Induction of cachexia in mice by a product isolated from the urine of cachectic cancer patients.

Urine from cancer patients with weight loss showed the presence of an antigen of M(r) 24,000 detected with a monoclonal antibody formed by fusion of splenocytes from mice with cancer cachexia. The antigen was not present in the urine of normal subjects, patients with weight loss from conditions other than cancer or from cancer patients who were weight stable or with low weight loss (1 kg month(-1)). The antigen was present in the urine from subjects with carcinomas of the pancreas, breast, lung and ovary. The antigen was purified from urine using a combination of affinity chromatography with the mouse monoclonal antibody and reversed-phase high-performance liquid chromotography (HPLC). This procedure gave a 200,000-fold purification of the protein over that in the original urine extract and the material isolated was homogeneous, as determined by silver staining of gels. The N-terminal amino acid sequence showed no homology with any of the recognized cytokines. Administration of this material to mice caused a significant (P<0.005) reduction in body weight when compared with a control group receiving material purified in the same way from the urine of a normal subject. Weight loss occurred without a reduction in food and water intake and was prevented by prior administration of the mouse monoclonal antibody. Body composition analysis showed a decrease in both fat and non-fat carcass mass without a change in water content. The effects on body composition were reversed in mice treated with the monoclonal antibody. There was a decrease in protein synthesis and an increase in degradation in skeletal muscle. Protein degradation was associated with an increased prostaglandin E2 (PGE2) release. Both protein degradation and PGE2 release were significantly reduced in mice pretreated with the monoclonal antibody. These results show that the material of M(r) 24,000 present in the urine of cachectic cancer patients is capable of producing a syndrome of cachexia in mice.     

Expression of dose in neutron therapy

A pragmatic approach in neutron dosimetry is to consider the energy spectrum to consist of a neutron and a gamma component. The relationship between the two components of dose in neutron radiotherapy has been investigated for energies currently in clinical use. Changes in the neutron component itself are not dealt with. Because the two components are given simultaneously there is some interaction between them so that the gamma fraction is more effective than if the neutron and gamma doses were separated in time. This interaction has been accounted for using a well-proven extension of the linear-quadratic (LQ) equation. Using values of the LQ parameters alpha and beta measured recently in vivo, we have modelled the total effect from the neutron and gamma dose-contributions in terms of an equivalent neutron dose. This allows a comparison of different methods of expressing the measured physical dose with the biologically effective dose. The current practice in neutron therapy is to give the total (neutron plus gamma) dose, quoting also the gamma contamination. In all cases within the range of energies used for therapy, the total dose will give an overestimate of the biologically effective dose by approximately 4% for each 5% of gamma contamination. Expression of the neutron dose only (ignoring the gamma component) will give an underestimate of the biologically effective dose by approximately 1.5% for each 5% of gamma contamination, i.e. the error is approximately three times less for neutron dose than for total dose.(ABSTRACT TRUNCATED AT 250 WORDS)     

Assessment of HTLV III screening tests in Christchurch

The Christchurch Hospital blood bank has assessed commercial kits designed to test blood donations for the presence of antibody to the retrovirus responsible for acquired immune deficiency syndrome (AIDS). Twenty of 1002 blood donations have been found to be repeatably, positive by one or more of these commercial kits. None was positive by the Western blot technique. Certain patient groups were found to have an elevated number of false positive reactions. Extreme caution is advised when interpreting screening test kit results from donor populations at low risk of AIDS.     

Effectiveness and efficacy of antenatal care

Antenatal care is recommended to pregnant women to improve the outcomes of childbirth. A common pattern of provision is seen in those parts of the industrialised world which have been influenced by British settlers. This paper presents the evolution of the current patterns of care, and the effectiveness and efficacy of the present system are discussed.     

Secretagogue-induced changes in membrane calcium permeability in chicken and chinchilla ileal mucosa. Selective inhibition by loperamide.

Substance P (SP), neurotensin (NT), bombesin (BB), serotonin (5HT), and carbamylcholine (CCH) transiently increase electrogenic anion secretion in chinchilla and chicken ileum. SP and CCH also transiently inhibit amiloride-sensitive Na/H exchange in isolated chicken enterocytes. Loperamide (LP) inhibits the short-circuit current responses caused by SP, NT, and BB, but not those caused by CCH, 5HT, Ca ionophore, or cyclic nucleotides. Similarly, LP inhibits the effects of SP, but not those of CCH, on Na/H exchange. LP inhibition of the SP effects was further studied in isolated chicken enterocytes. CCH and SP transiently increased cytosolic Ca activity by 20-50 nmol/liter, but only the response to SP was inhibited by LP (10(-5) M) and by the absence of extracellular Ca. We conclude SP and CCH effects on intestinal electrolyte transport are mediated by increasing enterocyte Ca activity and LP specifically inhibits peptide hormone-activated Ca entry by an opiate receptor-independent mechanism.     

