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Biomedical subjects

P Andrews

Publications and source records attributed to P Andrews.

At least 37 records · Page 2Linked to original sources
PubMed1999

Dental microwear of Griphopithecus alpani.

The examination of microscopic dental wear allows inferences to be made about diet in extinct species. This study reconstructs the diet of Griphopithecus alpani, a 15 Ma fossil hominoid from the Miocene site of Paşalar in north-western Turkey, using scanning electron microscopy (SEM) to examine the microscopic wear on its molar teeth. The microwear patterns of Griphopithecus are compared with those of three extant hominoid taxa-Gorilla gorilla gorilla, Pan troglodytes verus, and Pongo pygmaeus pygmaeus. The microwear on three occlusal wear surfaces is examined in this study, and sex and age differences are also included. Analysis of variance is performed on the following microwear variables-feature density, pit density, striation density, the ratio of pits relative to striations, pit widths, and striation widths. Griphopithecus has significantly higher microwear feature densities and higher percentages of pits than Gorilla. It also has larger pit frequencies and narrower striations than both Pan and Gorilla. There are no significant differences between the microwear patterns of Griphopithecus and Pongo. This suggests that the diet of Gripho-pithecus was more similar to that of Pongo, which consumes mainly fruit, and occasionally hard and unripe fruits and nuts, than to that of Pan and Gorilla. In addition, the high percentage of pits displayed by Griphopithecus may indicate that it was ingesting harder fruits and/or objects than the extant hominoids, although this is not a significant difference. There also are consistent variations in the microwear present on the three different wear facets examined in the study-Phase II facets display more microwear and pitting than the Phase I surface examined. The results of this study do not indicate variation in dental microwear according to sex or age.

Age Factors↗
PubMed1999

Medical treatment of the aorta. I.

Diseases of the thoracic aorta are serious conditions that require close observations. Impressive advances in imaging modalities such as magnetic resonance imaging, computed tomography sacs, and transesophageal echocardiography have aided diagnosis and provided insights into the pathogenesis and natural history of thoracic aortic aneurysms, dissection, and atherosclerosis. The current review highlights the etiology, epidemiology, and pathophysiology of these disorders and focuses on the diagnostic approach and suggested medical therapies in the current era.

Adrenergic beta-Antagonists↗
PubMed1999

Cyclooxygenase inhibitors increase Na-K-2Cl cotransporter abundance in thick ascending limb of Henle's loop.

Cyclooxygenase inhibitors, such as indomethacin and diclofenac, have well-described effects to enhance renal water reabsorption and urinary concentrating ability. Concentrating ability is regulated in part at the level of the thick ascending limb of Henle's loop, where active NaCl absorption drives the countercurrent multiplication mechanism. We used semiquantitative immunoblotting to test the effects of indomethacin and diclofenac, given over a 48-h period, on the expression levels of the ion transporters responsible for active NaCl transport in the thick ascending limb. Both agents strongly increased the expression level of the apical Na-K-2Cl cotransporter in both outer medulla and cortex. Neither agent significantly altered outer medullary expression levels of other thick ascending limb proteins, namely, the type 3 Na/H exchanger (NHE-3), Tamm-Horsfall protein, or alpha1- or beta1-subunits of the Na-K-ATPase. Administration of the EP3-selective PGE(2) analog, misoprostol, to indomethacin-treated rats reversed the stimulatory effect of indomethacin on Na-K-2Cl cotransporter expression. We conclude that cyclooxygenase inhibitors enhance urinary concentrating ability in part through effects to increase Na-K-2Cl cotransporter expression in the thick ascending limb of Henle's loop. This action is most likely due to elimination of an EP3-receptor-mediated tonic inhibitory effect of PGE(2) on cAMP production.

Animals↗
PubMed1999

Decreased abundance of collecting duct aquaporins in post-ischemic renal failure in rats.

