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Biomedical subjects

R W White

Publications and source records attributed to R W White.

At least 19 recordsLinked to original sources
PubMed2001

Phylogenetic relationships within the eared seals (Otariidae: Carnivora): implications for the historical biogeography of the family.

Phylogenetic relationships within the family Otariidae were investigated using two regions of the mitochondrial genome. A 360-bp region of the cytochrome b gene was employed for the primary phylogenetic analysis, while a 356-bp segment of the control region was used to enhance resolution of the terminal nodes. Traditional classification of the family into the subfamilies Arctocephalinae (fur seals) and Otariinae (sea lions) is not supported, with the fur seal Callorhinus ursinus having a basal relationship relative to the rest of the family. This is consistent with the fossil record which suggests that this genus diverged from the line leading to the remaining fur seals and sea lions about 6 million years ago (mya). There is also little evidence to support or refute the monophyly of sea lions. Four sea lion clades and five fur seal clades were observed, but relationships among these clades are unclear. Similar genetic divergences between the sea lion clades (D(a) = 0.054-0.078), as well as between the major Arctocephalus fur seal clades (D(a) = 0.040-0.069) suggest that these groups underwent periods of rapid radiation at about the time they diverged from each other. Rapid radiations of this type make the resolution of relationships between the resulting species difficult and indicate the requirement for additional molecular data from both nuclear and mitochondrial genes. The phylogenetic relationships within the family and the genetic distances among some taxa highlight inconsistencies in the current taxonomic classification of the family.

Animals↗
PubMed2000

Postsealing genetic variation and population structure of two species of fur seal (Arctocephalus gazella and A. tropicalis).

Commercial sealing in the 18th and 19th centuries had a major impact on the Antarctic and subantarctic fur seal populations (Arctocephalus gazella and A. tropicalis) in the Southern Ocean. The intensive and unrestricted nature of the industry ensured substantial reductions in population sizes and resulted in both species becoming locally extinct at some sites. However, both species are continuing to recover, through the recolonization of islands across their former range and increasing population size. This study investigated the extent and pattern of genetic variation in each species to examine the hypothesis that higher levels of historic sealing in A. gazella have resulted in a greater loss of genetic variability and population structure compared with A. tropicalis. A 316-bp section of the mitochondrial control region was sequenced and revealed nucleotide diversities of 3.2% and 4.8% for A. gazella and A. tropicalis, respectively. There was no geographical distribution of lineages observed within either species, although the respective PhiST values of 0.074 and 0.19 were significantly greater than zero. These data indicate low levels of population structure in A. gazella and relatively high levels in A. tropicalis. Additional samples screened with restriction endonucleases were incorporated, and the distribution of restriction fragment length polymorphism (RFLP) and sequence haplotypes were examined to identify the main source populations of newly recolonized islands. For A. tropicalis, the data suggest that Macquarie Island and Iles Crozet were probably recolonized by females from Marion Island, and to a lesser extent Ile Amsterdam. Although there was less population structure within A. gazella, there were two geographical regions identified: a western region containing the populations of South Georgia and Bouvetoya, which were the probable sources for populations at Marion, the South Shetland and Heard Islands; and an eastern region containing the panmictic populations of Iles Kerguelen and Macquarie Island. The latter region may be a result of a pronounced founder effect, or represent a remnant population that survived sealing at Iles Kerguelen.

Animals↗
PubMed1999

Immunohistochemical analysis of BCL-2 protein expression in renal cell carcinoma.

PURPOSE: To investigate the incidence, extent, and distribution of bcl-2 protein expression in human renal cell carcinomas. MATERIALS AND METHODS: Using immunohistochemical tissue staining techniques, bcl-2 protein expression was analyzed in archival nephrectomy specimens removed for renal cell carcinoma or trauma and in 3 renal cell carcinoma cell lines. RESULTS: Normal kidneys demonstrated bcl-2 immunopositivity primarily within the cytoplasm of distal tubule cells. Only rare and minor staining of the proximal tubular cells, thought to be the origin of renal cell carcinoma, was noted in histologically normal controls and areas adjacent to tumor. In contrast, bcl-2 protein expression was demonstrated in 70% of renal cell carcinomas and in all 3 experimental cell lines. CONCLUSIONS: Bcl-2 is a proto-oncogene known to regulate apoptosis (programmed cell death). Bcl-2 protein is overexpressed in the majority of renal cell carcinomas examined. Bcl-2 overexpression may have a role in tumorigenesis and may explain the relative resistance of renal cell carcinoma to chemotherapeutic agents and to radiation therapy.

