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Biomedical subjects

P Ross

Publications and source records attributed to P Ross.

At least 19 recordsLinked to original sources
PubMed1995

Characterisation of the copper uptake mechanism and isolation of the ceruloplasmin receptor/copper transporter in human placental vesicles.

In this paper we have studied copper (Cu) uptake by microvillar vesicles isolated from human term placenta. We have characterised Cu uptake from CuHis2 complexes and shown that ceruloplasmin (Cp) inhibits uptake. Inhibition is complex and variable; in one series of experiments, the Vmax for uptake drops from 31.3 +/- 1.2 nmol/min per mg vesicle protein without added Cp to 11.3 +/- 1 nmol/min per mg vesicle protein at 91 micrograms/ml Cp. Similarly, the K0.5 increases from 0.35 +/- 0.08 microM to 1.35 +/- 0.25 microM, while the n value (the Hill coefficient) falls from 1.9 +/- 0.23 in the absence of Cp to 1.1 +/- 0.13 In another series, Cp had no effect below concentrations of about 100 micrograms/ml and in a third series only increased K0.5. The variability in effect seems to be related to the specific activity of the ceruloplasmin, which in turn is related to the copper complexes of the protein. The effect is specific for Cp; apotransferrin and a2-macroglobulin have no effect. 67Cu-labelled ceruloplasmin binds specifically to vesicles of term placenta with an affinity of 2.8 microU/mg vesicle protein and a Bmax of 79 microU/mg vesicle protein. CuHis2, but not histidine alone, can block the uptake. The data can be reconciled by proposing that the binding site of the transporter is relatively small and recognises a Cu-dihistidine structure common to the low-molecular-weight complex and to the Type I and Type II coppers of ceruloplasmin. We have used these observations to develop an isolation method for the transporter and have identified it as a protein of M(r) 90,000 which is closely associated with alkaline phosphatase. There are also two proteins of M(r) 45,000 and 40,000 which may be breakdown products of the larger complex. Antibodies to the 45,000 protein block Cu binding and uptake from CuHis2 complexes, strongly implicating it as the copper transporter/ceruloplasmin receptor of human term placenta.

Carrier Proteins↗
PubMed1995

Predicting vertebral deformity using bone densitometry at various skeletal sites and calcaneus ultrasound.

We investigated the usefulness of bone density measurements from multiple skeletal sites and calcaneus ultrasound for evaluating the probability of vertebral deformation. Bone mineral density (BMD) was measured at the second metacarpal and middle phalanges using radiographic absorptiometry of hand radiographs, and at the lumbar spine using dual-energy x-ray absorptiometry. Distal radius and proximal radius were measured using single-energy x-ray absorptiometry (SXA), expressed as bone mineral content (BMC, grams per centimeter), and as BMD (grams per square centimeter). The calcaneus was measured using both SXA (BMD) and broadband ultrasound attenuation (BUA). Among the women in this study (mean age 74, SD = 5), 84 women developed new vertebral deformations (57 cases with one and 27 cases with two or more deformations), which were identified on serial radiographs during an average of 9 years prior to the measurements of bone density. Logistic regression analysis was used to calculate odds ratios for risk of deformation corresponding to a 1-SD difference in density or ultrasound, adjusted for age. All bone measurements were significantly associated with vertebral deformation, with odds ratios (95% confidence intervals) ranging from 1.40 (1.10, 1.78) for proximal radius BMD to 1.88 (1.45, 2.44) for calcaneus BMD measurements. Measurements of calcaneal BUA, calcaneal BMD, and hand BMD generally remained significant when included simultaneously with another measurement in the same model, suggesting that spine or radius BMD may not provide much additional information about risk of deformation. It appears that all of the measurements of bone density and ultrasound provide useful information regarding the probability of deformation. These findings await confirmation in a prospective study.

Absorptiometry, Photon↗
PubMed1992

Preferential osteopenia in women with osteoporotic fractures.

