Resistance to HIV infection may be genetically mediated.
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ATP Binding Cassette Transporter, Subfamily B, Mem↗
Biomedical subjects
D Mann
Publications and source records attributed to D Mann.
Fatal haemorrhage following liver biopsy in patients with HIV infection.
A retrospective review of all 248 liver biopsies performed in patients with HIV infection at two referral centres in London over a 12 year period revealed five cases of major bleeding following biopsy, with four deaths. The risk of major bleeding was 2.0%, and mortality was 1.6% following liver biopsy. The risk of bleeding as much higher than in published series of biopsies done in patients without HIV infection, owing in part to the high prevalence of thrombocytopaenia and clotting abnormalities in patients with HIV infection. HIV infection per se may also increase the risk of bleeding following liver biopsy.
Adult↗
Bovine gamma/delta T-cell proliferation is associated with self-derived molecules constitutively expressed in vivo on mononuclear phagocytes.
Bovine gamma/delta T cells have been shown previously to proliferate when cocultured with gamma-irradiated bovine monocytes in the 'autologous mixed leucocyte reaction' (AMLR). It was suggested that the response may be to culture-derived or culture-induced antigenic epitopes. Data presented here indicate that the gamma/delta T-cell stimulatory activity is attributable to a self-derived cell-surface molecule of mononuclear phagocytes that is constitutively expressed in vivo. The ability to induce an AMLR did not require in vitro culture or stress associated with in vitro isolation of cells or increased temperature since it could be induced by monocytes fixed by paraformaldehyde during blood collection from normal animals. Furthermore, stimulation by monocytes did not depend upon secreted molecules since fixed monocytes that had been incubated overnight at 37 degrees to allow secretion of preformed molecules, or subjected to hypotonic shock in H2O for 10 min before addition to the cultures, induced an AMLR as did plasma membranes prepared from ex vivo monocytes. In contrast, enzymatic treatment of monocytes to digest surface molecules followed by fixation destroyed their ability to stimulate an AMLR. The ability of monocytes to stimulate proliferation of gamma/delta T cells was distinguishable from their ability to stimulate alpha/beta T cells, since the former was destroyed by glutaraldehyde fixation whereas stimulation of alpha/beta T cells by major histocompatibility complex (MHC)-presented antigenic epitopes is not. Moreover, induction of proliferation of bovine gamma/delta T cells was not MHC-restricted. Finally, bovine alveolar macrophages, sheep monocytes and transformed bovine monocytes stimulated proliferation of bovine gamma/delta T cells whereas none of the following did so: human monocytes, murine macrophages, bovine myeloid cells other than mononuclear phagocytes, other nucleated cells found in bovine blood including activated MHC class II-bearing B cells, and a variety of species of bacteria. Thus, the stimulatory epitope is unique to and conserved among mononuclear phagocytes of ruminants. Demonstration of stimulation of bovine gamma/delta T cells by self-derived molecules is consistent with reports for murine gamma/delta T cells.
Animals↗
Distribution of lipids in 8,500 men with coronary artery disease. Department of Veterans Affairs HDL Intervention Trial Study Group.
In the present study we measured fasting lipid profiles in over 8,500 community-living men with coronary artery disease (CAD) to determine the distribution of lipid abnormalities in this population: 81% were white and 16% black; mean age 62.9 +/- 8 years; mean total cholesterol 214 +/- 41 mg/dl; low-density lipoprotein (LDL) cholesterol 140 +/- 37 mg/dl; high-density lipoprotein (HDL) cholesterol 39 +/- 11 mg/dl; and triglycerides 190 +/- 142 mg/dl. After adjusting for age, the only significant difference between blacks and whites was a higher HDL cholesterol in blacks (45 vs 38 mg/dl, p < 0.003). With use of cut points established by the National Cholesterol Education Program, 87% of subjects had high LDL cholesterol (> or = 100 mg/dl), 38% had low HDL cholesterol (< 35 mg/dl), and 33% had high triglycerides (> 200 mg/dl). We estimated that 42% of men with CAD would be definite candidates for cholesterol-lowering medication according to the National Cholesterol Education Program guidelines and that 41% of those in whom cholesterol-lowering medication would not be definitely indicated had low levels of HDL cholesterol. We conclude that (1) black men with CAD have substantially higher HDL cholesterol than white men, (2) almost 90% of male patients with CAD are candidates for dietary intervention and > 40% may need medications to lower LDL cholesterol, and (3) 40% of patients without a definite indication for cholesterol-lowering medications have low levels of HDL cholesterol.
