Poor outcome of adenovirus infections in adult hematopoietic stem cell transplant patients with sustained adenovirus viremia.

The outcome of adenovirus (ADV) infections in adult hematopoietic stem cell transplant (HSCT) patients remains poorly characterized. We studied 14 adults and 3 children, who had undergone HSCT and had developed ADV viremia. Peak ADV DNA levels were significantly higher in patients with ADV diseases than in those without (P=0.03). All children survived the ADV infections. Among the 14 adult HSCT patients, 11 were treated with cidofovir, 2 with ribavirin, and 1 did not receive antiviral treatment. Six of the 13 (46%) treated patients developed ADV diseases and 3 of them (23%) died of ADV infections. Sustained viremia (≥3 positive polymerase chain reaction assays during follow-up) was detected in all patients who finally died of ADV infections. However, 2 adults having had transient ADV viremia either survived or died of diseases other than ADV infections. Our study indicates that the outcome of adult HSCT patients with sustained ADV viremia may be poor, even for those who have received anti-ADV treatment.

Fitness and abdominal obesity are independently associated with cardiovascular risk.

OBJECTIVES: To examine the relationship between cardiovascular fitness (VO(2)max) and abdominal obesity (waist circumference) and individual cardiovascular disease (CVD) risk factors, as well as a clustered risk factor profile, and to study the impact of gender, age and smoking on these relationships. DESIGN: Cross-sectional. SETTING: Astrand Laboratory of Work Physiology, Swedish School of Sport and Health Sciences, Stockholm, Sweden. SUBJECTS: Men (n = 781) and women (n = 890) from two random population-based samples of Swedish women and men aged 20 to 65 years. MAIN OUTCOMES: Odds ratios. RESULTS: Each unit of higher fitness was associated with a decrease in all individual risk factors ranging from 2% to 4% independent of waist circumference, each unit of higher waist circumference was associated with an increased risk ranging from 2% to 5% independent of fitness. For clustering of three or more of the risk factors, each unit of fitness was associated with a 5% decrease in risk and each unit of waist circumference with a 5% increase in risk. The clustered risk was higher in unfit participants who were older or smoked daily, regardless of waist circumference. Obese participants were at higher risk if they were men or older, regardless of fitness level. However, neither a higher fitness level nor lean status reduced the risk associated with smoking. CONCLUSIONS: Higher fitness and lower waist circumference are each independently associated to a similar extent with a lower CVD risk. Simultaneous evaluation of both fitness and abdominal obesity status in clinical practice is important.

Quantification of adenovirus DNA in unrelated donor hematopoietic stem cell transplant recipients.

BACKGROUND: Adenovirus (AdV) infection is a life threatening condition in immunosuppressed patients. Quantitative AdV assays can improve the clinical management of these patients. OBJECTIVES: To evaluate quantitative measurement of AdV DNA with PCR in blood from hematopoietic stem cell transplant (HSCT) recipients. STUDY DESIGN: Quantitative PCR was used to measure viral DNA levels of AdV in consecutive blood samples from 40 HSCT recipients (27 adults and 13 children) during a 1-year post-engraftment period. All patients received grafts from unrelated donors and were given anti-T-cell antibodies in the conditioning regimen. RESULTS: In the group of 40 patients, six (15%) had detectable AdV DNA in blood for different lengths of time. None of these six patients suffered from severe graft-versus-host disease. In three of the patients a high AdV viral load (>10,000 copies/mL) was detected, one of whom also had high viral load of EBV and CMV and one of EBV only. These three patients died within 2 months after detection of ADV viremia. A low AdV viral load (<500 copies/mL) was detected in three surviving patients and they did not have concomitant high viral load of neither CMV nor EBV. CONCLUSIONS: AdV viremia was present in 15% of the HSCT recipients and a high AdV viral load was associated with fatal outcome. Screening for AdV DNA with quantitative PCR in blood may be of clinical importance in allogeneic HSCT recipients in order to prevent severe clinical virological complications.

Secular trends of physical fitness in Swedish adults.

