A selective decline of postheparin plasma hepatic triglyceride lipase in hypothyroid rats

The present study aimed to define the effect of thyroid status on two postheparin plasma lipases, i.e., lipoprotein lipase and hepatic triglyceride lipase. Rats with hypo- and hyperthyroidism were used for this purpose. Separate measurement of these two lipases was done by an immunochemical method utilizing antiserum specific to hepatic triglyceride lipase. The 5-wk thyroidectomized, hypothyroid rats had normal plasma concentrations of both triglyceride and cholesterol. These rats showed a selective decline in the activity of postheparin plasma hepatic triglyceride lipase with normal lipoprotein lipase activity. The rats made thyrotoxic by thyroxine treatment had normal plasma levels of both triglyceride and cholesterol. These rats showed normal activities of both hepatic triglyceride lipase and lipoprotein lipase. The observed finding of a selective decline of hepatic triglyceride lipase in hypothyroid rats is discussed in connection with the possible function of this enzyme in lipoprotein metabolism.     

Decline of postheparin plasma lipoprotein lipase in acromegalic patients

Lipoprotein lipase and hepatic triglyceride lipase in postheparin plasma were measured in seven patients with active acromegaly by an immunochemical method utilizing antiserum prepared against hepatic triglyceride lipase. A mild or moderate hypertriglyceridemia was shown, with plasma triglyceride concentrations between 156 and 544 mg/dl. Lipoprotein lipase was found to be decreased in all patients (p < 0.001). Hepatic triglyceride lipase was also low in these patients (p < 0.001). We speculate that acromegalic hypertriglyceridemia is mediated, at least in part, by the decline in lipoprotein lipase and possibly by the decline in hepatic triglyceride lipase activities.     

Accumulation of intermediate density lipoprotein in the plasma of cholesterol-fed hypothyroid rats

The present study aimed to characterize the high cholesterol diet-induced hyperlipoproteinemia developed in thyroidectomized hypothyroid rats, in such animals the activities of hepatic triglyceride lipase having been shown to be decreased. Feeding a diet containing 1% cholesterol to normal control rats resulted in hypercholesterolemia characterized by increases of VLDL, IDL and LDL. The feeding of cholesterol to hypothyroid rats produced a marked accentuation of hypercholesterolemia characterized by a large increase in IDL with a lesser increase in LDL. The IDL contained an increased amount of apo E. The VLDL of cholesterol-fed hypothyroid rats contained β-VLDL. These findings indicate a marked accumulation of remnant lipoproteins in the plasma of cholesterol-fed hypothyroid rats. Putting this and our previous findings together, we suggest that such an accumulation may be caused by impaired removal by the liver of remnant lipoproteins due to the decreased activities of hepatic triglyceride lipase.     

Effect of bombesin infused intrapancreatically on glucagon and insulin secretion

Synthetic bombesin was infused at a dose of 20 pmoles/kg/min for 10 min into the cranial pancreaticoduodenal artery of anesthetized dogs. Plasma immunoreactive glucagon concentrations in the cranial pancreaticoduodenal vein as well as in the femoral artery were concurrently and slowly elevated. However, the net release of glucagon from the pancreas did not increase significantly during infusion of bombesin. Plasma immunoreactive insulin concentrations in the pancreatic vein were transiently raised, and a delayed rise was noted in arterial plasma IRI. Net release of insulin was significantly augmented during infusion of the tetradecapeptide. Plasma glucose levels did not change after bombesin. These results indicate that the gastrointestinal tetradecapeptide may stimulate secretion of both insulin and gut glucagonlike immunoreactivity in the dog.     

Paradoxic elevation of serum growth hormone levels after splenectomy and/or paraesophagogastric devascularization in patients with portal hypertension

