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Biomedical subjects

C Stanley

Publications and source records attributed to C Stanley.

At least 55 records · Page 3Linked to original sources
PubMed1991

Gene transfer into rat airway epithelial cells using retroviral vectors.

Primary cultures of epithelial cells from adult rat tracheas were maintained in vitro on collagen matrices and were exposed to a murine retrovirus vector expressing the E. coli beta-galactosidase gene. Infection was carried out on cells grown as monolayers under medium and on cells grown on raised platforms. Cells maintained at an air-medium interface were highly susceptible to infection with the vector, showing an efficiency of infection of 20-25%, compared with an efficiency of less than 1% for cells grown under medium. Infected beta-galactosidase-expressing cells were seeded into denuded tracheas and were capable of partially repopulating the denuded tracheas grafted subcutaneously into host rats. The susceptibility of these cells to retroviral infection suggests an approach to the treatment of some pulmonary genetic disorders such as cystic fibrosis.

Aerosols↗
PubMed1991

A mathematical description of pressures in alveolar pores of Kohn.

Small interalveolar holes within the lung are called pores of Kohn. Some researchers have correlated enlarged pore size with diseases, e.g. emphysema, that are characterized by tissue destruction. Mathematical models of the pressures generated in closed, fluid-filled and open, fluid-lined pores demonstrate that pressures capable of rupturing lung tissue can be developed in a pore due to the surface tension and shape of the air-liquid interface. Pore enlargement accompanied by tissue destruction is presented as a possible mechanism for the disease process observed during aging and the development of emphysema in the lung.

Humans↗
PubMed1991

Metabolic and work efficiencies during exercise in Andean natives.

Maximum O2 and CO2 fluxes during exercise were less perturbed by hypoxia in Quechua natives from the Andes than in lowlanders. In exploring how this was achieved, we found that, for a given work rate, Quechua highlanders at 4,200 m accumulated substantially less lactate than lowlanders at sea level normoxia (approximately 5-7 vs. 10-14 mM) despite hypobaric hypoxia. This phenomenon, known as the lactate paradox, was entirely refractory to normoxia-hypoxia transitions. In lowlanders, the lactate paradox is an acclimation; however, in Quechuas, the lactate paradox is an expression of metabolic organization that did not deacclimate, at least over the 6-wk period of our study. Thus it was concluded that this metabolic organization is a developmentally or genetically fixed characteristic selected because of the efficiency advantage of aerobic metabolism (high ATP yield per mol of substrate metabolized) compared with anaerobic glycolysis. Measurements of respiratory quotient indicated preferential use of carbohydrate as fuel for muscle work, which is also advantageous in hypoxia because it maximizes the yield of ATP per mol of O2 consumed. Finally, minimizing the cost of muscle work was also reflected in energetic efficiency as classically defined (power output per metabolic power input); this was evident at all work rates but was most pronounced at submaximal work rates (efficiency approximately 1.5 times higher than in lowlander athletes). Because plots of power output vs. metabolic power input did not extrapolate to the origin, it was concluded 1) that exercise in both groups sustained a significant ATP expenditure not convertible to mechanical work but 2) that this expenditure was downregulated in Andean natives by thus far unexplained mechanisms.

Acclimatization↗
PubMed1991

Skeletal muscle metabolism and work capacity: a 31P-NMR study of Andean natives and lowlanders.

Two metabolic features of altitude-adapted humans are the maximal O2 consumption (VO2max) paradox (higher work rates following acclimatization without increases in VO2max) and the lactate paradox (progressive reductions in muscle and blood lactate with exercise at increasing altitude). To assess underlying mechanisms, we studied six Andean Quechua Indians in La Raya, Peru (4,200 m) and at low altitude (less than 700 m) immediately upon arrival in Canada. The experimental strategy compared whole-body performance tests and single (calf) muscle work capacities in the Andeans with those in groups of sedentary, power-trained, and endurance-trained lowlanders. We used 31P nuclear magnetic resonance spectroscopy to monitor noninvasively changes in concentrations of phosphocreatine [( PCr]), [Pi], [ATP], [PCr]/[PCr] + creatine ([Cr]), [Pi]/[PCr] + [Cr], and pH in the gastrocnemius muscle of subjects exercising to fatigue. Our results indicate that the Andeans 1) are phenotypically unique with respect to measures of anaerobic and aerobic work capacity, 2) despite significantly lower anaerobic capacities, are capable of calf muscle work rates equal to those of highly trained power- and endurance-trained athletes, and 3) compared with endurance-trained athletes with significantly higher VO2max values and power-trained athletes with similar VO2max values, display, respectively, similar and reduced perturbation of all parameters related to the phosphorylation potential and to measurements of [Pi], [PCr], [ATP], and muscle pH derivable from nuclear magnetic resonance. Because the lactate paradox may be explained on the basis of tighter ATP demand-supplying coupling, we postulate that a similar mechanism may explain 1) the high calf muscle work capacities in the Andeans relative to measures of whole-body work capacity, 2) the VO2max paradox, and 3) anecdotal reports of exceptional work capacities in indigenous altitude natives.

