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Biomedical subjects

N Seki

Publications and source records attributed to N Seki.

At least 217 records · Page 12Linked to original sources
PubMed1993

[Historical facts of Toan Hosokawa, a doctor of the Edo government].

There are many famous families of the medical bureaucracy in the Edo period, which have been studied before. But the Hosokawa family has not been researched. We therefore made researches on their documents and gravestones. The results were compiled as follows. The Hosokawas had been a distinguished family since the Muromachi period. This family had become engaged as doctors of the Edo government since Mototaka, the 10th generation. The 11th generation Motomichi, who represented himself as the first Tōan, was ordered to republish the "Tongi Pogam" by the Edo government. He received the title of Hōgen, the rank given by the government, for his accomplishment of this work. Motonobu, Tōan of the 2nd generation, was adopted from the Kurokawa family and lived in Kyoto. The previous head of the Kurokawas was Dōyū, who was famous as the first historian of medicine in Japan. Motonobu participated in republishing the "Taiping Huimin Hejiju Fang by the Edo government. His grave still exists at Sōkei-Temple in Tokyo and his epitaph has been identified.

History, Modern 1601-↗
PubMed1992

Type II collagen-induced murine arthritis: induction of arthritis depends on antigen-presenting cell function as well as susceptibility of host to an anticollagen immune response.

Two sets of ((resistant x susceptible) F1----parent) and (parent----F1) chimeric mice were prepared. In the chimeric combinations involving BALB/c and DBA/1 mice, all (F1----F1) chimeras developed arthritis as well as potent anticollagen responses after immunization with collagen, whereas all (F1----BALB/c) and (BALB/c----F1) chimeras induced neither arthritis nor immune responses. This type of F1 T cells could be activated with APC from DBA/1 but not from BALB/c mice. Thus, the failure of the [F1 in equilibrium with BALB/c] chimeras to mount anticollagen responses was due to a defect at the APC level. Another arthritis-resistant strain, C57BL/6, exhibited adequate APC function, but reduced T cell responsiveness, representing an intermediate responder. In the chimeric combinations involving C57BL/6 and DBA/1 mice, (F1----F1) and (C57BL/6----C57BL/6) chimeras developed very high and very low incidence of arthritis, respectively. (C57BL/6----F1) chimeras developed an appreciable incidence of arthritis under conditions in which this group of chimeras generated intermediate levels of anticollagen responses. In contrast, (F1----C57BL/6) chimeras developed low incidence of disease despite induction of strong responses. Moreover, cells from collagen-immunized (F1----C57BL/6) chimeras, when transferred into T cell-depleted B cell mice of F1 or C57BL/6 strain, produced comparable immune responses in both groups but induced much more severe arthritis in F1 than in C57BL/6 recipients. These results indicate that: i) two types of arthritis-resistant strains can be identified, each of which has anticollagen APC defect as a low responder and reduced T cell responsiveness as an intermediate responder and ii) a discrepancy between the degree of anticollagen responses and clinical arthritis is attributed to the differential susceptibility to anticollagen immune responses.

Animals↗
PubMed1992

Changes in the distribution of filipin-sterol complexes in the boar sperm head plasma membrane during epididymal maturation and in the uterus.

The distribution of filipin-sterol complexes (FSCs) and intramembranous particles (IMPs) in the plasma membrane of the late spermatid of the boar and of the sperm obtained from the epididymides, ejaculates, and uterus 2 hours after mating was examined by a freeze-fracture replica technique. In the late spermatid, the FSC density was found to be very low. A majority of the FSCs in the acrosomal plasma membrane (APM) appeared as protuberances on the E face in the epididymal, ejaculate, and uterine sperm. The density of the FSCs in the principal segment (PS) of the APM was 291 +/- 44 FSC/microns2 (mean +/- standard deviation, S.D.), 322 +/- 41 FSC/microns2 and 355 +/- 31 FSC/microns2 in the caput, corpus, and cauda epididymidis, respectively. In comparison with the cauda epididymal sperm, the FSC density gradually decreased in the PS of the ejaculated (277 +/- 39 FSC/microns2) and uterine sperm (243 +/- 50 FSC/microns2). The reduction was especially remarkable in the equatorial segment (ES), where the density of FSCs in ejaculated and uterine sperm decreased to about half and less than half of that in the cauda epididymal sperm, respectively. Large (13 nm) and small (8 nm) IMPs were distributed evenly and densely in the P face of the APM in the late spermatid, epididymal, and ejaculated sperm. In the uterine sperm, IMP-free areas were observed in the P face of the plasma membrane, a feature thought to represent one of the capacitation changes of the boar sperm.