Adult↗
Pseudoseptic inflammatory knee effusion caused by phagocytosis of sickled erythrocytes after fracture into the knee joint.
A 57-year-old black man with sickle cell disease was admitted to the hospital because of a painful crisis. After a fall with a fracture into the right knee joint, he developed an acutely painful, swollen knee. Synovial fluid from the right knee showed leukocyte counts of up to 154,000/mm3 and was negative for urate and calcium pyrophosphate dihydrate crystals. Gram stains and cultures were negative. Some sickled red cells were seen by light microscopy; electron microscopy revealed crystal-like arrays of sickled hemoglobin tactoids in erythrocytes which were enfolded and phagocytized by the cells of the synovial fluid. We suggest that this phagocytosis of sickled red cells is the likely cause for the otherwise unexplained inflammation.
Arthritis↗
Autonomic function in type I diabetes mellitus complicated by nephropathy. A cross-sectional analysis in the presymptomatic phase.
The purpose of this study was to determine the prevalence of parasympathetic and sympathetic autonomic dysfunction in long-standing type I diabetics with established nephropathy and to correlate autonomic function with cardiac risk factors. We used prospective analysis of heart rate variations to standardized testing and 24-hour blood pressure control prior to enrollment in a study utilizing various methods of intense diabetic control to prevent deterioration of kidney function. The settings were outpatient clinical research units. The patients were 42 type I diabetics with proteinuria (total urinary protein > or = 300 mg/day or urinary albumin > or = 100 mg/day) and creatinine clearance > or = 30 mL/min. Heart rate variation during respiratory cycles with change in posture from supine to upright, and during the Valsalva maneuver was recorded by a computerized method. Mean arterial blood pressure was recorded for 24 h by a computerized method. Heart rate variations in this group were abnormal during timed respiratory cycles in 26 of 40 patients (56%), during changes in posture in 15 of 40 patients (38%), and during Valsalva maneuver in 13 of 34 patients (38%) whose retinal disease permitted Valsalva testing. Blunted day/night mean arterial pressure ratios occurred in 18 of 41 (44%) patients and were more severe in men than in women (1.00 v 1.06, P < or = .05). Absence of deep tendon reflexes was associated with an increased incidence of both parasympathetic (respiratory rate variation) and sympathetic (postural rate variation) abnormalities (both P < or = .05). Loss of vibration sensation was not associated with autonomic functional abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Laparoscopic splenectomy offers advantages in selected patients with immune thrombocytopenic purpura.
BACKGROUND: Splenectomy plays a crucial role in the management of selected patients with immune thrombocytopenic purpura (ITP). Laparoscopic splenectomy has been suggested as an alternative to open techniques. MATERIALS AND METHODS: A retrospective chart review was made for all patients undergoing splenectomy for ITP at our institution from June 1987 to August 1994. RESULTS: Twenty-one patients underwent splenectomy for ITP. Fourteen open procedures (group 1) and 7 laparoscopic procedures (group 2) were performed. Eleven of 14 patients in group 1 and all 7 patients in group 2 had appropriate increases in platelet count following surgery. There were 3 complications in group 1 and no major complications in group 2. Operative time was longer in group 2 (154 versus 68 minutes, P < 0.05), but decreased with experience (210 to 135 minutes). Compared with patients in group 1, patients in group 2 tolerated liquids sooner (0.7 versus 2.6 days, P < 0.05), required less parenteral narcotic (14 versus 65 morphine equivalents, P < 0.05), and were discharged sooner (2.1 versus 5 days, P < 0.05). All patients in group 2 remain well and require no medication after a mean follow-up of 11 months. CONCLUSIONS: Laparoscopic splenectomy is safe and effective in the management of select patients with ITP and offers advantages over open techniques.
