Search PubMed⌕ Search

Biomedical subjects

T Homma

Publications and source records attributed to T Homma.

At least 145 records · Page 8Linked to original sources
PubMed1990

Epoxyeicosatrienoic acids activate Na+/H+ exchange and are mitogenic in cultured rat glomerular mesangial cells.

The present study examined responses of cultured rat glomerular mesangial cells to exogenous exposure of epoxyeicosatrienoic acids (EET's), products of cytochrome P450 epoxygenase. One day after administration of 8,9- or 14,15-EET, cultured rat mesangial cells demonstrated significant increases in [3H]thymidine incorporation (10(-7) M 14,15-EET: 120 +/- 7% of control; n = 6; P less than 0.025; 10(-6) M 14,15-EET: 145 +/- 10%; n = 20; P less than 0.0005; 10(-6) M 8,9-EET: 167 +/- 31%; n = 9; P less than 0.05), which was not affected by addition of the cyclooxygenase inhibitor indomethacin. In addition to stimulation of [3H]thymidine incorporation, the epoxides stimulated mesangial cell proliferation. 14,15-EET administration induced intracellular alkalinization of 0.2-0.3 pH units, which was prevented by extracellular Na+ removal and blunted by amiloride (0.5 mM). Following intracellular acidification with NH4Cl addition and removal, greater than 85% of 3 mM 22Na uptake into mesangial cells was inhibited by 1 mM amiloride, indicating Na+/H+ exchange. Under these conditions, 14,15-EET stimulated Na+/H+ exchange by 42% and 8,9-EET stimulated Na+/H+ exchange by 59%. Neither protein kinase C depletion nor addition of the protein kinase C inhibitor, staurosporine, affected this stimulation. In [3H]myo-inositol loaded mesangial cells, no significant stimulation of phosphoinositide hydrolysis was detected in response to administration of 14,15-EET. Twenty-four hours after addition of [14C]14,15-EET, greater than 90% was preferentially esterified to cellular lipids, with predominant incorporation into phosphatidylinositol, phosphatidylethanolamine, and diacylglycerol. Thus, these results demonstrate epoxyeicosatrienoic acids stimulate Na+/H+ exchange and mitogenesis in mesangial cells. These effects do not appear to be mediated via phospholipase C activation. In addition, 14,15-EET was selectively incorporated into cellular lipids known to mediate signal transduction. These observations extend the potential biologic roles of c-P450 arachidonate metabolites to include stimulation of cell proliferation and suggest a role for these compounds in vascular and renal injury.

8,11,14-Eicosatrienoic Acid↗
PubMed1990

Enhanced production of endogenous prostaglandin in obstructive jaundiced pancreas in dogs.

Endogenous pancreatic prostaglandin production in control and obstructive jaundice was investigated using isolated and perfused dog pancreas. In both groups, spontaneous production of prostaglandin E2 and prostaglandin I2 was recorded, and the levels did not change in both groups. The production of both prostaglandins in jaundice, however, was higher than that in the control on stimulation by 8 x 10(-11) mol of cholecystokinin-octapeptide. Amylase release with cholecystokinin-octapeptide at an amount of 8 x 10(-11) mol in jaundice was higher than in the control. The amylase release in both groups, however, showed further elevation on indomethacin pretreatment. On incubation of pancreatic dispersed cells in both groups, prostaglandin production in jaundiced cells was higher than that in control cells. These data showed that enhanced endogenous prostaglandin in obstructive jaundice might be caused by the characteristic change of pancreatic cells, which increased susceptibility to cholecystokinin-octapeptide because of long-term exposure to abnormal blood components, and enhanced prostaglandins might act as a cytoprotector of acinar cells in the pancreas damaged by cholecystokinin-octapeptide administration.

6-Ketoprostaglandin F1 alpha↗
PubMed1990

Loop diuretic-sensitive potassium flux pathways of rat glomerular mesangial cells.

