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Biomedical subjects

M Jacobs

Publications and source records attributed to M Jacobs.

At least 37 records · Page 2Linked to original sources

Implementation of guidelines for preventing early onset group B streptococcal infection.

Early onset Group B Streptococcus (EOGBS) disease, defined by an onset within the first 72 hours of life, occurs in 1.3 to 3.7 per 1,000 live births. The authors sought to determine the impact of the new CDC/AAP/ACOG guidelines on the prepartum screening practice, intrapartum management, incidence of EOGBS infection, and evaluation of neonates born to GBS colonized women at University Macdonald Women's Hospital (Cleveland, OH). A retrospective analysis by chart review was conducted from January 1, 1995 to December 31, 1997 of women identified as GBS colonized during prenatal screening. These women were then divided into 2 groups: period I, women who delivered January 1, 1995 to June 30, 1996 (before institutional implementation of the guidelines for management of GBS colonization]; and period II, women who delivered July 1, 1996 to December 31, 1997 after implementation of the guidelines. A chart review was conducted for infants 72 hours old, and GBS culture positive (blood or CSF) for the same time period. In complying with the new screening and treatment guidelines, there was a significant increase in the number of mothers screened and the detection of maternal colonization, plus a 63% reduction in EOGBS. There was also a substantial reduction in the number of invasive procedures on the neonates. The authors conclude that the new guidelines are both medically and economically effective.

Anti-Bacterial Agents↗

The effect of insemination/injection time on the results of IVF and ICSI.

BACKGROUND: The aim of this study was to investigate whether a pre-incubation time between oocyte retrieval and insemination or injection had any effect on the success rate of IVF or intracytoplasmic sperm injection (ICSI). Based on previously published data, many laboratories retain a time interval of several hours between oocyte retrieval and insemination/injection. In our setting, insemination and injection times are dependent only on the laboratory workload. METHODS: Totals of 881 IVF and 432 ICSI cycles performed between 1997 and 1999 were analysed retrospectively. Oocyte retrieval occurred 36 h after human chorionic gonadotrophin administration, and insemination or injection took place 1--7 or 0.5--8 h after oocyte retrieval respectively. RESULTS: No statistically significant differences were found between these time periods and outcome of IVF and ICSI with respect to fertilization rate, embryo quality, implantation rate, abortion and ongoing pregnancy rates, except for the abortion rate after IVF. As this finding may be due to chance and no differences were found in the ongoing pregnancy rates, this finding was considered to be of less importance. CONCLUSIONS: If laboratory control and efficiency demands early insemination or injection, it could be performed without reservation.

Abortion, Spontaneous↗

Evaluation of patients for implantable pain modalities: medical and behavioral assessment.

BACKGROUND: Advances in neurobiology serve as the basis for current and evolving implantable pain modalities, consisting of neurostimulation and neuraxial drug administration systems. Appropriate treatment of pain begins with an accurate diagnosis based on thorough physical and behavioral evaluations. MEASURES: The medical evaluation includes a review of the patient's medical history, diagnostic studies, physical examination, complete diagnostic workup, and screening trial of the proposed implantable therapy. The behavioral evaluation includes a review of the patient's history and medical records, clinical interview, mental status examination, psychological testing, and determination of suitability for implantation. CONCLUSIONS: Patients with chronic pain are subject to neurophysiological, emotional, and behavioral influences that govern their perception of pain and of pain relief. Therefore, treatment of chronic pain is multidisciplinary, drawing on cognitive and behavioral psychological therapies, functional rehabilitation, orthopedic and neurologic surgery, medications, nerve blockade, neuroaugmentative procedures, and sometimes neurodestructive procedures. Appropriate selection of patients helps ensure that implantable therapies are used for those who are most likely to benefit.

Behavior↗

ChvD, a chromosomally encoded ATP-binding cassette transporter-homologous protein involved in regulation of virulence gene expression in Agrobacterium tumefaciens.

