Serum IL-23 significantly decreased in obese patients with psoriatic arthritis six months after a structured weight loss intervention.

INTRODUCTION: Patients with psoriatic arthritis (PsA) are frequently obese. We have previously shown decreased disease activity in patients with PsA with a body mass index (BMI) ≥ 33 kg/m2 following weight loss treatment with Very Low Energy Diet (VLED), resulting in a median weight loss of 18.6% at six months (M6) after baseline (BL). In this study we assessed the effects of VLED on cytokines and adipokines at M6 in the same patients with PsA and controls (matched on sex, age and weight). METHODS: VLED (640 kcal/day) during 12 or 16 weeks, depending on BL BMI < 40 or ≥ 40 kg/m2, was taken and followed by an energy-restricted diet. Cytokines and adipokines were measured with Magnetic Luminex Assays at BL and M6. RESULTS: Serum interleukin (IL)-23, (median (interquartile range) 0.40 (0.17-0.54) ng/mL vs. 0.18 (0.10-0.30) ng/mL, p < 0.001) and leptin (26.28 (14.35-48.73) ng/mL vs. 9.25 (4.40-16.24) ng/mL, p < 0.001) was significantly decreased in patients with PsA. Serum total (tot)-adiponectin and high molecular weight (HMW) adiponectin increased significantly. Similar findings were found in controls. Also, in patients with PsA, ∆BMI was positively correlated with ∆IL-23 (rS = 0.671, p < 0.001). In addition, significant positive correlations were found between ΔBMI and ΔDisease Activity Score (DAS28CRP), ΔCRP, Δtumor necrosis factor (TNF)-α, ΔIL-13, ∆IL-17 and Δleptin, and negative correlations between ΔBMI and Δtot-adiponectin. CONCLUSIONS: Weight loss was associated with decreased levels of leptin and cytokines, in particular IL-23. These findings may partly explain the anti-inflammatory effect of weight reduction in PsA. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02917434, registered on September 21, 2016, retrospectively registered.

Fracture risk after three bariatric surgery procedures in Swedish obese subjects: up to 26 years follow-up of a controlled intervention study.

BACKGROUND: Previous studies have reported an increased fracture risk after bariatric surgery. OBJECTIVE: To investigate the association between different bariatric surgery procedures and fracture risk. METHODS: Incidence rates and hazard ratios for fracture events were analysed in the Swedish Obese Subjects study; an ongoing, nonrandomized, prospective, controlled intervention study. Hazard ratios were adjusted for risk factors for osteoporosis and year of inclusion. Information on fracture events were captured from the Swedish National Patient Register. The current analysis includes 2007 patients treated with bariatric surgery (13.3% gastric bypass, 18.7% gastric banding, and 68.0% vertical banded gastroplasty) and 2040 control patients with obesity matched on group level based on 18 variables. Median follow-up was between 15.1 and 17.9 years for the different treatment groups. RESULTS: During follow-up, the highest incidence rate for first-time fracture was observed in the gastric bypass group (22.9 per 1000 person-years). The corresponding incidence rates were 10.4, 10.7 and 9.3 per 1000 person-years for the vertical banded gastroplasty, gastric banding and control groups, respectively. The risk of fracture was increased in the gastric bypass group compared with the control group (adjusted hazard ratio [adjHR] 2.58; 95% confidence interval [CI] 2.02-3.31; P < 0.001), the gastric banding group (adjHR 1.99; 95%CI 1.41-2.82; P < 0.001), and the vertical banded gastroplasty group (adjHR 2.15; 95% CI 1.66-2.79; P < 0.001). CONCLUSIONS: The risk of fracture is increased after gastric bypass surgery. Our findings highlight the need for long-term follow-up of bone health for patients undergoing this treatment.

Cardiovascular risk factors are highly overrepresented in Swedish patients with psoriatic arthritis compared with the general population.

