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Biomedical subjects

T Iwamoto

Publications and source records attributed to T Iwamoto.

At least 91 records · Page 5Linked to original sources
PubMed2000

A synthetic channel-forming peptide induces Cl(-) secretion: modulation by Ca(2+)-dependent K(+) channels.

A synthetic Cl(-) channel-forming peptide, C-K4-M2GlyR, applied to the apical membrane of human epithelial cell monolayers induces transepithelial Cl(-) and fluid secretion. The sequence of the core peptide, M2GlyR, corresponds to the second membrane-spanning region of the glycine receptor, a domain thought to line the pore of the ligand-gated Cl(-) channel. Using a pharmacological approach, we show that the flux of Cl(-) through the artificial Cl(-) channel can be regulated by modulating basolateral K(+) efflux through Ca(2+)-dependent K(+) channels. Application of C-K4-M2GlyR to the apical surface of monolayers composed of human colonic cells of the T84 cell line generated a sustained increase in short-circuit current (I(SC)) and caused net fluid secretion. The current was inhibited by the application of clotrimazole, a non-specific inhibitor of K(+) channels, and charybdotoxin, a potent inhibitor of Ca(2+)-dependent K(+) channels. Direct activation of these channels with 1-ethyl-2-benzimidazolinone (1-EBIO) greatly amplified the Cl(-) secretory current induced by C-K4-M2GlyR. The effect of the combination of C-K4-M2GlyR and 1-EBIO on I(SC) was significantly greater than the sum of the individual effects of the two compounds and was independent of cAMP. Treatment with 1-EBIO also increased the magnitude of fluid secretion induced by the peptide. The cooperative action of C-K4-M2GlyR and 1-EBIO on I(SC) was attenuated by Cl(-) transport inhibitors, by removing Cl(-) from the bathing solution and by basolateral treatment with K(+) channel blockers. These results indicate that apical membrane insertion of Cl(-) channel-forming peptides such as C-K4-M2GlyR and direct activation of basolateral K(+) channels with benzimidazolones may coordinate the apical Cl(-) conductance and the basolateral K(+) conductance, thereby providing a pharmacological approach to modulating Cl(-) and fluid secretion by human epithelia deficient in cystic fibrosis transmembrane conductance regulator Cl(-) channels.

Amino Acid Sequence↗
PubMed2000

Transport of magnesium by two isoforms of the Na+-Ca2+ exchanger expressed in CCL39 fibroblasts.

Cytoplasmic concentrations of Ca2+ ([Ca2+]i) and Mg2+ ([Mg2+]i) were measured with fluorescent indicators in CCL39 cells, a cell line established from Chinese hamster lung fibroblasts, transfected with complementary deoxyribonucleic acid (cDNA) of the Na+-Ca2+ exchanger isolated either from canine heart (NCX1) or from rat brain (NCX3). Raising extracellular [Mg2+] to 10 mM increased Mg2+ influx and the resultant change in [Mg2+]i (delta[Mg2+]i) was monitored with furaptra under Ca2+-free conditions. In control (vector-transfected) cells, delta[Mg2+]i at 45 min was similar with or without extracellular Na+ (130 mM or 0 mM) and when [Na+]i was raised by 1 mM ouabain treatment. delta[Mg2+]i in NCX1-transfected cells was attenuated significantly in the presence of 130 mM Na+, but became comparable to (or slightly larger than) that in control cells on either removal of extracellular Na+ or treatment with 1 mM ouabain. Cells expressing NCX3 showed an intermediate dependence of delta[Mg2+]i on Na+, probably reflecting a lower degree of expression of the exchanger protein. Extracellular Na+-dependent changes in [Ca2+]i (measured with fura-2 in the presence of extracellular Ca2+ and 10 microM ionomycin, a Ca2+ ionophore) were minimal in control cells, marked in the NCX1-transfected cells and intermediate in the NCX3-transfected cells. These results suggest that the Na+-Ca2+ exchanger (either NCX1 or NCX3) can transport Mg2+ and may play a role in the extrusion of magnesium from cells.

