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Biomedical subjects

K McIntyre

Publications and source records attributed to K McIntyre.

At least 37 records · Page 2Linked to original sources
PubMed1994

Augmented tumor necrosis factor response to lipopolysaccharide after thermal injury is regulated posttranscriptionally.

BACKGROUND AND OBJECTIVE: Thermal injury has been shown to enhance macrophage sensitivity to lipopolysaccharide (LPS), resulting in augmented tumor necrosis factor alpha (TNF-alpha) production. This study was designed to examine whether enhanced TNF-alpha response after thermal injury and LPS stimulation is regulated at the level of transcription. DESIGN: Tumor necrosis factor alpha release in alveolar macrophages harvested from sham- or thermal-injured Wistar rats was determined using an L929 cytotoxicity bioassay on days 1, 3, and 5 following 40% scald burn and incubation for 24 hours with LPS (0 or 10 micrograms/mL). Separate groups of rats underwent intraperitoneal injection of LPS (5 mg/kg) 3 days following sham or thermal injury. Lung tissue RNA was isolated and probed for TNF-alpha messenger RNA (mRNA), using nuclease protection analysis. Finally, pooled alveolar macrophages were harvested 3 days following sham or thermal injury and cultured in the presence or absence of LPS (10 micrograms/mL) for 4 hours. The RNA from the pooled alveolar macrophages was extracted and probed for TNF-alpha mRNA levels. RESULTS: Thermal injury alone did not significantly increase alveolar macrophage TNF-alpha bioactivity, whole-lung TNF-alpha mRNA levels, or pooled alveolar macrophages TNF-alpha mRNA levels when compared with levels in sham-injured rats. However, alveolar macrophages from postburn day 3 (PBD 3) demonstrated increased sensitivity to LPS (10 micrograms/mL) compared with alveolar macrophages from sham-injured animals undergoing similar LPS treatment (2365 +/- 1011 vs 169 +/- 79 ng/mL; P < .05). Whole-lung mRNA levels in both sham-injured and PBD-3 rats receiving intraperitoneal LPS, while elevated approximately 2.5-fold from those of non-LPS treated rats, were not different from each other. Finally, pooled alveolar macrophages from sham-injured and PBD-3 rats cultured in the presence of LPS had approximately 1.7-fold and threefold increased TNF-alpha mRNA levels, respectively, compared with alveolar macrophages not cultured with LPS. CONCLUSIONS: Thermal injury induces priming of alveolar macrophages, resulting in significant increases in macrophage TNF-alpha production after exposure to LPS. The majority of this effect appears to be regulated at a posttranscriptional level, since there were only moderate increases in TNF-alpha mRNA levels after LPS stimulation, which did not coincide with large differences in bioactivity.

Animals↗
PubMed1994

Neuroinvasion and persistence of human herpesvirus 6 in children.

Human herpesvirus 6 (HHV-6) causes a febrile illness in children and has been implicated as a cause of encephalitis and recurrent seizures. Paired samples of cerebrospinal fluid (CSF) and peripheral blood mononuclear cells (PBMC) from 487 children were evaluated by nested polymerase chain reaction (PCR) for evidence of current or past infection with HHV-6. PBMC were also cultured for isolation of HHV-6. These data were correlated with the patients' clinical information. HHV-6 DNA was detected in 72 (14.8%) of 487 CSF samples. HHV-6 persistence was documented in 142 children by PCR detection of HHV-6 DNA in PBMC or CSF (or both) in the absence of primary HHV-6 infection; the central nervous system was the only site of HHV-6 DNA persistence in 28.9%. HHV-6 DNA can be detected in the CSF of children during and after primary infection, and the central nervous system may be the sole site of persistence.

Child, Preschool↗
PubMed1992

Primary human herpesvirus 6 infection in young children.

