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Biomedical subjects

R Smith

Publications and source records attributed to R Smith.

At least 1,063 records · Page 59Linked to original sources
PubMed1988

Bone status of senescent male rats: chemical, morphometric, and mechanical analysis.

The bone status of male rats 6, 12, and 24 months of age (n = 10) was examined. Femur calcium (Ca), phosphorus (P), and osteocalcin contents; serum chemistry; and mechanical properties of the bone were measured and correlated. Diaphyseal Ca, P, and osteocalcin contents were not different in animals 6 and 12 months of age but decreased significantly at 24 months: -7.4% for Ca, -4.2% for P, and -24% for osteocalcin compared to 12 months. Femurs from 24-month-old (senescent) rats were characterized by a scalloped appearance of the midfemoral endosteal surface and by cortical porosities. These age-associated changes coincided with nearly two-fold increases in serum immunoreactive parathyroid hormone (PTH) and osteocalcin. Serum Ca did not change with age, whereas serum P decreased (-14.8%) from 6 to 24 months. Maximum breaking force required to fracture femurs at midshaft did not change with age. Hence, the strength of the femur as an intact organ was not compromised with age despite the loss of diaphyseal Ca and P in the senescent animal. However, ultimate stress, a parameter that normalizes for differences in bone geometry and size, decreased 35% in femurs from 12- compared with 24-month-old animals. These mechanical results might be explained by the morphometric finding that, in contrast to the small but progressive age-associated increases in femur weight and length, the cortical and medullary areas increased at least two-fold. Therefore, the strength of the intact femur was maintained by architectural compensations, even though normalized tissue strength decreased with age. These findings suggest that bone status was compromised in the aged male rat.

Aging↗
PubMed1988

Interferon-inhibited human osteosarcoma xenografts induce host bone in nude mice.

The growth of human osteosarcoma xenografts in nude mice can be inhibited by human interferon-alpha (IFN-alpha). Histologic examination of growth-inhibited tumors has revealed mineralization and partial replacement of the tumor by normal bone tissue. We have investigated whether the normal bone tissue was formed by differentiated tumor cells or by induction of host stroma to differentiate into bone tissue. Employing antibodies to both murine and human type I collagen, it was found that the normal bone produced in IFN-inhibited osteosarcomas was host derived. These results suggest that IFN induced the osteosarcoma cells to produce a bone-inductive agent that interacts with the host cells, and leads to the formation of mature normal bone tissue in a heterotopic site.

Animals↗
PubMed1988

Bone mineral content in the senescent rat femur: an assessment using single photon absorptiometry.

The single photon absorptiometry technique was evaluated for measuring bone mineral content (BMC) of the excised femurs of the rat, and the system was used to examine the changes in cortical and trabecular bone from young adult (6 mo), mature adult (12 mo), and senescent (24 mo) male and female animals. BMC of the femur midshaft, representing cortical bone, apparently increased progressively with advancing age. The width of the femur at the scan site also increased with age. Normalizing the midshaft BMC by width partially compensated for the age-associated increase. However, when bone mineral values were normalized by the cortical area at the scan site, to take into account the geometric differences in the femurs of different aged animals, maximum bone densities were found in the mature adult and these values decreased slightly in the femurs from senescent rats. In contrast, the BMC of the femur distal metaphysis, representing trabecular bone, decreased markedly in the aged rat. The loss of trabecular bone was also evident from morphological examination of the distal metaphysis. These findings indicated that bone mineral loss with age was site specific in the rat femur. These studies provided additional evidence that the rat might serve as a useful animal model for specific experiments related to the pathogenesis of age-associated osteopenia.

Aging↗
PubMed1988

Bone status of senescent female rats: chemical, morphometric, and biomechanical analyses.

The bone status of female rats, 6, 12, and 24 months of age was examined. Femur Ca, Pi, and osteocalcin contents, as well as biomechanical properties, were measured and correlated to physical indices and serum chemistry. Diaphyseal Ca, Pi, and osteocalcin did not change significantly with increasing age. Serum Ca and Pi concentrations were not altered in the aged rat. Immunoreactive parathyroid hormone (PTH) levels increased significantly with age, when analyzed by linear regression. Serum osteocalcin decreased progressively from 6 to 12 months (-21%) and from 12 to 24 months (-23%). Maximum breaking force required to fracture femurs at midshaft did not change with senescence. Hence, the strength of the femurs as an intact organ was not compromised in aging. However, ultimate stress, a parameter that normalizes for differences in bone geometry and size, decreased 14% from 12 to 24 months. Changes in other biomechanical parameters, including yield and ultimate deformation, strain, and modulus of elasticity, were relatively small, but statistically significant, or were negligible. Morphometric measurements indicated a progressive age-related increase in second moment of area and cortical area. Medullary area did not change with age. Therefore, strength of the intact femur was maintained by architectural compensations, although normalized tissue strength decreased in senescence. The bone status and Ca/Pi homeostasis of the female rat were compared to similar findings, reported previously, for the male animal. The results suggest that bone status and mineral metabolism were compromised in the aged female rat, but the magnitude of change was less than that found for the senescent male rat.