A yeast two-hybrid screen searching for chromosomally encoded proteins that interact with the Agrobacterium tumefaciens VirB8 protein was carried out. This screen identified an interaction candidate homologous to the partial sequence of a gene that had previously been identified in a transposon screen as a potential regulator of virG expression, chvD. In this report, the cloning of the entire chvD gene is described and the gene is sequenced and characterized. Insertion of a promoterless lacZ gene into the chvD locus greatly attenuated virulence and vir gene expression. Compared to that of the wild-type strain, growth of the chvD mutant was reduced in rich, but not minimal, medium. Expression of chvD, as monitored by expression of beta-galactosidase activity from the chvD-lacZ fusion, occurred in both rich and minimal media as well as under conditions that induce virulence gene expression. The ChvD protein is highly homologous to a family of ATP-binding cassette transporters involved in antibiotic export from bacteria and has two complete Walker box motifs. Molecular genetic analysis demonstrated that disruption of either Walker A box, singly, does not inactivate this protein's effect on virulence but that mutations in both Walker A boxes renders it incapable of complementing a chvD mutant strain. Constitutive expression of virG in the chvD mutant strain restored virulence, supporting the hypothesis that ChvD controls virulence through effects on virG expression.

ATP-Binding Cassette Transporters↗

Effect of short-term cyclic stretch on sodium pump activity in aortic smooth muscle cells.

We previously demonstrated that expression of both the alpha1- and alpha2-subunits of Na+-K+-ATPase is elevated after a 2- to 4-day cyclic stretch in aortic smooth muscle cells. In this study, we determined the effect of short-term (2-30 min) cyclic stretch on the activity of the Na pump and investigated possible mechanisms that may be involved in the action of stretch. Na pump activity was significantly increased above the baseline activity between 2 and 30 min of stretch. This effect of stretch was reversible within 1 h. Intracellular Na was also elevated at corresponding time points. Blocking the entry of Na with Gd and amiloride did not affect the stretch-induced increase in Na pump activity. Inhibition of protein kinase A (PKA) activity attenuated the effect of stretch on the Na pump. Furthermore, inhibition of polymerization of actin and phosphatidylinositol 3-kinase (PI3K) activity prevented the action of stretch on Na pump activity. We conclude that the stimulation of the Na pump in response to cyclic stretch requires the integrity of the actin cytoskeleton as well as the activity of PI3K, which has a role in intracellular vesicular trafficking. PKA may also be involved in this effect of stretch on Na pump.

Actins↗

Phagocytosis and killing of Mycobacterium avium complex by human neutrophils.

Organisms belonging to the Mycobacterium avium complex (MAC) cause life-threatening bacteremia in immunocompromised patients. Monocytes and macrophages are thought to be responsible for ingestion and killing of MAC. However, it has been suggested that neutrophils may play a role in the early immune response to MAC infection. Here, neutrophils in autologous plasma were incubated (at 0 and 37 degrees C) with M. avium labeled with Auramine O, a potent fluorochrome. Neutrophil phagocytosis was measured by flow cytometry. Neutrophils incubated at 37 degrees C showed an increase in fluorescence over time with a maximum at 15 min, whereas neutrophils on ice showed no time-dependent increase in FL1. At 15 min Fl 1 at 37 degrees C was twice as high as FL1 at 0 degrees C. Examination under the fluorescent microscope showed multiple intracellular fluorescent mycobacteria. Results in nine independent experiments showed time-dependent decrease of colony-forming units in neutrophil-associated live M. avium. Significant killing was observed within 30 min and was complete by 120 min. Observation by electron microscopy clearly confirmed the presence of intraphagosomal MAC, both intact and with evidence of degradation. These data demonstrate that MAC is rapidly phagocytized and killed by human neutrophils. The newly established flow cytometry method should be useful in further studies of neutrophil function and of the role of G-CSF and other cytokines in MAC disease.

