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Biomedical subjects

G Ross

Publications and source records attributed to G Ross.

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

In vitro acetylation of rat pulmonary surfactant-associated glycoprotein(s) A primary translation products.

The primary translation products of pulmonary surfactant-associated glycoprotein(s) A, the major apolipoprotein in mammalian surfactants, exhibit extensive charge heterogeneity. After in vitro translation of poly(A)+ mRNA from rat lung, the primary translation products of glycoprotein(s) A were identified as a charge train of five proteins of 26 kDa (pI 4.6-5.0), the predominant forms being the more acidic members (pI less than 4.8). Inhibition of acetylation during in vitro translation of rat lung poly(A)+ mRNA resulted in a predominance of the more basic isoforms (pI greater than or equal to 4.8). Intracellular forms of glycoprotein(s) A were immunoprecipitated from rat Type II epithelial cells after treatment with tunicamycin or after deglycosylation with endoglycosidase H. Five intracellular precursors consisting primarily of acidic members of the charge train were identified, this being consistent with the intracellular acetylation of the protein. In contrast, canine glycoprotein(s) A translation products consisted of only three proteins of 26 kDa (pI 4.8-5.0), in which most of the radiolabel was concentrated in the more basic components. Acetylation may account for some, but not all, of the charge heterogeneity in the primary translation products and processed forms of surfactant-associated glycoprotein(s) A in the rat.

Acetylation↗
PubMed1986

Cytomorphological lesions induced by chemotherapeutic agents in transitional cell carcinoma in vitro.

Transitional cell carcinoma from 20 patients and two human cell lines were maintained in short-term tissue culture. Each was studied ultrastructurally before and after incubation with cisplatinum, adriamycin, or mitomycin C. Sequential ultrastructural changes were noted and were found to be specific for each agent tested. Ultrastructural changes in the nucleoli were produced by exposure to cisplatinum or mitomycin C; alterations in the heterochromatin of the nuclei were characteristic of treatment with adriamycin. The changes in the nucleoli seen with cisplatinum have not been described previously and support an alkylating property as a mechanism of action. Intravesical chemotherapeutic agents are now commonly used in clinical treatments. The morphological changes produced by these agents are specific and may be seen in the clinical setting.

Antineoplastic Agents↗
PubMed1986

Transitional explant reduction assay--a new in vitro testing system for intravesical chemotherapy.

Eighty-five tumors from 49 patients with transitional cell carcinoma were examined in a model for in vitro sensitivity using tumor explant reduction assay. Individual sensitivity patterns were obtained for each tumor tested. Explants were most frequently found to be sensitive to cis-platinum (49 per cent) and least frequently sensitive to thiotepa (20 per cent). Thirteen patients were studied on multiple sequential intervals, with resistance to specific agents noted to develop in 53 per cent of the patients. To date, a prospective cross-over study has been conducted on seven patients with 15 correlates. Overall, clinical correlation of this assay for both resistance and sensitivity is 93 per cent. We report a new assay for transitional cell carcinoma of the bladder that is adaptable to small specimen samples and provides adequate material for testing 73 per cent of the time.

Carcinoma, Transitional Cell↗
PubMed1986

Echinococcus granulosus infection in mice: host responses during primary and secondary infection.

The reaction of Balb/c mice to primary and secondary subcutaneous infection with Echinococcus granulosus protoscoleces (PSC) is described. From 3 to 14 days following primary exposure to PSC, draining lymph nodes increase in weight and there is expansion of T and B lymphocyte populations, enhancement of in vitro lymphocyte transformational responses and production of PSC-specific IgM and IgE antibodies. Despite the persistence of viable PSC in host tissues, lymphocyte responses decline to pre-infection values over the period 3-8 weeks post-infection. Secondary exposure to PSC immediately induces lymphoproliferation, enhancement of transformational responses, production of IgE antibody and encapsulation of PSC by inflammatory cells. Although specific antibody levels remain high until at least 8 weeks after challenge infection, lymphocyte activity begins to decline after 4 days and is profoundly suppressed by 10 days. Parasite viability appears to be significantly reduced in secondary, as opposed to primary, infection and is associated with the accumulation of large numbers of eosinophils, mast cells and macrophages in infected tissues.

Animals↗
PubMed1986

Echinococcus granulosus: changes in the transformational behaviour of murine lymph node cells during early infection.

