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Biomedical subjects

P Scott

Publications and source records attributed to P Scott.

At least 163 records · Page 9Linked to original sources
PubMed1988

Infants with cystic fibrosis: pulmonary function at diagnosis.

Meconium ileus (MEC), failure to thrive (FTT), and a combination of FTT and pulmonary symptoms (COMB) are the most frequent symptoms of cystic fibrosis (CF) at the time of diagnosis. The purpose of this study was to compare to normal controls (NC) the pulmonary function of CF infants at the time of diagnosis, when grouped by these symptoms. The measurements of pulmonary function included oxygen saturation (SaO2), functional residual capacity (FRC), mixing index (MI), total respiratory system compliance (Crs), and maximal flow at FRC (VmaxFRC). Compared to NC (n = 33), the MEC group (n = 5) had a higher MI (54 vs. 42%) and no difference in SaO2, Crs or VmaxFRC. There were no significant differences between FTT (n = 8) and NC groups although there was a tendency for Crs to be lower in the FTT group (5.1 vs. 6.8 ml/cm H2O). When compared to all other groups, the COMB group (n = 11) had significantly lower SaO2, MI, Crs, and VmaxFRC. The normal lung function in the MEC group is consistent with the normal anatomy reported in CF infants dying secondary to meconium ileus. Longitudinal evaluation of the infants in this study, following initiation of care as patients with a diagnosis of CF, may allow us to determine whether symptoms at diagnosis remain an important determinant of lung function in infancy.

Cystic Fibrosis↗
PubMed1988

Relationships between the cardiovascular effects of alpha-methyldopa and its metabolism in pontomedullary noradrenergic neurons of the rabbit.

We compared the biotransformation of equipotent intracisternal (i.c., 600 micrograms/kg) and intravenous (i.v., 50 mg/kg) doses of alpha-methyldopa (alpha-MD) to alpha-methylnorepinephrine (alpha-MeNE) in the five major (A1, A2, A5, A6, and A7) noradrenergic nuclei of the rabbit brain, in relation to their cardiovascular effects. Peak effects on blood pressure and heart rate occurred 2-3 h after administration and persisted for 8 h. Three hours after i.v. alpha-MD, norepinephrine (NE) content throughout the five cell group regions was greatly reduced. However, total catecholamine (CA) content (NE plus alpha-MeNE) in the five cell groups increased by up to 300% due to accumulated alpha-MeNE. Eight hours after the i.v. dose, CA content throughout all five cell groups remained elevated. Following i.c. alpha-MD, a similar pattern of effect was observed in the A1, A2, and A5 regions. In the A6 and A7 regions, the effects were small and transient. Three hours after the i.c. dose, there was some biotransformation of alpha-MD but CA content was not affected. By 8 h, alpha-MeNE accounted for only a small fraction of the CA content. These results suggest that A1, A2, and A5 areas could be contributing to alpha-MD's cardiovascular effects. The elevation in CA content may be responsible for the activation of noradrenergic depressor pathways and blood pressure reduction.

Animals↗
PubMed1987

Vaccination against cutaneous leishmaniasis in a murine model. II. Immunologic properties of protective and nonprotective subfractions of soluble promastigote extract.

We have previously demonstrated that BALB/c mice can be protected against a fatal infection with Leishmania major by i.p. immunization with a soluble leishmanial antigen (SLA) preparation in conjunction with the adjuvant, Corynebacterium parvum (CP). In this study, SLA was separated into nine distinct fractions by anion exchange liquid chromatography, and the fractions were analyzed for their ability to stimulate T cells obtained from immunized mice, to be recognized by vaccine-induced antibodies, and to induce protective immunity. While all but one of the fractions were recognized by antibodies from SLA + CP immunized mice, only two fractions (fractions 1 and 9) stimulated lymphocytes to produce macrophage-activating factor and elicited significant delayed-type hypersensitivity in vivo. When mice were immunized with the fractions, only fraction 9 stimulated significant immunity (76% protection in seven experiments). Proteins (accounting for 1.3% of the total in SLA) appear to be responsible for the protection elicited with fraction 9, since protease treatment of this fraction destroyed its immunogenicity. Thus, a partially purified protective protein antigen fraction has been obtained and protection with this fraction correlated with cell-mediated immune responses. However, these results also demonstrate that the ability of leishmanial antigens to be recognized by T cells and produce macrophage-activating factor does not in itself predict whether such molecules will induce immunity, suggesting that protective leishmanial antigens may have additional unique properties.

