Reversal of cerebral vasospasm using an intrathecally administered nitric oxide donor

A systematic approach to evaluation of suspected occupational lung disorders is presented to assist the health care professional with diagnosis, treatment, and prognosis, as well as management of the disease in the workplace.     

Vibrational normal modes and dynamical stability of DNA triplex poly(dA). 2poly(dT): S-type structure is more stable and in better agreement with observations in solution

A normal-mode and statistical mechanical calculation was carried out to determine the vibrational normal modes, contribution of internal fluctuations to the free energy, and hydrogen bond disruption of DNA triplex poly(dA).2poly(dT). The calculation was performed on both the x-ray fiber diffraction model with a N-type sugar conformation, and a newly proposed model with a S-type sugar conformation. Our calculated normal modes for the S-type structure are in better agreement with observed IR spectra for samples in D2O solution. We also find that the contribution of internal fluctuations to free energy, premelting hydrogen bond disruption probability, and hydrogen bond melting temperatures for the Hoogsteen and Watson-Crick hydrogen bonds all show that the S-type structure is dynamically more stable than the N-type structure in a nominal solution environment. Therefore our calculation supports experimental findings that the triplex d(T)n.d(A)nd(T)n most likely adopts a S-type sugar conformation in solution or at high humidity. Our calculations, however, do not preclude the possibility of an N-type conformation at lower humidities.     

Reproducibility of color Doppler flow quantification of aortic regurgitation

The preferred method for quantification of aortic regurgitation severity with color Doppler echocardiography is the assessment of the ratio of jet diameter to left ventricular outflow tract diameter and jet area to left ventricular outflow tract area. However, the reproducibility of these measurements is not known and may limit its clinical application. This study was performed to identify sources of variability and reproducibility of the echocardiographic data. We examined 62 color Doppler echocardiographic examinations of patients showing isolated aortic regurgitation after human tissue valve implantation. The mean differences with standard deviations between paired measurements were calculated. The interobserver, intraobserver, and interframe variability showed a close agreement for the jet diameter and left ventricular outflow tract diameter measurements. The agreement for jet area and left ventricular outflow tract area measurements showed a small bias, but a large variance. The reproducibility of jet-left ventricular outflow tract diameter is better than the jet-left ventricular outflow tract area measurement and is more accurate to assess the severity of aortic regurgitation from color Doppler images.     

Cytokine and antibody responses in women infected with Neisseria gonorrhoeae: effects of concomitant infections

The levels of interleukin (IL)-1, IL-6, IL-8, IL-10, and transforming growth factor-beta in sera and genital tract secretions from women with gonococcal cervicitis and other genital infections were examined. Cytokines were not elevated in genital secretions from gonococcus-infected compared with uninfected patients. The level of serum IL-6 was higher in gonococcus-infected than in uninfected patients at recruitment. Serum, but not local, IL-1 and IL-6 levels were elevated in patients concomitantly infected with Trichomonas vaginalis or Chlamydia trachomatis in addition to Neisseria gonorrhoeae compared with levels in patients infected with any single organism. Concomitant infection altered neither the total immunoglobulin concentrations nor the levels of antigonococcal antibodies in serum or local secretions. The results suggest that N. gonorrhoeae induces only a limited cytokine and antibody response during uncomplicated cervical infections; however, the presence of other sexually transmitted disease-causing organisms can alter the systemic cytokine but not the antigonococcal antibody levels.     

Haloacetate-induced oxidative damage to DNA in the liver of male B6C3F1 mice

Brominated and chlorinated haloacetates (HAs) are by-products of drinking water disinfection. Dichloroacetate (DCA) and trichloroacetate (TCA) are hepatocarcinogenic in rodents, but the brominated analogs have received little study. Prior work has indicated that acute doses of the brominated derivatives are more potent inducers of oxidative stress and increase the 8-hydroxydeoxyguanosine (8-OH-dG) content of the nuclear DNA in the liver. Since, DCA and TCA are also known as weak peroxisome proliferators, the present study was intended to determine whether this activity might be exacerbated by peroxisomal proliferation. Classical responses to peroxisome proliferators, cyanide-insensitive acyl-CoA oxidase activity and increased 12-hydroxylation of lauric acid, were elevated in a dose-related manner in mice maintained on TCA and clofibric acid (positive control), but not with DCA, dibromoacetate (DBA) or bromochloroacetate (BCA). Administration of the HAs in drinking water to male B6C3F1 mice for periods from 3 to 10 weeks resulted in dose-related increases in 8-OH-dG in nuclear DNA of the liver with DBA and BCA, but not with TCA or DCA. These findings indicate that oxidative damage induced by the haloacetates is, at least in part, independent of peroxisome proliferation. In addition, these data suggest that oxidative damage to DNA may play a more important role in the chronic toxicology of brominated compared to the chlorinated haloacetates.     