Subcutaneous inoculation of living Echinococcus granulosus protoscolices (PSC) caused blastic transformation in local lymph node cells (LNC). The effect was maximal seven days post-infection (p.i.), had declined by day 21, and was prevented by killing the PSC prior to inoculation. LNC from inoculated mice also showed marked enhancement of blastogenesis in response to a secondary stimulation by live PSC in vitro. This secondary reaction occurred after exposure to living or killed PSC. There was generally enhanced reactivity to T- and B-cell mitogens at day 7. Phytohaemagglutinin was exceptional in that the killed parasite caused early changes in reactivity as above, but the live parasite induced a rise at 56 days p.i. It is concluded that E. granulosus may cause a determinate change in T-cell function.

Animals↗
PubMed1986

Management of cranial diabetes insipidus with oral desmopressin (DDAVP).

The effect of oral administration of desmopressin (DDAVP) solution was investigated in six patients with cranial diabetes insipidus of varying aetiology. All patients experienced a prompt and prolonged antidiuresis. Nine patients have been managed with oral DDAVP tablets for up to 5 months and all preferred this route of administration to intranasal application using a rhinyle. Oral DDAVP gives excellent and convenient control in cranial diabetes insipidus.

Administration, Oral↗
PubMed1986

Early predictors of neurodevelopmental outcome of very low-birthweight infants at three years.

Seventy-nine premature infants weighting less than 1501 g at birth but appropriate for gestational age underwent a neurodevelopmental examination at one, three, six, nine and 12 months post-term, and a standard neurological examination and the Stanford-Binet Intelligence Scale at three to four years of age. Children were classified as normal, suspect or abnormal on the three-year neurological examination, on the IQ test, and on composite neurodevelopmental outcome at age three years. Results showed that items from both the nine- and 12-month neurodevelopmental examinations correctly classified about 80 per cent of the children as to composite outcome at three years. In addition, the 12-month examination enabled correct prediction for 89 per cent of the children as to neurological outcome and for 82 per cent as to IQ. Neurodevelopmental examination of high-risk infants in the last quarter of the first year of life (post-term) should assist pediatricians in predicting which children will be normal and which will require early intervention.

Cerebral Palsy↗
PubMed1986

Early predictors of one-year outcome for infants asphyxiated at birth.

This study attempted to identify within the first 48 hours of life those infants sustaining hypoxic-ischemic insults and destined to have neurodevelopmental abnormalities at one year of age. Neurological examination and cranial CT scan were quantitated to provide a post-asphyxia score and CT low-density index for each of 34 fullterm infants. The post-asphyxia score and CT infarction index were used to predict infants with normal and abnormal outcomes at one year of age, and both were valuable predictors of neurodevelopmental sequelae.

Asphyxia Neonatorum↗
PubMed1986

Rhythmic coronary arterial contractions: changes with time and membrane potential.

Responses of isolated rabbit coronary artery segments to KCl and 2-(2-aminoethyl)-pyridine (AEP) were studied. Vessels stored at 2 degrees C for 24 h developed spontaneous rhythmic contractions during the first 20 min in Krebs solution at 37 degrees C. The contractile response to KCl or AEP declined to a minimum at 60 min [i.e., time zero (to) +60], increased to a peak at to +150 and then again declined. Resting membrane potential (Em) was less than or equal to -40 mV at to +20, -70 mV at to +30-60 and -50 mV at to +240-360 min. Rhythmic contractile responses were frequent and were associated with changes in Em. Vessels that were not cold stored did not hyperpolarize, nor did they show the early decline in response. Vessels stored at 2 degrees C for 24 h and then tested at 22-23 degrees C exhibited a similar pattern of changes in contraction but the time course was more protracted. We conclude that contractile responses are initially modulated by changes in Em associated with an increase then decrease in the activity of the sodium pump. Later changes in reactivity are due to a different mechanism.

Animals↗
PubMed1986

Synthesis of surfactant-associated protein, 35,000 daltons, in fetal lung.

The major human pulmonary surfactant-associated protein of 35,000 daltons (Da) (SAP-35), consists of a group of related proteins of 27,000-36,000 Da, with isoelectric points ranging from pH 4.6 to 5.2. SAP-35 precursors were identified by immunoprecipitation of protein products of in vitro translation of normal adult human poly(A)+ mRNA with human SAP-35 antiserum. The translation products nearly comigrated with the most basic components of alveolar SAP-35 (mol mass = 24,500-27,000 Da). Processing of the primary translation products by canine pancreatic microsomal membranes increased their apparent molecular weight to 29,000-30,000-Da forms, which were sensitive to endoglycosidase F, suggesting the addition of asparagine-linked oligosaccharides to the molecules. A smaller protein of 24,500 Da was generated during treatment with canine microsomal membranes likely representing cleavage of a signal peptide. SAP-35 was not detected in explants of [35S]methionine-labeled fetal lung (20-24 wk gestation) after 1 day of culture or immunoprecipitates of in vitro translated poly(A)+ mRNA isolated from fetal human lung. However, after 3-5 days of organ culture, synthesis of SAP-35 was readily detected by immunoprecipitation of [35S] methionine-labeled tissue. Fully sialylated (neuraminidase-sensitive forms) comigrated with fully glycosylated SAP-35 isolated from human surfactant. High mannose (endoglycosidase H-sensitive precursors) were also synthesized by the organ cultures and were distinct from the secreted form in surfactant. Synthesis of surfactant-associated SAP-35 and its precursors was induced in association with morphological maturation of the type II epithelial cell during organ culture of human fetal lung.