Animals↗
PubMed2000

Lithium activates mammalian Na+/H+ exchangers: isoform specificity and inhibition by genistein.

Replacement of external NaCl with LiCl induced cytoplasmic alkalinization in CCL-39 cells and rat L6 myoblasts expressing the endogenous Na+/H+ exchanger isoform NHE1. This Li+-induced alkalinization is due to activation of the Na+/H+ exchanger because it was completely inhibited by 100 microM ethylisopropylamiloride (apparent Kd=1 microM) and because it did not occur in exchanger-deficient PS120 cells. The effect of Li+ was not mimicked by Na+, K+, Cs+ and choline+. Li+ caused cytoplasmic alkalinization in PS120 cells expressing NHE1 or NHE2, but not NHE3, when Li+ was added to cells at a concentration high enough to saturate their external transport sites as predicted from Li+ affinities. Li+ did not induce phosphatidylinositol (PI) turnover or intracellular Ca2+ mobilization. Li+-induced alkalinization was not affected by protein kinase C down-regulation, loss of glycogen synthase kinase 3beta caused by antisense oligonucleotide treatment, or pretreatment with calphostin C, pertussis toxin, MEK inhibitor PD98059 and PI3-kinase inhibitor LY294002. However, it was markedly suppressed by the tyrosine kinase inhibitor genistein (10 microM). Thus, externally added Li+ activates NHE1 and NHE2 via a mechanism possibly involving a tyrosine kinase, causing an increase in cytoplasmic pH that could potentially affect various cell functions.

Alkalies↗
PubMed2000

Molecular cloning of a novel human gene (SIRP-B2) which encodes a new member of the SIRP/SHPS-1 protein family.

A full-length cDNA encoding a novel protein was isolated and sequenced from a human placental cDNA library. This cDNA consists of 1,735 base pairs and has a predicted open reading frame (ORF) encoding 354 amino acids. It possesses a putative signal sequence, a long extracellular domain, a transmembrane region, a short intracellular domain, and no catalytic domain, which is highly homologous to signal-regulatory protein (SIRP)-beta suggesting that it seems to be a new member of the SIRP family. Polymerase chain reaction (PCR)-based mapping with both a monochromosomal hybrid panel and radiation hybrid cell panels placed the gene to human chromosome 20p13 near the marker D20S906.

Amino Acid Sequence↗
PubMed2000

alpha2-Adrenergic-receptor response in reversible increase in hemoglobin concentration in intermittent hypoxia.

We have previously shown that intermittent hypoxia (IHx, 10% O(2), 60 min/day) leads to an increase in the splenic alpha2-adrenoceptor response and results in a splenic contraction-induced reversible increase in hemoglobin concentration ([Hb]). In the present study, we determined whether IHx of shorter duration (15 min/day (15-min) and 30 min/day (30-min)), produced this phenomenon in rats. A significant increase in [Hb] during hypoxia was observed in both the groups, but its magnitude was larger in the 30-min IHx rats. Even when the cumulative exposure time (time/dayxdays) was shorter, the [Hb] increase was larger in the rats with longer daily hypoxic exposure. The alpha2-adrenoceptor antagonist yohimbine abolished the [Hb] increase of 15- and 30-min IHx. The increase in [Hb] following administration of the alpha2-adrenoceptor agonist oxymetazoline was also higher in 30-min IHx; indicating that the higher [Hb] produced by longer daily hypoxic exposure times is the result of increases in alpha2-adrenergic-receptor response of greater magnitude. In conclusion, IHx for periods as short as 15 and 30 min/day increases the splenic alpha2-adrenoceptor response and its magnitude reaches the maximum value depending on the daily hypoxic exposure time. A reversible increase in [Hb] constitutes a useful mechanism that protects organ oxygen supply during hypoxic episodes of variable duration and intensity.

Journal Article↗
PubMed2000

Implication of ESR signals from ceruloplasmin (Cu(2+)) and transferrin (Fe(3+)) in pleural effusion of lung diseases.

