Search PubMed⌕ Search

Biomedical subjects

S Blum

Publications and source records attributed to S Blum.

At least 37 records · Page 2Linked to original sources
PubMed2000

Fibronectin synthesis by activated T lymphocytes: up-regulation of a surface-associated isoform with signalling function.

Fibronectin (FN) is a major constituent of the extracellular matrix. We now provide evidence for a surface-associated isoform of FN that is synthesized by T cells upon activation. The T-cell-derived FN has an unusual splice pattern: an additional domain, EDB, is produced whereas sequences within another domain, IIICS, are spliced out. CS1, the binding domain for very late antigen-4 (VLA-4), however, is still generated. To study the potential function of surface-associated FN its synthesis was down-regulated by an antisense oligonucleotide, then proliferation of T cells was induced by cross-linked anti-CD3. Proliferation was reduced as was expression of CD25. Moreover, when T cells were cultured in high density, the synthetic peptide QILDVPST, corresponding to CS1, inhibited proliferation, as did antibodies to VLA-4. We propose that surface-associated FN is a ligand for VLA-4, which by binding to VLA-4 on an adjacent cell, provides a costimulatory signal, thus sustaining T-cell proliferation.

Antibodies, Monoclonal↗
PubMed2000

Activation of human peripheral blood mononuclear cells by nonpathogenic bacteria in vitro: evidence of NK cells as primary targets.

The interaction of commensal bacteria with immunocompetent cells may occur in definite compartments of the mucosal immune system, as limited translocation through the epithelial barrier cannot be excluded. In this study the stimulation of human peripheral blood mononuclear cells and purified lymphocyte subsets by nonpathogenic gram-positive lactobacilli (Lactobacillus johnsonii and Lactobacillus sakei) and gram-negative Escherichia coli was investigated. The various bacterial strains induced a differential cytokine pattern. Whereas L. johnsonii and L. sakei strongly induced gamma interferon (IFN-gamma) and interleukin-12 (IL-12), E. coli and lipopolysaccharide (LPS) preferentially induced IL-10 after 16 h of stimulation. Expression of activation antigens CD69 and CD25 was observed on (CD3(-) CD56(+)) natural killer (NK) cells after stimulation of total human peripheral blood mononuclear cells. All bacteria mediated the proliferation of human peripheral blood mononuclear cells, and the strongest proliferative response was observed with L. johnsonii. Purified CD4(+), CD8(+), and CD19(+) lymphocyte subsets were not activated upon bacterial stimulation but showed normal response to a mitogenic stimulus. In contrast, purified NK cells upregulated the IL-2Ralpha chain (CD25) and underwent proliferation when stimulated by L. johnsonii. E. coli and LPS were less effective in inducing proliferation. Expression of CD25 or secretion of IFN-gamma from purified NK cells was significantly increased in the presence of bacterially primed macrophages, indicating that full activation required both bacterium- and cell contact-based signals derived from accessory cells.

Antigen-Presenting Cells↗
PubMed2000

Non-pathogenic bacteria elicit a differential cytokine response by intestinal epithelial cell/leucocyte co-cultures.

BACKGROUND AND AIM: Intestinal epithelial cells (IEC) are thought to participate in the mucosal defence against bacteria and in the regulation of mucosal tissue homeostasis. Reactivity of IEC to bacterial signals may depend on interactions with immunocompetent cells. To address the question of whether non-pathogenic bacteria modify the immune response of the intestinal epithelium, we co-cultivated enterocyte-like CaCO-2 cells with human blood leucocytes in separate compartments of transwell cultures. METHODS: CaCO-2/PBMC co-cultures were stimulated with non-pathogenic bacteria and enteropathogenic Escherichia coli. Expression of tumour necrosis factor alpha (TNF-alpha), interleukin (IL)-1beta, IL-8, monocyte chemoattracting protein 1 (MCP-1), and IL-10 was studied by enzyme linked immunosorbent assays (cytokine secretion) and by semiquantitative reverse transcription-polymerase chain reaction. RESULTS: Challenge of CaCO-2 cells with non-pathogenic E coli and Lactobacillus sakei induced expression of IL-8, MCP-1, IL-1beta, and TNF-alpha mRNA in the presence of underlying leucocytes. Leucocyte sensitised CaCO-2 cells produced TNF-alpha and IL-1beta whereas IL-10 was exclusively secreted by human peripheral blood mononuclear cells. CaCO-2 cells alone remained hyporesponsive to the bacterial challenge. Lactobacillus johnsonii, an intestinal isolate, showed reduced potential to induce proinflammatory cytokines but increased transforming growth factor beta mRNA in leucocyte sensitised CaCO-2 cells. TNF-alpha was identified as one of the early mediators involved in cellular cross talk. In the presence of leucocytes, discriminative activation of CaCO-2 cells was observed between enteropathogenic E coli and non-pathogenic bacteria. CONCLUSION: The differential recognition of non-pathogenic bacteria by CaCO-2 cells required the presence of underlying leucocytes. These results strengthen the hypothesis that bacterial signalling at the mucosal surface is dependent on a network of cellular interactions.