Objectives: We aimed to determine the prevalence of cardiovascular risk factors in patients with psoriatic arthritis (PsA) followed at a large Swedish Rheumatology Clinic, and to compare differences in cardiovascular risk factors between men and women with PsA and with the general population.Method: A questionnaire was sent to patients with PsA registered at the Rheumatology Clinic at Sahlgrenska University Hospital, Gothenburg (n = 982). Comparisons with the general population were made using data from the Swedish National Public Health Survey. Descriptive statistics are presented. Body mass index (BMI) was calculated using self-reported height and weight.Results: Overall, 692 (70.6%) of the patients with PsA responded. The mean ± sd age was 55.6 ± 11.4 years and 52% were women. Obesity (BMI ≥ 30 kg/m2) was more prevalent (p < 0.001) in patients with PsA (28.6%) than in matched subjects from the general population (16.3%). Hypertension was also more prevalent (p < 0.001) in PsA (40.3%) than in matched subjects from the general population (24.1%), as was diabetes, with a prevalence of 10.5% in the PsA population compared with 6.2% in matched subjects (p < 0.001).Conclusion: We found obesity to be highly overrepresented in patients with PsA compared with matched subjects from the general population. This difference was particularly seen in women with PsA. Hypertension and ever smoking were also more prevalent in women with PsA compared with matched subjects from the general population.

SFPO and ESOP recommendations for the practical stability of anticancer drugs: an update.

The recommendations for the practical stability of anticancer drugs published in 2010 by the French Society of Hospital Pharmacists (SFPO) and the European Society of Oncology Pharmacists (ESOP) have been updated. Ten new molecules have been included (asparaginase, azacitidine, bevacizumab, clofarabine, eribuline mesylate, folinate sodium, levofolinate calcium, nelarabine, rituximab, temsirolimus).

Decreased energy density and changes in food selection following Roux-en-Y gastric bypass.

BACKGROUND/OBJECTIVES: The main objective was to test the hypothesis that dietary energy density (DED) decreases after Roux-en-Y gastric bypass (gastric bypass). SUBJECTS/METHODS: A total of 43 patients (31 women and 12 men) aged 43 (s.d. 10) years, with body mass index (BMI) 44.3 kg/m(2) (4.9), were assessed preoperatively at 6 weeks and 1 and 2 years after gastric bypass. Self-reported energy intake (EI), food weight (FW) and food choice were assessed using a dietary questionnaire. DED was calculated by dividing EI by FW (kcal/g). Number of dropouts was 4 of 203 visits. RESULTS: Percent weight loss (%WL) was 13.5% at 6 weeks, 30.7% at 1 year and 31.8% at 2 years post surgery (P<0.001 for all). EI decreased from 2990 to 1774, 2131 and 2425 kcal after 6 weeks and 1 and 2 years postoperatively, respectively (P<0.001 at all time points). FW changed from 2844 to 1870 g/day at 6 weeks (P<0.001) and 2416 g/day after 1 year (P<0.05), but was not significantly different from baseline 2 years postoperatively (2602 g/day, P=0.105). DED decreased from 1.07 to 0.78 kcal/g at 6 weeks (P<0.001) and 0.90 kcal/g (P<0.001) and 0.96 kcal/g (P=0.001) after 1 and 2 years, respectively. All statistical comparisons were made from baseline. There was no correlation between changes in DED and %WL, neither after 1 year (r=-0.215; P=0.183) nor after 2 years (r=-0.046; P=0.775) post surgery. CONCLUSIONS: Besides substantial reduction in EI and large variation in FW, patients reported decreased DED over 2 years following gastric bypass. Despite lack of association between the reduction in DED and percentage weight loss, changes in food choice were overall nutritionally beneficial.

Gene expression profiling of placentae from women with early- and late-onset pre-eclampsia: down-regulation of the angiogenesis-related genes ACVRL1 and EGFL7 in early-onset disease.

