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D Schwartz

Publications and source records attributed to D Schwartz.

At least 55 records · Page 3Linked to original sources
PubMed2000

Use of plots to define pollen-vegetation relationships in densely forested ecosystems of Tropical Africa.

Modern soil samples from South Congo were analyzed for pollen content and compared to forest inventories to define modern pollen-vegetation relationships. A correspondence analysis (CA) was applied independently to botanical and pollen data and a hierarchical cluster analysis to pollen data only. Subsequently, a CA using a presence-absence approach has been made to directly compare the two types of data. Results show that the pollen rain and floristic composition of the sampled sites are not directly linked to altitudinal or precipitation gradients, but clear evidence of variation in relation to hygromorphy and soil type is detected. The forests occurring in swampy environments are well differentiated from the forests developed on well-drained soils by pollen and floristic data. Among forests on well-drained soils, a good distinction can be made between those growing on sandy soils and those growing on ferralitic soils. The comparison between pollen spectra and vegetation shows site-to-site variations in pollen assemblages in relation to the floristic heterogeneity of forests, and it appears that few taxa show a good correlation between plant cover and pollen abundance.

Journal Article↗
PubMed2000

A fast signal-induced activation of Poly(ADP-ribose) polymerase: a novel downstream target of phospholipase c.

We present the first evidence for a fast activation of the nuclear protein poly(ADP-ribose) polymerase (PARP) by signals evoked in the cell membrane, constituting a novel mode of signaling to the cell nucleus. PARP, an abundant, highly conserved, chromatin-bound protein found only in eukaryotes, exclusively catalyzes polyADP-ribosylation of DNA-binding proteins, thereby modulating their activity. Activation of PARP, reportedly induced by formation of DNA breaks, is involved in DNA transcription, replication, and repair. Our findings demonstrate an alternative mechanism: a fast activation of PARP, evoked by inositol 1,4,5,-trisphosphate-Ca(2+) mobilization, that does not involve DNA breaks. These findings identify PARP as a novel downstream target of phospholipase C, and unveil a novel fast signal-induced modification of DNA-binding proteins by polyADP-ribosylation.

Animals↗
PubMed2000

A phase II study of two HIV type 1 envelope vaccines, comparing their immunogenicity in populations at risk for acquiring HIV type 1 infection. AIDS Vaccine Evaluation Group.

Several immunogens induce HIV-specific neutralization and in vitro lymphoproliferation in adults at low HIV-1 risk, but responses in persons at high HIV-1 risk are not known. We performed a multicenter, double-blinded, adjuvant-controlled trial with two gp120 vaccines in 296 HIV-1-uninfected volunteers, including 176 reporting higher HIV-1 risk activities. The immunogens were remarkably well tolerated. After three immunizations, 210 of 241 vaccinees (87%) developed neutralizing antibodies, which persisted in 59% after 2 years. The injection drug users receiving SF-2/gp120 had decreased antibody responses relative to the lower risk groups. Envelope-specific lymphoproliferation peaked after two immunizations, and 54% of vaccinees mounted a DTH reaction to gp120 after 4 years. In summary, these immunogens have low adverse reactogenicity and induce durable antibody and T cell responses to the prototype strains. Unexpected differences in antibody responses among diverse HIV-1 risk strata lend support to the conduct of expanded phase II trials in populations other than low-risk volunteers.

AIDS Vaccines↗
PubMed2000

In vitro correlates of HIV-2-mediated HIV-1 protection.

A prospective study of high-risk commercial sex workers in Senegal has shown that HIV-2 infection may reduce the risk of subsequent HIV-1 infection; these findings have been confirmed and extended, now with 13 years of observation. While exploring the biological mechanisms behind this natural protection, we found that a significant proportion of peripheral blood mononuclear cells obtained from HIV-2-infected subjects resisted in vitro challenge with CCR5-dependent HIV-1 viruses but not CXCR4-dependent viruses. High levels of beta-chemokines, the natural ligands of the CCR5 coreceptor, were correlated with low levels of viral replication, and resistance was abrogated by antibodies to beta-chemokines. Our results suggest that beta-chemokine-mediated resistance may be an important correlate of HIV protection against HIV-1 infection and relevant to HIV vaccine design.

AIDS Vaccines↗
PubMed2000

HLA B*5701 is highly associated with restriction of virus replication in a subgroup of HIV-infected long term nonprogressors.