Increased urine flow is often a feature of mild to moderate acute renal failure. This study examines the possible role of dysregulation of collecting duct aquaporins as a factor in this increase. In rats, the left renal pedicle was clamped for 45 min followed by contralateral nephrectomy. Control rats were identical except that the renal pedicle was not clamped. Rats were sacrificed and the kidneys were homogenized at various time points after release of the clamp for semiquantitative immunoblotting of collecting duct aquaporins, as well as the thick ascending limb Na-K-2Cl cotransporter and the proximal tubule water channel, aquaporin-1. Urinary flow rate was significantly increased 18 h after the ischemic insult and remained increased through 72 h. Whole kidney aquaporin-2 protein abundance was 45% of controls at 18 h, 55% of controls at 36 h, and returned to normal 72 h after ischemia. Whole kidney aquaporin-3 protein abundance was 37% of controls at 18 h, 13% of controls at 36 h, and 45% of controls at 72 h. The decline in aquaporin-2 and -3 was confirmed by immunocytochemistry. Abundance of the thick ascending limb Na-K-2Cl cotransporter protein was not significantly decreased. Aquaporin-1 protein abundance was not significantly decreased at 18 h after the ischemic insult, but was significantly reduced after 36 h. Thus, the post-ischemic state is associated with decreased levels of the collecting duct aquaporins, coinciding with an increase in water excretion. It is concluded that decreased aquaporin protein abundance in collecting duct cells is a contributing factor in the increased urine flow seen in moderate post-ischernic acute renal failure.

Acute Kidney Injury↗
PubMed1998

The polypeptide backbone of recombinant human zona pellucida glycoprotein-3 initiates acrosomal exocytosis in human spermatozoa in vitro.

Human gamete interaction is of fundamental biological importance, yet the molecular interactions between spermatozoa and the zona pellucida are poorly understood. Surprisingly, the role of the polypeptide backbone of zona pellucida glycoprotein 3 (ZP3), the putative ligand for spermatozoa activation, has been largely overlooked. Purified recombinant human ZP3 was expressed in Escherichia coli as a C-terminal fusion to the dimeric glutathione S-transferase (GST) from Schistosoma japonicum and was shown to induce acrosomal exocytosis in live, capacitated human spermatozoa. The level of exocytosis is comparable with that obtained using purified, glycosylated, recombinant human ZP3 [van Duin, M., Polman, J.E.M., DeBreet, I.T.M., Van Ginneken, K., Bunschoten, H., Grootenhuis, A., Brindle, J. and Aitken, R.J. (1994). Biol Reprod. 51, 607-617]. These data imply that the polypeptide chain of human ZP3 contributes to recognition of spermatozoa during acrosomal exocytosis in vitro.

Acrosome↗
PubMed1998

Taphonomy and palaeoecology of Olduvai Bed-I (Pleistocence, Tanzania).

Detailed taxonomic and taphomonic studies of rodents and palaeoecological analysis have been undertaken to investigate faunal change in Olduvai Bed-I. The palaeoenvironments inferred from rodent faunas recorded in Olduvai Bed-I suggest a change between the middle (FLK + FLKNN) and the top of the series (FLKN). Changes have also been observed from taxonomic studies of large mammals and from palynological studies. These differences have been attributed in the past to climatic change, but taphonomic studies suggest a more complex scenario. The environment at Olduvai Bed-I is here interpreted through analysis of fossil faunas and fossilization processes. Identification of the causative agents that could have altered the faunal composition provides information on the environment and on the nature of the change observed between the middle and top of Bed-I. This information can then be used to test conflicting hypotheses about the origins and amount of faunal and pollen change. Results show evidence of predation in all units of Bed-I and can be attributed to different predators along the series. Different predator behaviours explain some of the variability observed by previous authors in the small mammal species composition between the middle and the top of Bed-I. After taking taphonomy into account, the remaining faunal differences point to environmental differences between middle and upper Bed-I and even greater within the upper Bed-I sequence. These differences go beyond the range that is present today in the tropical woodland-savanna biome. Our interpretation of the palaeoenvironments is that the middle Bed-I faunas indicate a very rich closed woodland environment, richer than any part of the present-day savanna biome in Africa, changing to less rich woodland in upper Bed-I with a trend towards more open and seasonal woodlands at the top of the series.

Animals↗
PubMed1998

Impaired aquaporin and urea transporter expression in rats with adriamycin-induced nephrotic syndrome.

