PubMed Health⌕ Search

Biomedical subjects

V Ross

Publications and source records attributed to V Ross.

At least 37 records · Page 2Linked to original sources

Cyclization by a specific lactam increases the ability of human parathyroid hormone (hPTH)-(1-31)NH2 to stimulate bone growth in ovariectomized rats.

Human parathyroid hormone (hPTH)-(1-31)NH2 (Ostabolin), which only stimulates adenylyl cyclase (AC) instead of AC and phospholipase-C as do hPTH(1-84) and hPTH(1-34), strongly stimulates femoral cortical and trabecular bone growth in ovariectomized (OVX) rats. Two side-chain lactams have been introduced in the hydrophilic face of the receptor-binding region of the fragment's Ser17-Val31 amphiphilic alpha-helix in an attempt to develop improved analogs for the treatment of osteoporosis. Replacing the polar Lys27 with an apolar Leu on the hydrophobic face of this alpha-helix and stabilizing the helix with a lactam between Glu22 and Lys26 produced a fragment, [Leu27]-cyclo(Glu22-Lys26)-hPTH(1-31)NH2, which had six times the AC-stimulating ability of hPTH(1-31)NH2 in ROS 17/2 rat osteosarcoma cells, but the other helix-stabilizing lactam derivative [Leu27]-cyclo(Lys26-Arg30)-hPTH(1-31)NH2 did not have a greater AC-stimulating ability than hPTH(1-31)NH2, to stimulate AC in ROS 17/2 rat osteosarcoma cells. As expected from AC stimulation being responsible for PTH's anabolic action, [Leu27]-cyclo(Glu22-Lys26)-hPTH(1-31)NH2 was, depending on the experimental design, a 1.4 to 2 times better stimulator of trabecular bone growth in the OVX rat model than either hPTH(1-31)NH2 or [Leu27]-cyclo(Lys26-Arg30)-hPTH(1-31)NH2. Thus, there is now a more potently anabolic derivative of hPTH(1-31)NH2, [Leu27]-cyclo(Glu22-Lys26)-hPTH(1-31)NH2, which might ultimately prove to be one of the more effective therapeutics for osteoporosis.

Adenylyl Cyclases↗

No difference in catheter sepsis between standard and antiseptic central venous catheters. A prospective randomized trial.

OBJECTIVE: To determine the efficacy of antiseptic compared with standard triple lumen central venous catheters (CVCs) in reducing the incidence of catheter sepsis and catheter site infection in patients with CVCs for total parenteral nutrition. DESIGN: A prospective, randomized, controlled trial. SETTING: Truman Medical Center, the public teaching hospital for University of Missouri, Kansas City, School of Medicine. PATIENTS: Seventy-two inpatients on the Metabolic Support Service received a CVC for the infusion of total parenteral nutrition. Diagnoses included pancreatic disease, cancer, bowel obstruction, and intestinal surgery, among others. Patients who had a higher risk for contamination during insertion, such as those with a catheter placed through an introducer, inserted in the emergency department, or changed over a guidewire were excluded from the study. INTERVENTION: The control group received a standard CVC without antiseptics. The treatment group received a CVC with a coating of silver sulfadiazine and chlorhexidine gluconate. Each CVC was inspected for infection or malfunction by the Metabolic Support Service 5 times per week. A transparent occlusive dressing was changed every 7 days or more often if there were signs of infection or nonocclusion. When the CVC was removed, the catheter tip, the blood, and the insertion site were cultured. MAIN OUTCOME MEASURES: Although 88 catheters were inserted, only 72 catheters were evaluable. There were 40 patients in the standard group and 32 in the antiseptic group. There were no statistically significant differences between the 2 groups for diagnosis, sex, age, length of stay, days with a CVC, or catheter location. The catheter sepsis rate in the standard group was 8% and in the antiseptic group it was 6%. There were no statistically significant differences between the 2 groups in frequency of site infections or catheter sepsis. CONCLUSIONS: In this study, there were no statistically significant differences in the incidence of catheter-related sepsis or catheter site infections between the standard and antiseptic groups. Future prospective, randomized controlled trials with a larger number of antiseptic catheters are encouraged to confirm or refute these results.

Adult↗

Stimulation of the growth of femoral trabecular bone in ovariectomized rats by the novel parathyroid hormone fragment, hPTH-(1-31)NH2 (Ostabolin).

The human parathyroid hormone, hPTH-(1-84), and its hPTH-(1-34) fragment are promising anabolic agents for treating osteoporosis because they can strongly stimulate the production of biomechanically effective cortical and trabecular bone in osteopenic ovariectomized (OVX) rats and trabecular bone in osteoporotic postmenopausal humans. The ideal PTH fragment for treating osteoporosis would be the smallest and functionally simplest fragment that activates only one signal mechanism and still strongly stimulates trabecular bone growth. A new PTH fragment, hPTH-(1-31)NH2, which only stimulates adenylyl cyclase instead of stimulating both adenylyl cyclase and phospholipase-C as do hPTH-(1-84) and hPTH-(1-34), is this minimum, high-potency anabolic fragment. hPTH-(1-31)NH2 (which we have named Ostabolin) can greatly thicken trabeculae and increase the dry weight and calcium content of trabecular bone in the distal femurs of osteopenic, young, sexually mature OVX Sprague-Dawley rats when injected subcutaneously each day for 6 weeks at doses between 0.4 and 1.6 nmole/100 g of body weight.

