Search PubMed⌕ Search

Biomedical subjects

S Watts

Publications and source records attributed to S Watts.

At least 91 records · Page 5Linked to original sources

DNA sequence analysis of the C3H H-2Kk and H-2Dk loci. Evolutionary relationships to H-2 genes from four other mouse strains.

We generated nucleotide sequences for H-2Kk and H-2Dk from the C3H mouse, as well as for a genomic clone of H-2Db, in order to conduct an evolutionary analysis of the H-2 genes from three haplotypes, k, d, and b. H-2Kk from both the C3H and AKR strains, H-2Kd, H-2Kb, H-2Dk, H-2Ld, H-2Dd, H-2Db, and H-2Dp DNA sequences were aligned, and the alignments used to construct phylogenetic trees inferring the evolutionary relationships among the nine genes by two independent methods. Both approaches yielded trees with similar topologies. In addition, the sequence alignments revealed patterns of nucleotide substitutions which implicate both point mutation and recombination in the divergence of the H-2 genes. Future considerations for evolutionary analysis of class I genes are discussed.

Amino Acid Sequence↗

Assessing the functional value of relatives' knowledge about schizophrenia: a preliminary report.

An instrument for assessing and evaluating what relatives know about schizophrenia was evaluated as both a pre- and a post-test for an educational programme. The Knowledge About Schizophrenia Interview (KASI) places emphasis on the functional value of the reported knowledge rather than on the recall of information; it is quick, easy to administer, can be rated reliably, and has face-validity for the relative. The educational programme increased scores from pre-test to a post-test one week after the programme. Relatives with high criticism ratings on the Camberwell Family Interview had lower scores at both tests. Relatives of less chronic patients showed lower scores at pre-test and acquired significantly more information from the programme, while relatives of more chronic patients were less influenced by the information sessions.

Adolescent↗

Inhibition of tumor-cell-mediated extracellular matrix destruction by a fibroblast proteinase inhibitor, protease nexin I.

Human fibrosarcoma (HT-1080) cells, in contrast to normal fibroblasts, rapidly hydrolyze the glycoprotein, collagen, and elastin extracellular matrix (ECM) synthesized by cultured rat aortic smooth muscle cells. This degradation occurs at a rapid rate in the presence of serum, indicating that the cellular proteases responsible are relatively insensitive to serum proteinase inhibitors. Here it is shown that protease nexin I (PNI), a fibroblast-secreted inhibitor of urokinase, plasmin, and certain other serine proteinases, effectively inhibited the HT-1080 cell-mediated degradation of this ECM. PNI at 2.0 nM significantly inhibited matrix destruction for 1-2 days and at 0.2 microM caused a virtually complete inhibition that persisted for the entire 10-day period of observation. Inhibition of ECM destruction was accompanied by a transient arrest of HT-1080 cell proliferation that took place during the first 3 days after PNI addition. PNI did not inhibit the growth of normal fibroblasts and also did not inhibit the growth of HT-1080 cells that were seeded onto plastic dishes rather than onto ECM. Like many types of malignant cells, HT-1080 cells release large amounts of urokinase. Antibody against this plasminogen activator partially protected ECM from HT-1080 cell-mediated hydrolysis, indicating that it may have been a target of PNI. One potential physiological function of PNI could be to help maintain the integrity of connective tissue matrices, protection that malignant cells could overcome by secreting proteinases in excessive amounts.

Amyloid beta-Protein Precursor↗

Effects of 6-hydroxydopamine on the hypothalamo-pituitary-adrenocortical axis.

Female rats were treated with two intraventricular injections each of 350 micrograms 6-hydroxydopamine (6-OHDA) and used for experiment 4 or 14 days later. The response to laparotomy, as assessed by subsequent in vitro corticosterone release, was unaffected by the drug, but that to the smaller stress of a skin cut was significantly reduced. Both fast and delayed feedback responses to corticosterone administration were still evident in 6-OHDA-treated animals. When determined 14 days after treatment, hypothalamic concentrations of epinephrine (E) and norepinephrine (NE) were reduced by 46 and 84%, respectively. There was no significant change in content of immunoreactive corticotropin-releasing factor (CRF-41). The acetylcholine-stimulated release of CRF bioactivity from control hypothalami incubated in vitro was significantly inhibited by E or NE, with E being at least 10 times more potent on a molar basis. This effect of NE was enhanced in hypothalami removed from 6-OHDA-treated rats, complete inhibition of acetylcholine-stimulated release of CRF being produced by 0.6 nM NE, as opposed to 6.0 nM for untreated controls. At the level of the anterior pituitary gland, tissue content of adrenocorticotropin (ACTH) was unaffected by treatment, but that of luteinizing hormone (LH) in the same tissues was significantly increased. The corticotrophic response of fragments of the gland incubated or perifused in vitro to hypothalamic extract, CRF-41, arginine vasopressin or E was reduced. In contrast, the response of the tissue to gonadotropin-releasing hormone (GnRH) added in vitro was not significantly affected.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

Protease nexin. Properties and a modified purification procedure.

