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Biomedical subjects

Y Kasai

Publications and source records attributed to Y Kasai.

At least 109 records · Page 6Linked to original sources
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↗
PubMed1991

Increased methotrexate-induced DNA strand breaks and cytotoxicity following mutational loss of thymidine kinase.

The cytotoxicity and DNA lesions induced by methotrexate (MTX) were compared in wild-type, hypoxanthine-guanine phosphoribosyltransferase-deficient (HGPRT-) and thymidine-kinase-deficient (TK-) HL-60 cells. TK- and HGPRT- cells were approximately 10 and 3 times more sensitive to MTX than wild-type cells, respectively. Following incubation with 2 microM MTX for 16 hr, TK- cells showed a significantly higher number of DNA strand breaks. Concomitantly, DNA fragmentation at the nucleosomal linker region was detected more prominently in TK- cells. Although MTX tended to decrease TTP pools similarly in all 3 cells types, the initial TTP level in TK- cells was only about one-fifth of that found in the wild type. These results indicate that the thymidine salvage pathway has a pivotal role in mediating MTX-induced toxicity and DNA lesions.

Cell Line↗
PubMed1991

Evaluation of a new finger-type intraoperative epicardial echocardiographic probe for infants and small children.

A new finger-type epicardial echocardiographic probe was evaluated in 26 children with complex cardiac anomalies during open heart surgery. The probe is a small 3.75 MHz phased array transducer for 2-dimensional echo and color Doppler imaging. The tip is slightly angled to facilitate the apical approach through a median sternotomy. The patients included 4 neonates and 8 infants, and the major cardiac lesions were complete atrioventricular (AV) canal, transposition of the great arteries, double outlet right ventricle, and others. The intraoperative study was possible in most of the patients facilitating various approaches for the assessment of left-sided AV valve function, left ventricular outflow obstruction, residual shunt and intraatrial anatomy. Four patients received subsequent operative procedures after the assessment. This transducer appears to be useful in the intraoperative study during surgery for complex cardiac anomalies in neonates and small infants.

Child↗
PubMed1991

Pharmacological studies with the alpha 2-adrenoceptor antagonist midaglizole. Part II: Central and peripheral nervous systems.

Pharmacological properties of midaglizole (DG-5128, CAS 66529-17-7) on central and peripheral nervous systems were investigated in comparison with those of tolbutamide. 1. Central nervous system: Midaglizole showed little or no effects on general behavior (mouse), spontaneous motor activity (mouse), hexobarbital anesthesia (mouse), conditioned avoidance response (rat) and body temperature (rabbit) at an oral dose of 100 mg/kg. It also produced little or no changes in electroencephalogram (cat) and spinal reflex (cat) after intravenous dosing of 10 mg/kg. The drug lacked anticonvulsant and analgesic activities (mouse). Midaglizole produced clonic convulsion, mydriasis, lacrimation, increase in pinna reflex, decrease in spontaneous motor activity, increase in pain threshold (mouse) and rise in body temperature (rabbit) at oral dose of 300 mg/kg. Tolbutamide showed similar effects except that it potentiated hexobarbital anesthesia, slightly decreased convulsion and tended to decrease body temperature. 2. Autonomic nervous system: Midaglizole potentiated the pressor response to norepinephrine and inhibited the depressor response to acetylcholine at an intravenous dose of 10 mg/kg (anesthetized dogs). Similar results were observed after dosing of tolbutamide. Midaglizole potentiated the contractile response of nictitating membrane to pre- and post-ganglionic cervical sympathetic nerve stimulation after intravenous dosing of 1 mg/kg (cat). Tolbutamide lacked the activity on the contraction elicited by both stimulations. Midaglizole and tolbutamide had little or no effect on pupil size (rabbit). 3. Skeletal muscle contraction (neuromuscular junction): Midaglizole (3-10 mg/kg i.v.) slightly potentiated the tibialis anterior muscle contraction induced by peroneal nerve stimulation, but did not potentiate the contraction by direct (muscle) stimulation (rabbit). On the other hand, tolbutamide increased the contraction induced by both nerve and muscle stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗
PubMed1991

Pharmacological studies with the alpha 2-adrenoceptor antagonist midaglizole. Part III: Smooth muscle, gastrointestinal and miscellaneous systems.