One-hundred thirty-six women with spontaneous vertebral crush fractures had bone density measurements by photon absorptiometry. Their absolute and relative extent of osteopenia were expressed as Z scores with respect to values from normal white women. Absolute Z scores were used to express the mean bone mass of women with crush fractures vis-a-vis normal women at peak bone mass; relative Z scores were used to express the same means vis-a-vis age-matched controls. The skeletal sites measured included the distal radius, lumbar spine, and three sites on the femur (neck, Ward's triangle, and trochanter). The absolute deficit for the five sites ranged from -1.66 to -2.60. The relative deficit was close to 1 SD for all sites. A discriminant analysis revealed that the spine and femur were predictive for vertebral crush fractures but the radius was not. Comparison with a previously reported hip-fracture population (n = 31) showed that the low bone density of the spine separated the two fracture groups best. We propose the following: (a) vertebral-fracture patients have extensive generalized osteoporosis including the hip with a preferential deficit in the spine and (b) hip-fracture patients have generalized osteoporosis with preferential osteopenia of the hip and do not have a greater mineral deficit in the spine or radius than age-matched normal women. It may be that if a single site is to be selected for screening for spine and hip fractures, the greatest value would be in measurement of the femur, although ideally the skeletal site of interest would be measured. Prospective studies are needed to confirm the utility of measurements at the spine and hip in prediction of future fractures.

Absorptiometry, Photon↗
PubMed1992

Hereditary nonspherocytic hemolytic anemia due to pyruvate kinase deficiency: a prevalence study in Quebec (Canada).

Fifty-eight cases of hereditary nonspherocytic hemolytic anemia due to pyruvate kinase deficiency were collected from both laboratories that have performed the assay since 1972 and from attending physicians in the province of Quebec. Using the postal addresses of the probands, a prevalence map was constructed according to the administrative regions of the province of Quebec. The prevalence was found to be higher in eastern Quebec (1/81,838) than in western Quebec (1/139,086). Fifty probands were of French Canadian origin whereas the remaining 6 were recent immigrants.

Anemia, Hemolytic, Congenital Nonspherocytic↗
PubMed1992

Treatment of cryptosporidiosis with paromomycin. A report of five cases.

Cryptosporidiosis continues to be one of the most devastating complications of the acquired immunodeficiency syndrome, causing severe, chronic diarrhea that is largely refractory to treatment. More than 60 drugs have been tried in the treatment of cryptosporidiosis, none of which have been consistently successful. We describe the successful treatment of cryptosporidiosis in five patients with acquired immunodeficiency syndrome with oral paromomycin at a dose of 1500 to 2000 mg/d. All five patients had resolution of symptoms and normalization of bowel movements, although one patient later relapsed while receiving paromomycin. Three of five patients cleared Cryptosporidium from the stool. Paromomycin is a promising therapy for cryptosporidiosis in acquired immunodeficiency syndrome and further prospective clinical trials are warranted.

AIDS-Related Opportunistic Infections↗
PubMed1991

Polypeptide composition of bacterial cyclic diguanylic acid-dependent cellulose synthase and the occurrence of immunologically crossreacting proteins in higher plants.

To comprehend the catalytic and regulatory mechanism of the cyclic diguanylic acid (c-di-GMP)-dependent cellulose synthase of Acetobacter xylinum and its relatedness to similar enzymes in other organisms, the structure of this enzyme was analyzed at the polypeptide level. The enzyme, purified 350-fold by enzyme-product entrapment, contains three major peptides (90, 67, and 54 kDa), which, based on direct photoaffinity and immunochemical labeling and amino acid sequence analysis, are constituents of the native cellulose synthase. Labeling of purified synthase with either [32P]c-di-GMP or [alpha-32P]UDP-glucose indicates that activator- and substrate-specific binding sites are most closely associated with the 67- and 54-kDa peptides, respectively, whereas marginal photolabeling is detected in the 90-kDa peptide. However, antibodies raised against a protein derived from the cellulose synthase structural gene (bcsB) specifically label all three peptides. Further, the N-terminal amino acid sequences determined for the 90- and 67-kDa peptides share a high degree of homology with the amino acid sequence deduced from the gene. We suggest that the structurally related 67- and 54-kDa peptides are fragments proteolytically derived from the 90-kDa peptide encoded by bcsB. The anti-cellulose synthase antibodies crossreact with a similar set of peptides derived from other cellulose-producing microorganisms and plants such as Agrobacterium tumefaciens, Rhizobium leguminosarum, mung bean, peas, barley, and cotton. The occurrence of such cellulose synthase-like structures in plant species suggests that a common enzymatic mechanism for cellulose biogenesis is employed throughout nature.

