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Biomedical subjects

A Smith

Publications and source records attributed to A Smith.

At least 883 records · Page 49Linked to original sources
PubMed1991

Cytotoxic activity of ricin A chain immunotoxins recognising cluster 1, w4 and 5A antigens associated with human small cell lung cancer.

The potential of mouse monoclonal antibodies raised against the human small cell lung cancer (SCLC) cell line SW2 to form active immunotoxins was evaluated using an indirect assay of immunotoxin cytotoxicity. Monoclonal antibodies recognising different SCLC-associated antigens, designated as cluster w4 and cluster 5A antibodies by the First International Workshop on SCLC Antigens, mediated the cytotoxic action of a screening agent made by linking ricin A chain to sheep anti-mouse IgG Fab' fragment. In contrast, monoclonal antibodies belonging to cluster 1 gave no significant cytotoxic effects in conjunction with the screening agent. Immunotoxins made by the direct chemical conjugation of ricin A chain to SWA11 (cluster w4) and SWA20 (cluster 5A) both exhibited selective toxic effects upon the SW2 cell line in tissue culture, inhibiting the incorporation of 3H-leucine by 50% at a concentration (IC50) of approximately 3 x 10(-10) M. An immunotoxin made with SEN36 (cluster 1) was much less potent with an IC50 greater than 1 x 10(-8) M.

Antibodies, Monoclonal↗
PubMed1991

HIV/AIDS prevention.

Explore the source record for details and available documents.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Atrial morphologic features in tricuspid atresia.

We studied the atrial morphology in 110 hearts removed at autopsy from patients with tricuspid atresia. Ten of the patients had had a Fontan operation. We compared the findings in these hearts with those in 30 normal hearts. Prominent eustachian valves were common (40%). The tricuspid "dimple," present in 33 of 100 specimens, denoted the membranous atrioventricular septum and was never related to the right ventricle. Most interatrial communications (85/100) were nonobstructive. A minority of patients with obstructive interatrial communications (13/100 = small, 2/100 = severely obstructive) would be expected to benefit from balloon atrial septostomy early in life. Right atrial hypertrophy was greatest in specimens with restrictive interatrial communications (severely obstructive = 3.2 +/- 0.3 mm, small = 2.1 +/- 0.6 mm) and in those that had been subjected to a Fontan operation (3.2 +/- 0.7 mm), but thickness was also increased in hearts with nonobstructive interatrial communications (1.6 +/- 0.5 mm) compared with normal hearts (1.1 +/- 0.2 mm; p less than 0.001 versus all groups). Of the patients in the series, 11 of 100 had left juxtaposition of the atrial appendages, which may have important implications for the Fontan operation.

Adolescent↗
PubMed1991

Genetic and molecular approach for breeding and use of laboratory fish for the detection of agents with carcinogenic and/or promoting activity.

Xiphophorine fish from wild populations are insusceptible to develop neoplasia. In contrast, certain backcrosses of Xiphophorus maculatus (platyfish) with Xiphophorus helleri (swordtail) as the recurrent parent, produce offspring that develop neoplasia in a Mendelian fashion. We concentrated our research on melanoma. The starting signal for the development of melanoma comes from an accessory v-erbB-related oncogene, x-erbB*, which is highly homologous to the human EGF receptor gene, and is part of a platyfish-specific tumor gene-complex designated as Tu. Normally, the platyfish is protected from its own Tu by Tu-specific regulatory gene systems. The swordtail has neither evolved the Tu-complex nor the regulatory gene systems. Therefore, the backcross procedure dismantles the regulatory gene systems thus permitting Tu-directed melanoma formation. x-erbB* derived from the platyfish, together with the swordtail-derived oncogenes src, sis, pdgf-r, ras, myc, erbA are expressed or overexpressed in the melanoma, and inositol lipid turnover is considerably elevated. x-src and inositol lipid turnover have also been found elevated in the healthy tissues (eg brain) of the tumourous fish. To construct a fish strain which is highly susceptible to mutagenic carcinogens, we introduced a particular regulatory gene, ie an oncosuppressor gene (Bs), into the genome of the animals developing Mendelian inherited melanoma, by introgressive breeding. Bs prevents the strain from germ line-inherited melanoma but, following carcinogen-induced impairment in a somatic cell gives rise to the Tu-directed development of clonal melanoma in a particular fish, x-src activity and inositol lipid turnover are elevated in the tumor but, in contrast to the animals bearing the inherited melanoma, are not elevated in the brain. Promoting carcinogens (tumor promoters) do not induce melanoma in this strain. Similarly, in order to breed a fish strain susceptible to tumor promoters, we introduced a regulatory gene (the oncostatic gene g, golden) coding for a pre-transformational arrest of pigment cell differentiation in the stem cell stage of the fish that develop the Mendelian inherited melanoma. The new strain is incapable of developing melanoma. Its x-src activity and inositol lipid turnover is elevated in the brain indicating that the biochemical processes which were found to be correlated with the hereditary melanoma formation, are running in the new strain without the occurrence of melanoma. Following treatment with tumor promoters that overcome the arrest of pigment cell differentiation, melanoma develops within a very short latent period.

