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Biomedical subjects

S Solomon

Publications and source records attributed to S Solomon.

At least 19 recordsLinked to original sources

Purification of cationic cystine-rich peptides from rat bone marrow. Primary structures and biological activity of the rat corticostatin family of peptides.

Seven cationic, cystine-rich peptides of 29 to 32 amino acid residues have been purified from extracts of rat bone marrow (R-1, R-1a, R-1b, R-2, R-3, R-4 and R-5). Structural analysis clearly indicated that all seven peptides belong to the corticostatin/defensin family of leukocyte-derived peptides known to participate in oxygen-independent killing of phagocytosed bacteria. For R-1 to R-5, six cysteine residues were found at characteristic and highly conserved positions. R-1a and R-1b were partially characterized and appear to be structural variants of R-1. Aside from the conserved cysteines, there is a remarkable degree of structural diversity evident within the sequences of those members of the corticostatin/defensin family characterized so far. The structures of the peptides that we have purified can be compared directly with the sequences obtained for rat defensins isolated from extracts of peritoneal neutrophils (Lehrer, Ganz and Selsted, Cell, 64 (1991) 229-230). Some discrepancies are apparent which can be explained in terms of proteolytic cleavage of several of these peptides at both amino- and carboxyl-termini. The corticostatins owe their bioactivity to their ability to compete with corticotropin for occupancy of the corticotropin receptor (Zhu, Hu, Mulay, Esch, Shimasaki and Solomon, Proc. Natl. Acad. Sci. USA, 85 (1988) 592-596). The potency of these peptides can be expressed in terms of their capacity to inhibit the steroidogenic response of isolated rat adrenocrotical cells half-maximally stimulated by corticotropin (i.e., at the ED50 concentration for corticotropin in this assay, namely 33 pM). In this assay, the rat peptides R-1, R-2 and R-3 were shown to be inactive. In contrast, the more cationic peptides R-4 and R-5 were found to inhibit steroidogenesis. R-4 was somewhat less active than rabbit corticostatin (IC50 25 nM) showing an IC50 value of 50 nM. R-5 appeared to be significantly less potent than R-4. The lower yield of R-5 precluded an accurate estimate of the corticostatic potency of this peptide. R-4 differs in structure from R-5 in having an arginine to serine substitution at position 7. It can be concluded that an arginine at this position accounts, at least in part, for the corticostatic activity of R-4.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenocorticotropic Hormone

Dose ranging efficacy and safety of subcutaneous sumatriptan in the acute treatment of migraine. US Sumatriptan Research Group.

Sumatriptan, a specific serotonin1-like receptor agonist, was studied in the acute treatment of migraine. Two hundred forty-two adult migraineurs participated in a randomized, double-blind study in which one dose of 1, 2, 3, 4, 6, or 8 mg of subcutaneous sumatriptan succinate was evaluated in sequential ascending fashion. At each dose level, a placebo group was included. Efficacy was defined as reduction of moderate or severe pain to mild or no pain, without the use of rescue medication. Headache relief rates showed an approximate dose-response relationship and at 1 hour were as follows: placebo, 24%; 1 mg, 43%; 2 mg, 57%; 3 mg, 57%; 4 mg, 50%; 6 mg, 73%; and 8 mg, 80%. Relief of nausea and improvement in clinical disability were also approximately dose related. Adverse events were dose related; the most common types were injection site reactions and tingling. The 6-mg dose was as effective as the 8-mg dose but was associated with fewer adverse effects and so is optimal.

Adult

Terror management and tolerance: does mortality salience always intensify negative reactions to others who threaten one's worldview?

Terror management research has shown that reminding Ss of their mortality leads to intolerance. The present research assessed whether mortality salience would lead to increased intolerance when the value of tolerance is highly accessible. In Study 1, given that liberals value tolerance more than conservatives, it was hypothesized that with mortality salience, dislike of dissimilar others would increase among conservatives but decrease among liberals. Liberal and conservative Ss were induced to think about their own mortality or a neutral topic and then were asked to evaluate 2 target persons, 1 liberal, the other conservative. Ss' evaluations of the targets supported these hypotheses. In Study 2, the value of tolerance was primed for half the Ss and, under mortality-salient or control conditions, Ss evaluated a target person who criticized the United States. Mortality salience did not lead to negative reactions to the critic when the value of tolerance was highly accessible.

Attitude to Death

Childhood onset cluster headaches.

