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Biomedical subjects

S Komori

Publications and source records attributed to S Komori.

At least 37 records · Page 2Linked to original sources

Screening for deletions in interval D16-22 of the Y chromosome in azoospermic and oligozoospermic Japanese men.

The genetic basis of infertility remains unclear in a majority of infertile men. In this study, the Y chromosome long arm involving the DAZ (deleted in azoospermia) gene was screened in order to evaluate the occurrence of microdeletion in Japanese infertile men. One hundred and fifty-seven infertile Japanese men with azoospermia and oligozoospermia were analyzed for microdeletions in interval D16-22 of the Y chromosome, using polymerase chain reaction with sequence-tagged site markers. Sixteen sets of oligonucleotide primers were synthesized for the polymerase chain reaction, and Southern blot analysis was also performed. The men were divided into five categories on the basis of sperm concentration: functional azoospermia (A; n = 24), azoospermia caused by obstruction (AO; n = 20), oligozoospermia I (OI, sperm concentration less than I x 10(5)/ml; n = 33), oligozoospermia II (OII, sperm concentration less than 1 x 10(6)/ml; n = 30), and oligozoospermia III (OIII, sperm concentration less than 1 x 10(7)/ml; n = 50). Thirty fertile men with a sperm concentration of more than 2 x 10(7)/ml were also analyzed as controls. Microdeletions were identified, in 12 (7.6%) of the 157 infertile men, as follows: 1 man in category A, 1 in category AO, 5 in category OI, 4 in category OII, and 1 in category OIII. No deletion was identified in the fertile men. One common region around sY240 was identified in 11 of the infertile men with microdeletions. This locus may contain specific genes for spermatogenesis. The sperm concentration in the ten oligozoospermic men with microdeletions was below 1 x 10(6)/ml. There were no correlations between the severity of spermatogenic defects and the extent of the microdeletions. These results suggested that genes in the interval D16-22 of the Y chromosome might have important roles in spermatogenesis.

Base Sequence↗

Analysis for microdeletions of Y chromosome in a single spermatozoon from a man with severe oligozoospermia.

Since the association between Y chromosome deletions and spermatogenic failure was demonstrated in 1976, there have been many reports of Y chromosome microdeletions. Peripheral blood lymphocytes (PBLs) have been used for the analysis because the method is convenient, materials are easy to obtain, and PBL genomic DNA is similar to that of germ cells such as spermatozoa. However, PBLs originate from somatic tissue, not from germ cells. In this study, we analyzed 30 spermatozoa in semen ejaculated by an infertile male with Y chromosome microdeletions, while 50 spermatozoa from a normal fertile male were used as a control. The same Y chromosome microdeletion as that found in PBL was identified in each of the 12 spermatozoa which contained the Y chromosome in the infertile patient. These results indicated that spermatozoa (germ cells) had the same Y chromosome microdeletion as PBL (somatic cells). This supports the conjecture that microdeletions are transmitted to the next generation via the treatment of infertility by intracytoplasmic sperm injection.

Base Sequence↗

T lymphocyte activation and restenosis after percutaneous transluminal coronary angioplasty.

We investigated the relation between the activation of T lymphocytes and the occurrence of restenosis after percutaneous transluminal coronary angioplasty (PTCA) in 10 stable angina patients. Recent studies have suggested that PTCA causes an inflammatory response, which may affect restenosis after angioplasty. Soluble interleukin-2 receptor (sIL-2R) is a useful marker to evaluate the activation of T lymphocytes. sIL-2R was measured before and 2 h after successful PTCA, and 3-month follow-up coronary angiography was done to observe restenosis. Four of 10 patients showed restenosis. The restenosis group of 4 patients had a higher level of sIL-2R after PTCA than the no-restenosis group of 6 patients (495 vs. 274 U/ml, p < 0.01). This study suggests that sIL-2R may offer prognostic information after elective PTCA and identify a subgroup of patients at high risk for clinical restenosis in a few months.

Aged↗

Successfully treated unstable angina pectoris in a young Japanese female.