Animals↗
PubMed1992

The effect of age on the response of the detrusor to intracellular mechanical stimulus: DNA replication and the cell actin matrix.

Benign prostatic hypertrophy and posterior urethral valves present at both extremes of the age spectrum. Both disease processes can obstruct the urinary stream and ultimately have pathophysiological effects on detrusor structure and function. The mechanisms regulating the structural reorganization of the detrusor to a mechanical outflow obstruction are not known. In an attempt to identify maturational differences in myocyte ultrastructure and consequent effects these might have in modifying the response of the detrusor to mechanical stimulus, we studied differences in dynamic nuclear-cytoskeletal interactions in detrusor tissue in an animal model. Using a drug which specifically severs actin, cytochalasin D (CD), as an intracellular mechanical stimulus, we measured changes in nuclear area and the rate of DNA synthesis in detrusor myocytes from young (2-3 week) and old (8-12 mon) guinea pigs. We found that there were age specific differences to intracellular mechanical stimuli in detrusor muscle. Nuclei of myocytes from young animals showed elastic recoil on severing the cell actin matrix and the tissue from young animals increased replicative DNA synthesis with an intracellular stimulus. In contrast, nuclear shape changes in myocytes from old animals suggested less elasticity, and there was no increase in DNA synthesis with disruption of the cell actin matrix. Anti-alpha-smooth muscle actin antibody and rhodamine phalloidin staining of actin in cytochalasin D treated primary explants of detrusor myocytes showed dose dependent disruption of the actin component of the cytoskeleton. These results suggest that there are fundamental modifications in detrusor myocyte ultrastructure with age. These maturational changes might result in differences in the pathophysiological and structural reorganization of the detrusor in response to outflow obstruction in infancy and adulthood. Furthermore, they suggest that 1) a tensile equilibrium exists between the myocyte nucleus and cytoskeleton; 2) there appears to be a decrease in myocyte nuclear elasticity with ageing; 3) release of nuclear template restrictions increases activity of DNA polymerase alpha in young, but not old, detrusor myocytes; and 4) mechanico-chemical signal transduction in detrusor myocytes may be mediated via the cytoskeleton. In addition, based on previous reports of actin within the nucleus, the results suggest that 1) nuclear actin may have a homeostatic structural role, maintaining the tensile equilibrium between nucleus and cytoskeleton, and 2) integrity of nuclear actin may function to maintain the spatial template restriction on DNA polymerase alpha activity.

Actins↗
PubMed1992

Changes in action potential kinetics following experimental bladder outflow obstruction in the guinea pig.

The effect of experimental bladder outflow obstruction on membrane electrical activity of guinea pig detrusor smooth muscle was studied. Using an intracellular microelectrode technique, action potentials were recorded from single smooth muscle cells to determine the effect of outflow obstruction on action potential (AP) kinetics. Bladder outflow obstruction resulted in smooth muscle hypertrophy with bladder weight gain to 2.7 times control levels after 8-12 weeks' obstruction. The changes in the AP kinetics noted with obstruction-induced bladder hypertrophy were a prolongation of the AP duration and a decrease in the maximum velocity of depolarization and repolarization. The AP amplitude, after hyperpolarization and overshoot potential in addition to the resting membrane potential (RMP) did not change significantly with bladder outflow obstruction. The values of these AP parameters were not affected significantly by the application of atropine and guanethidine in smooth muscle tissue from either control or obstructed bladders. These results suggest that the active electrical properties of the detrusor smooth muscle membrane are changed significantly by obstruction-induced bladder hypertrophy. Furthermore, the results suggest that adrenergic and cholinergic neurotransmitters do not contribute to these changes in AP kinetics following obstruction. The changes in AP properties with outflow obstruction-induced bladder hypertrophy were compared with those previously reported for the hypertrophic myocardium and were discussed in relation to the known impaired contractile properties of obstructed bladder smooth muscle.

Action Potentials↗
PubMed1992

Analysis of the detrusor smooth muscle action potential.

A method is described to record bladder smooth muscle action potential (AP) data and subsequently in digitized form analyze the constitutive elements of the AP. Manipulation of digitized data can give accurate descriptive information on the AP configuration and kinetics. In the future this type of analysis will hopefully lead to more precise, quantitative information on changes in the smooth muscle AP kinetics with disease states and facilitate a clearer understanding of the pathophysiological processes underlying changes in detrusor contractility.

