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Biomedical subjects

P Walker

Publications and source records attributed to P Walker.

At least 217 records · Page 12Linked to original sources
PubMed1985

Comparison of prevalence of human papillomavirus antigen in biopsies from women with cervical intraepithelial neoplasia.

Human papillomavirus antigen was found in 39 (16%) of 253 colposcopic biopsies from a group of women at high risk for cervical cancer who had been examined in the early 1970s. Immunohistochemical evidence of papillomavirus infection was found in 20 (30%) of 67 cervical intraepithelial neoplasia lesions infected with wart virus from these patients. When these results were compared with results of a similar study carried out in the early 1980s there was no significant difference in the prevalence of human papillomavirus antigen in cervical intraepithelial neoplasia lesions infected with wart virus from women who had been examined over a decade apart.

Adolescent↗
PubMed1985

Increased pituitary thyroxine 5'-deiodinase activity in adult rats rendered hyper- or hypo-thyroid during perinatal life.

Perinatal thyroid dysfunction in the rat leads to permanent alterations in pituitary TSH secretion in the adult animal. Thus, neonatal hyperthyroidism (NH) and perinatal hypothyroidism (PH) both result in apparent increased pituitary sensitivity to the feedback effects of thyroid hormones in the adult rat. To determine if increased intrapituitary generation of triiodothyronine (T3) might account for these observations, we measured thyroxine (T4) 5'-deiodinase activity in pituitary homogenates of adult NH and PH rats. NH was induced by injecting neonatal rats with 12 daily sc injections of T4 (0.4 microgram/g body weight (BW]. Control rats received vehicle alone. PH was induced by administering 0.05% 6-n-propylthiouracil in the drinking water to pregnant dams from the 16th day of gestation through the 12th day postpartum. Thereafter, a normal water supply was substituted. NH and PH rats were allowed to mature and were sacrificed at 105 days of age. Serum T4, T3, and TSH concentrations were measured by radioimmunoassay. Pituitary T4 5'-deiodinase activity was assessed by the measurement of T3 formation by pituitary homogenates incubated in the presence of 0.65 microM T4 and 100 mM dithiothreitol at 37 degrees C for 90 min. Body weights of adult NH and PH rats were slightly but not significantly decreased compared with control rats. Relative pituitary gland weight (milligrams per 100 g BW) was significantly decreased in adult PH rats (P less than 0.005) but not in adult NH rats. In adult NH rats, serum T4 and T3 concentrations were significantly decreased (P less than 0.01) compared with control rats. Serum TSH concentrations were similar.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Neonatal hyperthyroidism alters submandibular gland epidermal growth factor response to thyroxine in the adult mouse.

Neonatal hyperthyroidism (NH) in the rat is associated with permanent reductions in serum thyroxine (T4), triiodothyronine (T3), and thyroid-stimulating hormone (TSH) concentrations in the adult, changes suggestive of a hypothyroid state. In the adult NH rat, the thyrotroph appears to be more sensitive to the feedback effects of thyroid hormones. To determine whether thyroid hormone sensitive tissues retain their responsiveness to thyroid hormones, the long-term effects of NH on mouse submandibular gland (SMG) epidermal growth factor (EGF) content were examined. NH was induced in female mice by 20 daily subcultaneous injections of 0.4 microgram of T4 per gram of body weight. Control female mice received daily injections of vehicle alone. At 21 days of age, NH and control mice were sacrificed and SMG EGF content was measured by specific radioimmunoassay, SMG EGF content and concentration in 21-day-old NH mice exceeded that of control mice by 2400- and 1500-fold, respectively (P less than 0.001). SMG EGF content and concentration in adult (90-day-old) NH mice were slightly, but not significantly, lower than those of control mice. Mean SMG weight, however, was significantly decreased in adult NH mice (P less than 0.01). Interestingly, SMG content and concentration of EGF in adult NH mice were lower than in 21-day-old NH mice. After 5 days T4 treatment (16 micrograms/d) of adult mice, SMG weight in NH mice increased significantly (P less than 0.01) but was unchanged in control mice. SMG EGF content and concentration increased significantly in both adult NH and control mice (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Transient neonatal hyperthyroidism results in hypothyroidism in the adult rat.

