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Biomedical subjects

A Cross

Publications and source records attributed to A Cross.

At least 55 records · Page 3Linked to original sources
PubMed1993

Epitope mapping identifies an exposed loop between the unique amino- and conserved carboxy-domains of the large subunit of herpes simplex virus type 1 ribonucleotide reductase.

The large subunits of herpes simplex virus types 1 and 2 ribonucleotide reductases contain unique amino-terminal regions comprising 311 and 318 residues respectively, which are not found in ribonucleotide reductases from other sources. We report the mapping of the epitope recognized by monoclonal antibody 1026, which is specific for the large subunit (R1) of HSV-1, and then deduce the structural relationship of the amino-terminal region of R1 with the rest of the protein. A panel of 10 fusion proteins containing sequences spanning the entire R1 subunit were constructed. They were used together with proteolytic fragments of R1 and several synthetic peptides to show that the epitope is discontinuous and appears to be a loop structure centered on a previously located trypsin-sensitive site at residue 305. The existence of the loop was suggested by the observation that reactivity of the antibody with R1 could be blocked by peptides corresponding to residues 289 to 303 and 308 to 313 which flank the trypsin-sensitive site. Our results suggest that the unique amino-terminal region of R1 consists of a structurally distinct domain which is linked to the conserved carboxy region by an exposed loop.

Amino Acid Sequence↗
PubMed1993

An epitope within the DNA-binding domain of the herpes simplex virus immediate early protein Vmw175 is conserved in the varicella-zoster virus gene 62 protein.

We have isolated a panel of monoclonal antibodies that recognize the DNA-binding domain of the herpes simplex virus type 1 (HSV-1) immediate early polypeptide Vmw175. The mice used for the fusions had been immunized with the isolated Vmw175 DNA-binding domain. This had been purified from bacteria that carried a phage T7 expression plasmid with the DNA-binding domain coding region. The epitopes recognized by the monoclonal antibodies were mapped by using a family of truncated versions of the DNA-binding domain, which had also been expressed in the bacterial expression system. The monoclonal antibodies divided into at least four different groups according to this mapping. Several of the monoclonal antibodies recognized Vmw175 expressed in infected BHK cells by HSV-1 strain 17 in Western blots. One of them also recognized the corresponding protein of varicella-zoster virus gene 62. This is further illustration of the relatedness of the two polypeptides.

Amino Acid Sequence↗
PubMed1993

Effect of fasting, hypocaloric feeding, and refeeding on the energetics of stimulated rat muscle as assessed by nuclear magnetic resonance spectroscopy.

A previous study suggested that muscles from hypocalorically fed rats were limited in their ability to rephosphorylate ADP. During muscle contraction hydrolysis of ATP results in an increase in phosphorus, free ADP, delta GATP, and a reduction in phosphocreatine levels that is reversed during rest by rephosphorylation of ADP to ATP and the resynthesis of phosphocreatine by ATP. We therefore hypothesized that these changes would be restored more slowly during postcontraction rest in hypocalorically fed rats as compared with controls. We compared controls fed ad lib to 2-d fasted and hypocalorically fed rats, losing 20% of their weight. We also compared hypocalorically fed rats that had been refed ad lib for 7 d with age-matched controls fed ad lib. The results showed that ATP, muscle pH, and total muscle creatine levels were not different in all groups. The raised phosphorus and delta GATP levels and lower phosphocreatine/phosphorus ratio at the end of contraction changed more slowly during rest in the hypocaloric rats. These abnormalities were partially corrected by refeeding. The data taken as a whole support the concept of impaired rephosphorylation of ADP in malnourished muscle that is not completely restored by refeeding in stimulated muscle.

Adenosine Diphosphate↗
PubMed1992

A controlled trial comparing continued zidovudine with didanosine in human immunodeficiency virus infection. The NIAID AIDS Clinical Trials Group.

BACKGROUND: Although zidovudine is effective in patients with human immunodeficiency virus (HIV) infection, its efficacy may decline with prolonged use. Didanosine is another inhibitor of HIV reverse transcriptase. We evaluated the effectiveness of changing anti-HIV treatment from zidovudine to didanosine. METHODS: This multicenter, double-blind study involved 913 patients who had tolerated zidovudine for at least 16 weeks. The patients had the acquired immunodeficiency syndrome (AIDS), AIDS-related complex with less than or equal to 300 CD4 cells per cubic milliliter, or asymptomatic HIV infection with less than or equal to 200 CD4 cells per cubic milliliter. They were randomly assigned to receive 600 mg per day of zidovudine, 750 mg per day of didanosine, or 500 mg per day of didanosine. RESULTS: There were significantly fewer new AIDS-defining events and deaths among the 298 subjects assigned to 500 mg per day of didanosine than among the subjects who continued to receive zidovudine (relative risk, 1.39; 95 percent confidence interval, 1.06 to 1.82; P = 0.015). With 750 mg of didanosine, there was no clear benefit over zidovudine (relative risk, 1.10; 95 percent confidence interval, 0.86 to 1.42). The efficacy of didanosine was unrelated to the duration of previous zidovudine treatment. In the two didanosine groups, there were improvements in the number of CD4 cells (P less than 0.001 for both groups) and in p24 antigen levels (P = 0.03 in the 500-mg group; P = 0.005 in the 750-mg group), as compared with the zidovudine group. CONCLUSIONS: Changing treatment from zidovudine to 500 mg per day of didanosine appears to slow the progression of HIV disease.

