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Biomedical subjects

K Sakai

Publications and source records attributed to K Sakai.

At least 325 records · Page 18Linked to original sources
PubMed1999

[Emergency coronary artery bypass grafting with integrated myocardial protection].

In the following retrospective study we reviewed the early postoperative results of emergency CABG; the myocardial management was achieved by utilization of integrated myocardial protection including warm cardioplegic induction, performed at our hospital. From April 1st 1994 to October 30th 1998; 63 patients underwent emergency CABG with integrated myocardial protection. All surgical procedures were performed within 6 hours from the onset of disease or admission transferred from another hospitals. Age ranged 48 to 86 years (mean 69.9 +/- 8.5; 41 male, 22 female). AMI was present in 52, UAP in 11. Preoperative PTCA was done in 20 and IABP was inserted in 53. Cardiogenic shock in 26, mechanical complications in 6, three vessel disease in 48 and LMT disease in 17 was present. Eight patients (12.7%) died in the early postoperative period. Among evaluated risk factors for early postoperative death; the occurrence of cardiogenic shock, mechanical complications of AMI, preoperatively done PTCA and prolonged CPB time were significantly increasing the mortality rate in early postoperative death.

Aged↗
PubMed1999

[Treatment of mild and moderate ulcerative colitis].

Selection of treatment for ulcerative colitis is based on the definition of clinical severity. In those medication is a main course. Mild and moderate cases are treated mainly with salicylazosulfapyridine or mesalazine. Patients with proctitis-type are added betamethazone suppositories and those with left-sided and total colitis-type predonisolone enema therapy simultaneously. If there is no response, they are given additional oral predonisolone. Even after remission, patients should be carefully observed. A good patient-physician relationship, continuation of maintenance therapy, and periodic follow-up examinations using colonoscopy or barium enema are essential to successful long-term management of this disease. Patients who have repeated relapsing should receive the stronger treatment, according to the endoscopic findings and clinical course in addition to the clinical severity.

Anti-Inflammatory Agents↗
PubMed1999

[Radiation-induced cancers following radiotherapy].

Improved radiotherapy for cancer has produced a large population of long-term survivors. These survivors, however, appear to have a greater risk of second primary cancers than would be expected based on the incidence of first primary cancers in the general population. The etiology of radiation-induced cancer is multifactorial and incompletely understood, and there is no firm diagnostic criteria for radiation-induced cancer because there are no specific histopathological findings. The incidence of radiation-induced cancers following radiotherapy was estimated to be about 0.3% in 5-year survivors, based on mail surveys (in 1979 & 1984) in Japan. It seems that the benefit of treatment outweighs the risk of developing secondary tumors. However, we should avoid excess treatment of patients with Hodgkin's disease or many pediatric malignancies who will be able to survive a long time after treatment. The relative carcinogenicity of various combinations of radiation and chemotherapeutic agents is now being established. Chemoradiotherapy is now frequently used for treatment of various malignancies which are considered to be uncontrollable by chemotherapy or radiotherapy alone. We should minimize their carcinogenic effects and the risk of developing secondary treatment-related tumors, to produce an optimal therapeutic gain. Long-term close follow-up is necessary for these patients.

Humans↗
PubMed1999

A case of ABO-incompatible renal transplant patient with non-insulin-dependent diabetes mellitus; long-standing observation of serial glomerular change by protocol biopsy.

A 41-yr-old patient with non-insulin-dependent diabetes mellitus (NIDDM), before and after ABO-incompatible renal transplant, is reviewed using serial protocol biopsy. Although she recovered from delayed hyperacute rejection (DHAR) immediately post-transplantation, her graft function deteriorated gradually. A mild acute transplant glomerulitis, noted at the 155th day post-transplantation, progressed to pronounced chronic transplant glomerulopathy over 5 yr. In the specimen of the last biopsy, at 5 yr post-transplantation, glomeruli demonstrated an exudative hyaline lesion, which was characteristic of diabetic nephropathy in addition to chronic transplant glomerulopathy. Therefore, we made a diagnosis of this glomerular lesion as chronic transplant glomerulopathy complicated by diabetic glomerulopathy. Considering the result of this case, the protocol biopsy is a useful procedure to diagnose an accurate cause of graft dysfunction in individual cases. It is concluded that the protocol biopsy is apparently useful for the detection of various pathological processes occurring in allograft and may contribute to a strategy for improvement of graft survival.

ABO Blood-Group System↗
PubMed1999

Systemic and coronary hemodynamic effects of JTV-506, a novel potassium channel opener, in conscious dogs: comparison with cromakalim and nicorandil.