Bacteria↗
PubMed2000

Routine DNA cytometry of benign and malignant pleural effusions by means of the remote quantitation server Euroquant: a prospective study.

AIM: To analyse the practicability and potential assistance of static DNA cytometry performed by means of the remote quantitation server Euroquant and the internet in routine diagnostic analysis of pleural effusions, and to outline the role of DNA cytometry on pleural effusions in distinguishing between benign and malignant (and herein primary versus metastatic) effusions. MATERIALS AND METHODS: Cytological smears of 294 pleural effusions were stained with the Feulgen method. The DNA content of a minimum of 300 randomly chosen analysis nuclei and 30 reference nuclei (lymphocytes) was measured by internet connection to the remote quantitation server Euroquant. Cytometric features were derived from the histograms, and the time needed for case evaluation, the reliability of staining and measurement procedures, and the contribution to the final diagnosis were evaluated. RESULTS: Only 120 of 294 pleural effusions could be measured. The total measurement time for each specimen was 60 minutes. The guidelines of the consensus report on DNA measurements were fulfilled. Seventy eight malignant (18 mesotheliomas, 60 metastatic tumours) and 42 benign effusions were measured. Seven of 78 malignant effusions were euploid and none of 42 benign effusions were aneuploid. The sensitivity and specificity were 91% and 100%, respectively, for distinguishing benign from malignant effusions, and 95% and 100%, respectively, for discriminating between benign and malignant effusions caused by metastatic malignant tumours. CONCLUSIONS: Static DNA cytometry using the remote quantitation server Euroquant can be performed reliably in the routine diagnosis of pleural effusions; however, only 40% of effusions meet the technical requirements for static DNA cytometry. Within the measurable cases, static DNA cytometry made an important contribution to the confirmation/exclusion of malignancy.

Aged↗
PubMed2000

Recent developments and present status of telepathology.

Telepathology which is the diagnostic work of a pathologist at a distance has been developed to routine application within the last ten years. It can be classified in relation to application, technical solutions, or performance conditions. Diagnostic pathology performance distinguishes primary diagnosis (for example, frozen section statement) from secondary diagnosis (for example, expert consultation) and quality assurance (diagnostic accuracy, continuous education and training). Applications comprise (a) frozen section service; (b) expert consultations; (c) remote control measurements; and (d) education and training. The technical solutions distinguish active (remote control, live imaging) systems from passive (conventional microscope handling, static imaging), and the performance systems with interactive (on-line, live imaging) use from those with passive (offline, static imaging) practice. Intra-operative frozen section service is mainly performed with remote control systems; whereas expert consultations and education/training are commonly based upon Internet connections with static imaging in an off-line mode. The image quality, transfer rates, and screen resolution of active and passive telepathology systems are sufficient for an additional or primary judgment of histological slides and cytological smears. From the technical point of view, remote control telepathology requires a fast transfer and at least near on-line judgement of images, i.e., image acquisition, transfer and presentation can be considered one performance function. Thus, image size, line transfer rate and screen resolution define the practicability of the system. In expert consultation, the pixel resolution of images and natural color presentation are the main factors for diagnostic support, whereas the line transfer rate is of minor importance. These conditions define the technical compartments, especially size and resolution of camera and screen. The performance of commercially available systems has reached a high quality standard. Pathologists can be trained in a short time and use the systems in a routine manner. Several telepathology systems have been implemented in large Institutes of Pathology which serve for frozen section diagnosis in small hospitals located in the local area. In contrast, expert consultation is mainly performed with international connections. There is a remarkable increase of expert consultations by telepathology according to the experiences of the Armed Forces Institute of Pathology or the Department of Pathology, Thoraxklinik, Heidelberg. In expansion of these experiences, a "globalization" of telepathology can be expected. Telepathology can be used to shrink the period necessary for final diagnosis by request for diagnostic assistance to colleagues working in appropriate related time zones. Telepathology is, therefore, not a substitute of conventional diagnostic procedures but a real improvement in the world of pathology.