Acclimatization↗
PubMed1991

Cardiovascular adaptations in Andean natives after 6 wk of exposure to sea level.

Six male Quechua Indians (34.0 +/- 1.1 yr, 159.5 +/- 2.1 cm, 60.5 +/- 1.6 kg), life-long residents of La Raya, Peru (4,350-m altitude with an average barometric pressure of 460 Torr), were studied using noninvasive methods to determine the structural and functional changes in the cardiovascular system in response to a 6-wk deacclimation period at sea level. Cardiac output, stroke volume, and left ventricular ejection fractions were determined using radionuclide angiographic techniques at rest and during exercise on a cycle ergometer at 40, 60, and 90% of a previously determined maximal O2 consumption. Subjects at rest were subjected to two-dimensional and M-mode echocardiograms and a standard 12-lead electrocardiogram. Hemoglobin and hematocrit were measured on arrival at sea level by use of a Coulter Stacker S+ analyzer. After a 6-wk deacclimation period, all variables were remeasured using the identical methodology. Hemoglobin values decreased significantly over the deacclimation period (15.7 +/- 1.1 to 13.5 +/- 1.2 g/dl; P less than 0.01). The results indicate that the removal of these high-altitude-adapted natives from 4,300 m to sea level for 6 wk results in only minor changes to the cardiac structure and function as measured by these noninvasive techniques.

Acclimatization↗
PubMed1991

Frontal periventricular cysts on the first day of life. A one-year clinical follow-up and its significance.

During a 6-year period, the prospective interpretations of routine screening cranial ultrasound on 1453 premature infants indicated frontal periventricular cysts in 7 infants without other intracranial abnormalities during the first 24 hours after birth. The medical records of these 7 infants and their mothers and a developmental assessment at age 1 year were also reviewed. The cysts were predominantly single and unilateral and ranged in size from 2 to 11 mm. One infant had bilateral subependymal cysts as well as frontal periventricular cysts. All 7 infants before 1 year of age demonstrated mild neurological deficiencies. However, 6 of 7 demonstrated partial or complete resolution of their neurological impairment by the end of 1 year. One infant was lost to clinical follow-up. The presence of these frontal periventricular cysts in the first 24 hours after birth suggests an in-utero event, such as antepartum hemorrhagic infarction, as their etiology.

Brain Diseases↗
PubMed1990

Neurosonographic features of periventricular echodensities associated with cerebral palsy in preterm infants.

We studied the value of neonatal neurosonograms in preterm infants for predicting the development of cerebral palsy (CP). All infants born at less than 33 weeks of gestation who were admitted to the intensive care nursery of Thomas Jefferson University Hospital from 1982 to 1986 were serially studied with cranial ultrasound methods that reliably detect neonatal periventricular echodensities (PVE) and cysts that are 2 mm in diameter or larger. PVE were graded as mild or as moderate to severe, and cyst size was classified by widest diameter as either large (greater than or equal to 3 mm) or small (less than 3 mm). All 127 surviving infants with PVE or cyst formation or both were followed until spastic forms of CP could be diagnosed or excluded during late infancy. All 26 of the infants in whom spastic CP developed had moderate or severe PVE in the area superior and lateral to the caudothalamic notch as noted on the parasagittal images of the neonatal neurosonograms. All these infants also developed cysts in the periventricular region within the area of the previously noted PVE. Mild or moderate to severe PVE were not associated with the development of spastic CP in 101 infants. Cysts developed in the area of PVE in the neurosonographic studies of 42 of these 101 infants. Mild PVE without cysts and moderate to severe PVE without cysts had negative predictive values for CP of 69% and 76%, respectively. By contrast, the presence of moderate to severe PVEs with large cyst formation had positive and negative predictive values of 90% and 93%, respectively, and was the most sensitive and specific neurosonographic finding for predicting CP, with an efficiency of 92%. The presence or absence of intracranial hemorrhage did not increase the efficiency of the ultrasound test results.

