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Biomedical subjects

L J Smith

Publications and source records attributed to L J Smith.

At least 235 records · Page 13Linked to original sources

Pathogenesis of massive pulmonary hemorrhage in acute leukemia.

Massive pulmonary hemorrhage is an uncommon complication of leukemia and is generally attributed to thrombocytopenia. However, a platelet deficiency cannot be the entire explanation, since most patients with thrombocytopenia never experience this complication. To better define the reason for intra-alveolar bleeding, we studied the clinical and pathologic findings in three patients with leukemia who died of massive pulmonary hemorrhage. Although the major finding at autopsy in all three cases were widespread intra=-alveolar hemorrhage, evidence of diffuse alveolar damage was also found. In one patient, a lung biopsy specimen (obtained five days before death) showed extensive intra-alveolar hemorrhage by light microscopy, while severe destruction of alveolar walls was detected by electron microscopy. The findings suggest that diffuse alveolar damage plus thrombocytopenia are necessary for massive pulmonary hemorrhage to occur in leukemia.

Adult↗

Influence of methylprednisolone on mouse alveolar type 2 cell response to acute lung injury.

To determine whether corticosteroids influence alveolar type 2 cell events after acute lung injury, we administered 30 mg/kg/day of methylprednisolone (MP) to mice at various times after a single injection of butylated hydroxytoluene (BHT). Tritiated thymidine (3H-T) autoradiographs were used to study type 2 cell proliferation and differentiation. Type 2 cell maturation was evaluated by ultrastructural analysis of lamellar body volume density and area in cells labeled with 3H-T. The BHT damaged type 1 cells and induced proliferation of type 2 cells. Sixty per cent of type 2 cells labeled with 3H-T on Day 3 differentiated into type 1 cells over a 4-day period. Lamellar body area per cell was unchanged. Early administration of MP (Days 1 and 2) inhibited type 2 cell proliferation when lung injury was mild; rebound proliferation occurred afer its discontinuation. The MP failed to inhibit proliferation when lung injury was severe. Prolonged MP administration (Days 1 to 5) resulted in greater type 2 cell proliferation, lung injury, and mortality. Late MP administration (Days 3 and 4) impaired differentiation of type 2 to type 1 cells and more than doubled lamellar body area per cell of new type 2 cells. Important interactions appear to exist between proliferation, differentiation, and maturation of alveolar type 2 cells suggesting that agents that influence one of these processes may influence all aspects of type 2 cell function.

Acute Disease↗

Cholinergic nervous system and immediate hypersensitivity. II. An analysis of pupillary responses.

We studied the pupillary responses of various subjects to carbamylcholine chloride (CCC) in order to assess cholinergic responsiveness. Using the concentration of topical CCC required to induce greater than or equal to 1 mm miosis in the dark as the end point, we compared the responses of five groups of subjects: normal controls; patients with allergic asthma, allergic rhinitis, or intrinsic asthma; and a group who had reproducibly positive skin tests in the absence of symptoms. Subjects with allergic rhinitis or allergic asthma were significantly more sensitive than were normal controls. The patients with positive skin test and negative history were as sensitive as their symptomatic cohorts, suggesting that pupillary cholinergic hyperresponsiveness exists in atopic individuals regardless of symptoms. A small group with intrinsic asthma was examined and found to be even more sensitive than any of the atopic subjects. Thus abnormal hyperresponsiveness of the pupillary constrictor muscles to a topically instilled cholinomimetic has been found in all groups of atopic subjects plus nonallergic asthmatics. Analysis of pupillary responses may prove useful in assessment of autonomic responsiveness.

Adolescent↗

Response of normal and beige mouse alveolar type 2 cells to lung injury.

To study the relation between normal and abnormal alveolar type 2 cells and lung repair after injury, and to gain insight into the defect responsible for the giant lamellar bodies in type 2 cells of the beige mouse (an animal model of the Chediak-Higashi syndrome), we produced lung injury with a single injection of butylated hydroxytoluene (BHT). Type 2 cell proliferation and differentiation were analyzed in light microscopic autoradiographs of mice that had received tritiated thymidine (3H-T) at intervals after the injection of BHT. The approximate age of 3H-T labeled type 2 cells and lamellar body volume density and area were correlated by combining light microscopic autoradiography with ultrastructural morphometry. Type 2 cell proliferation and differentiation were identical in normal and in beige mice. In normal mice, the lamellar body area per cell was unchanged at the time periods studied. In beige mice, the lamellar body area per cell, which was initially 9 times that of the normal mice, decreased to nearly normal values after mitosis, and then increased over the subsequent 7 days of study. Thus, the abnormal type 2 cell of the beige mouse was able to proliferate and differentiate in a normal fashion after lung injury. The beige mouse defect, which results in impaired lamellar body release, was transiently corrected in the perimitotic period. The postmitotic enlargement of lamellar bodies provided a model for studying the basic defect in the Chediak-Higashi syndrome and the process of type 2 cell maturation.

Animals↗

Back to back autoradiography: a method for ultrastructural analysis of light microscopic autoradiographs.

A method for studying radiolabeled cells is described that combines the simplicity of light microscopic autoradiography with the high resolution of electron microscopy. Serial thin (600 A) and thick (1 micron) sections are placed on Formvar-coated slot grids and glass slides, respectively. Labeled cells are visualized on the thick section by autoradiography and may then be studied in the electron microscope by locating the corresponding fields on the grid. This technique permits accurate ultrastructural identification and analysis of radiolabeled cells, yet avoids the need for electron microscopic autoradiography.

Animals↗

Embryonic axis orientation in the mouse and its correlation with blastocyst relationships to the uterus. Part 1. Relationships between 82 hours and 4 1/4 days.