Europe↗
PubMed2000

Folate deficiency in vitro induces uracil misincorporation and DNA hypomethylation and inhibits DNA excision repair in immortalized normal human colon epithelial cells.

Epidemiological studies have indicated that folic acid protects against a variety of cancers, particularly cancer of the colorectum. Folate is essential for efficient DNA synthesis and repair. Moreover, folate can affect cellular S-adenosylmethionine levels, which regulate DNA methylation and control gene expression. We have investigated the mechanisms through which folate affects DNA stability in immortalized normal human colonocytes (HCEC). DNA strand breakage, uracil misincorporation, and DNA repair, in response to oxidative and alkylation damage, were determined in folate-sufficient and folate-deficient colonocytes by single cell gel electrophoresis. In addition, methyl incorporation into genomic DNA was measured using the bacterial enzyme Sss1 methylase. Cultured human colonocyte DNA contained endogenous strand breaks and uracil. Folate deficiency significantly increased strand breakage and uracil misincorporation in these cells. This negative effect on DNA stability was concentration dependent at levels usually found in human plasma (1-10 ng/ml). DNA methylation was decreased in HCEC grown in the absence of folate. Conversely, hypomethylation was not concentration dependent. Folate deficiency impaired the ability of HCEC to repair oxidative and alkylation damage. These results demonstrate that folic acid modulates DNA repair, DNA strand breakage, and uracil misincorporation in immortalized human colonocytes and that folate deficiency substantially decreases DNA stability in these cells.

Aged↗
PubMed2000

Telecommunication--a new tool for quality assurance and control in diagnostic pathology.

Telepathology is the diagnostic work of a pathologist at a distance. It includes specific application fields which require specific system solutions. These comprise: a. frozen section service; b. expert consultations; c. remote control measurements, and d. education and training. Applications but, in addition, all aspects of diagnosis, especially those involved in the daily work flow of a pathologist. The image quality, transfer rates, and screen resolution of telepathology systems are sufficient for an additional or primary judgment of histological slides and cytological smears. It is, therefore, possible to include this technique into intralaboratory quality control of all steps of diagnostic procedures and to use this technique for quality assurance and control. Diagnostic quality is not a well defined term, and depends, in addition to external circumstances, on the diagnosis itself. The diagnostic quality can be maintained or even improved by use of telepathology systems. They can serve for control of image quality, access to various information sources, simultaneous transfer of images and diagnosis, and continuous education of the involved pathologists. For example, in continuous education and training, as a first step the pathologist should have access to an image data bank storing images related to the specific case, for example images taken from the same organ and from patients of similar age. The final stage would be an intra-diagnostic learning from the specific case; i.e. the time difference between questionnaires for a difficult diagnosis and the final diagnosis will become a minimum. Automated storing of the specific and diagnosis-associated images of the case will permit an open diagnostic system which will itself adjust to the micro-environment of the department of pathology. Although this future scenario has not been implemented to our knowledge, there is little doubt the development in telepathology will promote the technical procedures in the environment of a diagnostic pathologist. Telepathology is, therefore, not a substitute of conventional diagnostic procedures but a real improvement in the world of pathology.

Education, Medical, Continuing↗
PubMed1999

A mitogen-activated protein kinase cascade in the CA1/CA2 subfield of the dorsal hippocampus is essential for long-term spatial memory.