A unique cohort of HIV-1-infected long term nonprogressors (LTNP) with normal CD4(+) T cell counts and <50 copies/ml of plasma were prospectively recruited for study. HLA typing revealed a dramatic association between the HLA B*5701 class I allele and nonprogressive infection [85% (11 of 13) vs. 9.5% (19 of 200) in progressors; P < 0. 001]. Antigen-specific CD8(+) T cells were enumerated by flow cytometric detection of intracellular IFN-gamma in response to HIV antigens and HLA B*57-gag tetramer staining. No quantitative differences in the total HIV-specific CD8(+) T cell responses were observed between B*57(+) LTNP and five B*57(+) progressors (P = 0.4). Although similar frequencies of peptide specific CD8(+) T cells were also found, the gag-specific CD8(+) T cell response in the LTNP group was highly focused on peptides previously shown to be B*57-restricted. These findings indicate that, within this phenotypically and genotypically distinct cohort, a host immune factor is highly associated with restriction of virus replication and nonprogressive disease. They also strongly suggest a mechanism of virus specific immunity that directly operates through the B*5701 molecule. Further characterization of qualitative differences in the virus-specific responses that distinguish HLA B*57(+) LTNP from progressors may ultimately define mechanisms of effective immune mediated restriction of virus replication.

Alleles↗
PubMed2000

Genetic heterogeneity in Peutz-Jeghers syndrome.

LKB1, the human gene encoding a serine threonine kinase, was recently identified as a susceptibility gene for Peutz-Jeghers syndrome (PJS), a disease characterized by the constellation of intestinal hamartomata, oral mucocutaneous hyperpigmentation, and an increased risk for gastrointestinal as well as extraintestinal malignancies. To date, the majority of individuals with PJS have been found to have genetic alterations in LKB1, most of which result in protein truncation. Additionally, linkage analyses have suggested a modicum of genetic heterogeneity, with the majority of PJS families showing linkage to the LKB1 locus. In this study, we evaluated five kindreds with greater than two affected family members, five PJS probands with only one other affected family member, as well as 23 individuals with sporadic PJS for mutations within the LKB1 gene. Conformation sensitive gel electrophoresis was utilized for the initial screen, followed by direct sequence analysis for characterization. Long-range PCR was used for the detection of larger genetic insertions or deletions. Mutation analysis revealed genetic alterations in LKB1 in two probands who had a family history of PJS. LKB1 mutations were detected in only four of the remaining 23 cases of sporadic PJS. These data suggest the presence of significant genetic heterogeneity for PJS and the involvement of other loci in this syndrome.

AMP-Activated Protein Kinase Kinases↗
PubMed2000

Conjugation of protein to immunostimulatory DNA results in a rapid, long-lasting and potent induction of cell-mediated and humoral immunity.

Immunostimulatory DNA sequences (ISS) are a potent Th1 adjuvant. We hypothesized that conjugation of ISS to protein antigens would strongly enhance their immunogenicity because both antigen and adjuvant (ISS) would be delivered to the same locale/antigen-presenting cell. To test this hypothesis, we conjugated a 22-mer immunostimulatory oligodeoxynucleotide (ISS-ODN) to two test antigens of differing intrinsic immunogenicity, namely Escherichia coli beta-galactosidase and the HIV-1 envelope glycoprotein gp120. We show that the antigen-ISS conjugates rapidly induce Th1 cells secreting high levels of IFN-gamma, strong CTL activity, and high titer IgG2a and HIV-neutralizing antibodies, exceeding gene and protein vaccination alone or immunization with mixtures of antigen and ISS-ODN. The data suggest that this procedure generates a novel and unique vaccine that rapidly triggers strong humoral and cell-mediated immunity.

Animals↗
PubMed2000

Detachment of the glycolytic enzymes, phosphofructokinase and aldolase, from cytoskeleton of melanoma cells, induced by local anesthetics.

Cancer cells are characterized by a high rate of glycolysis, which is their primary energy source. An important mechanism that controls glycolysis is the reversible binding of glycolytic enzymes to cytoskeleton. We report here that the local anesthetics, lidocaine and bupivacaine, induced a dose-dependent detachment of the glycolytic enzymes, phosphofructokinase (EC 2.7.1.11) and aldolase (EC 4.1.2.13), from cytoskeleton of B16 melanoma cells. The detachment of glycolytic enzymes from cytoskeleton would reduce the provision of local ATP, in the vicinity of cytoskeleton-membrane and would also affect cytoskeleton structure. We show here that the local anesthetics decreased the viability of melanoma cells. The detachment of the glycolytic enzymes from cytoskeleton, induced by the drugs, preceded melanoma cell death, which indicates that this is an early effect and not a result of cell death. Bupivacaine was more potent than lidocaine both on the glycolytic enzymes and on cell viability. The present results suggest that local anesthetics, and especially bupivacaine, are promising drugs for the treatment of melanoma.

