Ultrasonographically assessed maximum carotid artery wall thickness in Mexico City residents and Mexican Americans living in San Antonio, Texas. Association with diabetes and cardiovascular risk factors

Measurements of carotid artery wall thickness are often used as a surrogate for atherosclerosis. However, few studies have performed these measurements in populations of Mexican origin. Since Mexicans in Mexico City consume high-carbohydrate diets and have carbohydrate-induced dyslipidemia (high triglyceride and low HDL cholesterol levels) compared with Mexican Americans living in San Antonio, Tex, we questioned whether they also had more atherosclerosis than San Antonio Mexican Americans. Mean maximum intimal-medial thickness (IMT) of the common (CCA) and internal (ICA) carotid arteries were measured in 867 subjects aged 35 to 64 years (40% men) in two Mexican-origin populations, one from San Antonio (n = 202) and the other from Mexico City (n = 665). IMT's in the two cities were compared, and their associations with cardiovascular risk factors were analyzed. Older age, male sex, high levels of total cholesterol, low levels of HDL cholesterol, and high systolic blood pressure were positively associated with both CCA IMT and ICA IMT. Cigarette smoking was significantly associated with ICA IMT. CCA and ICA IMTs in diabetic subjects were thicker than in nondiabetic subjects in both men and women (all P < = .05). CCA IMT was thicker in the San Antonio than the Mexico City subjects after adjustment for cardiovascular risk factors (0.81 versus 0.76 mm in men and 0.77 versus 0.71 mm in women; P < .001 for city difference). San Antonio men also had thicker ICA IMT than their counterparts in Mexico City (0.88 versus 0.83 mm), but the reverse was true for women (0.73 versus 0.77 mm; interaction between sex and city, P < .05). Our results indicate that men had higher carotid IMTs than women. CCA IMT was thicker in San Antonio Mexican Americans than in Mexico City residents. The differences in ICA IMTs between San Antonio and Mexico City were inconsistent. Thus, since Mexico City residents consume high-carbohydrate diets, the data do not support an atherogenic effect of such diets. The interaction between sex and city on ICA IMT deserves further study.     

The 70 kDa subunit of replication protein A is required for the G1/S and intra-S DNA damage checkpoints in budding yeast

The rfa1-M2 and rfa1-M4 Saccharomyces cerevisiae mutants, which are altered in the 70 kDa subunit of replication protein A (RPA) and sensitive to UV and methyl methane sulfonate (MMS), have been analyzed for possible checkpoint defects. The G1/S and intra-S DNA damage checkpoints are defective in the rfa1-M2 mutant, since rfa1-M2 cells fail to properly delay cell cycle progression in response to UV irradiation in G1 and MMS treatment during S phase. Conversely, the G2/M DNA damage checkpoint and the S/M checkpoint are proficient in rfa1-M2 cells and all the checkpoints tested are functional in the rfa1-M4 mutant. Preventing S phase entry by alpha-factor treatment after UV irradiation in G1 does not change rfa1-M4 cell lethality, while it allows partial recovery of rfa1-M2 cell viability. Therefore, the hypersensitivity to UV and MMS treatments observed in the rfa1-M4 mutant might only be due to impairment of RPA function in DNA repair, while the rfa1-M2 mutation seems to affect both the DNA repair and checkpoint functions of Rpa70.     

Visual association encoding activates the medial temporal lobe: a functional magnetic resonance imaging study

The involvement of structures in the medial temporal lobe during the encoding of visual associations was studied with functional magnetic resonance imaging. In 11 out of 12 normal healthy volunteers this task resulted in activation in posterior portions of the parahippocampal region, close to the collateral sulcus. In seven subjects activation was encountered in the hippocampal formation. The visual association task as adapted for this study may provide a sensitive measure to study anterograde amnesia prevalent in Alzheimer's disease. Therefore, the present paradigm enables the study of individual changes in learning and memory capacities over time.     