The aim of the present study was to study differences in fitness (maximal aerobic power (VO(2max)), balance control, abdominal strength and endurance) and anthropometric data in Swedish women and men (20-65 years of age) between two national cross-sectional samples, studied in 1990/1991 and 2000/2001, respectively. The absolute and relative VO(2max) (aerobic fitness), estimated from a submaximal test, declined with increasing age in both genders. The submaximal test was validated against running VO(2max). Furthermore, the relative aerobic fitness (mL/min/kg) was lower in the 2000/2001 sample in men but not in women. Overall physical activity level was unchanged in both genders. An unexpected finding was that in both samples there were no major differences in relative VO(2max) between men and women of the same age. Combined overweight and obesity (body mass index> or =25) is becoming more prevalent in men, but not in women with prevalence in 2000/2001 of 61% and 38% for men and women, respectively. Balance control and abdominal strength and endurance decrease with increasing age with no differences between the two samples. Thus, the near future health situation for men may be worse, while for women it may be less or no differences compared with today.

Lipopolysaccharide induces preproenkephalin transcription in hypophysiotropic neurons of the rat paraventricular hypothalamic nucleus suggesting a neuroendocrine role for enkephalins during immune stress.

Opioids have impact on stress responses and possess immune modulatory functions. We have previously shown that immune stress elevates the levels of preproenkephalin transcript in a variety of autonomic structures in the rat brain, including the paraventricular hypothalamic nucleus. By using in situ hybridization with an intronic probe recognizing the preproenkephalin heteronuclear RNA combined with retrograde tract tracing, we examined the efferent target of the enkephalinergic neurons in the paraventricular hypothalamic nucleus that display induced transcriptional activity during immune challenge. Rats were first given i.p. injections of the tracer substance Fluoro-Gold, which following this route of administration is taken up only by nerve terminals residing outside the blood-brain barrier, and were then given an i.v. injection of lipopolysaccharide. Neuronal cell bodies retrogradely labeled with Fluoro-Gold were detected by immunohistochemistry, and-using a dual-labeling approach-the same cells were then examined for their expression of preproenkephalin heteronuclear RNA. We found that over 90% of the neurons that expressed preproenkephalin heteronuclear RNA also contained Fluoro-Gold. In addition, approximately 40% of the neurons expressing preproenkephalin heteronuclear RNA co-expressed mRNA for corticotropin-releasing hormone, the main adrenocorticotropic hormone secretagogue. These data show that the paraventricular hypothalamic neurons that display induced preproenkephalin transcription following immune challenge are almost exclusively hypophysiotropic neurons, indicating a role for enkephalin in the hypothalamic control of hormone release during infectious and inflammatory conditions.

Can differences in benefit levels explain duration and outcome of sickness absence?

PURPOSE: The aim of this study is to examine the long- and short-term economic incentives inherent in the sickness and unemployment insurances. In particular, how the differences, in, for instance, benefit levels between the two systems, affect the duration and outcome of long-term sickness for the unemployed. METHOD: A sample of 280 sick-registered unemployed in the county of Värmland, Sweden was used in two regression models. Sickness duration was modelled in a linear regression and the outcome (healthy and non-healthy) in a logistic regression. RESULTS AND CONCLUSION: The study shows that economic incentives, i.e. differences in benefit levels, help in explaining sickness duration. The proven fact, that benefits from the sickness insurance are in general higher than from the unemployment insurance, results in the sickness spells being prolonged. Indications are also found of a preference for long-term income security through the sickness and disability insurances, using the length of unemployment before sickness registration, as a determinant of the outcome of the sickness spell.

Preproenkephalin mRNA expression in rat parabrachial neurons: relation to cells activated by systemic immune challenge.

By using a dual-labeling immunohistochemical/in situ hybridization technique we examined if enkephalin-expressing neurons in the pontine parabrachial nucleus, a major brain stem relay for ascending visceral and homeostatic information, were activated by systemic immune challenge. While rats subjected to intravenous injection of bacterial wall lipopolysaccharide expressed dense labeling for the immediate-early gene product FOS in parts of the parabrachial nucleus that also demonstrated dense preproenkephalin expression, only a small proportion of the enkephalin-positive neurons were FOS-positive. These data indicate that enkephalins, although implicated in a variety of autonomic responses, are not primarily involved in the transmission of immune-related information from the parabrachial nucleus to its different forebrain and brain stem targets.

