Regulation of DAF-2 receptor signaling by human insulin and ins-1, a member of the unusually large and diverse C. elegans insulin gene family

The activity of the DAF-2 insulin-like receptor is required for Caenorhabditis elegans reproductive growth and normal adult life span. Informatic analysis identified 37 C. elegans genes predicted to encode insulin-like peptides. Many of these genes are divergent insulin superfamily members, and many are clustered, indicating recent diversification of the family. The ins genes are primarily expressed in neurons, including sensory neurons, a subset of which are required for reproductive development. Structural predictions and likely C-peptide cleavage sites typical of mammalian insulins suggest that ins-1 is most closely related to insulin. Overexpression of ins-1, or expression of human insulin under the control of ins-1 regulatory sequences, causes partially penetrant arrest at the dauer stage and enhances dauer arrest in weak daf-2 mutants, suggesting that INS-1 and human insulin antagonize DAF-2 insulin-like signaling. A deletion of the ins-1 coding region does not enhance or suppress dauer arrest, indicating a functional redundancy among the 37 ins genes. Of five other ins genes tested, the only other one bearing a predicted C peptide also antagonizes daf-2 signaling, whereas four ins genes without a C peptide do not, indicating functional diversity within the ins family.     

Antibodies to staphylococcal enterotoxins and toxic shock syndrome toxin 1 in sera of patients and healthy people in Rio de Janeiro, Brazil.

Sera from 33 persons with staphylococcal infections and from 37 healthy persons were surveyed for the presence of antibody to staphylococcal enterotoxins A, B, C, D, and E and toxic shock syndrome toxin 1. Thirty-one (93.9%) of the patients and 35 (94.6%) of the control group had antibodies to one or more of the enterotoxins. The numbers of patients with antibody to the enterotoxins were as follows: A, 8; B, 9; C, 7; D, 17; E, 21; and toxic shock syndrome toxin 1, 11. The numbers of healthy individuals with antibody to the enterotoxins were as follows: A, 6; B, 12; C, 8; D, 27; E, 21; and toxic shock syndrome toxin 1, 9.     

Eel calcitonin induces creatine kinase BB activity in the rat kidney medulla.

We have studied the effect of intravenous injection of eel calcitonin (ECT) on creatine kinase E.C.2.7.3.2. BB isozyme (CKBB) in the kidney of male Wistar rats. CKBB immunoreactivity was detected by the peroxidase-antiperoxidase method. Eel calcitonin increased CKBB immunoreactivity in the renal medulla in a dose-dependent fashion. Its effect peaked at 2 h and lasted up to 24 h. The distribution of activated CKBB in the kidney occurs in the same areas where highly specific CT-binding sites have been previously demonstrated, and is in agreement with the current concepts on renal actions of this hormone.     

A behavioral analysis of chest pain in patients suspected of having coronary artery disease

A group of 83 men and women who had been referred to Johns Hopkins Hospital for cardiac catheterization for evaluation of chest pain and possible coronary artery bypass surgery were assessed behaviorally for their chest pains. During the approximately 2-week period between clinical evaluation and catheterization, the patients completed self-report forms about their chest pains. Patients completed one form for each episode of chest pain. Referring physicians also completed a form about the patients "typical" chest pain. The data were analyzed in terms of the antecedents, concomitants, and consequences of the chest pain, and patients' reports were compared to physicians' judgments. Major findings were as follows: 1) Antecedents--most episodes occurred while the patient was at home at times when his mood was one of contentment. 2) Concomitants--the average patient reported fewer than one episode per day which persisted for about 4 min and was rated as 36 on a scale of 0 to 100. The most common physical symptoms accompanying the episode were breathlessness and weakness, and the most common pain sensations were reported to be pressing or aching. There was no consistency among patients either in primary location or path of radiation of the pain. Duration of pain did not correlate significantly either with sensation or symptoms; however, severity rating did correlate with symptoms and sensations. 3) Consequences--most episodes were self-treated with nitroglycerin or rest. Patients typically returned to their ongoing activities; however, there were a number of interactions between the likelihood of returning to ones ongoing activity and the antecedents of the episodes. 4) The referring physicians significantly overestimated the frequency and severity of their patients' episodes; furthermore, they were selective in their abilities to identify correctly the antecedents or concomitants associated with their patients' pain--e.g., they were reliable in their judgments about subjects who had sleep-related episodes; however, they were inaccurate in characterizing the typical sensations or symptoms reported by their patients. It is suggested that a behavioral analysis may enable a physician to characterize his patient's chest complaints better, and perhaps also may facilitate the differentiation between chest complaints indicative of coronary artery disease and chest complaints of a noncoronary origin.     

