Wheelchair prescribing. A heavy load.
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Aged↗
Biomedical subjects
C Smith
Publications and source records attributed to C Smith.
Fundholding. Mythical monster.
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Contract Services↗
Expression and functionality of the trkA proto-oncogene product/NGF receptor in undifferentiated hematopoietic cells.
The expression of the low-affinity NGF receptor (p75) and the trkA proto-oncogene product was analyzed in a series of human hematopoietic cell lines at protein and RNA levels. We did not detect any form of NGF receptor in cell lines displaying a myelomonocytic phenotype (HL60 and U937). In contrast, cells displaying a more immature erythroleukemic phenotype (TF1 and K562) expressed TrkA in the absence of detectable p75. Scatchard analysis showed a single high-affinity site for NGF (kd = 10(-10) mol/L), with a copy number ranging from 300 to 3,000 sites per cell depending on the studied cell line. In addition, NGF induced autophosphorylation of TrkA and could substitute for granulocyte-monocyte colony-stimulating factor to trigger the proliferation of the TF1 cell line, with a half-maximal signal observed at 50 pmol/L, indicating that p75 is not required for DNA synthesis in this cell line. The physiologic relevance of NGF in early hematopoiesis was confirmed by showing that 12% to 15% of progenitor blood cells from mice treated with 5-fluorouracil expressed TrkA and that these cells could be induced to proliferate and differentiate in response to NGF in association with macrophage colony-stimulating factor. Our study demonstrates for the first time that trkA proto-oncogene expression and activation is not restricted to the nervous system, but is also an important element in early hematopoiesis.
Animals↗
Dyshematopoiesis in combined immune deficiency with congenital neutropenia.
This report describes a patient with combined immune deficiency associated with congenital neutropenia (CID/CN) and reports a partial characterization of his hematopoietic abnormalities. The CID/CN syndrome described is characterized by neutropenia and by deficiencies in B-lymphoid and T-lymphoid cell number and function. Red cell and platelet counts were normal. In vitro assays indicate that the myeloid lineage was developmentally arrested at the level of the committed monocyte/granulocyte progenitor (CFU-GM), while precursors to the CFU-GM progenitor were normal. In vitro studies showed that the defect in myeloid development was not corrected with G-CSF or GM-CSF. However, combinations of cytokines present in conditioned media from the T-cell lines MO or C5MJ, or defined multiple cytokine combinations containing IL-1, IL-3, GM-CSF, kit ligand, IL-6, and IL-9, restored myelopoiesis in-vitro. In contrast, C5MJ-conditioned media did not correct deficiencies in immune function in the patient's lymphocytes and accessory cells. No abnormalities in the production of G-CSF, GM-CSF, M-CSF, or IL-1 from the patient could be identified to account for the defects in myelopoiesis orimmune function.
B-Lymphocytes↗
Intratracheal administration of endotoxin and cytokines. VII. The soluble interleukin-1 receptor and the soluble tumor necrosis factor receptor II (p80) inhibit acute inflammation.
Intratracheal administration of endotoxin (LPS) causes acute neutrophilic inflammation via induction of pulmonary tumor necrosis factor alpha (TNF) and interleukin-1 (IL-1) expression. In the present study, the anti-inflammatory activity of soluble IL-1 receptor (sIL-1r) and soluble TNF receptor p80 (sTNFr-p80) in LPS-induced acute pulmonary inflammation was investigated. The sIL-1r coinjected intratracheally with LPS in rats significantly inhibits neutrophilic exudation into bronchoalveolar lavage (BAL) fluid by 47% after 6 hr compared to injection of LPS alone. TNF and IL-6 in the same BAL fluids were both lowered by approximately 50% after intratracheal coinjection of sIL-1r and LPS as compared to LPS alone. In the same model, the sTNFr-p80 inhibited acute inflammation. Paradoxically, TNF levels in BAL fluids were generally elevated after the intratracheal coinjection of LPS and monomeric sTNFr-p80 compared to injection of LPS injection alone. The combined anti-inflammatory effect of sIL-1r and sTNFr-p80 at the maximally effective individual doses is not significantly greater than the effect of either soluble receptor alone.
Animals↗
Organization of the human annexin V (ANX5) gene.
