[Mutations and diseases].
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Biomarkers, Tumor↗
Biomedical subjects
C Arnold
Publications and source records attributed to C Arnold.
Wide distribution of the cysteine string proteins in Drosophila tissues revealed by targeted mutagenesis.
The "cysteine string protein" (CSP) genes of higher eukaryotes code for a novel family of proteins characterized by a "J" domain and an unusual cysteine-rich region. Previous studies had localized the proteins in neuropil and synaptic terminals of larval and adult Drosophila and linked the temperature-sensitive paralysis of the mutants described here to conditional failure of synaptic transmission. We now use the null mutants as negative controls in order to reliably detect even low concentrations of CSPs by immunohistochemistry, employing three monoclonal antibodies. In wild-type flies high levels of cysteine string proteins are found not only in apparently all synaptic terminals of the embryonic, larval, and adult nervous systems, but also in the "tall cells" of the cardia, in the follicle cells of the ovary, in specific structures of the female spermatheca, and in the male testis and ejaculatory bulb. In addition, low levels of CSPs appear to be present in all tissues examined, including neuronal perikarya, axons, muscles, Malpighian tubules, and salivary glands. Western blots of isolated tissues demonstrate that of the four isoforms expressed in heads only the largest is found in non-neural organs. The wide expression of CSPs suggests that at least some of the various phenotypes of the null mutants observed at permissive temperatures, such as delayed development, short adult lifespan, modified electroretinogram, and optomotor behavior, may be caused by the lack of CSPs outside synaptic terminals.
Age Factors↗
A polio immunization pamphlet with increased appeal and simplified language does not improve comprehension to an acceptable level.
We used a randomized trial to compare two polio vaccine pamphlets written on a sixth grade level--the vaccine information statement prepared by the Centers for Disease Control (CDC) and an easy-to-read pamphlet we developed (LSU)--for reading ability, comprehension and preference among 610 parents with a broad range of demographic characteristics. Parents at all reading levels and incomes preferred LSU (76% vs. 21%, P < 0.001). Although readers of LSU achieved significantly higher comprehension (65% vs. 60%, P < 0.05) this difference may not be clinically significant. The information items presented with instructional graphics were the only items on which differences in comprehension levels achieved both clinical and statistical significance. Comprehension was lowest for the CDC mandated information on risks and the National Injury Compensation. Our findings demonstrate that simplifying written immunization material and making it more suitable will increase appeal, but such modification may not raise comprehension to an acceptable level without use of instructional graphics. Health education materials intended for general parent populations, which are written on a sixth grade reading level, may not adequately educate parents or prepare them for a discussion with their physicians.
Academic Medical Centers↗
The C-reactive protein to prealbumin ratio correlates with the severity of multiple organ dysfunction.
BACKGROUND: This study evaluates the correlation between a ratio of two hepatic proteins, C-reactive protein (CRP) and prealbumin (PALB), and the severity of organ dysfunction as measured by the multiple organ dysfunction score (MODS). METHODS: A prospective cohort study was undertaken in critically ill patients (n = 70) by measuring the serum levels of CRP and PALB, the energy expenditure via indirect calorimetry, and severity of organ dysfunction by the MODS. All three variables were recorded for a period of 5 days from admission and then assessed for correlation to each other and to the length of stay and mortality in the intensive care unit. RESULTS: The CRP/PALB ratio showed a statistically significant correlation at 48 hours (r = 0.45, P < .01) and 120 hours (r = 0.53, P < .01). This ratio showed higher degrees of correlation when applied to patients with a diagnosis of sepsis, multiple organ dysfunction, or single organ dysfunction, r = 0.71 and 0.56 at 48 and 120 hours, respectively. Receiver operating characteristics (ROC) curves show that a ratio of 2.07 correlated with a MODS of 16 with a sensitivity of 92% and a specificity of 71%. CONCLUSIONS: This study demonstrates a strong correlation between the severity of organ dysfunction and the ratio of two hepatic proteins, CRP and PALB. There was no correlation between the degree of energy expenditure and the MODS, Acute Physiology and Chronic Health Evaluation II score, or the ratio of CRP/PALB. The use of inflammatory markers may be an easy, inexpensive method of assessing severity of illness in the critically ill.
APACHE↗
Tuberculous colitis mimicking Crohn's disease.
