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Biomedical subjects

K Woods

Publications and source records attributed to K Woods.

14 recordsLinked to original sources
PubMed1992

Genetic linkage of Werner's syndrome to five markers on chromosome 8.

Werner's syndrome (WS) is a rare autosomal recessive disease in which the affected individuals display symptoms of premature ageing. The substantial phenotypic overlap between WS and normal ageing indicates that these two conditions may have pathogenetic mechanisms in common. The WS mutation has pleiotropic effects, and patients and their cells show many differences compared with normals. Despite extensive study of the clinical and biochemical features of this disorder, the primary genetic defect remains unknown. We have undertaken a genetic linkage study in an effort to identify the locus of the primary defect. Here we report close genetic linkage of the WS mutation to a group of markers on chromosome 8.

Chromosome Mapping↗
PubMed1992

Gelatinolytic metalloproteinase secretion patterns in ocular melanoma.

Fifteen posterior uveal melanoma cell lines were analyzed qualitatively for gelatinolytic and caseinolytic proteinase activity after one to five in vitro passages. All 15 cell lines secreted a gelatinolytic metalloproteinase, with an apparent molecular weight of 72 kD, into protein-free culture media; nine of these secreted an additional gelatinolytic metalloproteinase with an apparent molecular weight of 92 kD. Neither species had the ability to degrade casein. This approach may provide insight into the mechanisms of tumor metastasis in uveal melanoma.

Aged↗
PubMed1991

An investigation of parotid gland function and histopathology in autoimmune disease-prone mice of different age groups.

This work aimed to characterize parotid gland function in autoimmune disease-prone murine strains (MRL/n, MRL/l and NZB/W) in relation to increasing age and to relate the extent of functional impairment to the intensity of histopathologic changes observed at the different ages. Pilocarpine-stimulated parotid saliva was collected to assess salivary flow rate and composition. Parotid tissue was then removed for histopathologic assessment. Parotid flow rates were not significantly reduced in autoimmune strains compared to controls but were reduced with age in NZB/W mice and in males of the C57 (control) strain. Age-related salivary compositional changes were present in MRL/l mice and in male NZB/W mice. Focal lymphocytic adenitis increased with age in prevalence and intensity in both sexes. The functional and histopathologic changes were not closely correlated. These results suggest that the parotid gland of autoimmune disease-prone mice provides only a poor replication of the salivary changes in human Sjögren's syndrome. Nevertheless, both the functional and histopathological changes developing in these strains, even though of limited extent, are significantly influenced by age.

Aging↗
PubMed1990

The effects of a liquid diet on initial and sustained, stimulated parotid salivary secretion and on parotid structure in the rat.

Adult male rats were maintained on a nutritionally adequate liquid diet, or laboratory chow and water (controls), for 7 days. They were then anaesthetized and parotid flow was recorded after isoprenaline or pilocarpine stimulation, each collected over two, timed sampling periods--an initial 5 min and a subsequent 15 min. The isoprenaline-induced flow rates in liquid diet rats were reduced to 45 and 30% of those in control rats for the first and subsequent samples respectively (p less than 0.02). After pilocarpine stimulation there were no significant differences in the first samples, but in the subsequent samples the flow rate in liquid diet rats was reduced to 54% of that in controls (p less than 0.001). The parotid gland weights were reduced by 35% in liquid diet rats compared to controls (p less than 0.05). On computerized planimetric analysis, parotids (from rats that had not been given secretagogues) had significantly smaller mean acinar areas, mean acinar profile perimeters and mean acinar transection diameters after liquid feeding (p less than 0.001). The findings support the notion that there is a functional reserve capacity available in atrophied glands to support the relatively fast flow that occurs on initial stimulation but which becomes exhausted during sustained stimulation. This exhaustion occurs more severely and more rapidly in the low-volume, protein-rich saliva elicited by sympathomimetic stimulation than in the high-volume, low-protein saliva formed in response to parasympathomimetic stimulation.

Animals↗
PubMed1990

Biochemical pharmacology of acyclic nucleotide analogues.