Affinity Labels↗
PubMed1991

Biochemical short-term changes produced by hormonal replacement therapy.

Seventy-one white women within 6 months to 6 years postmenopause were randomly assigned to three treatment groups: (a) placebo, (b) calcium, (c) cyclic estrogen-progestin plus calcium. Calcium was given as calcium carbonate with meals to attain an intake of 1,700 mg daily in the latter two groups. All women received 400 IU of vitamin D daily. Samples were obtained at baseline and after 2 months therapy. The hormonal treatment group had a decline in serum calcium, osteocalcin and urinary hydroxyproline and an increase in levels of calcitonin, parathyroid hormone and calcitriol. The increase in the latter two measurements could have resulted from the drop in serum calcium, it is also possible that the increase in calcitonin levels was a result of calcium supplementation. Although all these changes were statistically significant for the estrogen treatment group when considered alone, analysis of variance including the 3 groups demonstrated significance for the estrogen group for the parameters of skeletal metabolism but not for the changes in the calciotrophic hormones. There was an increase in serum calcium (p = 0.05) in the calcium augmentation group. It would be of interest to determine the effects of higher intakes of calcium in both the calcium and the estrogen treatment groups and to further explore differences in effects on bone remodeling between the two treatment approaches as well as the possibility of a additive effects. Early effects of estrogen replacement reduce bone remodeling whereas calcium supplementation to 1,700 mg per day of Ca CO3 did not appear to affect the parameters of bone remodeling.

Bone Remodeling↗
PubMed1991

Relationship of menopause to skeletal and muscle mass.

Cross-sectional and longitudinal changes in body composition with age were examined in white women to determine the relationship of body cell mass to menopause and of body fat to bone mass. There was statistical evidence for a curvilinear component to loss of total body potassium with negligible rates of loss before menopause. Longitudinal measurements also indicated a relationship between the proximity to menopause and the rate of loss of potassium. Total body potassium was significantly related to total body calcium and bone density of the spine, radius, and femoral neck. Total body fat was not related to any of these measurements. We found no evidence that adiposity plays a major role in protecting against bone loss.

Adipose Tissue↗
PubMed1991

Cellulose biosynthesis and function in bacteria.

The current model of cellulose biogenesis in plants, as well as bacteria, holds that the membranous cellulose synthase complex polymerizes glucose moieties from UDP-Glc into beta-1,4-glucan chains which give rise to rigid crystalline fibrils upon extrusion at the outer surface of the cell. The distinct arrangement and degree of association of the polymerizing enzyme units presumably govern extracellular chain assembly in addition to the pattern and width of cellulose fibril deposition. Most evident for Acetobacter xylinum, polymerization and assembly appear to be tightly coupled. To date, only bacteria have been effectively studied at the biochemical and genetic levels. In A. xylinum, the cellulose synthase, composed of at least two structurally similar but functionally distinct subunits, is subject to a multicomponent regulatory system. Regulation is based on the novel nucleotide cyclic diguanylic acid, a positive allosteric effector, and the regulatory enzymes maintaining its intracellular turnover: diguanylate cyclase and Ca2(+)-sensitive bis-(3',5')-cyclic diguanylic acid (c-di-GMP) phosphodiesterase. Four genes have been isolated from A. xylinum which constitute the operon for cellulose synthesis. The second gene encodes the catalytic subunit of cellulose synthase; the functions of the other three gene products are still unknown. Exclusively an extracellular product, bacterial cellulose appears to fulfill diverse biological roles within the natural habitat, conferring mechanical, chemical, and physiological protection in A. xylinum and Sarcina ventriculi or facilitating cell adhesion during symbiotic or infectious interactions in Rhizobium and Agrobacterium species. A. xylinum is proving to be most amenable for industrial purposes, allowing the unique features of bacterial cellulose to be exploited for novel product applications.

Bacteria↗
PubMed1991

Clarification of the role of CT scan in the acute evaluation of blunt abdominal trauma.

