Myelin in femoral nerve segments obtained at autopsy was isolated quantitatively by a series of discontinuous and continuous flotation procedures. The total amount of myelin isolated from these nerves was expressed as the sum of cholesterol, glycolipid, phospholipid, and protein and averaged 2.6±0.4 mg/g in a group aged 60-77 yr compared with 10.8±1.9 mg/g of nerve in a group aged 35-58 yr. The lower value in the older group remained apparent whether the myelin content was related to the whole nerve segment, its unit length or weight. This indicates that the decrease is an absolute one, not related to a change with aging in the nonmyelin content of nerve.
Norton Spritz, Harbhajan Singh, Barbara Geyer
Three distinct immunoreactive species of parathyroid hormone (PTH) are present in human serum. One has an estimated mol wt of 9,500 and probably represents glandular hormone, the second 7,000-7,500 mol wt, and the third 4,500-5,000 mol wt. In order to assess the biological activity of these circulating forms of PTH, we determined their ability to activate renal cortical adenylate cyclase. The 9,500 mol wt and 4,500-5,000 mol wt fractions produced four- to sixfold increases in cyclic 3′,5′-AMP accumulation above control; the 7,000-7,500 mol wt fraction was inactive. None of the fragments had any effects on phosphodiesterase activity. Antiserum to bovine PTH did not block the activation of adenylate cyclase by either the gragments or bovine PTH. The data suggest that a large proportion of circulating immunoreactive human PTH is biologically active and that the biologically and immunologically active sites of the hormone are distinct.
Janet M. Canterbury, Gerald S. Levey, Eric Reiss
The administration of exogenous iodides (saturated solution of potassium iodide, SSKI) to normal male volunteers resulted in a significant decrease in the serum concentration of thyroxine (T4) and triiodothyronine (T3) and a significant increase in serum concentration of thyrotropin (TSH). During the control period (phase I), serum concentrations of T4 averaged 6.9±1.8 μg/100 ml (mean ±SD), T3 106±15 ng/100 ml, and TSH 3.7±1.3 μU/ml. During the administration of 1 drop of SSKI twice daily for 11 days (phase II), there was a small but significant decrease in the serum concentration of T4 and T3 (5.8±1.6 μg/100 ml and 91±19 ng/100 ml, respectively) and a small but significant increase in the serum concentration of TSH (6.0±3.5 μU/ml). During the administration of 5 drops of SSKI twice daily (phase III) over the following 12-19 days, these changes persisted, except for a small increase in the serum concentration of T3 (97±20 ng/100 ml), which was statistically significant when compared to values obtained during phase II. Values returned to control levels 14 days after withdrawal of SSKI. Almost all these observed changes took place within the limits of the normal range. It is postulated that, in euthyroid individuals, iodides specifically inhibit release of T4 and probably of T3. The resulting slight decrease in values for serum T4 and T3 elicits a small increase in TSH secretion which, it is postulated, antagonizes the inhibition of hormone release induced by iodides. As a result, a new equilibrium is reached which maintains the euthyroid state.
Apostolos G. Vagenakis, Patricia Downs, Lewis E. Braverman, Albert Burger, Sidney H. Ingbar
The relative roles of triiodothyronine (T3) and thyroxine (T4) in modulating pituitary responsiveness to thyrotropin-releasing hormone (TRH) have been assessed. (a) 10 hyperthyroid patients with elevated serum T2 and T4 levels showed no pituitary response to TRH. After 2 wk of propylthiouracil therapy T4 levels had fallen to normal in only five patients while T2 levels were normal in all. Pituitary responsiveness to TRH returned in all patients with normal or high T4 concentrations. (b) Patients with isolated elevations of serum T3 (T3 toxicosis) failed to respond to TRH. TRH responsiveness was restored when T3 levels fell to normal after propylthiouracil therapy. (c) When pituitary responsiveness to TRH was tested 60 min after a single oral dose of 50 μg of T3, which increased serum T3 levels to slightly above the normal range, no rise in thyrotropin (TSH) was seen in six subjects. These findings indicate that T3 elevations alone can rapidly inhibit pituitary responsiveness to TRH.
Louis Shenkman, Terunori Mitsuma, Charles S. Hollander
The effects of stimulation of the mixed autonomic nerve to the dog pancreas has been studied under conditions in which both pancreaticoduodenal vein blood flow and insulin concentration were determined. Stimulation resulted in increased insulin output, which was blocked by prior administration of atropine. Blood flow was reduced by stimulation in proportion to the rate of stimulation. At 40 stimuli/s a maximum effect was found at 1 min with a gradual return toward base line despite continued application of the stimulus. Atropinization had no effect on blood flow changes. Insulin responses to 0.1 g/kg glucose were reduced on the average 40% by simultaneous stimulation of the pancreatic nerve at 40 cycles/s in atropinized animals. These studies establish this preparation as a reproducible model for the direct examination of autonomic influences on endocrine pancreatic function. From them it is concluded that the nerve supply to the endocrine pancreas of the dog is sufficient to inhibit insulin secretion by activation of the sympathetic nerves and to stimulate insulin secretion by activation of the parasympathetic nerves.