Adult↗

Activity of telithromycin against 26 quinolone-resistant pneumococci with known quinolone-resistance mechanisms.

NCCLS agar dilution was used to test activity of telithromycin compared to clarithromycin, penicillin G, ciprofloxacin, levofloxacin, sparfloxacin and moxifloxacin against 26 pneumococci with defined quinolone resistance (type II topoisomerase and efflux) mechanisms. Thirteen strains were penicillin susceptible, six intermediate and seven resistant. Clarithromycin resistance (mef and/or erm) was seen in eight strains. Ciprofloxacin MICs (mg/L) were 8-64 compared to 1-32 (levofloxacin), 0.5 . or = 32 (sparfloxacin) and 0.125-4 (moxifloxacin). Telithromycin MIC50 and MIC90 values (mg/L) were 0.016 and 0.25, with only one strain having an MIC of 2 mg/L.

Anti-Bacterial Agents↗

Arabidopsis loss-of-function mutant in the lysine pathway points out complex regulation mechanisms.

In plants, the amino acids lysine, threonine, methionine and isoleucine have L-aspartate-beta-semialdehyde (ASA) as a common precursor in their biosynthesis pathways. How this ASA precursor is dispersed among the different pathways remains vague knowledge. The proportional balances of free and/or protein-bound lysine, threonine, isoleucine and methionine are a function of protein synthesis, secondary metabolism and plant physiology. Some control points determining the flux through the distinct pathways are known, but an adequate explanation of how the competing pathways share ASA in a fine-tuned amino acid biosynthesis network is yet not available. In this article we discuss the influence of lysine biosynthesis on the adjacent pathways of threonine and methionine. We report the finding of an Arabidopsis thaliana dihydrodipicolinate synthase T-DNA insertion mutant displaying lower lysine synthesis, and, as a result of this, a strongly enhanced synthesis of threonine. Consequences of these cross-pathway regulations are discussed.

Amino Acids↗

The Gla domain of human prothrombin has a binding site for factor Va.

The role of the Gla domain of human prothrombin in interaction with the prothrombinase complex was studied using a peptide with the sequence of the first 46 residues of human prothrombin, PT-(1-46). Intrinsic fluorescence measurements showed that PT-(1-46) undergoes a conformational alteration upon binding calcium; this conclusion is supported by one-dimensional (1)H NMR spectroscopy, which identifies a change in the chemical environment of tryptophan 41. PT-(1-46) binds phospholipid membranes in a calcium-dependent manner with a K(d) of 0.5 microm and inhibits thrombin generation by the prothrombinase complex with a K(i) of 0.8 microm. In the absence of phospholipid membranes, PT-(1-46) inhibits thrombin generation by factor Xa in the presence but not absence of factor Va, suggesting that PT-(1-46) inhibits prothrombin-factor Va binding. The addition of factor Va to PT-(1-46) labeled with the fluorophore sulfosuccinimidyl-7-amino-4-methylcoumarin-3-acetic acid (PT-(1-46)AMCA) caused a concentration-dependent quenching of AMCA fluorescence, providing direct evidence of a PT-(1-46)-factor Va interaction. The K(d) for this interaction was 1.3 microm. These results indicate that the N-terminal Gla domain of human prothrombin is a functional unit that has a binding site for factor Va. The prothrombin Gla domain is important for interaction of the substrate with the prothrombinase complex.

Amino Acid Sequence↗

Allograft loss in renal transplant recipients with Fabry's disease and activated protein C resistance.