Cluster headaches are rare in childhood. We identified 35 patients with cluster headaches starting at or before 18 years of age, including 7 patients with onset prior to age 10. All patients met the criteria of the International Headache Society for episodic or chronic cluster headaches. Patients experienced cluster headaches for as long as 20 years before seeking medical attention and required many medical contacts to establish the correct diagnosis. The clinical features of cluster headaches during childhood were similar to those which typically occur in adult life. Cluster headache patterns changed over 18 years of follow up. The frequency and duration of cluster periods increased in 14 subjects. The frequency of single headache attacks during cluster periods also increased in a similar number of subjects. We conclude that cluster headaches starting in childhood or adolescence closely resemble the adult form of the disease. In many patients, the frequency and duration of cluster periods and the frequency of the individual headache episodes increased over time. Cluster headache represent a treatable under-recognized cause of severe headaches in childhood and adolescence.

Adolescent

Isolation and mode of action of rabbit corticostatic (antiadrenocorticotropin) peptides.

Corticostatic peptides are a family of arginine-rich cysteine-rich peptides that inhibit ACTH-stimulated corticosterone (B) production in rat adrenal cell suspensions. In this communication we describe a new method for the facile isolation and purification of these basic peptides from rabbit adult lung. We then describe the isolation and sequences of the four rabbit peptides, CSI, CSII, CSIII, and CSIV, and compare their biological activities in the ACTH (150 pg/ml) inhibition assay. CSI is by far the most potent of the four peptides. Using CSI as a model, we then studied its effects on the proximal and distal parts of the pathway leading to the generation of cAMP. CSI had no effect on (Bu)2cAMP action on forskolin or cholera toxin in their ability to mimic ACTH and increase B production in rat adrenal cells, nor did CSI have any effect on the stimulation of B production by pertussis toxin. Endogenous cAMP stimulated by ACTH decreased after the addition of CSI, which pointed to the inhibition of ACTH binding to explain the mode of action of this corticostatin. Displacement of the specific binding of labeled ACTH by CSI and the ACTH antagonist ACTH-(6-24) was determined, and indeed, CSI did displace ACTH from its binding site. The question of what portion of the ACTH molecule was involved in the action of CSI was answered by studying ACTH-(1-13) acetyl amide (alpha MSH) and ACTH-(1-18) amide. CSI had no effect on alpha MSH stimulation of B production, but did lower the production of B stimulated by ACTH-(1-18) amide. Therefore, CSI must act on ACTH-(14-18), which is part of the so-called address region of ACTH, which is -Gly14-Lys15-Lys16-Arg17-Arg18-, the very basic part of the molecule. These results indicate that CSI acts by competing with ACTH for its binding receptor on the adrenal cell and that this competition is confined to amino acids 14-18 of the molecule when it is bound to the receptor.

Adrenal Glands

Exocrine ductal pCO2 in the rabbit pancreas.

An improved pCO2 microelectrode has been evaluated and used to investigate whether a significant barrier to diffusion of CO2 exists in the rabbit pancreas. The results of this study show the improved Carter and Caflisch pCO2 microelectrode to be an accurate and reliable tool for measuring pancreatic venous and ductal pCO2. The similarities between pCO2 values from the pancreatic ducts and small pancreatic veins suggest that there is no barrier to CO2 diffusion between small veins and exocrine ducts in the rabbit pancreas, and that ductal pCO2 is probably strongly influenced by the CO2 tension of the small pancreatic blood vessels.

Animals

Effects of paced respiration and expectations on physiological and psychological responses to threat.

While waiting to receive electric shocks, 105 males either (a) regulated their breathing at one half the normal rate, (b) regulated their breathing at the normal rate, or (c) did not regulate their breathing rate. Half of the subjects in each breathing condition were told that their breathing task would aid them in relaxing, whereas the other half were not given that expectation. Subjects in a no threat condition were not threatened with shocks, did not regulate their breathing, and were not provided with expectations. The results indicated that slowing respiration rate reduced physiological arousal as measured by skin resistance and finger pulse volume (but not heart rate) and reduced self-reports of anxiety. Expectations did not influence arousal. These data provide evidence for the effectiveness of paced respiration as a coping strategy, and they resolve the conflicting findings of previous investigations.

Adult

Congenital complete heart block in the newborn associated with maternal systemic lupus erythematosus and other connective tissue disorders.