Behavioral, biophysical, and pharmacological studies have implicated the hippocampus in the formation and storage of spatial memory. However, the molecular mechanisms underlying long-term spatial memory are poorly understood. In this study, we show that mitogen-activated protein kinase (MAPK, also called ERK) is activated in the dorsal, but not the ventral, hippocampus of rats after training in a spatial memory task, the Morris water maze. The activation was expressed as enhanced phosphorylation of MAPK in the pyramidal neurons of the CA1/CA2 subfield. In contrast, no increase in the percentage of phospho-MAPK-positive cells was detected in either the CA3 subfield or the dentate gyrus. The enhanced phosphorylation was observed only after multiple training trials but not after a single trial or after multiple trials in which the location of the target platform was randomly changed between each trial. Inhibition of the MAPK/ERK cascade in dorsal hippocampi did not impair acquisition, but blocked the formation of long-term spatial memory. In contrast, intrahippocampal infusion of SB203580, a specific inhibitor of the stress-activated MAPK (p38 MAPK), did not interfere with memory storage. These results demonstrate a MAPK-mediated cellular event in the CA1/CA2 subfields of the dorsal hippocampus that is critical for long-term spatial memory.

Amino Acid Sequence↗
PubMed1999

Combination antiretroviral therapy in human immunodeficiency virus-infected pregnant women.

OBJECTIVE: To describe the safety, efficacy, and perinatal transmission rates of human immunodeficiency virus (HIV) with combination antiretroviral therapy in pregnancy. METHODS: Retrospective study of all HIV-infected pregnant women treated with combination antiretroviral therapy after September 1, 1996, and who delivered by September 1, 1998, at Bronx-Lebanon Hospital Center. RESULTS: Thirty women received combination therapy, 13 with protease inhibitor. Median baseline CD4 was 285 cells/mm3; 16 (53%) had AIDS, 20 (67%) were antiretroviral-experienced, and 11 (37%) were illicit substance users. Fourteen were receiving antiretroviral therapy (eight with protease inhibitor) during the first trimester. Combination therapy was prescribed for a median of 26 weeks during pregnancy. One third changed antiretroviral therapy, and nearly half (47%) were nonadherent. Twenty-four women had a successful viral load and/or CD4 response. The median (range) delivery gestation was 39 (32-42) weeks, and the median (range) birth weight was 2892 (1430-3863) g. Adverse outcomes included one stillbirth; one case of microcephaly; and five infants less than 2500 g, two of which were under 36 weeks' gestation. Median birth weight did not differ with maternal protease exposure. None of the 26 infants studied for at least 4 months had HIV infection. Associated maternal complications were four cases of pregnancy-induced hypertension, one of gestational diabetes, and one exacerbation of hepatitis C virus. CONCLUSION: Combination antiretroviral therapy in pregnancy was efficacious in reducing viral load, increasing CD4, and preventing vertical HIV transmission in women with advanced HIV disease, extensive antiretroviral experience, prior history of vertical transmission, and/or substance abuse. The findings are promising in this preliminary report that combination antiretroviral therapy may not be related to major infant toxicity, but further study is warranted.

Adult↗
PubMed1999

Penicillin resistance and other predictors of mortality in pneumococcal bacteremia in a population with high human immunodeficiency virus seroprevalence.

Rates of invasive disease caused by penicillin-resistant pneumococci are rising. Previous reports have found no association between resistant pneumococci and increased mortality. To evaluate the impact of penicillin resistance and other variables on mortality, we retrospectively studied all cases of pneumococcal bacteremia identified by our microbiology laboratory from 1 January 1992 through 31 December 1996. There were 462 cases of pneumococcal bacteremia in 432 patients. The mean age was 35 years; 55% of the cases occurred in male patients, 58% were in black patients, and 40% were in Hispanic patients. One-half of the cases occurred in patients with documented human immunodeficiency virus (HIV) infection. Penicillin resistance was first noted in 1994 and increased yearly, accounting for 17% of 1996 isolates. Of all resistant isolates, 65% were resistant to penicillin at a high level. The overall mortality was 17%. On multivariate analysis, high-level penicillin resistance, older age, severe disease, multilobar infiltrates and/or effusion(s) on chest roentgenogram, and Hispanic ethnicity were independent predictors of mortality in pneumococcal bacteremia. In HIV-infected patients, a CD4 cell count below the median just missed statistical significance. This is the first report demonstrating penicillin resistance as an independent predictor of mortality among patients with pneumococcal bacteremia.