BACKGROUND: Human herpesvirus 6 (HHV-6) is a recently discovered virus that, on the basis of serologic evidence, appears to infect most children by the age of three years. However, the clinical manifestations of primary HHV-6 infection have not been well defined. METHODS: We studied consecutive children two years old or younger who presented to an emergency ward with febrile illnesses. Our evaluation included the isolation of HHV-6 from peripheral-blood mononuclear cells, an immunofluorescent-antibody assay, the detection of HHV-6 by the polymerase chain reaction (PCR), and restriction-endonuclease-fragment profiles of HHV-6 isolates. RESULTS: HHV-6 was isolated from 34 of 243 acutely ill children (14 percent). The children with viremia had irritability, high temperatures (mean, 39.7 degrees C), and inflammation of tympanic membranes (in 21), but few other localizing signs. Two children were hospitalized, but all 34 recovered after an average of four days of fever. The rash characteristic of roseola, which has been associated with HHV-6 infection, was noted in only three children. In 29 children (85 percent), serum samples obtained during convalescence had at least a fourfold increase in IgG antibody titers; 4 infants less than three months old who presumably had maternal antibody did not have this increase. HHV-6 was isolated from blood obtained during convalescence in only one child, but in two thirds of the children the virus could be detected by PCR. The isolates had genomic heterogeneity, indicating the presence of multiple strains. CONCLUSIONS: Primary infection with HHV-6 is a major cause of acute febrile illness in young children. Such infection is associated with varied clinical manifestations, viremia, and the frequent persistence of the viral genome in mononuclear cells.

Antibodies, Viral↗
PubMed1992

Overexpression, purification, and characterization of yeast cyclophilins A and B.

Two isoforms of yeast cyclophilins, yCyPA and yCyPB, have been subcloned, expressed in Escherichia coli, and purified to homogeneity. The full-length (163-amino acid) yeast CyPA was easily expressed and purified; however, only a genetically truncated, 186-residue form of yCyPB lacking a putative 20-amino acid signal sequence could be purified. Each yeast cyclophilin isoform is a peptidyl-prolyl isomerase, inhibitable by the immunosuppressive drug CsA (IC50's of 40 +/- 8 nM and 101 +/- 14 nM at 18 nM concentrations of yCyPA and yCyPB, respectively). Polyclonal antibodies raised against recombinant yCyPA detected native yCyPA in yeast cell extracts by both immunoprecipitation and Western blot analysis. However, polyclonal antibodies raised against recombinant yCyPB detected no native yCyPB in yeast cell extracts by Western blot analysis; small amounts of yCyPB were found in the culture broth, suggesting secretion extracellularly of this isoform. Northern analysis indicated that both yCyPA mRNA and yCYPB mRNA (at a much lower level) were detectable in cell-free extracts. Characterization of the yeast cyclophilin proteins demonstrated that their catalytic properties and sensitivity to CsA parallel those of the human cyclophilins.

Amino Acid Isomerases↗
PubMed1992

Phenotypic and genetic polymorphisms among human herpesvirus-6 isolates from North American infants.

Fifteen human herpesvirus-6 (HHV-6) isolates from North American infants with primary infection manifest as febrile or roseola (exanthem subitum) like illnesses were characterized phenotypically on the basis of their in vitro growth in continuous T-cell lines and primary human mononuclear cells and by their reactivity with monoclonal antibodies. All isolates replicated efficiently in primary human cord blood mononuclear cells, but five distinct patterns of viral replication in human cells lines were observed. Two of the HHV-6 isolates from infants were found to replicate in HSB-2 cells, a property associated with so-called group A viruses, which had previously been isolated only from adults. These same isolates also reacted with a panel of A-specific monoclonal antibodies. Genomic characterization of viral isolates using well-characterized restriction site polymorphisms indicated that these two isolates contained a mixture of both A- and B-type genomes, in different proportions. These data suggest that not all HHV-6 isolates can be categorized into one of two broad groups and that such segregation of HHV-6 isolates may in fact be misleading.

Cell Line↗
PubMed1992

A new method of diagnosing diaphragmatic injury using intraperitoneal technetium: case report.

The diagnosis of diaphragmatic laceration following blunt or penetrating trauma is often difficult to establish. Delay in recognition of this injury can be life threatening, resulting in herniation of abdominal viscera with possible strangulation or respiratory embarrassment. Previous animal studies from our institution have documented that intra-abdominal instillation of technetium sulfur colloid is a sensitive method to diagnose diaphragmatic disruption. We now present a case of diaphragmatic injury where the preoperative diagnosis was accurately made using this method when other imaging studies were inconclusive.

Adult↗
PubMed1989

In-patient psychiatric care: the patient's view.

Little attention has been paid to psychiatric patients' views on their treatment in the medical literature. We carried out a consumer survey of 99 in-patients at an inner London psychiatric hospital. Patients were asked to rate 10 non-treatment and treatment items. Most highly regarded was being free to leave the ward. Of the treatment items, talking to a member of staff was found to be most helpful. The relationships between different items and patient variables such as voluntary versus involuntary status, age and diagnosis are discussed. Sex and number of previous admissions exerted only minor effects. The results are compared with other studies and more work in this area is recommended in order to improve hospital care.