Our studies have shown that the acyclic nucleotide analogues PMEA and HPMPC are able to penetrate into cells and are then activated to mono- and diphosphate derivatives. The latter correspond to triphosphate analogues and presumably serve an important role in the biological activity exerted by these antiviral agents. In support of this idea, the inhibitory effect of PMEApp on HIV reverse transcriptase has been demonstrated with both RNA and DNA template-primer systems. Further studies will be undertaken to determine the effect of HPMPCpp on viral DNA polymerases. Whereas the metabolism of PMEA in CEM cells gives rise to only PMEAp and PMEApp, additional metabolites were obtained in MRC-5 cells; the identity of these metabolites remains to be determined. In the case of HPMPC, a third metabolite was obtained in addition to HPMPCp and HPMPCpp, which has been tentatively assigned as a phosphate-choline adduct by analogy with activation of cytosine-based nucleoside derivatives. The metabolism of HPMPC was unchanged between uninfected and infected cells, indicating that viral enzymes are not necessary for the activation of HPMPC. The long intracellular half-lives of the HPMPC metabolites may have implications for the antiviral efficacy of this compound. The persistence of activated metabolites suggests that infrequent dosing may be possible due to a prolonged antiviral effect. Our results on the effectiveness of infrequent dosing schedules with HPMPC in the treatment of HSV 2 infections in mice support this hypothesis. It is also possible that HPMPCp-choline may serve as a reservoir for HPMPC and therefore for the presumed active metabolite HPMPCpp.

Adenine↗
PubMed1989

Chloride handling by submandibular cells from young and old rats with and without duct ligation.

To examine the relation between structure and function in aging salivary glands, we have studied the duct-ligated submandibular gland of rats. Following 5-8 days ligation, glands from young (7-8 months) and old (21-23 months) rats exhibited approximately 90% loss in proportional volume of acinar cells. Most remaining epithelium was highly abnormal. No significant differences were detected in the ability of cells prepared from young and old animals, either control or ligated, to flux 36Cl-. Both basal uptake and muscarinic-cholinergic stimulated release were comparable.

Aging↗
PubMed1989

The human astrocytoma cell line 1321 N1 contains M2-glandular type muscarinic receptors linked to phosphoinositide turnover.

1. Muscarinic receptors present in the human astrocytoma cell line 1321 N1 were characterized in radioligand binding studies and in functional studies of carbachol-stimulated phosphatidylinositol (PI) turnover. 2. In radioligand binding studies the muscarinic receptor in intact cells could be labelled using [3H]-N-methylscopolamine ([3H]-NMS) but not by [3H]-pirenzepine. In the intact cells these receptors displayed low pirenzepine affinity (pKi = 6.83) indicating that they were not of the M1 subtype. Furthermore, the 1321 N1 muscarinic receptors displayed low affinity for the two M2-cardiac selective ligands methoctramine (pKi = 5.82) and AF-DX 116 (pKi = 6.29). This pharmacology was consistent with the 1321 N1 cells containing a single population of muscarinic receptors that displayed a similar pharmacology to the M2-receptor present in exocrine gland tissue. 3. The M2-gland nature of the receptors was further indicated in the functional studies where antagonist affinities were determined from their ability to antagonize carbachol-stimulated PI turnover in 1321 N1 cells. pA2 values for pirenzepine (7.31), methoctramine (6.10) and AF-DX 116 (6.52) were similar to those determined in the binding studies. 4. From these studies we conclude that 1321 N1 astrocytoma cells contain an M2-gland muscarinic receptor which mediates muscarinic receptor-mediated stimulation of PI turnover in these cells.

Animals↗
PubMed1989

Effects of acute ethanol administration on stimulated parotid secretion in the rat.

Young adult male rats previously never exposed to ethanol were given a single dose of 4 ml of 35% (v/v) ethanol in water by direct intragastric intubation (approximate weight related dose = 5.2 g/kg). Control rats were given distilled water in the same volume by the same route or were given no intragastric fluids. After administration of Valium-Hypnorm anesthesia, parotid salivary secretion was stimulated by subcutaneous pilocarpine HCI (10 mg/kg), and accurately timed samples were collected. No differences were recorded in the rate of salivary flow during the initial (5-min) high-flow phase of secretion, but during the subsequent 25-min phase of secretion the output in ethanol-treated rats was depressed by 60% compared to controls (p less than 0.01). Furthermore, electrolyte analyses of this saliva indicated that salivary ductal resorptive activity might be diminished in the presence of high blood ethanol. However, when rats were previously habitually exposed to ethanol at a twice daily dose of 4 ml of 35% (v/v) ethanol in water, the inhibitory action of acute ethanol administration was abolished. Moreover, in these rats there was significantly depressed [Na+] in both high-flow and low-flow saliva samples (p less than 0.01) with little change in [Na+] occurring at higher flow rates. This suggests the possibility of enhanced ductal resorption developing in rats exposed to long-term ethanol feeding.