Pleural effusions of seven lung cancer patients (mean age; 58) and seven non-cancer patients (mean age; 49) were examined and Cu(2+) was measured in ceruloplasmin and Fe(3+) in transferrin signals by electron spin resonance (ESR) method. The variations of total Fe and Cu ions, ceruloplasmin and transferrin, proteins, neutrophil cell counts, LDH and nitrite/nitrate were also examined. The Cu(2+) peak was decreased and the Fe(3+) peak was increased in the cancer group. The interrelationship among Cu(2+), total Cu and ceruloplasmin, and among Fe(3+), total Fe and transferrin clarified that Cu(2+) and Fe(3+) are not a representative of ceruloplasmin and transferrin, respectively. The ratio of Cu(2+)/Fe(3+) in pleural effusion distinguished lung cancer from benign inflammation as a cause. The ratio of total Cu/total Fe measured by the chemical analysis method also distinguished these, but the ratio of ceruloplasmin/transferrin was unable to distinguish the cancer. In conclusion, the simple and rapid measurement of Cu(2+)/Fe(3+) by ESR effectively abstracts the variation of total ion concentrations caused by malignant disease.

Journal Article↗
PubMed2000

Decapitated and decaudated spermatozoa in man, and pathogenesis based on the ultrastructure.

The ultrastructure of decapitated tails and decaudated heads of ejaculated spermatozoa from an infertile man were investigated. The decaudated heads had the nucleus and acrosome, but neither the implantation fossa nor the basal plate were observed at the caudal pole of the nucleus. The nuclear membrane at this portion showed numerous nuclear pores. The decapitated tails contained the proximal centriole at the proximal end. In addition, most decapitated tails had segmented columns, outer coarse fibres, axoneme, mitochondrial sheath and fibrous sheath in the normal position. The ultrastructure reflects the high motility of the decapitated tails of the spermatozoa. Drastic abnormalities were found in the developing spermatids in the biopsied testes. In spermatids later than the Golgi phase, the pair of centrioles were floating in the cytoplasm of the spermatid, but the distal centriole elongated the flagellum. Neither the implantation fossa nor the basal plate were observed at the caudal pole of the nucleus. It is concluded that the tail might be separated from the head before or after completion of tail formation in spermatids. The explanation for why the proximal centriole failed to connect to the nucleus is unknown.

Adult↗
PubMed2000

Conservative treatment of childhood phimosis with topical conjugated equine estrogen ointment.

PURPOSE: To assess the application of topical conjugated equine estrogen for the treatment of boys with phimosis. METHODS: Fifteen boys with phimosis were included in the study. Conjugated equine estrogen (Premarin) 0.1% ointment was applied on the prepuce once daily. The treatment was continued until the prepuce was fully retractable. The patient was examined each second week up to a maximum treatment of 8 weeks. Retractability and the appearance of the foreskin were graded before and after treatment. RESULTS: Thirteen of 15 boys (87%) referred with phimosis were successfully treated with conjugated equine estrogen ointment. An adverse effect of gynecomastia was seen in one boy (7%). CONCLUSION: Conjugated equine estrogen ointment application for phimosis may be an alternative to surgery.

Administration, Topical↗
PubMed2000

Delayed testosterone replacement restores nitric oxide synthase-containing nerve fibres and the erectile response in rat penis.