AIDS-Related Opportunistic Infections↗
PubMed1998

Characterization of human fibroleukin, a fibrinogen-like protein secreted by T lymphocytes.

We have recently cloned the human homologue of the murine pT49 cDNA (hpT49h), a transcript encoding a protein homologous to the beta- and gamma-chains of fibrinogen. Here, we report the identification of the hpT49h gene product using mAbs generated against a peptide corresponding to the carboxyl-terminal end of the deduced protein and a recombinant protein fragment expressed in Escherichia coli. mAbs 23A6, 7B12, and 3F4 specifically recognized a protein of 70 kDa in reducing SDS-PAGE in the culture supernatant of 293T cells transiently transfected with the full length hpT49h cDNA and freshly isolated PBMC. Under nonreducing conditions, the material migrated with a molecular mass of 250 to 300 kDa, indicating that the 70-kDa protein forms a disulfide bonded complex. Because of its homology with fibrinogen, we have termed this protein fibroleukin. Fibroleukin is spontaneously secreted in vitro by freshly isolated CD4+ and CD8+ T lymphocytes. RT-PCR analysis revealed preferential expression of fibroleukin mRNA in memory T lymphocytes (CD3+/CD45R0+) compared with naive T lymphocytes (CD3+/CD45RA+). Fibroleukin production by PBMC was rapidly lost in culture. Production could be partially maintained in the presence of IFN-gamma, while T lymphocyte activation had no effect. To demonstrate fibroleukin production in vivo, we analyzed colon mucosa by immunohistology. Fibroleukin staining was detected in the extracellular matrix of the T lymphocyte-rich upper portion of the lamina propria mucosa. While the exact function of fibroleukin remains to be defined, these data suggest that fibroleukin may play a role in physiologic lymphocyte functions at mucosal sites.

Amino Acid Sequence↗
PubMed1998

Different types of cerebellar hypometria associated with a distinct topography of the lesion in cerebellum.

We recorded ballistic wrist flexion movements in fifteen cerebellar patients exhibiting hypometria. The movement and the associated agonist and antagonist EMG activities were analysed. On the basis of the topography of the cerebellar lesion, our patients were divided into three groups. In the first group including five patients, lesions involved the efferent dentato-thalamo-cortical pathway and hypometria was associated with an imbalance between the rate of rise of the agonist EMG activity and the rate of rise of the antagonist EMG activity. In the three patients of group II, lesions were located at the level of the middle cerebellar peduncle, disrupting the crossed ponto-cerebellar projections. In these patients, the intensity of the agonist EMG activity was reduced and the duration of the antagonist EMG activity was increased. In the third group including seven patients presenting either a diffuse cerebellar atrophy or a stroke involving a large parenchymatous area, the agonist-antagonist EMG pattern showed a prolongation of the duration of the antagonist burst. Our results show that discrete mechanisms of cerebellar hypometria are associated with different anatomical lesions.

Adult↗
PubMed1998

Maintenance hemodialysis in patients with HIV-associated nephropathy.

