Relationships of gp70 of MuLV envelopes to gp70 components of mouse lymphocyte plasma membranes

The family of glycoproteins called gp70 includes molecules that are the main constituent of murine C-type viral envelopes, and some that are expressed as mendelian constituents of thymocyte plasma membranes in the absence of virions. To investigate further the relation of viral gp70s to plasma- membrane gp70s we compared peptide maps of gp70s derived by immunoprecipitation from cells infected with chosen viruses and from various thymocytes and leukemiacells known to express one or more of three immunogenetically defined gp70 types: Glx-gp70, X-gp70, and O-gp70. Maps of gp70 from cultured cells infected with ecotropic and xenotropic viruses were distinguishable from one another, and in general resembled gp70 maps prepared directly from ecotropic and xenotropic virions respectively. Maps of gp70s immunoprecipitated from thymocytes of five mouse strains and from two A strain T-cell leukemias also fell into two distinguishable and generally corresponding patterns. Thus peptide-mapping substantiates earlier conclusions that viral gp70s and plasma-membrane gp70s inherited independently of virus-production are highly related or identical molecules. The gp70 maps of thymocytes from B6, B6-G(+IX), 129, and A mice formed a group resembling the map from cultured cells infected with xenotropic virus. Thymocytes from AKR mice, and the two A strain leukemias, gave gp70 maps conforming more to the second pattern, that of cultured cells infected with ecotropic virus. This second pattern probably comprises at least two gp70 types, one of which is X-gp70. Our data indicate that the G(IX)-gp70 and O-gp70 sub-species of gp70 expressed in the cell populations we have studied are coded by xenotropic viral genomes, and X-gp70 by ecotropic viral genomes.     

The similarities and differences of migraine with aura and migraine without aura: a preliminary study

A preliminary study was undertaken to provide clinical evidence to support the hypothesis that: "Migraine with aura, migraine without aura and aura alone are the same condition, which differ in degree rather than pathophysiology." At the City of London Migraine Clinic, 50 patients consecutively attending the clinic with a past or present history of migraine with aura were questioned. Of the 50 patients questioned 36 (70%) had a combination of migraine with aura, migraine without aura and/or aura alone; i.e. 70% had had more than one type of migraine attack. The duration, severity and frequency of attacks did not differ between migraine with and migraine without aura. Conclusion--the results support the hypothesis that migraine with and migraine without aura, and aura alone are not separate conditions, because: (1) most patients suffer from more than one type of migraine attack; (2) there are no significant differences in the characteristics of the migraine attacks in the different groups; (3) there are no significant differences in the characteristics of the subjects.     

Nitric oxide synthase inhibition in the histamine headache model

Histamine has been widely used experimentally to induce headache in healthy subjects and migraine in migraineurs. There is evidence that the vascular effects of histamine are at least partially mediated by nitric oxide (NO). Hence we hypothesized that subjective symptoms and hemodynamic effects of histamine could be reduced by systemic NO-synthase inhibition. We therefore studied the effect of pretreatment with N-monomethyl-L-arginine (L-NMMA), a competitive inhibitor of NO-synthase, or placebo on headache, flush and discomfort scores during histamine infusion. Additionally, blood flow velocities in the middle cerebral and the ophthalmic artery and ocular fundus pulsations were measured. Whereas L-NMMA blunted the effect of histamine in the ophthalmic artery and the ocular circulation, NO-synthase inhibition did not mitigate subjective symptoms. Histamine did not affect mean blood flow velocities in the middle cerebral artery. Hence, we conclude that NO-synthase inhibition reduces the histamine-induced vascular effects in the ocular circulation, but is not sufficient to attenuate or abort the subjective symptoms provoked by histamine infusion.     

ALLERGIC REACTIONS TO LOCAL GLYCERYL TRINITRATE ADMINISTRATION

SUMMARY To assess the exact cause and extent of transdermal glyceryl trinitrate (GTN)-induced allergic reactions, a study of continuous and intermittent use of GTN patches was conducted in 320 patients with New York Heart Association (NYHA) class II and III angina pectoris. Three commercially available GTN patch systems were used. Twenty-one patients (6.5%) developed cutaneous reactions. In 17 patients (5.3%), the reactions were confined to the area of application and were characterised as irritant reactions. Four patients (1.2%) developed both localised and remote from the area of application lesions and one patient developed a generalised anaphylactic reaction. The rate of discontinuation of therapy was 3.4%. The irritant skin reactions were mainly due to contaminants and additives. Changing to a different transdermal system reduced the incidence of local reactions — a particularly desirable effect in patients who respond well to GTN therapy.     