AIDS-Related Complex↗
PubMed1992

Health of the public. The academic response. Health of the Public Mission Statement Working Group.

Aging of the population, increasing prevalence of chronic and disabling illnesses with multiple social and behavioral risk factors, concern about quality of care, and escalating costs of medical care require fundamental changes in the way that academic health centers discharge their mission. This article describes a newly developed "Mission Statement" for academic health centers that wish to contribute positively to the health of the populations that they serve. A shift toward addressing the needs of the public may produce increasing institutional strength, long-run stability, and enhanced productivity, as well as higher quality, more cost-effective care for patients. Seventeen centers in the Health of the Public Program are currently conducting activities that implement the described mission elements. The goals and objectives described herein create a foundation for change, with more balanced institutional goals, and could turn an emerging confrontation between academe and its public into an opportunity for both.

Academic Medical Centers↗
PubMed1991

Virulence determinants of Escherichia coli O6 extraintestinal isolates analysed by Southern hybridizations and DNA long range mapping techniques.

A total of 16 Escherichia coli O6 strains isolated from cases of extraintestinal infections were analysed for the genetic presence and phenotypic expression of fimbrial adhesins (P, S/FIC, type 1), aerobactin and hemolysin. In addition restriction fragment length polymorphisms (RFLPs) of Xbal-cleaved genomic DNA of seven selected strains, separated by orthogonal field alternation gel electrophoresis (OFAGE) were determined and virulence-associated DNA probes were used for Southern hybridization studies of the Xbal-cleaved genomic DNAs. The virulence characteristics and hybridization patterns obtained differed between the various isolates. In three isolates hemolysin genes and P fimbrial determinants were located on the same Xbal fragments. Furthermore, multiple copies of FIC determinants (foc) could be detected in two strains. Our data show that the new technique of pulse field electrophoresis together with Southern hybridization represents a powerful tool for the genetic analysis of pathogenic bacteria.

Adhesins, Escherichia coli↗
PubMed1990

Intratypic variation of herpes simplex virus type 2 isolates detected by monoclonal antibodies against viral glycoproteins.

Monoclonal antibodies (MAbs) to herpes simplex virus (HSV) glycoproteins gD, gG, gB, and gE were used to analyze antigenic variations of 128 genital HSV-2 isolates by an indirect enzyme-linked immunosorbent assay (ELISA). Isolates were considered significantly different from the standard HSV-2 strain 186 when their optical density (OD) in ELISA was less than half that of strain 186. This criterion gave 30 patterns of reactivity among the genital HSV-2 isolates. The MAbs to gB, gG, and 2 of the gD antibodies reacted with more than 90% of the isolates, suggesting that these MAbs recognized highly conserved epitopes. However, the gE MAb reacted with only 47% of the isolates, and one of the gD antibodies with only 39%. Thus, HSV-2 can readily tolerate modifications in some parts of the gD and gE molecules while remaining infectious.

Animals↗
PubMed1990

Mechanical function of the human lumbar interspinous and supraspinous ligaments.

The mechanical function of the interspinous and supraspinous ligaments has been examined by simulating, on excised specimens, the deformation caused during forward flexion of the spine in real life. The load extension curves showed that during the first half of flexion the ligaments carried very little load but towards the end of the range of flexion they resisted up to 134N. When the supraspinous ligament was sectioned the interspinous ligament alone resisted 75% of this load. Testing at high strain rates showed an increase in load-carrying capacity of up to 30%. The maximum extension moment that can be produced by these ligaments was calculated to be approximately 7 Nm, or 5% of the moment the back muscles can produce across any intervertebral joint. Hence, during active lifting, these ligaments in isolation provide little mechanical assistance.

Aged↗
PubMed1990

Localization on the herpes simplex virus type 1 genome of a region encoding proteins involved in adsorption to the cellular receptor.

We have previously shown that aminoglycosides such as neomycin and the polyamino acids polylysine and polyarginine selectively inhibit the binding of herpes simplex virus type 1 (HSV-1) to the cellular receptor, whereas HSV-2 infection is unaffected. In the present study we took advantage of this difference between HSV-1 and HSV-2 by using HSV(-1)-HSV(-2) intertypic recombinants to locate a region on the HSV-1 genome encoding proteins affecting the binding of the virion to the cellular receptor. The results were consistent with those obtained by marker rescue experiments. The identified region, which mapped between coordinates 0.580 and 0.687, contains two partial and eight complete genes, including the glycoprotein C (gC) gene and two others with potential transmembrane sequences. Various gC monoclonal antibody-resistant mutants of HSV-1 as well as a mutant completely lacking gC were found to be fully sensitive to neomycin, suggesting that gC is not the site of drug sensitivity and is not essential for adsorption of virus to the cellular receptor. However, the rate of adsorption was reduced in the absence of gC, indicating a facilitating function of the glycoprotein. The universal nature of this HSV-1 receptor binding was revealed by the similarity in drug sensitivity of infectivity in four different cell lines from various tissues and species.