Nephrotic syndrome is associated with abnormal regulation of renal water excretion. To investigate the role of collecting duct water channels and solute transporters in this process, we have carried out semiquantitative immunoblotting of kidney tissues from rats with adriamycin-induced nephrotic syndrome. These experiments demonstrated that adriamycin-induced nephrotic syndrome is associated with marked decreases in expression of aquaporin-2, aquaporin-3, aquaporin-4, and the vasopressin-regulated urea transporter in renal inner medulla, indicative of a suppression of the capacity for water and urea absorption by the inner medullary collecting duct. In contrast, expression of the alpha(1)-subunit of the Na,K-ATPase in the inner medulla was unaltered. Light and electron microscopy of perfusion-fixed kidneys demonstrated that the collecting ducts are morphologically normal and unobstructed. Inner medullary expression of the descending limb water channel, aquaporin-1, was not significantly altered, pointing to a selective effect on the collecting duct. Aquaporin-2 and aquaporin-3 expression was also markedly diminished in the renal cortex, indicating that the effect is not limited to the inner medullary collecting duct. Differential centrifugation studies and immunocytochemistry in inner medullary thin sections demonstrated increased targeting of aquaporin-2 to the plasma membrane, consistent with the expected short-term action of vasopressin on aquaporin-2 trafficking. The extensive down-regulation of aquaporin and urea transporter expression may represent an appropriate renal response to the extracellular volume expansion observed in nephrotic syndrome, but may occur at the expense of decreased urinary concentrating and diluting capacity.

Adenylyl Cyclases↗
PubMed1998

Concentrating defect in experimental nephrotic syndrone: altered expression of aquaporins and thick ascending limb Na+ transporters.

BACKGROUND: Several pathophysiological states associated with deranged water balance are associated with altered expression and/or intracellular distribution of aquaporin water channels. The possible role of dysregulation of thick ascending limb NaCl transporters, which are responsible for countercurrent multiplication in the kidney, has not been evaluated. METHODS: Semiquantitative immunoblotting and immunocytochemistry were carried out in the kidneys of rat with adriamycin-induced nephrotic syndrome and in vehicle-injected control rats. RESULTS: Preliminary studies confirmed the presence of a severe concentrating defect. Semiquantitative immunoblotting of outer medullary homogenates demonstrated a marked decrease in the abundance of three thick ascending limb Na+ transporters in nephrotic rats, namely the bumetanide-sensitive Na-K-2Cl cotransporter (BSC-1), the type 3 Na/H exchanger (NHE-3), and the alpha 1-subunit of the Na-K-ATPase. These results are predictive of a decrease in the NaCl transport capacity of the medullary thick ascending limb and therefore a decrease in countercurrent multiplication. Immunocytochemistry of outer medullary thin sections demonstrated broad (but highly variable) suppression of BSC-1 expression in the outer medullas of adriamycin-nephrotic rats. There was also a large decrease in outer medullary expression of two collecting duct water channels (aquaporin-2 and -3) and the major water channel of the thin descending limb of Henle's loop (aquaporin-1). CONCLUSION: The concentrating defect in adriamycin-induced nephrotic syndrome in rats is a consequence of multiple defects in water and solute transporter expression, which would alter both the generation of medullary interstitial hypertonicity and osmotic equilibration in the collecting duct. Whether a similar widespread defect in transporter expression is present in idiopathic nephrotic syndrome is, at this point, untested.

Animals↗
PubMed1998

Characterization of specular "dark events" in human donor corneal endothelium by scanning and transmission electron microscopy.

PURPOSE: To evaluate changes in the donor corneal endothelium in the intact globe and in the in vivo rabbit cornea to characterize more fully the formation of "dark events" without relief images in the endothelial mosaic. METHODS: Six ex vivo human donor corneas in the intact globe and an in vivo rabbit model were used to assess the morphological changes associated with osmotically increasing fluid movement from the anterior chamber into the stroma by specular (SM), confocal (CM), and transmission and scanning electron microscopy (TEM, SEM). RESULTS: After application of hyperosmotic solution on the anterior surface of the cornea, dark events without relief images were observed by SM and CM. In both human and rabbit corneas, SEM showed that apical pores at the Y-junctions between endothelial cells became enlarged. Large subendothelial spaces were observed on Descemet's membrane by TEM with some spaces communicating with the anterior chamber. CONCLUSIONS: The findings suggest that these openings at the Y-junctions may represent intercellular channels that may also act as pathways for the formation of intercellular and subendothelial vacuoles in both the rabbit and human donor corneal endothelium. By virtue of their location, these vacuoles are characterized by lack of relief images as seen with the contact SM.