The present paper describes chemical and functional properties of protease nexin, a serine protease inhibitor released from cultured human fibroblasts. It is shown that protease nexin is actually synthesized by fibroblasts and represents about 1% of their secreted protein. Analysis of the amino acid composition of purified protease nexin indicates that it is evolutionarily related to antithrombin III and heparin cofactor II. Protease nexin contains approximately 6% carbohydrate, with 2.3% amino sugar, 1.1% neutral sugar, and 3.0% sialic acid. The Mr calculated from equilibrium sedimentation analysis is 43,000. Protease nexin is a broad specificity inhibitor of trypsin-like serine proteases. It reacts rapidly with trypsin (kassoc = 4.2 +/- 0.4 X 10(6) M-1 s-1), thrombin (kassoc = 6.0 +/- 1.3 X 10(5) M-1 s-1), urokinase (kassoc = 1.5 +/- 0.1 X 10(5) M-1 s-1), and plasmin (kassoc = 1.3 +/- 0.1 X 10(5) M-1 s-1), and slowly inhibits Factor Xa and the gamma subunit of nerve growth factor but does not inhibit chymotrypsin-like proteases or leukocyte elastase. In the presence of heparin, protease nexin inhibits thrombin at a nearly diffusion-controlled rate. Two heparin affinity classes of protease nexin can be detected. The present characterization pertains to the fraction of protease nexin having the higher affinity for heparin. The low affinity material, which is the minor fraction, is lost during purification.

Amino Acids↗

An outbreak of dracunculiasis in a peri-urban community of Ilorin, Kwara State, Nigeria.

An outbreak of dracunculiasis was investigated at Egbejila, a peri-urban community near the city of Ilorin, the capital of Kwara State, Nigeria. Of 589 persons examined in June 1983, 265 (45.0%) had active ulcers with protruding guinea worms. The infection rates among males (42.1%) and females (47.8%) were not statistically different (p greater than 0.1) but children below 10 years of age were significantly less infected than the older subjects (p less than 0.001). Altogether, 67.2% of the infected subjects had more than one guinea worm lesion while 54.7% were incapacitated by the infection. The peculiar circumstances which led to the spontaneous outbreak of dracunculiasis and contributed to its severity in this community after the construction of the Asa Dam to solve the problem of acute water scarcity in the Ilorin municipality, were identified and discussed.

Adolescent↗

Identification of three distinct papillomavirus genomes in a single patient with epidermodysplasia verruciformis.

Benign papillomas from a patient with a family history of epidermodysplasia verruciformis were examined for the presence of human papillomavirus (HPV) DNA. Employing stringent hybridization conditions that allow identification of a single type of HPV and radioactively labeled HPV-5 DNA as a probe, we have detected HPV DNA exhibiting sequence homology to HPV-5 in these tumors. Restriction endonuclease analysis of this HPV DNA confirmed its identity as HPV type 5. However, when hybridization was performed under less stringent conditions that allow all of the known types of HPV to react with the radioactively labeled HPV-5 DNA probe, two additional species of HPV DNA unrelated to HPV-5 were identified. As these two HPV types do not hybridize with HPV 1, 2, 3, or 4 under stringent conditions, they appear unique and have, as yet, not been reported to be associated with patients exhibiting epidermodysplasia verruciformis. Thus we have observed three distinct HPV species in benign papillomas from a single patient. These observations have important implications when attempting to correlate the type of HPV present in the various wart disease syndromes that have been described to date and further suggest that extreme care must be taken when analyzing carcinomas, occupying similar anatomic sites and suspected to have arisen from papillomas, for HPV species.

Animals↗

Aspirin kinetics and platelet aggregation in man.

Our aims were (1) to determine the effect of six commercially available aspirin (ASA) preparations on in vitro platelet aggregation, and (2) to relate changes in platelet function to ASA kinetics. Each of six subjects took a single dose of one of the following preparations--600 mg Asproclear, 600 mg Bufferin, 600 mg Bi-prin, 600 mg compressed ASA, 650 mg Ecotrin, or 650 mg S.R.A.--in random order every 3 wk. Venous blood was drawn before and at 2, 4, 6, and 24 hr after ASA dosage to measure platelet aggregation in response to collagen and adenosine diphosphate and, at more frequent intervals, to characterize ASA kinetics. Asproclear, Bufferin, Bi-prin, and compressed ASA yielded peak plasma ASA levels of 28 to 56 mumol/l (5 to 10 mg/l) within 15 to 60 min and peak salicylic acid (SA) levels of 72 to 290 mumol/l (10 to 40 mg/l) within 2 hr. Ecotrin and S.R.A. yielded plasma SA levels of 14 to 87 mumol/l (2-12 mg/l) within 4 to 24 hr and no measurable ASA at any time after dosing. Platelet aggregation was inhibited to an equal extent by all preparations. The time course for this inhibition was the same for all preparations but Ecotrin (which led to a more delayed effect). There was significant recovery of collagen-induced platelet aggregation at 24 hr with all preparations but Ecotrin. With Ecotrin and S.R.A. there was inhibition of platelet aggregation in the absence of measurable circulating ASA. We postulate that this was due to acetylation of cyclooxygenase in the portal circulation and that inhibition of peripheral cyclooxygenase may be spared.

