaneous contractility (atrium and uterus), or transmural electrostimulation-induced contractility (vas deferens) at concentrations of < or = 3.2 x 10(-3) gI/ml in vitro. Iodixanol had no effect on the cardiovascular system of dog, except that it increased femoral blood flow and respiratory rate at doses of > or = 1,000 mgI/kg. Iodixanol at 3,200 mgI/kg i.v. reduced urine output with a decrease in Na+ and Cl- excretion, whereas at 320 mgI/kg i.v., it slightly increased urine output (rat). 2) Injections of iodixanol into the cerebroventricular (0.96, 9.6 mgI/mouse and 3.2, 32 mgI/rat), left ventricular (1,920, 6,400 mgI/dog) or coronary artery (640, 1,920 mgI/dog) had no conspicuous effect on the central nervous system or the cardiovascular system, respectively. There was no marked difference among iodixanol, iohexol and iopamidol in this respect. Vascular pain during injection into the femoral artery (300-320 mgI/guinea pig) appeared to be less intense with iodixanol, compared with the other contrast media iohexol and iopamidol. These results suggest that intravenous injection of iodixanol is relatively free from pharmacological activity, and effects of iodixanol on the central nervous system (intracerebroventricular injection) and cardiovascular system (intra-left ventricular and -coronary injections) are comparable to those of iohexol and iopamidol. Furthermore, intra-femoral injection of iodixanol has less of a tendency to produce vascular pain than those of iohexol and iopamidol.

Animals↗
PubMed1995

[A synchronous double cancer of esophagus and stomach treated with 5-fluorouracil and consecutive low-dose cisplatin].

We report a case of double cancer of esophagus and stomach treated with 5-fluorouracil and consecutive low-dose cisplatin. The patient was a 58-year-old man with liver cirrhosis. Using upper gastrointestinal fiberscopy, a superficial depressed lesion (O-IIc) in the middle thoracic part of the esophagus and Borrmann 2 type lesion in the fundus of the stomach were also detected. Microscopic examination of the biopsy specimen revealed moderately differentiated squamous cell carcinoma and adenocarcinoma. But laparotomy could not be done due to impaired liver function (KICG 0.051, ICGR15 45.2%). The patient was treated for 28 days with continuous 24 hour infusion 5-FU, 250 mg/body/day plus low dose CD-DP, 10 mg/body daily by bolus infusion d1-5, 8-12, 15-19, 22-26. One month after the chemotherapy, both the gastric cancer and the esophageal cancer were remarkably reduced (diagnosis: PR), and showed no malignancy in the histology. There was no change in the histological findings of the esophageal lesion at 31 months after the chemotherapy. This therapy is effective for patients with gastric cancer and esophageal cancer.

Adenocarcinoma↗
PubMed1993

Immortalization of normal human salivary gland cells with duct-, myoepithelial-, acinar-, or squamous phenotype by transfection with SV40 ori- mutant deoxyribonucleic acid.

BACKGROUND: Based on morphologic and functional differences mainly, 4 distinct types of cells are recognized in human salivary glands. For a better understanding of cellular proliferation and differentiation of human salivary glands as well as carcinogenesis of salivary gland neoplasms, we attempted to establish normal human salivary gland cells in an in vitro system. EXPERIMENTAL DESIGN: Primary cultured human salivary gland cells were transfected with origin-defective mutant DNA of SV40. After 2 to 3 weeks of transfection, slowly expanding colonies consisting of small compact cells emerged, whereas mock-transfected cells did not grow any more and eventually entered crisis, followed by cell death. RESULTS: Using limited dilution technique, we isolated 4 cell clones with distinct morphology from a single colony. Morphologic observation of cells cultured on plastic dishes precisely revealed the characteristics of constituent cells of salivary glands; i.e., three cell clones showing cuboidal (NS-SV-DC), spindle (NS-SV-MC), and flattened (NS-SV-SC) morphology were similar to duct, myoepithelial, and squamous cells, respectively. A remaining cell clone showing polygonal in shape with numerous secretory granules (NS-SV-AC) resembled acinar cells. Characterization of cell clones by the ultrastructural examination and the search for specific antigens showed the similarity of NS-SV-DC, NS-SV-MC, NS-SV-AC, and NS-SV-SC to duct, myoepithelial, acinar, and squamous cells, respectively. Integration and expression of SV40 DNA were confirmed by Southern blot and indirect immunofluorescence staining. Anchorage-independent growth in soft-agar and tumorigenicity in nude mice were not recognized in all cell clones. CONCLUSIONS: These results demonstrate that establishment of cell clones with duct-, myoepithelial-, acinar-, or squamous phenotype was accomplished in the in vitro system, and that based on the evaluation of colony-forming ability in soft-agar and tumorigenicity in nude mice, these cell clones are considered to be non-neoplastic.

