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Biomedical subjects

C McGee

Publications and source records attributed to C McGee.

14 recordsLinked to original sources

Collaboration between a state alliance for the mentally ill and a state mental health authority in monitoring the consequences of downsizing.

As consumers are released from hospitalization as a result of the downsizing of inpatient psychiatric facilities, their ability to sustain themselves in the community becomes a concern to a number of constituencies. This article describes the development of a program for monitoring persons who were released from hospitals into the community as a result of the downsizing of state psychiatric hospitals. The program's uniqueness was the collaboration between the state mental health authority and the state Alliance for the Mentally Ill in developing and implementing the monitoring system.

Case Management

Secondary amenorrhea leading to osteoporosis: incidence and prevention.

Osteoporosis is widely accepted as a "female disease" occurring primarily in postmenopausal women. The fact that this disease can affect premenopausal women experiencing menstrual dysfunction is less commonly known. Amenorrhea decreases bone density at an age when bone formation should still be occurring. The implications of this failure to attain sufficient bone density during the formative years are frightening. The adverse effects on skeletal strength may lead to devastating outcomes in this subgroup of women, either now or in the future. This article reviews causes, risk factors, and treatments associated with both osteoporosis and amenorrhea. Three causes of secondary amenorrhea are discussed in detail: rigorous physical training, anorexia nervosa, and use of the contraceptive agent medroxyprogesterone acetate injection. A review of the literature is presented in order to establish the link between amenorrhea and osteoporosis. A great many young women may be unknowingly placing themselves at risk for developing osteoporosis. This article includes interventions that may decrease this risk and improve quality of life.

Adolescent

Modulation of lysyl oxidase by dietary copper in rats.

Lysyl oxidase levels were estimated in rat tissues using an enzyme-linked immunosorption assay (ELISA) and a functional assay standardized against known amounts of purified lysyl oxidase. High concentrations of lysyl oxidase (> or = 150 micrograms/g of tissue or packed cells) were detected in connective tissues, such as tendon and skin. Values for aorta, kidney, lung and liver ranged from 30 to 150 micrograms/g of tissue; values for skeletal muscle and diaphragm were < 30 micrograms/g tissue. Purified rat skin lysyl oxidase catalyzed the release of 50-100 Bq of tritium per micrograms enzyme in assays that used 3H-elastin-rich substrates. In dense connective tissues, good agreement was obtained for the values from ELISA and those derived from measurements of functional activity in aorta, lung, skin and tendon (r2 > 0.9). When egg white-based experimental diets containing 2 or 10 micrograms/g added copper were fed to weanling rats, values for skin lysyl oxidase functional activity in the group fed 2 micrograms/g added copper were one-third to one-half the values for skin lysyl oxidase functional activity in rats fed 10 micrograms/g copper. This reduction in lysyl oxidase activity, however, had minimal effect on indices of collagen maturation in rat skin, e.g., collagen solubility in neutral salt and dilute acid or the levels of acid stable cross-links. Moreover, copper deficiency did not influence the steady-state levels of lysyl oxidase specific mRNA in rat skin or the apparent amounts of lysyl oxidase in rat skin as determined by ELISA. These observations underscore that the concentration of lysyl oxidase is relatively high in dense corrective tissues, and although decreasing dietary copper influences functional activity, there is little apparent effect on the production of lysyl oxidase protein.

Administration, Oral

The feasibility of HLA matching for lung transplantation.

The benefits of HLA matching have been clearly demonstrated in renal and cardiac transplantation. Recent studies suggest that HLA matching may be associated with improved survival rates for transplantation as well. However, the effect of HLA matching for lung transplantation has not been clearly demonstrated. Despite the possible benefits of HLA compatibility, matching for lung transplantation is based solely on ABO compatibility and lung size. Several factors limit the feasibility of utilizing HLA matching for lung transplantation. Among these factors is the time required to perform HLA typing, to identify appropriate recipients, and to allocate lungs; an additional constraint is the urgent need for transplantation in patients experiencing rapid clinical decline. The obstacles to using prospective HLA matching for lung allocation are significant, and matching lung donors and recipients according to histocompatibility status would require considerable effort. However, with supra-regional cooperation among transplant centers and procurement agencies, it appears feasible to consider HLA matching for lung transplantation. Given the potential for improved survival, a project should be undertaken to determine the impact of HLA matching on the outcome of lung transplantation.

ABO Blood-Group System

Effects of aging and caloric restriction on extracellular matrix biosynthesis in a model of injury repair in rats.

This study was designed to investigate the effects of aging and caloric restriction on collagen deposition in a model of wound healing. Polyvinyl alcohol sponges were implanted in Fischer 344 rats aged 6, 10, or 24 months. Sponges were removed after 7, 10, or 14 days and analyzed for hydroxyproline content and for enzymatic crosslinks. Aging was associated with a decrease in collagen accumulation as well as a delay in reaching peak rates of collagen accumulation. Levels of enzymatic crosslinks were increased in granulation tissue from old animals relative to young animals. Caloric restriction (60% of ad libitum intake) maintained only during the 2-week experimental period did not affect collagen accumulation, but did result in decreased levels of the difunctional crosslink dihydroxylysinonor-leucine (DHLNL) in sponges implanted for 10 days, but not 14 days. Caloric restriction initiated 4 months before sponges were implanted resulted in decreased collagen accumulation and decreases in DHLNL at all implantation times. These studies suggest that: (1) aging affects total collagen production as well as rate of collagen production in response to injury; (2) aging is not associated with impaired crosslinking in granulation tissue; (3) chronic caloric restriction is associated with decreased collagen production and decreased levels of DHLNL; (4) the adverse effects of chronic caloric restriction on wound healing may have a greater impact on wound healing in old animals.

