Biomedical subjects

S Mohri

Publications and source records attributed to S Mohri.

At least 19 recordsLinked to original sources

PubMed2004

Load independence of temperature-dependent Ca2+ recirculation fraction in canine heart.

Intramyocardial Ca(2+) recirculation fraction (RF) critically determines the economy of excitation-contraction coupling. RF is obtainable from the exponential decay of the postextrasystolic potentiation of left ventricular (LV) contractility. We have shown that RF remains unchanged despite increasing LV volume (LVV) at normothermia, but decreases with increasing temperature at a constant LVV. However, it remains unknown whether the temperature-dependent RF was not due to the simultaneously changed peak LV pressure (LVP) at a constant LVV. We hypothesized that this temperature-dependent RF would be independent of the simultaneous change in LVP. We used nine excised, cross-circulated canine hearts and allowed their LVs to contract isovolumically. During stable regular beats at 500 msec intervals, we inserted an extrasystolic beat at 360 msec interval followed by the postextrasystolic beats (PESs) at 500 msec intervals. We equalized the temperature-dependent peak LVPs of the regular beats at 36 degrees C and 38 degrees C to the peak LVP level of the stable regular beat at 33 degrees C by adjusting LVV. We fitted the same equation: nEmax = a.exp[-(i - 1)/tau(e)] + b.exp[-(i - 1)/tau(s)]cos[pi(i - 1)] + 1, used before to the normalized Emax (maximum elastance) values of PESi (i = 1-6) relative to the regular beat Emax. RF given by exp(-1/tau(e)) decreased by 19% to 38 degrees C from 33 degrees C. The temperature coefficient (Q(10)) of 1/RF was significantly greater than 1.3. The present results indicated a similar temperature dependence of RF and its Q(10) to those we observed previously without equalizing peak LVP. Thus, the temperature-dependent RF is independent of ventricular loading conditions.

Animals↗

PubMed2004

Arterial and left ventricular pressures illude transient alternans of contractility during postextrasystolic potentiation.

We have previously found that the postextrasystolic (PES) potentiation (PESP) of the left ventricular (LV) contractility (Emax) decays typically in transient alternans even in the normally ejecting canine heart. This contradicted the general expectation that arterial pressure (AP) and LV pressure (LVP) usually decay exponentially during PESP. We hypothesized this contradiction to be due to the different cardiodynamic behaviors of AP and LVP from LV Emax during PESP. We tested this hypothesis by measuring AP, LVP, LV volume, Emax, effective arterial elastance (Ea) as an index of afterload, and pulse pressure (PP) during PESP in eight anesthetized open-chest dogs by using the conductance catheter system. We changed Ea by changing the total peripheral resistance (TPR) with methoxamine hydrochloride (iv) and repeated the measurements. Although the Emax alternans patterns during PESP were comparable between the normal and high afterloads, LVP and PP were slightly potentiated and alternated under the normal afterload, whereas LVP and PP were obviously potentiated and alternated under the high afterload. We also simulated the effects of Ea/Emax on the transient alternans of AP and LVP on a computer. Despite the same alternans pattern of Emax, a higher Ea/Emax, which is typical in heart failure, caused a larger PP alternans, whereas a lower Ea/Emax, which is typical in normal hearts, almost eliminated it. These results suggest that a transient alternans of LV contractility during PESP could be overlooked when AP and LVP are monitored in in situ normal hearts.

Animals↗

PubMed2001

Scrapie removal using Planova virus removal filters.

As a possible method for reducing the risk of transmissible spongiform encephalopathy (TSE) infection, Planova virus removal filters were tested for their ability to remove scrapie agent ME7. Albumin solution was spiked with high-titre ME7 and filtered through three different pore sizes of Planova filters. Infectivity of the pre- and post-filtration samples was assayed in log dilutions by intracerebral inoculation into C57B1/6 mice. Filtration of albumin solution in the absence or presence of a detergent (Sarkosyl) with Planova 35N (35+/-2 nm mean pore size) removed the contaminating scrapie agent with reduction factors of 4.93 log10 and 1.61 log10, respectively. Filtration, both in the absence and presence of detergent with Planova 15N (15+/-2 nm mean pore size), and in the presence of detergent with Planova 10N (9+/-2 nm mean pore size), showed high levels of scrapie reduction of >5.87 log10, >4.21 log10, and >3.80 log10, respectively, with no residual infectively detected in any of the filtrate samples. The effectiveness of Planova 35N filtration for the removal of infectivity of this TSE agent is greatly reduced in the presence of a strong detergent, but Planova filters with 15 nm or smaller pore size membranes can remove such infectivity at high reduction rates.