Intestinal tuberculosis is a rare disease in western countries and may mimic a variety of gastrointestinal disorders. Here, we report the case of a 63-yr-old patient who presented with profuse bleeding from a deep rectal ulcer. Similar lesions were found in different parts of the colon. Multilocular colorectal carcinoma was suspected based on the macroscopic appearance. Histology, however, suggested Crohn's disease. Intestinal tuberculosis was initially ruled out by negative staining for acid-fast bacilli, mycobacterial culture, and polymerase chain reaction analysis. A treatment for Crohn's disease was started. Endoscopic reexamination revealed progressive disease with extensive ulcerations of the terminal ileum. Histopathological examination then revealed acid-fast bacilli in the colonic mucosa typical for mycobacterium tuberculosis infection. This case emphasizes the need to include intestinal tuberculosis in the initial differential diagnosis of ulcerative colorectal lesions also in the western population.
Colitis↗
Simian immunodeficiency virus (SIV) envelope-specific Fabs with high-level homologous neutralizing activity: recovery from a long-term-nonprogressor SIV-infected macaque.
An antibody phage display library was constructed from RNA extracted from lymph node cells of a simian immunodeficiency virus (SIV)-infected long-term-nonprogressor macaque. Seven gp120-reactive Fabs were obtained by selection of the library against SIV monomeric gp120. Although each of the Fabs was unique in sequence, there were two distinct groups based on epitope recognition, neutralizing activity in vitro, and molecular analysis. Group 1 Fabs did not neutralize SIV and bound to a linear epitope in the V3 loop of the SIV envelope. In contrast, two of the group 2 Fabs neutralized homologous, neutralization-sensitive SIVsm isolates with high efficiency but failed to neutralize heterologous SIVmac isolates. Based on competition enzyme-linked immunosorbent assays with mouse monoclonal antibodies of known specificity, these Fabs reacted with a conformational epitope that includes domains V3 and V4 of the SIV envelope. These neutralizing and nonneutralizing Fabs provide valuable standardized and renewable reagents for studying the role of antibody in preventing or modifying SIV infection in vivo.
Amino Acid Sequence↗
Development of a neutralizing antibody response during acute primary human immunodeficiency virus type 1 infection and the emergence of antigenic variants.
We monitored the primary humoral response to human immunodeficiency virus type 1 infection and showed that, in addition to antibodies to p24 and gp41, antigens which form the basis of most diagnostic assays, the response included a significant antibody response directed to the gp120 region of the infecting viral quasispecies. When tested in a recombinant virus neutralization assay, these antibodies were capable of inhibiting viral growth. We found the primary viral quasispecies to solely utilize the CCR-5 chemokine receptor; however, recombinant viruses differed in their cytopathology and in their sensitivity to beta-chemokine inhibition of viral growth. Sequence analysis of the gp120 open reading frames showed that amino acid changes in the C1 (D-->G at position 62) and C4 (V-->A at position 430) regions accounted for the phenotypic differences. These data demonstrate that early in infection, polymorphism exists in envelope glycoprotein coreceptor interactions and imply that therapeutic strategies targeted at this step in the viral life cycle may lead to rapid resistance.
Amino Acid Sequence↗
Unusual HIV transmissions through blood contact: analysis of cases reported in the United Kingdom to December 1997.
It is important to establish the likely route of infection for all reported HIV infected individuals if the HIV epidemic is to be understood. Investigating routes of infection may bring unusual infection routes to light. Steps have been taken in the United Kingdom (UK) to establish the likely mode of HIV acquisition for everyone reported as infected. If an initial report is incomplete the clinician caring for the patient is asked for relevant information. If further information is needed, and an interview is feasible and acceptable to both the clinician and the patient, information is collected from the patient through face-to-face semistructured interview. Such follow up has identified 19 cases (among 34,000 records of individuals with HIV and/or AIDS for which probable routes of infection have established) who seem to have acquired HIV infection in unusual circumstances. Seven of the 19 cases described in this paper are thought to have acquired HIV infection in the UK, two in Spain, and ten in countries with a high prevalence of HIV infection. This paper describes the circumstances in which HIV transmission is believed to have occurred.
Adult↗
Interaction of thyroid state and denervation on skeletal myosin heavy chain expression.
The goal of this study was to examine the effects of altered thyroid state and denervation (Den) on skeletal myosin heavy chain (MHC) expression in the plantaris and soleus muscles. Rats were subjected to unilateral denervation (Den) and randomly assigned to one of three groups: (1) euthyroid; (2) hyperthyroid; (3) and hypothyroid. Denervation caused severe muscle atrophy and muscle-type specific MHC transformation. Denervation transformed the soleus to a faster muscle, and its effects required the presence of circulating thyroid hormone. In contrast, denervation transformed the plantaris to a slower muscle independently of thyroid state. Furthermore, thyroid hormone effects did not depend upon innervation status in the soleus, while they required the presence of the nerve in the plantaris. Collectively, these findings suggest that both thyroid hormone and intact nerve (a) differentially affect MHC transformations in fast and slow muscle; and (b) are important factors in regulating the optimal expression of both type I and IIB MHC genes. This research suggests that for patients with nerve damage and/or paralysis, both muscle mass and biochemical properties can also be affected by the thyroid state.