We characterized the region of human chromosome 4q26-q28 that contains the gene encoding annexin V (placental anticoagulant protein I), a member of a family of calcium-dependent phospholipid binding proteins. A total of 14.5 kb, containing 9 introns, could be directly amplified from genomic DNA; the remainder was characterized from genomic clones in phage lambda and a yeast artificial chromosome. The gene was mapped with restriction enzymes BamHI, EcoRI, HindIII, SacI, StuI, and XbaI; the transcribed region spans 28 kb and contains 13 exons (44 tp 530 bp in size) and 12 introns (0.23 to 8.8 kb in size). Several putative transcription factor binding sites are present in the 5'-region, but the promoter has no recognizable TATA box. This study will facilitate further analysis of the functions of annexin V and its role in disease.
Animals↗
Cadmium encephalopathy: a report with elemental analysis and pathological findings.
We report a boy of East Indian origin, aged 2 years and 10 months, who died suddenly and unexpectedly. Autopsy findings showed marked cerebral swelling with herniation and histological evidence of marked cerebral edema with perivascular protein leakage, indicating blood-brain barrier disruption. Energy dispersive X-ray microprobe analysis of the brain demonstrated the presence of cadmium and a marked increase in sulfur, predominantly intracellular, both within neuroglial, and to a lesser degree endothelial, cells. Localization was predominantly in the nucleus. Analysis of the kidney showed cadmium deposition in renal tubules and in the basal lamina of podocytes within the glomerulus. Although the environmental source of cadmium remains unknown, we speculate that acute cadmium toxicity led to brain intracellular accumulation with resultant cellular dysfunction, blood-brain barrier disruption, and lethal cerebral edema.
Blood-Brain Barrier↗
Congenital mesoblastic nephroma presenting with hemoperitoneum and shock.
We describe an unusual presentation of a congenital mesoblastic nephroma in a 5-month-old boy. He was in hemodynamic shock in admission. Sonography revealed an echogenic right kidney and hemoperitoneum. Right nephrectomy was performed, and he is well one year later without any further treatment.
Hemoperitoneum↗
Clinical experience with Montgomery salivary bypass stents in the esophagus.
Thirty-seven patients with locally advanced malignancy (18, esophageal obstruction; 19, esophageal fistula formation) underwent attempted placement of a Montgomery salivary stent in the esophagus. This was unsuccessful in 3; in 2, because of inability to dilate, and, in 1, because of perforation. After dilation of the esophagus, there was no detectable underlying stricture in 11 patients; none of these patients experienced stent migration. Overall, there was 100% success in obliterating the fistulous tract, an 8.1% incidence of retrograde migration, no incidence of prograde migration, and no incidence of stent obstruction after discharge. Of the 34 patients with successfully placed stents, 27 were discharged from hospital, and were able to eat and drink without the need for intravenous supplementation or gastrostomy tube feedings. The survival in patients presenting with obstruction ranged from 1 to 13 months (mean, 8.0 months); the survival in patients presenting with a fistula ranged from 2 to 7 months (mean, 5.3 months).
Esophageal Fistula↗
Bacterial translocation in mesenteric ischemia-reperfusion injury: is dysfunctional motility the link?
The authors previously reported that mesenteric ischemia and reperfusion (I/R) in a chronic newborn piglet model creates dysfunctional intestinal motility. Whether this leads to inadequate bacterial clearance and translocation (BT) through the gastrointestinal tract remains unclear. To test this hypothesis the authors used their chronic piglet model (weight, 3.5 +/- 0.3 kg; age, 18 +/- 4 days; on formula feeding); nonocclusive mesenteric ischemia was induced via reversible pericardial tamponade. Mesenteric flow (SMA Doppler measurement via the retroperitoneal approach) was decreased to 25% +/- 5% of baseline for 300 minutes in the ischemia group (n = 7) and followed by 14 hours of reperfusion in the I/R group (n = 6). Control subjects had a sham operation (n = 7). Mesenteric lymph nodes (MLN), liver (L), spleen (S), ileum, peritoneum, and blood were harvested for blind quantitative microbial analysis. Subjects in the control group had no cultures positive for growth. Eighty-five percent of animals in the ischemia group had positive MLN cultures only (P < .05 v control). All piglets in the I/R group had positive MLN cultures (P < .05 v control), and one third of them manifested bacteremia. Histological examination did not show mucosal disruption in any group. The validity of this model is confirmed by the negative cultures in the control group and by the presence of normal ileal flora in all animals. In the ischemia and I/R groups, MLN cultures were consistently positive with gram-negative bacilli (Escherichia coli and/or Klebsiella pneumoniae). When subjects of the I/R group had more than 1,000 colonies in the MLN, bacteremia with the translocating organisms was also identified.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Signet ring cell adenocarcinoma of prostate.