Humans↗
Recombination rates across the HLA complex: use of microsatellites as a rapid screen for recombinant chromosomes.
Meiotic recombination does not appear to occur randomly across chromosomes, but rather seems to be restricted to specific regions. A striking example of this phenomenon is illustrated by the HLA class II region. No recombination within the 100 kb encompassing the DRB1-DQA1-DQB1 loci has been reported, whereas the random association of TAP1 with TAP2 alleles suggests the presence of a hotspot for recombination within the 15 kb separating the closest variant sites of these two loci. Recombination rates between loci may provide clues to the functional properties of haplotypes. Absence of recombination may suggest the necessity to keep alleles of certain genes in phase and, alternatively, high recombination rates may suggest selective pressure to diversify haplotypes within the population. To address this issue, recombination rates across the HLA complex were determined using the 59 Centre d'Etude Polymorphisme Humain (CEPH) pedigrees. The allele frequencies of four microsatellite markers which map at sites ranging from the telomeric to centromeric ends of the complex were determined and the markers were used as a rapid means for identification of recombinant chromosomes. Typing these as well as other polymorphic loci within the HLA class I, II and III regions allowed assignment of the segments where recombination occurred. Recombination rates within the class II region (defined here as DRB1 to DPB1) and class III region (defined here as HLA-B to DRB1) regions were 0.74% and 0.94%, respectively, both of which are within an expected range given the standard of 1% recombination rate per megabase of DNA per meiosis.(ABSTRACT TRUNCATED AT 250 WORDS)
Alleles↗
The relative distribution of T cell subsets is altered in Jamaican children infected with human T cell lymphotropic virus type I.
Early childhood infection with human T cell lymphotropic virus type I (HTLV-I) has been suggested to be involved in the pathogenesis of infective dermatitis and adult T cell leukemia/lymphoma. Since only a very small percentage of HTLV-I-infected children develop disease later in life, identification of early interim markers for persons at risk for developing disease would enable monitoring and might provide insight into the pathophysiology of the various diseases associated with HTLV-I infection. A cross-sectional study analyzed T cell subsets in 35 HTLV-I-seronegative and 16 HTLV-I-seropositive Jamaican children 11-31 months old. HTLV-I seropositivity was associated with an increase in the mean percentage of CD4 cells expressing HLA-DR, a marker for T cell activation (P = .02). This increase was positively correlated with duration of infection (r = .74, P = .009). These data demonstrate perturbation of regulatory cells of the immune system in HTLV-I-infected children.
Breast Feeding↗
[Effect of primary fracture management on craniocerebral trauma in polytrauma. An animal experiment study].
Severe head trauma (BI) associated with long bone fractures is present in about 60% of polytraumatized patients admitted to hospital. However, there is no consensus regarding early fracture stabilization in such patients. In an experimental sheep study, the influence of intramedullary nailing of the femur (IMNF) on a cold-induced, vasogenic brain edema (method of Klatzo) in combination with traumatic hemorrhagic shock (THS) was investigated. Three animal groups (n = 6) were explored: group A, only BI; group B, BI and THS; group C, BI, THS and IMNF. The animals remained intubated, on controlled ventilation, sedated and received analgesia during the whole experiment. For a period of 6 h after the cold-induced brain injury the hemodynamic changes were measured and the intracranial pressure (ICP) was recorded in the left and the right hemisphere continuously. The hemorrhagic shock (MAP = 60 mm Hg) was maintained over 1.5 h. At the end of the reperfusion period (2 h) the nailing of the femur was performed. The animals were killed and the percentage water content of the brain was determined and compared with the brain water content of a control group (n = 6). There were no significant differences in ICP between groups A, B and C before or after IMNF, but in group C the ICP increased significantly after nailing. Brain water content in group C was significantly higher than in the control group and slightly significantly higher than in groups A and B. Brain edema and ICP are increased by IMNF.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Apolipoprotein E epsilon 2 allele promotes longevity and protects patients with Down's syndrome from dementia.