Glomerular mesangial cells are smooth muscle-like contractile cells that mediate hormonal regulation of glomerular filtration. To gain better understanding of ionic events that accompany contraction/relaxation of these cells, flux pathways of K+ and their regulation by vasoactive agents were investigated in cultured rat mesangial cells using 86Rb+ as a tracer. Of total 86Rb+ influx (16.6 +/- 0.6 nmol x mg protein -1 x min-1), 46% was inhibited by 2 mM ouabain. Loop diuretics inhibited 43% of ouabain-insensitive 86Rb+ influx (3.9 +/- 0.2 nmol x mg protein-1 x min-1). Half-maximum inhibition was observed at 2 and 0.4 microM for furosemide and bumetanide, respectively. Loop diuretic-sensitive 86Rb+ influx was dependent on extracellular Na+ and Cl-; a hyperbolic dependency on extracellular Na+ was noted with apparent Michaels constant of 39 mM while a sigmoidal dependency on extracellular Cl- was present, which, assuming 1:1:2 stoichiometry for Na(+)-K(+)-Cl-, produced an apparent mean affinity constant of 64 mM. Moreover, a fraction of amiloride-insensitive 22Na+ influx was found to be sensitive to furosemide and dependent on extracellular K+ and Cl-, further indicating the presence of Na(+)-K(+)-Cl- cotransport. Efflux of 86Rb+ followed first-order kinetics, of which 60% was inhibitable by furosemide. Manipulations of extracellular osmolarity revealed that these furosemide-sensitive 86Rb+ flux pathways were coordinately regulated in response to osmotic stress. Concentration-dependent stimulation of Na(+)-K(+)-Cl- cotransport-mediated 86Rb+ influx was induced by two vasoconstrictors, angiotensin II (ANG II) and arginine vasopressin (AVP), and by a vasodilator, atrial natriuretic peptide (ANP).(ABSTRACT TRUNCATED AT 250 WORDS)

Amiloride↗
PubMed1990

Coronary artery fistula with left or right ventricular communication and sinus-node dysfunction.

Coronary artery fistulae that communicate with the left ventricle are quite rare; those accompanied by sinus-node dysfunction are even more unusual. We report 2 cases of congenital coronary-artery-to-left-ventricle fistula with sinus-node dysfunction. In each of these patients, fistulae arose from both left and right coronary arteries. One patient had, in addition, a right coronary artery fistula that communicated with his right ventricle. Sinusnode dysfunction encountered in these 2 patients was likely caused by chronic general ischemia arising from a steal syndrome associated with the fistulae.

Journal Article↗
PubMed1990

[The effect of DREZ (dorsal root entry zone) lesions on intractable pain in patients with spinal cord injury].

Some patients with spinal cord injury complain of a severe intractable pain. This intractable pain places new hurdles on the road to return to the ordinary daily life in these patients. The effective therapy for the intractable pain has not been established. Dorsal root entry zone (DREZ) lesion was originally reported by Nashold et al to alleviate deafferented pain syndrome. Three male and one female patients with intractable pain following spinal cord injury were treated with DREZ-lesions. One month after operation, all 4 patients obtained good pain relief. However, at a follow-up period till February 1989 (ranging 11 months from 2 years and 6 months), 2 patients had subjective pain relief. When other therapies on intractable pain following spinal cord trauma are not effective, the DREZ-lesion might be considered.

Adult↗
PubMed1989

Preparation and characterization of monoclonal antibodies against human myeloperoxidase.

We established 11 hybridomas producing monoclonal antibodies (MoAbs), designated AM, against human myeloperoxidase (MPO), by immunizing mice with the three forms of MPO (I, II, and III) purified from healthy human polymorphonuclear leukocytes (PMN) and characterized the specificity of the AM MoAbs. Ten of the AM MoAbs reacted similarly to each of the three forms using an enzyme-linked immunosorbent assay. When a cetyltrimethylammonium bromide (CETAB) extract of human PMN was electrophoresed in a CETAB polyacrylamide gel and transferred to a nitrocellulose filter, IgG1 class AM MoAbs immunostained only the MPO band of the proteins of the extract. In addition, the AM MoAbs reacted to two radioactive bands of 94 and 92 kDa in a HL-60 cell lysate labeled with [35S]methionine for 1 h. After a chase period of 24 h, these bands were replaced by four radioactive bands of 64.5, 43, 16.7, and 13.4 kDa, demonstrating that the MoAbs recognize not only mature MPO but also the MPO precursors of 94 and 92 kDa. The data also indicated that the two major bands of 64.5 and 13.4 kDa corresponded to heavy and light chains of mature MPO, respectively, and the additive intermediate bands of 43 and 16.7 kDa were MPO-related proteins. Moreover, AM MoAbs reacted to a similar extent to the deglycosylated form of MPO III with endo-beta-N-acetylglucosaminidase H (Endo-H). Thus, IgG1 class AM MoAbs recognized MPO with high specificity and reacted to the structure which is commonly conserved in the three mature forms of MPO (I, II, and III), MPO precursors, and deglycosylated MPO with Endo-H. AM MoAbs also specifically reacted to PMN and/or monocytes but did not react to lymphocytes when the cell staining method was used.