Who goes to sexually transmitted disease clinics? Results from a national population survey.

OBJECTIVES: To examine the pattern of attendance at sexually transmitted disease (STD) clinics in Britain. To compare the demographic characteristics, behaviours and attitudes of STD clinic attenders with those of non-attenders, and to assess the extent to which STD clinics are used by those with high-risk sexual lifestyles. DESIGN: Random sample general population survey of sexual attitudes and lifestyle. SUBJECTS: 18,876 randomly selected men and women resident in Britain aged 16-59 years. MAIN OUTCOME MEASURES: Demographic characteristics, pattern of homosexual partnerships, heterosexual partnerships, payment for sex, abortion, drug injection in the last five years, and attitudes to sexual behaviours amongst 512 respondents who had attended STD clinic in the last five years compared with those who had not. RESULTS: 8.3% of men and 5.6% of women had attended a clinic in their lifetime and 3.4% and 2.6% respectively in the last five years. Attendance rates varied substantially with area of residence. 11% of Inner London residents had attended in the last five years. In multivariate analysis, STD clinic attendance for men was most strongly associated with increased numbers of heterosexual partners, (OR = 6.01 (4.44-8.15) and homosexual partnerships (OR = 9.59 (5.83-15.8)) and more weakly associated with payment for sex, non-manual social class, age 25-44, unmarried status and smoking. Clinic attendance for women was most strongly associated with numbers of heterosexual partners (OR = 3.74 (2.76-5.08) and injecting drug use (OR = 4.39 (1.73-11.1)). A weaker independent association was found with a history of abortion, anal sex, non-manual social class, non-married status and age 16-24. From the total population, 1 in 6 men and 1 in 7 women in the top 5% of the distribution for numbers of heterosexual partners and 1 in 5 men paying for sex and 1 in 4 of those with a homosexual partner had attended a clinic in the last five years. The probability of attendance increased with multiple risk behaviours. Of women 64.2% and of men 69.7% attending clinics reported major risk markers for STD transmission. CONCLUSIONS: STD clinics in Britain are used by a wide demographic spectrum of the population. The behaviours, but not the attitudes, of attenders differed markedly from those of non-attenders. Clinics are relatively efficient in attracting only those with high-risk lifestyles, but, at a population level, the minority of those reporting risk-markers for STD transmission attend clinics. These findings suggest that STD clinics are an important focus for sexual health promotion, but that community programmes are also important for reaching non-attenders.     

Granulocyte-macrophage colony-stimulating factor: signals for its mRNA accumulation

Granulocyte-monocyte colony-stimulating factor (GM-CSF) is an important hematopoietic growth factor. Mesenchymal cells produce abundant GM-CSF in response to tumor necrosis factor alpha (TNF). We wished to determine (1) what cellular pathways enhanced levels of GM-CSF mRNA, and (2) if TNF used any of these pathways. Modulation in levels of GM- CSF mRNA in human fibroblasts (WI-38) was studied by using Northern blot analysis. Markedly increased levels of GM-CSF mRNA occurred in these cells after exposure to sodium fluoride (NaF) and the effect of NaF was slightly enhanced by aluminum chloride; these results suggest that accumulation of GM-CSF mRNA can occur by activating a G-binding protein. Stimulators of protein kinase C dramatically increased levels of GM-CSF mRNA; however, blockade of protein kinase C activity did not attenuate accumulation of GM-CSF mRNA stimulated by TNF and NaF. Exposure to ouabain increased levels of GM-CSF mRNA and this effect was prominently enhanced in the presence of low concentrations of extracellular K+ and was almost abolished in high concentrations of extracellular K+. A monovalent ionophore (monensin) also increased levels of GM-CSF mRNA. Both ouabain and monensin can increase intracellular Ca++ concentration (Cai++) through Na+-Ca++ exchange. A calcium channel blocker (diltiazem) blocked the increased levels of GM- CSF mRNA mediated by ouabain, but could not block the stimulation mediated by TNF alpha. Ca++ ionophores also increased levels of GM-CSF mRNA and rapidly increased levels of Cai++. TNF did not increase Cai++ and, moreover, was able to stimulate accumulation of GM-CSF mRNA in the absence of extracellular Ca++. Taken together, we have found that several different cellular pathways can lead to prominent accumulation of GM-CSF mRNA in mesenchymal cells including (1) activation of protein kinase C, (2) increase in Cai++, and (3) stimulation of G-binding protein. Our studies show that TNF appears to increase levels of GM-CSF mRNA independent of protein kinase C activity or levels of Cai++.