Animals↗
PubMed1992

Molecular cloning of murine monoclonal anti-idiotypic Fab.

Anti-idiotypic antibodies (Ab2) binding to idiotopes on antibodies with various antigen binding specificities (Ab1) are potential regulators of immunity in a variety of diseases, such as autoimmunity, cancer, and viral, bacterial, or parasitic infections. Furthermore, Ab2 are useful probes for the characterization of receptor/ligand interactions. Thus far, Ab2 production has been limited to the isolation of polyclonal Ab2 from immune sera or monoclonal Ab2 from hybridoma supernatants. However, both approaches have produced a limited number of Ab2. As an alternative approach, we demonstrate here the production of Ab2-Fab by using repertoire cloning. Using HIV-1 as a model system, the Ab2-Fab were generated from the spleens of mice immunized with the virus-neutralizing and syncytia-inhibiting anti-HIV-1 monoclonal antibody 0.5 beta. A bacteriophage lambda vector system was used to express a combinatorial library in Escherichia coli. Iodinated 0.5 beta was used to identify 17 Ab2-Fab clones. DNA sequence analysis of five clones revealed three similar kappa and Fd combinations. The Ab2-Fab bound with high affinity (3.5-6.5 x 10(9) liters/mol) specifically to the Ab1 and not to isotype-matched antibodies with unrelated specificities. The three Ab2-Fab probably bind to the same idiotope on the Ab1 as demonstrated in cross-competition binding studies. The Ab2-Fab inhibited binding of the Ab1 to antigen, and therefore, may functionally mimic the epitope defined by the Ab1. Repertoire cloning of Ab2-Fab may facilitate the generation of Ab2 that have potential as modulators of immune responses against various antigens.

Amino Acid Sequence↗
PubMed1992

Involvement of p53 mutation in the development of human salivary gland pleomorphic adenomas.

We examined the status of the p53 mutation, a putative tumor suppressor gene, as well as the expressions of myc and mos oncogene products in human salivary gland pleomorphic adenoma cells in culture derived from four individuals using techniques which enabled selective and favourable growths of tumor cells. Culture techniques empolyed in this study consisted of type I collagen gel-coated dishes and serum-free medium as substrates and growth medium, respectively. Cells grown under above conditions were subjected to the analyses of p53, myc and mos expression. When analyzed by both immunocytochemical staining and immunoblot, mutant forms of p53 specifically detected by PAb240 were observed in three of 4 cases. However, none of the 4 cases expressed myc and mos oncogene products. These results may imply a role for p53 mutation in the development of human salivary gland pleomorphic adenomas.

Adenoma, Pleomorphic↗
PubMed1992

Dorsal-ventral patterning in Drosophila: DNA binding of snail protein to the single-minded gene.

The Drosophila snail gene is required for proper mesodermal development. Genetic studies suggest that it functions by repressing adjacent ectodermal gene expression including that of the single-minded (sim) gene. The snail gene encodes a protein with a zinc-finger motif, and here we report that the snail gene product is a sequence-specific DNA binding protein. The snail protein recognizes a 14-base-pair consensus sequence that is found nine times in a 2.8-kilobase sim regulatory region. These results provide evidence for the direct control of sim transcription by snail.

Adenovirus Early Proteins↗
PubMed1992

Pre-treatment of a human T-lymphoblastoid cell line with L-asparaginase reduces etoposide-induced DNA strand breakage and cytotoxicity.

The effect of L-asparaginase (L-asp) pre-treatment on etoposide-induced DNA strand breakage and cytotoxicity was investigated. In a T-lymphoblastoid cell line, Molt 4, etoposide-induced DNA strand breaks, DNA-protein cross-links and cytotoxicity were reduced by pre-treatment with L-asp for 15 hr, but it did not cause these changes in a promyelocytic-leukemia cell line, HL-60, which is less sensitive than Molt 4 to L-asp. However, pre-treatment of Molt 4 cells with L-asp did not significantly alter the accumulation of [3H]-etoposide. Cell-cycle analyses showed an increase in G1-phase cells, a significant decrease in both S-phase cells and G2/M-phase cells pre-treated with L-asp in Molt 4 cells, but L-asp exposure did not result in any significant changes in HL-60 cells. On the other hand, L-asp pre-treatment did not affect topoisomerase-I (Topo-I) inhibitor, camptothecin (CPT)-induced DNA strand breaks or toxicity in Molt 4 cells. Our data imply that a decrease in S- and G2/M-phase cells following L-asp treatment may explain the reduction of etoposide-induced DNA lesions and cytotoxicity in Molt 4 cells, since topoisomerase-II (Topo-II) content or activity is a function of cellular proliferation status.