Animals↗
PubMed1989

The role of oxygen free radicals in experimental acute pancreatitis in the rat.

In order to elucidate the role of oxygen-derived free radicals in acute pancreatitis, scavengers and an inhibitor of production of these free radicals were administered to rats with experimentally-induced acute pancreatitis. Acute reflux pancreatitis was produced by the occlusion of the common bile duct (OCD). Catalase and superoxide dismutase (SOD) were used as scavengers, and allopurinol was used as an inhibitor of production of free radicals. Six h after surgery, serum amylase, lipase, and thiobarbituric acid (TBA) reactant levels were elevated significantly, and histological changes in the pancreas, consisting of edema, inflammatory cell infiltration, and necrosis, partially around the intralobular and interlobular ducts, developed in the control rats receiving no agent. However, serum lipase and amylase levels in the rats given each agent were significantly lower (p less than 0.05) than in the controls. The histological changes in the pancreas were less marked in agent-treated rats than in untreated rats. These results suggest that oxygen-derived free radicals participate in the development of acute pancreatitis.

Acute Disease↗
PubMed1989

Involvement of endogenous prostaglandins in pancreatic endocrine and exocrine secretion in dog pancreas.

The involvement of endogenous prostaglandins (PGs) in pancreatic endocrine and exocrine secretion was investigated, using the isolated and perfused dog pancreas. Spontaneous production of both PGE2 and 6-keto-PGF1 alpha was recorded in venous effluent. Prostaglandin production increased following stimulation with both 10 x 10(-11) and 20 x 10(-11) mol of CCK-8, but was not affected by a 5 x 10(-11) mol infusion. Insulin, glucagon, and amylase release was stimulated by 10 x 10(-11) mol of CCK-8. Indomethacin pretreatment with 10 mg/kg totally abolished endogenous PG production, but failed to suppress an insulin and glucagon response. On the other hand, an amylase response was accelerated by indomethacin pretreatment. Although low dose CCK-8 failed to stimulate endogenous prostaglandin production, a brisk exocrine secretion was not suppressed by indomethacin pretreatment. From the above results, we conclude that endogenous PGs do not appear to play an important role in pancreatic endocrine and exocrine secretion, but might have a cytoprotective effect on the pancreatic acinar cells damaged by CCK-8.

Amylases↗
PubMed1989

An experimental study of spinal cord evoked potentials and histologic changes following spinal cord heating.

To study the safety of hyperthermia cancer treatment, canine spinal cords were heated with radio waves to between 43 C and 47 C for 30 minutes. Spinal cord evoked potentials (SCEP) studied by epidural recording after epidural stimulation showed shortened latency and unchanged amplitude at 44 C or below. At 45 C or above, reduction of amplitude combined with shortened latency was observed, a phenomenon that has not hitherto been reported. After heating to 45 C, SCEP recovered with the reduction of temperature, but histologic examinations showed pigment exudation, vacuolation, and hemorrhage. These results suggest that tolerable spinal cord temperature should not exceed about 44 C.

Animals↗
PubMed1989

Visualization and finite element analysis of pulsatile flow in models of the abdominal aortic aneurysm.

