Gamete intrafallopian transfer. A cost-effective alternative to donor oocyte in vitro fertilization in women aged 40-42 years

Two cases of eumycotic mycetomas in the head and neck region are reported. The first case is the localized mycetoma which involved only the soft tissue of the neck. It was completely excised and the patient needed no further treatment. In the second case, the lesion extensively involved the structures in the parapharyngeal space, submandibular space and carotid sheath. The upper limit is the skull base. The patient was treated by combination of wide excision with radial forearm flap and antifungal agents, however, the prognosis is fair.     

Gemfibrozil treatment increases low-density lipoprotein particle size in Type 2 diabetes mellitus but does not alter in vitro oxidizability

The aim of this study was to determine the effect of the lipid modifying agent gemfibrozil on lipid and coagulation risk factors in patients with Type 2 diabetes mellitus (Type 2 DM). Twenty-six subjects with Type 2 DM and dyslipidaemia were treated for 24 weeks with either gemfibrozil 600 mg orally twice daily or placebo in a double-blind randomized trial. Lipid profiles, fibrinogen, Factor VII, and plasminogen activator inhibitor-1 (PAI-1) were measured by routine laboratory methods. Low density lipoprotein (LDL) size was determined by gradient gel electrophoresis and the resistance of LDL to copper-induced oxidation was assessed by measuring absorbance at 234 nm. Gemfibrozil significantly reduced total cholesterol (-0.9 (-0.48, -1.32) mmol l(-1); p < 0.05) and triglycerides (-2.7 (-1.55, -1.35) mmol l(-1); p < 0.001) vs placebo. The fall in triglyceride was reflected by a fall in VLDL cholesterol levels in the gemfibrozil treated group vs placebo (-1.31 mmol l(-1); p < 0.001). LDL-cholesterol level did not change but LDL particle size increased by 0.5 nm (0.01, 0.93); P < 0.02. The increase in particle size was inversely correlated with the change of triglyceride level (r = -0.79, p < 0.0001) but did not result in any reduction of susceptibility to copper-induced oxidation. There were no significant changes in the coagulation parameters studied. Because of its ability to correct the lipid abnormalities associated with Type 2 DM particularly hypertriglyceridaemia, gemfibrozil provides a useful therapeutic option in the management of diabetic dyslipidaemia but it does not alter in vitro oxidizability of LDL.     

Expression, characterization, and purification of C-terminally hexahistidine-tagged thromboxane A2 receptors

Thromboxane A2 (TxA2) receptors belong to the class of G-protein-coupled receptors. Knowledge of the relationship of structure to function for TxA2 receptors is limited because of their low levels of expression, lengthy purification procedures and poor recoveries. A C-terminal hexahistidine-tag (C-His) was ligated to the alpha-isoform of TxA2 receptors and expressed in COS-7 and Chinese hamster ovary cells. The C-His-TxA2 receptors bound the radioligands 125I-7-[(1R,2S,3S,5R)-6, 6-dimethyl-3-(4-benzenesulfonylamino)bicyclo[3.1. 1]hept-2-yl]-5(Z)-heptenoic acid, an antagonist, and 125I-[1S-1alpha, 2beta(5Z),3alpha(1E,3S*), 4alpha]-7-[3[(3-hydroxy-4-(4'-phenoxy)-1butenyl)-7-oxabicycl o-[2.2. 1]heptan-2-yl]-5-heptanoic acid, an agonist, with affinities not significantly different from those of the wild type (wt)-TxA2 receptors. LipofectAMINE transfection of the cDNAs resulted in high levels of expression (Bmax = 95 +/- 6 pmol/mg) of the C-His-TxA2 receptors. In competition binding studies the IC50 values of five different ligands were not significantly different between C-His-TxA2 and wt-TxA2 receptors. Agonist-induced stimulation of cAMP and total inositol phosphate formation were not significantly different between the two receptors. Purification on a Ni2+-NTA column resulted in a rapid (within 4 h) purification with a 36 +/- 2% recovery and a 30 +/- 6-fold purification (n = 5). The partially purified receptors were resolved on SDS-polyacrylamide gel electrophoresis, transferred to a nitrocellulose membrane, dissolved in acetone/trifluoroacetic acid/hexafluoroisopropanol/sinapinic acid, and successfully subjected to matrix-assisted laser desorption ionization-time of flight mass spectrometry analysis. The results suggest that the combination of a high level of expression of C-His-TxA2 receptors and a rapid purification procedure followed by SDS- polyacrylamide gel electrophoresis may provide a useful approach for mass-spectrometry based structure-function and other studies of TxA2 receptors.     

Delta9-tetrahydrocannabinol suppresses macrophage costimulation by decreasing heat-stable antigen expression

Delta9-tetrahydrocannabinol (THC) suppresses several immunologic functions of macrophages. The costimulatory activity of a THC-exposed macrophage hybridoma was investigated by its ability to elicit interleukin-2 secretion by a helper T cell hybridoma activated with immobilized monoclonal anti-CD3 antibody. THC added at culture initiation inhibited the T cell response in a dose-dependent manner. When the macrophages were fixed with paraformaldehyde before culture, THC had no effect on T cell stimulation. However, macrophages, which were preincubated with THC and then fixed, were impaired in delivering costimulatory signals to T cells cultured without THC. The drug's inhibitory effect on macrophage costimulatory activity was reversible. THC exposure also decreased macrophage expression of heat-stable antigen (HSA). Antibody blocking experiments showed that HSA expressed on the macrophages provided an important costimulatory signal, whereas B7-1 and B7-2 molecules had a minor role. Treatment of the macrophages with phosphatidylinositol-specific phospholipase C cleaved HSA, but not the transmembrane B7 molecules, from the cell surface. Similar to THC, enzyme treatment significantly diminished macrophage costimulatory activity, which was also reversible. After drug or enzyme removal, HSA expression returned to the control level by 4 h. Therefore, THC suppresses macrophage costimulatory activity by diminishing cell surface expression of HSA.     

