Direct and indirect actions of impromidine (a new H2-receptor agonist) on atrial tissue

The maximum chronotropic response of rabbit atria to impromidine, a new H₂ agonist is $\text{?72\%}$ of the histamine response, but the dose needed to cause a half-maximum increase in rate is 1,000 times less for impromidine than for histamine. Pharmacological data using propranolol strongly suggests that the release of norepinephrine is partially responsible for this response, and the effect of diphenhydramine suggests that histamine may be released as well. Improidine also appears to release both compounds when guines pig atria are tested.Before impromidine can be characterized as a specific and potent H₂-receptor agonist, additional data concerning some of its indirect actions must be obtained.     

Familial pseudohypoparathyroidism without somatic anomalies.

A family is described in which affected individuals showed pseudohypoparathyroidism, with hypocalcemia, hyperphosphatemia and increased serum levels of parathyroid hormone, but none of the somatic anomalies frequently associated with this disorder. The untreated individuals showed radiologic evidence of osteitis fibrosa. The administration of parathyroid hormone evoked only a slight increase in the excretion of cyclic adenosine monophosphate but no change in the renal tubular reabsorption of phosphate and no rise in the serum calcium level. The infusion of ethylenediamine tetra-acetic acid caused an appropriate increase in the serum level of parathyroid hormone, but again there was no apparent renal or skeletal response to the hormone. There were no associated abnormalities in calcitonin, thyrotropin or prolactin levels and no thyroid dysfunction. Therapy with vitamin D corrected the hypocalcemia but did not improve the renal and skeletal responsiveness to parathyroid hormone. The inheritance of the disorder in this family was compatible with an autosomal dominant mode with variable penetrance, but other modes could not be excluded.     

Isolation of a highly active H+-ATPase from beef heart mitochondria

The lysolecithin extraction procedure originally described by Sadleret al. (1974) has been modified to yield a H⁺-ATPase with high levels of P_i-ATP exchange activity (400–600 nmol × min^–1 × mg^–1). This activity is further enhanced (1400–1600 nmol × min^–1 × mg^–1) following sucrose density gradient centrifugation in the presence of asolectin. This enhancement results in part from a lipid-dependent activation and in part from removal of inactive complexes. The H⁺ translocating activity of the complex has been determined spectrophotometrically using binding of oxonol VI as an indicator of membrane potential. P_i-ATP exchange, ATP hydrolysis, and oxonol binding are sensitive to energy-transfer inhibitors (oligomycin, rutamycin) and/or uncouplers (DNP, FCCP).     

A computer program for the analysis of crossover designs.

We describe a program, CROSS, which we have written to obtain potency estimates and other parameters for bioassay data from assays of crossover design. The program permits testing of all assays for statistical validity and calculates the complete analysis of variance for assays of balanced design. The form of data input and the complete documentation of assay results make this program particularly useful for anyone carrying out crossover assays on a routine basis. The analysis of variance presented is also useful for more general biological or medical situations.     

Synthesis of enkephalins by guinea-pig striatum in vitro.

A method for obtaining incorporation of labelled amino acids into enkephalins of guinea-pig striatum in vitro and isolating the labelled enkephalins is described. The incorporation of [3H]tyrosine increases with time after a delay of 2 h. Cycloheximide added during this time, but not at later stages, inhibits incorporation. The results indicate that the enkephalins are produced locally, probably by ribosomal synthesis. The lag period may be due to the time required for the synthesis of precursors and their conversion to the enkephalins.     

Health Hazard Appraisal Counseling—Continuing Evaluation

A program of annual health examinations was expanded to include counseling based on a computerized appraisal of individual patients'' specific health risk factors. Data obtained from a specially designed questionnaire, laboratory tests and a physical examination yielded a health hazard appraisal showing a number of weighted risk factors and their relation to ten leading causes of death as determined for that patient. From all of this information, a “risk age” was developed which could then be compared with the patient''s “true age.” The results were reviewed with each patient, and methods of correcting health hazards were stressed. The first annual retesting of a group of 107 examinees showed a net risk age reduction of 1.4 years (formerly reported in this journal). The longer term follow-up reported in this paper showed a net risk reduction of 2.38 years in a group of 26 examinees. The net risk age reduction in the two groups represented 32 and 40 percent, respectively, of the achievable risk age reduction when patients comply with suggestions made during risk reduction counseling. These findings indicate that health hazard appraisal counseling is an effective method of altering priorities of health practices.