Familial dyslipidemic hypertension. Evidence from 58 Utah families for a syndrome present in approximately 12% of patients with essential hypertension

Population-based sibships with essential hypertension diagnosed before the age of 60 years are being screened in Utah to find two or more hypertensive siblings with the same biochemical abnormality as a clue to an inherited cause for their specific type of hypertension. Among 131 hypertensive subjects in 58 sibships, concordant abnormalities in fasting serum lipid concentrations were observed in two or more siblings in 48% of the sibships. After adjusting for effects of antihypertensive medications, abnormal values reported in only 10% of the Lipid Research Clinics data were observed in 30% of patients for serum triglycerides, 19% for serum low-density lipoprotein cholesterol, and 39% for high-density lipoprotein cholesterol. More than one lipid level was abnormal in almost all concordant sibships, suggesting an association between hypertension and a syndrome of mixed lipid abnormalities, probably familial combined hyperlipidemia (renamed "familial combined dyslipidemia" because of common low high-density lipoprotein cholesterol levels). We conclude that familial dyslipidemic hypertension may be a specific syndrome with lipid abnormalities more severe than blood pressure elevations.     

Human seminal relaxin is a product of the same gene as human luteal relaxin.

Unlike that of other species, which have only one gene encoding relaxin, the human genome contains two nonallelic genes for relaxin, designated H1 and H2, which encode markedly different relaxin peptides. Whereas human relaxin gene H2 is selectively expressed in the ovary, no ovarian expression of gene H1 has been detected. Since relaxin is actively produced in the human male, it is possible to postulate divergent gene expression of relaxin in the male and female. We examined this question directly through the structural determination of human seminal relaxin and its comparison with the structure of human luteal relaxin. Partially purified relaxin, prepared from pooled human seminal plasma which had been delipidated by extraction with acid acetone and hexane, subjected to two cycles of HPLC and an additional purification step by ion-exchange chromatography, was further purified by immunoaffinity chromatography, using a monoclonal antibody to the H2 relaxin A chain which cross-reacts with synthetic H1 relaxin, followed by an additional HPLC step performed on a C4 reverse-phase column. The recovered, purified relaxin was then analyzed by N-terminal gas-phase sequencing and fast atom bombardment mass spectroscopy for determination of the amino acid sequence and molecular ions of the A and B chains, respectively. The results demonstrate that the structure of the predominant relaxin in human semen plasma is derived from the product of the H2 gene, consisting of a N-terminal pyroglutamic acid A-24 A chain and a mixture of B-26 and B-27 B chains. With the exception of degradation of the seminal relaxin B chain C-terminus, this structure is identical to the structure of human luteal relaxin. Therefore, both human seminal and luteal relaxin are products of the H2 gene.     

Post-translational modifications in the large subunit of ribulose bisphosphate carboxylase/oxygenase.

Two adjacent N-terminal tryptic peptides of the large subunit of ribulose bisphosphate carboxylase/oxygenase [3-phospho-D-glycerate carboxy-lyase (dimerizing), EC 4.1.1.39] from spinach, wheat, tobacco, and muskmelon were removed by limited tryptic proteolysis. Characterization by peptide sequencing, amino acid composition, and tandem mass spectrometry revealed that the N-terminal residue from the large subunit of the enzyme from each plant species was acetylated proline. The sequence of the penultimate N-terminal tryptic peptide from the large subunit of the spinach and wheat enzyme was consistent with previous primary structure determinations. However, the penultimate N-terminal peptide from the large subunit of both the tobacco and muskmelon enzymes, while identical, differed from the corresponding peptide from spinach and wheat by containing a trimethyllysyl residue at position 14. Thus, tryptic proteolysis occurred at lysine-18 rather than lysine-14 as with the spinach and wheat enzymes. A comparison of the DNA sequences for the large subunit of ribulose bisphosphate carboxylase/oxygenase indicates that the N terminus has been post-translationally processed by removal of methionine-1 and serine-2 followed by acetylation of proline-3. In addition, for the enzyme from tobacco and muskmelon a third post-translational modification occurs at lysine-14 in the form of N epsilon-trimethylation.     

Latent Growth Curve Modeling of Non-Injection Drug Use and Condomless Sexual Behavior from Ages 18 to 21 in Gay,Bisexual, and Other YMSM: The P18 Cohort Study

Background: HIV/AIDS continues to be a health disparity faced by sexual minority men, and is exacerbated by non-injection drug use. Objectives: We sought to delineate growth in non-injection drug use and condomless sex in a sample of racially and economically diverse of gay, bisexual, and other young men who have sex with men (YMSM) as they emerged into adulthood between the ages of 18 and 21 and who came of age in the post-HAART era. Methods: Behavioral data on drug use and condomless sex, collected via a calendar based technique over 7 waves of a cohort study of 600 YMSM, were analyzed using latent growth curve modeling to document patterns of growth in these behaviors, their associations, and the extent to which patterns and associations are moderated by race/ethnicity and socioeconomic status. Results: Significant growth was noted in the frequencies of condomless oral and anal intercourse, alcohol to intoxication, marijuana use, and inhalant nitrate use. High levels of association were noted between all behaviors across time but associations did not differ by either race/ethnicity or socioeconomic status. The link between drug use and risky sexual behavior continue to be evident in YMSM with significant increases in these behaviors demonstrated as YMSM transition between adolescence and young adulthood. Conclusions/Importance: Healthcare for a new generation of sexual minority males must address the synergy of these behaviors and also nest HIV prevention and care within a larger context of sexual minority health that acknowledges the advances made in the last three decades.     