Anesthetics, Local↗
PubMed2000

The use of subcutaneous erythropoietin and intravenous iron for the treatment of the anemia of severe, resistant congestive heart failure improves cardiac and renal function and functional cardiac class, and markedly reduces hospitalizations.

OBJECTIVES: This study evaluated the prevalence and severity of anemia in patients with congestive heart failure (CHF) and the effect of its correction on cardiac and renal function and hospitalization. BACKGROUND: The prevalence and significance of mild anemia in patients with CHF is uncertain, and the role of erythropoietin with intravenous iron supplementation in treating this anemia is unknown. METHODS: In a retrospective study, the records of the 142 patients in our CHF clinic were reviewed to find the prevalence and severity of anemia (hemoglobin [Hb] <12 g). In an intervention study, 26 of these patients, despite maximally tolerated therapy of CHF for at least six months, still had had severe CHF and were also anemic. They were treated with subcutaneous erythropoietin and intravenous iron sufficient to increase the Hb to 12 g%. The doses of the CHF medications, except for diuretics, were not changed during the intervention period. RESULTS: The prevalence of anemia in the 142 patients increased with the severity of CHF, reaching 79.1% in those with New York Heart Association class IV. In the intervention study, the anemia of the 26 patients was treated for a mean of 7.2 +/- 5.5 months. The mean Hb level and mean left ventricular ejection fraction increased significantly. The mean number of hospitalizations fell by 91.9% compared with a similar period before the study. The New York Heart Association class fell significantly, as did the doses of oral and intravenous furosemide. The rate of fall of the glomerular filtration rate slowed with the treatment. CONCLUSIONS: Anemia is very common in CHF and its successful treatment is associated with a significant improvement in cardiac function, functional class, renal function and in a marked fall in the need for diuretics and hospitalization.

Aged↗
PubMed2000

Subtypes of victims and aggressors in children's peer groups.

This study reports an investigation of the behavioral profiles and psychosocial adjustment of subgroups of victims and aggressors in elementary school peer groups. Peer nomination scores for aggression and victimization were used to classify 354 inner-city children (mean age of 10.3 years) into one of four subgroups: aggressive victims, nonaggressive victims, nonvictimized aggressors, and normative contrasts. Subgroup comparisons were then conducted using multi-informant assessment of social behavior, social acceptance-rejection, behavioral regulation, academic functioning, and emotional distress. Children in each of the victim-aggressor subgroups were characterized by a degree of social and behavioral maladjustment. However, impairments in behavioral and emotional regulation were most evident for the aggressive victim subgroup. Aggressive victims were also characterized by academic failure, peer rejection, and emotional distress. The results of this investigation highlight the distinctive nature of the aggressive victim subgroup.

Aggression↗
PubMed2000

Use of short-term culture for identification of Mycobacterium avium subsp. paratuberculosis in tissue from Crohn's disease patients.

OBJECTIVE: To investigate the role of Mycobacterium avium subsp. paratuberculosis (MAP) in Crohn's disease (CD), using short-term mycobacterial culture media. METHODS: Sixty-three tissue specimens from 27 CD patients and 36 controls were processed and inoculated into a modified 7H9 broth base medium and incubated at 37 degrees C and 5% CO2 for up to 1 year. Acid-fast staining, determination of mycobactin dependency, PCR analysis using two IS900-derived oligonucleotides and hybridization with an internal probe were performed. RESULTS: MAP was present in six of seven (86%) surgically resected tissue samples and in four of 20 (20%) biopsies, with an overall 37% from CD patients, as compared to two of 36 (5.6%) of control specimens. The presence of MAP in Mycobacterial Growth Indicator Tube (MGIT) cultures was detected within 10-12 weeks for surgically resected tissue and after 40 weeks for biopsy specimens, with no MAP growth detected in 12B* Bactec cultures. CONCLUSIONS: Because MAP was present in 86% of resected tissue compared to 20% of biopsy specimens from CD patients, we speculate that MAP resides in the submucosal layer closer to the active part of the ulcer rather than on the surface of the mucosal cells. Thus, surgically resected tissue cultured in MGIT medium is a favorable protocol for rapid cultivation of MAP and for investigating its role in CD pathogenesis. The data support the mycobacterial role in CD pathogenesis.