Asparaginase↗
PubMed1992

Baculovirus recombinant expressing a secreted form of a transmembrane carcinoma-associated antigen.

GA733-2 is a monoclonal antibody-defined, 40-kDa glycoprotein antigen that is associated with carcinomas of various origins. Hydrophobicity analysis of the protein sequence predicted by complementary DNA (cDNA) has suggested that the GA733-2 antigen is a type I membrane protein. In this study, the polymerase chain reaction was used in a strategy to omit cDNA sequences for the transmembrane and cytoplasmic domains, thereby converting the extracellular domain into a secretory protein. Full-length and truncated cDNAs were cloned into the baculovirus transfer vector pVL1392 and introduced into Autographa californica nuclear polyhedrosis virus by homologous recombination. The full-length cDNA baculovirus recombinant directed the expression of a 40-kDa glycoprotein that was confined to infected Spodoptera frugiperda cells, whereas cells infected with the truncated cDNA baculovirus recombinant abundantly secreted a 31-kDa glycoprotein into the culture medium. Recombinant secretory antigen displayed an in vitro immunoreactivity to monoclonal antibody and an in vivo immunogenicity in mice that were similar to native antigen. The facile purification of mg quantities of carcinoma-associated antigen will enable an evaluation of its immunogenicity in cancer patients.

Animals↗
PubMed1992

Anatomy of an unusual RNA polymerase II promoter containing a downstream TATA element.

The adenovirus type 2 IVa2 promoter lacks a conventional TATA element yet directs transcription from two closely spaced initiation sites. To define elements required for in vitro transcription of this promoter, IVa2 templates carrying 5' deletions or linker-scanning mutations were transcribed in HeLa whole-cell extracts and the transcripts were analyzed by primer extension. Mutation of the sequence centered on position -47, which is specifically recognized by a cellular factor, reduced the efficiency of IVa2 transcription two- to threefold, whereas mutation of the sequence centered on position -30 selectively impaired utilization of the minor in vivo initiation site. Utilization of the major in vivo site was decreased no more than fivefold by deletion of all sequences upstream of position -15. By contrast, mutation of the region from +13 to +19 or of the initiation region severely impaired IVa2 transcription. The sequence spanning the initiation sites was sufficient to direct accurate initiation by RNA polymerase II from the major in vivo site. Thus, the two initiation sites of the IVa2 promoter are specified by independent elements, and a downstream element is the primary determinant of efficient transcription from both of these sites. The downstream element identified by mutational analysis altered the TATA element-like sequence TATAGAAA lying at positions +21 to +14 in the coding strand. Transcription from the wild-type IVa2 promoter was severely inhibited when endogenous TFIID was inactivated by mild heat treatment. Exogenous human TATA-binding protein (TBP) synthesized in Escherichia coli restored specific IVa2 transcription from both initiation sites when added to such heat-treated extracts. Although efficient IVa2 transcription requires both the downstream TATA sequence and active TFIID, bacterially synthesized TBP also stimulated the low level of IVa2 transcription observed when the TATA sequence was mutated to a sequence that failed to bind TBP.

Adenoviruses, Human↗
PubMed1992

Acute effect of manidipine on renal blood flow measured by pulsed-Doppler flowmeter in normal subjects.

The purpose of this study was to examine the effect of manidipine hydrochloride, a new calcium antagonist, on renal blood flow in healthy subjects, using the newly developed pulsed-Doppler flowmeter with colored flow imager and digital computer analyzer. Results in previous studies differed because the para-aminohippurate clearance method measures the average not real-time value. Sixteen healthy volunteers (n = 7, manidipine 20 mg; n = 9, placebo control) participated in the study. Before and 1 h after drug administration, pulsed-Doppler measurements were carried out by transabdominal approach with patients in the supine position. Manidipine hydrochloride increased renal blood flow significantly compared with placebo (13.8 +/- 4.7% vs. 6.1 +/- 5.6%; p < 0.05). There was a significant (p < 0.005) between group difference in the reduction in systolic blood pressure (-14.8 +/- 1.6 mmHg manidipine; -3.0 +/- 2.1 mmHg placebo). These data suggest that manidipine hydrochloride has a vasodilating effect on renal arterioles and a beneficial effect on the kidneys of hypertensive patients. Further, the pulsed-Doppler flowmeter may become a very useful tool for noninvasive measurement of renal blood flow.

