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Biomedical subjects

G Watson

Publications and source records attributed to G Watson.

At least 55 records · Page 3Linked to original sources
PubMed1994

Laser prostatectomy: which way forward?

A number of endoscopic laser strategies have been employed in the treatment of symptomatic benign prostatic hyperplasia at our hospital. The post-operative results in 102 patients are presented. Sidefiring fibres were coupled with the Nd:YAG laser to produce a deep coagulative necrosis within the prostatic adenoma. This approach was associated with a short operative time and a delay of up to three months before treatment effect. Contact laser techniques (with both the 1064 nm and 805 nm lasers) were used to vaporize prostatic tissue in an attempt to produce a defect similar to that following TURP. This provided an immediate treatment effect with early removal of catheters. The operative time, however, was long and this limited the procedure to glands of less than 40 ccs. The hybrid approach (combining laser prostatotomies with coagulation) provided an immediate relief of obstruction with an additional delayed effect as the coagulated cavity matured. All approaches were associated with minimal haemorrhage and limited morbidity with encouraging improvements in both symptom scores and uroflowmetry. The various advantages and disadvantages of each endoscopic laser strategy are discussed.

Follow-Up Studies↗
PubMed1993

Multi-level regulation of lysosomal gene expression in lymphocytes.

The expression of the gene coding for the lysosomal enzyme, beta-glucuronidase (Gus), was examined in functionally distinct T, B and plasma cell lines. Each of the different groups of cells had different intracellular levels of active Gus enzyme and numbers of Gus mRNA copies per cell. Analysis of the molecular forms of Gus mRNA and protein by Northern and Western blotting revealed that the different types of cells all produced a single mature 2.7 kb transcript and a 73 kDa polypeptide. However, the utilisation of the Gus mRNA to produce the Gus antigen, and the subsequent posttranslational processing of the polypeptide to generate the mature, enzymically active Gus, were found to be cell type-specific. Control of the functional expression of the Gus gene is thus exerted at both the transcriptional and translational levels, and appears to differ between different types of lymphocyte.

Animals↗
PubMed1993

The Gus-e locus regulates estrogen repression of androgen-induced beta-glucuronidase expression in mouse kidney.

Both enzyme activity and mRNA concentration of beta-glucuronidase were measured in kidneys of mice treated with testosterone and the synthetic estrogen, diethylstilbestrol. Six congenic strains, all having a C57BL6/J genetic background but each having a different haplotype of the beta-glucuronidase gene complex, were compared. In each strain the induction caused by androgen was partially repressed by estrogen. The extent of this antagonism varied among the six haplotypes and was not coordinate with the extent of induction by androgen alone. Antagonism appears to be regulated by at least two alleles of a new locus, Gus-e, within the beta-glucuronidase gene complex. Repression by estrogen, like induction by androgen, appears to take place primarily at the transcriptional level. Kinetic studies revealed that estrogen causes the androgen response curve to plateau earlier and at a lower level. This suggests that estrogen increases the rate of gene deactivation rather than decreasing the rate of gene activation. Isoelectric focusing of beta-glucuronidase from Gus-ea and Gus-eb mice and their F1 progeny revealed that the genes are regulated in cis. Together, these findings support a model in which both sex hormones exert their effects on separate DNA response elements located in close proximity to the gene or within the gene itself.

Androgens↗
PubMed1993

Regulation of metabolic water and protein compartments by insulin-like growth factor-I and testosterone in growth hormone-deficient lit/lit mice.

Insulin-like growth factor-I (IGF-I) and testosterone are major hormonal regulators of protein metabolism. We chose genetically GH-deficient little (lit/lit) mice to test whether these anabolic hormones act independently or in concert with each other to stimulate protein metabolism. Hormones were administered for 14 days at constant rates to 14-week-old lit/lit female mice, IGF-I was infused via mini-osmotic pumps at 30 micrograms/day and testosterone was administered using 30 mg pellets. Food consumption was measured during the experimental period, and at the end we measured: (a) serum IGF-I, IGF-I-binding proteins (IGFBPs) and blood urea nitrogen (BUN); (b) body and musculo-skeletal carcass weights; (c) musculo-skeletal carcass water, fat, protein and mineral; and (d) selected organ weights plus protein and DNA contents. We found that both of these growth-stimulatory hormones, IGF-I and testosterone, alone and in combination, had anabolic effects on different metabolic compartments in specific target organs. The most unexpected finding in this study was that the IGF-I-induced increase in musculo-skeletal carcass weight arose solely from increased water, revealing the importance of this compartment as an early target of IGF-I action. Other effects caused specifically by IGF-I, but not testosterone, included increases in serum IGFBP-3, body weight and spleen weight. The specific effect of testosterone, but not IGF-I, was to increase serum IGFBP-2. Independent effects were induced by each hormone alone for kidney and spleen weight, kidney and spleen protein content and BUN.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Modulation of androgen-responsive gene expression by estrogen.