Adult↗
PubMed1997

Effect of hepatic methyl donor status on urinary excretion and DNA damage in B6C3F1 mice treated with sodium arsenite.

This study evaluated the effect of hepatic methyl donor status on the ability of sodium arsenite (2.5, 5.0 and 10.0 mg/kg) administered by gavage once or on four consecutive days to induce DNA damage in male B6C3F1 mice. Maintenance on a choline-deficient (CD) diet prior to treatment resulted in mice with hepatic methyl donor deficiency (HMDD) and altered arsenical metabolism, as demonstrated by a decreased total urinary excretion of inorganic and organic arsenicals. The alkaline (pH > 13) Single Cell Gel (SCG) assay was used to evaluate for the induction of DNA damage (single strand breaks, alkali labile sites, DNA crosslinking) in blood leukocytes, liver parenchymal cells, and cells sampled from bladder, lung, and skin, while the bone marrow erythrocyte micronucleus (MN) assay was used to assess for the induction of chromosomal damage in bone marrow cells. Treatment with sodium arsenite once or four times induced a significant decrease in DNA migration (indicative of DNA crosslinking) in bladder and liver parenchymal cells of hepatic methyl donor sufficient (HMDS) mice, but in skin cells of HMDD mice. Both HMDD and HMDS mice exhibited a significant increase in the frequency of micronucleated polychromatic erythrocytes (MN-PCE) in bone marrow following four, but not following one, treatments. However, the positive response occurred at a lower dose for HMDS mice and, in these mice, bone marrow toxicity, as demonstrated by a significant reduction in the percentage of PCE, was present also. These results indicate that hepatic methyl donors deficiency significantly decreases the total urinary excretion of orally administered sodium arsenite and markedly modulates target organ arsenic-induced DNA damage, with an apparent shift from liver and bladder to skin.

Administration, Oral↗
PubMed1997

Cocaethylene toxicity.

Concurrent use of cocaine and alcohol produces another psychoactive substance known as cocaethylene which has pharmacological properties similar to that of cocaine but which has a plasma half-life three to five times that of cocaine. This slow removal from the body makes it an attractive drug for abuse. However, cocaethylene has been associated with seizures, liver damage, and compromised functioning of the immune system. It also carries an 18- to 25-fold increase over cocaine alone in risk for immediate death.

Alcoholism↗
PubMed1997

Reduced renal medullary water channel expression in puromycin aminonucleoside--induced nephrotic syndrome.

The aquaporins are molecular water channels that mediate transcellular water transport across water-permeable epithelia. To investigate the cause of the concentrating defect in the nephrotic syndrome, immunoblotting using membrane fractions from inner medulla was utilized to assess the level of expression of four aquaporin water channels in vehicle-treated versus puromycin aminonucleoside (PAN)-treated rats. Scanning electron microscopy demonstrating loss of glomerular foot processes and measurements of urinary protein excretion confirmed the efficacy of the PAN treatment. In rats receiving PAN, there was an increase in plasma vasopressin, without a change in plasma sodium concentration. Inner medullary tissue hypertonicity was sustained in PAN-treated rats while the urinary osmolality was low, pointing to defective osmotic equilibration across the collecting ducts in PAN-nephrosis. Among collecting duct aquaporins, there was an 87% decrease in aquaporin-2 expression and a 70% decrease in aquaporin-3 expression in the inner medulla, whereas aquaporin-4 expression was unaltered. Transmission electron microscopy of the inner medullary collecting ducts of PAN-treated rats showed normal-appearing cells. Thus, PAN-nephrosis is associated with an extensive downregulation of collecting duct water channel expression despite increased circulating vasopressin, providing an explanation for the concentrating defect associated with the nephrotic syndrome.

Animals↗
PubMed1997

Aggressiveness of colon carcinoma in blacks and whites. National Cancer Institute Black/White Cancer Survival Study Group.