Animals↗
PubMed1991

Probenecid pharmacokinetics in cystic fibrosis.

Probenecid pharmacokinetics were studied in 5 cystic fibrosis (CF) subjects and 5 control subjects at oral dosages of 5, 15, and 30 mg/kg. Serum and urine samples were collected for 8 h after administration and assayed by reverse phase high performance liquid chromatography. Pharmacokinetic parameters were estimated by model-independent methods. All parameters were compared by 2-tailed analysis of variance with two major groupings: patient and dose. Both CF subjects and controls demonstrated dose-dependent kinetics, i.e., decreased elimination constant and decreased total body clearance with increasing dosage. The volume of distribution and time to peak were the only parameters that were not significantly dose dependent. At all dosages studied, we found no significant difference in total body clearance by CF subjects. Urinary recovery in an 8-hour period was not significantly different between CF subjects and controls nor was the percentage of dose recovered in the urine at each dosage level. Time to peak concentration varied widely between 0.5 and 4 h in both CF subjects and controls. We conclude, that CF patients have normal probenecid clearance, and that the standard dose for a CF patient is sufficient to attain a serum area under the curve equivalent to that of controls.

Administration, Oral↗
PubMed1991

Discrimination of initiating and promoting carcinogens in fish.

Xiphophorine fish from wild populations are insusceptible of developing neoplasia. In contrast, certain backcrosses of Xiphophorus maculatus (platyfish) with Xiphophorus helleri (swordtail) as the recurrent parent produce offspring that develop neoplasia in a Mendelian fashion. We concentrated our research on melanoma. To construct a fish strain which is highly susceptible to mutagenic carcinogens, a particular regulatory gene, ie an oncosuppressor gene (Bs), was introduced into the fish developing the Mendelian inherited melanoma by introgression. Bs prevents the progeny from developing melanoma. However, Bs can be impaired by carcinogen-induced somatic mutation which gives rise to the development of clonal melanoma. Activity of the oncogene x-src (measured on pp60x-src kinase activity) and inositol lipid turnover is elevated in the tumor but, in contrast to the animals bearing the inherited melanoma, not in the brain. Tumor promoters do not induce melanoma in this strain. Similarly, in order to breed a fish strain which is highly susceptible to tumor promoters we introduced a regulatory gene, for instance an oncostatic gene (g) coding for a pretransformational arrest of pigment cell differentiation in the stem cell stage of the fish that develop the Mendelian inherited melanoma. The new strain is incapable of developing melanoma. Its x-src kinase activity and inositol lipid turnover is elevated in the brain, indicating that the biochemical processes which were found to be correlated with the hereditary melanoma formation, operate without the occurrence of melanoma. Following treatment of these animals with tumor promoters, melanoma develops within a very short latent period. Our tester strain can discriminate between tumor-initiating and tumor-promoting activities of agents of unknown carcinogenic potential.

Animals↗
PubMed1991

Critical aortic stenosis in early infancy. Anatomic and echocardiographic substrates of successful open valvotomy.