Reactive arthritis in patients attending an urban sexually transmitted diseases clinic

OBJECTIVE: To assess the prevalence, clinical manifestations, associated genital infections, and HLA associations of reactive arthritis (ReA) among patients attending an urban sexually transmitted diseases (STD) clinic. METHODS: Using a standardized questionnaire, 271 consecutive adults, primarily black, with possible or proven Chlamydia trachomatis genital infection were screened for symptoms of ReA. A followup questionnaire was administered 6 weeks later by mail. Patients who reported at least 1 symptom were evaluated by a rheumatologist. HLA-B typing was performed on patients with objective ReA features. RESULTS: Nine of 217 patients (4.1%) with genital infection/inflammation had objective ReA features. Chlamydial or nongonococcal STD syndromes were diagnosed in 8 of these 9 patients (88%). Genital infection/inflammation was asymptomatic in 78% of patients with ReA features. HLA-B27 or other B7-cross-reactive group antigens were not associated with the occurrence of ReA. CONCLUSION: Nongonococcal genital infections, often asymptomatic, can trigger a relatively mild ReA in a larger number of exposed patients than previously thought, irrespective of the individual's HLA status.     

Identification of novel susceptibility loci for inflammatory bowel disease on chromosomes 1p, 3q, and 4q: evidence for epistasis between 1p and IBD1

The idiopathic inflammatory bowel diseases, Crohn's disease (CD) and ulcerative colitis (UC), are chronic, frequently disabling diseases of the intestines. Segregation analyses, twin concordance, and ethnic differences in familial risks have established that CD and UC are complex, non-Mendelian, related genetic disorders. We performed a genome-wide screen using 377 autosomal markers, on 297 CD, UC, or mixed relative pairs from 174 families, 37% Ashkenazim. We observed evidence for linkage at 3q for all families (multipoint logarithm of the odds score (MLod) = 2.29, P = 5.7 x 10(-4)), with greatest significance for non-Ashkenazim Caucasians (MLod = 3.39, P = 3.92 x 10(-5)), and at chromosome 1p (MLod = 2.65, P = 2.4 x 10(-4)) for all families. In a limited subset of mixed families (containing one member with CD and another with UC), evidence for linkage was observed on chromosome 4q (MLod = 2.76, P = 1.9 x 10(-4)), especially among Ashkenazim. There was confirmatory evidence for a CD locus, overlapping IBD1, in the pericentromeric region of chromosome 16 (MLod = 1.69, P = 2.6 x 10(-3)), particularly among Ashkenazim (MLod = 1.51, P = 7.8 x 10(-3)); however, positive MLod scores were observed over a very broad region of chromosome 16. Furthermore, evidence for epistasis between IBD1 and chromosome 1p was observed. Thirteen additional loci demonstrated nominal (MLod > 1.0, P < 0.016) evidence for linkage. This screen provides strong evidence that there are several major susceptibility loci contributing to the genetic risk for CD and UC.     

The astrocytic response to afferent activity blockade in chick nucleus magnocellularis is independent of synaptic activation, age, and neuronal survival

Astrocytes in nucleus magnocellularis (NM) of the chick respond to afferent activity blockade with increased immunoreactivity for glial fibrillary acidic protein (GFAP). NM neurons respond to the same manipulations with reduced protein synthesis, ribosomal dissociation, and subsequent death of a subset of these neurons. In the present study, we sought to evaluate the relationship between these neuronal and glial responses and to determine if similar activity-dependent mechanisms mediate them. We first examined the anatomical relationship between NM neurons and astrocytic processes by electron microscopy and GFAP immunostaining. Both methods showed that NM neurons deprived of activity for 6 hr were apposed by more glial processes than active NM neurons. However, we found no preferential positioning of GFAP-immunoreactive processes near neurons of the dying or surviving populations, and there were no differences in glial process apposition to dying versus surviving neurons at the EM level. To determine whether the astrocytic response is similar to the neuronal response in age dependence, GFAP immunoreactivity was analyzed in adult chickens following unilateral afferent activity blockade. Unlike the neuronal response to activity blockade, the astrocytic response is equally strong in adult animals. These results imply an independence of the neuronal and astrocytic responses to activity blockade, raising the possibility that these two cell types may be responding to different activity-related signals. This possibility was tested using an in vitro slice preparation. Unilateral stimulation of NM was provided in three ways: orthodromically, antidromically, and orthodromically in a low-calcium medium. The regulation of astrocytic GFAP immunoreactivity by these manipulations of activity was then analyzed. The results of these experiments show that, unlike neuronal protein synthesis, astrocytic GFAP immunoreactivity can be suppressed by either presynaptic or postsynaptic neuronal activity. Therefore, the astrocytes and neurons are regulated by different activity-dependent signals and, by the present measures, their responses to activity blockade appear independent of one another.     

Systemic and cellular calcium metabolism and hypertension

The calcium status of humans with essential hypertension and genetic animal models of hypertension is characterized by low serum ionized calcium concentration, increased urinary calcium excretion, and increased parathyroid hormone (PTH) concentration. Calcitriol metabolism and bone mineralization are also altered in hypertension. These alterations in systemic calcium metabolism may be linked to factors responsible for the elevated blood pressure. Cytosolic free calcium tends to be increased in most cells that have been studied from hypertensive humans and animals. Changes in cellular calcium metabolism may be partly mediated by calcium-regulating hormones that tend to be elevated in essential hypertension such as PTH and calcitriol. Administration of supplemental dietary calcium tends to suppress PTH, calcitriol, and intracellular free calcium. Further research is need concerning the observed association among systemic markers of calcium metabolism, cellular calcium metabolism, and arterial blood pressure regulation.