OBJECTIVE: To elucidate the effect of testosterone on penile innervation. Materials and methods Three groups of six rats each were assessed; two groups (1 and 2) were castrated and the third (group 3) underwent a sham operation (control). Eight weeks after castration, group 2 received a subcutaneous injection with testosterone. At 8 weeks, the rats in group 1 and 3 underwent a final functional analysis while those in group 2 did so at 12 weeks. The evaluation included a subcutaneous injection with apomorphine to study centrally mediated erection, and cavernosal nerve electrostimulation and papaverine injection to study peripherally mediated erection. At death a penile mid-shaft specimen was taken for NADPH-diaphorase staining. RESULTS: In the apomorphine study, castration resulted in significantly fewer yawns and erections than in the control, and those in group 2 significantly better central erectile function than in the controls. The mean (SEM) number of nitric oxide synthase (NOS)-containing nerve fibres in the corpora cavernosa and both dorsal nerves of castrated rats, at 46.2 (9.1) and 203 (32.1), respectively, were significantly lower than in rats in group 2, at 84.1 (11.2) and 300.6 (17.1), and than in the controls, at 88.6 (10.9) and 306.3 (22.9), respectively. The intracavernosal pressure decreased significantly in the absence of testosterone, both after electrostimulation and intracavernosal papaverine injection. However, there was no difference between the control and group 2 rats in either the number of NOS-containing nerve fibres or in the peripheral erectile functional study. CONCLUSIONS: Testosterone acts on the nervous system to mediate erection; when it is absent there may be down-regulation of both the production and activity of NO, thereby decreasing the response to peripheral stimulation via the NO pathway. The restoration of erectile function seen in rats in group 2 supports this phenomenon. Delayed testosterone replacement has no detrimental effect on the restoration of the erectile mechanism after castration.

Animals↗
PubMed2000

Fentanyl augments block of sympathetic responses to skin incision during sevoflurane anaesthesia in children.

We studied 61 healthy ASA 1 patients (aged 2-6 yr) to determine if fentanyl affects the minimum alveolar concentration which blocks adrenergic responses to skin incision (MAC-BAR) in 50% of children in the presence of 60% nitrous oxide. Patients were allocated randomly to one of three fentanyl groups to receive 0, 2 or 4 micrograms kg-1. Patients also received sevoflurane at a preselected end-tidal concentration according to an 'up-and-down' design. After a steady-state sevoflurane concentration had been maintained for at least 15 min, fentanyl was given i.v. Skin incision was performed 5 min after administration of fentanyl. The response was considered positive if heart rate (HR) or mean arterial pressure (MAP) increased by 15% or more. The MAC-BAR of sevoflurane was 1.45 MAC (95% confidence intervals 1.25-1.65 MAC), and this was reduced markedly to 0.63 MAC and 0.38 MAC by addition of fentanyl 2 and 4 micrograms kg-1, respectively. A ceiling effect was not observed and there was a significant difference between the 2 and 4 micrograms kg-1 groups.

Adjuvants, Anesthesia↗
PubMed2000

S-Nitroso-N-acetylpenicillamine (SNAP) during hemorrhagic shock improves mortality as a result of recovery from vascular hyporeactivity.

UNLABELLED: Nitric oxide donors are protective against hemorrhagic shock (HS). However, no detailed investigation has been performed. We investigated this mechanism using S-nitroso-N-acetylpenicillamine (SNAP). HS (mean arterial pressure: 40 mm Hg) was induced in 20 dogs. Sixty min after HS, the animals were treated with saline (Cont-Gr: n = 7) or SNAP; 5 microg. kg(-1). 10 min(-1) followed by 5 microg. kg(-1). h(-1) (SNAP-Gr: n = 7). After another 60 min, the shed blood was reinfused. Reactivities to noradrenalin (NA), changes in hemodynamics, the plasma catecholamines, and nitric oxide derivatives were determined. In Cont-Gr, 3 dogs died at 90, 98, and 102 min after HS. In Cont-Gr, % changes of systolic arterial blood pressure to 1 and 2.5 microg/kg of NA after the recovery from HS decreased from 23.7% +/- 4.1% (before HS) to 6.5% +/- 0.6% and from 50.1% +/- 7.7% (before HS) to 14.5% +/- 2.6%, respectively (P < 0. 01). In SNAP-Gr, reactivity to NA was maintained. At 120 min after HS, mean arterial pressure and cardiac output in SNAP-Gr increased but not in Cont-Gr. Plasma catecholamine levels in SNAP-Gr were suppressed compared with those of Cont-Gr. In conclusion, a small dose of SNAP during HS decreased the mortality of the dogs. This might have been caused in part by residual vascular hyporeactivity. IMPLICATIONS: The administration of a small dose of S-nitroso-N-acetylpenicillamine (a nitric oxide donor), a dose which did not exert a significant vasodilator effect, was administered during hemorrhagic shock in dogs. S-nitroso-N-acetylpenicillamine improved the vascular hyporeactivity to noradrenaline and decreased the mortality rate.