Quantitative trait loci disposing for both experimental arthritis and encephalomyelitis in the DA rat; impact on severity of myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis and antibody isotype pattern

Quantitative trait loci (QTL) controlling inflammatory diseases with different organ specificity may hypothetically either be unique for one disease or shared among different diseases. We have investigated whether five non-MHC QTL controlling susceptibility to experimental arthritis in the DA rat also influence myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE) in an F2 intercross between inbred DA and PVG.RT1a rats. Two of the five chromosome regions affecting arthritis in the DA rat also regulate phenotypes of EAE. The DA allele at markers in Cia3 (collagen-induced arthritis QTL) on chromosome 4 is associated with more severe EAE and high levels of anti-MOG antibodies of the IgG2c subclass. Since production of antibodies of the IgG2c subclass may be stimulated by Th1 cells, and there is previous evidence that such cells promote EAE, it is possible that both of the studied phenotypes are controlled by the same gene or genes regulating Th1/Th2 cell differentiation. Furthermore, we show that Oia2 (oil-induced arthritis QTL) on chromosome 4 regulates levels of anti-MOG antibodies of the IgG1 subclass and of anti-MOG IgE, but that this gene region does not affect clinical disease severity in our study. Since production of IgE and IgG1 may be stimulated by Th2 cells, this QTL may also control Th1/Th2 bias. We conclude that Cia3 and Oia2 regulate MOG-induced EAE in rats. Furthermore, since both EAE and arthritis phenotypes co-localize to these gene regions, they may harbor genes which are key regulators of pathogenic immune responses.     

Interaction of cognitive balance and mood induction on self-descriptions: a Q methodological approach

Several neuropsychiatric disorders, including schizophrenia, are characterized by sensorimotor gating deficits. Prepulse inhibition of the acoustic startle response is an operational measure assessing sensorimotor gating and has been found to be reduced in schizophrenic patients. Much attention has therefore been paid to the neuronal mechanisms underlying the disruption of prepulse inhibition. The activity of limbic forebrain structures such as the septohippocampal system, the prefrontal cortex, and the nucleus accumbens has been the main focus of recent research into the regulation of prepulse inhibition in rats. We here provide a functional anatomical picture of forebrain structures probably involved in the regulation of prepulse inhibition. Stimulation of the ventral hippocampus with a subconvulsive dose of N-methyl-D-aspartate caused a significant and long-lasting disruption of prepulse inhibition. Immunostaining of the c-Fos protein revealed a characteristic pattern of neuronal activity in various forebrain areas, including the nucleus accumbens and different frontal cortical areas after hippocampal stimulation. Based on the present findings, we conclude that the overactivity within a network of cortico-limbic forebrain structures compromises the normal processing of sensory stimuli by disrupting a neuronal filter mechanism. Interestingly, there is a considerable overlap between the pattern of neuronal activity observed in our study and the brain pathology in schizophrenics reported in the literature.     

Human monocyte-derived macrophages secrete two forms of proteoglycan-macrophage colony-stimulating factor that differ in their ability to bind low density lipoproteins

This study evaluated whether human monocyte-derived macrophages synthesize specific types of proteoglycans with lipoprotein-binding capability that could contribute to lipid retention in the arterial wall. After labeling with either [35S]SO4 or [35S]methionine, macrophages secreted a high molecular mass proteoglycan, with glycosaminoglycan chains of approximately 18 kDa and core protein bands of approximately 100 and 55 kDa. Both core protein bands were recognized by an antibody to PG-100, an antibody that recognizes the proteoglycan form of macrophage colony-stimulating factor (PG-100/PG-MCSF). The interaction between PG-100/PG-MCSF and low density lipoproteins (LDL) was examined by gel mobility shift. In this system, PG-100/PG-MCSF was resolved further into two forms. The two forms had the same core proteins but differed in their overall size and glycosaminoglycan content. The larger form contained glycosaminoglycan chains that were entirely chondroitin ABC lyase-sensitive, whereas the smaller form contained chains that were sensitive to both chondroitin ABC lyase and heparinase. Both forms bound native LDL with high affinity, but the larger form bound LDL with higher affinity than the smaller form. The glycosaminoglycan chains of PG-100/PG-MCSF, but not the core proteins, were responsible for binding to native LDL. Mildly oxidized LDL and methyl-LDL, which have an electrophoretic charge similar to that of native LDL, also bound PG-100/PG-MCSF. In contrast, extensively oxidized LDL and acetyl-LDL, which are more electronegative than native LDL, did not bind to either form of PG-100/PG-MCSF. The demonstration of two forms of human monocyte-derived macrophage PG-100/PG-MCSF which bind LDL may represent an additional role for macrophages in the extracellular trapping of lipoproteins in atherosclerosis.