The underlying mechanisms behind the obstetric condition pre-eclampsia (PE) are still unclear. Manifestation of PE is heterogeneous and it has therefore been proposed to be a syndrome with different causes rather than one disease with a specific aetiology. Recently, we showed differences in circulating angiogenic factors between two subgroups-early- and late-onset PE. To further elucidate the differences between the two, we investigated placental gene expression profiles. Whole genome microarray technology and bioinformatic analysis were used to evaluate gene expression profiles in placentae from early- (24-32 gestational weeks, n = 8) and late-onset (36-41 gestational weeks, n = 7) PE. The results were verified by using quantitative real-time (qRT)-PCR. We found significant differences in the expression of 196 genes in early- compared with late-onset PE, 45 of these genes showing a fold change above 2. Bioinformatic analysis revealed alterations in angiogenesis and regulation of cell motility. Two angiogenesis-associated transcripts (Egfl7 and Acvrl1) showed lower expression in early-onset PE versus late-onset PE (P = 0.037 and P = 0.003) and versus gestational age-matched controls (P = 0.007 and P = 0.011). We conclude that angiogenesis-associated genes are regulated in a different manner in the two subgroups, and that the gene expression profiles of early- and late-onset PE diverge, supporting the hypothesis of early- and late-onset PE being at least partly two separate entities.

Changes in eating behaviour and meal pattern following Roux-en-Y gastric bypass.

BACKGROUND: Little is known about eating behaviour and meal pattern subsequent to Roux-en-Y gastric bypass (RYGB), knowledge important for the nutritional care process. The objective of the study was to obtain basic information of how meal size, eating rate, meal frequency and eating behaviour change upon the RYGB surgery. MATERIALS AND METHODS: Voluntary chosen meal size and eating rate were measured in a longitudinal, within subject, cohort study of 43 patients, 31 women and 12 men, age 42.6 (s.d. 9.7) years, body mass index (BMI) 44.5 (4.9) kg m(-2). Thirty-one non-obese subjects, 37.8 (13.6) years, BMI 23.7 (2.7) kg m(-2) served as a reference group. All subjects completed a meal pattern questionnaire and the Three-Factor Eating Questionnaire (TFEQ-R21). RESULTS: Six weeks postoperatively meal size was 42% of the preoperative meal size, (P<0.001). After 1 and 2 years, meal size increased but was still lower than preoperative size 57% (P<0.001) and 66% (P<0.001), respectively. Mean meal duration was constant before and after surgery. Mean eating rate measured as amount consumed food per minute was 45% of preoperative eating rate 6 weeks postoperatively (P<0.001). After 1 and 2 years, eating rate increased to 65% (P<0.001) and 72% (P<0.001), respectively, of preoperative rate. Number of meals per day increased from 4.9 (95% confidence interval, 4.4,5.4) preoperatively to 6 weeks: 5.2 (4.9,5.6), (not significant), 1 year 5.8 (5.5,6.1), (P=0.003), and 2 years 5.4 (5.1,5.7), (not significant). Emotional and uncontrolled eating were significantly decreased postoperatively, (both P<0.001 at all-time points), while cognitive restraint was only transiently increased 6 weeks postoperatively (P=0.011). CONCLUSIONS: Subsequent to RYGB, patients display markedly changed eating behaviour and meal patterns, which may lead to sustained weight loss.

Increased cystatin C expression in the pre-eclamptic placenta.

