We evaluated the hypothesis that thiazide-induced hypercalcemia reflects potentiation of the cAMP response to parathyroid hormone (PTH) consequent to inhibition of phosphodiesterase in bone and kidney. A panel of thiazide diuretics did inhibit low-Km phosphodiesterase activity from bone homogenates. However, furosemide, a nonthiazide diuretic that does not promote calcium retention, was more potent a phosphodiesterase inhibitor than either chloro- or hydrochlorothiazide (CTZ, HCTZ). Thiazides did not influence basal or PTH-stimulated cAMP levels in incubated calvaria or renal cortical slices. Administration of CTZ or HCTZ to rats for 4 days did not affect basal cAMP, nor did such treatment potentiate the cAMP response in Calvaria to infusion of parathyroid extract in vivo. CTZ, HCTZ, and furosemide increased basal adenylate cyclase from renal cortex but did not affect PTH-stimulated activity. Adenylate cyclase from bone was not affected by thiazides but was inhibited by furosemide. Thiazide treatment potentiated the calcemic response to parathyroid extract in vivo but did not affect the calcemic response to dibutyryl cAMP. We conclude that potentiation of the cAMP response to PTH does not underlie the unique effects of thiazides on calcium metabolism.

Animals↗

PubMed1978

Multidisciplinary group therapy for rheumatoid arthritis.

Explore the source record for details and available documents.

Adult↗

PubMed1977

Some characteristics of Mozambican Shangaans with primary hepatocellular cancer.

Certain characteristics of 328 Mozambican male Shangaans with primary hepatocellular cancer (PHC) have been compared with those of 163 Shangaan men with hepatomegaly from causes other than PHC and with those of 122 Black Southern African men with the same tumour but who belonged to tribes other than the Shangaan. Shangaans with PHC were significantly younger than non-Shangaans with the tumour (mean age 33,4 cf. 40,0 years; Pless than 0,001). They also had a significantly higher positivity rate of alpha-fetoprotein by immunodiffusion (71,4%) than the non-Shangaans (16%), although in other respects the tumours appeared to be similar. Cirrhosis of the non-tumorous part of the liver was present at necropsy in 62% of the Shangaans and in 66% of the non-Shangaans. The hepatitis B (surface) antigen (HBsAg) was detected in the serum of 60% of the Shangaans with PHC compared with only 9% of the controls. The antigen was present in 53,4% of the non-Shangaans with PHC (the difference between this fifure and that in the Shangaans was not significant). HBsAg was detected in the serum of 64% of the Shangaans with PHC and cirrhosis, but also in 74% of those with the tumour without associated cirrhosis. The possible role of the hepatitis B verus in the aetiology of PHC is considered in the light both of these findings and of the possibility that the frequency with which the tumour is associated with cirrhosis may be decreasing in Shangaans. Some of the dietary habits of the Shangaans with PHC were compared with those of the controls. Virtually all the patients with PHC, but also almost all the controls, ate groundnuts in large quantities from an early age, as well as cashew nuts in smaller amounts. Cycad pips, mopani leaves and pods, mopani worms and locusts were not eaten by significantly more of the Shangaans with PHC than the controls. The limitations of this type of dietary analysis are discussed.

Adolescent↗

PubMed1977

Chronic polyarthritis associated with hypogammaglobulinemia. A study of two patients.

Two adult patients with hypogammaglobulinemia and chronic synovitis were studied. Synovial tissue and fluid were examined by histologic, virologic, and immunologic methods. The synovium lacked characteristic histologic features of rheumatoid arthritis, and B lymphocytes were absent from the synovial tissue, fluid, and peripheral blood. These 2 patients may represent a form of chronic synovitis produced in the absence of any B lymphocyte response.

Agammaglobulinemia↗

PubMed1977

MacAndrew MMPI alcoholism scale: alcoholism and drug addictiveness.

MMPI Form R answer sheets of 222 successive black and white male inpatients referred for psychological testing in a VA general medical and surgical hospital were scored on the MacAndrew Alcoholism and the Cavior Heroin Addiction Scales. The MacAndrew Scale with 74% accuracy provided a practical screening device for identifying alcoholics. It did not significantly differentiate patients with a history of drug abuse from patients with a history of alcoholism. The Cavior He Scale was not so valid a screening device for identifying drug addicted patients in our total population. Each scale in a special way seems to be measuring a "general addictive propensity."

Alcoholism↗

PubMed1977

Cyclic AMP production in rat calvaria in vitro: interaction prostaglandins with parathyroid hormone.

