Histopathological studies on the local reactions induced by complete Freund's adjuvant (CFA), bacterial lipopolysaccharide (LPS), and synthetic lipopeptide (P3C) conjugates

The inflammatory reactions following subcutaneous application of adjuvants revealed characteristic pathological patterns. The injection of complete Freund's adjuvant (CFA) resulted in the formation of large lipid deposits encircled by an inflammatory reaction and concentrically arranged collagen bundles. Bacterial lipopolysaccharide (LPS) caused granulomatous aggregations of mononuclear cells with thrombotic vessel occlusions. Inoculation of the lipopeptide adjuvants induced accumulation of mononuclear cells with only minimal fibrotic changes which were resolved after day 28. Lipopeptide conjugates based on the head group tripalmitoyl-S-glyceryl-cysteinyl-serin (P3CS) can thus be used as effective immunogens and adjuvants without long-term tissue damage.     

Immunohistochemical differentiation between lymphangiographically verified lymphatic vessels and blood vessels

Summary In order to investigate the antigen profile in human lymphatic vessels when compared with blood vessels, postmortem retrograde lymphangiography was done via the thoracic duct on six patients. Formalin fixed, paraffin embedded tissue was stained immunohistochemically for Factor VIII-Related antigen (F VIII R:Ag), with Ulex Europaeus 1 lectin (UEA-1) and for laminin. The results show that the endothelium of blood vessels and lymphatics at all levels of the lymphatic system react positively following staining for Factor VIII-R:Ag and with UEA-1 lectin. The staining for F VIII R:Ag was generally weaker in the endothelial cells lining lymphatic vessels. Staining for the basement membrane component laminin can be used to distinguish lymphatic capillaries and smaller lymphatic collecting vessels from blood vessels.     

Resistance exercise training and the orthostatic response

Resistance exercise has been suggested to increase blood volume, increase the sensitivity of the carotid baroreceptor cardiac reflex response (BARO), and decrease leg compliance, all factors that are expected to improve orthostatic tolerance. To further test these hypotheses, cardiovascular responses to standing and to pre-syncopal limited lower body negative pressure (LBNP) were measured in two groups of sedentary men before and after a 12-week period of either exercise (n = 10) or no exercise (control, n = 9). Resistance exercise training consisted of nine isotonic exercises, four sets of each, 3 days per week, stressing all major muscle groups. After exercise training, leg muscle volumes increased (P?P = 0.00) by 2.0 (0.5)?kg, leg compliance and BARO were not significantly altered, and the maximal LBNP tolerated without pre-syncope was not significantly different. Supine resting heart rate was reduced (P = 0.03) without attenuating the heart rate or blood pressure responses during the stand test or LBNP. Also, blood volume (¹²⁵I and ⁵¹Cr) and red cell mass were increased (P?相似文献   

Effects of altered body fluid balance and high blood pressure on the plasma brain natriuretic peptide in rats.

The present study was aimed to investigate the regulatory mechanisms of BNP release. Effects of acute and chronic perturbations in body fluid balance, changes in BP, and regulatory roles of NO and endothelin systems on BNP release were examined in rats. Although acute extracellular volume expansion did not have significant effects on plasma BNP, prolonged high-salt intake increased plasma BNP levels. Plasma BNP levels were also higher in 2K1C rats compared with the control. Although infusion of L-NAME increased the plasma BNP in control, it did not further affect the plasma BNP in rats with high-salt intake. Although L-arginine (20 mg.kg-1 per min) per se did not have significant effects on plasma BNP, it blocked the stimulatory effect of L-NAME (200 micrograms.kg-1 per min). Plasma BNP was severalfold increased following a single injection of endothelin (0.3 micrograms/kg) in normal and high-salt intake groups, the magnitude of which was not significantly affected by the high-salt intake. Although indomethacin did not have significant effects on plasma BNP in normal rats, it blocked the stimulatory effect of 2K1C hypertension. It is concluded that BNP is regulated by chronic changes in body fluid balance and blood pressure. It is also suggested that endothelin and NO systems may directly regulate the secretion of BNP in vivo. An endogenous prostaglandin synthesis may be involved in the stimulated release of BNP in hypertension.     

Involvement of microtubules in Kunjin virus replication

Summary Induction of microtubulin paracrystals (Pc) by Kunjin (KUN) virus occurred after 15 hours post-infection and were often associated with convoluted membranes (cm) and virus particles. Vinblastine sulphate which disrupts microtubulin, had an inhibitory effect on the virus production when added during the viral latent period. When infected samples were extracted with Triton X-100 and analysed by SDS-PAGE, four viral proteins were observed.     

