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Biomedical subjects

J Young

Publications and source records attributed to J Young.

At least 415 records · Page 23Linked to original sources
PubMed1988

Distinct murine macrophage receptor pathway for human triglyceride-rich lipoproteins.

Murine P388D1 macrophages have a receptor pathway that binds human hypertriglyceridemic very low density lipoproteins (HTG-VLDL) that is fundamentally distinct from the LDL receptor pathway. Trypsin-treated HTG-VLDL (tryp-VLDL), devoid of apolipoprotein (apo)-E, fail to bind to the LDL receptor, yet tryp-VLDL and HTG-VLDL cross-compete for binding to P388D1 macrophage receptors, indicating that these lipoproteins bind to the same sites. The specific, high affinity binding of tryp-VLDL and HTG-VLDL to macrophages at 4 degrees C is equivalent and at 37 degrees C both produce rapid, massive, curvilinear (receptor-mediated) triglyceride accumulation in macrophages. Ligand blots show that P388D1 macrophages express a membrane protein of approximately 190 kD (MBP190) that binds both tryp-VLDL and HTG-VLDL; this binding is competed by HTG-VLDL, trypsinized HTG-VLDL, and trypsinized normal VLDL but not by normal VLDL or LDL. The macrophage LDL receptor (approximately 130 kD) and cellular uptake of beta-VLDL, but not MBP 190 nor uptake of tryp-VLDL, are induced when cells are exposed to lipoprotein-deficient medium and decreased when cells are cholesterol loaded. Unlike the macrophage LDL receptor, MBP 190 partitions into the aqueous phase after phase separation of Triton X-114 extracts. An anti-LDL receptor polyclonal antibody blocks binding of HTG-VLDL to the LDL receptor and blocks receptor-mediated uptake of beta-VLDL by P388D1 cells but fails to inhibit specific cellular uptake of tryp-VLDL or to block binding of tryp-VLDL to MBP 190. Human monocytes, but not human fibroblasts, also express a binding protein for HTG-VLDL and tryp-VLDL similar to MBP 190. We conclude that macrophages possess receptors for abnormal human triglyceride-rich lipoproteins that are distinct from LDL receptors in ligand specificity, regulation, immunological characteristics, and cellular distribution. MBP 190 shares these properties and is a likely receptor candidate for the high affinity uptake of TG-rich lipoproteins by macrophages.

Animals↗
PubMed1988

Whom do mutual-help groups help? A typology of members.

A total of 1,677 members of GROW, a mutual-help organization, were surveyed about the reasons they joined GROW and their perceptions of its effectiveness in meeting their needs. The organization was founded 30 years ago to enhance the rehabilitation of former mental patients, but it now includes members who have never been treated for mental illness. Cluster analysis of the survey data revealed five distinct groups of members. One group sought relief of symptoms, while others sought a supportive community, help in recovering from trauma, help in coping with bereavement, or the opportunity to help others. The interests of the different types of members in GROW, and in other mutual-help organizations, may be at odds because some members may need social support that encourages change (facilitative support), while others may need social support that provides stable relationships (palliative support).

Adaptation, Psychological↗
PubMed1988

Double-blind controlled trials of Cronassial in chronic neuromuscular diseases and ataxia.

We report three 12-month, double-blind, three-phase studies comparing the effect of placebo and 40 mg and 100 mg IM daily of purified bovine brain gangliosides (Cronassial) in chronic neuromuscular diseases. Thirty patients with Charcot-Marie-Tooth disease, 16 with idiopathic polyneuropathy, and 30 with spinocerebellar degeneration had neuromuscular function measured monthly by quantitative testing of motor and sensory function, coordination, and electrophysiologic factors. Analysis of these studies, and of longer term (up to 2 years) open studies of 100 mg daily of Cronassial in 67 patients failed to show therapeutic efficacy of Cronassial. Statistical power calculations indicated that five of the 37 measures had greater than a 70% chance of detecting a 20% difference in the rate of progression of the active-drug and placebo groups. A number of measures significantly improved during prolonged placebo treatment, suggesting that the placebo effect has a strong influence on "objective" measures of neuromuscular function.

Adult↗
PubMed1988

Nonspecific supersensitivity induced by reserpine in guinea pig cardiac ventricle tissue.

The depletion of norepinephrine stores by chronic reserpine pretreatment is thought to be responsible for the development of supersensitivity in cardiac tissue. The present study was designed to determine if reserpine-induced supersensitivity could be demonstrated in isolated guinea pig right ventricular strips, if it was associated with beta adrenoceptor proliferation and was specific for beta adrenoceptor agonists. In addition, reserpine dose-dependency of the phenomenon was tested for by using two pretreatment regimens to determine if supersensitivity was the result of direct or possibly toxic effects of reserpine. Pretreatment of guinea pigs with reserpine (0.1 mg/kg/day) for 7 days resulted in over 90% depletion of cardiac norepinephrine stores. Supersensitivity to the inotropic effects of isoproterenol, impromidine and forskolin was demonstrated. Associated with the supersensitivity was a significant increase in beta adrenoceptor density. Muscarinic receptor density was actually decreased. This pretreatment regimen also was associated with a significant (30%) drop in body weight suggesting that the phenomenon might be the result of a direct toxic effect of reserpine. Pretreatment of guinea pigs with a lower dose of reserpine (0.03 mg/kg/day) for 7 days produced the same degree of norepinephrine depletion, nonspecific inotropic supersensitivity and beta adrenoceptor proliferation in the absence of a significant reduction in body weight. The degree of supersensitivity induced by the two pretreatment regimens was between 2- to 3-fold for all three agonists tested.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Audit of support given to lay carers of the demented elderly by a primary care team.

