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Biomedical subjects

L J Smith

Publications and source records attributed to L J Smith.

At least 217 records · Page 12Linked to original sources
PubMed1985

Embryonic axis orientation in the mouse and its correlation with blastocyst relationships to the uterus. II. Relationships from 4 1/4 to 9 1/2 days.

Each of the three primary axes of the primitive streak (6 3/4 days p.c.) to C-shaped (9 1/2 days) stage mouse embryo has a specific relationship to the uterine horn axes. By a retrograde analysis of younger sectioned embryos it has been possible to construct an axis fate map for the implanting 4 1/4-day blastocyst and to show how its implantation in one or the other of two specific orientations to the ends and walls of the horn leads to these embryo-horn relationships. The implanting blastocyst axis fate map can be related to an axis fate map of the attached blastocyst (Smith, 1980) since these too are in one or the other of two orientations to the ends and walls of the horn. It is suggested that the asymmetries of the attached and implanting blastocysts that allowed the distinctive attachment and implantation orientations to be recognized, are the initial expressions of a three-dimensional system of positional information that is present in the attached blastocyst.

Animals↗
PubMed1984

Hemopoietic stem cells: their roles in human leukemia and certain continuous cell lines.

Hemopoietic stem cells may give rise to progeny like themselves or undergo determination; this event is followed by a series of maturation divisions ending in proliferatively inert but functional cells. In normal hemopoiesis and acute leukemia stem cell renewal is not exact; proliferative capacity is lost gradually. As a consequence, clonal populations cannot be continued indefinitely. Postdeterministic differentiation normally leads to cellular diversity; following transformation this diversity is increased, with the production of blast cells together with one or more myelopoietic lineage. The blasts are heterogeneous both in their proliferative capacity and their phenotypes, as determined using immunologically defined markers. Both self-renewal and determination are considered to be irreversible in vivo. By contrast, in continuous myelopoietic cell lines self-renewal is sufficiently precise to confer immortality on the populations. Furthermore, both determination and renewal may in some instances be reversible. The differences between normal or leukemic hemopoiesis in vivo and continuous lines in culture limits the value of the latter for studies of normal blood formation or the clonal hemopathies.

Azacitidine↗
PubMed1984

Objective structured clinical examination compared with other forms of student assessment.

Two hundred and twenty nine final year medical students were assessed in paediatrics using an objective structured clinical examination (OSCE) and a traditional viva voce examination, and the results were compared with other assessments of the students made during and at the end of the undergraduate course. Results of the OSCE correlated positively with other forms of assessment and more strongly than the viva voce examination. There was little correlation between the OSCE and viva results. Eighty per cent of students felt the OSCE to be a fairer system than other examinations and all external examiners commented favourably on it. An OSCE is an acceptable alternative to traditional means of examination in paediatrics and may be superior in certain aspects.

Education, Medical, Undergraduate↗
PubMed1984

Lung damage induced by butylated hydroxytoluene in mice. Biochemical, cellular, and morphologic characterization.

This study was designed to characterize the biochemical, cellular, and morphologic events produced in mice by butylated hydroxytoluene (BHT) and to relate these events to changes in extracellular angiotensin-converting enzyme (ACE) activity. On Day 1 after the administration of BHT, bronchoalveolar lavage (BAL) ACE activity increased 4-fold (p less than 0.001), its specific activity relative to BAL protein increased 3-fold (p less than 0.001), and both type 1 cell damage and endothelial cell damage were detected by electron microscopy. The early increase in BAL ACE activity preceded changes in plasma ACE levels, BAL cell number, protein, lactate, and lactate dehydrogenase (LDH) activity in both plasma and BAL, and the ACE content of alveolar macrophages. On Day 2, BAL ACE activity increased 9-fold, BAL protein increased 4-fold (p less than 0.001), BAL LDH activity increased 34% (p less than 0.05), and the BAL cell count doubled (p less than 0.01). Changes in each animal's appearance, body weight, wet and dry lung weights, and plasma ACE levels occurred between Days 3 and 5. The BAL differential cell count, which consisted of greater than 95% macrophages in uninjured mice, did not change until Day 5 when there was a small increase in polymorphonuclear leukocytes (PMN). On Day 7, the number of PMN peaked, and some of the other measures of lung injury began returning toward normal. These results indicate that BAL ACE activity is a sensitive, early marker of BHT-induced lung injury, which appears to reflect damage to the cells of the alveolar-capillary barrier. In addition, PMN do not appear to play a major role in this model of lung injury. Because of its effects on angiotensin, bradykinin, and prostaglandins, the early release of ACE from damaged cells may modulate the subsequent injury.