Animals↗

Restoration of severely depleted femoral trabecular bone in ovariectomized rats by parathyroid hormone-(1-34).

It is commonly believed that the parathyroid hormone's (PTH's) main function in bone is to stimulate osteoclastic resorption. However, intermittent injections of small doses of PTH holoprotein, but more often its bioactive hPTH-(1-34) fragment, have been shown to stimulate bone growth in animals and humans through their ability to stimulate adenylyl cyclase and not their ability to independently activate a protein kinases-C stimulating mechanism. This anabolic action suggests that PTH might be an effective therapeutic for osteoporosis. If so, the hormone must be able to restore severely depleted trabecular bone, and the goal of this study was to find out if it can. To do this, we started a multiweek program of daily subcutaneous injections of 0.8 nmoles of hPTH-(1-34)/100 g body weight into rats at 4, 8, or 16 weeks after ovariectomy (OVX) and the increasingly severe selective loss of trabecular bone. These injections strongly stimulated femoral trabecular bone to grow and mineralize at the same rate regardless of how much of it had been lost before the injections were started. Thus, the progressively depleting trabecular bone in the femurs of OVX rats does not lose its anabolic responsiveness to PTH. This finding is another indication of the likelihood of small, adenylyl cyclase-stimulating PTH fragments being effective therapeutics for osteoporosis.

Analysis of Variance↗

Parathyroid hormone fragments may stimulate bone growth in ovariectomized rats by activating adenylyl cyclase.

PTH is regarded conventionally as a catabolic hormone that stimulates osteoclastic resorption of bone. However, it has been known since 1932 that intermittent pulses of PTH stimulate bone formation in animals and humans. PTH independently activates two signal mechanisms: one that stimulates adenylyl cyclase and one that stimulates protein kinase C (PKC). The goal of this study was to use the 3- to 5-month-old ovariectomized (OVX) rat model to determine which of the two signal mechanisms is responsible for the anabolic action of PTH on bone. OVX triggered a large loss of trabecular bone without significantly affecting the normal slow growth of cortical bone in the distal halves of the femora. Daily injections of human hPTH(1-34) fragment (1 nmol/100 g body weight), which stimulated both adenylyl cyclase and membrane-associated PKC activity in osteoblast-like ROS 17/2 rat osteosarcoma cells, stimulated the growth of both cortical and trabecular bone in the OVX rats. Daily injections of the same dose of hPTH(1-31), which stimulated adenylyl cyclase but not PKC in ROS 17/2 cells, stimulated trabecular bone growth in the OVX rats less effectively than hPTH(1-34), but it stimulated cortical bone growth as rapidly and as dramatically as hPTH(1-34). Injections of equimolar amounts of desamino-hPTH(1-34) [N-propionyl(2-3)hPTH-amide], which stimulated PKC as strongly as hPTH(1-34) in ROS 17/2 cells but had a drastically reduced ability to stimulate adenylyl cyclase, or injections of recombinant hPTH(8-84) which stimulated PKC only in the ROS 17/2 cells, did not stimulate cortical or trabecular bone growth in the OVX animals. Thus, cyclic AMP and cyclic AMP-dependent protein kinases may be the primary mediators of the anabolic action of intermittent pulses of PTH on bone in OVX rats.

Adenylyl Cyclases↗

Bright light treatment of behavioral and sleep disturbances in patients with Alzheimer's disease.

OBJECTIVE: The authors tested the hypothesis that evening bright light pulses would improve sleep-wake patterns and reduce agitation in patients with Alzheimer's disease who have severe sundowning (a syndrome of recurring confusion and increased agitation in the late afternoon or early evening) and sleep disorders. METHOD: Ten inpatients with Alzheimer's disease on a research ward of a veterans' hospital were studied in an open clinical trial. All patients had sundowning behavior and sleep disturbances. After a week of baseline measurements, patients received 2 hours/day of exposure to bright light between 7:00 p.m. and 9:00 p.m. for 1 week. During the baseline week, the treatment week, and a posttreatment week, patients were rated by nurses for agitation, sleep-wake patterns, use of restraints, and use of prescribed-as-needed medication. On the last 2 days of each week, patients wore activity monitors. Activity counts were analyzed for circadian rhythmicity. RESULTS: Clinical ratings of sleep-wakefulness on the evening nursing shift improved with light treatment in eight of the 10 patients. The proportion of total daily activity occurring during the nighttime decreased during the light-treatment week. The relative amplitude of the circadian locomotor activity rhythm, a measure of its stability, increased during the light-treatment week. More severe sundowning at baseline predicted greater clinical improvement. CONCLUSIONS: Evening bright light pulses may ameliorate sleep-wake cycle disturbances in some patients with Alzheimer's disease. This effect may be mediated through a chronobiological mechanism.