Adult rats who had neonatal hyperthyroidism (NH) have reduced BW and serum T4, T3, and TSH concentrations. Pituitary TSH responses to TRH administration under basal, T4-suppressed, and propylthiouracil-stimulated conditions suggest that the thyrotroph of these animals is more sensitive to the feedback effects of thyroid hormones. These studies were undertaken to examine, with the use of various thyroid hormone-responsive variables, thyroid status of adult NH rats. NH was induced by 12 daily sc injections of T4 (0.4 microgram/g BW) to neonatal male Sprague-Dawley rats. Adult NH and control rats were then studied at 120 days of age. Adult NH rats had significantly decreased mean BW (P less than 0.001), and serum T4 (P less than 0.005), T3 (P less than 0.001), and TSH (P less than 0.001) concentrations. The percent decreases were 12% for T4, 20% for T3, and 27% for TSH in adult NH rats. Mean pituitary GH concentration and hepatic alpha-glycerophosphate dehydrogenase and malic enzyme activities were significantly decreased in adult NH rats to 54% (P less than 0.005), 52% (P less than 0.025), and 39% (P less than 0.001), respectively, of control values. Mean pituitary TSH concentrations were similar in adult NH and control rats. Mean hepatic T4 5'-deiodinase activity of adult NH rats [200 +/- (SE) 23 fmol T3/min X mg protein] was significantly decreased to 56% of control levels (355 +/- 31 fmol T3/min . mg protein; P less than 0.005). Mean pituitary T4 5'-deiodinase activity of adult NH rats (32.8 +/- 3.3 fmol T3/min . mg protein) was significantly increased compared with that of control rats (21.2 +/- 1.7 fmol T3/min . mg protein; P less than 0.025). These changes are consistent with a hypothyroid state in adult NH rats. The observation of decreased serum TSH concentration and enhanced thyrotroph sensitivity to thyroid hormones in the face of increased pituitary T4 5'-deiodinase activity suggests that increased thyrotroph monodeiodination of T4 may be the central biochemical aberration responsible for the hypothyroid state in adult NH rats.

Animals↗
PubMed1985

Subcellular localization of thyroxine 5'-deiodinase activity in bovine anterior pituitary.

Bovine anterior pituitary glands were fractionated by differential centrifugation. T4 5'-monodeiodination to T3 was found predominantly in microsomal fractions (M2; 105,000 . g pellet) enriched in glucose-6-phosphatase and 5'-nucleotidase activities. T4 5'-deiodinase activity in M2 fraction was 85.2 fmol T3/min X mg protein and represented an 8.5-fold enrichment over homogenate specific activity (10.6 fmol T3/min . mg protein). Further subcellular localization of the T4 5'-deiodinase was effected by discontinuous sucrose density gradient centrifugation. Maximum T4 5'-deiodinase activity was found in fraction P5 at the interface of densities 1.18/1.20 (200 fmol T3/min . mg protein) and correlated with the profile of glucose-6-phosphatase and not with that of 5'-nucleotidase, the maximum activity of which was recovered in fraction P1 at the interface of densities 1.03/1.12. Electron microscopic examination of the fractions confirmed that P5 contained in excess of 90% rough membranes in contrast to 10% or less in P1. Characterization of T4 5'-deiodinase activity was carried out in M2 preparations. The reaction was thiol dependent, requiring the presence of 50 mM dithiothreitol or more (Km, 38 mM), with a maximum velocity of 55-150 fmol T3/min . mg protein (n = 8). Enzyme activity was substrate dependent, with a Km for T4 between 35-70 nM. 5'-Monodeiodination of T4 was abolished by heating to 70 C for 30 min and was unaffected by EDTA. Propylthiouracil and methimazole did not inhibit T3 generation. Iopanoic acid, on the other hand, was a competitive inhibitor of the 5'-monodeiodination reaction, abolishing T3 production in a dose-dependent manner with a Ki of 3 microM. These data indicate that the bovine anterior pituitary contains significant T4 5'-deiodinase activity, which shares many properties of the type II 5'-deiodinase of the rat. Bovine anterior pituitary T4 5'-deiodinase appears to be predominantly localized in the rough endoplasmic reticulum.