Effects of gemfibrozil and ciprofibrate on plasma levels of tissue-type plasminogen activator, plasminogen activator inhibitor-1 and fibrinogen in hyperlipidaemic patients

Evaluation of fibrate treatment in humans has focused primarily on its anti-lipidaemic effects. A potentially favourable haemostasis-modulating activity of fibrates has also been recognized but the data are not consistent. We sought to learn more about this variability by examining the effects of gemfibrozil and ciprofibrate on plasma levels of tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1) and fibrinogen in primary hyperlipidaemic patients after six and twelve weeks of treatment using different assay systems for PAI-1 and fibrinogen. Although both fibrates effectively lowered triglyceride and cholesterol levels, no effect on the elevated baseline antigen levels of t-PA and PAI-1 was observed after fibrate treatment. However, both fibrates influenced plasma fibrinogen levels, albeit in a different way. Fibrinogen antigen levels were elevated by 17.6% (p <0.05) and 24.3% (p <0.001) with gemfibrozil after six and twelve weeks, respectively, whereas with ciprofibrate there was no effect. Using a Clauss functional assay with either a mechanical end point or a turbidity-based end point, no significant change in fibrinogen levels was seen after six weeks of gemfibrozil treatment. However, after twelve weeks, gemfibrozil enhanced functional fibrinogen levels by 7.2% (p <0.05) as assessed by the Clauss mechanical assay, but decreased functional fibrinogen levels by 12.5% (p <0.0001) when a Clauss assay based on turbidity was used. After six or twelve weeks of ciprofibrate treatment, functional fibrinogen levels were decreased by 10.1% (p <0.001) and 10.5% (p <0.0001), respectively on the basis of Clauss mechanical and by 14.2% (p <0.001) and 28.2% (p <0.0001), respectively with the Clauss turbidimetric assay. A remarkable and consistent finding with both fibrates was the decrease in functionality of fibrinogen as assessed by the ratio of functional fibrinogen (determined by either of the two Clauss assays) to fibrinogen antigen. Taken together, our results indicate that at least part of the variability in the effects of fibrates on haemostatic parameters can be explained by intrinsic differences between various fibrates, by differences in treatment period and/or by the different outcomes of various assay systems. Interestingly, the two fibrates tested both reduced the functionality of fibrinogen.     

Action of prostanoids on the emetic reflex of Suncus murinus (the house musk shrew)

Several prostanoids were investigated for a potential to induce emesis in Suncus murinus. The TP receptor agonist 11alpha,9alpha-epoxymethano-15S-hydroxyprosta-5Z,13E-dienoic acid (U46619) induced emesis at doses as low as 3 microg/kg, i.p. but the DP receptor agonist 5-(6-Carboxyhexyl)-1-(3-cyclohexyl-3-hydroxypropyl) hydantoin (BW245C) was approximately 1000 times less potent. The emetic action of U46619 (300 microg/kg, i.p.) was antagonized significantly by the TP receptor antagonist, vapiprost (P<0.05). EP (prostaglandin E(2), 17-phenyl-omega-trinor prostaglandin E(2), misoprostol and sulprostone), FP (prostaglandin F(2alpha) and fluprostenol) and IP (iloprost and cicaprost) receptor agonists failed to induce consistent emesis at doses up to 300-1000 microg/kg, i.p. Fluprostenol reduced nicotine (5 mg/kg, s.c.)-but not copper sulphate (120 mg/kg, intragastric)-induced emesis; the other inconsistently emetic prostanoids were inactive to modify drug-induced emesis. The results indicate an involvement of TP and possibly DP and FP receptors in the emetic reflex of S. murinus.     