We studied the cAMP response of cultured rat calvaria to parathyroid hormone (PTH) and prostaglandins (PG) in order to test the hypothesis that PTH action is mediated by PG. PTH and PGE1 each caused an 8-fold increase in tissue cAMP during 15 min incubation. There was an additive response to the combination of the two agonists at maximally effective individual concentrations. Similar results were obtained when adenylate cyclase activity in bone homogenates were measured. Calvaria incubated for 60 min with PGE1 were desensitized to further stimulation by PGE1, but responded normally to PTH. Indomethacin, aspirin and phenylbutazone, 10(-5)M, had no effect on the cAMP response to PTH. At millimolar concentration these agents did block the hormone response; however, the response to exogenous PGE1 and the fluoride-sensitive adenylate cyclase were also inhibited. Thus, it appears that the effects of high concentrations of the anti-inflammatory drugs on cAMP formation are non-specific. Our results suggest that receptors in bone for PTH and prostaglandins are separate and independent, and that the cAMP response to PTH is not mediated by prostaglandins.

Adenylyl Cyclases↗

PubMed1977

"Nursing" the organization.

Explore the source record for details and available documents.

Clinical Competence↗

PubMed1976

Morphine-based secondary reinforcement: effects of different doses of naloxone.

The effects of different doses of naloxone on morphine-based secondary reinforcement were studied in rats. On the first day a neutral stimulus (buzzer) was repeatedly paired with intravenous morphine infusions. Drug treatments consisted of Low, Medium, or High Naloxone doses, or No Naloxone. The next day the ability of the buzzer and saline infusion to support lever pressing was tested. High Naloxone blocked, and Low Naloxone partially blocked this morphine-based secondary reinforcement. Subjects in the Medium Naloxone group demonstrated an apparent avoidance of the lever, suggesting that the morphine infusions were aversive at this dosage level of naloxone. The secondary reinforcement tests reliably predicted behavior on a subsequent test for acquisition of morphine-seeking behavior.

Animals↗

PubMed1976

Narcotic blockade, length of addiction and persistence of etonitazene consumption in rats.

Rats were given daily trials to determine relative preference for an opiate (etonitazene, ETZ) or for water. Animals with a greater history of previous drug exposure developed ETZ preferences more rapidly than did relatively drug-naive animals. Pretreatment with adequate blocking doses of naloxone reduced drug intake to near zero in most subjects. However, animals with the greatest history of prior addiction continued to drink large quantities of ETZ, despite pretreatment with relatively large doses of naloxone. These results can be explained by assuming that stimuli associated with the reinforcing properties of the opioid solution become strong conditioned reinforcers, capable of maintaining responding for long periods of time despite blockade of the reinforcement properties of the drug.

Analgesics, Opioid↗

PubMed1976

Estrogens and the human male.

Explore the source record for details and available documents.

Adrenal Cortex↗

PubMed1976

Regulation of the beta- and delta-hemoglobin genes. A family with hereditary persistent fetal hemoglobin and beta-thalassemia.

We have studied a 41-year-old black male with the simultaneous occurrence of hereditary persistence of fetal hemoglobin (HPFH) and beta-thalassemia, and his two postadolescent sons, each heterozygous for one of the traits. The son heterozygous for beta-thalassemia had an elevated Hb A2, but the index case did not. The data from this pedigree indicate that the delta-allele trans to the beta-thalassemia gene was reponsible for the increased delta-chain production. Evidence from other cases of combination HPFH and beta-thalassemia indicates that regulation of the beta- and delta-chain production in beta-thalassemia is heterogeneous with respect to mechanism.

Adolescent↗

PubMed1976

Working together for our future.

Explore the source record for details and available documents.

Jews↗

PubMed1975

Cyclic nucleotide phosphodiesterase from bone: characterization of the enzyme and studies of inhibition by thyroid hormones.

Studies were carried out to characterize the cyclic nucleotide phosphodiesterase from rat calvaria. 25-40% of the total enzyme activity was membrane-bound. pH, magnesium, and temperature requirements conformed closely to those established for phosphodiesterase from other tissues. Kinetic evidence was found for dual enzyme activities with different substrate affinities for both the particulate and soluble enzyme. Apparent Kms for the soluble enzyme (3.5 times 10-6 and 2.5 times 10-5M) approximated those for the particulate enzyme (5.7 times 10-6 and 2.5 times 10-5M). L-Thyroxine, 10-5M, inhibited competitively the low- and high-Km enzymes from both the particulate and soluble fractions (Ki equals 1.7 times 10-5M). T4 was more potent an inhibitor than T3 with all enzyme fractions, but this relationship could be altered by adding protein to the incubation mixtures. Tests of diverse thyroid hormone analogues showed that 1) T4 and its derivatives were more potent than T3 and its analogues; 2) acetic and propionic acid derivatives were more potent than the thyronines; 3) "reverse T3," an antagonist of some T3 actions, also inhibited phosphodiesterase. These effects were not attributable to chelation, and were not duplicated by iodide or by other physiologically inactive thyroid hormone analogues.

Animals↗