We reviewed 100 patients sustaining blunt trauma whose initial evaluation included an abdominal computed tomographic scan (CT) to assess the role of this modality in managing these patients. Indications for CT scan were suspicion of abdominal injury based on mechanism of injury (46), tenderness (22), falling hematocrit (9), hematuria (5), pain (4), and hyperamylasemia (1). Thirty-four patients had abdominal injury, and four scans identified non-traumatic pathology; 66 patients had no evidence of abdominal injury. There were no additional abdominal injuries detected during the hospitalizations. Mechanism of injury was the only indication for CT scan in 20 patients, none of whom had evidence of abdominal injury. CT scan charges for these 20 patients accounted for 5.5% of the total hospital bill ($204,070). Hospital costs would have been reduced by $11,270 if these patients had been followed clinically. Fifteen patients with soft tissue contusions and normal CT scans were hospitalized less than 72 hours. Room and other hospital charges accounted for 38.5% of the hospital bill; these are costs that would have been saved if these patients had been discharged from the emergency service. Several conclusions can be made from this study. First, abdominal CT scan is a sensitive test for abdominal injury. Secondly, patients without objective signs of abdominal injury whose other injuries warrant admission allowing further observation should be followed clinically and do not need the additional expense of abdominal CT scan. Finally, mechanism of injury alone is not an indication for CT scan.

Abdominal Injuries↗
PubMed1990

Effect of thiazide on rates of bone mineral loss: a longitudinal study.

OBJECTIVE: To determine the effect of thiazide diuretic drugs on rates of bone mineral loss. DESIGN: Longitudinal, observational study with a mean follow up of five years. SETTING: Hawaii Osteoporosis Center, Honolulu. SUBJECTS: 1017 Japanese-American men born between 1900 and 1920, of whom 378 were treated for hypertension (study group) and 639 did not have hypertension (control group). INTERVENTION: Thiazide diuretics were taken by 325 men for a mean of 11.9 years; 53 men took antihypertensive drugs other than thiazides. MAIN OUTCOME MEASURE: Rate of bone loss estimated from serial photon absorptiometric scanning at three skeletal sites (calcaneus, distal radius, and proximal radius). RESULTS: Rates of bone loss at all three sites were significantly reduced among thiazide users when compared with controls. The reductions in loss rate ranged from 28.8% (p = 0.02) (distal radius) to 49.2% (p = 0.0005) (calcaneus) relative to the controls. At all three sites the men taking other antihypertensive drugs had faster loss rates (22.6-43.1%) than those of the controls but the difference was significant only for the distal radius. CONCLUSION: Thiazide diuretics slow the rate of bone loss in elderly men.

Absorptiometry, Photon↗
PubMed1990

The cyclic diguanylic acid regulatory system of cellulose synthesis in Acetobacter xylinum. Chemical synthesis and biological activity of cyclic nucleotide dimer, trimer, and phosphothioate derivatives.

An unusual compound, cyclic-bis(3'----5') diguanylic acid (c-di-GMP or cGpGp), is involved in the regulation of cellulose synthesis in the bacterium Acetobacter xylinum. This cyclic dinucleotide acts as an allosteric, positive effector of cellulose synthase activity in vitro (Ka = 0.31 microM) and is inactivated via degradation by a Ca2(+)-sensitive phosphodiesterase, PDE-A (Km = 0.25 microM). A series of 13 analogs cyclic dimer and trimer nucleotides were synthesized, employing a phosphotriester approach, and tested for the ability to mimick c-di-GMP as activators of cellulose synthase and as substrates for PDE-A. Seven of the synthetic compounds stimulate cellulose synthase activity and all of these activators undergo the Ca2(+)-inhibited degradation reaction. The order of affinities for synthase activators is cGpGp approximately cdGpGp approximately cGp(S)Gp (S-diastereomer) greater than cIpGp greater than cdGpdGp greater than cXpGp greater than cIpIp greater than cGp(S)Gp (R-diastereomer). Three cyclic dinucleotides of negligible affinity for either enzyme are cApAp, cUpUp, and cCpCp. This same order of affinities essentially pertains to the analogs as inhibitors of PDE-A activity, but at least one cyclic dinucleotide, cXpXp, which does not bind to cellulose synthase, is also a substrate for the degradation reaction, demonstrating that although the two enzymes share a similar, high degree of specificity for c-di-GMP, their cyclic dinucleotide binding sites are not identical. Phosphodiester bonds of activators in which an exocyclic oxygen is replaced with an atom of sulfur (cGp(S)Gp isomers) resist the action of PDE-A, and such derivatives may be prototypes for synthetic non-hydrolyzable c-di-GMP analogs.