Blood glucose, serum immunoreactive insulin (IRI), and serum growth hormone (GH) levels during 50-g oral glucose tolerance tests (OGTT) were determined before and after splenectomy with or without paraesophagogastric devascularization in patients with portal hypertension (13 liver cirrhosis and 8 idiopathic portal hypertension) and in 5 splenectomized patients with diseases other than portal hypertension. Before splenectomy with devascularization, only 1 of 15 patients with portal hypertension exhibited a paradoxic elevation of serum GH levels of more than 10 ng/ml above the fasting levels after glucose loads. After the operation, however, 10 of these 15 patients showed the paradoxic elevation. Frequency of the paradoxic elevation was significantly higher after the operation than before (p < 0.001). The abnormal response of serum GH levels to glucose loads did not correlate with any of the blood glucose concentrations, serum IRI levels, and values for liver function tests. The paradoxic elevation was also observed in 4 of 6 patients with portal hypertension who underwent splenectomy alone without devascularization. These 4 patients with paradoxic elevation were splenectomized 4 wk and $\text{2}\text{1}\text{2}$, 20, and 29 yr previously. However, none of 5 splenectomized patients without portal hypertension showed the paradoxic elevation. The reason why the paradoxic elevation was observed after splenectomy only in patients with portal hypertension but not in patients without portal hypertension may be sought for in the changes of portal venous flow rather than splenectomy itself.     

Serum levels of neurophysin in pregnancy and in the postpartum period: relation to 17beta-estradiol levels.

Changes in serum neurophysin levels were studied in women during normal pregnancy and after delivery. Neurophysin was elevated as early as the sixth week of gestation and gradually increased until, at the latest, the twentieth week. A significant positive correlation was obtained between serum concentrations of neurophysin and those of 17beta-estradiol. In serum samples with 17beta-estradiol levels exceeding 5 ng/ml, neurophysin was consistently elevated above the normal control range. After delivery, serum neurophysin concentrations declined quite rapidly. The levels returned to those of nonpregnant women by 6 days postpartum. These results support the view that a high rate of secretion of 17beta-estradiol may be one of the factors responsible for the elevated levels of serum neurophysin in pregnancy and that this effect disappears rapidly after the disposal of estrogen, independent of the duration of the elevated estrogen levels.     

Instability of fasting blood glucose values in noninsulin-dependent diabetic patients with long-term insulin treatment

We studied serum free C-peptide immunoreactivity (CPR) and the coefficient of variation (CV) of fasting blood glucose values (FBG) in 26 insulin-treated patients with non-insulin-dependent diabetes mellitus (NIDDM) in relation to the duration of insulin treatment. Serum free CPR responses during 100 g oral glucose tolerance test (OGTT) were significantly lower in patients with insulin treatment for five years or more than in those with insulin treatment for less than five years although their previous immunoreactive insulin (IRI) responses during OGTT before insulin treatment showed no significant difference. CV of FBG was found to be significantly higher at the time of this study (20.6 +/- 7.8%, mean +/- SD) than at the second year of insulin treatment (15.3 +/- 7.7%, P less than 0.05) in the patients with insulin treatment for five or more years but did not show any significant difference in patients with insulin treatment for less than five years at the corresponding times. Thus we measured CV of the FBG in NIDDM patients at various intervals during the long-term insulin or oral hypoglycemic agent treatment in another study. In 20 patients with insulin treatment, CV of FBG was found to be significantly different among the various intervals during insulin treatment (P less than 0.0025). It was significantly higher at the eight year (22.2 +/- 8.6%) and 12th year (21.9 +/- 9.1%) than at the second year (14.9 +/- 6.1%) and fifth year (15.0 +/- 6.7%) of insulin treatment (P less than 0.025, P less than 0.025; P less than 0.05, P less than 0.01, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of phentolamine on the somatostatin-induced inhibition of glucagon and insulin secretion.

Synthetic cyclic somatostatin was infused into either the cranial pancreaticoduodenal artery or the femoral vein of anesthetized dogs with or without previous administration of phentolamine. Somatostatin infused into the pancreatic artery at a dose of 50 ng/kg/min for 10 min caused significant decreases in blood flow and plasma basal concentrations of both glucagon and insulin in the cranial pancreaticoduodenal vein, resulting in a profound decline of bihormonal output during the infusion. Arterial plasma glucose was not reduced during the administration of somatostatin in the pancreatic artery. These somatostatin-induced decreases failed to be eliminated by a 0.2 mg/kg injection of phentolamine into the femoral vein followed by a 9-min infusion of this alpha-adrenergic blocker (0.02 mg/kg/min) into the pancreatic artery immediately prior to the somatostatin administration. An inhibition of glucagon and insulin output and a fall of plasma glucose caused by somatostatin (1.7 microgram/min) infused into the femoral vein for 30 min also were not abolished by a prolonged and simultaneous infusion of phentolamine (0.2 mg/min) into the femoral vein over a period of 2 hr. These results indicate that alpha-adrenergic receptor mechanisms do not play a major role in the inhibition of islet glucagon and insulin secretion by somatostatin.     