Primary signet ring cell adenocarcinoma of the prostate is a rare malignancy with a total of 13 cases reported to date in the English literature. We report a very unusual case of signet ring adenocarcinoma of the prostate occurring in a patient who presented initially with irritative voiding symptoms and a bladder mass. Results of immunohistochemical, flow cytometric, and cytogenetic analyses of the tumor are presented.
Carcinoma, Signet Ring Cell↗
Gene therapy for infectious diseases: the AIDS model.
Genetic manipulation of somatic cells may be of therapeutic value in a variety of infectious diseases, particularly in human immunodeficiency virus (HIV) infection. Stable insertion of custom-designed 'resistance genes' into cells susceptible to HIV could reduce the viral burden in infected individuals and potentially retard the characteristic progressive immune dysfunction. Alternatively, ectopic expression of genes that encode viral antigens might induce potent antiviral immune responses and form the basis for novel prophylactic and therapeutic vaccines. While laboratory studies have proved that the approach works in principle, preclinical and clinical studies will be necessary to evaluate the therapeutic benefit of such gene-based therapies.
Acquired Immunodeficiency Syndrome↗
Explanatory models of diabetes: patient practitioner variation.
Most cases of diabetes, a complex disorder that requires many lifestyle changes, can be controlled if persons adhere to their prescribed regimen. However, compliance is difficult to attain. Differences in explanatory models between client and practitioner have been suggested as one reason for non-compliance in several disorders. In this ethnographic investigation, individual explanatory models were elicited from persons with diabetes and from health professionals working with these patients. Professionals described models of diabetes in general and their model of a particular patient's diabetes. A composite professional model was constructed and compared with each of the patients' models. The models were most congruent regarding treatment. Etiology, pathophysiology, and severity had less congruence, and time and mode of symptom onset were least congruent. The Spearman correlation coefficient showed a positive but non-significant association of explanatory model congruence between professionals and patients with normal glycosylated hemoglobin levels. Patients and professionals seem to emphasize different domains; patients emphasized difficulties in the social domain and the impact of diabetes on their lives while staff saw diabetes primarily as a pathophysiological problem with impact on patients' physical bodies. This study's importance rests on its clear articulation of significant differences between patients' and staffs' models even when they are similar in demographic characteristics.
Diabetes Mellitus↗
Hemodynamic responses to dobutamine during acute normovolemic hemodilution.
The effects of dobutamine (DOB) on myocardial performance, systemic hemodynamics, and oxygen delivery during acute normovolemic hemodilution in anesthetized rats were studied. Forty-two Sprague Dawley rats (body weight 375 to 425 g) were divided into six equal groups. Hemodynamic and cardiac indices were measured or calculated at baseline, 30 minutes after the initiation of hemodilution (HD), and 15 minutes after DOB or saline infusion. Myocardial performance in response to acute pressure or volume loads was studied in all groups of animals. HD to a hematocrit (Hct) value of 20% resulted in no change in heart rate (HR), increased CI, SVI, and LV dP/dt, and decreased MAP, SVRI, and oxygen delivery index (O2DI). HD increased peak SV and CI after preload stress while the left ventricular developed pressure (LVDP) was unchanged. Infusion of DOB as 7.5 or 15 micrograms/kg/min increased HR, CI, and LV dP/dt as well as LVDP. At the same time, DOB decreased MAP and SVR, whereas the SVI remained unchanged. In non-HD animals both doses of DOB increased LVDP, but only the larger dose increased CI, whereas peak SV decreased with the smaller dose. Arterial carbon dioxide tension (PaCO2) increased, whereas pH and arterial oxygen tension (PaO2) decreased; however, O2DI remained unchanged. Concomitant hemodilution and DOB infusion resulted in attenuation of HR response to DOB, exaggerated the drop in MAP and SVR, and increased LV dP/dt. Only the larger dose of DOB increased the CI, whereas neither dose could alter the SVI in HD animals.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Clinical experience with the Hewlett-Packard M-1350A fetal monitor: correlation of Doppler-detected fetal body movements with fetal heart rate parameters and perinatal outcome.