Durable engraftment of major histocompatibility complex-incompatible cells after nonmyeloablative conditioning with fludarabine, low-dose total body irradiation, and posttransplantation cyclophosphamide.

Treatment of leukemia by myeloablative conditioning and transplantation of major histocompatibility complex (MHC)-mismatched stem cells is generally avoided because of the high risk of graft rejection or lethal graft-versus-host disease (GVHD). This study shows that MHC-incompatible cells can engraft stably after nonmyeloablative conditioning with immunosuppressive chemotherapy and low-dose total body irradiation (TBI). Long-term mixed hematopoietic chimerism, clonal deletion of donor-reactive T cells, and bidirectional cytotoxic T-cell tolerance were achieved by transplanting MHC-mismatched marrow cells into recipients conditioned with pretransplantation fludarabine or cyclophosphamide (Cy), 50 to 200 cGy TBI on day -1, and Cy 200 mg/kg intraperitoneally on day 3. In this model, long-term donor chimerism was proportional to the dose of TBI or donor marrow cells. Pretransplantation fludarabine and posttransplantation Cy were both required for alloengraftment, but the drugs had additional effects. For example, fludarabine sensitized host stem cells to the toxicity of TBI, because animals conditioned with both agents had higher chimerism than animals conditioned with TBI alone (P <.05). Also, posttransplantation Cy attenuated lethal and nonlethal GVH reactions, because F(1) recipients of host-reactive, parental spleen cells survived longer (P <.05) and had lower donor cell chimerism (P <.01) if they received posttransplantation Cy than if they did not. Finally, delayed infusions of donor lymphocytes into mixed chimeras prolonged survival after leukemia challenge (P <.0001) without causing lethal GVHD. These results indicate that stable engraftment of MHC-incompatible cells can be induced after fludarabine-based, nonmyeloablative conditioning and that it serves as a platform for adoptive immunotherapy with donor lymphocyte infusions.

A test for cleaning and disinfection processes in a washer-disinfector.

Disinfection processes such as heat, aldehydes or alcohols kill vegetative microorganisms but do not necessarily remove other organic contamination. Organic residues impair the result of low-temperature sterilisation processes. Heat-stable organic residues may give rise to clinical symptoms in the patient. Standards are available in Britain and in Sweden for the examination of cleaning processes in washer-disinfectors. The test substances are artificial soil or blood. These standards are based on visual inspection of instruments or equipment. They cannot be used for examination of tubular instruments, nor can they be quantified. For validation of cleaning procedures a simple quantifiable method, which can be performed in an infection control laboratory is needed. We have used suspensions in horse blood of Enterococcus faecalis bacteria and Bacillus subtilis spores to test disinfection and cleaning in a washer-disinfector. Instruments used for laparoscopic surgery were contaminated with a blood bacteria suspension containing 10(7) organisms/ml and then dried and processed in a washer-disinfector using a regular process. Remaining microbial contamination was cultured quantitatively. Nineteen objects were investigated in 10 experiments each. Cleaning, measured as log reduction >5-6 of B. subtilis, was achieved on surfaces that were adequately in contact with the water flow in the machine. Disinfection (and cleaning) measured as log reduction >5-6 of E. faecalis was successful at all points examined. The test method is simple and quantifiable, and can be used to evaluate and to improve cleaning and disinfection processes.

Effects of mixed hematopoietic chimerism in a mouse model of bone marrow transplantation for sickle cell anemia.