Aged↗

A single-case-study method for treating resistiveness in patients with Alzheimer's disease.

A single-case-study approach was used to identify the best medication for treating resistiveness to care in patients with moderately advanced dementia. The double-blind research design incorporated three medications, placebo washout periods, multiple baselines, frequent ratings by nurses of patients' resistiveness, and visual and statistical analysis of results to find the optimal drug, one that provided a stable response at a low dose. Six patients completed the trials. Thiothixene was more effective than oxazepam and diphenhydramine. Important features of the design were its avoidance of polypharmacy and high doses and its use of frequent ratings (each nursing shift) of patients' resistiveness. Although the single-case-study method is labor intensive, it can be beneficial when adapted for clinical use.

Aged↗

A successful aging project: pooling university and community resources.

1. In successful aging, the effects of aging are minimized by such extrinsic factors as nutrition, exercise, stress management, and social support. 2. Mutual and individual goal setting was encouraged at the outset of the successful aging sessions. The most frequently mentioned goals were learning more about health, staying well, feeling well, and helping others to be well. 3. A nonjudgmental attitude toward previous knowledge or lifestyle was prevalent. By tapping formal and informal community resources to deliver a program of health promotion, the project maximized cooperation within an aging services network.

Aged↗

Geriatric tinnitus: causes, clinical treatment, and prevention.

1. Tinnitus is seldom recorded in the clinical database of the elderly, despite the fact that next to hearing loss, tinnitus is the most commonly reported ear problem by the elderly population. 2. Common problems of the elderly that demand special counseling and teaching skills of the nurse are decreased tolerance to tinnitus due to coexistent complex morbidity, social problems, and losses; worry that the tinnitus is a sign of an impending crisis, such as stroke, brain tumor, or insanity; and boredom with excess time with little to do but to listen to one's tinnitus. 3. Tinnitus in aging is a symptom that is usually due to an identifiable disease, and is rarely of subjective type, high-pitched quality, chronic, irreversible, idiopathic, and bilateral. 4. The common causes and aggravating factors about tinnitus in aging can provide the clues to effective nursing-initiated measures, many of which are simple household activities or personal interactions.

Aged↗

Genetic heterogeneity of the human glutathione transferases: a complex of gene families.

The glutathione transferases (GSTs) are involved in the metabolism of a wide range of compounds of both exogenous and endogenous origin. There is evidence that deficiency of GST may increase sensitivity to certain environmentally derived carcinogens. In contrast, elevated expression has been implicated in resistance to therapeutic drugs. The GSTs are the products of several gene families. This review summarizes the present knowledge of the genetic interrelationships between the various isoenzymes, their deficiencies and the physical locations of their genes.

Animals↗

Diarrheal illness among infants and toddlers in day care centers: effects of active surveillance and staff training without subsequent monitoring.

From October 1981 to September 1984, the authors conducted a three-year longitudinal study of diarrhea among infants and toddlers attending day care centers in Maricopa County, Arizona. In the third year of study, they evaluated the effects on diarrhea rates of staff training without external monitoring and of active surveillance conducted throughout the study. From 21 study day care centers, they randomly selected 10 ("intervention day care centers") to receive staff training in procedures to reduce transmission of infectious diarrhea. Continuing active surveillance in the 10 intervention and 11 control day care centers found no difference between diarrhea rates in intervention day care centers in the pre- and posttraining years and no difference between diarrhea rates in the two groups of centers either before or after the training intervention. Biweekly family-based surveys during the two months after training also demonstrated no difference between infant-toddler diarrhea rates in intervention and control day care centers. These surveys found the 21 study day care centers to have significantly higher diarrhea rates than did day care homes or households not using day care, but significantly lower rates than day care centers not included in the active surveillance. Continuous surveillance without training was associated with a significant decrease in diarrheal illness during the course of longitudinal study. One-time staff training without subsequent monitoring did not result in additional decreases and did not lower day care center diarrhea rates to the levels observed in day care homes and households not using day care.

Arizona↗

Molecular cloning and characterization of esterase-6, a serine hydrolase of Drosophila.

The Est-6 gene of Drosophila melanogaster was cloned by screening libraries with synthetic oligonucleotides corresponding to tryptic peptides from purified esterase-6 (Est-6) protein. cDNA clones were isolated that hybridized in situ to the site of Est-6 on chromosome 3 at 69A1. Inserts in putative Est-6 cDNA clones were 1.85 kilobases (kb) long, and blot hybridization analysis of electrophoretically fractionated RNA, using a cDNA clone as a probe, revealed two transcripts, of 1.68 and 1.83 kb. The two transcripts showed the same developmental profile as the Est-6 protein. Neither transcript was detected in an Est-6-null line. The cDNA fragment was homologous to a 2.3-kb EcoRI-BamHI fragment in genomic clones, and this region was interrupted by the 8-kb B104 transposable element in the Est-6-null line. Conceptual translation of the cDNA sequence revealed a protein of 548 residues with 19% sequence similarity to acetylcholinesterase from the Torpedo ray.

Amino Acid Sequence↗