A 25-year-old Japanese female complaining chest oppression and palpitation was admitted to hospital under the presumptive diagnosis of ischemic heart disease (IHD), although no obvious underlying disease associated with IHD was detected. Coronary angiography showed stenosis at the proximal site of left anterior descending artery (LAD), with dilatation and tortuosity at the bifurcation of the first and the second septal branches. Intravascular ultrasound imaging of the LAD showed intimal thickness without calcification at the site of stenosis. The stenosis was successfully and smoothly dilated by percutaneous transluminal angioplasty. Even with precise evaluation, the cause of the coronary artery disease in this young female patient was not clarified. Further careful follow-up is needed.

Adult↗

Effects of hot bath immersion on autonomic activity and hemodynamics: comparison of the elderly patient and the healthy young.

Hot bathing has been associated with sudden death and so the present study investigated its effects on autonomic activity and hemodynamics in the elderly patient and the healthy young by analyzing heart rate variability (HRV). Subjects were 9 elderly men (mean age, 75 years) and 9 young men (mean age, 27 years), who were immersed up to shoulder level while in a sitting position for 10min with the bath temperature at 40 degrees C. Blood pressure (BP) and heart rate (HR) were monitored. BP in the young decreased during bathing (p<0.01), whereas in the elderly BP had a maximum value just at the start of immersion (p<0.05) with a slight decline at 4 min after the start of immersion. Although HR in the young increased (p<0.01), in the elderly there was an abrupt increase in HR just at the start of immersion (p<0.05), followed by a decrease in HR. With regard to HRV, the high-frequency (HF) component in the young men was suppressed during immersion (p<0.01), but was unaffected in the elderly. The LF (low frequency)/HF ratio in the elderly decreased at 4 min (p<0.05). In conclusion, hypotensive syncope may cause sudden death by drowning during hot bathing, and is a consequence of the decrease in sympathetic tone that develops approximately 4min after immersion.

Adolescent↗

Metastatic calcinosis circumscripta treated with an oral charcoal absorbent in a dog.

A five-year-old West Highland white terrier dog was admitted to the teaching hospital of Nippon Veterinary and Animal Science University due to swelling and pain of the foot pads. Examinations revealed that the dog had renal failure and calcinosis circumscripta on its foot pads. The diagnosis was metastatic calcinosis circumscripta secondary to renal failure. An oral charcoal adsorbent (Kremezin) was used to treat this condition. Following this treatment, a significant decrease in the Ca x P value (the serum calcium level x the serum phosphorus level) was observed, and the dog's condition improved dramatically. This case suggests that charcoal adsorbent (Kremezin) may be useful for treating metastatic calcinosis circumscripta in dogs.

Animals↗

Relaxing and contracting activities of heartworm extract on isolated canine abdominal aorta.

Effect of adult heartworm (HW) crude extract on isolated canine abdominal aortic strips precontracted with noradrenaline was examined by recording isometric changes in tension. HW extract caused contraction of the aortic strip at a low concentration (LC) and its relaxation at a high concentration (HC). In aortic strips without endothelium, LC extract elicited a contraction similar to that in the strips with endothelium, whereas HC extract failed to produce any relaxation but instead produced a contraction. The relaxing effect of HC extract was blocked after treatment with 300 microM NG-nitro-L-arginine methyl ester hydrochloride, with reversal by additional treatment with 3 mM L-arginine. It was also markedly reduced or abolished after treatment with 3 microM oxyhemoglobin or 1 microM methylene blue. Fractionation of HW extract by high-performance liquid chromatography revealed that the relaxing and contracting activities are due to different substances in the extract. The results indicate that HW extract contains 2 different vasoactive substances, 1 causing contraction of canine abdominal aorta via a direct action on the smooth muscle, and the other its relaxation indirectly by releasing nitric oxide from endothelial cells. These vasoactive substances might play a role in HW extract-induced shock in dogs, and in the pathogenesis of HW infection.

Animals↗

Neurotensin-induced Cl(-) current in guinea-pig dorsal root ganglion cells.