Although individuals with Down's syndrome nearly always develop the clinical and pathological features of Alzheimer's disease, some clearly do not become demented despite living into their sixth and seventh decades. Genetic variation at the apolipoprotein E locus has recently been shown to be an important determinant of Alzheimer's disease, with the epsilon 4 allele having been shown to be associated with the disease and, at least in some cases, the epsilon 2 allele being negatively associated with the disease. Here we show, in a series of clinically assessed individuals with Down's syndrome, that the epsilon 2 allele of ApoE is associated with both longevity and the absence of clinical evidence of dementia. These data show that the clinical phenotype of Down's syndrome can be modulated by genes on chromosomes other than chromosome 21. The importance of this observation to the pathogenesis of Alzheimer's disease, both in Down's syndrome and in general, is discussed.
Age of Onset↗
Effects of saline, mannitol, and furosemide on acute decreases in renal function induced by radiocontrast agents.
BACKGROUND: Injections of radiocontrast agents are a frequent cause of acute decreases in renal function, occurring most often in patients with chronic renal insufficiency and diabetes mellitus. METHODS: We prospectively studied 78 patients with chronic renal insufficiency (mean [+/- SD] serum creatinine concentration, 2.1 +/- 0.6 mg per deciliter [186 +/- 53 mumol per liter]) who underwent cardiac angiography. The patients were randomly assigned to receive 0.45 percent saline alone for 12 hours before and 12 hours after angiography, saline plus mannitol, or saline plus furosemide. The mannitol and furosemide were given just before angiography. Serum creatinine was measured before and for 48 hours after angiography, and urine was collected for 24 hours after angiography. An acute radiocontrast-induced decrease in renal function was defined as an increase in the base-line serum creatinine concentration of at least 0.5 mg per deciliter (44 mumol per liter) within 48 hours after the injection of radiocontrast agents. RESULTS: Twenty of the 78 patients (26 percent) had an increase in the serum creatinine concentration of at least 0.5 mg per deciliter after angiography. Among the 28 patients in the saline group, 3 (11 percent) had such an increase in serum creatinine, as compared with 7 of 25 in the mannitol group (28 percent) and 10 of 25 in the furosemide group (40 percent) (P = 0.05). The mean increase in serum creatinine 48 hours after angiography was significantly greater in the furosemide group (P = 0.01) than in the saline group. CONCLUSIONS: In patients with chronic renal insufficiency who are undergoing cardiac angiography, hydration with 0.45 percent saline provides better protection against acute decreases in renal function induced by radiocontrast agents than does hydration with 0.45 percent saline plus mannitol or furosemide.
Aged↗
Cystic fibrosis-related diabetes is associated with HLA DQB1 alleles encoding Asp-57- molecules.
The incidence of insulin-dependent diabetes in individuals with cystic fibrosis is nearly 100 times greater than in the general population. In the latter group, strong associations with specific HLA DQA1 and DQB1 alleles have been observed. To determine if a similar distribution of alleles occurs in cystic fibrosis patients with diabetes, a cohort of these individuals was typed for DQA1 and DQB1 alleles. HLA DQB1*0201 (Asp57-) was more frequent in diabetics compared to controls (40.4 vs 28%), while the frequency of alleles encoding Asp57+ molecules was lower in diabetics relative to both the cystic fibrosis-only controls (P = 0.025) and the general population (P = 0.008). The presence of at least one protective DQA1-DQB1 heterodimer (i.e., Arg52- and Asp57+, respectively) in cis or trans was significantly lower in the diabetics than in either of the control groups. Thus, the HLA alleles known to be associated with insulin-dependent diabetes mellitus in the general population are also found in diabetics with cystic fibrosis.
Adolescent↗
Major histocompatibility complex class II haplotypes and linkage disequilibrium values observed in the CEPH families.