Animals↗

PubMed2001

Synthetic study on novel immunosuppressant KF20444.

The two new synthetic routes to 6,7-dihydro-10-fluoro-3-(2-fluorophenyl)-5H- benzo[6,7]cyclohepta[1,2-b]-quinoline-8-carboxylic acid (1), a novel immunosuppressant KF20444, are described. The seven-membered ring construction from 2-[4-(2-fluorophenyl)phenyl]-3-(2-carboxyethyl)-4-chloromethyl-6-fluoroquinoline (17c) was achieved by intramolecular Friedel-Crafts reaction under acidic conditions as the key step. Subsequently, the oxidation of 4-chloromethyl group followed by reduction of carbonyl group on the seven-membered ring afforded 1. This route provides a new method for the synthesis of 1.

Biochemistry↗

PubMed2001

Coupling interval from slow to tachycardiac pacing decides sustained alternans pattern.

We discovered that the coupling beat interval from a slow to a tachycardiac pacing period considerably affected the pattern of the beat-to-beat alternation of the tachycardia-induced sustained contractile alternans. We analyzed the relationship between the coupling interval and the pattern and amplitude of the alternans in the isovolumic left ventricle of canine blood-perfused hearts. The alternans pattern and amplitude varied transiently over the first 30-50 beats and became gradually stable over the first minute in all 12 hearts. We discovered that stable alternans, even under the same tachycardiac pacing, had three different strong-weak beat patterns depending on the coupling interval. A relatively short coupling interval produced a representative sustained alternans of the strong and weak beats. A relatively long coupling interval produced a similar sustained alternans but in a reversed order of even- and odd-numbered beats counted from the coupling interval. However, sustained alternans disappeared after 1-3 specific coupling intervals. We conclude that ventricular pacing rate does not solely determine the pattern and amplitude of sustained contractile alternans induced by tachycardia.

Action Potentials↗

PubMed2001

New calculation of internal Ca(2+) recirculation fraction from alternans decay of postextrasystolic potentiation.

In our previous studies, we calculated the internal Ca(2+) recirculation fraction (RF) after obtaining the beat decay constant (tau(e)) of the monoexponential component in the postextrasystolic potentiation (PESP) of the alternans decay by curve fitting. However, this method sometimes suffers from the sensitive variation of tau(e) with small noises in the measured contractilities of the 5th and 6th postextrasystolic (PES) beats in the tail of the exponential component. We now succeeded in preventing this problem by a new method to calculate RF without obtaining tau(e). The equation for the calculation in the new method expresses an alternans decay of PESP as a recurrence formula of PESP. It can calculate RF directly from the contractilities of the 1st through the 4th PES beats without any fitting procedure. To evaluate the reliability of the new method, we calculated RF from the alternans decay of PESP of the left ventricle (LV) of the canine excised cross-circulated heart preparation by both the original fitting and the new method. Although there was no significant difference in the mean value of the obtained RF between these two methods, the variance of RF was smaller with the new method than with the original method. Thus the new method proved useful and more reliable than the original fitting method.

Animals↗

PubMed2001

Cardiovascular beneficial effects of electroacupuncture at Neiguan (PC-6) acupoint in anesthetized open-chest dog.

Neiguan (PC-6) is a traditional acupoint in the bilateral forearms, overlying the median nerve trunk. Neiguan electroacupuncture (EA) has been believed to affect cardiovascular function and used in traditional Chinese medicine to improve or treat a wide range of health conditions and diseases, including angina pectoris, myocardial infarction, hypertension, and hypotension. However, few physiological studies have assessed the beneficial effects of Neiguan EA on the cardiovascular function. In the present study, we investigated its effects on the cardiovascular function in normal open-chest dogs under pentobarbital and fentanyl anesthesia. We also obtained left ventricular (LV) pressure-volume (P-V) data with a micromanometer catheter and a volumetric conductance catheter. Mean arterial pressure, end-diastolic volume, heart rate, stroke volume, cardiac output, and end-systolic pressure gradually decreased by 5 to 10% over 1.5 h without Neiguan EA. Neiguan EA at 40 Hz, however, increased these cardiovascular variables by 10 to 15%, especially end-systolic elastance (Ees) by 40% (p<0.05) over 15 to 60 min. After Neiguan EA was stopped at 1 h, these facilitated cardiovascular variables decreased below the pre-EA level. This beneficial effect of electroacupuncture may contribute to the effectiveness of the acupuncture in Chinese medicine.

