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Biomedical subjects

G J Smith

Publications and source records attributed to G J Smith.

At least 163 records · Page 9Linked to original sources
PubMed1986

Altered morphology, growth, and biosynthetic activity of a type 2 pneumocyte-related cell strain induced by lymphokine-enriched supernatants of mitogen-stimulated spleen cells.

Hypertrophy and hyperplasia of type 2 pneumocytes during the evolution of subacute and chronic pulmonary injury cannot always be satisfactorily explained in terms of reparative responses to type 1 pneumocyte injury. We hypothesized that immunocompetent cells, evoked as part of the interstitial inflammatory response, may be secreting factors which affect proliferation and surfactant biosynthesis by type 2 pneumocytes. To evaluate this hypothesis in vitro, we tested the effects of lymphokine-enriched supernatants, from serum-free cultures of concanavalin A-stimulated spleen cells, upon the type 2 pneumocyte-related cell strain NAL 1A. Addition of these supernatants in culture induced irreversible morphologic and ultrastructural alterations in the NAL 1A cells, inhibited cell replication, and evoked increased and apparently abnormal surfactant phospholipid biosynthesis. Supernatants from unstimulated spleen cells had no effect. There was no evidence of toxic injury to the cells in culture, and an immunologically specific cytoplasmic protein continued to be expressed. The active factor(s) appeared to be a protein or peptide of greater than 10,000 molecular weight. A specific soluble factor such as is present in the mitogen-stimulated lymphoid cell supernatants may be capable of mediating a similar interaction with type 2 pneumocytes in vivo.

Animals↗
PubMed1986

Onset of neoplastic phenotype in an epithelial cell strain from adult BALB/c mouse lung alveolus.

Prolonged culture of NAL1A in 1 microM dexamethasone (CAS: 50-02-2) at low passage numbers resulted in the emergence of a morphologically altered and malignant cell strain, NAL1AM. (NAL1A was derived from lungs of normal adult female inbred BALB/c mice and exhibits several characteristics of epithelial cells.) A clone of NAL1A, B5, was shown to undergo a spontaneous morphologic alteration during culture in normal medium to resemble NAL1AM and cells of NUL1, a strain cultured directly from urethane (CAS: 51-79-6)-induced adenomas of mouse lung. Whereas NAL1A did not form colonies in soft agar, the clone B5 of NAL1A as well as NAL1AM and NUL1 showed quite high anchorage-independent growth (colony-forming efficiency, 6.3-7.8%). Compared with NAL1A cells, clone B5, NAL1AM, and NUL1 each exhibited a ninefold-reduced level of cellular binding of epidermal growth factor.

Animals↗
PubMed1986

Kinetics of cell death induced in 10T1/2 cells by methyl methanesulfonate and the effects of extracellular calcium on cell death.

The cytotoxic effect of methyl methanesulfonate (MMS) on C3H 10T1/2 cells is characterized by a complex pattern of changes in the permeability of the cell membrane to trypan blue and, therefore, presumably to extracellular calcium. 10T1/2 cells are temporarily, and reversibly, permeable to trypan blue during the initial 30 minutes following exposure to MMS when incubated in the presence of extracellular calcium. By 90-120 minutes after the exposure, the MMS treated cells have restored control of the membrane permeability, and for the next 6-7 hours they exhibit a level of trypan blue uptake comparable to that observed in the untreated cohort population. Between 9 and 15 hours after exposure to MMS the fraction of the population permeable to trypan blue increases rapidly, ultimately approximating the level of cell killing measured concurrently in a colony formation assay. Transient culture in calcium-free medium immediately after exposure to MMS does not protect 10T1/2 cells from cytotoxicity, but incubation in the calcium-free medium does prevent the initial transient episode of permeability to trypan blue observed when the 10T1/2 cells are incubated in calcium-containing medium. These observations suggest that MMS-induced cytotoxicity results from a complex course of events, possibly from damage to an intracellular target rather than from damage to the plasma membrane.

Animals↗
PubMed1985

Conditioning of an odor aversion in preweanlings with isolation from home nest as the unconditioned stimulus.

Four experiments assessed the acquisition of aversions by preweanling rats to odors experienced during isolation from their home-nest environment. Conditioned aversion occurred for animals given a second novel odor paired with the home-nest environment, depending upon the duration of the odor-isolation pairing. With a brief duration of pairing (two pairings of 3 min each) novel odors became more preferred when paired with isolation or, to a lesser extent, when paired with home. With longer durations of pairing (two pairings of 4 hr each) the odor paired with isolation became absolutely aversive, although the odor paired with home did not become absolutely preferred. With intermediate durations neither aversion nor preference for the odors was substantial. Animals conditioned at ages 9, 16, or 23 days postnatal acquired aversions to odors paired with isolation, but 30-day-old rats did not.

