Propranolol, a beta-adrenergic antagonist, retards response to MSH in skin of Anolis carolinensis

Lacking sympathetic innervation, the skin of A. carolinensis, an iguanid lizard, darkens within minutes in response to circulating melanocyte stimulating hormone (MSH) or beta adrenergic agonists such as epinephrine (EPI). This change is produced by dispersion of melanin from a perinculear position within dermal melanophores into superficial dendritic processes. These melanophores possess alpha-2 and beta-2 adrenergic as well as MSH receptors except in a patch of skin behind the eye, the eyespot, which lacks alpha receptors. Activation of beta or MSH receptors leads to stimulation of adenyl cyclase whereas alpha stimulation inhibits the enzyme to override the others. In a series of trials, injection of saline or propranolol was followed after 30 minutes by saline, EPI, or MSH. Propranolol inhibited chromatophore response to EPI. It also, unexpectedly, retarded the response to MSH, increasing latency to eyespot formation and body color change as well as the duration of darkening for both. Alteration of MSH response by a beta blocker could be explained by linkage of both adrenergic receptors and the MSH receptor to a common adenyl cyclase molecule to form a functional unit in the membrane of the melanophore.     

Staphylococcal toxin-induced T cell proliferation in atopic eczema correlates with increased use of superantigen-reactive Vbeta-chains in cutaneous lymphocyte-associated antigen (CLA)-positive lymphocytes

Staphylococcal superantigens have been implicated in the pathogenesis of atopic dermatitis (AD). This may occur through superantigenic activation of T lymphocytes and their subsequent induction of the skin homing receptor CLA on activated cells. We investigated the proliferative responses of peripheral blood mononuclear cells (PBMC) from 10 patients with an infective exacerbation of AD and six normal controls to the staphylococcal superantigens, staphylococcal enterotoxin A and B (SEA, SEB) and toxic shock syndrome toxin-1 (TSST-1), and the mitogens phytohaemagglutinin (PHA) and concanavalin A (Con A). We also assessed CLA and T cell receptor (TCR) Vbeta-chain expression by immunofluorescence and flow cytometry before and after stimulation. PBMC from AD patients showed two-fold increased proliferation to SEA and SEB (P < 0.01) compared with normals, whereas the response to mitogenic stimulation was identical. Analysis of (TCR) Vbeta-chain expression demonstrated increased use of superantigen-reactive Vbeta families in freshly isolated PBMC in AD patients compared with controls. This pattern of Vbeta-chain expression was only observed in the CLA+ but not the total population of T cells. Furthermore, there was a positive correlation between the enhanced PBMC proliferative response and increased expression of superantigen-reactive Vbeta families in atopic patients. These data support the concept that superantigens are important in the pathogenesis of this common condition, and also provide evidence that the increased use of certain Vbeta families in circulating, CLA+, skin homing lymphocytes is of functional significance.     

The development of respiratory syncytial virus-specific IgE and the release of histamine in nasopharyngeal secretions after infection

We studied the development of respiratory syncytial virus (RSV)-specific IgE and the release of histamine in nasopharyngeal secretions from 79 infants with various forms of respiratory illness due to RSV. RSV-IgE was measured by an enzyme-linked immunosorbent assay; specificity was confirmed by appropriate blocking experiments. Histamine content in the secretions was determined by fluorimetric methods. RSV-IgE was detectable in only one of 19 patients with RSV infection without wheezing, but was detectable in the majority of 60 patients with wheezing (P less than 0.01). Titers of RSV-IgE were significantly higher in patients with wheezing (P less than 0.05). Histamine was detectable in secretions of some patients with all forms of illness but was detected significantly more often (P = 0.05) and in higher concentrations in patients with wheezing. Peak titers of RSV-IgE and concentrations of histamine correlated significantly with the degree of hypoxia (P less than 0.001). Formation of RSV-specific IgE and release of histamine may adversely affect the outcome of RSV infection.     

