Vasoactive intestinal peptide (VIP) activation of nuclear protein kinase C in purified nuclei of rat splenocytes

We have examined the actions of vasoactive intestinal peptide (VIP) and certain other known immune modulators on a nuclear pool(s) of protein kinase C (PKC) in isolated rat splenocyte nuclei. Rat splenocyte nuclei pure by enzymatic and electron microscope criteria demonstrated a time- and concentration-dependent activation of nuclear PKC (nPKC) by VIP. A biphasic pattern of three bell-shaped curves was observed with peak phosphorylation at 10⁻¹⁵, 10⁻⁹ and 10⁻⁶M VIP. The phosphorylation of endogenous nuclear substrates was characterized as a PKC-mediated event by use of three known PKC inhibitors, 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7), sphingosine, and staurosporine, which produced similar phosphate incorporation measurements. Also, this activity was blocked with the addition of a monoclonal antibody to PKC. Inhibitors of the ability of VIP to activate nPKC included somatostatin, 8-bromo-cAMP, peripheral benzodiazepine receptor modulators, and the PKC inhibitors, sphingosine and staurosporine. These data have direct relevance to our knowledge of cell-mediated immunity.     

MANAGEMENT OF VARICELLA-ZOSTER VIRUS INFECTION DURING PREGNANCY AND THE PERIPARTUM

This paper reviews the important concepts about varicella-zoster virus (VZV) infection, varicella (chickenpox), and herpes zoster (shingles, zoster) during pregnancy and the peripartum period. The majority of the U.S. population has had chickenpox during childhood, leaving only about 10% of adults over the age of 15 susceptible to the virus. However, nonimmune adults, including pregnant women, are at greater risk for complications and mortality when they contrac varicella. The virus is also teratogenic. The implication of VZV infection during pregnancy and the perinatal period are presented. Risks such as varicella pneumonia and congenital defects can be serious even though the incidence during pregnancy is low, one to five per 10,000 pregnancies. Management and treatment plans are presented. Counseling and education aimed at prevention or modification of the infection in the mother and baby is outlined.     

Comparison of the potential therapeutic effects of interleukin 2 or interleukin 4 secretion by a single tumour.

Engineering of a variety of rodent tumour cells to secrete either interleukin 2 (IL-2), or interleukin 4 (IL-4), has been demonstrated to reduce their tumorigenicity. However the mechanisms of action of secreted IL-2 and IL-4 have not been compared in a single rodent tumour. Here we demonstrate that the weakly immunogenic murine fibrosarcoma FS29 had reduced growth rate and in some cases was rejected by syngeneic animals, when modified to secrete either IL-2 or IL-4, but not IL-5. Immunohistochemical analysis of tumour nodules undergoing regression showed stimulation of a largely lymphocytic infiltrate by IL-2 and a macrophage and granulocyte infiltrate, with a small number of lymphocytes by IL-4. Indeed, secretion of low levels of IL-2 and IL-4 in combination resulted in optimal rejection, suggesting that the two cytokines might mobilise different and complementary effector cell mechanisms. Both IL-2 and IL-4-secreting cells failed to induce the rejection of admixed, unmodified FS29 cells. The loss of cytokine secreting cells from such admixtures occurred more rapidly for IL-2-secreting cells. Injection of IL-4-secreting, but not IL-2-secreting FS29 cells could protect mice from a delayed challenge with unmodified FS29 cells. These data suggest that IL-4 secretion stimulates the better long-term host anti-tumour response.     

Memory and attention.

The effect of attention on memory was examined in three studies. In all three, the subjects were instructed to remember the items of one color from an array that contained items of two colors. Subsequently, the subjects were asked to reproduce items of both colors. Almost all of the items that the subjects remembered were those to which they had attended. The parameters of sex, color, and mode of presentation (verbal and drawing) were not significant. Head injury did not disrupt this effect. On the basis of this effect, it was theorized that the strength of a memory store is related directly to the strength of attention.     

Menorrhagia management options.

A prospective study of the management of menorrhagia in new patients presenting to gynaecological outpatients was undertaken at four centres in Northern Ireland and two in Great Britain. 325 patients were enrolled, the majority of whom (87%) had severe menorrhagia. Patients in all six centres were similar in relation to age, marital status, parity, use of contraception and severity of symptoms. 62% of the patients were managed medically, improved and were discharged. The rates of surgical intervention, in particular in women aged less than 40, appeared higher in the Northern Ireland hospitals than Great Britain. There is a need to review and audit current practices in the management of menorrhagia.     

Nasal nicotine spray: a rapid nicotine delivery system

Plasma nicotine concentrations following administration by two types of nasal nicotine spray were compared in ten subjects. Absorption was particularly rapid during the first 2.5 min, the average rise in blood nicotine concentrations during this time being 8.6 ng/ml for the two products, followed by a small further rise to an average peak increase of 10.5 ng/ml 5 min after the dose of 2 mg nicotine base (mean 27.8 micrograms/kg). Despite a four-fold Cmax variation between subjects, the levels of individual subjects were fairly consistent across the two products. There were no significant differences between the two products in blood nicotine concentrations or cardiovascular responses, and the correlation between the AUCs from the two products was 0.68 (P = 0.01). Eight subjects reported subjective feelings of light-headedness or slight dizziness, which are not typical after slower absorption from nicotine gum or skin patches. Blood nicotine levels within the smoking range were soon built up with repeated doses, even in the subject with the least efficient nasal absorption. In a second study of ad libitum use under clinical conditions both products appeared sufficiently acceptable for therapeutic use as an aid to smoking cessation. There was no tendency to escalate to excessive use over 4 weeks, and blood nicotine concentrations in nine subjects averaged only 44% of their prior smoking levels. Only one subject had levels equivalent to prior smoking and possible reasons why this was not more common are discussed.