Aging

Expression and accumulation of lysyl oxidase, elastin, and type I procollagen in human Menkes and mottled mouse fibroblasts.

Menkes syndrome in humans is an X-linked disorder characterized in part by abnormal copper transport, cellular copper sequestration, and defective crosslinking of collagen and elastin. A decrease in the functional activity of lysyl oxidase, a cuproenzyme, is thought in part to be responsible for the decreased crosslinking of collagen and elastin. It has also been suggested that low levels of lysyl oxidase activity may occur secondarily to disturbances in intracellular copper translocation and consequently impaired incorporation of copper into lysyl oxidase. Herein, we examine the expression and accumulation of selected extracellular matrix proteins in fibroblasts from a Menkes patient, as well as fibroblasts from the tortoiseshell (MoTo/y) mouse. The MoTo mutation is an allele of the mottled (Mo) locus, which is considered to be a murine analog of the human Menkes locus. In both Menkes and tortoiseshell fibroblasts, levels of lysyl oxidase mRNA transcripts were less than 15% of levels for corresponding controls. The level of elastin mRNA transcripts was also markedly lower in both cell lines in comparison to controls. In contrast, the levels of procollagen Type I mRNA were similar or enhanced in Menkes and MoTo/y fibroblasts compared to their respective controls. Consequently, we conclude that the connective tissue defects associated with Menkes syndrome and those occurring in mottled mouse mutants involve more than abnormal copper utilization in the formation of lysyl oxidase holoenzyme. Based on the present studies in cell culture, the production of essential enzymes and matrix proteins, such as lysyl oxidase and elastin, appear to be altered at the level of transcription or mRNA turnover.

Animals

Chemical modifications of proteins in vivo: selected examples important to cellular regulation.

The synthesis and degradation pathways for individual proteins and functional peptides often involve numerous co- and post-translational modifying steps. This review focuses on the diversity of such reactions. The reactions are organized into functional categories. An overall goal is to highlight post-translational events as often having the same importance to functional protein production as the transcriptional and translational events that initiate their synthesis.

Amino Acids

Electromechanical analogs of human reflexes.

The conclusion to be drawn from our modeling is that the combined stretch and tendon reflexes alone can endow artificial muscle with a springlike feel as well as give it a baseline tone. In response to questions that motor physiologists often ask as to what variables the system controls, the answer here is clear: the stretch and tendon reflexes act together to maintain both a tension set-point and a length set-point, but in so doing they also give the system a springlike feel because of the existence of a servo error. The main goal of our studies is to understand the integration of reflexes, and thus far we have only begun to explore the two lowest-level spinal reflexes. We are in the process of expanding this work by developing a much more refined arm explicitly modeled after the human arm. This new arm is to be activated by a minimum of 10 muscles, each of which is reflexively driven, and it will allow us to explore the integration of higher-level reflex action such as automatic inhibition of antagonists and facilitation of synergists.

Humans

Effects of catecholamines on serum lipoproteins of normally fed and cholesterol-fed rabbits.

The effects of catecholamines on the regulation of lipoprotein metabolism have not been defined. We examined the effects of subcutaneously administered slow-release preparations of norepinephrine (2 mg/kg) and isoproterenol (0.2 mg/kg) on the serum lipoproteins of New Zealand White rabbits. Drugs or control suspension were administered daily to three groups of normally fed and three groups of cholesterol-fed rabbits, and lipoprotein analysis was performed at intervals over a 60-hour period. In the normally fed animals, norepinephrine increased the serum levels of triglyceride and phospholipid by factors of 2.4 (P less than .01) and 1.35 (P less than .05), respectively, compared with control animals at 60 hours, but had no effect on serum cholesterol. All components of serum very low density lipoproteins (VLDL: triglyceride, cholesterol, phospholipid, and protein) were significantly (P less than .01) elevated by norepinephrine in the normally fed animals. In the cholesterol-fed animals, norepinephrine at 60 hours significantly increased total serum cholesterol, triglyceride, and phospholipid concentrations by factors of 1.7 (P less than .05), 5.0 (P less than .01), and 1.6 (P less than .05), respectively, compared with controls. The norepinephrine effects in these animals was due to significant elevation of total VLDL and low density lipoproteins (LDL) and all their elemental components. Isoproterenol produced no significant effect on serum lipoprotein levels in the normally fed rabbit, but in cholesterol-fed animals it produced a rise in total serum VLDL and LDL triglyceride concentrations compared with controls at 60 hours. These data demonstrate that catecholamines are involved in the regulation of lipoprotein metabolism.

Animals

Mineral excretion in premature infants receiving various diuretic therapies.

The association of various diuretic therapies with the renal handling of minerals, important factors in the development of nephrocalcinosis and osteopenia, was studied in low birth weight infants. Twenty-four-hour urine specimens (n = 65) were collected from 30 patients who were treated with (1) furosemide with or without spironolactone and hydrochlorothiazide (2) spironolactone with hydrochlorothiazide, (3) spironolactone alone, or (4) no diuretic (control; i.e., after diuretic). Hypercalciuria (urinary calcium greater than or equal to 0.15 mmol/kg/day) was observed in all but the control group. Covariate analysis demonstrated a significant effect of sodium, calcium, and vitamin D intakes (p less than 0.01) and sodium excretion (p less than 0.05) on urinary calcium excretion. Treatment with any of these diuretics in neonates may be associated with abnormal renal losses of calcium, sodium, chloride, and potassium. From a nutritional perspective, neonates requiring long-term diuretic therapy thereby require special consideration, including monitoring of mineral excretion and renal ultrasonography.

Birth Weight