Animals↗
PubMed1985

Characterization of a neoplastic epithelial cell strain derived by dexamethasone treatment of cultured normal mouse type 2 pneumocytes.

The epithelial cell strain NAL1A cultured from normal adult mouse lung has been transformed by culturing in dexamethasone into an invasive neoplastic cell strain. The criteria for neoplastic transformation include the capacity for anchorage independent growth in soft agar as well as the formation of invasive neoplastic nodules after subcutaneous transplantation in thymectomized irradiated newborn mice. The cells of the invasive neoplastic nodules induced by dexamethasone culturing of NAL1A were indistinguishable histopathologically and by electron microscopy from invasive nodules evoked by the subcutaneous inoculation of CMT64, a cell line cultured from a metastasizing mouse lung tumour and cell strain NUL1 derived from mouse pulmonary adenomata induced by urethane. Cells of the nodules derived from all three cultured strains possessed desmosomes, surface microvilli and phospholipid lamellar bodies characteristic of the type 2 pneumocyte. It is concluded that cultured cell strains NAL1A, cultured in dexamethasone, NUL1 and CMT64 evoke invasive subcutaneous neoplasms derived from a common ancestor, presumably a type 2 pneumocyte related stem cell.

Adenoma↗
PubMed1985

A comparison of several hypertonic solutions for resuscitation of bled sheep.

Small volumes (4 ml/kg) of 2400 mOsm NaCl restore cardiac output and mean arterial pressure to 80% of baseline after hemorrhage (65% of blood volume) in unanesthetized sheep. An equal volume of normal saline is less effective. To identify an optimal hypertonic solution, we screened six 2400 mOsm solutions in 18 randomized experiments in 8 sheep: NaCl, NaHCO3, NaCl/sodium acetate, NaCl/mannitol, NaCl/6% Dextran 70, and glucose. Cardiovascular function, as determined by cardiac output and mean arterial pressure, was restored best with NaCl, NaCl/NaAc, and NaCl/Dex. These three solutions were then evaluated using 18 sheep in 36 experiments. Following a 1-hr baseline period, the sheep were bled to a mean arterial pressure of 50 mm Hg for 2 hr. One of the solutions was then given in a volume of 4 ml/kg over 2 min and the sheep were monitored for 3 hr. Within 3 min of the infusion, cardiac output increased to greater than 100% of baseline for all three solutions. The NaCl-Dex solution sustained a significantly higher cardiac output over the 3-hr observation period than the other solutions. Plasma volume increased for all solutions following infusion. NaCl-Dex maintained plasma volume significantly better than the other solutions. As a further control, an isotonic solution of 6% Dextran 70 in normal saline was studied. It was not as effective as the hypertonic NaCl-Dex in maintaining cardiac output, mean arterial pressure, or plasma volume. Osmolality increased 10% (309 to 326 mOsm/kg H2O), plasma [NA] increased 7% (151 to 161 meq/liter), and plasma [K] decreased from 3.9 to 2.6 meq/liter following the hypertonic infusions. The sheep appeared to tolerate these electrolyte changes well. We conclude that a single bolus infusion of 2400 mOsm NaCl with 6% Dextran 70 best resuscitates sheep that have been subjected to a moderate degree of hemorrhagic shock compared to several other solutions. Its beneficial effects are caused in part by a sustained reestablishment of plasma volume. More studies are needed to document the safety of dextran in the clinical setting of hemorrhagic shock. Small volumes of hypertonic solutions may be valuable in the initial fluid resuscitation of patients in hemorrhagic shock.

Animals↗
PubMed1985

Analysis of appetitive motivation in preweanling rats: application of bromocryptine mesylate.