Pharmacological properties of midaglizole (DG-5128, CAS 66529-17-7) on smooth muscle, gastrointestinal and miscellaneous systems were investigated in comparison with those of tolbutamide. 1. Isolated smooth muscle: Midaglizole inhibited the contractile responses of the ileum to nicotine, acetylcholine, serotonin and BaCl2, and especially the response to histamine (guinea pig). Tolbutamide also reduced the contractions. On spontaneous motility of the uterus (estrus, diestrus, pregnant), midaglizole produced an increase in tonus and frequency, and decrease in contractile amplitude (rat). Tolbutamide reduced the motility of the uterus. The contractile response of the vas deferens to norepinephrine was potentiated after midaglizole and tolbutamide (guinea pig). Midaglizole inhibited the contractile response of the trachea to histamine, whereas it had little or no effect on the response to acetylcholine (guinea pig). Tolbutamide reduced the responses to both spasmogens. 2. Gastrointestinal system: Midaglizole induced an increase in gastrointestinal transit (mouse) and potentiated the gastrointestinal motility (dog). Tolbutamide was without any effect on these parameters. Gastric emptying rate, gastric secretion and gastric mucosa were not influenced after midaglizole (rat). Tolbutamide decreased gastric secretion and produced injury of gastric mucosa. 3. Urine volume: Midaglizole and tolbutamide showed a diuretic activity (rat). 4. Anti-inflammatory activity: Midaglizole and tolbutamide inhibited carrageenin-induced paw edema (rat).

Adrenergic alpha-Antagonists↗
PubMed1991

[Cooperative study of surgical adjuvant chemotherapy for colorectal cancer (third report): five-year results. Cooperative Study Group of Surgical Adjuvant Chemotherapy for Colorectal Cancer in Japan].

A randomized controlled study was carried out by the envelope method with 491 institutions in participation across the country in order to find an optimal surgical adjuvant chemotherapy for curatively resected colorectal cancer. The schedules for drug administration were different in four districts: ACNU + Futraful (FT) group and FT alone group in the Hokkaido-Shikoku district; the same schedule groups plus untreated group in the Chubu-Kinki district; MMC+FT group, FT alone group in the Tohoku-Kanto district; and ADM+FT group and FT alone group in the Chugoku-Kyushu district. The numbers of patients admitted to this study were 2,450 cases with colon cancer and 2,456 cases met the evaluation criteria of this study. The 5-year survival rate on the whole did not differ from combination therapy to single drug therapy in either colon cancer or rectal cancer, but in Dukes C rectal cancer the five-year survival rate tended to be higher with the combination therapies. In n2 (+) or a2(s) rectal cancer in particular, combination therapies with MMC and FT and with ADM and FT achieved significantly higher five-year survival rate, and the rate of local recurrence was significantly lower with ADM+FT.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Two naturally-occurring isoforms and their expression of a glucocorticoid receptor gene from an androgen-dependent mouse tumor.

We have isolated cDNAs encoding the glucocorticoid receptor from an androgen-dependent mouse tumor, Shionogi Carcinoma 115. The nucleotide sequence of the receptor revealed two different forms, designated as SC-GR I and SC-GR II. Both forms have a one-base substitution in the DNA binding domain of the wild-type mouse glucocorticoid receptor. Furthermore, SC-GR II has a three-base insertion in the interfinger region of this domain. By expressing the receptor cDNAs in cultured cells with MMTV-CAT reporter plasmid, SC-GR II was found to have about half of the activity of the wild-type mouse glucocorticoid receptor induced by either physiological or pharmacological doses of dexamethasone.

Androgens↗
PubMed1990

Inhibition of both etoposide-induced DNA fragmentation and activation of poly(ADP-ribose) synthesis by zinc ion.

Treatment of a human promyelocytic leukemia cell line (HL-60) with etoposide for 3-4 hrs produced an extensive degradation of DNA. Agarose gel electrophoresis showed DNA fragmentation in a nucleosomal ladder pattern. Simultaneous addition of zinc ion (ZnSO4, 1 mM) inhibited DNA fragmentation, although the amount of DNA strand breakage introduced initially by etoposide did not change significantly as measured by the DNA unwinding assay. Furthermore, zinc ion abrogated both the activation of poly(ADP-ribose) synthesis and the morphologic changes characteristic of apoptosis by etoposide. These results suggest that zinc ion inhibits a metabolic process somewhere between initial DNA cleavage through an interference with type II topoisomerase and delayed degradation of cellular DNA to a nucleosome-like pattern.

Cell Line↗
PubMed1990

Molecular cloning of cDNA for the human tumor-associated antigen CO-029 and identification of related transmembrane antigens.

The human tumor-associated antigen CO-029 is a monoclonal antibody-defined cell surface glycoprotein of 27-34 kDa. By using the high-efficiency COS cell expression system, a full-length cDNA clone for CO-029 was isolated. When transiently expressed in COS cells, the cDNA clone directed the synthesis of an antigen reactive to monoclonal antibody CO-029 in mixed hemadsorption and immunoblot assays. Sequence analysis revealed that CO-029 belongs to a family of cell surface antigens that includes the melanoma-associated antigen ME491, the leukocyte cell surface antigen CD37, and the Sm23 antigen of the parasitic helminth Schistosoma mansoni. CO-029 and ME491 antigen expression and the effect of their corresponding monoclonal antibodies on cell growth were compared in human tumor cell lines of various histologic origins.