Crohn Disease↗
PubMed2000

Conjugation of immunostimulatory DNA to the short ragweed allergen amb a 1 enhances its immunogenicity and reduces its allergenicity.

BACKGROUND: Allergen immunotherapy is inconvenient and associated with the risk of anaphylaxis. Efforts to improve the safety of immunotherapy by means of chemical modification of allergens have not been successful because it greatly reduced their antigenicity. Recently, immunostimulatory DNA sequences (ISS or CpG motifs) have been shown to act as strong T(H)1 response-inducing adjuvants. OBJECTIVE: We sought to determine whether conjugation of ISS to the major short ragweed allergen Amb a 1 results in enhanced immunotherapeutic potential in mice and decreased allergenicity in human subjects. METHODS: A 22-mer ISS oligodeoxynucleotide (ISS-ODN) was coupled to Amb a 1 and used for immunization of mice, rabbits, and monkeys. RESULTS: In mice the Amb a 1-ISS conjugate induced a T(H)1 response (IFN-gamma secretion), whereas Amb a 1 induced a T(H)2 response (IL-5 secretion). The T(H)1 response was not observed with an Amb a 1-non-ISS conjugate. Coinjection of Amb a 1 with ISS-ODN was much less effective in inducing a T(H)1 response. In mice primed for a T(H)2 response, injection with Amb a 1-ISS conjugate induced a de novo T(H)1 response and suppressed IgE antibody formation after challenge with Amb a 1. Amb a 1-ISS conjugate induced high-titer anti-Amb a 1 IgG antibodies in rabbits and cynomolgus monkeys, whereas Amb a 1 alone or Amb a 1 coinjected with ISS-ODN did not induce a detectable response. Amb a 1-ISS conjugate was less allergenic than Amb a 1 alone, as shown by a 30-fold lower histamine release from human basophils of patients with ragweed allergy, whereas mixing ISS-ODN with Amb a 1 did not reduce histamine release. CONCLUSION: Amb a 1-ISS conjugate has an enhanced T(H)1-biased immunogenicity and reduced allergenicity. It may offer a more effective and safer approach for allergen immunotherapy than currently available methods.

Allergens↗
PubMed2000

Epidemiology of vascular catheter-related bloodstream infections in a large university hospital in Israel.

Intravascular catheter-related infection and associated bacteraemia constitute a serious and increasing problem among nosocomial infections. As a part of an ongoing survey of positive blood cultures, all catheter-related bloodstream infections (CR-BSI) were reviewed in the authors' Medical Center in 1996, in order to evaluate the magnitude and seriousness of this problem. The largest group (28%) of hospital-acquired bacteraemia by 1 source of infection during 1996 was CR-BSI, identified in 110 patients with 126 episodes. The vascular line was central in 83 (66%), peripheral in 24 (19%), tunnelled in 18 (14%) and arterial in 1 (1%). Among the 83 central CR-BSI no sign of local inflammation was detected in 65%. Gram-positive and gram-negative bacteria shared equal parts among the 145 blood isolates; Staphylococcus aureus was the most common species (43/145, 30%) followed by Klebsiella pneumoniae (15/145, 10%); 11 (8%) isolates were Candida species. Fungal isolates were more common among tunnelled catheter infections than among others (6/18, 33% vs. 5/108, 5%, p < 0.001). Crude mortality was 35% (38/110), while attributable mortality was 14% (15/110), mostly associated with central line infection. Catheter-associated bacteraemias cause significant morbidity and mortality, and have become the most common source of hospital-acquired bacteraemia. There is a need to implement more effective infection-control measures and more advanced technologies in an effort to reduce this unacceptably high incidence.

Adult↗
PubMed2000

High- and low-risk prostate cancer treated with 3D CT-guided brachytherapy: 1-to 5-year follow-up.