Adult↗
PubMed1992

Effect of high-dose methotrexate on plasma hypoxanthine and uridine levels in patients with acute leukemia or non-Hodgkin lymphoma in childhood.

We investigated the effect of high dose methotrexate (HDMTX) therapy on plasma hypoxanthine (Hx) and uridine (UR) concentrations in 12 children with acute lymphoblastic leukemia (ALL) or non-Hodgkin lymphoma (NHL). The initial plasma Hx level before the first administration of HDMTX (1 g/m2) was significantly higher in patients (25.5 +/- 17.5 microM) than that in healthy adult controls (4.0 +/- 1.4 microM). By 48 or 72 hours after the beginning of MTX infusion, the Hx concentration had decreased to 7.9 +/- 7.7 microM and 4.7 +/- 4.1 microM, respectively. This decrease of plasma Hx concentration after MTX infusion was also observed with the second course of HDMTX (3 g/m2) therapy. On the other hand, the plasma UR level did not change significantly. The in vitro treatment with 2 microM MTX of hypoxanthine-guanine phosphoribosyltransferase (HGPRT)-deficient mutant cells selected from HL-60 lowered the excretion of Hx into the culture medium. These data suggest a possible new explanation of the synergism of HDMTX and 6-thiopurines, for example 6-mercaptopurine and 6-thioguanine, since plasma Hx is considered to counteract 6-thiopurine toxicity through competition at the level of HGPRT.

Adolescent↗
PubMed1992

General pharmacology of the new quinolone antibacterial agent levofloxacin.

The general pharmacological properties of (-)-(S)-9-fluoro-2,3-dihydro-3- methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido[1,2,3-de][1,4] benzoxazine-6-carboxylic acid hemihydrate (levofloxacin, DR-3355, CAS 100986-85-4), an optically active isomer of ofloxacin, were examined. 1. Central nervous system (CNS): DR-3355 at 200-600 mg/kg p.o. showed depressant activity on the CNS, as was indicated by the depressant syndrome (mice), decreased spontaneous motor activity (mice) and hypothermia (mice and rabbits). In the cat behavior and EEG experiments, it had both stimulant and depressant effects at 30-100 mg/kg i.p., and caused transient slow waves followed by seizures at 20-30 mg/kg i.v. DR-3355 had no effect on convulsion, hexobarbital anesthesia, pain reaction to a tail pinch, or conditioned avoidance response, except that it showed mild analgesic activity in acetic acid writhing at 600 mg/kg p.o. 2. Respiratory and cardiovascular system: DR-3355 produced a hypotensive and a bradycardiac effect after the rapid i.v. injection of 6 mg/kg or more in anesthetized dogs, accompanied by an increase in plasma histamine concentration. Both changes were markedly reduced when the test drug was administered by continuous i.v. infusion. 3. Autonomic nervous system: DR-3355 inhibited nictitating membrane contraction induced by both pre- and post-ganglionic stimulation, and inhibited the depressor response to acetylcholine at 20 mg/kg i.v. It had no influence on pupil size or on pressor response to norepinephrine. 4. Gastrointestinal system: DR-3355 at 600 mg/kg p.o. inhibited gastric secretion. Dog gastrointestinal motility was slightly inhibited, and was then stimulated over the dose range of 2-20 mg/kg i.v. It had no influence on gastrointestinal propulsion, the gastric emptying rate or the gastric mucosa. 5. Isolated smooth muscle: At a concentration of 5 x 10(-4) g/ml, DR-3355 was devoid of spasmogenic or smasmolytic activity, except for showing a slight relaxation effect (trachea), inhibition of nicotine-induced contraction (ileum) and spontaneous or oxytocin-induced motility (pregnant uterus). 6. Miscellaneous: DR-3355 inhibited the urine output and carrageenin-induced paw edema at 600 mg/kg p.o. It had no effect on skeletal muscle contraction or the corneal reflex.

Animals↗