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Biomedical subjects

S B Porter

Publications and source records attributed to S B Porter.

At least 19 recordsLinked to original sources
PubMed2001

Effective suppression of vancomycin-resistant Enterococcus species in asymptomatic gastrointestinal carriers by a novel glycolipodepsipeptide, ramoplanin.

Nosocomial bloodstream infections due to vancomycin-resistant enterococci (VRE) are associated with increased morbidity rates, mortality rates, and hospitalization costs. Gastrointestinal carriage of VRE is an important risk factor for subsequent infections. This 3-arm, phase II, double-blinded, randomized, multicenter, placebo-controlled study evaluated the safety and efficacy of oral ramoplanin (a novel, nonabsorbed glycolipodepsipeptide) versus placebo for suppression of gastrointestinal VRE colonization. Sixty-eight patients who were colonized with VRE were enrolled and received 2 daily doses of ramoplanin (100 mg or 400 mg) or placebo orally for 7 days. The primary end point was the proportion of persons per group from whom VRE were not recovered (VRE-free) on days 7, 14, and 21 after screening. After treatment, VRE-free status was as follows: day 7, none of the 20 patients in the placebo group, and 17 of 21 (P<.001) and 18 of 20 (P<.001) in the 100-mg and 400-mg ramoplanin groups, respectively; on day 14, 2 of 20 patients in the placebo group, and 6 of 21 (P=.134) and 7 of 17 (P=.028), in the 100-mg and 400-mg ramoplanin groups, respectively. By day 21, there were no differences between treatment groups. Adverse events were similar for all treatment groups. Ramoplanin was safe and effective in temporarily suppressing gastrointestinal VRE carriage.

Adult↗
PubMed1999

A double blind, randomized, placebo-controlled phase II study to assess the safety and efficacy of orally administered SP-303 for the symptomatic treatment of diarrhea in patients with AIDS.

OBJECTIVE: The aim of this study was to investigate the safety and effectiveness of orally administered SP-303 in patients with AIDS and diarrhea. METHODS: This is a multicenter, phase II, randomized, double blind, placebo-controlled study. HIV-positive subjects with a history of a CD4 count <200 or an AIDS-defining illness were admitted to an inpatient study unit and screened for diarrhea defined as at least three abnormal (i.e., soft or watery) stools and >200 g of abnormal stool weight over a 24-h period. Subjects discontinued all antidiarrheal agents >24 h before enrollment. Stool samples were studied for routine pathogens. Subjects received 500 mg p.o. of SP-303 or placebo every 6 h for 96 h (4 days). Stool frequency and weights were recorded. Subjects were monitored for symptoms and side effects and were seen 1 wk later in follow-up. RESULTS: A total of 26 subjects received SP-303, and 25 received placebo. There were no significant demographic differences between treatment arms. A total of 41 subjects (80%) were receiving antiretroviral therapy and 39 subjects (77%) were receiving at least one protease inhibitor. Stool studies revealed no pathogens in 48 of 51 patients (94%). There were no serious adverse events or laboratory abnormalities. The SP-303 treatment group demonstrated a mean reduction from baseline stool weight of 451 g/24 h versus 150 g/24 h with placebo on day 4 of treatment (p = 0.14), and a mean reduction in abnormal stool frequency of three abnormal stools in 24 h versus two in 24 h in the placebo group (p = 0.30). Daily measures analysis over 4 days of treatment demonstrated that SP-303 subjects had a significant reduction in stool weight (p = 0.008) and abnormal stool frequency (p = 0.04) when compared to placebo-treated subjects. CONCLUSIONS: SP-303 is safe and well tolerated. These results suggest that SP-303 may be effective in reducing stool weight and frequency in patients with AIDS and diarrhea.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Variable region domain exchange influences the functional properties of IgG.

In the present study we have characterized a family of anti-dansyl Abs with the variable region of the heavy chain on human Ckappa and the variable region of the light chain on different human gamma constant regions (creating inside-out molecules). Although fully assembled molecules were secreted, this variable region exchange slowed the kinetics of Ab assembly. Although the variable region exchange does not lead to a detectable change in the microenvironment of the combining site, it did alter the kinetic parameters of binding to immobilized Ag, slowing both the on and off rates. When effector functions were evaluated, inside-out IgG1 and IgG3 were more effective in complement-mediated cytolysis than their wild-type counterparts. Variable region domain exchange may be one approach to obtaining Abs of identical specificity with altered binding characteristics.

Antigens↗
PubMed1996

Erythropoiesis and vasculogenesis in embryoid bodies lacking visceral yolk sac endoderm.

