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Biomedical subjects

M Ostrowski

Publications and source records attributed to M Ostrowski.

At least 55 records · Page 3Linked to original sources

Influence of ureterovesical anastomosis technique on the incidence of vesicoureteral reflux in renal transplant recipients.

Urological complications of allogenic kidney transplantation include vesicoureteral reflux which can result in graft threatening urinary tract infection. To prevent this complication several ureterovesical anastomosis techniques have been developed. Authors present a comparison of three different techniques: extravesical without antireflux mechanism, extravesical Witzel-Lich with antireflux mechanism and intravesical Laedbetter-Politano with antireflux mechanism. 39 patients were selected randomly from a cohort of 420 allogenic kidney recipients (follow up time 10-147 months). All patients had voiding cystography and urine culture performed. The incidence of vesicoureteral reflux varied from 13.3% to 50%, depending on the anastomosis technique. No correlation between type of anastomosis and urinary tract infection was found.

Adolescent↗

CC-chemokines enhance the replication of T-tropic strains of HIV-1 in CD4(+) T cells: role of signal transduction.

This study demonstrates that several CC-chemokines, including those that inhibit entry and replication of macrophage-tropic strains of HIV, increase the replication of T cell (T)-tropic strains in CD4(+) T cells. Enhancement of T-tropic HIV replication is observed at early stages of replication, requires signaling through inhibitory guanine nucleotide-binding regulatory (Gi) proteins, and is associated with increased cell surface colocalization of CD4 and the T-tropic HIV coreceptor CXCR4. These findings may further our understanding of the factors that influence the replication and spread of T-tropic strains of HIV in vivo and suggest that the use of cell signaling CC-chemokines as therapeutic agents for the purpose of limiting HIV replication in vivo should be approached with caution.

Anti-HIV Agents↗

Dendritic cells express multiple chemokine receptors used as coreceptors for HIV entry.

Cells of the dendritic lineage are thought to be among the first cells infected after mucosal exposure to HIV. In this study, we have identified the presence of multiple chemokine receptors on dendritic cells (DC) that may function as coreceptors for HIV entry. DC effectively used CCR5 for entry of macrophage (M)-tropic isolates. CCR3, the eotaxin receptor, initially identified on eosinophils, is expressed on DC and may be used as an entry coreceptor by certain dual-tropic strains. CXCR4 was not expressed on DC, although SDF-1 induced a calcium flux and DC could be infected by T cell line (T)-tropic HIV. Our findings provide evidence for the presence of a non-CXCR4 SDF-1 receptor on DC that is used mainly by T-tropic strains of HIV. DC from individuals homozygous for a 32-bp deletion of the CCR5 gene are also infectable with M-tropic strains of HIV-1, and this infection is inhibited by stromal cell-derived factor (SDF)1, suggesting that this receptor can also be used by M-tropic HIV for entry. Delineation of the spectrum of coreceptor usage on DC may offer new approaches to interfere with the initiation and propagation of HIV infection.

Base Sequence↗

Susceptibility to periodic breathing with assisted ventilation during sleep in normal subjects.

Assisted ventilation with pressure support (PSV) or proportional assist (PAV) ventilation has the potential to produce periodic breathing (PB) during sleep. We hypothesized that PB will develop when PSV level exceeds the product of spontaneous tidal volume (VT) and elastance (VTsp . E) but that the actual level at which PB will develop [PSV(PB)] will be influenced by the DeltaPCO2 (difference between eupneic PCO2 and CO2 apneic threshold) and by DeltaRR [response of respiratory rate (RR) to PSV]. We also wished to determine the PAV level at which PB develops to assess inherent ventilatory stability in normal subjects. Twelve normal subjects underwent polysomnography while connected to a PSV/PAV ventilator prototype. Level of assist with either mode was increased in small steps (2-5 min each) until PB developed or the subject awakened. End-tidal PCO2, VT, RR, and airway pressure (Paw) were continuously monitored, and the pressure generated by respiratory muscle (Pmus) was calculated. The pressure amplification factor (PAF) at the highest PAV level was calculated from [(DeltaPaw + Pmus)/Pmus], where DeltaPaw is peak Paw - continuous positive airway pressure. PB with central apneas developed in 11 of 12 subjects on PSV. DeltaPCO2 ranged from 1.5 to 5.8 Torr. Changes in RR with PSV were small and bidirectional (+1.1 to -3.5 min-1). With use of stepwise regression, PSV(PB) was significantly correlated with VTsp (P = 0.001), E (P = 0.00009), DeltaPCO2 (P = 0.007), and DeltaRR (P = 0.006). The final regression model was as follows: PSV(PB) = 11.1 VTsp + 0.3E - 0.4 DeltaPCO2 - 0.34 DeltaRR - 3.4 (r = 0.98). PB developed in five subjects on PAV at amplification factors of 1.5-3.4. It failed to occur in seven subjects, despite PAF of up to 7.6. We conclude that 1) a PCO2 apneic threshold exists during sleep at 1.5-5.8 Torr below eupneic PCO2, 2) the development of PB during PSV is entirely predictable during sleep, and 3) the inherent susceptibility to PB varies considerably among normal subjects.