Animals↗
Acute hemoperitoneum after large-volume paracentesis.
Hemoperitoneum resulting from rupture of mesenteric varices is a rare complication of portal hypertension with a high mortality of up to 70%. This case report describes the symptoms, clinical course, and treatment of 4 patients with acute hemoperitoneum caused by mesenteric variceal bleeding after large-volume paracentesis. Abdominal pain and/or hemorrhagic shock developed in 4 patients (age, 48-68 years), admitted for refractory ascites, 3 hours to 4 days after 1-4 large-volume paracenteses (> 4000 mL). Duplex sonography, performed in 3 of the 4 patients before onset of bleeding, showed retrograde flow in the mesenteric veins, suggesting large-caliber mesenteric collateralization. Treatment consisted of surgical ligation followed by transjugular intrahepatic portosystemic shunt (TIPS) (2 patients) and emergency TIPS with embolization of the bleeding vessel (1 patient). One patient died before any intervention could be initiated. In these 4 patients, the concurrence of large-volume paracentesis and hemoperitoneum suggests their causal relationship. The mechanism may be a sudden reduction in intraperitoneal pressure increasing the pressure gradient across the wall of the mesenteric varices, resulting in rupture and bleeding. The awareness of this complication may accelerate the diagnostic process and treatment.
Acute Disease↗
Tobacco use among male high school athletes.
PURPOSE: The purpose of this study was to compare tobacco use among high school male athletes with their nonathlete counterparts. We hypothesized that there was an inverse correlation between the intensity level of the sport and frequency of tobacco use. METHODS: Students were surveyed at seven high schools in northwest Louisiana using a 109-item questionnaire. Of the 1,200 males tested, 83% participated in one or more sports. The mean age was 15.8, and mean grade level was 10th. Sixty-seven percent were white, 27% African-American (AA), and 6% other. RESULTS: Forty-one percent of the adolescent males tested were one or more tobacco products, 31% reported cigarette smoking, 21% chewed tobacco, and 18% used snuff. Eleven percent reported using all three tobacco products. Race was a significant determinant of tobacco use, with whites being more likely to use each of the three tobacco products (P < .001). Medium- and high-intensity athletes were significantly (P < .01) less likely to be heavy smokers than athletes participating in low-intensity sports and nonathletes. However, athletes of each intensity sport used chewing tobacco and snuff at significantly higher rates (P < .001) than nonathletes. When race and grade point average were controlled, sports intensity was a significant predictor of smokeless tobacco use but not overall smoking behavior. Both AA and white high school male athletes at all sport intensity levels were using chewing tobacco and snuff at a rate higher at least 1.5 times that of their nonathlete counterparts. CONCLUSIONS: In our study, high school males' sports participation was a predictor of smokeless tobacco use but not overall smoking behavior. Although the probability of AA high school athletes using smokeless tobacco was low compared to whites, the pattern of use was similar across intensity levels of sports.
Adolescent↗
Analysis of promoters in Borrelia burgdorferi by use of a transiently expressed reporter gene.
A transient chloramphenicol acetyltransferase (CAT) expression system was developed for Borrelia burgdorferi. An Escherichia coli vector containing a promoterless Streptococcus agalactiae cat gene was constructed. Promoters for ospA, ospC, and flaB were placed upstream of this cat gene, and CAT assays were performed in E. coli from these stably maintained plasmids. The plasmids with putative promoters ospA and flaB were found to be approximately 20-fold more active than were the plasmids with ospC or no promoter. The level of activity correlated well with the resistance to chloramphenicol that each plasmid provided. Next, the nonreplicative plasmid constructs were transformed by electroporation into B. burgdorferi. CAT assays were performed by both thin-layer chromatography and the fluor diffusion method. Measurement of CAT activity demonstrated that the ospA promoter was again about 20-fold more active than the promoterless cat gene. The flaB and ospC promoters increased the activity seven- and threefold, respectively, over that with the promoterless construct. This simple transient-expression assay was shown to be an effective method to study promoter function in B. burgdorferi in the absence of a well-developed genetic system.
Antigens, Bacterial↗
Length polymorphism within the second variable region of the human immunodeficiency virus type 1 envelope glycoprotein affects accessibility of the receptor binding site.