OBJECTIVE: End-stage renal disease (ESRD) patients infected with human immunodeficiency virus (HIV) have poor survival on maintenance hemodialysis. Only a few studies have evaluated survival time on the basis of demographic and clinical factors. The clinical category of the HIV infection and total CD4 counts are commonly considered determining factors of survival in these HIV-infected dialysis patients. PATIENTS AND METHODS: A retrospective case review of all ESRD patients with HIV infection on maintenance hemodialysis, from January 1987 through December 1996, was performed to determine the impact of different clinical categories of HIV infection and CD4 counts on survival and to see if there are other factors that can predict survival among these patients. From a total of 75 ESRD patients with HIV infection, 58 patients with ESRD due to HIV-associated nephropathy (HIVAN) on maintenance hemodialysis are reported here. RESULTS: During the 10 year study period, 52 of 58 ESRD patients with HIVAN expired. Infection (60%), cardiogenic conditions (13%), cerebro-vascular accidents (6%), HIV wasting (8%) and noncompliance with dialysis (11%) were common causes of death. Fifty patients who were on long term hemodialysis (Group I), had a median survival time of 11 months (4-69). Among 44 diseased patients in Group I, various demographic, clinical and laboratory markers, including age, sex, race, acquired immunodeficiency syndrome (AIDS)-associated conditions, HIV clinical categories, hemodialysis access and initial serum albumin level were not significantly associated with mean or median survival time. Those with initial CD4 counts of more than 50 had a significantly longer median survival (11.3 months) than those whose counts were below 50 (5.3 months). Patients with < or = 2.5 g/100 ml initial serum albumin level and < or = 50 initial CD4 counts had a median survival time of 5.3 months compared to 13.6 months in the group of patients with initial serum albumin level of > 2.5 g/100 ml and initial CD4 counts > 50. Both of these findings were statistically significant. CONCLUSIONS: Our 10 year experience of maintenance hemodialysis in ESRD patients with HIVAN shows that long term survival is possible. Initial CD4+ T cells of < or = 50 in these patients is a poor prognostic marker. HIV clinical categories, as reported by others, failed to predict survival in our long term experience. Initial serum albumin of < or = 2.5 g/100 ml was associated with poor survival, though statistically not significant. When initial serum albumin of < or = 2.5 g/100 ml was combined with CD4+ T cells of < or = 50, it became another marker of poor survival.

AIDS-Associated Nephropathy↗
PubMed1997

Factors influencing time to sputum conversion among patients with smear-positive pulmonary tuberculosis.

For hospitalized patients with smear-positive pulmonary or laryngeal tuberculosis, the Centers for Disease Control and Prevention recommends that three consecutive sputum samples be negative for acid-fast bacilli (AFB) before respiratory isolation is discontinued. Limited data are available to predict the length of time to obtain three negative sputum smears and cultures and to determine factors associated with a prolonged interval before sputum smear and culture conversion, especially among patients infected with human immunodeficiency virus (HIV). For 100 consecutive patients with smear-positive pulmonary tuberculosis, the mean and median numbers of days from the initiation of appropriate therapy to the first of three consecutive negative smears were calculated, and associated risk factors were determined. The mean number of days before the first of three consecutive negative sputum smears was 33 days; the median was 23 days. On stepwise multiple regression analysis, cavitary disease, numerous AFB on the initial smear, and no prior history of tuberculosis were the factors independently associated with an increased number of days for both smear and culture conversion. HIV does not prolong the period of infectiousness.

AIDS-Related Opportunistic Infections↗
PubMed1997

Culicidae (Diptera) in the diet of predatory stages of anurans (Amphibia) in humid biotopes of the Rhine Valley in Germany.

A three-year field study was conducted during 1993 to 1995 to determine the importance of mosquitoes in the diet of anurans. The study was aimed to assess the impact of biological mosquito control on the populations of amphibia in the Rhine Valley, Germany. Sampling took place in two areas with stands of different deciduous trees at the western bank of the Rhine (north of Karlsruhe, Germany) from early May to late October. The frequency and species composition of the terrestrial stages of Amphibia was monitored by hand catches and by live pitfall trapping. A total of 2,419 Amphibia were caught in the three years. Of these, 95.8% were anurans, consisting of 77% Ranidae, with 25.5% Rana arvalis, and 4.2% were Urodela, Salamandridae. All anura caught were subjected to "stomach flushing" to yield their stomach contents before they were released again. The stomachs of 2,163 anuran specimens contained an average of 7.7 prey items, of which only 0.16% were Culicidae. In R. arvalis the total diet consisted of 33% Collembola, spiders and beetles; 0.1% of the specimens in the diet were Culicidae. The most common culicid species in the study area, Aedes vexans, was also most often found in the anuran stomachs. However, no correlation existed between the number of mosquitoes and their number as prey of Anura. It is concluded that anurans will not be negatively affected by biological mosquito control in the Rhine Valley. Furthermore, the impact of anurans on Culicidae seems to be negligible.

Aedes↗