Adjuvants, Anesthesia↗

PubMed2001

Frank-Starling mechanism retains recirculation fraction of myocardial Ca(2+) in the beating heart.

Myocardial Ca(2+) handling in excitation-contraction coupling is the second primary determinant of energy or O(2) demand in a working heart. The intracellular and extracellular routes remove myocardial Ca(2+) that was released into the sarcoplasma with different Ca(2+): ATP stoichiometries. The intracellular route is twice as economical as the extracellular route. Therefore the fraction of total Ca(2+) removed via the sarcoplasmic reticulum, i.e., the recirculation fraction of intracellular Ca(2+) (RF), determines the economy of myocardial Ca(2+) handling. RF has conventionally been estimated as the exponential decay rate of postextrasystolic potentiation (PESP). However, we have found that PESP usually decays in alternans, but not exponentially in the canine left ventricle beating above 100 beats/min. We have succeeded in estimating RF from the exponential decay component of an alternans PESP. We previously found that the Frank-Starling mechanism or varied ventricular preload did not affect the economy of myocardial Ca(2+) handling. Then, to account for this important finding, we hypothesized that the Frank-Starling mechanism would not affect RF at a constant heart rate. We tested this hypothesis and found its supportive evidence in 11 canine left ventricles. We conclude that RF at a constant heart rate would remain constant, independent of the Frank-Starling mechanism.

Action Potentials↗

PubMed2001

Total Ca2+ handling for E-C coupling in the whole heart: an integrative analysis.

We assessed total Ca2+ handling (transport, flux) in excitation-contraction (E-C) coupling in a beating left ventricle (LV). We developed a new integrative analysis method that utilizes the internal Ca2+ recirculation fraction (RF), O2 consumption (V(O2)) for Ca2+ handling, and O2 cost of Emax (contractility index) of the LV. We obtained the RF from the beat constant of the exponential decay component of the postextrasystolic potentiation, and the O2 cost of Emax from V(O2) measured at different Emax. Our equation calculated the unknown total Ca2+ handling, futile Ca2+ cycling, and Ca2+ reactivity of Emax from the RF and Ca2+ handling V(O2). The calculated total Ca2+ handling fell between 30 and 110 micromol/kg, depending on Emax and pathological conditions. Our method also allowed an assessment of futile Ca2+ cycling and Ca2+ reactivity of Emax in a beating LV. These data are not available using conventional methods. Our method can be used to better understand the pathophysiology of total Ca2+ handling in a beating heart.

Animals↗

PubMed2000

Genetic changes in sweat gland carcinomas.

The molecular pathogenesis of malignant appendageal tumors is poorly understood. Immunohistochemical staining, polymerase chain reaction (PCR)-based loss of heterozygosity (LOH) and sequencing analyses were performed in a mixed group of 21 sweat gland carcinomas. LOH was mostly confined to the chromosome arm 17p. None of the remaining 17 tumors showed LOH at any loci. Nuclear accumulation of p53 protein was observed in 3 tumors, all of which also showed LOH of 17p. One eccrine gland adenocarcinoma showed allelic loss of 17p and a Cys 176 Arg mutation in the p53 gene. The other three tumors that showed LOH of 17p, however, had wild-type p53 genes. A clear transition from benign eccrine poroma to porocarcinoma that was associated with p53 protein stabilization and allelic loss was observed in one tumor. One eccrine porocarcinoma/undifferentiated adnexal carcinoma showed prominent microsatellite instability, probably reflecting an underlying defect in DNA mismatch repair. Overexpression of erbB-2 was observed in three tumors. The low frequencies of LOH and p53 alterations in sweat gland carcinomas contrasted with the multiple genetic defects normally observed in cutaneous squamous cell carcinomas, and may be partly explained by the relative protection of cutaneous appendages from ultraviolet light and other environmental mutagens.

Adenocarcinoma↗

PubMed2000

Energy-wasteful total Ca(2+) handling underlies increased O(2) cost of contractility in canine stunned heart.

Postischemic myocardial stunning halved left ventricular contractility [end-systolic maximum elastance (E(max))] and doubled the O(2) cost of E(max) in excised cross-circulated canine heart. We hypothesized that this increased O(2) cost derived from energy-wasteful myocardial Ca(2+) handling consisting of a decreased internal Ca(2+) recirculation, some futile Ca(2+) cycling, and a depressed Ca(2+) reactivity of E(max). We first calculated the internal Ca(2+) recirculation fraction (RF) from the exponential decay component of postextrasystolic potentiation. Stunning significantly accelerated the decay and decreased RF from 0.63 to 0. 43 on average. We then combined the decreased RF with the halved E(max) and its doubled O(2) cost and analyzed total Ca(2+) handling using our recently developed integrative method. We found a decreased total Ca(2+) transport and a considerable shift of the relation between futile Ca(2+) cycling and Ca(2+) reactivity in an energy-wasteful direction in the stunned heart. These changes in total Ca(2+) handling reasonably account for the doubled O(2) cost of E(max) in stunning, supporting the hypothesis.