Alcohol Drinking↗
PubMed1988

Evidence for inhibition of growth related to compromised DNA synthesis in the interaction of daunorubicin with H-35 rat hepatoma.

The H-35 rat hepatoma is relatively insensitive to the anthracycline antibiotic, daunorubicin (DNR), requiring 0.25 microM daunorubicin for inhibition of cell proliferation by 50%. Studies were undertaken to investigate the basis for the apparent intrinsic resistance in this cell line. The relative insensitivity of the H-35 cells to DNR is not a function of metabolic inactivation of DNR to deoxyaglycone derivatives; after a 2-h incubation, less than 10% of drug is metabolized, exclusively by conversion to daunorubicinol. The limited toxicity of DNR to the rat hepatoma may be explained, in part, by the absence of DNA strand breaks at daunorubicin concentrations up to 1 microM while higher (supraclinical) DNR concentrations (5 and 10 microM) produce direct, "non-protein-associated" DNA strand breaks. Limited daunorubicin toxicity in this tumor cell line may also be related to the apparent absence of free radical-mediated cellular damage as the free radical scavengers dimethyl sulfoxide, catalase, methanol, and mannitol fail to reverse the inhibitory effect of 1 microM DNR on cell proliferation. Daunorubicin does not induce leakage of the cytoplasmic enzyme, glutamic oxaloacetate transaminase, or diminish mitochondrial enzyme function. Conversely, while drug effects on RNA synthesis are small, and protein synthesis is minimally diminished, inhibition of cell proliferation corresponds closely with inhibition of DNA synthesis.

Animals↗
PubMed1988

Salivary flow rate, protein and electrolyte concentrations in chronic alcoholic patients.

Stimulated and unstimulated parotid salivas were examined in a series of non-cirrhotic patients under treatment for alcohol dependence and in age-sex matched, non-alcoholic, healthy, control subjects. Resting salivary flow was raised threefold in the alcohol group and the protein and electrolyte concentrations were also altered in this saliva. However, there were no intergroup differences in parotid flow or composition following gustatory stimulation by 6% citric acid. The results contrast with the wide parotid functional changes known to occur in stimulated parotid saliva in alcoholic cirrhosis and suggest, therefore, that the direct salivary effects of chronic alcohol abuse may be less important than the damaged liver function in contributing to the salivary disturbance reportedly occurring in alcoholic cirrhosis.

Adult↗
PubMed1986

Who cares what care?: an inverse interest law?

The paper attempts to systematise some of the ideas on medical dominance as the inverse interest law, which is broadly seen as the more commonplace the problem and the more people affected, the less will be the medical interest. The law or rather laws are exemplified by reference to the symptom iceberg, health education and welfare, hospital expenditure, priority groups and community care and class, locality and ethnicity. The inverse interest laws, which ensure the operation of the inverse care law, are seen as products of medicine definition and practice in relation to their containing society.

Community Health Services↗
PubMed1976

Further evidence for the humoral stimulation of the liver: effect of a pituitary peptide.

The capacity of a peptide isolated from hypophysis (HTH) to affect liver function is further supported by the results of pilot experiments on lipid and protein metabolism. Administration of purified peptide to rats induces reduction in plasma proteins and increase in plasma cholesterol with an abnormal free/esterifield cholesterol ratio in liver. Cholesterol in bile and bile volume excretion increase above normal and the concentration of other substances known to be modified by liver activity shows values different to normals.

Adrenal Glands↗
PubMedDate not supplied

Image segmentation in digital mammography: comparison of local thresholding and region growing algorithms.

Local thresholding and region-growing algorithms are developed and applied to digitized mammograms to quantify the parenchymal densities. The algorithms are first evaluated and optimized on phantom images reflecting varying image contrast, X-ray exposure conditions, and time-related changes. The difference between the segmentation results of the two techniques is less than 6% on the phantom images and 11% on the mammograms. The agreement between the computerized procedures and a manual one is in the range of 74-98%, depending on the breast parenchymal pattern and segmentation algorithm. The results show that computerized parenchymal classification of digitized mammograms is possible and independent of exposure.

Algorithms↗