Measurement of left ventricular ejection fraction in pediatric patients using the nuclear stethoscope

Left ventricular (LV) ejection fraction (EF) was measured in 25 patients, aged 2 weeks to 20 years (mean 8.6 years), using a portable nonimaging scintillation stethoscope. Technically satisfactory studies were obtained in 23 patients. LVEF was validated by cineangiography in 19 patients and by standard gated blood pool scintigraphy in 4. EF measured by the nuclear stethoscope correlated well with values obtained by cineangiography or scintigraphy (r = 0.869, p less than 0.001) over a wide range of EF values (18 to 79%). In children younger than 5 years (n = 11), the correlation (r = 0.728, p less than 0.02) was less satisfactory than in those older than 5 years (r = 0.926; p less than 0.001). Although modifications in the instrument and further clinical trials with the stethoscope are needed before the device becomes clinically useful to pediatric cardiologists, our data indicate that the nuclear stethoscope can provide reliable assessment of LVEF in pediatric patients.     

Effect of glycerol on triglyceride metabolism in the rat

Lipid metabolic studies were carried out on the male Wistar rats fed on glycerol-rich diet in order to elucidate the mechanism of glycerol-induced hypertriglyceridemia. No difference was found between the glycerol fed rats and the control rats in the rate of triglyceride secretion from the liver measured by the Triton WR-1339 method as well as in the rate of incorporation of labeled glycerol into liver triglyceride. The facts that the half-life of the intravenously injected intralipid^® in the blood was significantly delayed in the glycerol fed rats and that the lipoprotein lipase activity released from epididymal adipose tissue of the glycerol fed rats was markedly decreased to 19% of that of the control rats seem to account for the serum triglyceride elevation induced by the glycerol feeding.     

Hepatic triglyceride lipase in diabetic dogs

Circulating triglyceride is cleared by a combination of hepatic triglyceride lipase (H-TGL) and lipoprotein lipase (LPL). Although LPL has been extensively studied in diabetes, the effect of insulinization on H-TGL activity has not been well characterized. To determine whether H-TGL activity is altered in insulin-deficient diabetes, postheparin plasma was obtained from eight beagle dogs: three normal (nondiabetic) control dogs and five pancreatectomized diabetic dogs were studied acutely in poor diabetic control (underinsulinized), and again in short-term good control (well insulinized). Plasma glucose, measured at the start of the studies, was 88 +/- 10 mg/100 mL (mean +/- SD) in the normal control dogs, 434 +/- 31 mL in pancreatectomized dogs in poor diabetic control, and 87 +/- 16 in good diabetic control. Peak (five minutes) postheparin plasma H-TGL activity was increased in dogs in poor diabetic control (212 +/- 43 nmol FFA/min/mL) v the normal control dogs (135 +/- 21 nmol FFA/min/mL, P less than 0.02). When the dogs were in good diabetic control, the peak H-TGL (202 +/- 40 nmol FFA/min/mL) was also significantly increased compared with the level in normal dogs, while the sum of five and 45 minute postheparin H-TGL levels for the dogs in good diabetic control was less than when they were in poor diabetic control (P less than 0.01). Thus, insulin-deficient diabetes in dogs increases H-TGL, and short-term improvement of glycemic control with insulin partially corrects this increase.     

The effects of streptozotocin diabetes on hepatic triglyceride lipase activity in the rat

