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Biomedical subjects

A K Taylor

Publications and source records attributed to A K Taylor.

At least 73 records · Page 4Linked to original sources

Selective removal of alpha heavy-chain glycosylation sites causes immunoglobulin A degradation and reduced secretion.

The importance of carbohydrate in the secretion of immunoglobulin A (IgA) has previously been suggested by results of studies with tunicamycin, which prevents N-linked glycosylation of all cell glycoproteins. To directly evaluate the role of individual oligosaccharides in the secretion of IgA, we have used site-directed mutagenesis to selectively eliminate the two N-linked attachment sites reported to be glycosylated in alpha heavy chains. Transfected wild-type and mutant alpha genes were expressed in kappa light-chain-producing MPC-11 variant myeloma cells, and secretion kinetics of the IgAs were compared. Removal of either or both glycosylation sites led to intracellular alpha heavy-chain degradation and a 90 to 95% inhibition of IgA secretion. These results reveal that both N-linked oligosaccharides of the alpha heavy chain are essential for intracellular stability and normal secretion of IgA. This suggests that the key function of carbohydrate here is to maintain proper conformation of the glycoprotein. We also found that when expressed in the MPC-11 variant cells, alpha heavy chains were glycosylated at a third, normally unused site.

Animals↗

Skeletal growth factor is produced by human osteoblast-like cells in culture.

Human bone cells isolated from femoral heads were cultured in BGJb medium containing bovine serum albumin (100 micrograms/ml), insulin (1 microgram/ml) and epidermal growth factor (10 ng/ml), and the conditioned medium collected. The medium was concentrated, chromatographed using HPLC gel filtration (TSK 2000 SW), and assayed for mitogenic activity using [3H]thymidine incorporation into embryonic chick calvarial cells. The conditioned medium contained mitogenic activity which eluted with a different elution time than insulin or epidermal growth factor. Characterization of this activity suggests that it was due to human skeletal growth factor (SGF), a mitogen which had been previously isolated from human bone matrix. Common properties include: stimulation of DNA synthesis in cultured embryonic chick calvarial cells, competition with human SGF for binding to anti-SGF antibodies, elution from HPLC gel filtration as a large factor (Mr 100,000) under native conditions but as a small factor (Mr 10,000) under dissociative conditions (4 M guanidine HCl), elution time on HPLC reverse-phase chromatography (small SGF), inactivation by dithiothreitol, stability to heat, acidic or alkaline conditions and inactivation by trypsin and chymotrypsin. These observations provide evidence that human bone cells produce SGF. Conditioned medium from human skin cell cultures also contained mitogenic activity. However, the activity was less than that from bone cells and did not cross-react with the rat anti-SGF antibodies.

Animals↗

Direct effects of ethanol on bone resorption and formation in vitro.

In vitro studies indicate that low concentrations of ethanol can have direct effects on bone formation and resorption. Bone resorption was increased when embryonic chick tibiae were exposed to ethanol at 0.03-0.3% (v/v), and bone formation was inhibited when tibiae were exposed to 0.2% ethanol in the presence of NaF or parathyroid hormone (P less than 0.01 for each). Ethanol also had direct effects on isolated bone cells in vitro, increasing both cAMP and PGE2 production (P less than 0.001 for each), and affecting cell proliferation in a biphasic, time- and dose-dependent manner. After 24 h of exposure, 0.03% ethanol increased bone cell proliferation (P less than 0.001), but 0.3% ethanol was inhibitory (P less than 0.01). Paradoxically, mitogenic doses of ethanol prevented the effects of two other mitogens, NaF and human skeletal growth factor, to increase bone cell proliferation (P less than 0.001). But how were these effects produced? Several observations suggest that these direct effects of ethanol on skeletal tissues in vitro were mediated by changes in bone cell membrane fluidity. (a) Dimethyl sulfoxide, ethylene glycol, and lecithin, which act, like ethanol, to increase membrane fluidity, mimicked the effects of ethanol on bone cell proliferation. Dimethyl sulfoxide also mimicked the effect of ethanol to increase cAMP (P less than 0.001). (b) Cholesterol, which decreases cell membrane fluidity, acted oppositely to ethanol and enhanced the mitogenic response to human skeletal growth factor (P less than 0.001). (c) Preincubation of calvarial cells with ethanol or with cholesterol altered the in situ reaction kinetics of the membrane-bound enzyme, alkaline phosphatase. Together, these data demonstrate that ethanol has direct effects on skeletal tissue in vitro, and suggest that those effects may be secondary to changes in bone cell membrane fluidity.