Amino Acid Sequence↗
PubMed1990

Molecular cloning of cDNA for the carcinoma-associated antigen GA733-2.

Defined by monoclonal antibody GA733, the GA733-2 antigen is a cell surface 40-kDa glycoprotein associated with human carcinomas of various origins. Molecular clones for the GA733-2 antigen were isolated from a colorectal carcinoma cell line cDNA library using the high-efficiency COS cell expression system. A 1.4-kilobase cDNA species was enriched by immunoselection with monoclonal antibody. The authenticity of individual clones was established by immunologic and sequence criteria. At the amino acid sequence level, GA733-2 was found to be greater than 99% identical to the previously described KSA antigen defined by monoclonal antibody KS1/4. The amino acid sequence derived from the previously described GA733-related gene, GA733-1, was found to be 49% identical to GA733-2. The positions of 12 cysteine residues in the extracellular domains of the two GA733 antigens are conserved, as is the overall distribution of hydrophobic and hydrophilic residues. A 1.45-kilobase transcript of the GA733-2/KSA gene was found to be expressed in cell lines derived from colorectal and pancreatic carcinoma.

Amino Acid Sequence↗
PubMed1990

Role of bradykinin in the regulation of blood pressure and renal blood flow in DOCA-salt hypertensive rats.

We examined the role of bradykinin in the onset and/or the maintenance of blood pressure and renal blood flow in deoxycorticosterone acetate (DOCA)-salt hypertensive rats by using a competitive antagonist of bradykinin [Arg-Pro-Hyp-Gly-Thi-Ser-Dphe-Thi-Arg; Hyp, L-4-hydroxyproline; Thi, beta-(2-theinyl-L-alanine)]. The intravenous injection of the bradykinin antagonist (25, 50 and 100 micrograms) produced an increase in mean arterial pressure in all rats treated with tap water, 1% NaCl and DOCA + 1% NaCl. However, the magnitude of the increase in mean arterial pressure was significantly lower in the DOCA-hypertensive rats than in the two groups of rats drinking tap water and 1% NaCl after 4 and 6 weeks, but there was no significant difference after 2 weeks. The bradykinin antagonist induced a decrease in renal blood flow in all rats. However, the extent of the fall in renal blood flow was reduced in the DOCA-hypertensive rats compared with the control rats drinking tap water. These results suggest that endogenous bradykinin is depressed in the established phase of hypertension in DOCA-hypertensive rats. It is also suggested that endogenous bradykinin may counteract the elevation of vascular resistance in the early stages of this model.

Animals↗
PubMed1990

A TATA-like sequence located downstream of the transcription initiation site is required for expression of an RNA polymerase II transcribed gene.

TFIID, the TATA-binding protein, was found to stimulate transcription from the adenovirus IVa2 promoter, a promoter considered to lack the TATA motif. Remarkably, a TATA-like sequence element located downstream of the transcription start site binds TFIID and is required for TFIID-dependent transcription from the IVa2 promoter. Transcription from the IVa2 and the adjacent adenovirus major late promoter (Ad-MLP) is divergent, and the cap sites are separated by 212 nucleotides. Nevertheless, the TATA motifs of the IVa2 promoter and Ad-MLP were found to be oriented in the same direction. An initiator motif around the transcription start site is located in the IVa2 promoter, and in contrast to the TATA motifs, the IVa2-initiator is in the opposite orientation with respect to the initiator of the Ad-MLP. A model is presented in which the polar nature of the initiator governs the direction of transcription. We propose that RNA polymerase II and accessory factors recognize the initiator in an orientation-dependent fashion. The recognition of the IVa2 initiator by RNA polymerase is enhanced by the binding of TFIID to the downstream TATA motif.

Adenoviridae↗
PubMed1990

Hand-made valved conduit with high-porosity knitted graft and glutaraldehyde-treated autologous pericardial trileaflet valve.

In 10 patients with various congenital heart defects requiring reconstruction of right ventricle to pulmonary artery continuity, a new hand-made valved conduit was introduced. To avoid late stenosis with peel formation of the graft, high-porosity Golaski knitted graft was chosen. The graft was sealed by fibrin glue, and autologous pericardium was treated with glutaraldehyde and used to construct a trileaflet valve inside the graft. This hand-made graft was pliable with good conformability. The valve function was found good in the intermediate follow-up in 8 patients. This composite valved conduit may be a good alternative to the xenograft valved conduit when allograft conduit is not available.

Bioprosthesis↗