The function of the hepatic triglyceride lipase (H-TGL) is not yet clear. The purpose of the present study was to investigate the possible hormonal regulation of H-TGL. Postheparin plasma was obtained 3 min after the intravenous injection of 50 U/250 g body weight of heparin into male Wistar rats. The lipase activities were measured using substrate containing [¹⁴C] triolein emulsified with gum arabic and were expressed in μmoles of free fatty acid released/ml/hour (mean ± SD). H-TGL was the lipase activity remaining after inhibition of lipoprotein lipase (LPL) by 1.0 M NaCl. Diabetic rats were prepared by intravenous injection of streptozotocin (STZ), 65 mg/kg body weight. The contributions of H-TGL and LPL to the total plasma triacylglycerol hydrolase (TGH) activity depend on the amount of heparin injected and the time of blood withdrawal after heparin injection. H-TGL was maximally released at higher heparin (50 U/250 g body weight) concentrations, compared to LPL which was maximally released at lower heparin (5 U/250 g body weight) concentrations. H-TGL was significantly higher at 3 min after the injection of 50 U of heparin/250 g body weight than at 20 min. Twenty-four-hour fasting produced a significant fall in H-TGL compared to H-TGL in fed rats. Total TGH was significantly lower in diabetic rats 3 days after STZ injection. In diabetic rats 3, 5, and 7 days after STZ injection, H-TGL were significantly lower than those in control rats. H-TGL and H-TGL/total TGH were 9.49 ± 0.99 and 0.551 ± 0.071, respectively, in rats 3 days after STZ injection, compared to H-TGL (13.46 ± 0.69) and H-TGL/total TGH (0.739 ± 0.052) in control nondiabetic rats. When diabetic rats were treated with insulin, total TGH (14.37 ± 3.01) and H-TGL (6.77 ± 4.12) rose to 25.16 ± 1.02 (total TGH) and 16.46 ± 1.13 (H-TGL), that were comparable to activities in control nondiabetic rats. Separation of H-TGL and LPL was performed using heparin-Sepharose affinity chromatography of postheparin plasma. The enzyme activity of peak I from STZ rats, which is eluted by 0.72 M NaCl-Veronal buffer, pH 7.4 and corresponds to H-TGL, was approximately half the activity from control rats. TGH released by heparin from isolated rat liver parenchymal cells was investigated. The enzyme activities released from isolated liver parenchymal cells prepared from STZ rats was approximately half that from control rats. The role of insulin in the regulation of LPL has been well documented. Our findings suggest that H-TGL also is under hormonal regulation by insulin in rats.     

Failure to demonstrate stimulatory effect of prolactin on vitamin D metabolism in vitamin-D-deficient rats.

The effect of administration of bovine prolactin in vivo on renal 1 alpha-hydroxylase (1 alpha-OHase) activity was investigated using thyroparathyroidectomized and sham-operated vitamin-D-deficient male rats. A high dose (1.5 IU/hr) and a low dose (0.3 IU/hr) of bovine prolactin was constantly infused into the cannulated femoral vein for 6 hr or 30 hr. The accumulation of 1 alpha, 25-hydroxyvitamin D3 [1 alpha, 25-(OH)2-D3] in plasma produced from 25-hydroxy-vitamin D3 (25-OH-D3) was calculated from the 6-hr conversion of intravenously injected [3H]-25-OH-D3 to [3H]-1 alpha, 25-(OH)2-D3. Both high dose and low dose of prolactin administration caused no significant stimulatory effect on 1 alpha-OHase activity in TPTX animals. Also, in sham-operated rats the prolactin treatment produced no significant change in the 1 alpha-OHase activity. Plasma calcium concentrations showed a tendency to increase slightly. These results suggest that prolactin has no direct stimulatory role on renal 1 alpha-OHase activity in rats. Its effect on calcium metabolism may be mediated by a different mechanism(s).     

Effect of vasoactive intestinal polypeptide infused intrapancreatically on glucagon and insulin secretion

Synthetic vasoactive intestinal polypeptide (VIP) was infused at a dose of 50 ng/kg/min for 10 min into the cranial pancreaticoduodenal artery in anesthetized dogs. Both mean blood flow and plasma glucagon concentration in the cranial pancreaticoduodenal vein were significantly enhanced during the infusion, indicating a great augmentation in glucagon output. The pancreatic venous plasma concentration of insulin was not significantly raised, but its output increased during the infusion, again due to the increase in plasma flow. Plasma concentration of glucagon in the femoral artery was not significantly augmented, whereas that of insulin was enhanced during VIP infusion. Mean arterial plasma glucose levels rose gradually during the infusion. Intrapancreatic pretreatment with propranolol failed to exert any significant inhibiting effect upon the VIP-induced enhancement in plasma glucose, pancreatic venous blood flow, or bihormonal output. These results suggest that the vasoactive polypeptide of intestinal origin may regulate the function of the endocrine pancreas and that this effect may not be mediated mainly via the β-adrenergic receptor system.     

Pseudo right atrial overloading pattern in complete defect of the left pericardium

Two cases with complete defect of the left pericardium showing tall and peaked P waves in the right precordial leads are described. A review of the literature has yielded nine cases with uncomplicated complete defect of the left pericardium showing similar P wave changes.Right heart catheterization, performed in nine cases, including the present two cases, revealed no evidence of an intracardiac shunt in any case and normal intracardiac pressures in eight cases. Therefore, this P wave change seems to be related to intra-throacic shift in cardiac position permitted by the absence of the restraining pericardium.     