Carcinoma, Renal Cell↗
PubMed1998

p53 and bcl-2 immunohistochemical alterations in prostate cancer treated with radiation therapy.

OBJECTIVES: Radiation therapy is definitive treatment for localized prostate cancer. It causes cellular deoxyribonucleic acid (DNA) damage, which, if irreparable, results in apoptosis or programmed cell death. Overexpression of mutant p53 and/or bcl-2 proteins prolongs cell survival despite exposure to damaging agents. We examined whether abnormal expression of either gene could help to explain radiation therapy failures in prostate cancer. METHODS: Archival tissue from patients who had failed radiation therapy as treatment for prostate cancer was obtained before and after treatment. These cancer samples were examined immunohistochemically for accumulation of p53 and bcl-2 proteins. Comparison was made with specimens from patients who had no evidence of recurrent or persistent disease at least 3 years following radiation therapy. RESULTS: High rates of p53 immunopositivity were found in the prostate tissue from all groups studied. More patients who had failed radiation therapy were found to have bcl-2 immunopositive specimens than were those without evidence for recurrent disease (41% preradiation and 61% postradiation versus 8%, P <0.05). More patients who failed radiation therapy had both p53 and bcl-2 immunopositive prostate tissue than did those who were treated successfully (32% preradiation and 48% postradiation versus 8%). CONCLUSIONS: bcl-2 immunopositivity, with or without concomitant detection of p53, was found in significantly more cancers of patients who failed radiation therapy. Positive staining for bcl-2 may serve as a marker for determining the radiation sensitivity of a tumor and thus may help to guide treatment options. It is also notable that a high proportion of the prostate cancers examined were immunopositive for p53.

Humans↗
PubMed1996

An inhibitor of the sodium pump obtained from human placenta.

BACKGROUND: Much effort has been expended in the search for an endogenous inhibitor of the cellular sodium/potassium pump, a compound of major physiological importance, which has been implicated in the mechanism of essential hypertension. Others have suggested that ouabain or an isomer of ouabain may be the endogenous pump inhibitor. Neonatal cord serum contains an inhibitor of the sodium pump; we attempted to isolate and characterise this substance from human placentas. METHODS: Homogenised placentas were dialysed and the resulting solutes were trapped on octadecylsilyl silica and then separated by high-performance liquid chromatography. Measurement of the activity of the sodium pump of human leucocytes was used to test each fraction for the presence of the inhibitor. FINDINGS: An inhibitor of the sodium pump was obtained by this technique in a mass spectrometrically pure form with a mass of 370 Da, an empirical formula of C24H34O3 and only one hydroxyl group. The characteristic fragmentation pattern observed in negative-ion mass spectrometry was compared with those of various model compounds; this comparison suggested that the active material was a dihydropyrone-substituted steroid. INTERPRETATION: These results suggest that a dihydropyrone-substituted steroid is an endogenous regulator of the sodium pump in humans and, presumably, other mammals. Proof of the endogenous origin will require the demonstration of a previously unrecognised biosynthetic pathway.

Bufanolides↗
PubMed1996

Post-prostatectomy incontinence and the artificial urinary sphincter: a long-term study of patient satisfaction and criteria for success.

PURPOSE: We investigated patient satisfaction with the artificial urinary sphincter and established criteria for a successful outcome by inquiring about patient perceived satisfaction, continence achieved and comparison with the surgeon office records. MATERIALS AND METHODS: During 9 years 65 patients with post-prostatectomy incontinence underwent placement of the AMS800 artificial urinary sphincter. Review of charts and a telephone questionnaire were conducted to determine patient perceived satisfaction. RESULTS: A total of 50 patients participated in the survey. Median followup was 23.4 months. Preoperative incontinence was severe. Of the patients 90% reported continuous leakage, and 70% wore an average of 6 diapers and 24% wore an average of 7.4 pads daily. The long-term complete continence rate was 20%. Of the patients with wetness 55% had leakage of a few drops daily and 22% had leakage of less than a teaspoon. Of all patients 50% had leakage daily, 24% had leakage 1 or more times a week and wore an average of 1.5 pads per day, and 6% reported changing clothes due to wetness. A total of 90% of the patients reported satisfaction with the artificial urinary sphincter and 96% stated that they would recommend or had recommended the artificial urinary sphincter to a friend. In retrospect, 92% of the patients would have the artificial urinary sphincter placed again, 90% of those undergoing revision reported no change in satisfaction and 14% reported improved sexual activity. CONCLUSIONS: Patient satisfaction with the artificial urinary sphincter for post-prostatectomy incontinence is uniformly high. Although postoperative continence was not 100%, relative improvement in continence was the most significant factor affecting patient perceived outcome. Using these parameters criteria for a successful outcome can be established, and patient concerns regarding the artificial urinary sphincter can be dispelled.