Animals↗
PubMed1984

Ultrasound-guided periventricular stereotaxis.

Intraoperative ultrasound can aid the biopsy of deep intracranial lesions. It is, perhaps, less clear whether ultrasound could be useful in functional neurosurgery, where the target is not abnormal in echogenicity. As an example, we chose to investigate in a dog model the periventricular gray target, which is frequently the choice for the placement of electrodes to control intractable pain. Autopsies showed the placement of our electrodes with less than 1 mm of error in four of five brains and a 1.5-mm error in the fifth brain. The largest error was seen to occur on the video screen and was due to our failure to tighten the guide properly. The potential advantages of this technique over conventional stereotaxis include the avoidance of: ventricular catheterization, the injection of contrast agent into the ventricles, the necessity for a stereotactic frame, and multiple x-ray exposures. Also, with real time scanning the surgeon has instant visual confirmation of electrode placement and can observe quickly any significant hematoma formation.

Animals↗
PubMed1984

Enzymatic responses to radiation in cultured vascular endothelial and smooth muscle cells.

Confluent monolayers of bovine aortic endothelial and smooth muscle cells were exposed to 0-5.0 Gy of 60Co gamma rays. From 0 to 72 hr after irradiation, the monolayer and culture medium were analyzed for cell (nuclei) number, DNA and protein content, the activities of angiotensin converting enzyme (ACE), lactate dehydrogenase (LDH), and superoxide dismutase (SOD), and LDH isoenzyme profile. Irradiated endothelial cells exhibited a time- and dose-dependent increase in cell detachment, decreased DNA and protein content and reduced ACE active per attached cell, increased LDH and SOD activities per microgram of DNA, and increased LDH activity in the culture medium. The latter was accompanied by a shift from LDH 1 to LDH 4 and 5. The release of LDH activity, observed after 0.5 Gy, was the most sensitive endothelial response, and occurred independent of or preceding cell detachment. Vascular smooth muscle cells contained two to three times more SOD activity than did endothelial cells and exhibited no significant responses to 5.0 Gy.

Animals↗
PubMed1984

Lineage infidelity following exposure of T lymphoblasts (MOLT-3 cells) to 5-azacytidine.

The appearance on single leukemic blast cells of markers of at least two different lineages has been termed lineage infidelity. MOLT-3 cells, a continuous line of human T lymphoblasts, express T cell markers as defined immunologically with monoclonal antibodies. Following a single exposure to 5-azacytidine, other markers, usually associated with non-T cell lineages, appeared transiently. A stable clone with lineage infidelity was obtained by selection from colonies expressing novel markers. Marker expression followed reproducible kinetics during growth. 5-Azacytidine-treated MOLT-3 subclones may be useful models in the study of lineage infidelity and gene expression.

Antibodies, Monoclonal↗
PubMed1983

Airway response to leukotriene D4 in rhesus monkeys.

We studied the effect of leukotriene D4(LTD4) given by aerosol challenge on asthmatic and normal monkeys. The response to LTD4 occurred within 2 min., was prolonged at higher concentrations, was reversed by epinephrine, and more closely resembled an antigen response than a histamine response. Since LTD4 concentrations of 30-100 micrograms/ml produced a response similar to 2-20 mg/ml of histamine, the LTD4 was 300-900 times as potent as histamine on a molar basis. Thus, LTD4, which appears to reproduce an antigen-induced response in rhesus monkeys, may be a mediator of allergic asthma in these animals.

Airway Obstruction↗
PubMed1983

Lineage infidelity in acute leukemia.

Blast cells from 20 patients with acute leukemia (13 diagnosed myeloblastic and 7 as lymphoblastic, using the FAB classification) were studied using antibodies to lineage-specific differentiation markers. The phenotypic findings were usually consistent with the clinical diagnosis. However, examples were encountered where individual blast cells had a cytoplasmic marker of one lineage and a surface marker of a different lineage (lineage infidelity). Six examples of intramyeloid (two different myeloid lineages in the same cell) and three examples of interlineage infidelity (myeloid and lymphoid markers in the same blast cell) were encountered. No doubly marked cells were found in control material consisting of normal marrow cells, marrow regenerating after transplantation, or multilineage colonies derived from marrow in culture. A significant trend was observed relating the presence of lineage infidelity and failure of remission-induction. The data are interpreted as support for abnormal gene expression in leukemia.