Adult↗
PubMed1989

Calcium channel antagonists modulate the acrosome reaction but not capacitation in mouse spermatozoa.

Mouse spermatozoa require micromolar concentrations of calcium for capacitation but millimolar levels to initiate an acrosome reaction. Sperm suspensions were capacitated by incubation for 120 min in modified Tyrode's medium containing 90 microM-CaCl2 and then verapamil (0.5-50 microM) or nifedipine (0.1-100 nM), drugs shown to inhibit voltage-sensitive calcium channels in other cell types, was added before the introduction of 1.80 mM-CaCl2. Verapamil at 5-50 microM and nifedipine at 1-100 nM significantly inhibited the calcium-stimulated acrosome reaction response, relative to the drug-free control samples. The possibility that these compounds might inhibit calcium entry during capacitation was examined by incubating suspensions for 120 min in medium containing 90 microM-CaCl2 plus either 5 microM-verapamil or 1 nM-nifedipine, diluting to reduce drug concentration to one-tenth and then adding 1.80 mM-CaCl2. The considerable acrosome reaction response obtained indicated that spermatozoa had undergone capacitation and were able to respond to calcium, despite the continuous presence of calcium channel antagonist at a concentration able to inhibit the response at the end of capacitation. In-vitro fertilization studies indicated that both drugs significantly decreased ability of the spermatozoa to fertilize eggs, consistent with acrosome reaction data. However, results indicated that 50 microM-verapamil was able to induce initial stages of egg activation and thus prevent sperm-egg fusion in zona-intact eggs. The addition of verapamil or nifedipine to suspensions capacitated for 120 min in 1.80 mM-CaCl2 significantly potentiated the acrosome reaction response, compared with drug-free controls. Similar treatment of suspensions incubated for only 30 min, and hence only partly capacitated, failed to evoke a response. The potentiation of the acrosome reaction response by verapamil in cells capacitated in high calcium may indicate either retention, due to the action of antagonists, of released intracellular calcium stores, resulting in intracellular calcium concentrations above the threshold required to trigger the acrosome reaction or action of an activated guanine nucleotide binding (G) protein to produce an agonistic rather than an antagonistic response. These results suggest that calcium channels similar to those termed voltage-sensitive in other cell types may exist and play an important role in calcium movements at the end of capacitation, but not during earlier phases of capacitation.

Acrosome↗
PubMed1989

Diagnosis of diaphragmatic injury using intraperitoneal technetium.

The diagnosis of diaphragmatic injury following blunt or penetrating trauma is often made after appreciable delay. The purpose of the present study was to evaluate the use of intraperitoneal technetium in diagnosing diaphragmatic tears in dogs. Six dogs were divided into two groups. In Group 1, thoracotomy was performed bilaterally and 1 cm diaphragmatic tears were made. Peritoneal lavage with technetium-99 sulphur colloid was then performed after closure of the thoracotomy sites. In Group 2 animals, only lavage instillation of technetium was done. Scans were then performed and counts recorded over the chest and abdomen. A ratio of two body areas was then computed and compared between the two groups of animals. There was a statistically significant difference in the ratio between the two groups (P less than 0.05). We conclude that intraperitoneal technetium is a sensitive test for diagnosing diaphragmatic injuries.

Animals↗
PubMed1988

Calcium function in affective disorders and healthy controls.

Calcium metabolism has been reported to be disturbed in some forms of affective disorder. We studied concurrently a battery of calcium measures in 29 unipolar, 14 bipolar depressed, 11 manic, and 10 healthy control subjects. In addition to measures of extracellular calcium, we studied intracellular calcium concentration in platelets and measures that reflect cellular capability to maintain a low intracellular Ca++ concentration in red blood cells (RBCs) and platelets. Plasma calcium was lower in unipolar and manic patients than in control subjects. Platelet calcium concentration was lower in unipolar than bipolar depressed patients. RBC Ca++ adenosine triphosphatase (ATPase) was lower in unipolar and control subjects than in bipolar depressed and manic patients. Platelet Ca++ ATPase and Ca++ uptake were inversely correlated with severity of illness in unipolar patients. In bipolar depressed patients, RBC Ca++ ATPase and platelet Ca++ uptake were inversely correlated with severity. In addition to indicating abnormalities in calcium activity in affective disorders, the data suggest that unipolar and bipolar patients differ in several measures and may have different pathophysiological disturbances in calcium metabolism.