Trophoblast invasion is regulated by proteinases and their inhibitors. Cystatin C inhibits cysteine proteinases. The serum concentration of cystatin C is increased in late pregnancy and pre-eclampsia. We aimed to investigate whether the expression of cystatin C is increased in the pre-eclamptic placenta and to investigate the expression pattern of cystatin C mRNA and protein in placental tissue. Tissue samples from the central part of the placenta from 13 normal and 22 pre-eclamptic pregnancies were included. We used real-time polymerase chain reaction (RT-PCR) and in situ hybridization for mRNA expression analysis and immunohistochemistry and Western blotting for protein expression analysis. RT-PCR showed a significantly higher expression of cystatin C mRNA in pre-eclampsia than in normal pregnancy, with the highest expression in cases with severe pre-eclampsia. In situ hybridization revealed a distinct pattern of high expression in the extravillous trophoblast cells of the basal plate and low expression in the syncytiotrophoblast covering villi. The cystatin C protein distribution matched the mRNA expression pattern. Western blot analysis revealed an increased protein expression in cases with severe pre-eclampsia and confirmed the presence of cystatin C in amniotic fluid samples. The high expression of cystatin C mRNA in the extravillous trophoblast cells of the basal plate suggests a role for cystatin C in the regulation of proteases in placentation. Placental expression and secretion of cystatin C could contribute to the elevated maternal plasma levels seen in pre-eclampsia.

Gene expression profiling of human placentas from preeclamptic and normotensive pregnancies.

The aim of this study was to investigate patterns of gene expression in placental samples from patients with preeclampsia (PE), persistent bilateral uterine artery notching (without PE), and normal controls. This study included placental tissue from nine women with PE, seven with uncomplicated pregnancies and five with bilateral uterine artery notching in Doppler velocimetry tracings. Human cDNA microarrays with 6500 transcripts/genes were used and the results verified with real-time PCR and in-situ hybridization. Multidimensional scaling method and random permutation technique demonstrated significant differences among the three groups examined. Within the 6.5K arrays, 6198 elements were unique cDNA clones representing 5952 unique UniGenes and 5695 unique LocusLinks. Multidimensional scaling plots showed 5000 genes that met our quality criteria; among these, 366 genes were significantly different in at least one comparison. Differences in three genes of interest were confirmed with real-time PCR and in-situ hybridization; acid phosphatase 5 was shown to be overexpressed in PE samples and calmodulin 2 and v-rel reticuloendotheliosis viral oncogene homolog A (RELA) were downregulated in PE and uterine artery notch placentas. In conclusion downregulation of RELA and calmodulin 2 might represent an attempt by the placenta to compensate for elevations in intracellular calcium, possibly caused by hypoxia and/or apoptosis, in both pregnancies with uterine artery notching and preeclampsia.

Important differences in nitric oxide synthase activity and predominant isoform in reproductive tissues from human and rat.

For the extrapolation of data obtained from experimental animals to the human situation, it is important to know the similarities and differences between human and animal species. Some important characteristics of nitric oxide synthase (NOS) in myometrium and vagina from human and rat were compared. NOS-activity was measured by the formation of 14C-citrulline from 14C-arginine and the expression of NOS isoforms was examined by Western blotting. NOS activity in human uterus and vagina was significantly lower than in the tissues from rat. In contrast to the rat where NOS activity was predominantly found in the cytosolic fractions, NOS activity in particulate and cytosolic fractions from both human myometrium and vagina was similar. Data from Western blots confirmed that eNOS and nNOS isoforms were concentrated in the particulate and cytosolic fractions, respectively. Estrogen treatment of rats resulted in a down regulation of uterine cytosolic NOS activity. A down regulation of NOS in the cytosolic fraction was also seen in the human pregnant myometrium as compared with the nonpregnant myometrium. The vaginal NOS activity was considerably higher than the uterus in both species. In spite of some clear-cut qualitative and other differences between human and rat tissues, there are some interesting similarities. Downregulation in pregnancy of human uterine NOS is probably due to, at least in part, the influence of estrogen and progesterone.

Effect of ovarian steroids on nitric oxide synthase in the rat uterus, cervix and vagina.