In guinea-pig dorsal root ganglion cells held under voltage-clamp at -80 mV, neurotensin elicited an inward current (I(NT)) whose amplitude increased with increasing neurotensin concentration (40-4000 nM). The effect was blocked by a nonpeptide neurotensin antagonist. I(NT) occurred in the absence of the extracellular Na(+), but not in the absence of the intracellular Cl(-), and it was outward directed by reversing the driving force for Cl(-). I(NT), like the gamma-amino-butyric acid (GABA)-induced Cl(-) current (I(GABA)), remained little changed after virtual elimination of cytosolic free-ionized Ca(2+) or after treatment with a Ca(2+)-activated Cl(-) channel blocker, but, in contrast to I(GABA) it was resistant to the I(GABA) blocker picrotoxin, slower in time course and more easily desensitized when repeatedly elicited. I(NT) and I(GABA) were additive to each other. AG-protein inhibitor markedly reduced I(NT), and a G-protein activator produced an inward current during which no current could be elicited by neurotensin. These results show that neurotensin exerts an effect to activate Ca(2+)-insensitive Cl(-) channels distinct from those activated by GABA in guinea-pig dorsal root ganglion cells, and the effect may arise through a G-protein-dependent mechanism.

Animals↗

Rabies virus infection prevents the modulation by alpha(2)-adrenoceptors, but not muscarinic receptors, of Ca(2+) channels in NG108-15 cells.

In mouse neuroblastoma x rat glioma hybrid (NG108-15) cells, we examined whether rabies virus infection affects the voltage-dependent Ca(2+) current (I(Ca)) and agonist-induced I(Ca) inhibition. The viral infection had little effect on the current-voltage relationship for peak I(Ca) or on the late I(Ca) that remained at the end of a 200-ms step depolarization. Noradrenaline and carbachol, via alpha(2)-adrenoceptors and muscarinic receptors, respectively, reduced I(Ca) concentration dependently. The maximum effect of noradrenaline was attained at 10 microM with 19.4+/-1.8% inhibition of I(Ca), which was significantly decreased to 9.9+/-1.3% after viral infection. The decrease was not reversed with 100 microM noradrenaline, suggesting that it does not result from a decrease in agonist sensitivity of cells. The maximum effect of carbachol (300 microM; 27.7+/-2.9% inhibition) remained unchanged, despite carbachol sharing intracellular signaling pathways with noradrenaline. These results indicate that in NG108-15 cells, rabies virus infection does not alter the functional expression of voltage-dependent Ca(2+) channels, but it attenuates the alpha(2)-adrenoceptor-mediated I(Ca) inhibition, possibly through some change at the receptor level.

Adrenergic Agonists↗

Molecular analysis of familial androgen insensitivity syndrome due to replacement of glutamic acid 802 by lysine.

We studied a Japanese family presenting at least two cases of complete androgen insensitivity syndrome (CAIS) and negative androgen receptor binding. The index subject showed a 46, XY karyotype and a complete female phenotype. For the purpose of further diagnosis and genetic counseling, molecular analysis of the androgen receptor (AR) gene was performed. Direct sequencing of the AR gene identified a mutation at nucleotide 2935 (A-->G). This replacement was a novel missense mutation, resulting in the substitution of glutamic acid 802 by lysine which deleted a recognition site for EcoRI in exon 6 of the AR gene. We identified another affected individual, using chromosome and molecular analysis of the AR gene at exon 6. Furthermore, although heterozygote carriers could not be identified on clinical grounds, molecular identification of healthy individuals and heterozygote carriers in the family members provided definitive information for genetic counseling. We believe that the molecular analysis of familial CAIS is very informative for both the affected individuals and other family members.

Adolescent↗

Effects of HNS-32, a novel antiarrhythmic drug, on ventricular arrhythmias induced by coronary artery occlusion and reperfusion in anesthetized rats.