An audit was undertaken to determine how well a primary care team supported lay carers of the demented elderly. The following standards were set: (1) primary care teams should know of the existence of symptomatic demented elderly patients in the community; (2) lay carers should be knowledgeable about dementia; and (3) the resources which the lay carers felt they needed should be supplied unless they were unavailable.The primary care team knew of the existence of all symptomatic demented elderly patients in the practice but lay carers lacked knowledge about dementia and had unmet needs. Giving lay carers a booklet about dementia and reporting their unmet needs to the primary care team led to improvements in standards 2 and 3. In addition, stress among lay carers was reduced. In spite of a reduction in the number of carers' unmet needs, there was no overall change in the use of available resources following intervention.It is concluded that structured support is necessary and worthwhile in order to provide effective support for lay carers of the demented elderly in the practice.

Aged↗
PubMed1987

A novel vasoactive intestinal peptide (VIP) from elasmobranch intestine has full affinity for mammalian pancreatic VIP receptors.

A peptide that cross reacted with N-terminal, but not C-terminal, antisera to vasoactive intestinal peptide (VIP) was isolated from extracts of intestine from the dogfish Scyliorhinus canicula. Microsequence analysis gave the structure His-Ser-Asp-Ala-Val-Phe-Thr-Asp-Asn-Tyr-Ser-Arg-Ile-Arg-Lys-Gln-Met-Ala-Val-Lys - Lys-Tyr-Ile-Asn-Ser-Leu-Leu-Ala-NH2. C-terminal amidation was determined by HPLC analysis of phenylthiocarbamyl amino acid derivatives after carboxypeptidase Y digestion. The peptide differs at five positions from the porcine octacosapeptide. Dogfish VIP was equipotent with its porcine counterpart in inhibiting binding of 125I-labelled VIP to guinea pig dispersed pancreatic acini, and in stimulating amylase secretion by the same preparation. The data indicate a strong conservation of VIP during evolution and permit identification of residues crucial for bioactivity.

Amino Acid Sequence↗
PubMed1987

Post-translational processing of the porcine gastrin precursor by phosphorylation of the COOH-terminal fragment.

The gene sequence encoding porcine preprogastrin is known; in order to clarify pathways of post-translational processing of the predicted precursor peptide we have characterized material reacting with antibodies to a synthetic peptide corresponding to the expected extreme COOH-terminal portion of the precursor. Radioimmunoassay was used to identify and monitor the purification of peptides in porcine antral mucosa. Two peptides (I and II) were isolated to homogeneity by steps involving gel filtration, ion exchange, and reversed-phase high performance liquid chromatography. The two co-eluted on gel filtration but were separated on anion-exchange chromatography. The more acidic peptide (II) was less hydrophobic on high performance liquid chromatography. Automated gas-phase microsequencing revealed the less acidic peptide (I) to have the sequence of porcine preprogastrin 96-104 (SAEEGDQRP); it would be produced by tryptic-like cleavage of Arg95-Ser96. The second peptide did not yield a phenylthiohydantoin-derivative on the first cycle but thereafter it sequenced as the first peptide (i.e. -AEEGDQRP). Incubation in alkali liberated almost equimolar amounts of phosphate from peptide II but not from I. In addition, alkaline phosphatase liberated phosphate and converted the acidic peptide to the less acidic one. The results suggest that serine in the first position is phosphorylated in peptide II but not I. The tripeptide -Ser(P)-Ala-Glu- also occurs in adrenocorticotropic hormone; this tripeptide is a substrate for physiological casein kinase. Potential phosphorylation sites occur at comparable positions in the precursors of a number of regulatory peptides.

Alkaline Phosphatase↗
PubMed1987

Isolation and characterization of the intact gastrin precursor from a gastrinoma.

Antibodies to the extreme C-terminal region of human progastrin have been used to monitor the isolation of high-Mr immunoreactive material in a gastrinoma extract. Microsequence analysis of the product revealed amino acid residues in the first 18 positions corresponding to those predicted from the cDNA sequence for preprogastrin starting at position 22; the sequence and immunochemical data together allow the identification of this material as intact progastrin. Implications for gastrin biosynthesis are discussed.

Amino Acid Sequence↗
PubMed1987

Free and microvascular bone grafting in the irradiated dog mandible.