The effects of estrogen (E2), progesterone (P) and E2 and P (E2 + P) were examined on nitric oxide synthase (NOS) activity in both cytosolic and particulate fractions isolated from the rat uterus, vagina, cervix and cerebral cortex. Additionally plasma nitrate + nitrite (NO3 + NO2) levels were measured in control and hormone treated rats. Cytosolic NOS was the predominant form being approximately 80% of the total in all four tissues. NOS activity in both fractions from all tissues was highly Ca-dependent (> 90%). Among the reproductive tract tissues, the highest activity was found in the cervix, which was nearly 5- and 2-fold higher than the uterus and vagina, respectively. NOS activity in the cerebral cortex was by far the highest being 5-fold higher than in the cervix. In contrast to the cortex, E2 treatment downregulated cytosolic NOS in all reproductive tract tissue, but this was statistically significant in only uterus. When compared with E2 treated rats, P increased cytosolic NOS in uterus, vagina, and particulate NOS in the cervix. The data do not give any indication whatsoever of differential effects of P in the uterus and cervix.

Paranasal sinus ventilation in healthy subjects and in patients with sinus disease evaluated with the 133-xenon washout technique.

Ventilation of the paranasal sinuses is of great importance in sinus pathophysiology. Therefore, methods of measuring sinus ventilation are important for the evaluation of patients with sinus disease. In the present study, a 133-xenon washout technique was used to evaluate the ventilation of the paranasal sinuses in 34 healthy subjects and in 13 subjects with sinus disease (5 patients with nasal polyposis and 8 patients with chronic sinusitis). For this purpose, a 133-xenon-air mixture was insufflated in each nostril and the washout of the radioactive gas from the paranasal sinuses was monitored with a dynamic single-photon-emission computed tomography camera. The half-time (+/-SD) was found to be 18 +/- 18 minutes for the maxillary sinus, 10 +/- 8 minutes for the frontal sinus, and 18 +/- 23 minutes for the posterior ethmoid and sphenoid sinuses in the healthy subjects. Repeated measurements in 18 of the healthy subjects indicated that the method had acceptable reproducibility according to a Bland-Altman plot. The 133-xenon washout was not influenced by insufflation pressure, nasal patency, or body position. The subjects with sinus disease exhibited half-times of 77 +/- 101 minutes for the maxillary sinus, 91 +/- 124 minutes for the frontal sinus, and 60 +/- 60 minutes for the posterior ethmoid and sphenoid sinuses. For patients with nasal polyposis, the half-time was significantly longer than that in healthy subjects, while patients with chronic sinusitis did not differ from healthy subjects in this respect.

Mitochondrial and microsomal peripheral benzodiazepine receptors in human ovarian cancer xenografts.

To investigate whether the density of peripheral benzodiazepine receptors (PBR) in human ovarian tumors is related to the degree of histological differentiation and possibly elucidate their pathophysiology, PBR were measured in mitochondrial (m) and microsomal (p) fractions isolated from six different human ovarian carcinomas heterotransplanted into nude mice. A specific ligand PK11195 for PBR was employed and the density of binding sites and binding affinity (KD) were computed from Scatchard analysis. The PBR density in m-fractions was 3- to 4-fold higher than in p-fractions from all tumors. PBR density in both m- and p-fractions was highest in mucinous tumors with mid-high degree of differentiation. The density in serous tumor with mid-high differentiation was significantly lower than the mucinous tumor, but higher than the serous tumor with low degree of differentiation (OVCAR-3) in both m- and p-fractions. However, the PBR density in the undifferentiated tumor (IGROV1) was higher than in OVCAR-3. The KD values for PBR were very low ranging from 5.8 to 14.0 nM in all preparations. The KD values for p-fractions were generally lower than m-fractions and highly significant differences were observed in three of the six tumors. These data suggest two separate classes of PBR pertaining to m- and p-fractions and indicate that there is no clear relationship between PBR density and degree of differentiation.