Animals↗
PubMed2000

Physiological functions of the regulatory domains of the cardiac Na(+)/Ca(2+) exchanger NCX1.

Physiological functions of the intracellular regulatory domains of the Na(+)/Ca(2+) exchanger NCX1 were studied by examining Ca(2+) handling in CCL39 cells expressing a low-affinity Ca(2+) regulatory site mutant (D447V/D498I), an exchanger inhibitory peptide (XIP) region mutant displaying no Na(+) inactivation (XIP-4YW), or a mutant lacking most of the central cytoplasmic loop (Delta246-672). We found that D447V/D498I was unable to efficiently extrude Ca(2+) from the cytoplasm, particularly during a small rise in intracellular Ca(2+) concentration induced by the physiological agonist alpha-thrombin or thapsigargin. The same mutant took up Ca(2+) much less efficiently than the wild-type NCX1 in Na(+)-free medium when transfectants were not loaded with Na(+), although it appeared to take up Ca(2+) normally in transfectants preloaded with Na(+). XIP-4YW and, to a lesser extent, Delta246-672, but not NCX1 and D447V/D498I, markedly accelerated the loss of viability of Na(+)-loaded transfectants. Furthermore, XIP-4YW was not activated by phorbol ester, whereas XIP-4YW and D447V/D498I were resistant to inhibition by ATP depletion. The results suggest that these regulatory domains play important roles in the physiological and pathological Ca(2+) handling by NCX1, as well as in the regulation of NCX1 by protein kinase C or ATP depletion.

Adenosine Triphosphate↗
PubMed2000

Effectiveness of the fold plication method in lung volume reduction surgery.

OBJECT: The fold plication method is a new operative procedure for lung volume reduction surgery whereby the target area is obliterated by plicating the folded tissue using a knifeless stapler, without the use of bovine pericardium. The effectiveness of this new method was evaluated in patients with advanced pulmonary emphysema. PATIENTS AND METHODS: Two weeks before and 6 months after surgery, pulmonary function, static lung compliance, maximal esophageal pressure, maximal inspiratory and expiratory mouth pressures, 6-min walking distance and the Borg scale were determined in twenty consecutive patients who underwent video-assisted thoracoscopic unilateral surgery. RESULTS: There was an increase in forced expiratory volume in one second (31%), forced vital capacity, peak expiratory flow rate and maximal voluntary ventilation, and a decrease in functional residual capacity (-16%) measured by plethysmograph. Static lung compliance decreased, and maximal esophageal pressure, and maximal inspiratory and expiratory mouth pressures increased. The 6-min walking distance increased (20%) and the Borg scale decreased (5.9 to 3.5). CONCLUSION: The results compare favorably with those obtained with other methods. Thus, the fold plication method could be considered an alternative procedure for lung volume reduction surgery.

Aged↗
PubMed2000

Interpersonal constructs of pregnant married women during pregnancy and postpartum period as perceptions of family members.

Interpersonal constructs and their dynamics in pregnant women during the perinatal period were investigated using a symbol figure placement technique and a semantic differential test. 16 pregnant women represented their interpersonal perceptions of family members (husband, mother, father, mother-in-law, father-in-law, and child) at four different times (34 weeks of pregnancy, 37 weeks of pregnancy, and 3 days and 30 days after delivery). Two tests indicated positive perceptions of the pregnant women (cohesion, confidence, and dependence) of family members changed over the perinatal period and their interpersonal perceptions of self-husband and self-child were the most positive next to self-mother. Based upon these findings, the support system for pregnant women was discussed.