Allosteric Regulation↗
PubMed1990

Intermittent cyclical etidronate treatment of postmenopausal osteoporosis.

BACKGROUND: To determine the effects of etidronate (a bisphosphonate that inhibits osteoclast-mediated bone resorption) in the treatment of postmenopausal osteoporosis, we conducted a prospective, two-year, double-blind, placebo-controlled, multicenter study in 429 women who had one to four vertebral compression fractures plus radiographic evidence of osteopenia. METHODS: The patients were randomly assigned to treatment with phosphate (1.0 g) or placebo twice daily on days 1 through 3, etidronate (400 mg) or placebo daily on days 4 through 17, and supplemental calcium (500 mg) daily on days 18 through 91 (group 1, placebo and placebo; group 2, phosphate and placebo; group 3, placebo and etidronate; and group 4, phosphate and etidronate). The treatment cycles were repeated eight times. The bone density of the spine was measured by dual-photon absorptiometry, and the rates of new vertebral fractures were determined from sequential radiographs. RESULTS: After two years, the patients receiving etidronate (groups 3 and 4) had significant increases in their mean (+/- SE) spinal bone density (4.2 +/- 0.8 percent and 5.2 +/- 0.7 percent, respectively; P less than 0.017). The rate of new vertebral fractures was reduced by half in the etidronate-treated patients (groups 3 and 4 combined) as compared with the patients who did not receive etidronate (groups 1 and 2 combined) (29.5 vs. 62.9 fractures per 1000 patient-years; P = 0.043); the effect of treatment was most striking in the subgroup of patients with the lowest spinal bone mineral density at base line, in whom fracture rates were reduced by two thirds (42.3 vs. 132.7 fractures per 1000 patient-years; P = 0.004). The addition of phosphate provided no apparent benefit. There were no significant adverse effects of treatment. CONCLUSIONS: Intermittent cyclical therapy with etidronate for two years significantly increases spinal bone mass and reduces the incidence of new vertebral fractures in women with postmenopausal osteoporosis.

Aged↗
PubMed1990

Protein synthesis and secretion in the human epididymis and immunoreactivity with sperm antibodies.

The synthesis and secretion of proteins in the different regions of the human epididymis were studied in vitro. Epididymal tissues obtained from patients undergoing castration for prostatic carcinoma or from cadavers were incubated in the presence of [35S]methionine, and the resulting radiolabeled proteins were analysed on SDS-PAGE. The corpus region was found to be the most active segment in total protein synthesis. Significant qualitative and quantitative changes were observed in the pattern of proteins secreted from the different epididymal regions. To establish those epididymal proteins that interact with maturing sperm, the secreted products were immunoreacted with antibodies raised against a Triton X-100 extract of ejaculated human sperm heads. The antibodies react mainly with the head region of ejaculated spermatozoa as judged by indirect immunofluorescence. Protein A-gold labeling of freeze-fracture images showed gold particle distribution on the sperm plasma membrane. Western blot analysis of the secreted proteins revealed four bands (66, 37, 32, and 29 kDa) in the proximal regions and six additional bands (80, 76, 48, 27, 22, and 17 kDa) in the distal part of the epididymis. Immunoprecipitation of the secreted proteins with these antibodies revealed six radioactive bands of 170, 80, 76, 60, 48, and 37 kDa, which indicates that certain proteins of epididymal origin bind to the sperm plasma membrane.

Adult↗
PubMed1990

Aging bone loss from the femur, spine, radius, and total skeleton.

In order to establish a comprehensive model for involutional bone loss, the following measurements were made of healthy white women: total body calcium by neutron activation analysis, bone density of the distal radius by single-photon absorptiometry, and dual-photon absorptiometry of the lumbar spine and femur (neck, Ward's triangle, and intertrochanteric areas). Longitudinal measurements were made for each of these skeletal sites except the femur. Evidence for a curvilinear component to the pattern of bone loss with aging was found for total body calcium and bone density of the radius, but not for the other measurements on analysis of cross-sectional data. Longitudinal studies confirmed that substantial bone loss begins only after menopause for the radius, whereas there is substantial premenopausal loss of bone from the lumbar spine. Prevention of vertebral osteoporosis requires maximizing bone mass before menopause. If longitudinal data confirm the model of linear rates of bone loss for the femur, there will be important implications for prevention of hip fractures.

Adult↗