We compared the coronary and systemic hemodynamic effects of JTV-506, a novel potassium channel opener, with those of cromakalim and nicorandil in chronically instrumented conscious dogs. Experiments were performed in 7 dogs which had undergone the implantation of flow probes on the ascending aorta and left circumflex coronary artery, and of catheters into the descending thoracic aorta and left ventricular cavity, respectively. On different days at least 10 days after the implantation, dogs were randomly assigned to the doses of JTV-506 (2, 5 or 10 microg/kg), cromakalim (10 microg/kg), nicorandil (0.2 mg/kg) or glibenclamide (5 mg/kg) plus JTV-506 (5 microg/kg). Each dose of the three drugs produced dose-related increases in heart rate, coronary blood flow, cardiac output, dP/dt(max) and %SS, and produced decreases in arterial blood pressure, left ventricular systolic pressure, and coronary and systemic vascular resistance. JTV-506 at doses of 2 and 5 microg/kg reduced arterial blood pressure only slightly as compared to its significant coronary vasodilating effect. An increase in myocardial oxygen consumption (as estimated by pressure-work index) was also observed in response to each dose of three drugs. At doses that reduced coronary vascular resistance by 75%, JTV-506 produced a greater increase in coronary blood flow, as compared with cromakalim and nicorandil. JTV-506 has the longest duration of action as compared with cromakalim and nicorandil. Glibenclamide pretreatment completely abolished the effects of JTV-506 on coronary and systemic hemodynamics. These results suggest that JTV-506 is relatively more potent in the coronary bed with minimal systemic influence, and exerts a longer time course of action.

Animals↗
PubMed1999

Are there non-monoaminergic paradoxical sleep-off neurons in the brainstem?

Using extracellular single unit recording in the medulla of freely moving cats, we have found a population of PS-off ("Type II") neurons that are distinct from the classically described monoaminergic PS-off ("Type I") neurons. The presumed non-monoaminergic Type II PS-off neurons (n=22) showed a relatively high rate of tonic discharge during both quiet waking and slow-wave sleep (10.4+/-4.1 and 9.3+/-3.1 spikes/sec, mean +/- S.D., respectively) and a marked overall decrease in discharge rate during PS (0.3+/-0.4 spikes/sec). In contrast to the presumed monoaminergic PS-off neurons (n=62), Type II PS-off neurons showed short-lasting phasic discharges during PS, often in association with rapid eye movement and PGO wave bursts. These Type II neurons were all characterized by a short action potential which was significantly different from that of the monoaminergic PS-off neurons described so far. Five out of 22 neurons were identified antidromically by stimulation of the ventrolateral reticulospinal tract (vlRST) at the caudal medulla, while 2 of the 22 were identified antidromically by stimulation of the peri-locus coeruleus alpha of the mediodorsal pontine tegmentum. Their mean conduction velocity (7.2+/-1.9 m/sec) was significantly higher than that (0.9+/-0.3 m/sec) of the presumed monoaminergic PS-off neurons which were identified exclusively by stimulation of the vlRST. In addition, when examined during the sleep-waking cycle, the antidromic responses of Type II PS-off neurons were either completely blocked or reduced, with a prolongation of antidromic latency during PS. Most of these neurons were located in medullary structures containing no, or virtually no, monoaminergic neurons, and none responded by inhibition to systemic administration of serotonergic or adrenergic autoreceptor agonists. These findings indicate the existence, in the medulla, of non-monoaminergic PS-off neurons that would play an important role in PS generation.

Action Potentials↗
PubMed1998

Sperm-activating proteins obtained from the herring eggs are homologous to trypsin inhibitors and synthesized in follicle cells.

The activation of sperm motility by the egg is an ubiquitous phenomenon in the animal kingdom, but the molecules by which the egg activates sperm motility have been clarified in only a few invertebrate species. In the Pacific herring, Clupea pallasii, mature unfertilized eggs release the sperm-activating proteins which are prerequisite to successful fertilization. Complementary DNA clones encoding herring sperm-activating proteins were isolated from a herring ovarian complementary DNA library and amino acid sequences were deduced. The herring sperm-activating protein(s) is a secretory product(s) with a strong homology to Kazal-type trypsin inhibitors, such as mammalian acrosin inhibitors. The sperm-activating proteins were globally distributed in the outermost layer of the egg chorion and its gene was found to be expressed in the follicle cells which surround developing oocytes. These results suggest that in the Pacific herring, trypsin inhibitor-like proteins are synthesized in the follicle cells, secreted, accumulated in the egg chorion during oocyte development, and released into the milieu at spawning to activate the motility of spermatozoa at the time of gamete interaction.