Animals↗
PubMed1987

Vaccination against cutaneous leishmaniasis in a murine model. I. Induction of protective immunity with a soluble extract of promastigotes.

BALB/c mice can be protected against a fatal Leishmania major infection by immunization with whole radio-attenuated promastigotes; however, neither the antigens responsible for protection nor the protective immunologic mechanisms have been defined. In this study, the ability of promastigote fractions to elicit similar immunity to that obtained with whole organisms, and the immune responses associated with such protection were analyzed. Intraperitoneal immunization with a soluble, membrane-free parasite extract was found to induce protection against L. major challenge equal to that obtained with whole organisms. Induction of immunity (89% protection in seven experiments) was most effective with 100 micrograms of the soluble leishmanial antigen (SLA) and required concomitant injection of the bacterial adjuvant, Corynebacterium parvum (CP), followed by an i.p. boost of SLA alone 1 wk later. Vaccinated animals exhibited Leishmania-specific cell-mediated immunity, as assessed both by lymphocyte transformation and the production of macrophage-activating factors (MAF). In addition, although SLA + CP-immunized mice failed to exhibit delayed-type hypersensitivity (DTH) before challenge, splenic lymphocytes from these mice could transfer a local DTH reaction to naive recipients. Immunization also induced the production of antibodies against two major metabolically labeled proteins of m.w. 30,000 and 53,000, but failed to stimulate a detectable humoral response against promastigote surface antigens. Thus, these experiments demonstrate that vaccine-induced immunity against cutaneous leishmaniasis is strongly associated with the induction of cell-mediated immunity, but does not require the development of an antibody response to promastigote surface antigens. In addition, these studies establish the feasibility of employing soluble, nonmembrane-derived parasite material as a source of protective immunogens.

Adjuvants, Immunologic↗
PubMed1987

Evaluation of pulmonary parenchymal disease by magnetic resonance imaging.

Thirty-eight patients with a wide variety of different disorders of the lung have been imaged using magnetic resonance. The disorders studied include congenital abnormalities, acute and chronic inflammation, vascular disorders, primary and secondary tumours of the lung, haematomas and infarcts. Magnetic resonance imaging identified all lesions seen on chest radiographs, but it is not quite as sensitive as computed tomography is for detection of very small abnormalities. Magnetic resonance may provide information to aid in differentiation of a wide variety of disorders causing diffuse pulmonary abnormality and might also prove helpful in differentiating acute inflammation from pulmonary collapse or fibrosis. In some disorders, such as lobar emphysema, cystic adenomatoid malformation and sequestration, the findings on the magnetic resonance scan alone will permit a correct diagnosis to be made in many cases. It is believed that magnetic resonance imaging has more potential for pulmonary imaging than has previously been recognised.

Adolescent↗
PubMed1986

B lymphocytes are required for the generation of T cells that mediate healing of cutaneous leishmaniasis.

The role that B lymphocytes and/or antibodies play in the healing of Leishmania major infections in genetically resistant C3H/HeN mice was investigated by monitoring the course of infection in animals that had been B cell depleted by treatment from birth with anti-IgM sera (mu-suppressed). L. major infection of mu-suppressed C3H/HeN mice produced lesions that were significantly larger than those induced in control animals, and failed to heal. Moreover, vaccinated mu-suppressed mice also developed chronic nonhealing infections, although their lesions were initially smaller than those developed by nonvaccinated mu-suppressed controls. The enhanced susceptibility of mu-suppressed mice could be completely overcome by adoptive transfer of T lymphocytes from mice that had spontaneously healed their lesions, and to a lesser extent by T lymphocytes from normal animals. Anti-leishmanial antibody responses were completely absent in mu-suppressed mice, regardless of whether they were lymphocyte reconstituted, whereas delayed type hypersensitivity (DTH) to leishmanial antigens was present in normal and mu-suppressed animals. The ability of immune T cells to protect mu-suppressed mice without restoring humoral responsiveness clearly indicates that antibodies are not necessary for healing leishmanial infections. Instead, the observed effect of mu-suppression argues that B lymphocytes are required for the generation of an effector T cell population, apparently unrelated to DTH, which mediates the healing of cutaneous lesions. These results thus provide the first evidence for the B cell and/or Ig dependency of a T cell population that is critical for the development of immunity against a microbial agent.