Animals↗
PubMed1984

Evolution of vitellogenin genes: comparative analysis of the nucleotide sequences downstream of the transcription initiation site of four Xenopus laevis and one chicken gene.

Electron microscopic analysis of heteroduplexes between the most distantly related Xenopus vitellogenin genes (A genes X B genes) has revealed the distribution of homologous regions that have been preferentially conserved after the duplication events that gave rise to the multigene family in Xenopus laevis. DNA sequence analysis was limited to the region downstream of the transcription initiation site of the Xenopus genes A1, B1 and B2 and a comparison with the Xenopus A2 and the major chicken vitellogenin gene is presented. Within the coding regions of the first three exons, nucleotide substitutions resulting in amino acid changes accumulate at a rate similar to that observed in globin genes. This suggests that the duplication event which led to the formation of the A and B ancestral genes in Xenopus laevis occurred about 150 million years ago. Homologous exons of the A1-A2 and B1-B2 gene pairs, which formed about 30 million years ago, show a quite similar sequence divergence. In contrast, A1-A2 homologous introns seem to have evolved much faster than their B1-B2 counterparts.

Amino Acid Sequence↗
PubMed1984

Sequence homologies in the region preceding the transcription initiation site of the liver estrogen-responsive vitellogenin and apo-VLDLII genes.

In the liver of oviparous vertebrates vitellogenin gene expression is controlled by estrogen. The nucleotide sequence of the 5' flanking region of the Xenopus laevis vitellogenin genes A1, A2, B1 and B2 has been determined. These sequences have been compared to each other and to the equivalent region of the chicken vitellogenin II and apo-VLDLII genes which are also expressed in the liver in response to estrogen. The homology between the 5' flanking region of the Xenopus genes B1 and B2 is higher than between the corresponding regions of the other closely related genes A1 and A2. Four short blocks of sequence homology which are present at equivalent positions in the vitellogenin genes of both Xenopus laevis and chicken are characterized. A short sequence with two-fold rotational symmetry (GGTCANNNTGACC) was found at similar positions upstream of the five vitellogenin genes and is also present in two copies close to the 5' end of the chicken apo-VLDLII gene. The possible functional significance of this sequence, common to liver estrogen-responsive genes, is discussed.

Animals↗
PubMed1984

Impact of introduction of colposcopy to a district general hospital.

During the first 18 months of operation of a new colposcopy clinic, established in a district general hospital, 608 women were seen. Most (568 (93.0%] were referred from within the local district, on the whole by their general practitioner. In 466 cases a repeat cervical smear was taken, and all women underwent colposcopic examination together with directed punch biopsy of any abnormal area. Positive cytology was seen in 356 women, but 85 (23.9%) of these were found to have no histological evidence of malignancy or premalignancy and were consequently discharged from the clinic. Cervical intraepithelial neoplasia was confirmed histologically in 379 women, of whom 259 were under 35 and 175 nulliparous. As a result of the use of colposcopy and local destructive methods of treatment only 42 patients (11.1%) were required to undergo cone biopsy. The initial overall incidence of success in the treatment of cervical intraepithelial neoplasia was 86.2% for cone biopsy, 88.5% for diathermy, and 81.1% for laser ablative treatment. Colposcopy has an important role in the management of cervical neoplasia in the district general hospital.

Adolescent↗
PubMed1984

Hyperalphalipoproteinaemic activity of BRL 26314--I. Enhanced cholesterol turnover in rats.