Chemical Phenomena↗
PubMed1986

Hydrophobic surfactant-associated protein in whole lung surfactant and its importance for biophysical activity in lung surfactant extracts used for replacement therapy.

Hydrophobic protein of 6,000 and 14,000 daltons was isolated from mammalian pulmonary surfactant obtained from canine, human, and bovine alveolar lavage material. Low molecular weight, hydrophobic, surfactant-associated protein (SAP), herein referred to as SAP 6-14, was distinguished from SAP-35, the major glycoprotein in mammalian surfactants (the 35,000 dalton glycoprotein A or apolipoprotein A) by amino acid composition, peptide mapping, and by resistance of SAP 6-14 to digestion by endoglycosidase F, collagenase, trypsin, and other proteases. The amino acid composition of SAP 6-14 was found to be highly enriched in leucine and other hydrophobic amino acids. The characteristics of protein isolated from bovine replacement surfactant extracts utilized for the treatment of hyaline membrane disease in humans were also studied. SAP 6-14 isolated from calf lung surfactant replacement extracts (CLSE) and surfactant-TA were found to be identical to SAP 6-14 isolated from ether/ethanol extracts of various mammalian surfactants. By contrast, SAP-35, the major surfactant-associated glycoprotein of molecular weight = 35,000, and other higher molecular weight proteins were not detected in significant quantities in the CLSE or surfactant-TA replacement surfactants, either by highly sensitive silver stain analysis or by immunoblot using monospecific antisera generated against bovine SAP-35. Biophysical studies of the CLSE replacement surfactant containing only SAP 6-14 and native phospholipids demonstrated full surface activity compared to natural lung surfactant. Dynamic surface tension lowering and adsorption properties of CLSE were essentially identical to those of freshly isolated bovine whole surfactant. Thus, hydrophobic SAP 6-14 is the only protein detected in bovine lung extract surfactants with full biophysical activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Immunologic identification of a pulmonary surfactant-associated protein of molecular weight = 6000 daltons.

Hydrophobic, small molecular weight, surfactant-associated protein of Mr = 6000 (SAP-6) was isolated from bovine, canine, and human alveolar lavage and identified by silver staining after sodium dodecyl sulfate polyacrylamide gel electrophoresis gels. Lesser amounts of protein of Mr = 14,000, 20,000, and 26,000 daltons also copurified with SAP-6, likely representing oligomers of the Mr = 6,000 dalton protein. In the absence of sulfhydryl-reducing agents, increased amounts of the larger forms of the protein were observed. Antisera generated against bovine SAP-6 were used to further characterize the protein and distinguish it from the more abundant surfactant-associated glycoprotein of Mr = 35,000 (SAP-35) present in mammalian surfactants. Rabbit antisera generated against the bovine hydrophobic protein recognized SAP-6 and lesser amounts of the proteins of Mr = 14,000, 20,000, and 26, 000 daltons. The SAP-6 antisera were reactive against the hydrophobic proteins from human, bovine, and canine surfactants as assessed by immunoblot analysis after sodium dodecyl sulfate polyacrylamide gel electrophoresis. SAP-6 antisera did not detect bovine SAP-35 the abundant surfactant-associated glycoprotein, by immunoblot analysis; however, some reactivity of the anti-SAP-6 was detected against purified bovine SAP-35 by a sensitive enzyme-linked immune-adsorbant assay. Anti-SAP-6-did not react with bovine serum components either by immunoblot or by enzyme-linked immune-adsorbant assay. Monospecific antisera generated against bovine SAP-35 did not detect SAP-6 by immunoblot analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Glycosylation and secretion of surfactant-associated glycoprotein A.