Sickle cell anemia (SCA) is an inherited disorder of beta-globin, resulting in red blood cell rigidity, anemia, painful crises, organ infarctions, and reduced life expectancy. Allogeneic blood or marrow transplantation (BMT) can cure SCA but is associated with an 8% to 10% mortality rate, primarily from complications of marrow-ablative conditioning. Transplantation of allogeneic marrow after less intensive conditioning reduces toxicity but may result in stable mixed hematopoietic chimerism. The few SCA patients who inadvertently developed mixed chimerism after BMT remain symptom free, suggesting that mixed chimerism can reduce disease-related morbidity. However, because the effects of various levels of mixed chimerism on organ pathology have not been characterized, this study examined the histologic effects of an increasing percentage of normal donor hematopoiesis in a mouse model of BMT for SCA. In lethally irradiated normal mice that were reconstituted with varying ratios of T-cell-depleted marrow from normal and transgenic "sickle cell" mice, normal myeloid chimerism in excess of 25% was associated with more than 90% normal hemoglobin (Hb). However, 70% normal myeloid chimerism was required to reverse the anemia. Organ pathology, including liver infarction, was present in mice with sickle Hb (HbS) levels as low as 16.8% (19.6% normal myeloid chimerism). Histologic abnormalities increased in severity up to 80% HbS, but were less severe in mice with more than 80% HbS than in those with 40% to 80% HbS. Therefore, stable mixed chimerism resulting from nonmyeloablative BMT may reduce the morbidity from SCA, but prevention of all disease complications may require minimizing the fraction of circulating sickle red cells. (Blood. 2001;97:3960-3965)

Mxi1, a Myc antagonist, suppresses proliferation of DU145 human prostate cells.

BACKGROUND: Mxi1, an antagonist of c-Myc, maps to human chromosome 10q24-q25, a region altered in a substantial fraction of prostate tumors. Mice deficient for Mxi1 exhibit significant prostate hyperplasia. We studied the ability of Mxi1 to act as a growth suppressor in prostate tumor cells. METHODS: We infected DU145 prostate carcinoma cells with an Mxi1-expressing adenovirus (AdMxi1) in vitro, and measured Mxi1 expression, cell proliferation, soft agar colony formation, and cell cycle distribution. To explore mechanisms of Mxi1-induced growth arrest, we performed gene expression analysis. RESULTS: AdMxi1 infection resulted in reduced cell proliferation, reduced soft agar colony formation, and a higher proportion of cells in the G(2)/M phase of the cell cycle. This G(2)/M growth arrest was associated with elevated levels of cyclin B, and reduced levels of c-MYC and MDM2. CONCLUSIONS: The ability of AdMxi1 to suppress prostate tumor cell proliferation supports a role for Mxi1 loss in the pathogenesis of a subset of human prostate cancers. Prostate 47:194-204, 2001.

Regulation of death receptor expression and TRAIL/Apo2L-induced apoptosis by NF-kappaB.

TRAIL (tumour-necrosis factor-related apoptosis ligand or Apo2L) triggers apoptosis through engagement of the death receptors TRAIL-R1 (also known as DR4) and TRAIL-R2 (DR5). Here we show that the c-Rel subunit of the transcription factor NF-kappaB induces expression of TRAIL-R1 and TRAIL-R2; conversely, a transdominant mutant of the inhibitory protein IkappaBalpha or a transactivation-deficient mutant of c-Rel reduces expression of either death receptor. Whereas NF-kappaB promotes death receptor expression, cytokine-mediated activation of the RelA subunit of NF-kappaB also increases expression of the apoptosis inhibitor, Bcl-xL, and protects cells from TRAIL. Inhibition of NF-kappaB by blocking activation of the IkappaB kinase complex reduces Bcl-x L expression and sensitizes tumour cells to TRAIL-induced apoptosis. The ability to induce death receptors or Bcl-xL may explain the dual roles of NF-kappaB as a mediator or inhibitor of cell death during immune and stress responses.

Inhibition of the Ca(2+)-ATPase Pmc1p by the v-SNARE protein Nyv1p.