Administration of BRL 26314 [N-(4-chlorobenzyl)-L-phenylalanine] raises circulating high-density lipoprotein (HDL) cholesterol and lowers total triglyceride levels in rats whether maintained on stock or semi-synthetic diets. HDL is also elevated by BRL 26314 in hypothyroid rats and in rats with pre-existing hyperlipidaemia where aortic total cholesterol concentration is decreased. BRL 26314 promotes the excretion of a dose of radiolabelled cholesterol as faecal sterols and bile acids, and decreases the extent of cholesterol-radiolabelling in tissue pools, particularly the aorta and adipose tissue. The increase in cholesterol and bile acid (cholic acid) turnover distinguishes BRL 26314 from a cholestatic agent such as 1-naphthyl isothiocyanate where a superficially similar change in HDL concentration disguises an impaired cholesterol transport. BRL 26314 is not a general protein inducer but part of the mechanism of action may involve enhancement of white adipose tissue lipoprotein lipase activity.

1-Naphthylisothiocyanate↗
PubMed1984

Hyperalphalipoproteinaemic activity of BRL 26314--II. Inhibition of atherosclerosis in rabbits.

Optimization of a combination of balloon catheter-induced aortic de-endothelialization with provision of a palatable atherogenic diet to rabbits leads to hyperbetalipoproteinaemia and atherosclerosis rather than to the cholesterol-storage disease which characterized earlier models. Administration of BRL 26314 [N-(4-chlorobenzyl)-L-phenylalanine] during the induction of atherosclerosis specifically raised high-density lipoprotein (HDL) and decreased the arterial content of cholesterol and collagen in association with reduction in severity of thoracic sudanophilic lesions and intimal-thickening. This anti-atherosclerotic activity was superior to that observed for various standard compounds, and the present studies, using BRL 26314 as a pharmacological tool, provide evidence in vivo for an association between the elevation of HDL and reduction of arterial disease.

Animals↗
PubMed1984

Stroop interference based on the synaesthetic qualities of auditory pitch.

The equivalence of perceptual experience across the sensory modalities, most vividly observed in synaesthetes, is rarely discussed in contemporary cognitive psychology. It is suggested, however, that the concepts and paradigms of human information processing are ideally suited to test, for example, the fundamental assumption that the synaesthetic qualities of a stimulus are rapidly and automatically encoded. In a preliminary experiment subjects were asked to rate each of four auditory tones on a series of 7-point scales defined by pairs of antonyms. The results confirmed that a pure auditory tone has a range of qualities, determined by its pitch, that are shared by stimuli in other modalities. The main experiment used a paradigm based on the Stoop interference effect. Here the 50 Hz and 5500 Hz tones served as incidental stimuli and the subjects were required to respond as quickly as possible by pressing one of two keys depending on which one of four possible words appeared in the centre of the screen. Subjects were found to respond more slowly when the qualities of the tone were incongruent with the synaesthetic qualities represented by the test word. The results confirm that synaesthetic qualities of pitch are rapidly and automatically encoded and that the products of this encoding automatically interact with the mechanisms responsible for identifying word meaning and/or with the post-identification decision processes.

Concept Formation↗
PubMed1983

Vitellogenin B2 gene in Xenopus laevis: isolation, in vitro transcription and relation to other vitellogenin genes.

The isolation of the four Xenopus laevis vitellogenin genes has been completed by the purification from a DNA library of the B2 gene together with its flanking sequences. The overlapping DNA fragments analyzed cover 34 kilobases. The B2 gene which has a length of 17.5 kilobases was characterized by heteroduplex and R-loop mapping in the electron microscope and by in vitro transcription in a HeLa whole-cell extract. Its structural organization is compared with that of the closely related B1 gene. The mRNA-coding sequence of about 6 kilobases is interrupted 34 times in the B1 gene and 33 times in the B2 gene. Sequence homology between the two genes was not only found in exons. In addition, 54% of the intron sequences as well as 63% and 48.5% respectively of the 5' and 3' flanking sequences, show enough homology to form stable duplexes. These findings are compared with earlier results obtained with the two other closely related members of the vitellogenin gene family, the A1 and the A2 genes.

Animals↗
PubMed1983

Sequence homologies within the 5' end region of the estrogen-controlled vitellogenin gene in Xenopus and chicken.