Adult↗

Neosartorya fischeri: an invasive fungal pathogen in an allogeneic bone marrow transplant patient.

Invasive fungal infections are a complication of allogeneic BMT. We report the first case of a Neosartorya fischeri fungal infection in a patient following allogeneic BMT. Neosartorya fischeri is related to Aspergillus fumigatus, but it is a distinct fungal species. Despite granulocytic engraftment and aggressive anti-fungal therapy with amphotericin B, the patient died of overwhelming fungal infection on day 60 post-BMT. Neosartorya fischeri is a pathogen that grows slowly in culture which can delay or confuse identification. This case further supports the need for more effective prophylaxis and treatment of non-Candida fungal infections in the allogeneic BMT population.

Aspergillus fumigatus↗

Primary repair without augmentation for early neglected Achilles tendon ruptures in the recreational athlete.

From 1987 to 1994, the senior author performed 41 Achilles tendon repairs. We identified 11 patients during this period (age, 35.3 years; range, 26-60 years) who fit the criterion for neglected Achilles tendon rupture (repair > or = 4 weeks and < or = 12 weeks from injury). All patients underwent proximal release of the gastrocsoleus complex, imbrication of the early fibrous scar without excision of any local tissue, and primary repair of the tendinous ends with two No. 5 Ticron sutures (5R, 6L). Several (three to five) No. 0 Vicryl sutures were used to augment the repair. The ankle was placed in a 20 degree plantarflexion nonweightbearing short leg cast for 3 weeks. All skin closures were primary. At 3 weeks, weightbearing as tolerated was initiated in a short leg cast. The cast was discontinued at 6 weeks, and physical therapy was initiated, consisting of range of motion exercises and closed kinetic exercises, progressing to functional exercises as swelling, strength, and pain allowed. Minimal follow-up was 18 months (mean, 3.5 years; range, 1.5-5.8 years). There have been no subsequent ruptures to date. All patients returned to a preinjury level of activity at a mean of 5.8 months (range, 2.5-9 months). Total range of motion was not different (P > 0.05) between the involved (67 degree) and uninvolved (74 degree) ankle. Plantarflexion loss of strength in the involved ankle was the same (98.4%, 88.1%, and 87.6% respectively, involved to uninvolved) as that seen after acute repair at all speeds tested. Visual analog pain scale (0 to 10) revealed a mean score of 0.7 (range 0-2) during activities of daily living and 1.0 (range, 0-3) during sports activity. The subjective and objective outcome was similar (P > 0.05) to that seen after an acute repair by the same surgeon. There were no complications including skin sloughs or nerve damage. We believe this is the first article to report the results after primary repair without augmentation for the neglected Achilles tendon rupture. We conclude that this approach can result in excellent clinical and functional outcome, a low rate of subsequent rupture, and a high rate of return to sports in the recreational athlete whose repair is performed between 4 and 12 weeks after injury.

Achilles Tendon↗

Synthesis and HIV inhibition activity of 2',3'-dideoxy-3'-C-hydroxymethyl nucleosides.

A series if 2',3'-dideoxy-3'-C-hydroxymethyl purine nucleosides were prepared based on the photochemical ring expansion of a chiral cyclobutanone precursor, (2S)-trans-2,3-bis[(benzoyloxy)methyl]cyclobutanone, in the presence of a 6-substituted purine. Both alpha- and beta-anomers are produced in this transformation. Deprotection was effected by reaction of the photoadducts with saturated methanolic ammonia. Nine purine nucleosides were tested for their inhibitory effect of HIV IIIB virus on H9 cells. The 6-hexyloxy and adenine derivatives 4e,c, respectively, appeared to be most effective at inhibiting viral reproduction with 4c comparable in activity to ddI and AZT.

Anti-HIV Agents↗

HIV replication in CD4+ T cells of HIV-infected individuals is regulated by a balance between the viral suppressive effects of endogenous beta-chemokines and the viral inductive effects of other endogenous cytokines.