Aged↗
PubMed1996

Relationship of p53 and bcl-2 to prognosis in muscle-invasive transitional cell carcinoma of the bladder.

PURPOSE: We examined the presence of the p53 and Bcl-2 oncoproteins, as detected by immunohistochemistry, in muscle-invasive bladder cancer and correlated this with survival. MATERIALS AND METHODS: Formalin-fixed cystectomy specimens from 41 consecutive patients with mean follow-up of 52 months were used. Five patients were either lost to follow-up or died of other diseases and were not included in the survival evaluation. RESULTS: Eighteen of 36 patients died of metastatic transitional cell carcinoma. p53 immunostaining was found in 61% of patients. In 21 of 23 this staining was homogeneous, with more than 75% of cancer cells staining using a DO-1/DO-7 antibody cocktail. p53 staining was not correlated with stage (p>0.25) or grade (p<0.10) in these invasive cancer specimens. Contrary to recent studies p53 immunostaining was not correlated with disease-specific survival. Bcl-2 immunostaining was found in 28% of patients and was not correlated with grade (p>0.25) or disease-specific survival. No combination of p53 and Bcl-2 staining gave added predictive information. CONCLUSIONS: Cytoplasmic Bcl-2 is found in a small percentage of these cancers and does not correlate with prognosis. Further, p53 molecular overexpression is detected in the majority of muscle-invasive bladder tumors as a field defect. However, in patients undergoing cystectomy, it does not correlate with prognosis.

Carcinoma, Transitional Cell↗
PubMed1992

Who was Morton Prince?

Morton Prince, a Boston neurologist, founded the Journal of Abnormal Psychology in 1906 as an outlet especially for those who took a psychogenic view of neurotic disorders. Through experiments with hypnotism, he added appreciably to knowledge of subconscious and coconscious mental processes; The Dissociation of a Personality (Prince, 1905) still ranks as a classic. He early saw that studying normal people in the depth and detail with which one studied patients could make significant contributions to our whole understanding of human nature. Before his death he established and briefly directed the Harvard Psychological Clinic, devising the research environment out of which presently sprang major contributions to the study of personality.

History, 19th Century↗
PubMed1990

Mitochondrial and allozyme genetics of incipient speciation in a landlocked population of Galaxias truttaceus (Pisces: Galaxiidae).

Galaxias truttaceus is found in coastal rivers and streams in south-eastern Australia. It spawns at the head of estuaries in autumn and the larvae spend 3 months of winter at sea before returning to fresh water. In Tasmania there are landlocked populations of G. truttaceus in a cluster of geologically young lakes on the recently glaciated Central Plateau. These populations have no marine larval stage and spawn in the lakes in spring. Speciation due to land locking is thought to be a frequent occurrence within Galaxias. To investigate the nature of the speciation event which may be occurring within lake populations of G. truttaceus we studied the mitochondrial DNA (mtDNA) and allozyme diversity of both lake and stream populations. Using the presence or absence of restriction sites recognized by 13 six-base restriction endonucleases, we found 58 mtDNA haplotypes among 150 fish collected from 13 Tasmanian and one south-east Australian mainland stream populations. The most parsimonious network relating the haplotypes by site loss or gain was starlike in shape. We argue that this arrangement is best explained by selection upon slightly beneficial mutations within the mitochondrial genome. Gene diversity analysis under Wright's island model showed that the populations in each drainage were not genetically subdivided. Only two of these stream haplotypes were found among the 66 fish analyzed from four lake populations. Despite the extreme lack of mtDNA diversity in lake populations, the observed nuclear DNA heterozygosity of 40 lake fish (0.10355) was only slightly less than that of 82 stream fish (0.11635). In the short time (3000-7000 years) that the lake fish have been landlocked, random genetic drift in a finite, stable-sized population was probably not responsible for the lack of mtDNA diversity in the lake populations. We infer the lake populations have probably experienced at least one, severe, but transitory bottleneck possibly induced by natural selection for life-history characters essential for survival in the lacustrine habitat. If speciation is occurring in the landlocked populations of G. truttaceus, then it may be driven by genetic transilience.

Animals↗
PubMed1989

Low incidence of loss of chromosome 10 in sporadic and hereditary human medullary thyroid carcinoma.