Cloning of beta-microseminoprotein of the rat: a rapidly evolving mucosal surface protein.

beta-Microseminoprotein is a small, nonglycosylated protein, rich in disulfide bonds, which is present in the secretions of the airways, the gastrointestinal tract, and the urogenital tract. Its function is unknown. It was originally characterized in the human and it has been difficult to identify the homologous protein in species other than primates. We have purified beta-microseminoprotein from rat prostate and from amino acid sequencing we have been able to clone the protein. The results reinforce conclusions reached earlier that beta-microseminoprotein is a rapidly evolving protein. Overall amino acid identities are only 45, 50, and 40% when the rat protein is compared with the proteins from the human, the ape, and the pig, respectively. However, the 10 cysteines are all completely invariant between these four species. The cloning of beta-microseminoprotein in the rat have substantially improved the possibilities to reveal the function of this mucosal surface protein.

Binding of vinblastine and estramustine to isolated plasma membrane fractions from human prostate and prostatic tumors.

The binding of vinblastine (VLB) and estramustine (EM) to plasma membranes isolated from human prostate, prostatic tumors as well as from Dunning rat prostatic AT-1 tumors was studied. In addition, the uptake of these drugs in AT-1 tumor cells in culture was examined. Binding of VLB was six-fold lower than that of EM in membrane preparations from all three sources. The uptake of VLB in the intact AT-1 cells was nearly five-fold lower than that of EM. At concentrations comparable to those achieved clinically the binding of EM was 100-fold higher than that of VLB. The data suggest that, owing to a very high membrane concentration of EM relative to that of VLB, the active efflux VLB in drug resistant cells would be impeded. This in turn would lead to a higher accumulation of VLB in cells that actively transport cytotoxic drugs.

The human I alpha 1 region contains a TGF-beta 1 responsive enhancer and a putative recombination hotspot.

It appears that the switch recombination machinery of a B lymphocyte targets preferentially unrearranged heavy chain genes that have been rendered transcriptionally active. Transcriptional activation of the 'germline' human C alpha 1 and C alpha 2 genes is triggered by TGF-beta 1 and is controlled by proximal positive and distal negative regulatory elements residing upstream of the alpha 1 and alpha 2 switch regions respectively. In this report we characterize the positive proximal regulatory elements and analyse their interaction with DNA binding proteins. Our data demonstrate that a 100 bp fragment that contains a cAMP responsive element (CRE)/activating transcription factor (ATF) motif, a putative Ets binding site and an element that is created by two previously described neighbouring direct repeats (DRE), can increase the basal level of transcription and confer TGF-beta 1 inducibility to a heterologous promoter in an orientation- and position-independent manner. Ubiquitously expressed DNA binding proteins interact specifically with the CRE/ATF, the Ets site and the DRE element. Additionally, nuclear proteins interact with sequences which are located downstream of this enhancer are not essential for transcription in the transient expression assays utilized; however, they contain motifs that have been previously implicated in regulating DNA recombination events. These motifs include a Chi motif and a Chi-like element previously found in the recombination hotspot region of the Bcl-2 proto-oncogene and close to chromosomal breakpoints in T-ALL lines. Our findings raise the possibility that the intervening region associated regulatory elements in addition to regulating the transcriptional activation of the Ig heavy chain genes could also facilitate the physical interaction of transcription and recombination controlling molecular mechanisms.

Genomic organization of mouse and human Bruton's agammaglobulinemia tyrosine kinase (Btk) loci.