INTRODUCTION: Fabry's disease is associated with an increased incidence of thrombotic events and rejection. Spontaneous thrombosis of a functioning cadaveric renal allograft in a recipient with Fabry's disease prompted prospective evaluation of all transplant candidates with Fabry's disease for hypercoagulability. MATERIALS AND METHODS: Transplant candidates with Fabry's disease were tested for hypercoagulability, analyzed for HLA-type and ABO group, and comorbid conditions suggestive of hypercoagulability. RESULTS: A unique association of Fabry's disease with activated protein C Resistance was documented in a cohort of Caucasian male renal transplant recipients with Fabry's disease. Four of five patients were blood group A and had no significant comorbid conditions suggestive of hypercoagulability. The resistance to activation of protein C (APCR)(+) patients shared HLA loci-B8 and Dr3, although the APCR(-) patients shared HLA loci-B27 and -B38. CONCLUSIONS: Due to the observed increase in the incidence of APCR in our Fabry's cohort, we suggest screening all patients with Fabry's disease for APCR. Because factor V and factor Va receptors are found on vascular endothelium and peripheral blood monocytes, APCR in the presence of Fabry's disease may be a nonimmunological stimulus for rejection. Analysis of HLA typing in patients with Fabry's disease may further elucidate HLA-based association of Fabry's disease and resistance to activated protein C with the risk of thrombosis and rejection.

ABO Blood-Group System↗

The nitration of platelet cytosolic proteins during agonist-induced activation of platelets.

The nitration of protein tyrosine residues by peroxynitrous acid has been associated with pathological conditions. Here it is shown, using a sensitive competitive enzyme-linked immunosorbent assay and immunoblotting for nitrotyrosine, that spontaneous nitration of specific proteins occurs during a physiological process, the activation of platelets by collagen. One of the main proteins nitrated is vasodilator-stimulated phosphoprotein. Endogenous synthesis of nitric oxide and activity of cyclo-oxygenase were required for the nitration of tyrosine. The nitration was mimicked by addition of peroxynitrite to unstimulated platelets, although the level of nitrotyrosine formation was greater and its distribution among the proteins was less specific.

Aspirin↗

Withdrawal of mycophenolate mofetil in stable renal transplant recipients.

BACKGROUND: Mycophenolate mofetil (MMF) has been demonstrated to decrease episodes of acute rejection in renal transplant recipients during the first year after transplantation. The utility of MMF after 1 year is less clear. METHODS: Forty-five stable renal transplant recipients on maintenance therapy of cyclosporine microemulsion, MMF, and prednisone had MMF withdrawn at approximately 1 year after transplantation. A matching concurrent group of 45 stable renal transplant recipients served as the case control group. RESULTS: Two of 45 patients in the MMF withdrawal group suffered an acute rejection episode as opposed to 1 of 45 in the control group. Both patients who rejected in the withdrawal group had adequate cyclosporine levels and had no recent decrease in prednisone dose. There was no evidence of an increased incidence of proteinuria or increased creatinine levels in the MMF withdrawal group. CONCLUSION: In general, withdrawal of MMF in stable renal transplant recipients is well tolerated. No increased risk of rejection could be demonstrated in this patient group. A larger study will be needed to confirm our result.

Adult↗

Characterization of a cDNA encoding a rice mitochondrial voltage-dependent anion channel and its gene expression studied upon plant development and osmotic stress.

The voltage-dependent anion channel (VDAC) of mitochondria forms a large pore in the outer envelope membrane. Here, the full Oryza sativa OSVDAC1 cDNA was sequenced and is shown to belong to a small multigene family in the rice genome. This cDNA is 1093 bp long and codes for a protein of 274 amino acids. Expression studies of the osvdac1 gene show a regulation of its level in function of the plantlets maturation and organs. In contrast with several bacterial porins, osmotic stress does not have any effect on the plant osvdac1 gene expression.

Amino Acid Sequence↗

Fatal Mycobacterium bovis BCG infection in TNF-LT-alpha-deficient mice.