Sequential mutations were introduced into the V2 region of human immunodeficiency virus (HIV) type 1 HXB2, affecting the length, charge, and number of potential glycosylation sites. The insertions had no effect on cytopathicity or on the ability of virus to replicate in peripheral blood mononuclear cells and established T-cell lines. However, deletion of amino acids 186 to 188, encoding a conserved glycosylation site, resulted in a nonviable virus, suggesting a minimal length requirement of 40 amino acids for a functional V2 loop. However, all amino acid insertions affected the sensitivity of the variants to neutralization by soluble CD4 and monoclonal antibodies specific for epitopes in the V3 and CD4 binding site regions. Furthermore, these mutant viruses showed resistance to neutralization by HIV-positive human sera. Soluble gp120 mutant glycoproteins showed increased affinities for soluble CD4 and monoclonal antibodies specific for a number of epitopes overlapping the CD4 binding site, confirming that length increases in V2 affect exposure of the CD4 binding site. In summary, these data demonstrate that differences in V2 length modulate immunoreactivity of the envelope glycoprotein and support an association between the V2 and CD4 binding site regions.
Binding Sites↗
From ABI sequence data to LASERGENE's EDITSEQ.
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Sequence Analysis, DNA↗
MEGALIGN. The multiple alignment module of LASERGENE.
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Sequence Alignment↗
Knowledge and attitude on screening mammography among low-literate, low-income women.
BACKGROUND: Low-income women utilize screening mammography less frequently, present at more advanced stages of disease, and have higher breast cancer mortality rates then women with higher incomes. The purpose of this study was to examine the relationship of reading ability to the knowledge and attitudes that low-income women have regarding screening mammography. METHODS: A convenience sample of 445 women were interviewed for this study. These women, age 40 years and older, had not had a mammogram in the past year. They were waiting to see a doctor in one of two outpatient clinics at Louisiana State University Medical Center in Shreveport when they were interviewed. A structured questionnaire assessed mammography knowledge and attitudes. Each patient's reading ability was assessed with the Rapid Estimate of Adult Literacy in Medicine (REALM). RESULTS: The women interviewed had a mean age of 56 years. Sixty-nine percent were African American, and 97% lived in households with annual incomes of less than $20,000. On the average, the highest grade completed in school was tenth grade. The average reading level was fourth to sixth grade, with 76% reading below a 9th-grade level. Lower reading ability correlated significantly with less mammography knowledge (P < 0.0001). A lack of accurate information about mammography was prevalent among low-level readers. Thirty-nine percent of women reading at or below a third-grade level did not know why women are given mammograms, compared with 12% of those reading at or above a ninth-grade level. Cost was a great concern in general, but cost concerns did not vary by reading level; 41% of all participants were very concerned about cost. CONCLUSIONS: Limited literacy skills and lack of knowledge about screening mammography may contribute considerably to the underutilization of screening mammograms in low-income women. Screening for reading level may identify a subset of low-income patients who could benefit from specialized education. These results could help guide effective educational interventions and better provider-patient communication about screening mammography for low-literate, low-income women.
Adult↗
Chimeric viruses expressing primary envelope glycoproteins of human immunodeficiency virus type I show increased sensitivity to neutralization by human sera.
We constructed a number of HXB2 viruses chimeric for the gp 120 glycoprotein derived from a number of viable molecular clones obtained from a primary isolate. Comparative biological characterization of the parental primary viruses with the gp 120.HXB2 chimeras demonstrated identical patterns of cell tropism and cytopathicity. Furthermore, both parental and chimeric viruses were insensitive to neutralization by sCD4 and a panel of conformation-dependent monoclonal antibodies, demonstrating that transfer of the gp 120 protein alone was sufficient to confer a "neutralization-resistant" phenotype to the T-cell-adapted clone HXB2. We assessed the contribution of gp 120 epitopes to the neutralizing immune response by comparing the sensitivity of these viruses to neutralization by a panel of sera from HIV-infected individuals. Seven of eleven sera tested were able to neutralize HXB2 and two or more of the chimeric viruses; in contrast, only one serum neutralized more than one of the parental primary virus clones. The association of gp 120-gp41 envelope at the surface of infected PBMC cultures was measured in the presence or absence of soluble CD4. No differences in CD4-induced gp 120 dissociation were seen between the chimeric and parental virus-infected cultures. Since gp 120 conformation appeared the same between primary and chimeric viruses, we suggest that the ability of human sera to neutralize the chimeric viruses may be mediated by epitopes within gp41.
Amino Acid Sequence↗
Diverse HIV-1 genetic subtypes in UK.
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Female↗