Inhibitory effect of adenosine on electrically evoked contractions in the rat vas deferens: pharmacological characterization

The inhibitory effects of adenosine as well as its related analogues on the contractile response of the rat vas deferens to field stimulation were compared in the absence and in the presence of nitrobenzylthioguanosine (NBTGR), a potent adenosine uptake inhibitor. In the presence of NBTGR, the order of potency was N6-cyclohexyladenosine (CHA) greater than or equal to L-N6-phenylisopropyladenosine (L-PIA) greater than 2-chloroadenosine greater than D-N6-phenylisopropyladenosine (D-PIA) greater than or equal to adenosine greater than 2'-deoxyadenosine. The inhibitory effect of adenosine but not that of clonidine, beta-endorphin and somatostatin was blocked by 1,3-diethyl-8-phenylxanthine (DPX, pA2 = 7.2), a potent P1-purinergic antagonist. The results suggest that adenosine inhibited the electrically evoked contractions of the rat vas deferens via the activation of the A1 subtype of P1-purinergic receptors.     

Malignant fibrous histiocytoma arising in a recurrent chordoma

Summary We present the case of a sacrococcygeal chordoma which recurred 15 years after the radical removal as a soft tissue tumor in the gluteal musculature. This tumor consisted of two parts: a chordoma without symptoms of aggressive cellular proliferation and a malignant fibrous histiocytoma. During the following 4 years several local recurrences of the malignant fibrous histiocytoma occurred in the gluteal musculature. The patient finally died of lung metastases. No chordoma tumor tissue was found in the lungs, in the gluteal musculature or in the sacrococcygeal bone area. Histology including electron microscopy revealed no proof of a transition of chordoma into malignant fibrous histiocytoma. It must be assumed that the secondary soft tissue tumor originated from residual chordoma cells which were implanted during the operation of the primary tumor. It remains unclear whether the malignant fibrous histiocytoma arose from mesenchymal stromal cells within the chordoma or directly from primitive neuroectodermal chorda cells which possess the ability to differentiate into a variety of cell types including mesenchymal cells.     

p53 codon 72 polymorphism and risk of cervical carcinoma in Korean women

A common polymorphism of the wild type p53 is known at codon 72 of exon 4, with 2 alleles encoding either arginine (CGC, p53Arg) or proline (CCC, p53Pro). A recent study suggested that this polymorphism affects the susceptibility of p53 protein to human papillomavirus E6 oncoprotein mediated degradation and that individuals homozygous for p53Arg are seven times more susceptible to HPV-associated carcinogenesis of the cervix than heterozygotes. To examine whether the p53Arg genotype could be a risk factor for HPV-associated cervical carcinomas in the Korean population, we analyzed the p53 codon 72 polymorphism status of HPV-positive invasive cervical carcinomas from 52 Korean women and 103 healthy control samples. The proportion of individuals homozygous for p53Arg, homozygous for p53Pro, and heterozygous for the two alleles were 40%, 19%, and 41% in normal healthy controls; 42%, 17%, and 40% in women with HPV-positive invasive cervical carcinoma. There were no significant differences in the distribution of p53 genotypes between controls and cervical carcinomas. This finding indicates that the p53Arg genotype is not associated with an increased susceptibility to cervical carcinoma in Korean women.     

Effects of acetaldehyde on responses of rabbit corpus cavernosal smooth muscle

Ethanol has various effects on male sexual activity under the influence of direct and indirect, in acute and chronic alcohol ingestion. However, whether acetaldehyde, a principal metabolite of ethanol, may affect penile erection directly has still not been elucidated. This present study was, therefore, designed to clarify the pharmacologic effects of the acetaldehyde on corpus cavernosal smooth muscle. Corpus cavernosal strips were prepared from rabbit penises. Isometric tension changes of rabbit corpus cavernosal strips to various drugs and electrical field stimulation (EFS) in an organ chamber were recorded with a pressure transducer after active muscle tone had been induced by phenylephrine (10(-5) mol/L). At the concentrations employed, acetaldehyde had no effect on the pH of the bathing medium. Acetaldehyde in each concentration did not significantly affect resting tone of the smooth muscle during 30 min incubation. Acetaldehyde suppressed contractility induced by phenylephrine and KCI at 10(-4) mol/L, and relaxation induced by EFS and bethanechol at 10(-3) mol/L and 10(-4) mol/L respectively, but acetaldehyde enhanced relaxation induced by ATP at high acetaldehyde level. Sodium nitroprusside-induced relaxation was not affected at any employed acetaldehyde concentration. This suggests that increasing the acetaldehyde level may contribute to male erectile dysfunction mainly by the inhibition of nitric oxide formation.     

Norepinephrine transporter (NET) promoter and 5'-UTR polymorphisms: association analysis in panic disorder

Several biochemical and pharmacological studies suggest that the catecholaminergic system involving the norepinephrine transporter (NET) is relevant for the pathogenesis of panic disorder. Three single nucleotide polymorphisms in the promoter or untranslated 5' region of the NET gene were investigated by means of RFLP analysis in a sample of 115 German patients with panic disorder and 115 matched controls. Statistical analysis failed to show association with the overall diagnosis of panic disorder. In the subgroup of patients with panic disorder without agoraphobia, however, two polymorphisms were found to be associated with the disease (G/C (rs2397771): p < 0.05; T/C (rs2242446): p < 0.01). While our data do not support a major function of the NET gene in the development of panic disorder, it may play a role in the subgroup of panic disorder without agoraphobia.