HNS-32 (N1,N1-dimethyl-N2-(2-pyridylmethyl)-5-isopropyl-3, 8-dimethylazulene-1-carboxamidine: CAS 186086-10-2) is a newly synthesized compound, and possesses antiarrhythmic properties with vasodilator action in dog hearts. The aim of this study was to investigate the dose-dependent effects of HNS-32 on ischemia- and/or reperfusion-induced ventricular arrhythmias in anesthetized rats in vivo and compared with those of mexiletine. Saline or drugs were administered intravenously 5 min prior to coronary artery occlusion. On the ischemia-induced ventricular arrhythmias, HNS-32 showed dose-dependent reduction of total number of premature ventricular complexes (PVC) from 2091+/-225 to 656+/-116 and 286+/-69 beats/30 min (p < 0.05), the ventricular tachycardia (VT) duration from 183+/-33 to 28+/-9 and 4+/-2 sec (p < 0.05), the incidence of VT from 100 to 90 (n.s.) and 40% (p < 0.05), and the incidence of ventricular fibrillation (VF) from 50 to 0 and 0% (p < 0.05) with 3 and 5 mg/kg, respectively. Mexiletine also reduced these parameters to 936+/-159 beats/30 min (p < 0.05), 39+/-22 sec (p < 0.05), 90% (n.s.) and 10% (n.s.), respectively. HNS-32 completely suppressed the late reperfusion-induced arrhythmias, however mexiletine did not affect them. On the early reperfusion-induced ventricular arrhythmias, HNS-32 showed dose-dependent reduction of VT duration from 126+/-34 to 37+/-12 and 3+/-2 sec (p < 0.05), incidence of VT from 100 to 90 (n.s.) and 40% (p < 0.05), incidence of VF from 100 to 10 and 0% (p < 0.05), and mortality rate from 90 to 0 and 0% (p < 0.05), with 3 and 5 mg/kg, respectively. Mexiletine also reduced these parameters to 16+/-9 sec (p < 0.05), 80 (n.s.), 50 (p < 0.05), and 10% (p < 0.05), respectively. HNS-32 significantly reduced the heart rate in a dose-dependent manner, from 399+/-14 to 350+/-8 and 299+/-10 beats/min (p < 0.05) with 3 and 5 mg/kg, respectively. The antiarrhythmic effects of HNS-32 were more potent than that of the similar dose of mexiletine against occlusion-induced and reperfusion-induced arrhythmias in in vivo rats.

Animals↗

Protein kinase C is involved in cardioprotective effects of ischemic preconditioning on infarct size and ventricular arrhythmia in rats in vivo.

Protein kinase C (PKC) has been known to play an important role in ischemic preconditioning (IP). This study was designed to examine whether the translocation of PKC is associated with the cardioprotective effects of IP in vivo on infarct size and ventricular arrhythmias in a rat model. Using anesthetized rats, heart rate, systolic blood pressure, infarct size and ventricular arrhythmias during 45 min of coronary occlusion were measured. PKC activity was assayed in both the cytosolic and cell membrane fraction. Brief 3-min periods ofischemia followed by 10 min ofreperfusion were used to precondition the myocardium. Calphostin C was used to inhibit PKC. Infarct size was significantly reduced by IP (68.1 (2.5)%, mean (S.E.) vs. 45.2 (3.4)%, p < 0.01). The reduction in infarct size by IP was abolished by pretreatment with calphostin C. The total number of ventricular premature complex (VPC) during 45 min of coronary occlusion was reduced by IP (1474 (169) beats/45 min vs. 256 (82) beats/45 min, p < 0.05). The reduction the total number of VPC induced by IP was abolished by the administration of calphostin C before the episode of brief ischemia. The same tendency was observed in the duration of ventricular tachycardia and the incidence of ventricular fibrillation. PKC activity in the cell membrane fraction transiently increased immediately after IP (100 vs. 142%, p < 0.01) and returned to baseline 15 min after IP. Pretreatment with calphostin C prevented the translocation of PKC. The translocation of PKC plays an important role in the cardioprotective effect of IP on infarct size and ventricular arrhythmias in anesthetized rats.

Animals↗

The inhibitory effects of carvedilol against arrhythmias induced by coronary reperfusion in anesthetized rats.

BACKGROUND: Previous study has shown the antiarrhythmic effects of carvedilol on isolated rat hearts, but little is known about the mechanism of this protective action. This article examines the inhibitory effect of carvedilol against arrhythmias induced by reperfusion in anesthetized rats. In addition, the results are compared with those with propranolol, superoxide dismutase (SOD) plus catalase, and a combination of both in order to elucidate the mechanism of the protective actions. METHODS AND MATERIALS: Ninety percent of the rats in the control group showed lethal ventricular fibrillation (VF). Carvedilol at the doses of 0.03, 0.1, and 0.3 mg/kg significantly reduced the incidence of lethal VF to 0%, 0%, and 10%, respectively (P <.05). In contrast, propranolol at the doses of 0.3, 1.0, and 3.0 mg/kg and SOD (35,000 units/kg) plus catalase (400,000 units/kg) did not reduce the incidence of lethal VF (80%, 60%, 70%, and 70%, respectively). However, administration of a combination of propranolol (1.0 mg/kg) and SOD plus catalase completely inhibited the occurrence of lethal VF to 0% (P<.05). CONCLUSION: These results indicate that carvedilol has the inhibitory effect against reperfusion arrhythmias in rats and suggest that the mechanism of action of this compound is related to the combined effects of beta-blocking and antioxidant.