During mouse embryogenesis the first hematopoietic and endothelial cells form in blood islands located between layers of visceral endoderm and mesoderm in the yolk sac. The role of visceral endoderm in primitive hematopoiesis and vasculogenesis is not well understood. We have assessed the consequences of a lack of visceral endoderm on blood cell and vessel formation using embryoid bodies derived from mouse embryonic stem (ES) cells deficient in GATA-4, a transcription factor expressed in yolk sac endoderm. When differentiated in vitro, these mutant embryoid bodies do not develop an external visceral endoderm layer. We found that Gata4-/- embryoid bodies, grown either in suspension culture or attached to a substratum, are defective in primitive hematopoiesis and vasculogenesis as evidenced by a lack of recognizable blood islands and vascular channels and a reduction in the expression of the primitive erythrocyte marker epsilon y-globin. Expression of the endothelial cell transcripts FIk-1, FIt-1, and platelet-endothelial cell adhesion molecule (PECAM) was not affected in the mutant embryoid bodies. Gata4-/- ES cells retained the capacity to differentiate into primitive erythroblasts and endothelial cells when cultured in methylcellulose or matrigel. Analysis of chimeric mice, generated by injecting Gata4-/- ES cells into 8-cell stage embryos of ROSA26 transgenic animals, showed that Gata4-/- ES cells can form blood islands and vessels when juxtaposed to visceral endoderm in vivo. We conclude that the visceral endoderm is not essential for the differentiation of primitive erythrocytes or endothelial cells, but this cell layer plays an important role in the formation and organization of yolk sac blood islands and vessels.

Animals↗
PubMed1995

Pseudotumor of infancy and congenital muscular torticollis.

Pseudotumor of infancy presents as a discrete, firm mass in the distal sternocleidomastoid muscle in infants two to four weeks of age. Congenital muscular torticollis may develop from the resultant fibrosis in 10 to 20 percent of cases. Hip dysplasia is an associated feature of congenital muscular torticollis in approximately 10 percent of cases. Pseudotumor of infancy must be differentiated from other causes of cervical soft tissue masses. Diagnostic choices include fine-needle aspiration biopsy, cervical radiography, ultrasonography, computed tomographic scanning of the head and neck, and magnetic resonance imaging. Left untreated, congenital muscular torticollis may lead to significant craniofacial asymmetry and scoliosis. Heat, massage and passive stretching exercises are the preferred initial treatments for pseudotumor and torticollis. More than 70 percent of patients will respond to this approach. Surgery should be reserved for treatment of cases that persist past the first year of life.

Diagnosis, Differential↗
PubMed1993

Public knowledge and attitudes about AIDS among adults in Calcutta, India.

Despite the relatively recent introduction of human immunodeficiency virus (HIV) into India, the acquired immunodeficiency syndrome (AIDS) is rapidly becoming a significant health problem in that country. Education about AIDS remains the most effective strategy to prevent its spread. To assess the level of knowledge and the associated attitudes about AIDS among Indians in Calcutta, 153 English-speaking adults were surveyed during April and May 1990. Sixty-five of 75 men (87%) and 77 of 78 women (99%) questioned had heard of AIDS, the majority within the past 2-3 years. Newspaper and television were the most frequently cited sources of information. Of respondents who had heard of the disease, 95% knew AIDS was transmitted by sexual intercourse; less than half, however, also knew that AIDS could not be acquired through kissing, insect bites or by using public toilets. In general, respondents had little specific knowledge regarding the symptoms of AIDS, and 29% were unaware that infected persons could be asymptomatic and appear healthy. Level of education was the only variable that independently correlated with knowledge of AIDS. More than one-third of respondents would not have dinner with or continue to work with an AIDS patient and 50% believed all AIDS patients should be quarantined. More effective and widespread public education is necessary to help slow the rapidly developing AIDS epidemic in India.

AIDS Serodiagnosis↗
PubMed1992

Toxoplasmosis of the central nervous system in the acquired immunodeficiency syndrome.

BACKGROUND AND METHODS: Toxoplasmosis is the most common opportunistic infection of the central nervous system in patients with the acquired immunodeficiency syndrome (AIDS). To investigate its clinical course, we reviewed the records of 115 patients with AIDS and central nervous system toxoplasmosis treated at San Francisco General Hospital between 1981 and 1990. RESULTS: The most common presenting symptoms were headache (in 55 percent), confusion (52 percent), and fever (47 percent). Focal neurologic deficits were present in 79 patients (69 percent). The median CD4 cell count at presentation was 50 per cubic millimeter (50 x 10(6) per liter). Thirteen of 80 patients with clinical toxoplasmosis (16 percent) and 4 of 18 patients with pathologically proved disease (22 percent) had undetectable antitoxoplasma IgG antibodies by indirect immunofluorescence assay. Of 103 patients, 94 (91 percent) had enhancing lesions on CT. Single lesions were seen in 28 of 103 patients (27 percent) on CT, and such lesions were seen in 3 of 21 patients (14 percent) on magnetic resonance imaging. Over 90 percent of patients who eventually had clinical and radiographic improvement had evidence of improvement by day 14 of therapy. Adverse drug reactions occurred in 71 patients (62 percent) and led to a change in therapy in 50 patients (43 percent). Among the patients who survived a first episode of toxoplasmosis, the median survival was 265 days. CONCLUSIONS: Toxoplasmosis occurs in advanced stages of human immunodeficiency virus infection, and the absence of antitoxoplasma antibodies on immunofluorescence assay does not exclude the diagnosis. The clinical and radiographic response to therapy is usually rapid, but treatment is frequently limited by adverse drug effects.