Adult↗

Characterization of two HPV-3 related papillomaviruses from common warts that are distinct clinically from flat warts or epidermodysplasia verruciformis.

We have recently identified two unusual human papillomavirus (HPV) isolates while engaged in an ongoing study of wart disease in meat handlers and veterinarians. The papillomas from which these two viruses were isolated clinically resembled verruca vulgaris rather than either flat warts or epidermodysplasia verruciformis (EV). These two previously uncharacterized HPVs were molecularly cloned and characterized with respect to known HPVs. The genomes of the two viruses exhibited dramatically different restriction endonuclease cleavage patterns but were found to have significant sequence homology to each other, as well as to HPV-3 and a new virus isolated from a patient with EV. Neither of the two new HPV isolates exhibit detectable sequence homology under stringent conditions of hybridization or share similar restriction endonuclease cleavage patterns with previously characterized HPV types 1,2,4,5,6b, or a previously isolated HPV from meat handlers.

Adolescent↗

Immunology of human papillomavirus: warts.

Great progress has been made over the last five years in our understanding of papillomavirus (PV) biology. New technology has enabled investigators to understand the relationship between the PV and its host. The PV cannot be cultured in vitro, and this has led to limitations for those wishing to study the biology of this virus. However, utilizing recombinant DNA technology, investigators now have abundant quantities of human papillomavirus (HPV) DNA for study. Such HPV genomes may be labeled with a radioisotope such as P32 and used as a "probe" in hybridization studies to see if a given tissue contains HPV DNA. No longer are we limited to electron microscopy and immune studies in our efforts to identify HPV within benign or malignant tissues. Ultimately, we hope to understand the relationship between the virus and its host. This paper will concentrate on one aspect of this relationship--the immunology of HPV.

Animals↗

Detection of human papillomavirus DNA in anogenital neoplasias.

The presence of papillomaviruses in epithelial-derived cancers from several animal species has led to the speculation that these viruses may also have a pathogenic role in the development of certain human carcinomas, particularly those associated with the anogenital tract. Recently, human papillomavirus (HPV) DNA has been detected in epithelial-derived cancers, both cutaneous and metastatic, from patients exhibiting the rare, chronic flat wart disease, epidermodysplasia verruciformis (EV). Except for patients exhibiting this chronic wart syndrome, the association of HPV genomes with human epithelial cancers has not been demonstrated. In an attempt to delineate the association and possible involvement of papillomaviruses with human anogenital carcinomas, we have begun an analysis of these cancers for the presence of HPV-specific nucleotide sequences by using highly sensitive hybridization procedures capable of detecting distantly related papillomaviruses at low copy number. Here we demonstrate the presence of HPV DNA in several types of anogenital tumours: Bowenoid papulosis, carcinoma in situ, and verrucous carcinoma. These data indicate that HPV can be detected in several types of premalignant and malignant tumours, supporting the contention that this group of viruses may be involved in the development of certain types of human epithelial-derived cancers.

Adult↗

The premenstrual syndrome. A psychological evaluation.

The aim of the present study was to verify the presence of certain psychological factors in women complaining of the premenstrual syndrome which would differentiate these women from others. Of 42 women initially interviewed, 25 were finally selected for study, on the basis of clear premenstrual/menstrual symptoms. Twenty-three women who did not suffer premenstrual symptoms acted as controls. Women suffering from the premenstrual syndrome had significantly higher levels of 'trait' anxiety (STAI), 'neuroticism' (EPI-B), and more negative attitudes towards their bodies, genitals, sex and masturbation, as measured by a 'Role Acceptance Scale'. Both premenstrual syndrome sufferers and controls held negative attitudes toward menarche and menses.

Adult↗

Studies on blood from the original Rhnull proposita and relatives.

A relative of the original Rh proposita, of group R1R2, shows weak expression of his Rh antigens, and is thought to be an Rhnull heterozygote. His wife and 3 of their 4 children show normal Rh antigen expression, but one daughter showed weak Rh antigen expression, as determined by quantitative haemagglutination. The observations support the proposition that the father is heterozygous for an unlinked modifier of Rh antigen expression. Stomatocytosis, observed in the Rhnull proposita and other Rhnull individuals, was also observed, but to a lesser degree, in the blood of an other individual thought to be an Rhnull heterozygote. This observation also supports the earlier conclusion that the Rhnull phenotype of the proposita is due to homozygosity for inactive alleles at a locus which controls the biosynthesis of precursor for Rh and LW antigens. Osmotic fragility tests showed that the Rhnull cells were more fragile than cells with normal Rh antigen expression, and cells from Rhnull heterozygotes had intermediate fragility. This is consistent with the proposition that Rh antigens are normal structural components of the red cell membrane, and the Rhnull heterozygotes show a deficiency of the Rh antigenic structures.

Erythrocytes, Abnormal↗