Black patients with colon cancer in the Black/White Cancer Survival Study were found to have a poorer survival than white patients. More advanced-stage disease at diagnosis was the primary determinant, accounting for 60% of the excess mortality. After adjusting for stage, factors such as poverty, other socioeconomic conditions, and treatment did not further explain the remaining survival deficit. This study examined the aggressiveness of colon tumors in blacks and whites to explore its role in the racial survival differences. Tumor characteristics of 703 cases of newly diagnosed invasive colon adenocarcinoma were centrally evaluated by a gastrointestinal pathologist, blinded in regard to the age, race, and sex of the patients. Blacks were less likely to have poorly differentiated (grade 3) tumors [odds ratio (OR), 0.44; 95% confidence interval, 0.22-0.88] and lymphoid reaction (OR, 0.49; 95% confidence interval, 0.26-0.90) when compared with whites. These black/white (B/W) differences remained statistically significant after adjusting for age, sex, metropolitan area, summary stage, socioeconomic status, body mass index, and health care access and utilization. In addition, blacks were less likely to have high-grade (grade 3) nuclear atypia, mitotic activity, and tubule formation, although these ORs did not reach a statistical significance level of 0.05. Similar B/W differences were observed for patients with advanced disease but not with early stage. Comparison by anatomical subsite showed that blacks had statistically significantly better differentiated tumors for cancers of the proximal and transverse colon but not for the distal. No racial differences were found for blood vessel and lymphatic invasion, necrosis, fibrosis, and mucinous type of histology. The findings, therefore, are the opposite of those hypothesized. After adjusting for stage, more aggressive tumor characteristics do not explain the adverse survival differential in blacks. This suggests that there may be racial differences in environmental exposure, and that the intensity and mode of delivery of carcinogen insult as well as host susceptibility may differ by race and anatomical subsite. Future studies should explore the B/W differences in tumor biology using molecular markers that precede the conventional histological parameters evaluated here.

Adult↗
PubMed1997

Protocol design considerations that relate to demonstrating the safety and effectiveness of chemopreventive agents.

As with other drugs, applications for marketing approval of new chemopreventive agents in the United States must include data from adequate and well-controlled clinical trials that demonstrate effectiveness and safety for the intended use. Knowledge of a drug's pharmacologic actions and metabolism may benefit protocol design, by identifying the patient populations and dosing schedules associated with a favorable risk/benefit profile. With availability of appropriate preclinical data, including standard assessments of an agent's toxicology, effects on reproductive performance, and genotoxicity, initial Phase I studies of 1-3 months may be performed in normal volunteers or an appropriate higher risk population. For chronic dosing studies of longer duration, preclinical toxicology studies of longer duration are relevant. Enrollment in chemoprevention studies should be directed toward individuals at sufficient risk of developing cancer so that potential benefit may counterbalance the unpredictable and possibly serious adverse effects that may be observed with prolonged administration of a study drug. Phase I and II studies with clinical dosing lasting up to 12 months often afford opportunities to assess drug effect on surrogate endpoint biomarkers that may correlate with endpoints of clinical effectiveness. Phase III and late phase II chemopreventive investigations should routinely utilize a prospective, randomized study design (double-masked and placebo-controlled, when possible). To support marketing approval, there must be evidence that a chemopreventive agent significantly delays or prevents the occurrence of malignancy, with acceptable safety. In some circumstances, modulation of a surrogate marker may provide a basis for marketing approval, before more definitive endpoint data become available. However, the acceptability of a surrogate depends on the nature and quality of the data supporting its predictive value. Given the considerations of large study size, long duration, and high cost that may hamper development of potential agents, studies designed to examine the predictive value of surrogate endpoint biomarkers are of great importance to the future development of chemoprevention research.

Anticarcinogenic Agents↗
PubMed1996

A new specimen of Ankarapithecus meteai from the Sinap Formation of central Anatolia.

Hominoid fossils from the Middle and Late Miocene are exceedingly rare, yet such material is necessary for determining hominoid phylogeny. We report here the discovery of a fossil hominoid partial skull from the Upper Miocene Sinap Formation of central Turkey that is the most complete known from the period of 18 to 3 Myr. Our fieldwork places the hominoid locality within a precisely dated geochronological and biostratigraphical framework that permits detailed comparisons with other fossil hominoids. Earlier discoveries of more fragmentary remains of Ankarapithecus meteai suggested affinities with the Asian hominoids Sivapithecus and Pongo. This new and nearly complete specimen reveals a combination of facial, mandibular, and dental features including a relatively narrow interorbital region, extensive frontal and maxillary sinuses, moderately developed supraorbital tori, square orbits, robust mandibular corpus, and incisor heteromorphy that is not matched in any extant or fossil hominoid. This configuration of features seems to support its placement as a stem member of the great ape and human clade.

Adult↗