AIDS-Related Opportunistic Infections↗
PubMed1988

Calcium transport by basal lateral membrane vesicles from rat small intestine decreases with age.

There is a marked decrease in active Ca2+ transport by the rat small intestine with age, particularly between 2 and 12 months. Much evidence suggests that the active component of Ca2+ transport resides in the energy-dependent pumping of Ca2+ across the intestinal basal lateral membrane. Therefore, we have characterized Ca2+ uptake by basal lateral membrane vesicles isolated from young (2-3 month old) and adult (12-14 month old) rats. In vesicles from the proximal duodenum, ATP-dependent Ca2+ uptake was about 4-times greater in the young animal than in the adult. There were no age differences in Ca2+ uptake in the absence of ATP. In vesicles from the ileum, Ca2+ uptake was much less than in the duodenum. The age differences in the ileum were smaller, and ATP-dependent Ca2+ uptake in the young was only twice that seen in the adult. Osmotic lysis of duodenal vesicles reduced Ca2+ uptake to low levels in both age groups, indicating that most of the Ca2+ was being taken up into an osmotically active space. Kinetic studies of Ca2+ uptake showed that there was no change in the apparent affinity but a 5-fold decrease in the Vmax of the adult Ca2+ transport system compared to that of the young animal. This marked decrease in the capacity of basal lateral membrane vesicles to actively transport Ca2+ may contribute to the decline in intestinal Ca2+ absorption with age.

Aging↗
PubMed1988

Dermonecrotic toxin and tracheal cytotoxin, putative virulence factors of Bordetella avium.

We examined Bordetella avium for virulence factors common to Bordetella pertussis, including pertussis toxin, filamentous hemagglutinin, adenylate cyclase, dermonecrotic toxin, and tracheal cytotoxin. B. avium produced a dermonecrotic toxin and a tracheal cytotoxin. The dermonecrotic toxin of B. avium is a 155,000-molecular-weight, heat-labile protein which was lethal for mice, guinea pigs, young chickens, and turkey poults and produced dermonecrosis when injected intradermally into guinea pigs, chickens, and turkey poults. High-pressure liquid chromatography of B. avium culture supernatant fluid revealed the presence of a tracheal cytotoxin chemically identical to that produced by B. pertussis. B. avium isolates were negative for B. pertussis-like filamentous hemagglutinin and pertussis toxin when assayed with antibody against B. pertussis filamentous hemagglutinin and pertussis toxin. Furthermore, B. avium failed to induce the clustered CHO cell morphology characteristic of pertussis toxin. Adenylate cyclase assays indicated that B. avium does not produce an extracytoplasmic adenylate cyclase, even after passage through embryonated turkey eggs. Since production of virulence proteins by B. pertussis is regulated by growth in media containing nicotinamide or MgSO4 or by growth at reduced temperatures, we determined the effect of these supplements and growth conditions on production of dermonecrotic toxin by B. avium. Production of dermonecrotic toxin in B. avium was not altered by growth in media containing 100 microM FeSO4 or 500 micrograms of nicotinamide per ml or by growth at 25 or 42 degrees C, but production was significantly decreased by growth in media containing 20 mM MgSO4 and slightly reduced by growth in media containing 500 micrograms of nicotinic acid per ml. These studies revealed that B. avium is similar to B. pertussis in that both species produce a dermonecrotic toxin and a tracheal cytotoxin and production of dermonecrotic toxin is regulated by nicotinamide and MgSO4. The presence of dermonecrotic toxin and tracheal cytotoxin in all Bordetella species indicates that these products may be important virulence factors in bordetellosis.

Adenylate Cyclase Toxin↗
PubMed1986

Vitamin A status affects chromatin structure.

We have examined RNA synthesis by nuclei isolated from testes of rats of varying vitamin A status. Nuclei from retinol-deficient animals showed substantially decreased RNA synthesis by polymerase II when compared to nuclei from normal animals. Within 4 hours after oral administration of retinyl acetate (as the source of retinol) to deficient animals, RNA synthesis by polymerase II had significantly increased. Administration of retinoic acid had a similar but lesser effect. Nucleoside analysis after alkaline hydrolysis of the RNA synthesized by the endogenous polymerase II suggested that the increased activity was due to a greater number of actively transcribing polymerase II molecules on the DNA. Further, when the template capacity of testicular chromatin isolated from deficient and retinyl acetate refed animals was compared, the number of sites recognized by E. coli RNA polymerase was increased twofold after retinyl acetate administration. We conclude that these retinol-induced changes in transcription are due at least in part to changes in chromatin structure.