OBJECTIVE: Our purpose was to correlate measures of Doppler-detected fetal movements with standard fetal heart rate parameters and perinatal outcomes. STUDY DESIGN: This prospective, multiinstitutional trial used the Hewlett-Packard M1350A monitor to record simultaneous fetal heart rate baseline, variability, accelerations, decelerations, and number of fetal movements, and duration and percent of total time. These data were compared at 10- and 30-minute intervals during nonstress tests and were correlated with fetal heart rate baseline parameters and maternally perceived fetal movements and with outcomes of infants delivered within 7 days of the last test. RESULTS: At six centers 1704 actocardiograms from 884 third-trimester patients were analyzed. Doppler-detected fetal movement counts, durations, and percent of total time correlated weakly with all baseline fetal heart rate parameters (all values < 0.20). All fetal movement parameters increased significantly in successive 10-minute blocks and in periods of increased or normal fetal heart rate variability compared with those with fetal heart rate variability. The sensitivity, specificity, and predictive values of the percent of total movement time were comparable to those of standard nonstress test parameters. The risk of poor perinatal outcomes after nonreactive nonstress tests was lower in cases with fetal movements than in those without. CONCLUSIONS: Doppler actocardiography may help to discriminate fetal states during antepartum testing. It may prevent inappropriate diagnosis of fetal compromise when the nonstress test is nonreactive or nonreassuring.
Female↗
Relation of percentage of body fat and maximal aerobic capacity to risk factors for atherosclerosis and diabetes in black and white seven- to eleven-year-old children.
OBJECTIVE: To determine whether body fatness, aerobic capacity, and fat distribution are associated with levels of cardiovascular risk factors in children. METHODS: Subjects (N = 57) were 7 to 11 years of age; their percentage of body fat ranged from 10% to 58%. The percentage of fat was measured with dual-energy x-ray absorptiometry, maximal aerobic capacity was measured on a treadmill, fat distribution was expressed as the waist/hip circumference ratio, and blood pressures were measured with an automated monitor. Measurements of several lipoproteins and apoproteins were combined into one atherogenic index. RESULTS: The percentage of fat was related to the atherogenic index (p = 0.38; p > 0.01) and insulin level (p = 0.78; p > 0.001). Aerobic capacity was inversely related to the atherogenic index (p = -0.27; p > 0.05) and insulin level (p = -0.72; p > 0.001). The waist/hip ratio was not related to the risk factors, and blood pressures were not related to fatness or aerobic capacity. In multiple regression analyses, only fatness explained significant independent proportions of the variance in the atherogenic index and insulin level. After control for fatness, the black children had higher insulin levels (p > 0.05). CONCLUSION: At early ages (7- to 11-year-old children), fatness was related to risk factors for cardiovascular disease and diabetes.
Absorptiometry, Photon↗
Transurethral puncture of ectopic ureteroceles in neonates and infants.
Ten neonates and infants with 11 ectopic ureteroceles prospectively underwent transurethral puncture as the primary form of therapy. Of the 10 patients 6 had a prenatal diagnosis of uropathy and 4 presented postnatally with urinary tract infection. One patient had bilateral single system ectopic ureteroceles and 9 had a single ectopic ureterocele in a duplex system. Significant associated ipsilateral and/or contralateral urological pathology was noted in addition to the ectopic ureterocele in 7 patients. Transurethral puncture adequately decompressed 10 of the 11 ectopic ureteroceles (91%) and improved drainage of nonureterocele moieties in 3 cases. Iatrogenic reflux was found in 3 of the 11 ureterocele ureters. Urinary tract infection developed in 6 infants (4 with fever). Of the 10 patients 8 (80%) eventually required secondary surgical intervention because of recurrent urinary tract infections, persistent or iatrogenic reflux, or unresolving hydronephrosis. Although transurethral puncture rarely constitutes definitive treatment for ectopic ureterocele, there appears to be immediate benefit in cases of bilateral hydronephrosis or significant ipsilateral lower pole hydronephrosis. Decompression of the ureterocele is reliably obtained but it seldom obviates the need for more definitive reconstruction.
Female↗
Separate cis sequences and trans factors direct metabolic and developmental regulation of a potato tuber storage protein gene.
The expression of genes encoding patatin, a major tuber protein, is highly tissue-specific but is also modulated by exogenous sucrose. The patterns of transcription observed in potato plants could be due to mechanisms conferring tuber-specificity or they could reflect the concentrations of sucrose found in different tissues. To distinguish between these possibilities, a detailed examination was made of the function of a region of the promoter previously implicated in conferring tissue-specific and sucrose-inducible expression. Internal deletions of this region revealed three separate functional domains regulating expression. The B repeat region acted as a positive activator of transcription in the tuber and was also responsible for a degree of sucrose-inducibility. The distal region of the A repeat repressed transcription in leaf and tuber tissue, while the proximal region of the A repeat was able to confer sucrose-responsiveness. Each of these regions specifically bound nuclear proteins which may be putative transcription factors involved in conferring these responses. The region found to confer sucrose-inducible expression was conserved among some other genes that are also regulated by exogenous sucrose.
Base Sequence↗