Acute Disease↗
PubMed1983

Cellular lineages in normal and leukemic hemopoiesis.

Certain human hemopoietic disorders (the clonal hemopathies) originate in pluripotent stem cells. These include acute myeloblastic leukemia (AML), chronic myelocytic leukemia (CML), polycythemia vera (P vera), and idiopathic myelofibrosis. In each affected individual a single abnormal clone becomes dominant, occupying all hematologic spaces. An understanding of the cellular basis of normal hemopoiesis and these diseases requires consideration of stem cell properties, clonal expansion, and the differentiation programs of various myelopoietic lineages. The blast cells of AML provide a test of hypotheses about normal and leukemic hemopoiesis. The suggestion is advanced that these blasts do not develop because normal programs are blocked or aborted, but rather follow novel programs, assembled abnormally from normal components. The finding of individual blast cells expressing markers of more than one lineage simultaneously is advanced as support for this model.

Animals↗
PubMed1983

The effect of type 2 cell mitosis on the surfactant system of injured mouse lungs.

This study was designed to evaluate the effect of type 2 cell proliferation, and specifically mitosis, on the surfactant system after lung injury. Lung injury was produced in mice with butylated hydroxytoluene (BHT). The LB volume density and the LB area of tritiated thymidine (3H-T) labeled and mitotic type 2 cells were determined by combining light microscopic autoradiography with electron microscopic morphometry. Over a 48-hr period, the LB volume density of proliferating (3H-T-labeled) type 2 cells decreased from 20.7% to 7.6% (p less than 0.001) and the LB area per cell decreased from 9.1 to 2.4 mumol2 (p less than 0.001). These changes were closely related to type 2 cell mitosis, since the LB volume density decreased from 19.2% to 2.9% (p less than 0.001) and the LB area per cell decreased from 9.1 to 1.7 mumol2 (p less than 0.01) between prophase and telophase, but they were independent of the time elapsed since injury. These results indicate that mitosis influenced the LB content of type 2 cells after lung injury and suggest a previously unrecognized link between cell division and the surfactant system of the lung.

Animals↗
PubMed1983

The effect of methylprednisolone on lung injury in mice. Prevention of type 1 cell and endothelial cell damage.

This study was designed to determine whether MP could prevent the BHT-induced damage to the cells comprising the alveolar capillary barrier. Lung injury was produced in mice with an intraperitoneal injection of BHT. MP, 30 mg/kg, or saline was given 1 and 2 days later. Type 1 cell and endothelial cell damage and the percentage of capillaries containing PMNs and platelets were determined by electron microscopic morphometry. The type 2 cell LI was determined by light microscopic autoradiography. After the BHT injection, type 1 cell and endothelial cell damage occurred simultaneously and preceded an increase in the type 2 cell LI. The administration of MP before the appearance of electron microscopic evidence of type 1 cell and endothelial cell injury decreased the type 1 cell damage 2 and 3 days after the BHT injection by 89% (p less than 0.01) and 86% (p less than 0.005), decreased the endothelial cell damage by 46% and 76% (p less than 0.02), and prevented the increase in the type 2 cell LI. However, the administration of MP after type 1 cell and endothelial cell damage failed to prevent further damage or to inhibit the type 2 cell LI. MP had no effect on the percentage of capillaries containing PMNs or platelets. Thus, in the BHT model of acute lung injury, MP can prevent type 1 cell and endothelial cell damage, but its effect depends on the amount of injury present when the corticosteroid is given.

Animals↗
PubMed1982

Autonomic nervous system abnormalities and allergy.

Abnormal autonomic nervous system responsiveness may contribute to the pathogenesis of asthma and other allergic diseases. Therefore, we measured alpha- and beta-adrenergic and cholinergic responsiveness in allergic subjects. Allergic asthmatic subjects had an abnormal adrenergic (alpha = hyperresponsive; beta = hyporesponsive) and cholinergic (hyperresponsive) profile. However, subjects with allergic rhinitis and preallergic subjects (those with positive allergen skin tests without any disease manifestation) had equivalent beta-adrenergic and cholinergic abnormalities. Thus, all allergic subjects showed abnormal beta-adrenergic hyporeactivity and cholinergic hypersensitivity whereas allergic asthma was singularly associated with excessive alpha-adrenergic responsiveness. Autoantibodies against beta-receptors were found predominantly in subjects with beta-adrenergic hyporeactivity. The presence of these autoantibodies and the physiologic abnormalities associated with their presence suggests a causitive relationship.

Adult↗