Isolation and characterization of two peptides with prolactin release-inhibiting activity from porcine hypothalami.

Two peptides with in vitro prolactin release-inhibiting activity were purified from stalk median eminence (SME) fragments of 20,000 pig hypothalami. Monolayer cultures of rat anterior pituitary cells were incubated with aliquots of chromatographic fractions and the inhibition of release of prolactin in vitro was measured by RIA in order to monitor the purification. The hypothalamic tissue extract was separated into 11 fractions by high-performance aqueous size-exclusion chromatography with one fraction showing a 4-fold increase in prolactin release-inhibiting factor (PIF) activity. This material was further purified by semipreparative reversed-phase (RP) HPLC. This process resulted in the separation of two distinct fractions that showed high PIF activity. These were further purified by semipreparative and analytical RP-HPLC to apparent homogeneity as judged by the UV absorbance profiles. Neither of the two peptides showed cross-reactivity with gonadotropin releasing hormone-associated peptide or with somatostatin-14 antibodies. Protein sequence analysis revealed that one of the PIF peptides was Trp-Cys-Leu-Glu-Ser-Ser-Gln-Cys-Gln-Asp-Leu-Ser-Thr-Glu-Ser-Asn-Leu-Leu- Ala-Cys - Ile-Arg-Ala-Cys-Lys-Pro, identical to residues 27-52 of the N-terminal region of the proopiomelanocortin (POMC) precursor (corresponding to amino acids 1-26 of the 16-kDa fragment). The sequence of the other PIF was Ala-Ser-Asp-Arg-Ser-Asn-Ala-Thr-Leu-Leu-Asp-Gly-Pro-Ser-Gly-Ala-Leu-Leu- Leu-Arg - Leu-Val-Gln-Leu-Ala-Gly-Ala-Pro-Glu-Pro-Ala-Glu-Pro-Ala-Gln-Pro-Gly-Val- Tyr, representing residues 109-147 of the vasopressin-neurophysin precursor. Synthetic peptides corresponding to the N-terminal region of POMC had significant PIF activity in vitro.     

Public perceptions of child abuse and neglect in a midwestern urban community

This study found that the majority of urban adults did not believe that any of the characteristics of children posed to them predisposed a child to abuse. In contrast, 40% of respondents claimed child abuse could not occur in a family like the one in which they grew up. The majority perceived only one characteristic, alcohol abuse, as a characteristic of child abusers. Few respondents (10%) believed that child abusers could not be helped, and 25% were not sure. Adults' perceptions of child abuse and abusers varied by sex, age, socioeconomic status, and whether the respondents had children. The data indicate that there are significant deficits in the respondents' knowledge of child abuse and neglect.     

Self-adhesive monitor/defibrillation pads improve prehospital defibrillation success

We compared self-adhesive, dual-function monitor/defibrillation electrode pads to standard chest monitoring leads and hand-held electrode paddles in the management of prehospital ventricular fibrillation in a single urban paramedic service. Shocks were delivered more quickly following paramedic arrival with self-adhesive pads than with hand-held paddles (1.6 vs 2.5 min; P less than .001). Ventricular fibrillation was terminated more frequently when shocks were delivered using the self-adhesive pads (55 of 58 patients, 95%) than when shocks were delivered using hand-held paddles (49 of 69 patients, 71%; P less than .005). Initial shocks delivered with self-adhesive pads were especially effective, converting 40 of 58 (69%) patients to an organized rhythm on the first or second shock; this was true of only 24 of 69 (35%) patients shocked with hand-held paddles (P less than .001). Patient survival to hospital admission improved when self-adhesive pads were used: 30 of the 58 (52%) patients shocked with self-adhesive pads achieved hospital admission, while only 21 of 69 patients (30%; P less than .025) survived to admission when hand-held paddles were used. In addition, electrical artifact that interfered with accurate rhythm interpretation was far more prevalent when standard monitoring electrodes were used, including artifact that resulted in inappropriate shock delivery (23% of patients monitored with standard electrodes vs 3% of patients monitored with self-adhesive pads; P less than .005). Self-adhesive monitor/defibrillation pads are superior to standard monitoring leads and hand-held electrode paddles in the management of prehospital ventricular fibrillation.