Two experiments investigated discrimination learning with preweanling rats (Rattus norvegicus) following different experimental deprivation treatments. In Experiment 1, 10- to 11-day-old Sprague-Dawley rats were deprived for 24 h of either nutrients and maternal contact through placement in an incubator or only nutrients by placement in the nest of a bromocryptine mesylate-treated dam. Bromocryptine mesylate inhibits prolactin release and thereby prevents lactation with only minimal effect on maternal behaviors. After the deprivation period, pups were trained to perform a spatial discrimination for milk infusion into the oral cavity or for the opportunity to suckle the dry nipples of an anesthetized dam. The results revealed, irrespective of deprivation treatment, that pups failed to acquire a simple T-maze spatial discrimination for milk reward although they rapidly learned to approach and locate an anesthetized dam to suckle. Experiment 2 followed up with a different procedure. Results indicated that during bouts of suckling rat pups preferred an active, lactating dam letting down milk to an identical dam not letting down milk due to her pretreatment with bromocryptine mesylate. These results illustrate a constraint on learning which affects immature rats. The capability to learn on appetitively motivated spatial discrimination appears intricately tied to the context in which training occurs. Results are discussed according to how the organism's expectancy can mediate performance.

Animals↗
PubMed1985

Expression of a type 2 pneumocyte-specific antigen by a cell strain from normal adult mouse lung.

The mouse lung epithelial cell strain NAL 1A has been confirmed as type 2 pneumocyte-related by immunostaining with a type 2 pneumocyte-specific antiserum. Cytoplasmic immunoreactivity with the antiserum paralleled the appearance of phospholipid-containing osmiophilic cytoplasmic inclusions, which were much more abundant in confluent cell cultures at low passage number than in exponentially growing cultures. However, phospholipid analysis indicated that NAL 1A cells were impoverished in phosphatidylglycerol as compared to lung type 2 pneumocytes. Confluent cultures of the neoplastic cell lines NAL 1AM and NUL 1 did not reveal any reactivity with the specific antiserum.

Animals↗
PubMed1985

An analysis of nuclear and chromatin proteins in rat livers exhibiting hyperplastic growth induced by chemical carcinogens.

Hyperplastic growth and expression of gamma-glutamyl transpeptidase were induced in adult rat hepatocytes using a model of chemical hepatocarcinogenesis. The hyperplastic response was maximal at 10 weeks after initiation of the model, at which time some 20-25% of the cross-sectional area of liver sections showed hepatocyte expression of gamma-glutamyl transpeptidase. The altered growth patterns appeared to be independent of carcinoma development since at 12 months after initiation only one of 10 animals showed evidence of hepatocellular carcinoma. A 43,000 dalton protein of isoelectric point 6.9 was solubilized by DNASE I from nuclei derived from livers at 10 weeks after initiation of the regime. This protein was scarcely detectable in the nuclei of control livers or in control and treated livers at other times after initiation of the regime. These observations suggest that alterations to a prominent nonhistone protein associated with the transcriptionally active fraction of chromatin occurred during hyperplastic growth of hepatocytes induced by chemical carcinogens.

Animals↗
PubMed1984

Right-sided infective endocarditis as a consequence of flow-directed pulmonary-artery catheterization. A clinicopathological study of 55 autopsied patients.

We studied 142 consecutively autopsied patients prospectively to determine the frequency and clinical importance of right-sided endocardial lesions in patients who had undergone flow-directed pulmonary-artery catheterization within one month of death. Of the 55 catheterized patients, 29 (53 per cent) had one or more right-sided endocardial lesions: 12 (22 per cent) had subendocardial hemorrhage, 11 (20 per cent) sterile thrombus, 2 (4 per cent) hemorrhage and thrombus, and 4 (7 per cent) infective endocarditis. Of 41 lesions seen in the 29 patients, 23 (56 per cent) were located on the pulmonic valve, 6 (15 per cent) on the tricuspid valve, 6 (15 per cent) in the right atrium, 4 (10 per cent) in the right ventricle, and 2 (5 per cent) in the main pulmonary artery. All four patients with infective endocarditis had had positive antemortem blood cultures while the catheter was in place, but in only one had the diagnosis of endocarditis been suspected clinically. The unusual locations of the infected vegetations (on the pulmonic valve in three and in the right atrium in one) and the similar location of the uninfected lesions suggest that the infective endocarditis was a consequence of catheter-induced endocardial damage with concurrent or subsequent bacteremia. Among the 87 non-catheterized patients, there were two subendocardial hemorrhages and one resolving right atrial thrombus. We conclude that endocardial damage from flow-directed pulmonary-artery catheterization is common and that right-sided infective endocarditis should be suspected in bacteremic catheterized patients.

Adolescent↗
PubMed1984

Rabbit lung after acute smoke inhalation. Cellular responses and scanning electron microscopy.