Action Potentials↗
PubMed1992

Rapid preparation of diagnostic probes for the fragile X syndrome by direct PCR amplification of human chromosomal DNA.

The fragile X syndrome is a common familial form of mental retardation and is associated with a rare fragile site at Xq27.3 (FRAXA). This disorder has recently been reported to correlate with length variations of restriction genomic DNA fragments which may due to the amplification of (CCG)n trinucleotide repeats located at the FRAXA locus. We described here a rapid preparation method of diagnostic DNA probes for the fragile X syndrome by direct enzymatic amplification of human chromosomal DNA. The PstI-assay, which is Southern blot analysis of DNA samples probed by PCR products, was shown to be sensitive method for diagnostic purposes to detect the size variations specific in the fragile X syndrome.

Base Sequence↗
PubMed1992

Chromosome abnormalities and rare fragile sites detected in azoospermia patients.

We have examined constitutional chromosome abnormalities and fragile sites in 40 patients with azoospermia. Chromosome abnormalities were found in four cases. Three cases showed a deletion of the long arm of the Y chromosome 46,X,del(Yq) and the other case had a ring of G group chromosome 46,XY,r(G). In a rare fragile sites test, four fragile site carriers were detected and three rare autosomal fragile sites were identified; fra(8)(q24.1), fra(11)(p15.1), and fra(17)(p12). The expression of these fragile sites were induced specifically by AT-specific DNA ligands, such as distamycin A and Hoechst 33258. In addition, one patient was found to be the case of double ascertainment of fragile sites, fra(8)(q24.1) and fra(17)(p12). The overall frequency of distamycin A-inducible fragile sites in azoospermia patients appeared to be higher than those reported for Japanese healthy subjects and cancer patients. However, no significant relation among fragile sites, clinical and histological findings has been detected so far.

Chromosome Aberrations↗
PubMed1992

The effect of experimental urethral obstruction and its reversal on changes in passive electrical properties of detrusor muscle.

The passive electrical properties of guinea pig detrusor muscle were studied in order to determine how bladder outflow obstruction and reversal might modify the electrical activity of the bladder and, thus, contractility. Experimental bladder outflow obstruction was produced in guinea pigs and resulted in an increase in bladder weight with a decrease in spontaneous electrical activity, membrane time constant and space constant. In addition, the membrane Na-K pump activity increased with obstruction. Following reversal of obstruction, bladder weight gain associated with obstruction was only partially reversible. The decrease in the membrane time constant induced by obstruction was almost fully reversible following release of obstruction. In contrast, the membrane space constant which reflects spread of current, in addition to spontaneous electrical activity, were only partially reversible. The membrane Na-K pump activity of the detrusor muscle decreased to control levels following reversal of bladder outflow obstruction. There was no significant change in the resting membrane potential of detrusor smooth muscle with either obstruction or following reversal of obstruction. These results suggest, that, the changes in the bladder smooth muscle membrane electrical properties induced by experimental bladder outflow obstruction are only partially reversible following release of obstruction. Furthermore, the results suggest that, the dysfunctional cystometric patterns associated with bladder outflow obstruction might not only be due to changes in detrusor innervation but, fundamental reorganization of the detrusor's electrical syncytium with irreversible suppression of cell-to-cell transfer of electrical activity.

Action Potentials↗
PubMed1992

Membrane hyperpolarization inhibits agonist-induced synthesis of inositol 1,4,5-trisphosphate in rabbit mesenteric artery.