Synthesis of glycoprotein A, the major surfactant-associated protein, was demonstrated in Type II epithelial cells isolated from rat lung. Predominant, secreted forms migrated as glycoproteins with asparagine-linked, complex-type oligosaccharides (32,000-36,000 daltons, pI 4.2-4.8). Primary in vitro translation products of the glycoprotein migrated as five distinct proteins of approximately 26,000 daltons which were processed by pancreatic microsomal membranes in vitro to 30,000-34,000-dalton, endoglycosidase F-sensitive forms. These in vitro processed forms of glycoprotein A co-migrated with intracellular forms immunoprecipitated from [35S]methionine-labeled, Type II cells. Pulse-chase experiments with [35S]methionine-labeled cells demonstrated rapid synthesis of endoglycosidase H-sensitive precursors of 34,000 daltons, pI 4.7-4.8, which were neither secreted from Type II cells nor detected in surfactant from alveolar lavage. These high-mannose forms were slowly processed to more acidic, endoglycosidase H-resistant, neuraminidase-sensitive forms. At between 10 and 180 min, fully sialylated or other endoglycosidase H-resistant forms were a minor fraction of intracellular glycoprotein A. After 16 h, intracellular glycoproteins A were primarily present as endoglycosidase H-resistant forms. Secretion of mature, sialylated, glycoprotein A was first detected 1 h after labeling, and was also readily detected after 16-24 h chase period. Tunicamycin, which blocks N-linked protein glycosylation, resulted in synthesis of three major 26,000-dalton proteins which co-migrated with the nonglycosylated, surfactant-associated proteins A1 present in surfactant from alveolar lavage and with the major in vitro translation products of rat lung poly(A+) mRNA. Tunicamycin inhibited secretion of glycoprotein A. Swainsonine, which inhibits Golgi alpha-mannosidase II, completely inhibited synthesis of the fully sialylated molecule. Swainsonine produced forms of glycoprotein A which were both neuraminidase- and endoglycosidase H-sensitive and were readily secreted. Monensin, an ionophore that alters protein transport, markedly inhibited intracellular sialylation and secretion. These studies demonstrate that pulmonary Type II cells rapidly synthesize and process surfactant-associated glycoprotein A precursors to endoglycosidase H-sensitive forms, which are slowly sialylated prior to secretion.

Alkaloids↗
PubMed1985

Synthesis of surfactant-associated glycoprotein A by rat type II epithelial cells. Primary translation products and post-translational modification.

Surfactant-associated glycoproteins A, 38 (A3), 32 (A2) and 26 (A1) kDa, pI (4.2-4.8), were identified as related proteins present in surfactant isolated from rat lung lavage fluid. Differences in size and charge among surfactant-associated glycoproteins A were related to differences in glycosylation as determined by reduction of the larger forms (38 and 32 kDa) to 26 kDa by endoglycosidase F and by increased isoelectric points of the glycosylated forms after treatment with neuraminidase. Synthesis and secretion of surfactant-associated glycoproteins A and precursors were demonstrated in purified rat Type II epithelial cells by immunoprecipitation of [35S]methionine-labelled proteins with anti-surfactant-associated glycoprotein A antisera. In pulse-chase experiments, labelled proteins 26-34 kDa, appeared within 10 min and smaller forms co-migrated with surfactant-associated glycoprotein A from alveolar lavage. The relative abundance of the larger molecular mass forms (30-34 kDa, pI 4.8) increased at later times up to 3 h. More acidic mature forms, which co-migrated with surfactant-associated glycoproteins A2 and A3 in surfactant (38 and 32 kDa), were readily detectable in the media, but were not abundant forms in lysates of labelled Type II cells after 1-3 h of incubation. Primary translation products of surfactant-associated glycoprotein A were immunoprecipitated with monospecific anti-surfactant-associated glycoprotein A antiserum after in vitro translation of poly(A)+ mRNA isolated from adult rat lung. The immunoprecipitated translation product migrated at 26 kDa, pI 4.8, and migrated slightly faster than surfactant-associated glycoprotein A1 from surfactant. Treatment of surfactant-associated glycoprotein A with bacterial collagenase resulted in proteolytic fragments 23-20 kDa, pI 4.2-4.8, which no longer underwent sulfhydryl-dependent cross-linking, suggesting that the collagen-like domain was required for the sulfhydryl-dependent oligomerization. Surfactant-associated glycoproteins A are synthesized by rat Type II epithelial cells as pre-proteins, 26-34 kDa. Larger forms result primarily from N-linked glycosylation of the 26 kDa primary translation product. Mature, more acidic forms result from further addition of sialic acid.

Animals↗
PubMed1985

Lobar pneumonia caused by Haemophilus influenzae type B.

Haemophilus influenzae type b is a rare cause of adult lobar pneumonia and we are unaware of any reported British cases. However in the United States this condition is well described and the incidence is increasing (Levin et al. 1977).

Adult↗