Four babies with complete heart block associated with maternal systemic lupus erythematosus (SLE) are described, together with a 5th baby whose mother had serological abnormalities only. One baby had a rapidly fatal outcome, one has required digoxin for heart failure, and the remaining 3 are asymptomatic but remain in complete heart block. Additional manifestations were present in 2 of them. The spectrum of neonatal abnormalities that may occur in association with maternal SLE and related connective tissue disorders is discussed, together with the possible causes and the prognosis. We conclude that congenital heart block is more common than had previously been appreciated.

Adult

Renal response to Ringer expansion in developing rats.

Male rats were studied between 20 and 60 days of age. Standard renal clearance techniques were used. The efficiency of the diuretic response, the sodium response, and the potassium response were calculated as defined previously. Results indicate that both diuretic and sodium efficiency is lower between the ages of 20 and 30 days as compared to 40 and 60 days of age, whereas potassium efficiency shows no age dependence. In morphological studies, it has been observed that the proximal tubule cells of 22-day-old rats show changes in lateral intercellular spaces with comparable features to those of mature animals. The spaces widened during volume expansion. The change is quantitatively the same as that found in mature rats. Both blood pressure and hematocrit show continuous increase with age. The response of Ringer infusion in both immature and mature animals may be a mixed response involving changes in physical factors and renal responses to volume expansion per se.

Age Factors

Evidence that the renal response to volume expansion involves a blood-borne factor.

The effect of blood volume expansion in immature rats by blood from infants (J to J expansion) and mature animals (A to J) has been studied. A to J expansion results in an increased renal response to expansion which is greater than J to J, but not as great as when mature animals are expanded with blood from other matures (A to A) or pooled blood from infants (J to A). A to A and J to A expansions show no significant differences in renal responsiveness. The lack of an immature response is not due to differences in animal hydration since 2.5% volume expansion is on the flat part of dose response curve. Part of the scatter of the adult response is related to absolute levels of GFR which might indicate the existence of a filterable natriuretic factor or, alternatively, a dependence of renal responsiveness on filtered load. These results are interpreted to indicate that mature rats contain a natriuretic factor or an inhibitor of an antinatriuretic factor which is blood borne and is probably secreted in blood volume expanded rats.

Age Factors

Antigenic subtypes of HBsAg: their distribution and pattern of occurence among blood donors and patients with liver diseases and leprosy in Tamilnadu, India.

One hundred and seventy hepatitis B Surface antigen positive sera derived from blood donors, patients with liver diseases and leprosy were antigenically subtyped by Rheophoresis and 107 of them by agar-gel diffusion. For the first time in India HBsAg/adr as a predominant subtype (64.0%) is documented. Of the two methods adopted, Rheophoresis showed a greater sensitivity of typing, namely 82.3% in contrast to 39.2% only by agar-gel diffusion (p less than 0.001). Analysis of the Hepatitis Be antigen and antibody (anti HBe) positive sera for subtype predeliction revealed the same pattern as in HBe system negative sera.

Blood Donors

Formation of 20-hydroxyprostaglandins by lungs of pregnant rabbits.

Homogenates or particulate fractions (1,000 to 100,000 X g) from lungs of pregnant rabbits were incubated with prostaglandins or prostaglandin metabolites and the products were purified by chromatography and identified by gas chromatography-mass spectrometry. In the presence of NADPH, particulate fractions from pregnant rabbit lungs converted prostaglandins E1, E2, and F2alpha as well as 13,14-dihydro-15-oxoprostaglandin E2 and 13, 14-dihydro-15-oxoprostaglandin F2alpha to their 20-hydroxy derivatives. In the cases of the 3 primary prostaglandins, the corresponding omega-carboxylic acids were also isolated. The omega-hydroxylation reaction occurred in the presence of the microsomal fraction. The mitochondrial fraction was much less active whereas the cytosol fraction converted prostaglandins to their 13, 14-dihydro-15-oxo derivatives. When prostaglandin F2alpha was incubated with homogenates of lungs from pregnant rabbits, omega-oxidation was combined with oxidation of the 15-hydroxyl group and reduction of the 13, 14-double bond to give 13, 14-dihydro-20-hydroxy-15-oxoprostaglandin F2alpha as well as the corresponding derivative with an omega-carboxylic acid group. Lungs from nonpregnant rabbits were much less active than lungs from pregnant rabbits in the omega-oxidation of prostaglandins.

Animals