Genetic linkage has been recently documented between a centromeric region of chromosome 10 and familial multiple endocrine neoplasia type II (MEN II). This syndrome consists of initial thyroid C-cell and adrenal chromaffin cell hyperplasia which result in multifocal medullary thyroid carcinomas and bilateral adrenal pheochromocytomas. Other hereditary cancers, such as retinoblastoma, appear to result from a series of genetic events involving, first the inheritance of a germ line abnormality, and subsequent loss of chromosome loci opposite this initial defect. In these cancers, this loss of the normal alleles in both familial and sporadic cases, is frequently manifest as a reduction to homozygosity for polymorphic DNA markers near the involved locus. It might then be expected that chromosome 10 regions would be lost with high frequency in tumor DNA from patients with MEN II and sporadic medullary thyroid carcinoma (MTC). We now demonstrate that only two of 16 MTC tumors studied by analysis of restriction fragment length polymorphisms for multiple regions of the short and long arms of chromosome 10 showed loci reduced to homozygosity. One of these tumors was from a patient with MEN II and the other from a patient with nonfamilial MTC. Importantly, no such chromosome 10 changes were noted in pheochromocytomas from the patient with MEN II or his sister. These findings strongly suggest that the sequence of genetic events for familial MTC is either different from that for retinoblastoma or that loss of normal alleles opposite the germ line genetic defect occurs by mechanisms other than gross loss of chromosomal material in MTC. A model is proposed suggesting that the mechanism involving loss of alleles opposite one another is operative in hereditary tumors, such as retinoblastoma, which do not arise within a setting of initial polyclonal cellular hyperplasia. In contrast, in tumors such as familial MTC and polyposis coli which arise as individual clones of neoplastic cells from a setting of preexistent polyclonal hyperplasia, the first genetic event may underlie hyperplasia, and additional events, frequently at other chromosomal loci, may cause individual clonal neoplasms.

Adrenal Gland Neoplasms↗
PubMed1989

Exploration of mechanical and electromyographic responses of trunk muscles to high-intensity resistive exercise.

The purposes of this study were to determine the effects of high intensity exercise on fatigue of the trunk muscles within a test session, and on multiple kinetic and electromyographic (EMG) variables over a 6-week training period. Fourty-five normal men and women (20-40 years of age) completed the study. The KIN/COM trunk testing unit (Chattecx Corporation, Chattanooga, Tennessee) was used for both testing and training. The results of the study follow: 1) The KIN/COM trunk testing system was very accurate, and the method used was highly reproducible for the kinetic variables. Reproducibility for the endurance variables was mixed, and isolated EMG variables were poor. 2) Kinetic and EMG decrements associated with fatigue did occur in the trunk muscles with ten continuous cycles of maximal concentric and eccentric contractions. 3) Trunk muscle strength gains were highest for the same mode of exercise used in training (specificity), but significant strength gains also were seen in different modes of muscle contraction (transfer of training). For the trunk extensors, the eccentric form of exercise was superior. 4) The rate of isometric torque development and decay was increased by exercise in men. 5) Trunk muscle endurance was retained when gains in strength occurred. 6) The majority of variables reflecting strength and endurance were retained. The methods and results can serve as guidelines for the evaluation of trunk muscle function and resistive exercise in the clinic.

Abdominal Muscles↗
PubMed1988

Prostatic-specific antigen: clinical experience utilizing immunoperoxidase staining techniques in patients with metastatic prostate cancer.

A human prostatic-specific antigen was first purified in 1979 by M.C. Wang et al. In the years to follow, investigators have been able to develop antisera to prostatic-specific antigen. Using an immunoperoxidase technique to stain both fresh and archival specimens, tissue of prostatic origin can be identified. The stain in our experience has been both specific and sensitive as an indicator of extraprostatic spread of carcinoma. We describe five cases where this technique has been useful in clinical practice.

Aged↗
PubMed1987

Comparison of clinical and objective methods of assessing trunk muscle strength--an experimental approach.

An objective method was used to evaluate the validity of the sit-up, prone trunk extension, and double leg lowering clinical tests. Normal men and women and patients with a history of backache served as subjects. The vast majority of the subjects were able to perform the Grade 1 level, which was the highest resistance imposed by the sit-up and prone extension tests. The double leg lower was superior to the other two clinical tests but was able to identify only broad differences in strength capability. In the main, the subjective clinical tests were poor discriminators and seemed to lack the range of resistance necessary to be definitively useful as methods of assessing trunk muscle strength and may not provide appropriate resistance for improving trunk muscle strength in most patients.

Adult↗