Brain Diseases↗
PubMed1989

Amenorrhea in an ovulatory woman despite a normal uterine cavity: case report.

A 35-year-old nulliparous woman came to us for treatment of amenorrhea. Evaluation demonstrated normal ovulation with appropriate results of sequential endometrial biopsies during the luteal phase. The only abnormality found was an elevated serum level of follicle-stimulating hormone in the early follicular phase, and it is hypothesized that this somehow leads to atrophy of the endometrium without shedding.

Adult↗
PubMed1989

Effect of isozyme-selective inhibitors of phosphodiesterase on histamine-stimulated cyclic AMP accumulation in guinea-pig hippocampus.

Addition of histamine (0.1 mM) to guinea-pig hippocampal slices causes a 20- to 30-fold increase in the accumulation of cyclic AMP compared with basal levels. This accumulation represents a balance between cyclic AMP production by adenylate cyclase and cyclic AMP breakdown mediated by phosphodiesterase (PDE). However, brain tissues are known to contain several different PDE isozymes. To determine which are involved in this response to histamine, the effect of isozyme-specific PDE inhibitors on cyclic AMP accumulation was examined in the hippocampus. MB 22948 (0.1 mM), an inhibitor of PDEs I and II, had no significant effect on the response to either 1 microM or 0.1 mM histamine. SKF 94120 (0.1 mM), a PDE III inhibitor, was also without effect in the presence of 1 microM histamine, although with 0.1 mM histamine, it caused a weak (1.25-fold compared with control), but statistically significant, enhancement of cyclic AMP accumulation. However, both rolipram (0.1 mM), a PDE IV inhibitor, and 3-isobutyl-1-methylxanthine (0.1 or 1 mM), an inhibitor of all forms of PDE, significantly increased cyclic AMP accumulation (2.8- to 6.5-fold compared with controls), and the relative size of this effect decreased with increasing histamine concentration. It is concluded that PDE IV is the main PDE isozyme involved in cyclic AMP turnover in guinea-pig hippocampal slices responding to histamine.

1-Methyl-3-isobutylxanthine↗
PubMed1989

Acute profound dystonia in infants with glutaric acidemia.

Acute profound dystonia developed in three previously well infants who were found to have glutaryl-CoA dehydrogenase deficiency in cultured skin fibroblasts. Two patients had excessive urinary excretion of glutaric acid, but one did not. Neuroradiologic studies performed in all three patients at the onset of their illnesses revealed large CSF-containing spaces both within the sylvian fissures and anterior to the temporal lobes. Pathologic examination of the brain of one patient demonstrated cerebral and cerebellar atrophy, shrinkage of the putamen, and white matter vacuolation. Glutaric acidemia may be a common cause of acquired persistent dystonia or choreoathetosis in infancy.

Atrophy↗
PubMed1988

Immunity to hepatitis B: analysis of antibody and cellular responses in recipients of a plasma-derived vaccine using synthetic peptides mimicking S and pre-S regions.