The cellular responses in the lungs of rabbits and the morphologic features of the tracheobronchial tree by scanning electron microscopy were examined 24 hours following acute inhalation of Douglas fir wood smoke. Thermal injury to the upper airway was excluded. Injury to proximal tracheal lining cells was severe and consisted of loss of the epithelium. The changes of the epithelial barrier in the proximal major bronchi were less severe in nature. However, the alterations observed by scanning electron microscopy suggested dysfunction of the mucociliary blanket. Both cell counts of bronchoalveolar lavage fluid and morphologic findings reflected an increase in alveolar macrophage response. Smoke-exposed alveolar macrophages showed significant changes in the surface features. These findings may explain the tracheobronchitis seen clinically, and the propensity of patients to lung infection following smoke inhalation.

Acute Disease↗
PubMed1984

Lymphoblastoid cell-produced immunoglobulins: preparative purification from culture medium by hydroxylapatite chromatography.

Hydroxylapatite (HA) is a chromatography matrix capable of separating nucleic acid as well as protein species. HA adsorbs biomolecules as a function of the extent and distribution of their surface charge. HA has been evaluated for its ability to differentially retain immunoglobulin molecules, which are planar relative to the generally globular serum proteins, particularly albumin, contained in tissue culture medium. HA chromatography provides a single-step method to purify and concentrate immunoglobulin proteins secreted by lymphoblastoid cells into culture medium from the vast excess of serum proteins used to supplement the medium. A human lambda light-chain protein was recovered in 5% of the applied volume of medium, and was separated from 95% of the total protein. More than 75% of a hybridoma-produced complete immunoglobulin was recovered essentially free of serum protein contamination. HA appears to provide a valuable alternative chromatographic medium for the purification of immunoglobulin proteins secreted by lymphoblastoid cells.

Cells, Cultured↗
PubMed1984

Establishment of epithelial cell strains from normal adult mouse lung resembling a urethane-induced lung adenoma cell strain and a metastasizing mouse lung carcinoma cell line.

Epithelial cell strains, designated NAL, have been established from normal lungs of adult female Balb/c mice. The ultrastructural characteristics, effect of dexamethasone on cellular morphology and proliferation rate, and the cytoskeletal protein pattern of NAL suggests that these cell strains may be related to a urethane-induced mouse lung adenoma cell strain NUL and to a metastasizing mouse lung tumour cell line CMT. NAL exhibited no anchorage-independent growth under normal conditions, however extensive passaging in the presence of 5 X 10(-6)M dexamethasone resulted in a colony forming efficiency in soft agar of 8.4% at passage number 30.

Adenoma↗
PubMed1984

Psychiatric assessment of children. II. Comparison with mothers.

An attempt is made to demonstrate the relevance of a diagnostic method described in a preceding paper by comparing observations in 95 children aged 7-8 with independent findings in their mothers. The mothers had been chosen at random and exhaustively studied by another team at the time of the pregnancies which resulted in the birth of the children of our study.

Attention Deficit Disorder with Hyperactivity↗
PubMed1984

Hermansky-pudlak syndrome and interstitial lung disease: report of a case with lavage findings.

Clinical and pathologic evidence for interstitial pulmonary fibrosis occurring in some patients with the Hermansky-Pudlak syndrome is well described in the literature, but data on immunologic mechanisms operating in this form of lung disease have not been published. In this case report, we describe bronchoalveolar lavage (BAL) findings in a patient with this syndrome. Recovered alveolar macrophages (AM) contained the characteristic ceroidlike material previously described in interstitial macrophages in pathologic specimens. The BAL analysis was similar to that seen in idiopathic pulmonary fibrosis, with increased levels of immunoglobulins and numbers of IgG and IgA secreting cells, and normal percentages of putative helper and suppressor T-cell subsets. In addition, superoxide production by stimulated AM was increased, possibly secondary to phagocytosis of the ceroidlike material. The lavage in this patient was compatible with a mild inflammatory process that was consistent with gallium scan results and the patient's clinical course.

Adult↗
PubMed1984

A model of bile duct hyperplasia in the rat induced by diethylnitrosamine and selective cytotoxicity.

Adult Wistar rats were subjected to a chemical carcinogenesis regimen involving initiation with diethylnitrosamine (DEN) and cytotoxic selection of initiated cells following partial hepatectomy. The livers of treated rats exhibited sequential changes of vacuolar degeneration and hepatocellular nodular hyperplasia up to 5 mth after completion of the experimental regimen. The hyperplastic nodules regressed slowly at that time. Cystic bile duct hyperplasia emerged with high frequency between 5 and 15 mth after completion of the regimen. The nitrosamine-initiated nodular and biliary hyperplasias could not be unequivocally accepted as preneoplastic lesions since frankly neoplastic transformation under these conditions was a relatively rare occurrence.

Animals↗