Excitatory synaptic potentials due to activation of neurons with short projections in the myenteric plexus

Intracellular microelectrodes have been used to examine the effects, on excitatory inputs to myenteric nerve cells, of lesions of intrinsic pathways in the myenteric plexus of the guinea-pig small intestine. The lesions consisted of circumferential cuts (myotomies) which severed the external musculature to the depth of the submucosa and thus interrupted pathways in the myenteric plexus. Sufficient time was allowed between creating the lesions and recording from the neurons for the endings of severed neurites to degenerate and this was confirmed histochemically by examining the distribution of varicose fibres with 5-hydroxytryptamine immunoreactivity in myenteric ganglia from which recordings were made. Two types of excitatory input, eliciting fast and slow excitatory post-synaptic potentials, respectively, were demonstrable in response to focal stimulation of nerves in the ganglia from which recordings were made. There were no differences in the proportions of neurons in which fast or slow excitatory synaptic potentials were evoked in unoperated preparations (controls), in islands 1.5-4 mm wide between myotomies, or within 1 mm on the oral or anal sides of myotomies. Possible differences in the amplitudes, durations at half amplitude, and threshold numbers of stimuli for initiation of slow excitatory synaptic potentials were analyzed. The only significant differences were found when data from control and oral areas were pooled and compared with combined data from island and anal areas (this assessed differences that could arise from severing nerve fibres running from oral to anal).(ABSTRACT TRUNCATED AT 250 WORDS)     

A pharmacological analysis of the neuronal circuitry involved in distension-evoked enteric excitatory reflex

Isolated segments of guinea-pig small intestine were set up in a partitioned bath to study the enteric excitatory reflex evoked by distension. The gut was distended by a rubber balloon inserted at the aboral end and contractions of the circular muscle were recorded at the oral end. The oral and aboral ends of the gut were separated by an intermediate compartment of the bath. Inflation of the intraluminal balloon with 0.075-0.35 ml water elicited reproducible and distension-dependent contraction. This enteric orally directed (ascending) excitatory reflex was abolished by tetrodotoxin irrespective of the compartment in which it was applied. Hyoscine (0.3 microM) almost abolished the enteric excitatory reflex when it was applied to the oral compartment. This indicates that the transmission from the final motor neurons to the circular muscle is mainly cholinergic, acting via muscarinic receptors. Hyoscine had no effect on the enteric excitatory reflex when added to the intermediate compartment. When hyoscine was added to the aboral compartment, it decreased the enteric excitatory reflex elicited by low distension stimuli to 70% of control and decreased the enteric excitatory reflex elicited by higher distension stimuli to 95% of control. This indicates that ganglionic transmission involving muscarinic receptors at the site of distension in the aboral bath contributes to the enteric excitatory reflex. Hexamethonium (100 microm) greatly depressed the enteric excitatory reflex when applied to any compartment indicating that nicotinic transmission is most important in the afferent, intermediate and efferent components of the reflex and that the reflex pathway involves a polysynaptic chain of cholinergic interneurons.(ABSTRACT TRUNCATED AT 250 WORDS)     

Heterogeneity of the polyribocytidilic acid tract in aphthovirus: changes in the size of the poly(C) of viruses recovered from persistently infected cattle

A sample of aphthovirus type C3 strain Resende carrying two polyribocytidilic acid [poly(C)] tracts was cloned in tissue culture. One clone with a poly(C)-rich tract of about 145 nucleotides long (clone 3B) and another with a poly(C)-rich tract of about 230 nucleotides long (clone 12) and a mixture of both were injected intralingually into three steers. Samples from all three animals were recovered during the acute phase of the disease, from the blood and from the feet, and at various days after inoculation from the oesophageal-pharyngeal (OP) fluids. Analysis of the viral RNAs of the positive samples by means of RNase T1 maps on one- and two-dimensional gels showed (1) changes in the electrophoretic mobility of the poly(C)-rich tracts of viruses recovered from the OP fluids at various times after infection; (2) selection of virus populations with poly(C)-rich tracts of increased size; (3) later on, changes in the patterns of oligonucleotides of persistent viruses. These variations may lead to the production of new strains with altered biological properties that may contribute to the maintenance and spread of these viruses in the field.