Rectal involvement by carcinoma of the prostate.
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Biomedical subjects
Publications and source records attributed to H Chang.
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Activation of adenosine receptors leads to the inhibition of lipolysis in the fat cells of several species including humans. We have examined the effects of the adenosine analog phenylisopropyladenosine (PIA) on lipolysis in vivo in intact rats. PIA suppresses markedly serum-free fatty acid (FFA) concentrations when injected s.c. (-)-PIA is more potent than (+)-PIA in suppressing FFA concentrations; also, this effect of (-)-PIA is blocked by the adenosine receptor antagonist 8-(p-sulfophenyl)theophylline. (-)-PIA also suppressed plasma triglyceride (TG) concentrations by approximately 50% in these rats. Utilizing Triton WR1339 injections, we found that the decrease in serum TG concentrations was associated with a marked fall in very low density lipoprotein secretion rate. We also examined the effects of (-)-PIA on FFA and TG concentrations in two models of hypertriglyceridemia in rats: stretozotocin-induced diabetes and sucrose feeding. Both groups had elevated FFA and TG concentrations compared with controls. An injection of (-)-PIA suppressed markedly FFA concentrations and essentially normalized the serum concentration of TG in these rats. We conclude that (-)-PIA suppresses markedly lipolysis and triglyceride secretion in control and hypertriglyceridemic rats suggesting that the activation of adenosine receptors may have major metabolic effects in vivo.
Electrophysiological properties of a cloned monkey kidney cell line, JTC-12, were studied. The mean resting potential and input resistance were -15.3 mV and 78 M omega, respectively. Spontaneous hyperpolarizations with increased membrane conductance were observed. Similar hyperpolarization could be elicited by mechanical and electrical stimulations. The mean reversal potential of these hyperpolarizations was -72.7 mV. Hyperpolarization could be also elicited in a chloride-free solution. These data indicate that: JTC-12 cells exhibit spontaneous and induced hyperpolarizations, and occurrence of hyperpolarization is related to an increase in membrane permeability to potassium ions.
Sixty (60) out-patients with DSM III generalized anxiety disorder were treated after a 1-week placebo washout in a 4-week double-blind study with buspirone, diazepam and placebo; after which they were withdrawn abruptly from medication or assigned to a 2-week period of placebo. The HAM-A score was significantly lower in the diazepam group at week 2 (p less than .02) and the buspirone group at week 3 (p less than .04) as compared to the placebo group. A similar pattern was evident in the female group, but not in the male group. Dizziness was the most prominent adverse effect in the buspirone group, whereas the diazepam group had more adverse effects including sedation, fatigue, dizziness and impaired concentration. Withdrawal symptoms were more evident in the diazepam group than the buspirone group.
The effect of streptozotocin-induced diabetes mellitus on maximal insulin-stimulated glucose uptake in the rat was studied in isolated adipocyte, perfused hindlimb, and the intact organism. Basal glucose transport per fat cell was reduced by approximately two-thirds (P less than 0.001), being associated with a similar decrease in glucose oxidation per fat cell (P less than 0.001). There was also a significant decrease (P less than 0.001) in basal glucose uptake by perfused hindlimb of diabetic rats of approximately 40%. Furthermore, maximal insulin-stimulated glucose transport and oxidation were approximately 50% lower (P less than 0.001) in fat cells of diabetic as compared with control rats. In contrast, maximal insulin-stimulated glucose disposal by perfused hindlimbs from diabetic and control rats was similar, and this was also true of the ability of insulin to maximally stimulate glucose uptake in the intact normal and diabetic rat. These findings indicate that variation exists in the manner in which insulin-sensitive tissues respond to experimentally induced insulin deficiency and support the view that total body glucose disposal is primarily related to insulin action on muscle.