Adrenergic beta-Antagonists↗

Effect of imidapril in dipper and nondipper hypertensive patients: comparison between morning and evening administration.

The purpose of the study was to identify differences in the patterns of efficacy and duration of effects of imidapril administered at different times of the day (morning versus evening) in dipper and nondipper hypertensive patients. Twenty patients with untreated hypertension were classified into two groups: dippers (n = 9) and nondippers (n = 11). Imidapril (10 mg) was given at 07:00 or 18:00 for 4 weeks in a crossover fashion. Blood pressure (BP) and heart rate (HR) were monitored before and after morning and evening treatment every 30 min for 48h by ambulatory BP monitoring (ABPM). In dipper hypertension, the mean 48h BP was reduced with both doses. The decrease in the diurnal BP was stronger when the drug was administered in the evening than morning, but without significant difference. In nondipper hypertension, the systolic BP decreased at night with both doses, but the extent of the nocturnal reduction in systolic BP was greater after morning therapy. There were no significant differences in the decrease in BP during the day or night between the morning and evening administrations. When imidapril was administered in the morning, its serum concentration reached a maximum at 16:00, and when the drug was administered in the evening, it reached a maximum at 6:00. In dipper hypertension, the time taken for the blood concentration of imidapril to reach a maximum changed depending on its time of administration, and the time when the maximum antihypertensive effect of the drug appeared was different. In nondipper hypertension, decreases in the BP were confirmed at night regardless of the time of administration; this might be caused by angiotensin converting enzyme (ACE) inhibitors effectively blocking the BP from increasing by activating the parasympathetic nervous system. Therefore, when assessing the effectiveness of antihypertensive agents, factors such as the various patterns of BP before therapy and administration time must be considered.

Angiotensin-Converting Enzyme Inhibitors↗

Characteristics of ropivacaine block of Na+ channels in rat dorsal root ganglion neurons.

UNLABELLED: When used for epidural anesthesia, ropivacaine can produce a satisfactory sensory block with a minor motor block. We investigated its effect on tetrodotoxin-sensitive (TTX-S) and tetrodotoxin-resistant (TTX-R) Na(+) currents in rat dorsal root ganglion (DRG) neurons to elucidate the mechanisms underlying the above effects. Whole-cell patch-clamp recordings were made from enzymatically dissociated neurons from rat DRG. A TTX-S Na(+) current was recorded preferentially from large DRG neurons and a TTX-R Na(+) current preferentially from small ones. Ropivacaine shifted the activation curve for the TTX-R Na(+) channel in the depolarizing direction and the inactivation curve for both types of Na(+) channel in the hyperpolarizing direction. Ropivacaine blocked TTX-S and TTX-R Na(+) currents, but its half-maximum inhibitory concentration (IC(50)) was significantly lower for the latter current (116 +/- 35 vs 54 +/- 14 microM; P: < 0.01); similar IC(50) values were obtained with the (R)-isomer of ropivacaine. Ropivacaine produced a use-dependent block of both types of Na(+) channels. Ropivacaine preferentially blocks TTX-R Na(+) channels over TTX-S Na(+) channels. We conclude that because TTX-R Na(+) channels exist mainly in small DRG neurons (which are responsible for nociceptive sensation), such selective action of ropivacaine could underlie the differential block observed during epidural anesthesia with this drug. IMPLICATIONS: Whole-cell patch-clamp recordings of tetrodotoxin-sensitive and tetrodotoxin-resistant Na(+) currents in rat dorsal root ganglion neurons showed ropivacaine preferentially blocked tetrodotoxin-resistant Na(+) channels over tetrodotoxin-sensitive Na(+) channels. This could provide a desirable differential sensory blockade during epidural anesthesia using ropivacaine.

Amides↗