Adsorption↗
PubMed1990

Home visitors and child health: analysis of selected programs.

The relationships between selected child health outcomes and programmatic interventions using home visitors are analyzed. The following features of seven programs are systematically reported: program characteristics; description of the home visitors; program objectives, sample size, and research design; outcome measures and reported data. A number of issues such as funding and long-term viability, use of professional or paraprofessional visitors, visitor selection and supervision, and evaluation of home visitor programs require clarification and are discussed. It is concluded that home visitor programs can contribute to child health outcomes such as increased birth weight, improved prenatal care, improved maternal-infant interaction, and improved use of community resources. Pediatricians can be supportive of such programs at many levels: becoming aware of the existence and range of services of home visitor programs in their area that serve families with children and referring families to those programs; being available to advise programs that are in the planning stages; providing advocacy at the local, state, and national level for the funding and development of such programs; and taking the initiative to join multidisciplinary efforts to develop new programs.

Alabama↗
PubMed1989

A descriptive analysis of emergency visits to an inner city family practice center.

A six-month prospective study of daily emergency visits was performed at an inner city family practice center in order to understand the utilization pattern of emergency services. 487 visits were identified during the study period. In general, patients of junior residents made more visits. The majority of visits (97%) were nonemergent. The most common presenting complaint was a general symptom (17%), although the most frequent diagnosis was in the supplementary category (17%) that includes medication renewals, the completion of forms and maternal and child health care. Females, the unemployed, the elderly, and individuals with poverty levels of income were most frequently seen in the emergency setting. The reasons for these patterns and the need for further investigations in this area are discussed.

Community Health Centers↗
PubMed1988

Survey of purported virulence factors of Escherichia coli isolated from blood, urine and stool.

One hundred randomly selected urinary and blood isolates and 50 stool isolates of Escherichia coli were analyzed for phenotypic characteristics which may contribute to their virulence potential. Bacteremic isolates were more likely to have K1 capsules and express mannose-sensitive hemagglutination compared to stool isolates. Blood-stream isolates more frequently contained complete 0 side-chains in their lipopolysaccharide layer and less frequently exhibited mannose-resistant hemagglutination when compared to urinary isolates. Total plasmid content, hemolysin, total colicin and colicin V production were not significantly increased in Escherichia coli from blood or urine when compared to those recovered from stool.

Antigens, Bacterial↗
PubMed1988

Quantitative relationship between capsular content and killing of K1-encapsulated Escherichia coli.

Since there are conflicting reports in the literature on a possible relationship between the K1 capsular polysaccharide (CP) content of Escherichia coli and its susceptibility to killing, we reexamined this issue in a strain that had a smooth lipopolysaccharide (LPS) phenotype (E. coli O18:K1:H7 Bort) and in a strain with a deep rough LPS phenotype (E412, spontaneously agglutinable: K1:H-). When cell-associated K1 capsular content was greater than 90 micrograms of K1 polysaccharide per 10(10) CFU, neither strain was lysed by 20% normal human serum. In contrast, at equivalent but lower levels of K1 CP content, E412 but not strain Bort was lysed by normal human serum. Thus, LPS phenotype is an additional surface determinant that affects bacterial susceptibility to killing. Organisms obtained from very early log phase, when cell-associated K1 CP is greatest, were significantly more virulent for mice than were bacteria harvested in stationary phase, when cell-associated K1 polysaccharide is lowest. We conclude that (i) there is a threshold level of K1 CP needed to confer protection from lysis by serum, and this is usually exceeded under standard growth conditions; (ii) at a given level of K1 CP the LPS phenotype is an important determinant of bacterial killing; and (iii) the loss of capsule at low pH may be an additional mechanism by which hosts defend against invasive infection by K1-encapsulated E. coli.

Antibodies, Bacterial↗
PubMed1988

Identification of the gene encoding the 65-kilodalton DNA-binding protein of herpes simplex virus type 1.

Hybrid arrest of in vitro translation was used to localize the region of the herpes simplex virus type 1 genome encoding the 65-kilodalton DNA-binding protein (65KDBP) to between genome coordinates 0.592 and 0.649. Knowledge of the DNA sequence of this region allowed us to identify three open reading frames as likely candidates for the gene encoding 65KDBP. Two independent approaches were used to determine which of these three open reading frames encoded the protein. For the first approach a monoclonal antibody, MAb 6898, which reacted specifically with 65KDBP, was isolated. This antibody was used, with the techniques of hybrid arrest of in vitro translation and in vitro translation of selected mRNA, to identify the gene encoding 65KDBP. The second approach involved preparation of antisera directed against oligopeptides corresponding to regions of the predicted amino acid sequence of this gene. These antisera reacted specifically with 65KDBP, thus confirming the gene assignment.

DNA-Binding Proteins↗