Pulsatile flows in glass models simulating fusiform and lateral saccular aneurysms were investigated by a flow visualization method. When resting fluid starts to flow, the initial fluid motion is practically irrotational. After a short period of time, the flow began to separate from the proximal wall of the aneurysm. Then the separation bubble or vortex grew rapidly in size and filled the whole area of the aneurysm circumferentially. During this period of time, the center of the vortex moved from the proximal end to the distal point of the aneurysm. The transient reversal flow, for instance, which may occur at the end of the ejection period, passed between the wall of the aneurysm and the centrally located vortex. When the rate and pulsatile frequency of flow were high, the vortex broke down into highly disturbed flow (or turbulence) at the distal portion of the aneurysm. The same effect was observed when the length of the aneurysm was increased. A reduction in pulsatile amplitude made the flow pattern close to that in steady flow. A finite element analysis was made to obtain velocity and pressure fields in pulsatile flow through a tube with an axisymmetric expansion. Calculations were performed with the pulsatile flows used in the visualization experiment in order to study the effects of change in the pulsatile wave form by keeping the time-mean Reynolds number and Womersley's parameter unchanged. Calculated instantaneous patterns of velocity field and stream lines agreed well with the experimental results. The appearance and disappearance of the vortex in the dilated portion and its development resulted in complex distributions of pressure and shear fields. Locally minimum and maximum values of wall shear stress occurred at points just upstream and downstream of the distal end of the expansion when the flow rate reached its peak.

Aorta, Abdominal↗
PubMed1989

[The clinical picture of terminally ill patients with lung cancer].

An investigation has been made with regard to the clinical picture of 87 terminally ill patients with lung cancer. It has yielded the following points. 1) Seven patients had been informed of their diagnosis. 2) Intravenous hyperalimentation was administered in 78 cases (90%), oxygen therapy in 68 cases (78%), and morphine in 35 cases (40%). 3) The most frequent cause of death in these patients was respiratory failure, due to progress of cancer, then infection, pleural, or pericardial effusion, or interstitial pneumonitis. 4) Psychic disturbances involved anxiety over breathing, depression, and delirium. In only 12% of the patients did the mental condition seem normal until death. 5) To deal with the dying patient's needs, it is necessary to establish proper treatment for the control of sensory dyspnea and for psychosocial support by a psychiatrist and other professionals for members of the family.

Adult↗
PubMed1988

Radioimmunotherapy of transplanted small cell lung cancer with 131I-labelled monoclonal antibody.

Monoclonal antibody TFS-4 has previously been shown to react selectively with human small cell lung cancer (SCLC). We evaluated the use of 131I-labelled TFS-4 for the treatment of established human SCLC transplanted in nude mice. The specific accumulation of the antibody in the transplanted tumour was recorded by both scintigraphic and biodistribution studies. Administration of 200 microCi 131I-labelled TFS-4 inhibited tumour growth when compared with the same radiation dose of the control monoclonal antibody. The therapeutic effect was dose-dependent and complete disappearance of the tumour was observed transiently in one out of the three animals following the administration of 500 microCi 131I-labelled TFS-4.

Adenocarcinoma↗
PubMed1988

Long-term follow-up of patients with sick sinus syndrome: a comparison of clinical aspects among unpaced, ventricular inhibited paced, and physiologically paced groups.

To analyze the prognosis of the sick sinus syndrome (SSS), we compared the clinical aspects among unpaced, ventricular paced, and physiologically paced patients who were followed over a long period. Unpaced intrinsic SSS was not always progressive and patients did not necessarily require permanent pacing. The incidence of concomitant AV conduction disturbance was 65.6% before pharmacologic autonomic block, (PAB), but this was significantly reduced to 31.7% after PAB. Follow-up study of the physiologically paced groups revealed no development of either new or more than second degree AVB. The VVI group had significantly more complications (68%) than the physiologically paced groups, mainly chronic atrial fibrillation (36%) and thromboembolism (20%). In addition, cardiothoracic ratio (CTR) in the VVI group was significantly greater compared with that in the physiologic groups. Nine deaths occurred during the follow-up period in the pacing groups, including six with VVI and three with physiologic pacing. In the VVI pacing group, heart failure and thromboembolism were most commonly the causes of death, while in the physiologic pacing groups, the causes of death were noncardiac. Although the survival rate in the ventricular paced group was not significantly different from that in the physiologic pacing groups, cardiac deaths were fewer in the latter group. Considering our clinical data, the decision to use ventricular pacing needs to be carefully weighed in patients with sick sinus syndrome, and physiologic pacing is more highly recommended.

Adolescent↗
PubMed1988

Vortex generation in pulsatile flow through arterial bifurcation models including the human carotid artery.