Animals↗
PubMed1983

Localization of cellular retinol-binding protein in several rat tissues.

The distribution of cellular retinol-binding protein (CRBP) in rat liver, ileum, and epididymis was examined by the peroxidase-antiperoxidase immunolocalization technique. Positive cytoplasmic staining was seen in the liver when antiserum prepared against purified CRBP was used but not when antiserum absorbed with purified CRBP was used. Ileal mucosa, a tissue that contains no detectable CRBP, showed no positive staining. The epididymis showed strong positive staining in the caput but not in the cauda. Staining was present in principal and basal cells but not in peritubular or interstitial cells. Radioimmunoassay revealed that the CRBP within the caput epididymidis was localized in the initial segment and proximal region, areas known to be involved in the synthesis and secretion of factors necessary for sperm maturation. The results demonstrate that the expression of CRBP may vary within the same cell type, as well as between different cell types within the same tissue.

Animals↗
PubMedDate not supplied

Localization of cellular retinol-binding protein and cellular retinoic acid-binding protein in the rat testis and epididymis.

The distribution of cellular retinol-binding protein (CRBP) and cellular retinoic acid-binding protein (CRABP) in rat testis and epididymis was examined by the peroxidase-antiperoxidase immunolocalization technique. In the testis, cellular retinol-binding protein was localized exclusively in the Sertoli cells. Staining varied with the stages of the seminiferous epithelium cycle and was maximal prior to the maturation divisions. Cellular retinoic acid-binding protein was localized exclusively in the germinal cells in the adluminal compartment. The results suggest that retinoic acid may be the retinoid form used by the germinal cells, and that Sertoli cells may use the cellular retinol-binding protein to transfer retinol from the basal to the adluminal compartment. In the epididymis, cellular retinol-binding protein was localized in the cytoplasm and stereocilia of the principal cells in the proximal caput epididymidis, while cellular retinoic acid-binding protein was localized in the spermatozoa and the stereocilia of the principal cells throughout the epididymis and in the epithelial cells of the distal vas deferens. Sperm staining intensity decreased from the initial segment to the cauda. The presence of high levels of cellular retinol-binding protein in the epithelial cells and high levels of cellular retinoic acid-binding protein in the spermatozoa of the caput epididymidis, known to be involved in the synthesis and secretion of factors necessary for sperm maturation, suggests that vitamin A may have a role in this process.

Animals↗
PubMedDate not supplied

Virulence of Salmonella typhimurium mutants for White Leghorn chicks.

A strain of Salmonella typhimurium that is highly virulent for 1-day-old white leghorn chicks was genetically modified by deletion (delta) of the adenylate cyclase (cya) and cyclic AMP receptor protein (crp) genes or by removal (curing) of the 91-kilobase virulence plasmid. These mutants were then compared with the wild-type S. typhimurium strain for virulence in 1-day-old chicks and for their ability to colonize chicks of various ages. The plasmid-cured mutant showed a slight reduction in virulence, whereas the delta cya delta crp mutant was completely avirulent. The wild-type strain and both mutant strains were capable of colonizing various organs within the chicks. At all time points, the delta cya delta crp strain colonized chicks at lower levels than the wild-type strain. Titers of the plasmid-cured strain increased more slowly in visceral organs than did those of the wild type.

Animals↗
PubMedDate not supplied

Effect of infective dose on humoral immune responses and colonization in chickens experimentally infected with Salmonella typhimurium.

The influence of infective dose on chicken immunogenicity was examined in 1-week-old chickens. Chickens were infected orally with various doses of chi 3761 or chi 3985. Fecal shedding, colonization of the cecum, and induction of Salmonella-specific serum immunoglobulin isotypes were analyzed over a 5-week period. The delta cya delta crp Salmonella typhimurium vaccine strain chi 3985 was used to assess the effect of vaccination dose on protection after oral vaccination of chickens at 1 day and 2 weeks of age. Wild-type S. typhimurium strain chi 3761 was used to challenge vaccinated and unvaccinated chickens at 6 weeks of age, and the recovery of Salmonella from the cecum was used as a measure of protection. Infection of 1-week-old chickens with chi 3985 was more effective in reducing fecal excretion and cecal colonization than was infection with chi 3761. Double vaccination with 10(8) or 10(7) CFU of chi 3985 at 1 day and 2 weeks of age protected vaccinated chickens against cecal colonization by the challenge strain chi 3761. Immunogenicity of Salmonella is dose and genotype-dependent.

Administration, Oral↗