Angiotensin-converting enzyme in diseases of the liver

Serum angiotensin-converting enzyme activity was measured in various diseases of the liver. Activity increased in progressive order in patients with chronic persistent hepatitis, chronic aggressive hepatitis, and liver cirrhosis. Activity was increased also in patients with acute hepatitis. On the other hand, patients with fatty liver had normal angiotensin-converting enzyme activity and patients with extrahepatic obstructive jaundice showed subnormal activity. Although the mechanism for these enzymatic changes in diseases of the liver remains to be elucidated, serum angiotensin-converting enzyme determination may be useful in the diagnosis of diseases of the liver under certain conditions.     

Clinical and experimental studies of the effects of atrial extrastimulation and rapid pacing on atrial flutter cycle: Evidence of macro-reentry with an excitable gap

To investigate the mechanism of atrial flutter in human beings, effects of atrial pacing and extrastimulation on flutter cycle length were studied. In four cases, properly timed extrastimuli shortened the F-F interval after the extrastimulus without affecting the stimulus-encompassing interval. The width of the excitable gap ranged from 14 to 25 percent of the basic flutter cycle length (mean ± standard deviation 20.4 ± 4.1). Entrainment to rapid atrial pacing was demonstrated in each case. The width of the entrainment zone nearly coincided with that of the excitable gap in each case.In 16 dogs, atrial flutter was induced by electrical stimulation after an obstacle was placed between the superior and the inferior venae cavae according to Rosenblueth and Garcia Ramos. In 11 dogs, extrastimuli shortened the F-F interval next to the stimulus-encompassing interval as in the clinical study. The excitable gap, measured in six dogs, ranged from 15 to 24 percent of the basic flutter cycle length (mean 20.6 ± 3.0). Entrainment was observed in six dogs studied and, during entrainment, the atrial activation sequence was almost the same as that during the basic flutter cycle.It is concluded that shortening of the F-F interval next to the stimulus-encompassing interval that is not affected favors macro-reentry as the mechanism of atrial flutter in human beings.     

Age-related changes in auto- and natural antibody in the werner syndrome

To assess the immunologic disturbance in Werner syndrome, antibodies to “intrinsic” (auto)antigens (anti-DNA antibodies and rheumatoid factors) and “natural” antibodies to “extrinsic” antigens (hemagglutinins for sheep red cells and antibodies against ABO blood type antigens) were measured in serum samples from 16 patients with Werner syndrome and compared with those from 150 healthy persons ranging in age from less than a year to 98. Employing a sensitive solid-phase radioimmunoassay, we found that the levels of both anti-double-stranded and anti-single-stranded DNA antibodies in the IgG class gradually increased with age in normal donors; a more abrupt increase with age was observed In those with Werner syndrome, although they lacked any complication of renal disease and hypocomplementemia. The titers of rheumatoid factor detected by sensitized sheep cell agglutination also gradually rose in normal persons and patients with Werner syndrome. In contrast, the titers of natural antibodies declined with age in both groups. These disturbances in antibody production suggested that Werner syndrome expresses an accelerated form of aging in immunologic aspect.     

Clinical features and course of aortitis syndrome in Japanese women older than 40 years

The clinical features and course of aortitis syndrome were studied in 11 women older than 40 years of age. The patients were Japanese women, mean age 57 +/- 6 years old, who were followed for 6.9 +/- 3.8 years. Data from 24 young patients were used for comparison. In the older patients, systemic hypertension (73%), calcification of the aorta (73%), left ventricular hypertrophy (92%) and cardiomegaly (82%) were frequent, whereas the erythrocyte sedimentation rate was normal in 5 patients and only slightly accelerated in 6. C-reactive protein was positive in 2. The incidence of cardiac involvement and inflammatory signs was significantly different from findings in the young patients. Aortic regurgitation (AR) (55%) was significantly more frequent and renal artery stenosis was not observed. Other arterial lesions revealed a pattern similar to those seen in the young patients. An irregular luminal surface, kinking and calcification were present in the lesions in the older patients. The survival rate at 5 years was 80%. Five of 6 patients with AR had congestive heart failure, 4 of whom died. One died after a stroke. Thus, aortitis syndrome in older patients has a long course. There is usually an associated AR, renal artery stenosis is rare and other arterial lesions do not change a great deal. The prognosis may be good, but depends on the association of AR.