Alkaline Phosphatase↗

Variations in health insurance coverage: benefits vs. premiums.

Renewed national interest in market forces to promote more efficient and cost-conscious behavior by patients and providers increasingly focuses on the structure of private health insurance benefits. Two features of procompetitive legislative proposals are considered: a ceiling on tax-free employer insurance premiums and offering greater choice of insurance plans. The interests of efficiency and equity invoke different kinds of risks and transfers; no single institutional approach is likely to yield the promised benefits.

Costs and Cost Analysis↗

The use and availability of medical care in health manpower shortage areas.

Data from the National Medical Care Expenditure Survey were used to examine access to care and utilization of health services in federally designated health manpower shortage areas (HMSAs). It was confirmed that residents of shortage areas experience some deprivation in access to care and use of services. Further analysis, however, indicated that shortage area designation has little direct effect on indicators of access and use. Factors such as income and health insurance coverage appear to be more closely associated with access and use than is an area's designation as a HMSA. The assumptions concerning access to care in federally designated shortage areas should therefore be reexamined.

Demography↗

Government health policy and hospital labor costs: the effects of wage and price controls on hospital wage rates and employment.

This study examines the rapid growth of hospital wage rates and employment levels over the past decade, with particular attention to the period 1971-73, when wage and price controls were in effect throughout the economy. The analysis shows that the hospital regulations under the Economic Stabilization Program reduced real hospital wages below what they would have been in the absence of controls; a similar but smaller effect of the controls on hospital employment levels is also shown. This suggests that if the current HEW proposal for hospital cost containment is enacted, its impact would be a significant decrease in the rate of growth of hospital wages and employment.

Cost Control↗

Employer acquisition of health care facilities: a possible outcome of escalating premiums?

The price of health care is rising faster than most other prices; the increasing number of employer-financed health insurance plans means that insurance premiums are a significantly growing expense. Some companies might save money without sacrificing the quality of care by building or buying health care facilities. The authors analyze hospital costs and corporate experience with in-house care.

Cost Control↗

Comparison of the adrenocorticotrophic activities of two synthetic polypeptides: synacthen and DW 75.

The adrenocorticotrophic activities of two synthetic polypeptides, Synacthen (Ciba) and DW 75 (Sandoz), were compared in two groups of patients having a variety of arthritic disorders. Compared with Synacthen, injected either intramuscularly or intravenously, intravenous DW 75 was found to have a longer duration of adrenocorticotrophic activity (measured by plasma 11-hydroxycorticosteroid levels) in both groups of patients, while intramuscularly administered DW 75 did not appear to be absorbed well.

Adrenal Cortex Hormones↗

Fragile X syndrome in a normal IQ male with learning and emotional problems.

The present case study features an adult male who was diagnosed with fragile X syndrome after the identification of this syndrome in his more affected brother. The patient presented with a Full Scale IQ within the broad range of normal and has been diagnosed with a schizotypal personality disorder. He shows significant deficits in the social and emotional aspects of daily life, but has striking cognitive strengths relating to reading and vocabulary as compared to most males affected with fragile X syndrome. DNA testing of blood leukocytes revealed that he has a fully expanded FMR1 CGG repeat mutation associated with almost complete lack of methylation. Protein studies demonstrate a limited production of FMRP, the protein produced by the FMR1 gene. It is believed that the near absence of methylation of the fully expanded mutation and the resultant expression of the FMR1 protein is responsible for the strong cognitive abilities of this fragile X patient.

Adult↗

Medical expenditures and insurance coverage for people with diabetes: estimates from the National Medical Care Expenditure Survey.

Access to health insurance and protection against expenditures for medical care are of special concern to diabetic patients in the United States. This study examines some information on the extent and breadth of public and private health insurance for individuals with diabetes, as well as some estimates of their use of health-care services and their mean expenses for this care. About 12% of all diabetic patients less than 65 yr old (approximately 311,000 individuals) were uninsured throughout 1977, a rate not much different from that for the rest of the United States population. Those with diabetes who are uninsured tend to be younger, Black or Hispanic, in excellent or good health, and live outside of metropolitan areas and in the South or West. As expected, diabetic patients use more medical care than others of their age and sex, and their medical expenses are also much higher, particularly in younger age groups. In 1977, average total medical-care expenses for people with diabetes were $1514 compared with $548 for the rest of the population. They and their families paid approximately 20% out of pocket (approximately $355). Their health insurance premiums were not much different from those without diabetes, averaging approximately $1000 in 1977 for those under age 65. The private insurance coverage for diabetic patients was similar to that for others, although slightly fewer had major medical coverage than the general population.

Adult↗