Pmc1p, the Ca(2+)-ATPase of budding yeast related to plasma membrane Ca(2+)-ATPases of animals, is transcriptionally up-regulated in response to signaling by the calmodulin-calcineurin-Tcn1p/Crz1p signaling pathway. Little is known about post-translational regulation of Pmc1p. In a genetic screen for potential negative regulators of Pmc1p, a vacuolar v-SNARE protein, Nyv1p, was recovered. Cells overproducing Nyv1p show decreased Ca(2+) tolerance and decreased accumulation of Ca(2+) in the vacuole, similar to pmc1 null mutants. Overexpression of Nyv1p had no such effects on pmc1 mutants, suggesting that Nyv1p may inhibit Pmc1p function. Overexpression of Nyv1p did not decrease Pmc1p levels but decreased the specific ATP-dependent Ca(2+) transport activity of Pmc1p in purified vacuoles by at least 2-fold. The effect of Nyv1p on Pmc1p function is likely to be direct because native immunoprecipitation experiments showed that Pmc1p coprecipitated with Nyv1p. Complexes between Nyv1p and its t-SNARE partner Vam3p were also isolated, but these complexes lacked Pmc1p. We conclude that Nyv1p can interact physically with Pmc1p and inhibit its Ca(2+) transport activity in the vacuole membrane. This is the first example of a Ca(2+)-ATPase regulation by a v-SNARE protein involved in membrane fusion reactions.

Regional, demographic and national influences on attitudes and beliefs with regard to physical activity, body weight and health in a nationally representative sample in the European Union.

INTRODUCTION: Although the benefits of physical activity regarding body-weight gain and health in general are now widely accepted, physical activity levels remain low among citizens in the western world. This could be attributed to certain attitudes and beliefs about physical activity. Identifying and understanding these parameters would be the first step in an attempt to increase the levels of physical activity in populations generally characterized as having a sedentary lifestyle. OBJECTIVE: The aim of the present study was to identify the attitudes and beliefs regarding physical activity, body weight and health in a nationally representative sample in the EU and in particular to explore the demographic and national (cultural) influences on attitudes towards physical activity. DESIGN: In each member state of the EU, approximately 1000 adults aged 15 years and over, were selected to complete an interviewer-assisted face-to-face questionnaire. Overall, a sample of 15,239 individuals in the EU participated in the study. Subject selection was quota-controlled to ensure samples in each country were nationally representative. RESULTS: On a European level wide variations were observed regarding the levels, beliefs and attitudes towards physical activity. More positive beliefs were observed among Finns, while less positive beliefs were observed among southern Europeans. A similar pattern was observed for attitudes, with the Portuguese having the highest percentage feeling that they do not need to be more physically active than they already are. However, most southern Europeans felt that a campaign would encourage them to become more active than they already are. On a demographic level, the youngest, more educated and most physically active subjects had more positive attitudes and beliefs towards physical activity and the health benefits derived from it; while for the overweight, beliefs and attitudes toward physical activity were related primarily to the benefits related to weight control. CONCLUSIONS: Lower levels of physical activity, an unwillingness to become active among non-participants and confusion regarding the weight gain benefits and general health benefits of exercise were reported more frequently among southern Europeans and older and less educated subjects. The Finns scored highest in all these parameters, possibly due to the programmes implemented and the beliefs and behaviour changes observed in this country during the last few years. The actions taken in Finland and their benefits could be employed appropriately in the other European states.

Stages of change towards physical activity in a nationally representative sample in the European Union.

OBJECTIVE: To examine the distribution of the stages of change towards physical activity across Europe and the influence of sociodemographic variables on this distribution. DESIGN: A cross-sectional study in which quota-controlled, nationally representative samples of approximately 1000 adults from each country completed a face-to-face interview-assisted questionnaire. SETTING: The survey was conducted in the 15 member states of the European Union between March and April 1997. SUBJECTS: The questionnaire was completed by 15,239 subjects (aged 15 years upwards). Data were weighted by population size for each country and by sex, age and regional distribution within each member state. RESULTS: Twenty-nine per cent of subjects were in the precontemplation stage, while a similar proportion (30%) were in the maintenance stage. Ten per cent had been physically active but had relapsed recently. Considerable intercountry variation existed with Scandinavian countries tending to be lower in the precontemplation stage and southern countries tending to be higher (particularly Greece and Portugal). Men and younger subjects with a higher education level were more likely to be in the maintenance stage. Overweight and obese subjects were more likely to be in the precontemplation stage than normal-weight subjects. In terms of barriers to participating in physical activity 'not being the sporty type' was more important for those in precontemplation stages, while 'work/study commitments' was more important for those people in the maintenance stage. CONCLUSIONS: The model of the stages of behavioural change towards physical activity was able to distinguish people according to their level and attitude to physical activity. The considerable intercountry and sociodemographic variation in the distribution of stages of change suggest that targeted programmes aimed at specific subgroups in the population identified using the model may be more effective in promoting physical activity.