To establish noninvasive criteria by which to manage infants with critical aortic stenosis, we examined 20 heart specimens from infants under 3 months of age and reviewed the clinical course and real time echocardiograms of 20 patients in the same age group. All 20 infants underwent open valvotomy, and in five cases both echocardiographic and postmortem measurements were available for the same heart. The anatomic specimens showed a spectrum of valvular, ventricular, and vascular abnormalities that could be accurately identified by echocardiography. A small left ventricular cavity was usually associated with a narrow ventriculoarterial junction, small ascending aorta, and narrow subaortic region. In these hearts, the mitral valve had a single or grossly hypoplastic papillary muscle with short or "arcuate" tendinous cords. A dilated left ventricular cavity had wider inflow and outflow orifices, and the tension apparatus of the mitral valve was either normal or supported by hypertrophic papillary muscles, at the other end of the spectrum. The survivors (n = 15) and nonsurvivors (n = 5) of open valvotomy showed significant differences in the echocardiographic dimensions of the left ventricle (p less than 0.005), the subaortic region (p less than 0.05), the ventriculoaortic junction (p less than 0.05), the ascending aorta (p less than 0.005), and the mitral valve orifice (p less than 0.001). Moreover, the papillary muscle of the mitral valve was invariably single or hypoplastic with short tendinous cords in the early nonsurvivors. Infants with unfavorable cardiac anatomy tended to present earlier (p less than 0.05) and to have a lower systemic blood pressure (p less than 0.05), and they required prostaglandin E2 to maintain right ventricular support of the circulation through a persistent arterial duct. This study suggests that patients with a small left ventricle (echocardiographic inflow dimension less than 25 mm), a narrow ventriculoaortic junction (less than 5 mm), and a small mitral valve orifice (less than 9 mm) will not achieve a satisfactory surgical result from aortic valvotomy. Such patients should be considered for cardiac transplantation or the Norwood-type of palliation for hypoplastic left heart syndrome.

Aortic Valve↗
PubMed1990

How district health authorities organise cervical screening.

OBJECTIVES: To examine how district health authorities organised cervical screening with respect to Department of Health guidelines and to determine their assessment of the problems encountered. DESIGN: Postal questionnaire sent to all 190 district health authorities in England in 1989. PARTICIPANTS: 190 District health authorities in England. MAIN OUTCOME MEASURES: Population coverage of screening, quality of smear testing, and follow up of abdominal test results in comparison with national guidelines for district cervical screening services, and problems encountered by districts. RESULTS: Replies were received from 178 (94%) of districts, in 143 of which the person named as responsible for cervical screening contributed. All districts implemented a computer managed scheme, 150 by the target date of 31 March 1988, but not all of these conformed with the guidelines. At the time of the survey only just over half called women in the target age group of 20-64 and only 70% expected to meet the target date of 13 March 1993 for completing the call. Considerable variation was evident among the schemes with regard to how they dealt with issues related to population coverage, quality of testing, and follow up of abnormal results. The problems most commonly identified by the districts (n = 174) were laboratory workload (107, 61%), computer software (104, 60%), availability of resources (78, 45%), non-attendance (77, 44%), rate of opportunistic screening (62, 36%), and investigation and treatment (60, 34%). CONCLUSIONS: Current practice in running cervical screening schemes needs to be examined to determine the extent to which it contributes to the goal of reducing mortality from cervical cancer.

Adult↗
PubMed1990

Seasonal affective disorder and season-dependent abnormalities of melatonin suppression by light.

Twelve patients with seasonal affective disorder (SAD) and eleven normal controls were exposed to 2000 lux and 300 lux of artificial full-spectrum light on consecutive nights during the winter. Suppression of melatonin secretion under the two light intensities was measured and the difference between their effects was taken as a measure of light sensitivity. The test was repeated in summer in both groups, when the SAD subjects were well. The SAD but not the normal group showed a significant seasonal variation in sensitivity to light. There was evidence of supersensitivity in the winter but also of subsensitivity to light in the summer.

Adult↗
PubMed1990

Tissue aluminum concentrations stability over time, relationship to age, and dietary intake.

Aluminum concentration was measured in serum, whole blood, hair, and urine by neutron activation analysis. Seventy-six nondemented subjects were investigated. Not all assays were done on all subjects (e.g., serum aluminum on 76 subjects, whole blood aluminum on 42 subjects), but tissue aluminum concentrations were estimated on more than one occasion on 32 subjects. The mean +/- SD aluminum concentration in serum was 0.219 +/- 0.063 micrograms/ml (N = 76), in whole blood 0.368 +/- 0.091 micrograms/ml (N = 42), in urine 0.092 +/- 0.076 micrograms/ml (N = 42), and in hair 6.42 +/- 2.22 micrograms/g (N = 42). Using product moment correlation coefficient there was no significant correlation between age and tissue aluminum concentrations, nor between dietary intake of aluminum and tissue aluminum. The tissue aluminum concentrations were not stable over time even when dietary intake was constant. Tissue aluminum concentrations were measured in 14 patients after 7 days of dietary control and repeated approximately 6 weeks later, again after 7 days of dietary control. There was no significant correlation between the two estimations in any tissue measured. These results suggest that raised tissue aluminum concentrations reported in Alzheimer's disease are not an exaggeration of a normal ageing process, are not likely to be simply secondary to increased dietary aluminum intake, and that Alzheimer's disease does not represent the chronic toxic effect of moderately raised aluminum levels at the upper end of the normal distribution.

Adult↗