A reappraisal of frog muscle chloride conductance-voltage relations at pH 9

Voltage clamp experiments in muscle show that the steady state chloride conductance at pH 9 remains rather independent of [Cl^–]_o, for [Cl^–]_o in the range 165–265 mM. The steady state conductance-voltage relation has a maximum near V _rest — 20 mV. The initial-conductance — voltage relation obtained when the voltage is stepped away from a constant conditioning value (e.g. the resting potential) approaches an asymptotic maximum for hyperpolarizing steps and a minimum for depolarizing steps. The conductance declines with time if the test voltage is more negative than the resting potential, but remains constant if it is more positive. When the conditioning voltage is varied and the test kept constant the initial conductance at the step is also seen to be sigmoidal, if the test step is hyperpolarizing: for large negative conditioning steps the conductance at the test potential approaches the same asymptotic value as does the steady state relation, independent of the test voltage. At positive conditioning voltages it approaches a maximum asymptote which is dependent on the test voltage. When the test step is positive-going the initial conductance at the step is weakly dependent on the conditioning voltage and for large negative conditioning potentials is larger than predicted from the steady state relation. In summary, during hyperpolarizing voltage steps the chloride conductance seems to decline due to a gating phenomenon, but openstate conductance seems to be voltage-dependent, and at membrane potentials more positive than the resting it rapidly (within the settling time of the clamp) assumes a value almost independent of any preceding (conditioning) voltage.     

Effect of therapeutic dosages of prednisone on human immunoglobulin G metabolism

In order to evaluate factors possibly responsible for the increased incidence of infections in patients treated with corticosteroids, immunoglobulin G (IgG) metabolism was studied in 8 patients before and during the administration of prednisone in a therapeutic range (30 mg. per day). The survival of intravenously administered IgG was determined, and total circulating IgG, fractional catabolic rate, and synthetic rate were calculated. There was no significant decrease in the measured levels of circulating IgG, but all patients had a shortened half-time (5 to 45 percent) and an increased fractional catabolic rate (p < 0.01). Since corticosteroid therapy was the only variable in these paired studies, it appears that corticosteroids can cause a hypercatabolism of IgG in some patients. Therefore, the maintenance of normal levels of IgG must be the result of an increased synthetic rate.     

The role of the autonomic innervation in the control of glucagon release during hypoglycaemia in the calf

1. The extent to which the autonomic innervation to the pancreas is implicated in the control of glucagon release during hypoglycaemia has been investigated in calves 3-6 weeks after birth.2. A pronounced rise in plasma glucagon concentration occurred in normal conscious calves in response to hypoglycaemia following administration of insulin (0.1 u./kg). Prior treatment with atropine caused no significant change in the hypoglycaemic response to insulin in these animals but the rise in plasma glucagon concentration was delayed.3. Section of both splanchnic nerves produced no significant change in the tolerance of conscious calves to this small dose of insulin and the changes in plasma glucagon concentration in these animals were within the normal range.4. In contrast, the same dose of insulin produced severe hypoglycaemia, accompanied by convulsions, in atropinized calves with cut splanchnic nerves. In spite of the intensity of the hypoglycaemic stimulus the rise in plasma glucagon concentration was both delayed and diminished in these animals.5. Administration of atropine alone (0.2 mg/kg) to normal fasting calves produced a significant fall in the mean plasma concentrations of both glucose and glucagon (P < 0.01) within 30 min, without affecting that of insulin.6. A significant increase in plasma glucagon concentration also occurred in response to stimulation of the peripheral ends of the thoracic vagi in adrenalectomized calves with cut splanchnic nerves under barbiturate anaesthesia. A rise in mean plasma glucose concentration was also observed in these experiments and found to be significantly correlated with the glucagon response.7. It is concluded that changes in either sympathetic or parasympathetic efferent activity may modify plasma glucagon concentration in the conscious calf, but that only the latter mechanism is likely to be implicated in the response to changes in plasma glucose concentration within the physiological range.     