In oviparous vertebrates vitellogenin, the precursor of the major yolk proteins, is synthesized in the liver of mature females under the control of estrogen. We have established the organization and primary structure of the 5' end region of the Xenopus laevis vitellogenin A2 gene and of the major chicken vitellogenin gene. The first three homologous exons have exactly the same length in both species, namely 53, 21 and 152 nucleotides, and present an overall sequence homology of 60%. In both species, the 5'-non-coding region of the vitellogenin mRNA measures only 13 nucleotides, nine of which are conserved. In contrast, the corresponding introns of the Xenopus and the chicken vitellogenin gene show no significant sequence homology. Within the 500 nucleotides preceding the 5' end of the genes, at least six blocks with sequence homologies of greater than 70% were detected. It remains to be demonstrated which of these conserved sequences, if any, are involved in the hormone-regulated expression of the vitellogenin genes.

Amino Acid Sequence↗
PubMed1983

Detection of cell surface antigen in cancer of renal pelvis and ureter.

Thirty-five patients with transitional cell carcinoma of the renal pelvis or ureter of all stages and grades were studied for presence or absence of ABO(H) antigens utilizing an improved technique for staining and preserving the slides. Seventy per cent of the grade I tumors retained their antigens. Patients with antigen present had a longer duration of disease-free interval. Specific red cell adherence (SRCA) may predict the clinical course of patients with low-stage, low-grade transitional cell carcinomas and may be helpful in selecting patients for optimal therapy.

ABO Blood-Group System↗
PubMed1983

Bipolar outcome in the course of depressive illness. Phenomenologic, familial, and pharmacologic predictors.

Twenty percent of a cohort of 206 outpatient depressives with no past bipolar history switched during prospective observation. These 41 probands developed manic periods on the average of 6.4 years (median 4, range 1-25) after their first depressive episode. The change in polarity occurred throughout the life span, but was most common in adolescence and early adulthood. The following variables were found useful in predicting this outcome: onset less than or equal to 25 years, bipolar family history, loaded pedigrees, precipitation by childbirth, hypersomnic-retarded phenomenology, and pharmacologically-mobilized hypomania. Although the respective sensitivities of these findings were relatively low (32-71%), their specificities ranged from 69% to 100% for bipolar outcome; the diagnostic specificity of any 3 of these variables when combined was 98%. When compared with nonbipolar depression, bipolar disorder was seldom chronologically secondary to nonaffective psychiatric disorders. These findings suggest that many young depressives with lethargy and oversleeping are not manifesting a "neurotic" disorder, but rather a precursor of primary bipolar affective disorder. Finally, a psychotically depressed adolescent or young adult with positive bipolar family history should be observed for eventual bipolar outcome, especially when the clinical presentation is that of stupor.

Adolescent↗
PubMed1983

Rat ovarian epidermal growth factor receptors: characterization and hormonal regulation.

Rat ovarian epidermal growth factor (EGF) receptors were characterized in total ovarian homogenate obtained from animals at random stages of the estrous cycle. A single class of specific and high-affinity binding sites with an apparent dissociation constant (KD) of 1.1 +/- 0.2 nM and a total site number of 78 +/- 4 fmoles/mg protein (652 +/- 17 fmoles/100 mg wet tissue) was observed. In 4-day cycling rats, ovarian EGF receptor levels are high (200 fmoles/100 mg ovary) on the morning of estrus as well as in the afternoon of proestrus and are lower by 30, 60 and 55% on the morning of diestrus I, diestrus II and proestrus, respectively. Chronic administration of an LHRH agonist is accompanied by low ovarian EGF receptor levels comparable to those observed on diestrus II. In intact or hypophysectomized female rats pretreated with pregnant mare's serum gonadotropins, administration of ovine follicle-stimulating hormone or human chorionic gonadotropin increases ovarian EGF receptor concentration and content while the administration of ovine prolactin, 17 beta-estradiol or progesterone has no effect. Treatment with dihydrotestosterone or testosterone slightly reduces ovarian EGF binding in intact but not hypophysectomized animals. The variation of ovarian EGF receptor levels observed during the estrous cycle as well as the modulation of these receptors by the administration of exogenous gonadotropins suggest that EGF could well play a physiological role in the regulation of ovarian functions.

Animals↗