Erythrocytic protein kinase C activity in primary hypertension.

OBJECTIVES: Increased protein kinase C activity has been reported in erythrocytes from patients with primary hypertension and also from hypertensive rats. In this phenomenological study, we investigated whether a possible increased activity was the result of an augmented amount of enzyme molecules or a more active enzyme. DESIGN: Collect blood samples, separate erythrocytes from other blood cells. After partial purification of protein kinase C in the erythrocyte lysate, assay the enzyme activity under optimal conditions using a specific peptide substrate. SETTING: Central Hospital in Eskilstuna and University Hospital in Uppsala, Sweden. SUBJECTS: Healthy individuals: 47 persons (20 women and 27 men). Ten patients with untreated primary hypertension. MAIN OUTCOME MEASURES: Erythrocytes were separated from leucocytes and platelets by passing through a cellulose column followed by repeated washings. Some proteins in the erythrocyte lysate interfering with protein kinase C assay were removed by chromatography on DEAE-cellulose. RESULTS: The mean protein kinase C activity in erythrocytes from healthy individuals was 0.18 +/- 0.02 pmol [32P]phosphate min(-1) x 10(6) cells, regardless of sex and age. The corresponding value for patients with primary hypertension was 0.16 +/- 0.04 pmol [32P]phosphate min(-1) x 10(6) cells. CONCLUSIONS: The amount of protein kinase C, measured as the activity at optimal assay conditions, in erythrocytes from patients with primary hypertension is not critical for the development of moderate hypertension.

Diabetes and it's complications in a Swedish county.

A cross-sectional survey with the aim to study the prevalence of diabetes and long-term complications was carried out in a health care district in Sweden with 125,500 inhabitants. Information was extracted from the medical records. 4127 people with diabetes were identified of whom 87% were classified as NIDDM (non-insulin-dependent diabetes mellitus), 12% as IDDM (insulin-dependent diabetes mellitus) and 0.7% as secondary or unclassified diabetes. The prevalence of diagnosed diabetes was 3.3%. A total of 83% received their regular routine care at primary health care centres, 31% were treated with diet only, 36% had oral hypoglycaemic agents, 31% had insulin and 2% had combination therapy. The mean HbA1c was 7.2% (ref. range 4.0-5.3%). Of the adults (> 18 years) 27% had retinopathy, 13% had nephropathy and 27% had loss of pallaesthesia. 50% had hypertension, 21% angina pectoris, 11% had had myocardial infarction, 11% stroke, 21% had signs of peripheral arterial disease, 2% had been amputated and 21% were smokers. The conclusion is that in a population of patients with diabetes with acceptable metabolic control, complications are still a great problem.

Role of fluidity of membranes on the guanyl nucleotide-dependent binding of cholecystokinin-8S to rat brain cortical membranes.