Amino Acid Sequence↗
PubMed1998

Preparation and characterization of thermally responsive block copolymer micelles comprising poly(N-isopropylacrylamide-b-DL-lactide).

The thermally sensitive block copolymer, poly(N-isopropylacrylamide-b-dl-lactide) (PIPAAm-PLA), was synthesized by ring-opening polymerization of dl-lactide initiated from hydroxy-terminated poly (N-isopropylacrylamide) (PIPAAm). A PIPAAm bearing a single terminal hydroxyl group was prepared by telomerization using 2-hydroxyethanethiol as a chain-transfer agent. Successful preparation of PIPAAm and the PIPAAm-PLA block copolymer was verified by gel permeation chromatography (GPC) and 1H-NMR spectroscopy. Polymeric micelles were prepared from block copolymers using a dialysis method. Their solutions showed reversible changes in optical properties: transparent below a lower critical solution temperature (LCST) and opaque above the LCST. Dynamic light scattering measurements were used to observe the formation of micellar structures approximately 40 nm in diameter, which do not change between 20 degreesC and 30 degreesC. Above the LCST, polymer micelles aggregated, a phenomenon found to be reversible since the aggregates dissociated again by cooling below the LCST. Further observations using atomic force microscopy (AFM) confirmed this behaviour. The properties of this block copolymer system are interesting from both applied and fundamental perspectives, particularly for active targeting as drug carriers.

Acrylamides↗
PubMed1998

Adrenomedullin synergistically interacts with endogenous vasodilators in rats: a possible role of K(ATP) channels.

To examine synergistic interactions among naturally occurring vasodilators, we investigated the effects of i.v. infusion of adrenomedullin (ADM) alone and in combination with low-dose vasoactive intestinal polypeptide (VIP) or calcitonin gene-related peptide (CGRP) on adenosine-induced vasodepression in rats. I.v. infusion of the combination of low-dose ADM (0.1 ng kg(-1) min(-1)) and VIP (3 ng kg(-1) min(-1)), as well as that of ADM (1 ng kg(-1) min(-1)) alone, significantly enhanced the vasodepressor responses to bolus i.v. doses of adenosine (3-100 microg kg(-1)), but not those to acetylcholine (0.1 microg kg(-1)). The observed potentiation did not occur in the presence of glibenclamide (20 mg kg(-1) i.v.), an antagonist of K(ATP) channels. Simultaneous i.v. infusion of low-dose ADM and CGRP (0.1 ng kg(-1) min(-1)) failed to enhance the effects of adenosine as well as acetylcholine. In the whole-cell voltage clamp experiments using single cells of the rat mesenteric artery, ADM (10(-11)-10(-7) M) as well as CGRP (10(-11)-10(-7) M) produced increases of inward current in a concentration-dependent manner. The ADM-induced current was not affected by iberiotoxin, a specific blocker of large conductance Ca2+-activated K+ channels, but suppressed markedly by glibenclamide and CGRP(8-37), a selective antagonist of CGRP1 receptors. From the results, we conclude that several naturally occurring vasodilators involving ADM synergistically interact, probably in link with K(ATP) channels, and furthermore that ADM may act, in part through CGRP1 receptor activation.

Adenosine↗
PubMed1998

Emergence of D-aspartic acid in the differentiating neurons of the rat central nervous system.

The rat embryonic brain was probed with anti-d-aspartic acid (d-Asp) antiserum at different stages of development. At gestational day (E) 12, weak immunoreactivity (IR) of d-Asp was apparent at the hindbrain, midbrain and caudal forebrain, whereas it became more intense and extended over the whole brain at E20. However, IR markedly decreased after parturition. In the region of the immature forebrain at an early stage of development (E12), IR was mainly a characteristic of the cytoplasm of the neuronal cells, while in the more mature hindbrain it was localized in the axonal zone. In the more differentiated forebrain at a later stage of development (E18), the IR became restricted to zones which mainly consisted of axons and processes. Consequently, in the rat central nervous system, d-Asp first emerges during embryonic development as a feature of the cytoplasm and thereafter spreads into the axonal regions of neuronal cells, before disappearing almost completely after parturition.

Animals↗
PubMed1998

A composite CMV-IE enhancer/beta-actin promoter is ubiquitously expressed in mouse cutaneous epithelium.