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ATP Binding Cassette Transporter, Subfamily B, Mem↗
Bradykinin (Bk) increases cytosolic calcium in cultured rat myenteric neurons via Bk-2 type receptors coupled to mobilization of extracellular and intracellular sources of calcium: evidence that calcium influx is prostaglandin dependent.
We examined the effect of bradykinin (Bk) on cytosolic calcium ([Ca++]i) in cultured rat ileal myenteric neurons. The receptor subtype(s) and calcium pool(s), e.g., extracellular and/or intracellular calcium that mediate Bk's effect on [Ca++]i in myenteric neurons, have not been reported. Superfusion with Bk (10 nM) increased [Ca++]i by 96 +/- 10 nM over basal levels in approximately 80% of the neurons tested that were not affected by a Bk-1 receptor antagonist but were inhibited 72% by a Bk-2 receptor antagonist. The Bk-generated increase in [Ca++]i was reduced by 45% and 52% of control response in calcium-free buffer and indomethacin, respectively, supporting involvement of extracellular and intracellular pools of calcium and mediation, in part, by a prostaglandin-dependent pathway. Bk increased [Ca2++]i by 54 +/- 6 nM in calcium-free buffer that was indomethacin insensitive, suggesting that Bk stimulation of extracellular calcium influx was mediated by a prostaglandin-dependent pathway. Bk (1 microM) increased tissue prostaglandin E2 (PGE2) production by 62% over basal levels in isolated rat ileal myenteric ganglia. Finally, superfusion with PGE2 (10 microM) increased [Ca++]i by 105 +/- 16 nM over basal levels that were blocked in calcium-free buffer. In summary, our studies suggest that cultured rat ileal myenteric neurons express the Bk-2 receptor subtype that is coupled to mobilization of extracellular and intracellular pools of calcium. Bk stimulates influx of extracellular calcium via a prostaglandin-dependent pathway.
Animals↗
Characterization of HLA-DMB polymorphism.
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Alleles↗
Large granular lymphocytosis in a patient infected with HTLV-II.
HTLV-II has been associated with a variety of lymphoproliferative disorders, including atypical hairy cell leukemia, chronic T cell leukemia, T prolymphocytic leukemia, and large granular lymphocytic leukemia. However, a direct or indirect role for HTLV-II in these disorders is not yet firmly established. We studied a patient diagnosed as having leukemia of the large granular lymphocyte (LGL) type who was HTLV-II seropositive, to determine if the expanded cell population was infected. Two populations of CD3-CD16+ LGL were identified; one was CD8+, the other CD8-. Populations of cells with these surface markers as well as normal CD3+CD4+ and CD3+CD8+ cells were separated by flow cytometric methods, DNA extracted, and gene regions of HTLV-II pol and tax amplified, using the polymerase chain reaction, and probed after Southern blotting. HTLV-II was detected in the CD3+CD8+ population, and not in the CD3-CD16+ large granular lymphocyte population. This finding indicates that the role of HTLV-II, if any, in LGL proliferation is indirect.
Antigens, CD↗
Hippocampal and neocortical ubiquitin-immunoreactive inclusions in amyotrophic lateral sclerosis with dementia.
Amyotrophic lateral sclerosis (ALS) patients with dementia were found to have ubiquitin-immunoreactive (IR) inclusions in the dentate granule cells of the hippocampus. These inclusions were also present in some patients with minor cognitive changes but otherwise typical ALS. Ubiquitin-IR inclusions were also found in neurons of superficial layers of the frontal and temporal cortex and in the entorhinal cortex in patients with ALS and dementia. These ubiquitin-IR inclusions were non-argyrophilic, and were not labelled by antibodies which identify Alzheimer's neurofibrillary tangles and Pick bodies, nor were they typical of cortical Lewy bodies. Our findings indicate that ubiquitin-IR inclusions in small neurons of the hippocampus, entorhinal area and neocortex are a characteristic feature of degeneration of non-motor cortex in ALS, and are particularly associated with cognitive impairment and dementia of frontal lobe type.
Adult↗