1. Effects of membrane hyperpolarization induced by pinacidil on Ca2+ mobilization induced by noradrenaline (NA) were investigated by measuring intracellular Ca2+ concentration ([Ca2+]i), isometric tension, membrane potential and production of inositol 1,4,5-trisphosphate (IP3) in smooth muscle cells of the rabbit mesenteric artery. 2. Pinacidil (0.1-10 microM) concentration dependently hyperpolarized the smooth muscle membrane with a reduction in membrane resistance. Glibenclamide (1 microM) blocked the membrane hyperpolarization induced by 1 microM-pinacidil. NA (10 microM) depolarized the smooth muscle membrane with associated oscillations. Pinacidil (1 microM) inhibited this response and glibenclamide (1 microM) prevented the action of pinacidil on both the NA-induced events. 3. In thin smooth muscle strips, 10 microM-NA produced a large phasic and a subsequent small tonic increase in [Ca2+]i with associated oscillations. These changes in [Ca2+]i seemed to be coincident with phasic, tonic and oscillatory contractions, respectively. Pinacidil (0.1-1 microM) inhibited the increases in [Ca2+]i and in tension induced by NA, but not by 128 mM-K+. Glibenclamide inhibited these actions of pinacidil. Pinacidil (1 microM) also inhibited the contraction induced by 10 microM-NA in strips treated with A23187 (which functionally removes cellular Ca2+ storage sites), suggesting that membrane hyperpolarization inhibits Ca2+ influxes activated by NA. 4. In Ca2(+)-free solution containing 2 mM-EGTA, NA (10 microM) transiently increased [Ca2+]i, tension and synthesis of IP3. Pinacidil (over 0.1 microM) inhibited the increases in [Ca2+]i, tension and synthesis of IP3 induced by 10 microM-NA in Ca2(+)-free solution containing 5.9 mM-K+, but not in a similar solution containing 40 or 128 mM-K+. Glibenclamide (1 microM) inhibited these actions of pinacidil. These inhibitory actions of pinacidil were still observed in solutions containing low Na+ or low Cl-. These results suggest that pinacidil inhibits NA-induced Ca2+ release from storage sites through an inhibition of IP3 synthesis resulting from its membrane hyperpolarizing action. 5. In beta-escin-treated skinned strips, NA (10 microM) or IP3 (20 microM) increased Ca2+ in Ca2(+)-free solution containing 50 microM-EGTA and 3 microM-guanosine triphosphate (GTP) after brief application of 0.3 microM-Ca2+, suggesting Ca2+ is released from intracellular storage sites. Heparin (500 micrograms/ml, an inhibitor of the IP3 receptor), but not pinacidil (1 microM) or glibenclamide (1 microM), inhibited the Ca2+ release from storage sites induced by NA or IP3. These results suggest that membrane hyperpolarization is essential for the inhibitory action of pinacidil on the NA-induced Ca2(+)-releasing mechanism.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

Stretch-mediated visceral smooth muscle growth in vitro.

An in vitro model of smooth muscle stretch was developed to study mechanical stimulus as a possible mediator of visceral smooth muscle growth and differences in the growth response of smooth muscle from young and old animals. De novo DNA synthesis as measured by the aphidicolin-sensitive specific activity of DNA was used as an index of cell growth. Compared with old tissue, the rate of aphidicolin-sensitive DNA synthesis in smooth muscle from young animals was 3-5 and 1.5-2 times greater in bladder and taenia coli, respectively. Stretch of bladder muscle and taenia coli strips from young animals for 6 h increased the aphidicolin-sensitive specific activity of DNA 3-fold (P less than 0.01) and 1.5-fold (P less than 0.01), respectively. Tissue from old animals, however, under the same conditions increased the rate of aphidicolin-resistant DNA synthesis, possibly implying DNA repair. Autoradiography showed only labeled myocyte nuclei. These results indicate that homeostatic mechanisms modulating myocyte growth in visceral smooth muscle can respond to mechanical stimulus in the absence of other trophic factors.

Aging↗
PubMed1992

Detrusor hyperplasia and expression of "immediate early" genes with onset of abnormal urodynamic parameters.

To determine the stimulus for growth of the detrusor with a pathophysiological obstruction to the urinary stream, we studied urodynamic parameters, detrusor weight, detrusor DNA content, and the expression of early growth-related protooncogenes in a model of gradual onset bladder outflow obstruction and reversal of obstruction. Silver jeweler's jump rings were placed loosely round the urethra of immature guinea pigs, allowing an obstruction to develop gradually with animal growth. At 1, 2, 4, and 8 wk after surgery, animals were killed after urodynamic studies under urethan anesthesia. Bladders were removed, and mucosa-free detrusor was weighed and frozen for assay of DNA content and expression of c-fos and c-myc protooncogenes. Results were compared with sham-operated age-matched control animals. One week after surgery there was no change in the urodynamic parameters, detrusor weight, or DNA content. At 2, 4, and 8 wk after placement of the silver rings, animals developed obstructive voiding patterns, an increase in detrusor weight, and total DNA content. The onset of obstructive voiding patterns correlated with transient increased levels of c-fos and c-myc mRNA by Northern blot analysis. Autoradiography of in vivo [methyl-3H]thymidine-labeled detrusor muscle from obstructed animals showed myocyte DNA synthesis and mitosis, implying myocyte hyperplasia. After removal of the silver ring, the obstructive voiding patterns resolved and detrusor weight and DNA content returned to levels of the control animals. These results suggest that in the guinea pig bladder subjected to a gradual onset outflow obstruction, detrusor growth is initiated by the development of obstructive voiding patterns.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Changes in electrical properties of guinea pig smooth muscle membrane by experimental bladder outflow obstruction.