Monocytes and macrophages synthesize and secrete thrombospondin

Thrombospondin, one of the major glycoproteins released from alpha- granules of thrombin-stimulated platelets, is a disulfide-linked trimer of 160,000-dalton subunits. Cultured human monocytes secreted thrombospondin (determined by an enzyme-linked immunosorbent assay) into the culture medium in a time-dependent manner (1.45 micrograms/10(6) cells/24 hr); secretion was totally blocked by cycloheximide (1 microgram/mL). 35S-thrombospondin was isolated from 35S-methionine-labeled human monocyte postculture medium with rabbit polyclonal anti-thrombospondin coupled to protein A-Sepharose. The immunoisolated 35S-thrombospondin migrated in sodium dodecyl sulfate- polyacrylamide gels after reduction with a molecular weight of 159,000. Similar results were obtained using mouse resident peritoneal macrophages. Elicited peritoneal macrophages harvested from mice pretreated with endotoxin, casein, or thioglycollate secreted much less thrombospondin than did resident macrophages harvested from control mice. Thus, monocytes and macrophages from two different species synthesize and secrete thrombospondin, and the rate of synthesis of thrombospondin appears to depend on the state of activation of the cells.     

Atrial natriuretic peptide and the development of congestive heart failure in the oldest old: a seven-year prospective study

BACKGROUND: Atrial natriuretic peptide (ANP) levels are elevated in symptomatic heart failure and correlate with invasively measured left heart pressures. OBJECTIVE: To examine the association between plasma ANP level and the subsequent development of congestive heart failure (CHF) in older subjects with no history of CHF. DESIGN: A 7-year, prospective, blinded, cohort study. SETTING: A life care facility in Boston, Massachusetts. PARTICIPANTS: Two hundred fifty-six frail older subjects (mean age 88 +/- 7) with no history of CHF at study entry. MAIN OUTCOME MEASURE: Clinical episodes of CHF with confirmatory chest roentgenogram findings. Cox proportional hazard analyses were performed to examine the relationship between ANP levels and the development of CHF while controlling for 19 clinical, physical, and laboratory parameters. A Kaplan-Meier estimator (log-rank test) was used to determine if the development of CHF differed by tertile of ANP. RESULTS: During the follow-up period, 32% of the cohort developed CHF. The mean ANP level in the CHF group was 95 pmol/L +/- 11 pmol/L versus 60 pmol/L +/- 5 pmol/L in the no CHF group (two tailed t test P = .005). On multivariate analysis, a high ANP level was found to be associated significantly (P = .01) with the development of CHF. CONCLUSIONS: There is a statistically significant association between ANP level and the subsequent development of CHF in frail older individuals with no history of CHF.     

CHEK2*1100delC homozygosity in the Netherlands—prevalence and risk of breast and lung cancer

The 1100delC mutation in the CHEK2 gene has a carrier frequency of up to 1.5% in individuals from North-West Europe. Women heterozygous for 1100delC have an increased breast cancer risk (odds ratio 2.7). To explore the prevalence and clinical consequences of 1100delC homozygosity in the Netherlands, we genotyped a sporadic breast cancer hospital-based cohort, a group of non-BRCA1/2 breast cancer families, and breast tumors from a tumor tissue bank. Three 1100delC homozygous patients were found in the cohort of 1434 sporadic breast cancer patients, suggesting an increased breast cancer risk for 1100delC homozygotes (odds ratio 3.4, 95% confidence interval 0.4–32.6, P=0.3). Another 1100delC homozygote was found in 592 individuals from 108 non-BRCA1/2 breast cancer families, and two more were found after testing 1706 breast tumors and confirming homozygosity on their wild-type DNA. Follow-up data was available for five homozygous patients, and remarkably, three of them had developed contralateral breast cancer. A possible relationship between 1100delC and lung cancer risk was investigated in 457 unrelated lung cancer patients but could not be confirmed. Due to the small number of 1100delC homozygotes identified, the breast cancer risk estimate associated with this genotype had limited accuracy but is probably higher than the risk in heterozygous females. Screening for CHEK2 1100delC could be beneficial in countries with a relatively high allele frequency.     

Systemic use of non‐biologic agents in orofacial diseases: other immunomodulatory agents

Systemic non‐biologic agents have long been in clinical use in medicine – often with considerable efficacy, albeit with some adverse effects – as with all medications. With the advent of biologic agents, all of which currently are restricted to systemic use, there is a growing need to ensure which agents have the better therapeutic ratio. The non‐biologic agents (NBAs) include a range of agents, most importantly the corticosteroids (steroids). Previous articles by us in this series have discussed systemic use of corticosteroids and purine synthesis inhibitors; the other immunomodulating agents (calcineurin inhibitors, thalidomide, dapsone, colchicine and cyclophosphamide) are reviewed in this final article.