Aging↗
PubMed1988

Comparison of alprazolam plasma levels in normal Asian and Caucasian male volunteers.

Single-dose pharmacokinetics of alprazolam was studied in 42 normal male volunteers (14 Caucasians, 14 American-born Asians, and 14 foreign-born Asians), after both oral and parenteral (IV) administration of a small dose (0.5 mg) of the test drug. Asians manifested significantly higher Cmax, larger AUC, slower CL and longer t1/2 under both testing situations. When body surface area was used as a covariate, these cross-ethnic differences remained statistically significant (except Cmax) after oral but not IV drug administration. There were no differences between the two Asian groups in any of these parameters examined in this study. These results confirmed previous observations of ethnic differences in the pharmacokinetic response between Asians and Caucasians and suggested that smaller doses of alprazolam may be required for Asians for similar clinical effects as compared to their Caucasian counterparts.

Administration, Oral↗
PubMed1988

A simple apparatus for controlling nucleation and size in protein crystal growth.

A simple device is described for controlling vapor equilibrium in macromolecular crystallization as applied to the protein crystal growth technique commonly referred to as the "hanging drop" method. Crystal growth experiments with hen egg white lysozyme have demonstrated control of the nucleation rate. Nucleation rate and final crystal size have been found to be highly dependent upon the rate at which critical supersaturation is approached. Slower approaches show a marked decrease in the nucleation rate and an increase in crystal size.

Crystallization↗
PubMed1988

Thumb reconstruction by the posterior interosseous osteocutaneous flap.

An island osteo-fasciocutaneous flap, based on the posterior interosseous vessels, is described for thumb reconstruction. The artery supplies the fascial plexus of the posterior forearm as well as the superficial and deep extensor muscles. A vascularised bone segment of the upper third of the ulna can be harvested, including a cuff of the extensor pollicis longus muscle. The flap was used successfully in two clinical cases.

Adolescent↗
PubMed1988

Forms and intracellular distribution of alpha-D-mannosidases in murine liver and spleen.

1. The intracellular distribution of alpha-D-mannosidase in homogenates of murine liver and spleen was investigated by differential and gradient density centrifugation. 2. In both tissues an enzyme with a neutral pH optimum was found in the cytosol together with an alpha-D-mannosidase with optimal activity between pH 5.5 and 6.0 which was also partially membrane-bound. 3. In liver the acidic alpha-D-mannosidase was obtained almost entirely in a particulate form distributed equally between a heterogeneous low density region and heavy density lysosomes. 4. The lysosomal form of the liver enzyme was purified to electrophoretic homogeneity and shown to be a glycoprotein composed of four identical subunits of molecular weight 65 kDa. 5. Antibody raised against the purified liver alpha-D-mannosidase immunoprecipitated a polypeptide from spleen which had the same molecular size. This acidic enzyme was the predominant type of alpha-D-mannosidase in spleen, but in contrast to liver, it was obtained mainly in a cytosoluble form, the remaining activity being present in the heterogeneous light density compartment. 6. Although both tissues contain the same molecular form of the acidic alpha-D-mannosidase, in murine spleen this enzyme does not appear to be associated with stable heavy density lysosomes.

Animals↗
PubMed1988

An examination of the association between vertebral deformities, physical disabilities and psychosocial problems.

In order to measure the clinical consequences of spinal osteoporosis, we correlated a number of physical and psychosocial dysfunctions with the degree of vertebral deformity in 204 women aged 55-75 yr. We employed 5 standardized questionnaire instruments: the physical dimension of the Sickness Impact Profile (SIP), an analog back pain scale, a 24-question instrument eliciting back-related disabilities, and assessments of self-esteem and mastery. Using these results as the dependent variables, we performed 5 separate stepwise regression analyses; independent variables were vertebral deformity score and 11 possible confounders. Using Pearson correlation coefficients, we found a high degree of correlation between each of the 5 primary outcome variables. Vertebral deformity score played a small but statistically significant role in the 3 models whose dependent variable was related to physical dysfunction, but it accounted for only 4-10% of the variance of these models. Mastery and self-esteem were related to overall poor health and attendant physical disabilities but not to vertebral deformity score. In this selected cohort of women, the occurrence of mild to moderate vertebral deformities caused little loss of physical function or function of psychosocial problems because of vertebral deformity. Although we were able to demonstrate a statistically significant handicap related to the total vertebral deformity score, several other clinical variables appeared to have a greater impact.