Visualization experiments were performed to elucidate the complicated flow pattern in pulsatile flow through arterial bifurcations. Human common carotid arteries, which were made transparent, and glass-models simulating Y- and T-shaped bifurcations were used. Pulsatile flow with wave forms similar to those of arterial flow was generated with a piston pump, elastic tube, airchamber, and valves controlling the outflow resistance. Helically recirculating flow with a pattern similar to that of the horseshoe vortex produced around wall-based protuberances in circular tubes was observed in pulsatile flow through all the bifurcations used in the present study. This flow type, which we shall refer to as the horseshoe vortex, has also been demonstrated to occur at the human common carotid bifurcation in steady flow with Reynolds numbers above 100. Time-varying flows also produced the horseshoe vortex mostly during the decelerating phase. Fluid particles of dye solution approaching the bifurcation apex diverged, divided into two directions perpendicularly, and then showed helical motion representing the horseshoe vortex formation. While this helical flow was produced, the stagnation points appeared on the wall upstream of the apex. Their position was dependent upon the flow distribution ratio between the branches in the individual arteries. The region affected by the horseshoe vortex was smaller during pulsatile flow than during steady flow. Lowering the Reynolds number together with the Womersley number weakened the intensity of helical flow. A separation bubble, resulting from the divergence or wall roughness, was observed at the outer or inner wall of the branch vessels and made the flow more complicated.

Adult↗
PubMed1988

Serial micropuncture analysis of glomerular function in two rat models of glomerular sclerosis.

We have recently developed a micropuncture technique to assess repeatedly function of the same nephrons in chronic renal disease and subsequently examine the morphology of their glomeruli by serial thin-section histological analysis. Using this approach, a potential causal linkage between early functional patterns and late structural abnormalities was examined in glomeruli of two established rat models of glomerular sclerosis. The models are (a) puromycin aminonucleoside (PAN) administration in unilaterally nephrectomized Munich-Wistar rats and (b) adriamycin (ADM) treatment in nonnephrectomized Munich-Wistar rats. Single nephron GFR (SNGFR) and glomerular capillary hydraulic pressure (PGC) were measured repeatedly for 8 (PAN rats) or 31 wk (ADM rats). In all animals studied, values for PGC remained at, or slightly below, levels measured before PAN or ADM administration. SNGFR values declined progressively in all glomeruli in PAN rats. Although some glomeruli in ADM rats had an increase in SNGFR above levels observed in nonnephrectomized control rats, these hyperfiltering glomeruli did not have abnormally high PGC nor did they exhibit glomerular sclerosis at the completion of the study. Histological analysis revealed the existence of a significant inverse correlation between the degree of sclerosis and SNGFR assessed at the time of sacrifice in both PAN and ADM groups. Chronic administration of captopril, an angiotensin I converting enzyme inhibitor, in PAN rats substantially attenuated development of glomerular sclerosis without affecting PGC in earlier stages. The observations in these models indicate that glomerular hyperfiltration and hypertension are not required for the development of glomerular sclerosis in renal diseases, and angiotensin I converting enzyme inhibitor can exert its protective effect independently of its effect on glomerular capillary pressure.

Animals↗
PubMed1988

A logistic-type curve fits pressure-diameter relationship for relaxed and contracted dog renal arteries.

In order to describe a possible effect of smooth muscle cell (SMC) activation on arterial wall distensibility, the present study derived a mathematical equation applicable to relaxed and contracted arterial walls. Pressure(P)-diameter(D) relationship of dog renal arteries was investigated in vitro under a cyclic loading and unloading process in the pressure range of 5-180 mmHg. Smooth muscle cells were activated by 10(-5)M norepinephrine. On the basis of the P-D curves obtained with fully contracted arteries, the vessel wall compliance dD/dP was assumed to be given by a second order polynomial of D, (formula; see text) The equation, including three parameters, Dmin, Dmax, and E, is integrated to yield the solution similar to the logistic curve as follows (formula; see text) where M(O) = (Dmax - D(O]/(D(O) - Dmin), and D(O) is the diameter at the point P = O. The constant, E, has the same dimension as the modulus of elasticity. The calculated P-D relationships coincided well with the experimental data for contracted and relaxed arteries. The most significant change due to wall contraction took place in the magnitude of M. This result, therefore, suggests that the parameter M is a good index of the degree of SMC contraction.

Animals↗