Return to alertness after brain-stem hemorrhage. A case with evoked potential and roentgenographic evidence of bilateral tegmental damage

After a 65-year-old man had received anticoagulation therapy for brain-stem ischemia, a large, bilateral pontomesencephalic hemorrhage developed in the ischemic region. He survived a period of being "locked in" to attain a limited functional recovery. When he first became alert, brain-stem auditory evoked potentials and short-latency somatosensory evoked potentials (SEPs) demonstrated bilateral brain-stem damage; computed tomography revealed a bilateral tegmental hematoma. Results of repeated studies changed little as clinical improvement occurred. Recovery from brain-stem hemorrhage is rare, and return of consciousness with bilateral tegmental involvement is even more rare. The short-latency SEPs are useful in defining the extent of brain-stem damage, but they evaluate structures distinct from those regulating consciousness and cannot predict a return to alertness.     

Rapid accurate absolute granulocyte count determination during severe leukopenia using the flow cytometer

The absolute granulocyte count (AGC) in 125 blood samples from patients with total white blood cell counts of less than 1,000/microliter was estimated using three different methods, which were then compared for efficiency and accuracy. The three methods were 25 cell differential counts using Wright's-stained blood smears, granulocyte percentage estimates from WBC counting chambers, and combined narrow- and wide-angle light-scatter characteristics determined on a flow cytometer. A survey of clinical laboratories at University Hospital Cancer Centers revealed that the smear differential was the most-often-used method in those laboratories even when less than 25 cells could be counted. Consequently the data obtained from the counting chamber and flow cytometer methods were compared to the smear differential "standard" using linear regression, and outliers were identified. There was good correlation between AGC determined by smear differential and WBC counting chamber (correlation coefficient .911) and excellent correlation between the AGC determined by smear differential and the flow cytometer method (correlation coefficient .970). The flow cytometer method used in this investigation required minimal specimen preparation, and test results were available at a rate of 60 seconds/sample. The ease of sample preparation, speed, and statistical reliability of test results makes the flow cytometer an attractive alternate method of determining granulocyte counts on leukopenic patients as compared to the stained blood smear differential.     

Feeling Good About Your Partners’ Relationships: Compersion in Consensually Non-Monogamous Relationships

Archives of Sexual Behavior - Compersion is a well-known term in polyamorous communities that connotes the positive emotion an individual may experience in relation to their partner’s...     

Loss of heterozygosity on chromosome-8 in squamous-cell carcinomas of the head and neck

LOH studies provide evidence for the implication of novel TSGs in human tumours. The p arm of chromosome 8 has been reported to harbour tumour suppressor genes (TSGs) which are very likely to be involved in the development of colon, lung, bladder and hepatocellular carcinomas. In addition, the c-myc proto-oncogene which is located on the 8q arm, has been found to be overexpressed in SCCHN. In the present study we have investigated the incidence of loss of heterozygosity (LOH) in chromosome 8 in 37 tumour specimens of squamous cell carcinomas of the head and neck (SCCHN), using a bank of 11 polymorphic microsatellite markers. The aim of this work was to assess whether there was an 8p TSG(s) in SCCHN, as reported in other tumours and also to investigate whether other areas of chromosome 8 exhibit a high LOH. A relatively high incidence of LOH was found for the markers D8S87 (29%) on 8p12 and ANK1 (20%) on 8p21.2-p11. These two markers are located in the area in which TSG(s) for other cancers have been previously described. When the data on D8S87 and ANK1 were analyzed together it was found that 13/35 (37%) of the SCCHN specimens had a loss at one or other of these markers, thus indicating that a putative TSG(s) in this region may play a role in the development of the SCCHN. No correlation was found between the LOH data and any of the clinicopathological parameters. We also investigated the incidence of c-myc amplification in 144 SCCHN specimens but only 4% were found to have an amplified c-myc allele, thus indicating that the overexpression of c-myc in SCCHN was not the result of gene amplification.