Neutralization of TNF or disruption of TNF-R1 leads to fatal Mycobacterium bovis BCG infection. Here we used TNF-LT-alpha-deficient mice to test whether a complete disruption of TNF and LT-alpha reduces further host resistance to BCG infection. The bacterial burden especially in the lungs of TNF-LT-alpha-deficient mice was significantly increased and the mice succumbed to infection between 8 and 10 weeks. In the absence of TNF-LT-alpha the granulomatous response was severely impaired and delayed. The cells in the granulomas of TNF-LT-alpha-deficient mice expressed low levels of MHC class II and ICAM-1. They contained a few T cells and F4/80-positive macrophages expressing little iNOS and acid phosphatase activity. By contrast, the lethal action of endotoxin was dramatically reduced in BCG-infected TNF-LT-alpha-deficient mice. In summary, in the absence of TNF-LT-alpha the recruitment and activation of mononuclear cells in response to BCG infection were significantly delayed and reduced resulting in immature granulomas allowing uncontrolled fatal infection.

Animals↗

Correction of defective host response to Mycobacterium bovis BCG infection in TNF-deficient mice by bone marrow transplantation.

Tumour necrosis factor-alpha (TNF) plays a central role in the recruitment and activation of mononuclear cells in mycobacterial infection. In the absence of type 1 TNF receptor, Mycobacterium bovis Bacillus Calmette-Guerin (BCG) infection of mice is not contained, leading to fatal disease. Because type 1 TNF receptor binds both TNF and lymphotoxin-a, we used TNF-deficient mice to determine the specific role of TNF in the host resistance to BCG infection. The bacterial burden of the lungs of TNF-deficient mice was substantially increased and the mice succumbed to pneumonia between 8 and 12 weeks with a defective granuloma response. Atypical granulomas developed by 4 weeks expressing low levels of MHC class II, intracellular adhesion molecule (ICAM-1), CD11b and CD11c. Macrophages showed little signs of activation and had low levels of acid phosphatase activity and inducible nitric oxide synthase (INOS) expression. Despite the defective cellular recruitment, the chemokines, monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1 (MIP-1alpha), were increased in broncho-alveolar lavage fluid of TNF-deficient mice. The defective host response was corrected by the transplantation of normal bone marrow cells into irradiated TNF-deficient mice. These results demonstrate that TNF derived from hemopoietic cells rather than from mesenchymal origin are essential for a normal host response to BCG infection. Furthermore, TNF dependent expression of adhesion molecules may be essential for the recruitment of mononuclear cells for the formation of bactericidal BCG granulomas.

Acid Phosphatase↗

Lethal Mycobacterium bovis Bacillus Calmette Guérin infection in nitric oxide synthase 2-deficient mice: cell-mediated immunity requires nitric oxide synthase 2.

The role of nitric oxide (NO) in Mycobacterium bovis Bacillus Calmette Guerin (BCG) infection was investigated using nitric oxide synthase 2 (nos2)-deficient mice, because NO plays a pivotal protective role in M. tuberculosis infection. We demonstrate that nos2-deficient mice were unable to eliminate BCG and succumbed within 8 to 12 weeks to BCG infection (10(6) CFU) with cachexia and pneumonia, whereas all infected wild-type mice survived. The greatest mycobacterial loads were observed in lung and spleen. Nos2-deficient mice developed large granulomas consisting of macrophages and activated T cells and caseous necrotic lesions in spleen. The macrophages in granulomas from nos2-deficient mice had reduced acid phosphatase activities, suggesting that NO is required for macrophage activation. The absence of NOS2 affected the cytokine production of the Th1 type of immune response, except IL-18. Serum amounts of IL-12p40 were increased and IFN-gamma was decreased compared with wild-type mice. The lack of NOS2 resulted in an overproduction of TNF, observed throughout the infection period. Additionally, TNFR1 and TNFR2 shedding was altered compared with wild-type mice. Up-regulation of TNF may be compensatory for the lack of NOS2. The late neutralization of TNF by soluble TNF receptors resulted in heightened disease severity and accelerated death in nos2-deficient mice but had no effect in wild-type mice. In conclusion, the inability of nos2-deficient mice to kill M. bovis BCG resulted in an accumulation of mycobacteria with a dramatic activation of the immune system and overproduction of pro-inflammatory cytokines, which resulted in death.

Animals↗