In most existing transgenic mouse models developed for the study of specific genes in the skin, the goal has been to target transgene expression to defined populations of cells in the cutaneous epithelium. Keratin promoters have been especially useful for this purpose. In some instances, however, it may be desirable to express a transgene in all the cells of the cutaneous epithelium. Since no ubiquitously expressed promoter sequences had previously been identified, we used lacZ reporter transgenes to test two enhancer/promoter sequences for ubiquitous expression in the skin of adult transgenic mice. We find that a CMV enhancer/CMV promoter is not active in most cell types in the skin, whereas a CMV enhancer/modified beta-actin promoter sequence is active in the suprabasal and basal cells of the epidermis as well as in the epithelial cells of the hair follicles, sebaceous glands, and the dermal papillae.

Actins↗
PubMed1998

Angiogenesis in adenocarcinoma of the uterine cervix.

BACKGROUND: Angiogenesis is essential for tumor growth, progression, and metastases. Microvessel density (MVD), a measure of tumor angiogenesis, has been found to have prognostic significance in many tumor types for predicting metastasis and survival. METHODS: Between 1979-1989, 56 cases of FIGO Clinical Stage I and II adenocarcinoma of the uterine cervix treated by hysterectomy were reviewed histologically. All hysterectomy specimens were stained immunohistologically for factor VIII-related antigen. MVD was counted in a x200 field (0.785 mm2 per field) in the most active area of neovascularization. Results were expressed as the highest number of microvessels identified within any single x200 field. MVD and several other prognostic parameters were examined for correlation with progression free survival (PFS) and overall survival (OS) by a multivariate analysis according to the Cox proportional hazards model. RESULTS: In early adenocarcinoma of the uterine cervix, MVD was increased significantly in invasive areas compared with adjacent nonneoplastic areas (median: 62.5 [range, 30-105] vs. median: 36.5 [range, 23-47]; P=0.0003). MVD also was significantly correlated with ascites cytology (P=0.0377). There was no correlation between microvessel count and lymph node status, depth of invasion, disease stage, lymph-vascular space invasion, grade, or parametrial involvement. Patients with high MVD (> or=75) had significantly worse PFS and OS than those with low MVD (< 75) (log rank test, P=0.0180 and 0.0199, respectively). Multivariate analysis showed that MVD correlated significantly and independently with PFS and OS. CONCLUSIONS: In adenocarcinoma of the cervix, MVD is an independent prognostic factor for PFS and OS.

Adenocarcinoma↗
PubMed1998

The genomic organization of the human corticotropin-releasing factor type-1 receptor.

We determined the genomic organization of human CRF type-1 receptor (hCRF-R1). The gene coding for hCRF-R1 consists of at least 14 exons and spans over 20 kilobases. hCRF-R1's three reported isoforms originate from the same gene by alternative splicing. The first hCRF-R1, which binds to CRF with the highest affinity and transduces the most sensitive cAMP accumulation in response to CRF, is encoded in a total of 13 exons, the only one excluded being exon 6. The second isoform contains an additional 29-amino acid sequence which corresponds to exon 6. Unlike the first isoform, the third lacks a 40-amino acid sequence, corresponding to exon 3. Exon-intron boundaries are the same as that of the consensus sequence. Locations of introns in the coding sequence are similar to human CRF-R1, rat CRF-R1, human CRF-R2alpha and others belonging to the human glucagon receptor family.

Amino Acid Sequence↗
PubMed1998

Role for adenosine A1 and A2 receptors in femoral vasodilatation induced by intra-arterial adenosine in rabbits.

The vasodilator effects of adenosine injected into the femoral artery (i.a.) of rabbits were analyzed. Single bolus i.a. doses of adenosine (0.3-10 microg) and 5'-(N-cyclopropyl)-carboxamidoadenosine (CPCA) (0.03-1 microg), an adenosine A2-receptor agonist, produced dose-dependent increases in femoral blood flow and decreases in resistance, almost without affecting blood pressure, heart rate, left ventricular (LV) pressure, and LVd P/dt max, even though CPCA elicited slight decreases in arterial blood pressure and LV pressure. On the other hand, bolus i.a. injections of N6-cyclopentyladenosine (CPA) (1-30 microg), an adenosine A1 receptor agonist, caused a relatively weak increase in blood flow, but markedly affected cardiac parameters, especially heart rate and LVd P/dt max. I.v. treatment with 3,7-dimethyl-1-propargylxanthine (DMPX)(2 mg kg(-1)), an antagonist of adenosine A2 receptors, or 8-phenyltheophylline (1 mg kg(-1)), an antagonist of adenosine A1 receptors, significantly attenuated the vasodilator response to adenosine, but not that to acetylcholine. Decreases in blood pressure, heart rate, LV pressure, LVdP/dt max and femoral vascular resistance, and increases in the blood flow elicited by CPA were not significantly modified by the DMPX treatment, but when this was combined with 8-phenyltheophylline, the responses to CPA were completely abolished. The present results indicate that the adenosine-induced femoral vasodilatation in rabbits may be mediated throughout activation of both adenosine A1 and A2 receptors.