Btk is a cytoplasmic protein tyrosine kinase (PTK) that has been directly implicated in the pathogenesis of X-linked agammaglobulinaemia (XLA) in humans and X-linked immunodeficiency (Xid) in mice. We have isolated phage and cosmid clones that allowed us to deduce the genomic structure of mouse and human Btk loci. The mouse and human genes are contained within genomic regions that span approximately 43.5 kb and 37.5 kb, respectively. Both loci contain 18 coding exons ranging between 55 and 560 bp in size with introns ranging in size from 164 bp to approximately 9 kb. The 5'-untranslated regions are encoded by single exons located approximately 9 kb upstream of the first coding exon. Exon 18 encodes for the last 23 carboxyl-terminal amino acids and the entire 3'-untranslated region. The location of intron/exon boundaries in the catalytic domains of the mouse and human Btk loci differs from that found in other described sub-families of intracellular PTKs, namely that of Src, Fes/Fer, Csk, and Abl/Arg. This observation is consistent with the classification of Btk together with the recently characterized kinases, Tec and Itk, into a separate sub-family of cytoplasmic PTKs. Putative transcription initiation sites in the mouse and human Btk loci have been determined by using the rapid amplification of cDNA ends assay. Similar to many other PTK specific genes, the putative Btk promoters lack obvious TATAA and CAAAT motifs. Putative initiator elements and potential binding sites for Ets (PEA-3), zeste, and PuF transcription factors are located within the 300 bp which are located upstream of the major transcription start site in both species. These sequences can mediate promoter activity when placed upstream of a promotorless chloramphenicol acetyl transferase reporter gene in an orientation-dependent manner. The present analysis will significantly facilitate the mutational analyses of patients with XLA and the further characterization of the function and regulation of the Btk molecule.

Effects of certain inflammatory mediators on bovine neutrophil migration in vivo and in vitro.

Migration of bovine neutrophils towards endotoxin, recombinant bovine interleukin-1 beta (rBoIL-1 beta), recombinant human tumor necrosis factor-alpha (rhTNF-alpha), platelet-activating factor (PAF), complement factor C5a, leukotriene B4 (LTB4), and recombinant human interleukin-8 (rhIL-8) was studied in vivo, using the teat cistern model, and in vitro using the modified Boyden chamber method. Infusion of endotoxin, rBoIL-1 beta, rhTNF-alpha, PAF, or C5a into the teat cistern induced significant accumulation of leukocytes, mainly neutrophils, during the sampling period. Endotoxin was, on a molar basis, the most potent inducer of cell accumulation in vivo, followed by rBoIL-1 beta, while C5a, PAF and rhTNF-alpha were less potent. No significant cell accumulation was observed after infusion of LTB4 or rhIL-8. A significant migration of cells into the teat cistern was first observed 2 h after the infusion of endotoxin or rBoIL-1 beta, the rBoIL-1 beta-induced response started somewhat earlier. The first significant cell accumulation after infusion of PAF or C5a was observed already 1.5 h post infusion. The largest numbers of cells were reached 2.5-4.5 h after the infusion of endotoxin, rBoIL-1 beta, rhTNF-alpha, PAF or C5a. In vitro, significant migration of bovine blood neutrophils was observed towards C5a or rhIL-8, and to a lower extent towards LTB4, while no chemotactic response to endotoxin, rBoIL-1 beta, rhTNF-alpha, and PAF was observed. Possible roles of the different substances as inducers of neutrophil migration into the bovine teat are discussed.

Allelotyping of human prostatic adenocarcinoma.

Allelotyping (using at least one probe detecting a restriction fragment length polymorphism on each chromosomal arm, with the exception of the short arms of the acrocentric chromosomes), showed loss of genetic information in 11 of 18 prostate adenocarcinoma specimens analyzed (61%). Frequent allelic deletions were detected on the long arm of chromosome 16 (6 of 10 informative cases, 60%), on the short arm of chromosome 8 (3 of 6 informative cases, 50%), and on the short and/or the long arms of chromosome 10 (6 of 11 informative cases (10p), 55% and 4 of 13 informative cases (10q), 30%, respectively). No losses of alleles were detected in any case unless at least one of the chromosomes 8, 10, or 16 also showed deletions. The long arm of chromosome 18 also showed a high frequency of allelic deletions (3 of 7 informative cases, 43%). Allelic deletions on the following chromosomes were detected at lower frequencies: chromosomes 2, 3, 7, 12, 13, 17, 22, and XY. Tumors with allelic deletions on more than one chromosome had a higher histological malignancy grade. Tumors from patients with advanced disease all showed allelic deletions.