Animals↗

PubMed2000

Postextrasystolic contractile decay always contains exponential and alternans components in canine heart.

In isolated, blood-perfused canine hearts, postextrasystolic potentiation (PESP) decays monotonically after a noncompensatory pause following a spontaneous extrasystole (ES). The monotonic PESP decay yields myocardial internal Ca(2+) recirculation fraction (RF). We have found that after a compensatory pause (CP), PESP decays in alternans, consisting of an exponential and a sinusoidal decay component. We have proposed that this exponential component also yields RF. In the present study, we examined the reliability of this alternative method by widely changing the ES coupling interval (ESI), CP, and heart rate in the canine excised, cross-circulated left ventricle. We found that all PESP decays consisted of the sum of an exponential and a sinusoidal decay component of variable magnitudes whether a CP existed or not. Their decay constants as well as the calculated RF were independent of the ESI and CP. This confirmed the utility of our alternative RF determination method regardless of the ESI, CP, and heart rate. Direct experimental evidence of Ca(2+) dynamics supportive of this alternative method, however, remains to be obtained.

Animals↗

PubMed2000

A novel neuropeptide, Hym-355, positively regulates neuron differentiation in Hydra.

During the course of a systematic screening of peptide signaling molecules in Hydra a novel peptide, Hym-355 (FPQSFLPRG-NH(2)), was identified. A cDNA encoding the peptide was isolated and characterized. Using both in situ hybridization and immunohistochemistry, Hym-355 was shown to be expressed in neurons and hence is a neuropeptide. The peptide was shown to specifically enhance neuron differentiation throughout the animal by inducing interstitial cells to enter the neuron pathway. Further, co-treatment with a PW peptide, which inhibits neuron differentiation, nullified the effects of both peptides, suggesting that they act in an antagonistic manner. This effect is discussed in terms of a feedback mechanism for maintaining the steady state neuron population in Hydra.

Amino Acid Sequence↗

PubMed2000

Mechanoenergetics characterizing oxygen wasting effect of caffeine in canine left ventricle.

Caffeine causes a considerable O(2) waste for positive inotropism in myocardium by complex pharmacological mechanisms. However, no quantitative study has yet characterized the mechanoenergetics of caffeine, particularly its O(2) cost of contractility in the E(max)-PVA-VO(2) framework. Here, E(max) is an index of ventricular contractility, PVA is a measure of total mechanical energy generated by ventricular contraction, and VO(2) is O(2) consumption of ventricular contraction. The E(max)-PVA-VO(2) framework proved to be powerful in cardiac mechanoenergetics. We therefore studied the effects of intracoronary caffeine at concentrations lower than 1 mmol/l on left ventricular (LV) E(max) and VO(2) for excitation-contraction (E-C) coupling in the excised cross-circulated canine heart. We enhanced LV E(max) by intracoronary infusion of caffeine after beta-blockade with propranolol and compared this effect with that of calcium. We obtained the relation between LV VO(2) and PVA with E(max) as a parameter. We then calculated the VO(2) for the E-C coupling by subtracting VO(2) under KCl arrest from the PVA-independent (or zero-PVA) VO(2) and the O(2) cost of E(max) as the slope of the E-C coupling VO(2)-E(max) relation. We found that this cost was 40% greater on average for caffeine than for calcium. This result, for the first time, characterized integratively cardiac mechanoenergetics of the O(2) wasting effect of the complex inotropic mechanisms of intracoronary caffeine at concentrations lower than 1 mmol/l in a beating whole heart.

Animals↗

PubMed2000

Logistic time constant of isometric relaxation force curve of ferret ventricular papillary muscle: reliable index of lusitropism.