Up until at least 7 1/4 days p.c., the orientation of all axes in the mouse conceptus, embryonic axis included, is directly correlated with two orientations of the 82 h blastocyst within the lumen. These two are: the almost horizontal position of the blastocyst's inner cell mass-abembryonic pole axis and the fixation of its abembryonic pole to either the right wall of the uterine horn (type-R orientation) or to the left (type-L orientation). At 88 h and at 4 1/4 and 6 3/4 - 7 1/4 days equal numbers of conceptuses are found in type R and L orientations. Axes of symmetry also are recognizable in some developmentally advanced 82 h blastocysts and in all older conceptuses. For example, when the inner cell mass-abembryonic axis has become vertically oriented within the lumen by 4 1/4 days, the inner cell mass is oblique to this axis. It is concluded that the 82 h blastocyst's orientation to the uterine walls and floor provides it with positional information used in the location of its axes.

Animals↗

Alpha-adrenergic hyper-responsiveness in asthma.

Because alpha-adrenergic stimulation causes bronchoconstriction, the alpha-adrenergic responsiveness of 21 subjects with allergic asthma was compared with that of 16 subjects with allergic rhinitis and 38 normal control subjects. None of the patients had taken medications for at least 30 days before study. Alpha-adrenergic responsiveness was measured by the capacity of phenylephrine to constrict the cutaneous vascular bed and to dilate the pupillary sphincter muscle. Asthmatic subjects required 4.0 +/- 0.6 ng to reduce their cutaneous blood flow by 50 per cent, whereas normal controls required 32.0 +/- 7.5 ng (P less than 0.005) and subjects with allergic rhinitis required 23.7 +/- 9.4 ng (P less than 0.02). The pupils of asthmatic subjects dilated by greater than 0.5 mm in response to 1.8 +/- 0.14 per cent phenylephrine, patients with allergic rhinitis required 2.4 +/- 0.16 (P less than 0.01), and normal controls needed 2.7 +/- 0.07 (P less than 0.00001). Therefore, the patients with allergic asthma had significantly enhanced alpha-adrenergic responses when compared both to normal subjects and patients with allergic rhinitis; the possibility that increased alpha-adrenergic activity contributes to the asthmatic diathesis warrants further exploration.

Adolescent↗

Serologic distinction between the rabbit kappa L chain allotype b4 and an allele b4.

Rabbit kappa light (L) chain allotypes are controlled by the allelic genes b4, b5, b6, b9 and a recently described allele b4v. The product of the b4v gene differs from that of b4 by at least two amino acid substitutions in the constant region. A serologic distinction between the b4 and b4v allotyes has now been detected by a radioimmune assay using one of six anti-b4 sera tested. The distinction was enhanced by fractionation of this antiserum on an immunoadsorbent containing cottontail rabbit IgG. IgG with L chains of the b4v type are deficient in their ability to inhibit binding of b4 IgG to the antibody preparation. L chains isolated from b4 and b4v IgG samples could not be distinguished by this assay indicating that interaction with an H chain is required for expression of the L chain determinants that differentiate b4 from b4v.

Alleles↗

Effects of methacholine and hypocapnia on airways and collateral ventilation in dogs.

We studied the effects of hypocapnia and methacholine on small airways resistance (Rsaw) and collateral ventilation in anesthetized paralyzed dogs. The animals were ventilated with air while either 10% CO2 or air (hypocapnia) was infused through a segment obstructed with a fiber-optic bronchoscope. Measurements were made before and after instillation of methacholine into the obstructed segment. Collateral resistance (Rcoll) and Rsaw increased with hypocapnia and methacholine. The time constant for collateral ventilation increased with hypocapnia, but did not change with methacholine because of decreases in the compliance of the obstructed segment. We conclude that collateral channels respond to methacholine and hypocapnia in a manner similar to small airways and that local parasympathomimetic stimulation, unlike lung deflation does not increase the time constant for collateral ventilation.

Airway Resistance↗

Plasma pyridoxal-5'-phosphate levels and clinical correlations in chronic hemodialysis patients.

Plasma pyridoxal-5'-phosphate (PLP) was measured by a specific method in 45 stable, chronic hemodialysis patients and 13 normal adults. Despite oral pyridoxine supplements (1 to 5 mg/day) a majority (64%) of patients had low levels. The difference between normals (8.5 +/- 3.7 ng/ml) and dialysis patients (3.6 +/- 3.6 ng/ml) was significant at P less than 0.01. Plasma PLP appeared to decrease with increasing duration of time on dialysis therapy. In vivo clearance studies as well as pre- and postdialysis plasma levels indicated that PLP was not removed by the dialyzer. Mean plasma PLP levels were normal in patients with stable motor nerve conduction velocity and a low transfusion requirement and low in those with decreasing motor nerve conduction velocity or a high transfusion requirement but the difference between the means in each group was not statistically significant. High oral doses of pyridoxine (100 to 200 mg/day) but not low doses (1 to 5 mg/day) restored PLP levels to normal in a majority of patients after 2 weeks.

Adult↗

Expression of group b light chain allotypes in cottontail rabbits.

Group b allotypic determinants (b4, b5, b6, and b9) were detected on cottontail IgG by several assays including immunodiffusion, radioimmune binding, and inhibition of radiobinding. The results indicate that cottontail IgG possess some but not all of the subspecificities present on domestic rabbit IgG. Several cottontail rabbits exhibited three of the four possible allotypic markers. In these instances, however, only two populations of IgG molecules (i.e., phenogroups) could be detected, each bearing one, two, or three of the allotypes. Five separate and distinctive phenogroups were identified. The results suggest that the phenogroups represent products of multiple allelic genes for the constant region of cottontail rabbit kappa light chain.

Animal Population Groups↗