A 5-week placebo washout comparison of trimipramine 150 mg/day and maprotiline 150 mg/day was carried out in 15 male and 24 female patients with unipolar major affective disorder. There were no significant differences between the two groups in age, sex, weight, height, or vital signs. Both groups showed significant improvement over time, with no difference between the groups on the Severity and Improvement factors of the Clinical Global Impression scale, on the total and factor subscales of the Hamilton Depression Rating Scale, and on the Anxiety Status Inventory. The maprotiline group showed a greater increase in weight over the study period than did the trimipramine group. There was a significant lowering of systolic blood pressure in the trimipramine group only and a significant and linear increase in pulse rate by Week 3 in the maprotiline group. Analysis of ECG showed that the atrial rates were significantly increased in the maprotiline group (p less than .002) but not in the trimipramine group. Trimipramine had significantly fewer anticholinergic, neurologic, and cardiovascular adverse effects than maprotiline.
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Rats treated with high (3.0 mg/kg) or low (0.3 mg/kg) doses of prazosin had significantly lower (p less than 0.01) plasma triglyceride levels and a lower triglyceride secretion rate than control rats. Propranolol had no effect on triglyceride levels when compared with controls. There was a significant elevation of plasma cholesterol concentrations in propranolol-treated rats when compared with animals given prazosin. The ratio of high-density lipoprotein cholesterol to total cholesterol was significantly greater in prazosin-treated rats than in controls and propranolol-treated rats. Free fatty acid levels were significantly lower in the prazosin-treated group, a finding that may explain reduced very low-density lipoprotein and triglyceride secretion. These data demonstrate that the disparate effects on lipid metabolism of the alpha- and beta-receptor antagonists studied, previously shown to occur in hypertensive man, can be duplicated in the normal rat. This animal model may prove useful for the study of adrenergic mechanisms in lipid metabolism.
Although almost every U.S. pulp mill has a biological wastewater treatment system, these systems based on bacteria, are largely ineffective in the removal of color. For this reason, we have attempted to utilize Phanerochaete chrysosporium, a fungus known to degrade lignin, as the primary organism in a novel waste treatment scheme named the MyCoR Process. Color from bleached Kraft mills originates principally from the first extraction stage of the bleach plant. It is this waste stream which is sent to the MyCoR Process reactor, a rotating biological contactor, for decolorization. We have found that under optimal conditions up to 2,000 color units/L/day can be removed from the waste stream. There is also a concomitant removal of COD and BOD. In addition, chlorolignins originating from the bleaching process were found to be dechlorinated; this is of interest to those concerned with the impact of bleach plant effluents on the environment. The process uses conventional wastewater treatment equipment. However, the use of a pure culture of fungus in a secondary metabolic state has not been attempted previously in a waste treatment scheme. Minor equipment modification and close operator attention may therefore be required. A preliminary economic analysis shows that the MyCoR Process, in its present state, would cost about US$30/metric ton of bleached Kraft pulp produced. This cost will decrease as improved or new strains of fungi are developed for the process.
A preliminary study was conducted to correlate vascular invasion with metastasis in testicular tumors. A lectin-immunoperoxidase procedure was used to identify the vessels. Together with standard hematoxylin and eosin staining, the presence of tumor cells in vessels was detected. Primary tumor specimens from 37 cases and retroperitoneal lymph nodes from 10 cases of germ cell tumors were studied. The results showed good correlations between vascular invasion in primary tumors and metastasis to lymph nodes in nonseminomatous germ cell tumors, and between vascular invasion in retroperitoneal lymph nodes and the presence of other metastases. Eight of the 9 nonseminomatous germ cell tumor patients with vascular invasion had metastases, and all 4 patients that had vascular invasion in the lymph nodes had other metastases. However, there seemed to be no correlation between vascular invasion and clinical staging in cases with seminoma in which retroperitoneal lymph node dissection was not performed. These observations, although based on a limited number of cases, warrant more extensive investigations.
Streptozotocin-induced insulin deficient rats allowed to run at will had significantly (P less than 0.001) lower mean (+/- SEM) plasma glucose levels (12.1 +/- 0.9 vs 22.6 +/- 1.7 mM/l) than did equally insulin deficient sedentary rats. Muscle glycogen phosphorylase and synthase activities were similar in exercise-trained and sedentary diabetic rats, and were unchanged from control values. In contrast, muscle phosphofructokinase activity was reduced (P less than 0.001) in sedentary rats with insulin deficiency, and the defect was significantly reversed (P less than 0.01) when such rats were allowed to run spontaneously. These results are consistent with the view that the ability of exercise-training to attenuate the magnitude of hyperglycemia in streptozotocin-induced insulin deficiency is associated with an effect on a key regulatory enzyme in the glycolytic pathway.