Adenosine↗
PubMed1998

Separate cerebellar areas for motor control.

Cerebellar activation was measured using functional magnetic resonance imaging, while seven normal subjects tapped their fingers paced by tone sequences with or without tone omission. The cerebellar anterior lobe (Larsell's H IV-V) ipsilateral to the movement was activated to a similar degree irrespective of the presence or absence of the tone omission. In contrast, the lateral part of the bilateral posterior lobe (H VIIa) was significantly highly activated for the tone sequence with random omission, compared with either that without omission or that with regular omission. The result suggests that the H IV-V is involved in motor execution, while the lateral part of H VIIa is involved in on-line motor adjustment to unpredictable sensory stimuli.

Acoustic Stimulation↗
PubMed1998

Synergism between low-dose nicorandil and neuropeptides on adenosine-induced vasodepression in rats.

We hypothesized that the effect of nicorandil may be enhanced by interaction with naturally occurring vasodilators. To clarify this hypothesis, the effects of low-dose nicorandil alone and in combination with low doses of vasoactive intestinal polypeptide (VIP) or calcitonin gene-related peptide (CGRP) on adenosine-induced vasodepression were studied in rats. Intravenous (i.v.) bolus injections of adenosine (3-100 microg kg(-1)) elicited dose-dependent decreases in blood pressure, accompanied by slight decreases (except for 100 microg kg(-1)) in heart rate. Simultaneous i.v. infusion of either nicorandil (1 microg kg(-1) min(-1)) and VIP (0.003 microg kg(-1) min(-1)) or CGRP (0.1 ng kg(-1) min(-1)) significantly enhanced the adenosine-induced vasodepression, although each agent alone in the dose used had no effects on vasodepressor responses to adenosine. The potentiation of the effect of adenosine was not observed in the presence of 3,7-dimethyl-1-propargylxanthine (DMPX) (1 mg kg(-1), i.v.) or glibenclamide (20 mg kg(-1), i.v.). The present results suggest that low-dose nicorandil modifies the response to adenosine in interaction with low levels of endogenous neuropeptides such as VIP and CGRP, and that the reciprocal interaction is mediated partly through K(ATP) channel activation in vascular smooth muscle.

Adenosine↗
PubMed1998

Paired-pulse magnetic stimulation of the human motor cortex: differences among I waves.

1. In paired-pulse cortical stimulation experiments, conditioning subthreshold stimuli suppress the electromyographic (EMG) responses of relaxed muscles to suprathreshold magnetic test stimuli at short interstimulus intervals (ISIs) (1-5 ms) and facilitate them at long ISIs (8-15 ms). 2. We made paired-pulse magnetic stimulation studies on the response of the first dorsal interosseous muscle (FDI) produced by I1 or I3 waves using our previously reported method which preferentially elicits one group of I waves when subjects make a slight voluntary contraction. In some experiments the conditioning and test stimuli were oppositely directed, in the others they were oriented in the same direction. Single motor unit responses were recorded with a concentric needle electrode, and surface EMG responses with cup electrodes. 3. In post-stimulus time histograms (PSTHs) of the firing probability of motor units, the peaks produced by I3 waves were decreased by a subthreshold conditioning stimulus that preferentially elicited I1 or I3 waves at an ISI of 4 ms. The amount of decrement depended on the intensity of the conditioning stimulus. The stronger the conditioning stimulus, the greater the suppression. In contrast, the peaks produced by I1 waves were little affected by any type of subthreshold conditioning stimulus, given 4 ms prior to the test stimulus. At an ISI of 10 ms, a subthreshold conditioning stimulus slightly decreased the size of the peak produced by the I3 waves, but did not affect the peaks evoked by I1 waves. 4. Surface EMGs showed that a subthreshold conditioning stimulus suppressed the responses produced by I3 waves irrespective of its current direction (anterior or posterior). Both the amount and duration of suppression depended on the intensity of the conditioning stimulus, but not on its current direction. Both parameters increased when the intensity increased. At a high intensity conditioning stimulus, suppression was evoked at ISIs of 1-20 ms, compatible with the duration of GABA-mediated inhibition found in animal experiments. Responses produced by I1 waves were little affected by any type of subthreshold conditioning stimulus. 5. We conclude that a subthreshold conditioning stimulus given over the motor cortex moderately suppresses I3 waves but does not affect I1 waves. The duration of suppression of the I3 waves supports the idea that this is an effect of GABAergic inhibition within the motor cortex.

Adult↗