Adult↗
PubMed1988

Factors affecting the patency of infrainguinal bypass.

Two hundred forty-nine well-characterized difficult distal bypasses, entered into a multicenter dextran 40 trial, were reevaluated after 3 years. Seventy in situ (IS) vein grafts, 49 reversed saphenous (RS) vein grafts, 60 polytetrafluoroethylene (PTFE) grafts, and 70 umbilical vein (UV) grafts were used. Primary and secondary patency rates at 3 years were, respectively, 84% and 90% for IS, 66% and 73% for RS, 35% and 48% for PTFE, and 24% and 32% for UV. Subgroup analysis according to the site of distal anastomosis showed no significant differences in primary patency among these grafts at the above-knee level but significant differences between both vein grafts (IS and RV) and the others (PTFE and UV) below the knee (78% vs 31%, respectively). This difference increased at the tibial level (78% vs 10%) but there was also a significant difference between IS grafts (88%) and RS grafts (63%) at this level. Hazard functional analysis showed all grafts except IS grafts begin to fail at an increasing rate again by 24 months. Although overall results appeared to favor PTFE over UV, 62% of PTFE vs 16% of UV terminated at the above-knee level and the patency results of these two grafts were not significantly different at any level. The only other factor than graft type and distal anastomotic site that consistently correlated with late patency was tobacco use. Diabetic patients actually fared significantly better than nondiabetic patients, presumably because of the higher use of IS grafts and lower use of tobacco. The choice of graft overshadows all other factors affecting patency and its influence is magnified with more distal terminal anastomosis.

Anastomosis, Surgical↗
PubMed1987

Mueller maneuver and LV function in coronary artery disease.

Decreasing pleural pressure impedes the ejection of blood from the left ventricle (LV), may lead to decreased LV compliance because of interdependence effects and leads to increased transmural LV systolic and diastolic pressure. Previous work from this laboratory has shown that patients with coronary artery disease (CAD) often develop akinetic segments of the LV wall during the Mueller maneuver. In the presence of increased LV transmural pressure regional akinesis could be caused either by the development of regional ischemia or by mechanical inhibition of motion of an area of nonfunctional myocardium as would be caused by previous myocardial infarction (MI). The present study was designed to distinguish between these two mechanisms by determining if the presence of CAD alone is sufficient to lead to regional akinesis or if prior MI is necessary. We used first pass radionuclide ventriculography (RVG) in the 30 degrees LAD supine position to measure LV ejection fraction (EF), end-diastolic (EDV) and end-systolic (ESV) volumes, heart rate and to assess regional wall motion during the Mueller maneuver. This was done in four groups of subjects: 13 normal subjects, 25 patients with CAD but no prior MI, 13 patients with prior nontransmural MI and 36 patients with prior transmural MI. All subjects had angina pectoris and underwent contrast coronary arteriography. Most also underwent routine contrast left ventriculography as well. There were no significant differences among the three patient groups as regards medications, extent and severity of CAD, and response to routine exercise tolerance testing. EF decreased significantly in the three patient groups (4%-9%, p less than 0.01) but not in the normals during the Mueller maneuver. Heart rate increased (5-10 bpm, p less than 0.05) in the normals and in patient groups 2 and 4. EDV decrease in all four subject groups (8%-10%, p less than 0.01), while ESV remained unchanged. Akinesis of the LV wall developed during the Mueller maneuver only in one group-2 patient, but did so in 17/36 patients with prior transmural MI (group 4, p less than 0.001). One-half of the akinetic LV wall segments seen during the Mueller maneuver on RVG were not seen on routine contrast ventriculography. We tested the effects of posture (supine versus upright) on the response to the Mueller maneuver in six normal subjects and found no changes in the response of EDV and ESV to the Mueller maneuver.(ABSTRACT TRUNCATED AT 400 WORDS)

Coronary Disease↗
PubMed1984

Weak D antigen testing using the groupamatic system.

Reliable detection of the weak D (Du) antigen has been a problem for the Groupamatic typing equipment. Using several anti-D sera of known concentration and Du red cells, dose-response curves produced by the Groupamatic revealed variation in the ability to detect the Du antigen by commercial anti-D reagents. Variation in the reactivity of the Du antigen among Du-positive donors was noted. Studies were conducted to determine optimal conditions for the Groupamatic to detect the weakest Du cells. When these conditions were applied to the retesting, 28 cell samples previously found falsely negative by a number of blood centers were accurately detected.

Blood Grouping and Crossmatching↗