Given a suitable trigger signal, cardiac synchronized magnetic resonance (MR) imaging is simple to implement; however, single section techniques are not efficacious, especially when the heart rate sets the repetition interval. We demonstrate multi-section, double, and single-echo imaging, any of which rapidly covers the cardiac volume; 3-D modes capable of achieving very thin sections; and cycled multi-section imaging capable of efficaciously providing dynamic data on heart motion. These modes form a complementary, powerful set of options for clinical work.
In an effort to determine whether differences in basal and maximum insulin-stimulated glucose transport by isolated adipocytes are a function of donor sex, we measured glucose transport rates in the absence and presence of 8 nM insulin in adipocytes isolated from the abdominal subcutaneous fat tissue of nine male and ten female subjects with varying degrees of obesity and in adipocytes isolated from the abdominal subcutaneous and retroperitoneal fat tissue of (180-220 g) male and female rats. Because maximal insulin-stimulated glucose transport rate per cell of adipocytes isolated from subcutaneous abdominal tissue of male and female subjects was constant in each sex, the data have been normalized on the basis of transport per cell. The results demonstrated that basal and maximal insulin-stimulated glucose transport per cell was 53-75% higher per cell in the females versus males in adipocytes from human subcutaneous abdominal adipose tissue (P less than 0.01). A similar difference in glucose transport rate between males and females (P less than 0.001) was also found in rat abdominal subcutaneous adipose tissue. Adipocytes isolated from rat retroperitoneal adipose tissue had higher transport rates (approximately three-fold) and smaller sex differences (35% higher in females) than found in adipocytes from rat and human subcutaneous tissue. These results indicate that basal and maximum insulin-stimulated glucose transport is higher by adipocytes isolated from females and that this difference is independent of adipose cell size and species.
The ability of hormones to activate responses in a variety of tissues decreases with age. The mechanism(s) responsible for these alterations are unclear. We have confirmed that the ability of a beta-adrenergic receptor agonist to activate lipolysis in isolated rat adipocytes decreases with age. Maximum response to isoproterenol was greater in 2-mo-old rats (600 +/- 30 nmol of glycerol released/10(5) cells per h) than 12-mo-old rats (250 +/- 25 nmol/10(5) cells per h), P less than 0.001. Similarly, ACTH is less effective in activating lipolysis in the adipocytes from the older rats. However, the cAMP analogue 8-(4-chlorophenothio)adenosine 3',5'-monophosphate cyclic activated lipolysis equally in the two groups, suggesting that the deficit in adipocytes from the older rats was proximal to cAMP-dependent protein kinase activation. Both isoproterenol and ACTH were significantly less effective in promoting cAMP accumulation in adipocytes isolated from 12-mo-old rats. There was no difference in phosphodiesterase activity of the adipocytes between the two groups. beta-Adrenergic receptors were measured using the antagonist radioligand [125I]cyanopindolol. The number of beta-adrenergic receptors was actually increased in the adipocytes from 12-mo-old rats (26,000 +/- 2,600 receptors/cell) compared with cells from 2-mo-old rats (7,200 +/- 1,300 receptors/cell). The results suggest that diminished cAMP production is responsible for the diminished lipolytic response in the adipocytes of older rats. The mechanism responsible for this change is uncertain but cannot be explained by a loss in beta-adrenergic receptors.
The ability of a variety of hormones to activate cells declines with age. We have investigated the mechanism for the reduced ability of beta adrenergic stimulation to activate lipolysis in fat cells from older rats. Previously, we have found that these cells have an intact lipolytic response to a cAMP analogue but diminished cAMP accumulation after isoproterenol stimulation, suggesting that the blunted cAMP response is rate limiting. In the present study we have tested the hypothesis that enhanced inhibition of lipolysis by endogenously released adenosine accounts for the diminished lipolysis. Adenosine deaminase was added to media containing the adipocytes from older rats to remove endogenous adenosine. Under these conditions beta adrenergic stimulation of lipolysis is intact in fat cells from older rats. The adenosine analogue N6-phenylisopropyladenosine more effectively inhibited lipolysis in the older group (77 +/- 6%) than in the younger group (46 +/- 5%), suggesting that enhanced efficacy of endogenous adenosine may account for the reduced lipolytic response to catecholamines. When pertussis vaccine was used to functionally inactivate adenosine receptors in adipocytes from the younger and older rats, the ability of isoproterenol to activate lipolysis was restored in the older group. All the data are consistent with the hypothesis that enhanced inhibitory effects of adenosine explain the diminished ability of beta adrenergic agonists to activate lipolysis. It is possible that enhanced inhibitory pathways may be involved in blunting responses to stimulatory hormones in other tissues from older animals.