We have found that a logistic function fits the left ventricular isovolumic relaxation pressure curve in the canine excised, cross-circulated heart more precisely than a monoexponential function. On this basis, we have proposed a logistic time constant (tau(L)) as a better index of ventricular isovolumic lusitropism than the conventional monoexponential time constant (tau(E)). We hypothesize in the present study that this tau(L) would also be a better index of myocardial isometric lusitropism than the conventional tau(E). We tested this hypothesis by analyzing the isometric relaxation force curve of 114 twitches of eight ferret isolated right ventricular papillary muscles. The muscle length was changed between 82 and 100% L(max) and extracellular Ca(2+) concentrations ([Ca(2+)](o)) between 0.2 and 8 mmol/l. We found that the logistic function always fitted the isometric relaxation force curve much more precisely than the monoexponential function at any muscle length and [Ca(2+)](o) level. We also found that tau(L) was independent of the choice of the end of isometric relaxation but tau(E) was considerably dependent on it as in ventricular relaxation. These results validated our present hypothesis. We conclude that tau(L) is a more reliable, though still empirical, index of lusitropism than conventional tau(E) in the myocardium as in the ventricle.

Animals↗

PubMed2000

2,3-Butanedione monoxime suppresses primarily total calcium handling in canine heart.

Whether 2,3-butanedione monoxime (BDM, < or = 5mmol/l) suppresses primarily crossbridge cycling or total Ca(2+) handling in the blood-perfused whole heart remains controversial. Although BDM seems to suppress primarily total Ca(2+) handling in canine hearts, more evidence is lacking. We therefore analyzed the cardiac mechanoenergetics, namely, E(max) (contractility), PVA (total mechanical energy), and O(2) consumption of canine BDM-treated hearts by our recently developed integrative method to assess myocardial total Ca(2+) handling. This method additionally required the internal Ca(2+) recirculation fraction. We obtained this from the beat constant of the exponential decay component of the postextrasystolic potentiation. Our analysis indicated significant decreases in both internal Ca(2+) recirculation fraction and total Ca(2+) handling in the BDM-treated heart, but virtually no change in the reactivity of E(max) to total Ca(2+) handling. This result corroborates the view that BDM suppresses primarily total Ca(2+) handling rather than crossbridge cycling in the canine blood-perfused heart.

Animals↗

PubMed2000

A case of Penicillium marneffei infection in an AIDS patient: the first case in Japan.

A 38-year-old Japanese AIDS patient developed papular lesions which rapidly increased in number, eroded and crusted, and spread over not only skin but also the mucosal surface. High fever, sore throat, malaise and hepatosplenomegaly were also noted, and he died despite 2 months of intensive treatment. An autopsy revealed numerous histiocytes infected with Penicillium marneffei in the lymph nodes, liver, spleen, bone marrow, skin, and mucosal surface of the oral cavity to the pharynx. This case is thought to be the first Japanese case of penicilliosis marneffei.

AIDS-Related Opportunistic Infections↗

PubMed1999

Clonal dissemination of T-lymphocytes in scid mice from familial hemophagocytic lymphohistiocytosis.

BACKGROUND: Although familial hemophagocytic lymphohistiocytosis (FHL) has been considered a disorder of T-cell dysfunction, there is no evidence of the clonal origin of T-cells in this disease. PROCEDURE: We engrafted mononuclear cells (MNCs) from five FHL patients into scid mice and examined the infiltration of human cells in mouse organs. The characterization of human cells that infiltrated in the mouse organs was then performed. RESULTS: A diffuse infiltration of human lymphoid cells was detected in scid mice treated with 1 x 10(6) MNCs from one of the five patients. These cells were positive for HLA-DR and CD3, but negative for CD4, CD8, CD20, and CD68, suggesting the infiltration of double negative (DN) T-cells. The MNCs from the other four patients induced murine lymphoma-like disease; T-cell lymphoma in one and lymphoma of unknown origin in three. The characterization of these human DN T-cells was performed. The analysis of the Vbeta repertoire showed no preferential usage of the Vbeta family in MNCs, while the dominant expression of Vbeta13 was detected in T-cells infiltrating in the spleen and lung. A Jbeta analysis showed the restricted usage of Jbeta1.2 for Vbeta13 in these cells, and the clonality of Vbeta13-Jbeta1.2 fragment was confirmed by a single-strand confirmation polymorphism analysis. The analysis of the Valpha repertoire showed that Valpha24 was exclusively used in these DN T-cells, but no usage of JalphaQ for Valpha24 was observed. CONCLUSIONS: A clonal expansion of T-cells was induced in scid mice by the engraftment of MNCs from an FHL patient. The infiltration of DN alphabeta T-cells bearing invariant Valpha24 T-cell receptor in mouse organs may provide a useful clue to the pathogenesis of FHL. In the patients whose MNCs induced murine lymphoma-like disease, some cytokines or unknown factors that stimulate the growth and the tumorigenicity of murine lymphocytes might be produced by the MNCs engrafted in scid mice. Further study is needed to confirm the validity of our experimental approach and the findings observed in scid mice by using more FHL samples.

Animals↗