Aged↗
PubMed1988

The effects of chronic vitamin D deficiency on the skeleton in the adult rabbit.

Albino rabbits were fed a 1.0% Ca, 0.5% P, vitamin D-deficient diet for 11.7 to 31.3 mo. Control rabbits were fed either this diet with the addition of 2.2 units/gm of vitamin D3 or a standard laboratory rabbit ration. Serum levels of 25-OH-D and 1,25-(OH)2D were both undetectable in all vitamin D-deficient rabbits but were present at levels typically found in other species in the control rabbits. Vitamin D deficiency resulted in elevated serum PTH values but did not produce significant changes in serum Ca levels, femur length, femur ash weight to body weight ratio, or tibial breaking strength. The vitamin D-deficient rabbits could be readily separated into two distinct subgroups. Four of these rabbits were normophosphatemic (P = 3.7 +/- 0.4 mg/dl) whereas the other five were severely hypophosphatemic (P = 0.8 +/- 0.2 mg/dl). During the last 10 days of the study the control and normophosphatemic vitamin D-deficient rabbits were in positive Ca and zero P balance. The hypophosphatemic vitamin D-deficient rabbits were in zero Ca and negative P balance. This negative P balance resulted from a net intestinal secretion, as urinary P excretion was negligible. Femur ash weight as a percentage of dry weight was decreased in hypophosphatemic but not the normophosphatemic vitamin D-deficient rabbits. Histomorphometric analyses indicated the bones from the normophosphatemic vitamin D-deficient rabbits were normal. In contrast, vertebral trabecular bone from the hypophosphatemic rabbits contained large amounts of osteoid that was not mineralizing, as indicated by a failure to take up the fluorescent label calcein.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Differences in action potential configuration in ventricular trabeculae correlate with differences in density of transverse tubule-sarcoplasmic reticulum couplings.

The goal of the present study was to identify structural correlates to an observed variability in the response of ventricular muscle action potential configuration to ryanodine. In a previous study, rabbit ventricular trabeculae were shown to display either a shortened action potential (Group I) or lengthened action potential (Group II) in response to the negative inotropic drug ryanodine. The configuration of control action potentials were also different in these two groups. Action potentials in Group I trabeculae exhibited a prominent early repolarization and low plateau, while those in Group II exhibited a small early repolarization and high plateau. Electron microscope morphometric data showed that there is a significant, positive linear correlation between the number of transverse tubules displaying internal couplings with sarcoplasmic reticulum and the change in action potential duration in the presence of ryanodine. No other differences in internal coupling structure were observed. Although variability in the prominence of M-lines was also apparent between myocytes in both Group I and Group II, there is no correlation between the M-line prominence and ryanodine-induced change in electrophysiological behavior. No other structural variability was noted between Group I and Group II trabeculae. It is suggested that the difference in electrophysiological characteristics in the two groups might be due to a difference in T-tubular density. This hypothesis seems most plausible if there is a differential distribution of ion channels between the surface membrane and T-tubular membrane.

Action Potentials↗
PubMed1988

A new model for providing prehospital medical care in large stadiums.

To determine proper priorities for the provision of health care in large stadiums, we studied the medical incident patterns occurring in a major college facility and combined this with previously reported information from four other large stadiums. Medical incidents were an uncommon occurrence (1.20 to 5.23 per 10,000 people) with true medical emergencies being even more unusual (0.09 to 0.31 per 10,000 people). Cardiac arrest was rare (0.01 to 0.04 events per 10,000 people). However, the rates of successful resuscitation in three studies were 85% or higher. The previous studies were descriptive in nature and failed to provide specific recommendations for medical aid system configuration or response times. A model is proposed to provide rapid response of advanced life support care to victims of cardiac arrest. We believe that the use of this model in large stadiums throughout the United States could save as many as 100 lives during each football season.

Adolescent↗
PubMed1988

Protein-induced glomerular hyperfiltration: role of hormonal factors.