Microvascular and free rib grafts were placed in 4.5 cm defects in an edentate mandibular body defect 18 to 28 days after completion of 50 Gy of irradiation from a 60Co source. The animals were sacrificed from two to forty weeks postoperatively and evaluated clinically, radiographically, and histologically. There was a marked difference in the alveolar mucosal viability with the two grafts. Mucosal dehiscence was not observed over any of the microvascular grafts, but was present in seven-eighths of the free grafts. Union of the microvascular bone graft to the host bone occurred within six weeks. In contrast, after six weeks the free graft was sequestered in all the animals. An unexpected finding with both types of graft was the marked subperiosteal bone formation. This bone appeared to be derived from the host bed, stabilizing and bridging the defects bilaterally. The results suggest that radiated periosteum may play an important role in osteogenesis.

Animals↗
PubMed1987

Identification of HLA-DP polymorphism with DP alpha and DP beta probes and monoclonal antibodies: correlation with primed lymphocyte typing.

Thirty-four lymphoblastoid cell lines that had been previously typed for HLA-DP antigens by primed lymphocyte typing (PLT) were tested by Southern blotting and by ELISA. Using two DP beta probes and a DP alpha probe with a series of enzymes, it is possible to identify restriction fragment length polymorphism (RFLP) patterns characteristic of DPw1, -2, -3, -4, and possibly -5. ELISA typing results, based on two polymorphic DP antibodies DP11.1 and ILR1, were compared with PLT-defined and RFLP-defined types. Thus, using a range of probes and enzymes it is possible to identify DP polymorphism. The value of monoclonal antibodies for such studies is demonstrated, and the molecular data can, in some cases, pinpoint the amino acids responsible for the specificity of the monoclonal antibodies.

Alleles↗
PubMed1987

Splinter haemorrhages in the elderly.

We have determined the frequency and significance of finger-nail splinter haemorrhages in 220 patients over the age of 65 years admitted to acute geriatric wards. Splinter haemorrhages were found in 35 (16%) patients. Splinters are less common in the elderly than in younger people. They are associated with the use of walking aids; trauma to the nails seems to be the main causative factor. We found no association between splinter haemorrhages and specific medical disorders, bacteraemia or senile purpura. Splinter haemorrhages are an unhelpful physical sign in the elderly.

Aged↗
PubMed1987

Prevention of streptozotocin-induced alterations in the rat heart by 3-O-methyl glucose and insulin treatments.

Streptozotocin-induced diabetes has previously been shown to alter the sensitivity and responsiveness of rat myocardial tissues to cardiotonic agonists. The objective of the present study was to determine if these alterations were due to the diabetogenic or possible direct cardiotoxic effects of streptozotocin. One month after streptozotocin treatment the following changes were observed in the rat: decrease in body weight; elevation of blood glucose and glycosylated hemoglobin levels; decrease in spontaneously beating atrial rate; elevation in basal developed force of electrically driven right ventricle; and inotropic subsensitivity of right ventricle to isoproterenol, which was associated with decreased beta-adrenoceptor density and supersensitivity to calcium. Pretreatment with the nonmetabolizable glucose analog 3-O-methyl glucose prevented these alterations. Chronic insulin replenishment also reversed the effects of streptozotocin, with the exception of complete normalization of elevations in blood glucose and basal developed force. Acute exposure to high glucose in the medium preserved the subsensitivity to isoproterenol but resulted in an elevated basal developed force in both control and streptozotocin groups. These observations indicate that myocardial alterations after streptozotocin treatment are not the result of direct cardiotoxic effects but rather a consequence of the drug-induced diabetic state. They also suggest that the increase in basal developed force might be related to elevated glucose concentrations.

3-O-Methylglucose↗
PubMed1987

Comparative efficacies of erythromycin-sulfisoxazole and cefaclor in acute otitis media: a double blind randomized trial.

A prospective double blind trial compared the fixed combination of erythromycin-sulfisoxazole (E/S) with cefaclor in the treatment of acute otitis media. One hundred nineteen children in six centers across Canada were studied. Diagnostic tympanocentesis of 134 ears yielded 135 bacterial isolates: Streptococcus pneumoniae (42%); Haemophilus influenzae (21%); Branhamella catarrhalis (10%); Streptococcus pyogenes (5%); and other bacteria (22%). Seventy-seven percent of strains of B. catarrhalis and 14% of strains of H. influenzae were beta-lactamase producers. E/S exhibited greater in vitro activity against H. influenzae and B. catarrhalis. Twenty-three patients had bacteriologically sterile middle ear fluid. The overall clinical outcome at Days 10 and 31 was identical in both treatment groups. Otoscopic findings improved more rapidly in the E/S group than in the cefaclor group at 10 and 31 days (P less than or equal to 0.04). In cases where pre-treatment middle ear fluid was negative on routine bacterial culture, complete cure at 10 days was observed in 75% of patients treated with E/S but only in 14% of those treated with cefaclor (P = 0.02). Side effects were infrequent and comparable between the test drugs. E/S is at least as effective as cefaclor in the management of acute otitis media and may be superior, particularly for cases not yielding bacteria on routine culture.

Acute Disease↗