Daniel Porte Jr., Lucien Girardier, Josianne Seydoux, Yasunori Kanazawa, Jean Posternak
Deficiency of cystathionine synthase activity results in the clinical syndrome of homocystinuria. Using phytohemagglutinin (PHA)-stimulated lymphocytes as a readily available source of this enzyme, its activity has been compared in 48 control subjects, seven homozygotes affected with homocystinuria, and 17 obligate heterozygotes. PHA-induced enzyme levels were highest in controls (mean ±SEM, 666.9±70.2 pmol cystathionine formed/mg protein per 4 h), intermediate in heterozygotes (114.4±27.3), and absent to severely deficient in homozygotes (2.0±1.6). Since only three of the 17 values from the obligate heterozygotes overlapped into the control range, this simple method may become clinically useful for heterozygote detection of carriers of the gene for abnormal cystathionine synthase. In addition, this system for induction of cystathionine synthase in lymphocytes has a more general relevance to human biochemical genetics in that it demonstrates that the absence of an enzyme in a normal cell does not preclude using that source for diagnosis of genetic disease if the enzyme can be induced.
Joseph L. Goldstein, Barbara K. Campbell, Stanley M. Gartler
Human red blood cells display under appropriate circumstances a ouabain-sensitive K-K exchange when the flux measurements are made using radioisotopes. Such an exchange complicates measurements of the coupling of Na outflux to K influx in cells which are partially depleted of energy sources by deprivation of glucose since the K-K exchange has been found to be increased in depleted cells. When the measurements of flux are made by estimating net cation movements chemically, it is found that glucose deprivation results in a fall in both ouabain-sensitive Na outflux and ouabain-sensitive K influx. Since both fluxes fell in concert, there is no reason for believing that the fluxes are not coupled or that the source of ATP for the Na outflux is different from that for the K influx.
John R. Sachs
Studies were performed on 11 healthy men to evaluate the role of low pressure baroreceptors in the reflex forearm vasoconstrictor responses (plethysmography) to venous pooling produced by lower body negative pressure. Lower body negative pressure (LBNP) at - 5, - 10, - 20, and - 40 mm Hg lowered central venous pressure by 42, 59, 74, and 93%, respectively, and decreased forearm vascular conductance by 24, 29, 34, and 40%, respectively. The decreases in forearm blood flow and conductance during the low levels of venous pooling (LBNP - 5 and - 10 mm Hg) occurred without significant changes in arterial pressure, arterial dP/dt. and heart rate. These results with the low levels indicate that maneuvers which decrease venous return and central venous pressure in man can influence forearm vascular tone without significant changes in the determinants of carotid and aortic baroreceptor activity. During high levels of venous pooling (LBNP - 20 and - 40 mm Hg), significant decreases in arterial pressure and dP/dt and significant increases in heart rate accompanied the further reductions in central venous pressure, forearm blood flow, and forearm vascular conductance. About 73% of the decrease in conductance during venous pooling at LBNP - 40 mm Hg, which was sufficient to decrease arterial pressure and activate high pressure baroreceptor reflexes, occurred during low levels of venous pooling at LBNP - 10 mm Hg without changes in arterial pressure. This suggests that much of the forearm vasoconstriction with the high levels of venous pooling, which were sufficient to decrease arterial pressure, may be accounted for by reflexes originating in areas other than high pressure baroreceptors. The results of these studies suggest that low pressure baroreceptors exert an important influence on forearm vascular tone during decreases in venous return and central venous pressure in man.
Robert P. Zoller, Allyn L. Mark, Francois M. Abboud, Phillip G. Schmid, Donald D. Heistad
A collagenase and a neutral protease have been insolated and characterized from primary cultures obtained from rheumatoid subcutaneous nodules. Release of both active enzymes was maximal between the 3rd and 7th days of culture and was stimulated by the presence of small amounts of colchicine (0.1 μg/ml) added to the culture medium.
Edward D. Harris Jr.
Histocompatibility antigen HL-A8 was found in 58% of 26 patients with dermatitis herpetiformis (DH) compared to 24% of a normal group. This difference in antigen frequency is significant at the P < 0.003 level. In a previous study, the frequency of this same genetic marker was found to be significantly increased in patients with gluten-sensitive enteropathy (GSE) (88% in patients vs. 22% in controls). The finding of an increased incidence of the HL-A8 antigen in both DH and GSE supports the concept that these diseases are related and provides a genetic basis for the association between the two.
Stephen I. Katz, Z. Myron Falchuk, Mark V. Dahl, G. Nicholas Rogentine, Warren Strober
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