Dilauroylphosphatidylethanolamine dispersion forms a crystalline phase at physiological pH and temperature and in the presence of excess water. This phenomenon was observed and studied by differential scanning calorimetry, scanning densitometry and X-ray diffraction. The crystalline phase is stable at pH 5.5-9.5 and below 40 degrees C. The crystalline phase formed at pH 5.5 and pH 9.5 index according to orthorhombic cells with a = 9.41, b = 8.15, c = 46.0 and a = 9.33, b = 8.05, c = 45.8 (A), respectively. Around 43 degrees C, the crystalline phase is transformed into a multilayer liquid crystal phase. Cooling from 44 degrees C results in the disappearance of the original transition at 43 degrees C and the appearance of a second transition at around 30 degrees C. Below 30 degrees C the lipid forms a gel phase. This gel phase is metastable at pH 5.5 and a crystalline phase may be recovered from it by dispersing or aging methods. Suspensions of dilauroylphosphatidylethanolamine show similar phase transition behaviour at pH 5.5 and pH 9.5, although the transitions are somewhat broader at the higher pH. The thermotropic phase behaviour of dilauroylphosphatidylethanolamine dispersions may be governed by changes in hydration.
The effects of 14 days of daily intraperitoneal injections of prazosin hydrochloride (3.0 or 0.3 mg/kg) or propranolol (5 mg/kg) on various aspects of the lipid metabolism of normal rats was studied. The results indicate that plasma triglyceride and cholesterol concentrations were lower and the ratio of plasma HDL-cholesterol to total cholesterol concentration higher in prazosin-treated rats compared with propranolol-treated rats. The decline in plasma triglyceride levels in prazosin-treated rats was associated with a commensurate reduction in triglyceride secretion rates. Plasma free fatty acid levels were also lower in prazosin-treated rats, and this change may have contributed to the fall in triglyceride secretion rates. These data demonstrate that the disparate effects of alpha and beta receptor antagonists, previously shown to occur in hypertensive humans, can be duplicated in normal rats.
The ability of exercise and diet to modify the effects of moderate streptozotocin-induced insulin deficiency on triglyceride metabolism has been studied in the rat. Insulin-deficient rats allowed to run spontaneously in exercise wheel cages had significantly lower (P less than 0.001) plasma glucose levels (187 +/- 19 mg/dl) than either sedentary (374 +/- 24 mg/dl) or sucrose-fed (450 +/- 13 mg/dl) diabetic rats, despite the fact that plasma insulin levels were comparable in all these groups. Plasma triglyceride (TG) levels in exercise-trained rats with diabetes (51 +/- 5 mg/dl) were actually lower than in control rats with normal glucose tolerance (90 +/- 14 mg/dl). In contrast, plasma TG levels were higher than control levels in diabetic sedentary rats (128 +/- 11 mg/dl), and severe hypertriglyceridemia developed in sucrose-fed diabetic rats (369 +/- 35 mg/dl). The ability of exercise training to attenuate diabetic hypertriglyceridemia, which was observed in both chow-fed and sucrose-fed rats, was secondary to a decrease in TG secretion, and appeared to be related to lower plasma FFA concentrations. In contrast, the accentuation of diabetic hypertriglyceridemia seen in sucrose-fed rats was related to a defect in TG catabolism. Adipose tissue lipoprotein lipase (LPL) activities were essentially identical in all diabetic rats, suggesting that the observed difference in TG kinetics could not be attributed to concomitant increases or decreases in adipose tissue LPL activity. These results emphasize the powerful impact of exercise and diet on TG metabolism in rats with moderate degrees of insulin deficiency.