The potential of a panel of synthetic HBsAg peptides as components of a synthetic hepatitis B vaccine was assessed. Each was used in turn as probes to analyse human immune responses to a licensed plasma-derived HBV vaccine. Both humoral and cellular responses were analysed with synthetic peptides representing residues 124-147 of the surface antigen of the virus (HBsAg) and residues 126-140 of the pre-S2 region. Antibody levels and affinities were assessed in radioimmunoassays with synthetic linear and cyclical forms of surface antigen peptides 124-137 and 139-147, with the gp30p25 polypeptide complex of HBsAg and with the linear pre-S2 peptide 126-140. Levels and affinities of antibodies to the antigens increased with time during immunization. However, antibodies binding the cyclical peptide representing amino acids 139 to 147 (C139) were present at higher levels and had higher affinities than were antibodies binding the other peptides, indicating that C139 more closely approximates a domain on the native antigen than do the other peptides. No humoral responses were measured with the pre-S2 peptide. Cellular responses were assessed by in vitro stimulation of peripheral blood lymphocytes by HBsAg and by the synthetic peptides. All vaccine recipients had demonstrable lymphocyte responsiveness to HBsAg after both second and third doses of the vaccine. Of the S and pre-S peptides used, only L124 failed to induce lymphocyte stimulation in all recipients. However, there were individual variations in both the time of initial responsiveness to peptides and in the level and time of maximal stimulation. Stimulation by native HBsAg particles, which corresponded to the appearance of anti-HBs antibody, preceded that observed using synthetic peptides. In all recipients, maximum stimulation indices with HBsAg were significantly higher than those observed with the peptides. In contrast to the absence of pre-S2 antibody, the lymphocytes from all recipients showed positive stimulation in response to the peptide representing residues 126-140 of the pre-S2 region. None of these individuals had antibodies to pre-S or an HB core peptide sequence nor did their lymphocytes respond to a synthetic peptide representing an HB core sequence.

Hepatitis B↗
PubMed1986

Late effects after treatment of twenty children with soft tissue sarcomas of the head and neck. Experience at a single institution with a review of the literature.

Twenty children with soft tissue sarcomas of the head and neck, treated at the Children's Hospital of Philadelphia and the Hospital of the University of Pennsylvania from 1972 to 1981, were evaluated for the late deleterious effects of treatment. All patients received radiation therapy and combination chemotherapy with vincristine, dactinomycin, and cyclophosphamide; certain patients also received Adriamycin (doxorubicin). All had ophthalmologic, otologic, growth, and cosmetic evaluations; 15 also had dental and maxillofacial examinations. The median age at diagnosis was 6 years (range, 7 months-13 years). Median follow-up from time of diagnosis was 5.5 years with a minimum of 3 years in all but four patients. The major problems encountered were related to the eyes (xerophthalmia and cataracts), ears (hearing loss), teeth (maleruption and caries), glandular structures (xerostomia, hypopituitarism), and development (craniofacial deformity). It is concluded that children treated for soft tissue sarcomas of the head and neck with combined modality therapy, including radiation enhancers, may show a variety of late treatment-related adversities. These children require close multidisciplinary follow-up for detection of late effects in order that appropriate prophylactic or symptomatic treatment can be instituted to minimize their consequences.

Adolescent↗
PubMed1986

Antibody responses to recombinant and plasma derived hepatitis B vaccines.

The antibody response to hepatitis B surface antigen (anti-HBs) induced in 25 recipients of a recombinant hepatitis B vaccine derived from yeast was compared with that induced in 25 recipients of a vaccine prepared from hepatitis B surface antigen (HBsAg) derived from plasma. Anti-HBs affinity and specificity were compared using assays of antibody affinity with two different antigens, a complex of the major polypeptide of HBsAg (p25; molecular weight 25 000 daltons) covalently linked to its glycosylated form (gp30) prepared from native purified HBsAg, and a cyclical synthetic peptide representing amino acid residues 139-147 of the major polypeptide of HBsAg and known to represent a major part of an a determinant. There was no difference in anti-HBs affinity or molar antigen binding sites of the antibody measured with either antigen between the two groups. All subjects in both groups produced antibody that bound to the gp30/p25 complex antigen, whereas 22 of the recipients of the plasma derived vaccine compared with 24 of those receiving the yeast derived vaccine produced antibodies that bound to the cyclical synthetic peptide 139-147. These results support the finding of similar levels of anti-HBs, measured by commercial solid phase radioimmunoassay, in the two vaccine groups after three doses of vaccine. These results show no significant difference in the quantity, quality, or specificity of the anti-HBs response induced by the recombinant hepatitis B vaccine and the plasma derived hepatitis B vaccine.

Antibodies, Viral↗
PubMed1986

Antibody affinity maturation in selectively bred high and low-affinity mice.