This study demonstrates that the beta-chemokines macrophage inflammatory proteins 1 alpha and 1 beta (MIP-1 alpha and MIP-1 beta) and, RANTES (regulated on activation, normally T-cell expressed and secreted) inhibit human immunodeficiency virus (HIV) replication in anti-CD3 or recall antigen-stimulated peripheral blood mononuclear cells (PBMCs) of asymptomatic HIV-infected subjects. Significant levels of beta-chemokines were produced by both CD4+ and CD8+ PBMC subsets from HIV-infected individuals. Neutralization of endogenous MIP-1 alpha, MIP-1 beta, and RANTES did not rescue HIV replication in cultures to which greater than 10% CD8+ T cells had been added, indicating that the HIV suppressor activity of CD8+ T cells cannot be explained entirely by the beta-chemokines. However, significant enhancement of viral replication was observed upon neutralization of endogenous beta-chemokines in CD8-depleted or CD4+ PBMCs from most donors, particularly in cultures with low inducible levels of HIV production. In contrast, certain endogenous proinflammatory cytokines induced HIV replication in these same cells. These data suggest that the levels of HIV replication in CD4+ PBMC reflect the balance of the opposing effects of endogenous suppressive factors, such as the beta-chemokines, and HIV-inducing cytokines, such as tumor necrosis factor alpha and interleukin 1 beta.

CD4-Positive T-Lymphocytes↗

Stimulation of the P-450 side chain cleavage enzyme (CYP11A1) promoter through ras- and Ets-2-signaling pathways.

Expression of the ovine P-450 side-chain cleavage enzyme gene (CYP11A1) is stimulated by epidermal growth factor (EGF) through a pathway that involves c-Jun in JEG-3 placental cells. Growth factor signaling involves ras-dependent and ras-independent signaling pathways, which in turn regulate gene transcription through related but distinct mitogen-activated protein kinase pathways (MAPKs) including the extracellular signal-regulated kinases (ERKs) and the stress-activated protein kinases (SAPKs). We investigated the intracellular signaling pathways governing EGF induction of the CYP11A1 promoter. EGF stimulation of the CYP11A1 promoter (4-fold) was reduced 60% by a dominant negative mutant of ras (N17), and 30-40% by antisense ras. EGF induced both ERK and SAPK activity in JEG-3 cells. EGF-induced CYP11A1 promoter activity was reduced 60% by the MEK1 inhibitor PD098059 and 50% by a dominant negative mutant of the ERK-specific regulator MEK1. In contrast, dominant negative mutants of the SAPK-specific activator, SEK1, induced a further increase in EGF-induced CYP11A1 promoter activity. Constitutively active mutants of ras (V12 or L61) increased CYP11A1 promoter activity 6- to 8-fold. Deletion of the EGF response element (EGF-RE) between -92 and -77 bp reduced ras induction by 60%; however, a residual 3-fold induction remained through the proximal -77 bp. Mutation of the EGF-RE AP-1-like sequence in the context of the native promoter reduced CYP11A1 promoter activation by ras 60%. The EGF-RE sequence was sufficient for 6-fold activation by ras in the context of an heterologous thymidine kinase promoter. Candidate transcription factor targets (c-Jun, c-Ets-2) for the ras-signaling cascade were examined for their effects on CYP11A1 promoter activity. Overexpression of c-Jun induced the CYP11A1 promoter through the EGF-RE; however, c-Ets-2 activation of the CYP11A1 promoter (12-fold) required the proximal ras-responsive promoter sequences that are distinct from the EGF/MEK/c-Jun-responsive element. Induction of the CYP11A1 promoter by EGF involves a ras/MEK1/AP-1-dependent pathway that is distinct from induction by ras/c-Ets-2.

Calcium-Calmodulin-Dependent Protein Kinases↗

[Treatment outcome for dysplastic hip after overhead traction].

Clinical and radiological analysis has been carried out in series of 71 dysplastic hips in children aged 7-21 months of life (mean 16 months) treated with an over head traction. At one year follow-up there were clinically 22% excellent results, radiologically 10% excellent results and 25% poor ones. At the age of 5 complete remodeling of the hip was found in 21% of cases, and poor radiological result in 29% of cases. Avascular necrosis of the femoral head was found in 25% of patients at 1 year follow-up.

Femur Head Necrosis↗

[Urinary excretion of alpha-1-microglobulin and complement components in patients with chronic glomerulonephritis].

The urinary excretion of alpha-1-micro-albumin (alpha 1m) and complement components (CCs) was evaluated in the urine of 49 patients suffering from chronic glomerulonephritis (GN). Nephrotic syndrome (NS) was shown in 18 cases and increased serum creatinine level (Pcr: 115.0-159.1 mumol/l) in 9 patients. The most frequent CCs presence and the highest values of alpha 1m excretion were found in patients with membranous GN. In the early phase of the disease the alpha 1m urinary excretion was higher in subjects with NS than in those not showing the feature of it, independently of the morphological basis of the disease. Also CCs were detected mainly in the nephrotic patients. As the glomerular filtration improved a significant decrease in the urinary alpha 1m excretion was observed. The application of steroid immunosuppressive therapy resulted in the decrease of alpha 1m as well as CCs excretion. The results seem to point out that the increased alpha 1m and CCs excretion may be secondary to the activity of glomerular alternations as well as to the disturbances in glomerular blood flow.

Adult↗