The binding of [3H]cholecystokinin octapeptide (sulphated) ([3H]CCK-8S), an agonist of the cholecystokinin receptors, to rat cortical membranes was fast, specific and saturable, with pH optimum at 6.5-7.0. The divalent cations Mg2+ and Ca2+ clearly enhanced [3H]CCK-8S binding, whereas the monovalent cations Na+ and K+ were inhibitors. Inactivation of the ligand binding ability of these membranes was dependent on the incubation temperature and corresponding tau1/2 values were 11 days at 4 degrees , 12 hr at 21 degrees , 154 min at 30 degrees and 51 min at 37 degrees , which revealed the apparent activation energy of this process to be 130+/-4 kJ/mol. Scatchard analysis of the saturation curves of [3H]CCK-8S binding was best described by a one site binding model with a Kd = 0.63+/-0.18 nM and a maximum binding of 32+/-2 fmol/mg protein. The stable GTP analogue guanosin-5'-O-(3-thiotriphosphate) (GTPgammaS) decreased the affinity of [3H]CCK-8S binding only up to 2-fold without significant influence on maximal binding. Modulation of membrane properties by different detergents revealed that only in the case of digitonin (0.03-0.04%) did the GTP-dependence of [3H]CCK-8S binding considerably increase without significant influence on the ligand binding properties in the absence of GTPgammaS. Other detergents studied (sodium cholate, sodium deoxycholate, 3-(3-cholamidopropyl)dimethylammonio-1-propanesulfonate (CHAPS), sucrose monolaurate, series Triton X and Tween) either had little influence on GTP-gammaS-dependence of [3H]CCK-8S binding or inactivated the receptor. Parallel studies of fluorescent polarization of diphenylhexatriene (DPH) in rat cortical membranes indicated that digitonin was the only detergent which at low concentrations caused a rapid increase in membrane fluidity and thereafter stabilized it at a certain level. Other detergents studied had only moderate influence on membrane fluidity (CHAPS, cholate, deoxycholate) or caused fast and continuous increase of membrane fluidity (Triton X-100, Tween 80). These data together point to the essential influence of the fluidity of membranes on the regulation of the interactions between G proteins and CCK receptors in rat cortical membranes. Under standard experimental conditions (temperature lower than 30 degrees), the CCK receptor-G protein complex is active for quantitative characterization of the receptors, but the membranes are too rigid for natural communication and regulation.

Enhanced generation of interleukins 1 beta and 6 may contribute to the cachexia of chronic disease.

The cachexia of disease may be promoted by proinflammatory cytokines, eg, interleukin (IL) 1 beta, tumor necrosis factor alpha (TNF-alpha), and IL-6. These, as well as some antiinflammatory cytokines, eg, IL-1 receptor antagonist (IL-1ra), IL-10, and transforming growth factor beta 1 (TGF-beta 1), were analyzed in serum (IL-6, IL-1ra, IL-10, TGF-beta 1) and stimulated blood monocytes (IL-1 beta, TNF alpha, IL-6) obtained from elderly patients with protein-energy malnutrition (PEM). Twenty-one uninfected malnourished patients aged 75 +/- 1 y (mean +/- SD), with a body mass index (BMI; in kg/m2) of 17.2 +/- 0.5 and various noncancer disorders, and 22 healthy matched control subjects aged 72 +/- 1 y, with a BMI of 25.4 +/- 0.7 (significantly different from patients, P < 0.001), were included. Fifteen patients and their corresponding control subjects were reexamined 3 mo later. Isolated monocytes were stimulated with lipopolysaccharide (LPS) and concentrations of IL-1 beta, TNF-alpha, and IL-6 were determined. Serum concentrations of IL-6, IL-1ra, IL-10, TGF-beta 1, and acute-phase reactants were analyzed. Serum concentrations of orosomucoid and IL-6 were higher in the malnourished subjects than in the control subjects (1.14 +/- 0.1 compared with 0.8 +/- 0.3 g/L, P < 0.001; and 5 ng/L compared with undetectable concentrations, P < 0.01, respectively). Higher generation of IL-1 beta (2.7-fold; P < 0.05) and IL-6 (3.7-fold; P < 0.05) was found in monocytes from patients with PEM relative to the control subjects when monocytes were stimulated with 0.1 microgram LPS/L. Monocyte TNF generation and serum concentrations of IL-10, IL-1ra, and TGF-beta 1 did not differ. Similar results were obtained at follow-up. IL-1ra was negatively correlated with delayed cutaneous hypersensitivity (r = -0.34, P < 0.05). We conclude that enhanced generation of proinflammatory cytokines such as IL-6 and IL-1 beta in malnourished patients may contribute to the PEM often encountered in chronic nonmalignant disorders.