The affinity of serum antibodies produced by selectively bred lines of mice [high affinity, low affinity, low nonmaturing (N/M)] injected with T-dependent [human serum albumin (HSA), dinitrophenylated bovine gamma-globulin (DNP-BGG)] and T-independent (DNP-Ficoll) antigens in saline and adjuvant has been determined. The lines of mice differ significantly in the affinity of antibody produced to T-dependent antigens injected in saline but not to the T-independent antigen. Unlike mice of the high and low-affinity lines, low-affinity N/M mice failed to show affinity maturation to HSA and DNP-BGG injected in Freund's incomplete adjuvant. However, low-N/M mice responded to DNP-Ficoll injected in adjuvant by the production of antibody of affinity comparable to that produced in the other lines and with a similar maturation in affinity. Carrier priming resulted in the suppression of anti-hapten antibody affinity in all lines but low-N/M mice showed significantly greater suppression late in the response to challenge. Low doses of cyclophosphamide produced a significant increase in affinity in low-N/M mice. These results suggest that the failure of low-N/M mice to show affinity maturation results from increased suppressor T cell activity. The availability of the selectively bred mice provides a useful model for the detailed study of the cellular basis of the control of antibody affinity maturation.

Adjuvants, Immunologic↗
PubMed1986

Neonatal neurosonographic correlates of cerebral palsy in preterm infants.

Serial neurosonographic examinations are routinely performed at frequent intervals during the nursery course of all preterm infants of 33 weeks or less gestation who are admitted to the intensive care nursery of Thomas Jefferson University Hospital. After discharge, the following survivors during the past 5 years had repeated ultrasound examinations until the anterior fontanel closed and clinical assessments until the presence or absence of cerebral palsy at a minimum age of 12 months was established: all infants with grade III/IV intracranial hemorrhage, periventricular echodensity and periventricular cyst formation, selected infants with either normal ultrasound findings or grade I/II intracranial hemorrhage. Fifteen survivors were found to have cerebral palsy, and all had at least one of the following ultrasound abnormalities: diffuse, bilateral, and multiple periventricular cysts 3 mm or more in diameter that persisted beyond term age, bilateral asymmetrical dilation of the lateral ventricles following grade III intracranial hemorrhage with small periventricular cysts, and ventricular porencephaly following an ipsilateral grade IV intracranial hemorrhage. The periventricular cysts were usually preceded by extensive echodensities of the white matter surrounding the lateral ventricles; these findings were suggestive of periventricular leukomalacia and were the most common abnormal findings on ultrasound in the infants with cerebral palsy. Of 124 infants without cerebral palsy, 121 had no or less severe abnormal findings on ultrasound; the exceptions were three infants with bilateral persistent large periventricular cysts who had normal motor development in late infancy.

Brain↗
PubMed1985

Cranial ultrasound and clinical studies in preterm infants.

Serial ultrasound imaging of the brain was used to determine the ventricular index (VI), and the ratio (VR) of the VI to the cranial hemidiameter during the nursery course and first year post-term in preterm infants of less than 33 weeks gestation. Twenty-nine of the infant survivors with no intracranial hemorrhage or major medical complication during their nursery course composed group 1. Twenty-two survivors with intracranial hemorrhage unassociated with early ventricular dilation composed group 2. Group 3 was comprised of 10 other survivors who had neonatal intraventricular hemorrhage with early ventriculomegaly; all 10 infants had at least one major medical complication during their neonatal course. In groups 1 and 2 the VR decreased and the VI increased significantly with age post-conception. Infants in group 3, compared with those in groups 1 or 2, had decreased occipitofrontal growth during the early postnatal period and increased VR and VI during the neonatal period and first year post-term. These results suggest that the ventriculomegaly associated with neonatal intracranial hemorrhage cannot be explained by posthemorrhagic hydrocephalus alone and may also be related to cerebral atrophy or decreased brain growth or both. Neurodevelopmental assessments at 20 to 30 months of age disclosed significantly lower Bayley Motor Development scores in group 3 compared with groups 1 or 2. Four infants in group 3, but none in groups 1 or 2, had cerebral palsy. The neurodevelopmental deficits in group 3 infants may reflect the complex pathogenesis of the ventriculomegaly as well as the effects of the intraventricular hemorrhage and posthemorrhagic hydrocephalus.

Cephalometry↗