Adult↗
PubMed2000

[Dementia and disability after initial cerebral thrombosis evaluated by MRI and their clinical course].

This study was conducted to clarify the relationship between long-term prognosis of functional status after stroke and the magnetic resonance imaging (MRI) findings as well as complications in the course. A total of 98 patients with initial cerebral thrombosis were enrolled, and 65 patients surviving 5 years after the event, were studied in terms of cognitive function and activity of daily living (ADL). Mean age at registration (3 months after the event) was 72.0 years-old and 44 were male. MRI findings were divided into eight categories including the size and laterality of infarction, in addition to six categories as previously described. The presence of dementia was identified according to the HDS-R and the DSM-III-R scales, and the extent of dementia, assessed with the CDR scale, was divided into 3 grades: none, mild, and severe. The extent of ADL status was also graded into 3 classes: independent, partially dependent, and completely dependent. Recurrence of stroke, pneumonia, and motor disorders (hip joint fracture) were counted as complications during the course. At baseline, dementia was identified in 44, consisting of 30 mild and 14 severe dementias. During 5 years, 11 cases with mild dementia showed deterioration, and 1 case without dementia developed mild dementia. At registration, there were 46 cases with partially dependent ADL status and 22 cases completely dependent, while deterioration of ADL was seen in 17 during 5 years. Multiple regression analyses showed that diffuse PVH and pneumonia were contributory factors to the development of dementia, while dementia, pneumonia and motor disorders were risk factors for deterioration of ADL. These findings suggested that in patients with cerebral thrombosis, especially in patients with diffuse PVH, pneumonia and motor disorders should be taken care of in order to prevent functional decline.

Activities of Daily Living↗
PubMed2000

[Ultrasonographic findings of carotid arteries in female patients with arteriosclerosis obliterans and aortic aneurysm].

To clarify carotid arterial changes in female patients with arteriosclerosis obliterans (ASO) and aortic aneurysm (AA), ultrasonographic (US) findings of the extra-cranial carotid arteries were studied in 26 patients with ASO (ASO group), and 31 patients with AA (AA group), compared to 38 controls (control group) with neither ASO nor AA. ASO was diagnosed with an ankle pressure index less than 0.9, while AA was done with computed tomography or angiography. Half of the patients with ASO were in stage II of the Fontaine clinical staging, and angiography, performed in 12, showed femoral arterial obstruction in 10. Most AA patients were abdominal aortic aneurysm. Using a high-resolution, real-time, B-mode US instrument, the diameter and wall thickness of the common carotids were measured bilaterally in the end-diastolic phase, and occlusive changes and plaque were estimated. As a risk factor for arteriosclerosis, hypertension, diabetes, hyperlipidemia, and cigarette smoking were assessed, in addition to the age, body height and weight. Mean ages of each group were 73 to 76.3 year-old. There was no significant difference between them in body height and weight. Diabetes, cigarette smoking, and cerebrovascular disease were frequent in the ASO group, whereas ischemic heart disease was frequent in the AA group. US findings revealed that carotid lesions were mostly plaque, and bilateral carotid lesions were significantly more frequent in the ASO and AA groups. The mean wall thickness of the carotids was greater in the AA and ASO groups, although dilated carotid arteries, namely arteriomegaly, was more frequent in the AA group than in the ASO and control groups. Stepwise regression analyses demonstrated that strong correlations were seen between carotid lesion and two variables [vessel diseases (ASO/AA) and cigarette smoking], between carotid diameter and three variables (age, AA, and wall thickness), and between the wall thickness and three variables (age, vessel diseases and diameter). These findings showed that atherosclerosis was not only frequent in female patients with ASO and AA, but arteriomegaly was characteristic in female patients with AA. Therefore, it suggested that circulatory disturbance in whole organs due to arteriosclerosis should be paid attention even in female patients with ASO and AA as well as male patients. Furthermore, it is considered that systemic fragility of the arterial media and ectasia could be present extensively in patients with AA.

Age Factors↗