High protein diets acutely elevate the glomerular filtration rate. To characterize this response we administered 1 g of protein/kg body weight as a beef steak meal to nine, healthy male subjects and measured glomerular filtration rate (inulin clearance), renal plasma flow (p-amino hippurate clearance), plasma renin activity, aldosterone and plasma and urinary catecholamines. The subjects ingested the meal on three separate days and were pretreated with either placebo, 50 mg indomethacin (to inhibit renal prostaglandin synthesis), or 10 mg enalapril (to inhibit angiotensin II synthesis). Following placebo treatment protein feeding significantly increased the glomerular filtration rate, from a pre-meal level of 101 +/- 7 ml/min/1.73 m2 to a post-meal level of 130 +/- 6 ml/min/1.73 m2, P less than 0.005. A parallel rise in renal plasma flow and a fall in renal vascular resistance were noted. Indomethacin pretreatment attenuated the increase in glomerular filtration rate following the protein meal, 105 +/- 6 ml/min/1.73 m2 pre-meal level to 118 +/- 4 ml/min/1.73 m2 post-meal, P greater than 0.1. Enalapril pretreatment had no significant effect on protein-induced glomerular hyperfiltration. Protein feeding following placebo increased plasma aldosterone concentration while the concentrations were unchanged in the studies where enalapril or indomethacin was administered. Protein feeding following placebo or indomethacin did not alter plasma renin activity while plasma renin activity rose following enalapril administration. Urinary norepinephrine excretion rose while plasma norepinephrine concentration was unchanged in all three study groups. A decrease in urinary dopamine excretion was also noted four hours after the protein meal was ingested.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

The effect of repetitive haemorrhage on plasma cortisol, beta-endorphin and N-terminal pro-opiomelanocortin in conscious sheep.

We measured the effect of repeated haemorrhagic stress, performed on four consecutive days in conscious adult sheep, on the plasma concentrations of cortisol and ACTH-related peptides to determine whether the pituitary-adrenal response was altered by stress repetition. Peptides from the C-terminus of the ACTH pro-hormone was measured by beta-endorphin RIA. Glycopeptides derived from the N-terminus of the ACTH pro-hormone were measured by tau 3-MSH RIA. The immunoreactive tau 3-MSH in sheep plasma was found to have an apparent molecular weight of approximately 10,000 by gel chromatography through Sephadex G-75, which is similar to the size of the major circulating form of pro-tau-MSH found in human and rat plasma. Daily haemorrhage consistently elevated plasma concentrations of cortisol and pro-tau-MSH. There was no significant difference in the daily responses of either cortisol or pro-tau-MSH when considered individually. However, there was a significant change over the four days in the relationship between the cortisol and pro-tau-MSH responses, as judged by analysis of variance of the difference in daily z-scores of cortisol and pro-tau-MSH. This trend indicated a relative increase in the secretion of pro-tau-MSH from the pituitary compared to the cortisol response, and suggested that repeated exposure to stressful stimuli may alter the pituitary-adrenal-axis.

Animals↗
PubMed1988

A finite state machine algorithm for finding restriction sites and other pattern matching applications.

Existing algorithms for finding restriction endonuclease recognition sites use brute-force algorithms which run in time 0(NM) where N is the number of nucleotides in the sequence under analysis and M is the total number of nucleotides in all the different sites being searched for. This paper presents a deterministic finite state machine algorithm which runs in time 0(N). Memory use can be as high as 0(M4) but a slight modification to the basic algorithm can impose a theoretical upper bound of 0(M) at the cost of some added complexity in the execution of the state machine. The algorithm can operate with a single pass through the sequence under analysis, with no need to back up or (for non-circular sequences) store more than a single input character at a time. This type of algorithm can be adapted to many pattern-matching tasks and is simple enough to implement in hardware that it could, for example, be built into a disk controller as part of a specialized database machine.

Algorithms↗
PubMed1988

Renal scintigraphy with technetium Tc 99m succimer: clinical utility in newborns with cystic renal dysplasia.

We have presented the case of a neonate with bilateral cystic renal dysplasia and normal pulmonary development, in whom technetium Tc 99m succimer scintigraphy demonstrated absence of normal renal cortical tubular tissue and correctly predicted that life-sustaining renal function would not occur. Since renal uptake of this radioactive agent depends on the functional mass of cortical tubular tissue, and the cystic dysplasias are characterized by abnormal dysplastic renal ductal and tubular tissue, this imaging agent can provide important prognostic information concerning renal function in these patients.

Humans↗