PURPOSE: To provide a preliminary report of 301 patients treated for prostate carcinoma with three-dimensional CT-guided transischiorectal stereotactic brachytherapy using either iodine-125 or palladium-103 seeds as monotherapy. PATIENTS AND METHODS: Patients with clinical stage T1, T(2ab), or T(3ab) disease with prostate volumes 23 to 180 cm3 and serum prostate specific antigen (PSA) concentrations of 0.9 to 143 ng/mL had seeds placed 10 mm apart under CT guidance. No androgen blockade was used postoperatively, but 47% of the patients had hormonal therapy preoperatively. RESULTS: At 12 to 63 months (median 26 months) of follow-up, PSA concentrations had decreased to <2 ng/mL in 90% of the patients and to <1 ng/mL in 83%. Four patients underwent transurethral resection or incision at least 12 months after implantation; none became incontinent. Three patients had rectal ulceration that lasted for several months. CONCLUSIONS: Computed tomography-guided transischiorectal brachytherapy allows accurate placement of radionuclide seeds in prostate glands of all sizes. The early results, as judged by serum PSA, are encouraging.

Adult↗
PubMed2000

EEG-Linked functional magnetic resonance imaging in epilepsy and cognitive neurophysiology.

The ability to trigger functional magnetic resonance imaging (fMRI) acquisitions related to the occurrence of EEG-based physiologic transients has changed the field of fMRI into a more dynamically based technique. By knowing the temporal relationship between focal increases in neuronal firing rates and the provoked focal increase in blood flow, investigators are able to maximize the fMR-linked images that show where the activity originates. Our mastery of recording EEG inside the bore of a MR scanner has also allowed us to develop cognitive paradigms that record not only the fMR BOLD images, but also the evoked potentials (EPs). The EPs can subsequently be subjected to localization paradigms that can be compared to the localization seen on the BOLD images. These two techniques will most probably be complimentary. BOLD responses are dependent on a focal increase in metabolic demand while the EPs may or may not be related to energy demand increases. Additionally, recording EPs require that the source or sources of that potential come from an area that is able to generate far-field potentials. These potentials are related to the laminar organization of the neuronal population generating that potential. As best we know the BOLD response does not depend on any inherent laminar neuronal organization. Therefore, by merging these two recording methods, it is likely that we will gain a more detailed understanding of not only the areas involved in certain physiologic events, e.g. focal epilepsy or cognitive processing, but also on the sequencing of the activation of the various participating regions.

Artifacts↗
PubMed2000

University of Miami Division of Clinical Pharmacology therapeutic rounds: irritable bowel syndrome-pathophysiology, diagnosis, and treatment.

Irritable bowel syndrome, or IBS, is a common disorder of the bowels that causes significant patient morbidity, work-absenteeism, physician visits, and, frequently, extensive evaluations. The syndrome has been classified as a functional disorder because of the lack of clearly elucidated pathophysiology, although altered visceral sensitivity, intestinal motility, and psychosocial factors all likely play a role. Treatment includes fostering a strong, trusting relationship with the patient, with pharmacotherapy directed at the predominant symptoms. The authors review the pathophysiology, diagnosis, and treatment of this difficult disorder.

Adult↗
PubMed2000

Clinical significance and antibiotic resistance patterns of Leminorella spp., an emerging nosocomial pathogen.

Although Leminorella spp., members of the family Enterobacteriaceae, were previously isolated from feces and urine specimens, clinical correlates have not been studied. We conducted a retrospective study to investigate the clinical significance and disease spectrum of these organisms, as well as their antibiotic susceptibility patterns. Identification and susceptibility testing were performed by an automated system. Eighteen cases were identified retrospectively during a 28-month period (1/97 to 4/99), representing an incidence of 11 cases per 100,000 patient admissions. The medical records of 14 patients were reviewed. The average patient age was 67 years, and 78% were males. Patients had multiple and diverse underlying conditions which might have predisposed them to infection. Leminorella spp. were classified as definite pathogens in 43% of the cases, probable pathogens in 29%, and possible pathogens in 21%. In one case of asymptomatic bacteriuria, the isolate had no clinical significance. All infections but one were nosocomial. Clinical syndromes included urinary tract infection in six patients, surgical site infection in three patients, and primary bacteremia, peritonitis, respiratory tract infection, and soft tissue infection in one patient each. Isolates were uniformly susceptible to imipenem. Other beta-lactam agents had poor activity against the isolates. We conclude that Leminorella spp. are significant nosocomial pathogens that are capable of causing a variety of clinical syndromes and are resistant to multiple antibiotic agents.

Adult↗