A study of the ethical duty of physicians to disclose errors

A quantitative immunocytochemical procedure was used for evaluation of the blood-brain barrier (BBB) to endogenous albumin in plaque-forming (PF) and non-plaque-forming (NPF) groups of scrapie-infected mice at the clinical stage of disease. Ultrathin sections of brain samples (cerebral cortex, hippocampus and cerebellum) embedded in resin (Lowicryl K4M) were exposed to anti-mouse albumin antiserum followed by protein A-gold. Using morphometry, the density of immunosignals (gold particles per microns2) was recorded over four compartments: vascular lumen, endothelium, subendothelial space, and brain parenchyma (neuropil). Morphometric and statistical analyses did not reveal significant differences in the barrier function of the microvasculature of the cerebral cortex and hippocampus in either group of mice, although a slight increase in the number of leaking vessels in the PF group was noted. In contrast, in the cerebellum, the permeability of the microvessels to albumin was significantly higher in the PF than in the NPF mouse group, and this was paralleled by the infiltration of the walls of numerous vascular profiles with amyloid deposits (amyloid angiopathy). These data also indicate the existence of distinct regional differences in BBB function in the brain of scrapie-infected mice. The vascular amyloid deposits and the amyloid plaques present in the cerebral cortex of PF mice were labeled with numerous immunosignals suggesting the affinity of extravasated albumin to these deposits. In conclusion, no convincing evidence was obtained indicating that impairment of the BBB, manifested by increased permeability of vascular segments, is directly related to the deposition of amyloid in the vascular wall and in plaques. Segmental impairment of the barrier function seems to be rather the result of disturbed structural integrity of the components of the vascular wall.     

Parenteral nutrition in oncologic patients]

A B16 melanoma-specific CD8+ T cell line (AB1) was established from the spleen cells of C57BL/6 mice cured of B16 melanoma with interleukin (IL)-12 treatment. The AB1 line exclusively used T cell receptor Vbeta11. The AB1 cells exhibited a cytolytic activity against both syngeneic B16 melanoma and allogeneic P815 mastocytoma, whereas a cold inhibition assay revealed specificity of the AB1 cells against B16 melanoma. Their lostability to kill a class I loss variant of B16 melanoma was restored by the transfection of H-2Kb gene. In addition, their interferon (IFN)-gamma production was significantly suppressed by the addition of anti-H-2Kb monoclonal antibody, and RT-PCR analysis showed that the AB1 line expressed the mRNA encoding IFN-gamma, but not IL-4 or IL-10. The experiment using synthetic peptides of tyrosinase-related protein-2 (TRP-2) revealed that the AB1 cells could recognize TRP-2(181-188) peptide. Moreover, the AB1 cells showed an in vivo antitumor effect against established pulmonary metastases of B16 melanoma. Overall, these results indicate that the Tc1-type Vbeta11+ AB1 cells exert an antitumor activity against syngeneic B16 melanoma through recognition of TRP-2(181-188) peptide in an H-2Kb-restricted manner.     

Clinical effects of longitudinal division of the corpus callosum in normal dogs

Longitudinal division of the corpus callosum was performed in six normal beagles to determine surgical morbidity. The corpus callosum was divided sagittally on the midline and the effect on neurological function was determined. Five of six dogs were clinically normal within 14 days or less after surgery. One dog had persistent but improving clinical signs consistent with a forebrain disturbance at 30 days after surgery. Overall, minimal morbidity and no mortality was associated with this surgical procedure. Further study is indicated to determine the efficacy of this surgical treatment for seizure control in dogs with idiopathic epilepsy.     

Immunological mimicry between retinal S-antigen and group A streptococcal M proteins

Immunological mimicry between host and microbial proteins has been suggested as a potential mechanism in the development of uveitis in humans. In this study immunological crossreactivity between anti-streptococcal monoclonal antibodies (MAbs) and the human eye was investigated. In indirect immunofluorescence, we demonstrated novel immunological crossreactivity of two anti-streptococcal MAbs (27 and 112) with the rod outer (and inner) segments of the retina of the human eye. In further studies, retinal S-Ag, a uveitogenic protein in the rod outer (and inner) segments, was found to react with the anti-streptococcal MAbs. In addition, several uveitogenic peptides of S-Ag were recognized by the anti-streptococcal MAbs. In the ELISA and Western immunoblot, anti-S-Ag MAbs crossreacted with group A streptococci and the streptococcal M protein further demonstrating sites of antigenic similarity. Homology between the retinal S-Ag and streptococcal M protein was observed in amino acid sequences repeated in the B repeat region of the streptococcal M5 protein. These data show that retinal S-antigen has immunological similarities with streptococcal M protein, a major virulence determinant and strong bacterial cell surface antigen.