The changes in membrane electrical properties of guinea pig bladder smooth muscle following experimental bladder outflow obstruction were studied by means of an intracellular microelectrode technique. The results of this study can be summarized as follows. 1) Bladder outflow obstruction resulted in a threefold increase in bladder weight after 4-8 wk. 2) The resting membrane potential was unchanged with obstruction; however, the obstructed smooth muscle membrane was more quiescent, with less spontaneous electrical activity compared with control tissue. 3) The membrane constants, space constant and time constant, were both reduced in the obstructed bladders. 4) There was no detectable difference in membrane depolarization induced by high extracellular K+ solution between control and obstructed bladders. 5) Both the membrane depolarization induced by K(+)-free solution or ouabain-containing Krebs solution and ouabain-sensitive membrane hyperpolarization by K(+)-containing solution after application of K(+)-free solution were significantly increased in the obstructed bladders. 6) Low extracellular Cl- solution evoked greater membrane depolarization in obstructed bladders. These results suggest that bladder outflow obstruction results in suppression of the cell-to-cell transfer of electrical activity and activation of a membrane electrogenic Na(+)-K+ pump mechanism in guinea pig detrusor.

Animals↗
PubMed1992

Induction of a BrdU-enhanceable fragile site-like lesion and sister chromatid exchanges at 11q23.1 in EBV-transformed lymphoblastoid cell lines.

We examined the expression of a fragile site-like lesion and induction of sister chromatid exchanges (SCEs) at 11q23.1 in EBV-transformed lymphoblastoid cell lines derived from carriers of distamycin A-inducible fragile sites and ataxia telangiectasia patients. The fragile site-like lesion at 11q23.1 was found to be BrdU-enhanceable in all cell lines examined, and the expression frequencies increased linearly with the rates of BrdU substitution in replicated DNA. In addition, an increased frequency of SCEs was observed at 11q23.1 on the expressed chromosome. Thus, the BrdU-enhanceable fragile site-like lesion at 11q23.1 is a "hot spot" for the formation of SCEs, as has been reported for other rare and common fragile sites.

Bromodeoxyuridine↗
PubMed1992

Effect of pinacidil on the membrane electrical activity of guinea pig detrusor muscle.

The effects of pinacidil on the guinea pig detrusor smooth muscle membrane were studied to investigate the electrophysiological mechanisms by which this drug relaxes smooth muscle tissue and, thus, might be of value in the treatment of detrusor instability. Pinacidil (> or = 3 x 10(-7) M) hyperpolarized the membrane in a concentration-dependent manner, with a reduction in spontaneous spike discharges. The membrane hyperpolarization induced by pinacidil was consistently associated with an increase in membrane ionic conductance. Glybenclamide (10(-6) M) completely inhibited the membrane hyperpolarization induced by pinacidil (up to 10(-5) M). Membrane hyperpolarization with pinacidil was consistently greater in a low-K+ solution, and it decreased in the presence of a high-K+ solution, compared with that measured in normal Krebs solution. Pinacidil consistently suppressed carbachol-induced depolarization of the membrane, with a reduction in the frequency of spontaneous action potentials. Glybenclamide (10(-6) M) did not inhibit the effect of pinacidil on increased action potential frequency induced by carbachol but blocked the membrane hyperpolarization induced by pinacidil (10(-5) M). In addition, the amplitude and maximum velocity of depolarization of carbachol- and current-induced action potentials were significantly decreased by pinacidil in the presence of glybenclamide. These results suggest that pinacidil blocks action potential generation in detrusor smooth muscle by inducing membrane hyperpolarization secondary to an increase in K+ permeability. Pinacidil, at high concentrations (> or = 10(-5) M), might block action potentials by inhibiting the voltage-sensitive Ca++ influx independently of hyperpolarization of the membrane. These mechanisms might be of benefit therapeutically in relaxation of unstable detrusor contractions.

Animals↗