Animals↗
PubMed1986

A spectrum in the susceptibility of leishmanial strains to intracellular killing by murine macrophages.

The susceptibility of 26 strains and clones of Leishmania to in vitro killing by lymphokine (LK)-activated macrophages was determined. A spectrum in the susceptibility of Leishmania to macrophage killing was observed. Some leishmanias were completely resistant to killing, including some but not all of the L. mexicana strains studied. This resistance was expressed in amastigotes and stationary growth-phase promastigotes, but not in logarithmic promastigotes. In contrast, some L. braziliensis parasites failed to survive within either activated or nonactivated macrophages. Between these two extremes were strains that survived within nonactivated macrophages, but were readily killed within activated macrophages. These included L. donovani, L. major, and some L. mexicana strains. Finally, one L. mexicana strain (WR357) was found to be susceptible to killing at high LK concentrations, but was relatively resistant at lower LK concentrations or at cutaneous temperatures. The observed differences in susceptibility to macrophage-mediated microbicidal activity may explain, in part, the variable pathogenesis of leishmanial infections.

Animals↗
PubMed1986

A semiquantitative probe for radiation-induced normal tissue damage at the molecular level.

Sheep antibodies to bovine type I collagen were employed in the immunohistochemical detection of type I collagen in lung tissue sections of irradiated LAF1 mice. A video image digitizing system was developed to estimate collagen levels, by assigning a numerical value (0-63) to each of approximately 53,800 picture elements (pixels) in the microscope field, according to the collagen-dependent fluorescence intensity at each locus. For lungs harvested 52 weeks subsequent to graded doses of 60Co gamma radiation between 0 and 10 Gy, a dose-dependent increase in type I collagen was observed in the alveolar walls. A reproducible increase was evident for doses as low as 5 Gy: doses of 7 to 10 Gy elicited type I collagen levels significantly elevated with respect to those of age-matched controls. These results are consistent with a role for type I collagen in the development of radiation-induced pulmonary fibrosis. The assay system developed here will be used to explore the role of connective tissue macromolecules in the development of radiation pneumonitis and fibrosis.

Animals↗
PubMed1985

Sarcoidosis and its neurological manifestations.

Neurosarcoidosis is a disorder that is difficult to diagnose and manage. We assessed its neurological manifestations in 649 patients seen at The Johns Hopkins Hospital, Baltimore, from 1975 through 1980. Neurological problems could be attributed to neurosarcoidosis in 33 patients (5.1%). The presenting manifestation of sarcoidosis was neurological in 16 (48%) of them. Cranial neuropathy was the most frequent problem, and a peripheral facial nerve palsy was the single most common abnormality. Other manifestations were aseptic meningitis, hydrocephalus, parenchymatous disease of the central nervous system, peripheral neuropathy, and myopathy. Three-quarters of the patients were treated with steroids. The outcome was good in 27 (82%) of 33 episodes of neurological dysfunction in 25 patients with a well-documented clinical course. A thorough investigation of patients with suspected neurosarcoidosis is recommended to establish the diagnosis, delineate the extent of disease, and guide therapy.

Adult↗
PubMed1985

The respiratory burst is not required for killing of intracellular and extracellular parasites by a lymphokine-activated macrophage cell line.

The macrophage cell line, IC-21, was found to be incapable of producing the oxygen products associated with the respiratory burst. However, IC-21 cells were activated by lymphokine (LK) to kill intracellular (Leishmania donovani amastigotes) and extracellular (Schistosoma mansoni larvae) parasites, as well as tumor cells. In each case, the cytotoxicity exhibited by activated IC-21 cells and activated peritoneal macrophages was indistinguishable. However, nonactivated IC-21 cells were unable to kill L. donovani log-growth phase promastigotes, while nonactivated peritoneal macrophages destroyed greater than 90% of the initial infection. These results indicate that amastigotes and schistosome larvae are susceptible to killing by nonoxidative cytotoxic mechanism induced by lymphokine activation but, on the other hand, support the concept that the killing of log-growth phase promastigotes by nonactivated cells is dependent upon the respiratory burst. We propose that the IC-21 cell line may be a useful model for studying nonoxidative killing functions of activated macrophages.

Animals↗