Studies on hormonal action frequently focus on a single hormone. In intact animals, however, genes may respond to the balance of multiple hormones. Therefore, we have studied the mutual influence of sex steroids on eight genes previously known to be testosterone-responsive in kidneys of mice. A variety of responses to estrogen were recorded. Effects occurred primarily at the transcriptional level although in several cases there was also evidence of decreased mRNA stability. Estrogen did not affect the nuclear location of the androgen receptor. Apparently each gene interacts with both androgen-receptor complex and estrogen-receptor complex, and the ultimate outcome depends on each gene's detailed regulatory structure.

Animals↗
PubMed1992

Analysis of the genomic and derived protein structure of a novel human serum amyloid A gene, SAA4.

We have determined the structure of the novel SAA gene, SAA4. The gene is 6.2 kb in length and comprises three introns and four exons. Introns 2 and 3 are significantly longer than those of the other human SAA genes. We have sequenced the exons and junction fragments and have shown that the sequence is the same as c-SAA[1] and does not correspond to the pseudogene carried on GSAA4[2]. The predicted SAA4 protein sequence has an eight amino acid insertion relative to the other human SAA proteins and is more closely related to rabbit and mouse SAA proteins than to the other human SAA proteins, or to those of animal species which also possess an insertion. We have analysed the predicted SAA4 protein relative to the other human SAA proteins and have identified three important structural regions. We predict that region 1 of SAA4 represents a lipid binding domain. Region 2 forms an extensive, distinctive, hydrophobic beta sheet region in place of a helical region. In region 3, SAA4 is the only SAA protein having an alpha helix which is not amphipathic. We predict that the SAA4 protein retains a modified function of the conserved region, retains the Ca2+ binding site, has an amino terminal surface site and has a potentially distinct secretion pattern. Together, these differences indicate a distinct function from those of the other SAA proteins.

Amino Acid Sequence↗
PubMed1992

Clinical significance of early vs late hypotensive blood pressure response to treadmill exercise.

BACKGROUND: It is generally believed that exercise-induced hypotension is the result of severe left-main or triple-vessel disease. Since this is not invariably so, and since most studies were performed in male populations, this study was done to determine the frequency of, and the significance of, exercise-induced hypotension in a more general population. METHODS: The treadmill exercise tests of 4850 consecutive patients performed at a university medical center over a period of 7.5 years were reviewed. To identify patients for further analysis, a hypotensive blood pressure response was initially defined (1) as a progressive fall in systolic blood pressure, (2) as a failure of the systolic blood pressure to rise more than 5 mm Hg during exercise, or (3) as an initial rise followed by a fall below the resting standing systolic blood pressure. RESULTS: The incidence of exercise-induced hypotension so defined was less than 2%. Exercise-induced hypotension occurred in two patterns. An early hypotension response was defined as a fall in systolic blood pressure of more than 10 mm Hg, associated with symptoms or ST-segment depression, during the first 5 minutes of exercise or as a progressive fall in systolic blood pressure of at least 20 mm Hg. The majority of patients (nine of 10) with an early hypotensive response had severe coronary artery disease. The late hypotension pattern was characterized by an initial rise, followed by a fall in the systolic blood pressure with continued exercise. Only half of the patients with this pattern had significant coronary artery disease, and half of the patients had other causes for exercise-induced hypotension. A late hypotensive response was six times more frequent than an early hypotensive response. CONCLUSIONS: This study identified two patterns of exercise-induced hypotension. Early, almost always due to severe coronary artery disease, and late, six times more common than early in which only half were due to coronary artery disease. Causes of a late hypotensive response to exercise that were not due to severe coronary artery disease included valvular heart disease, orthostatic hypotension, cardiomyopathy, idiopathic causes, and drugs. Drugs that contributed to a late exercise-induced hypotension response were diuretics, vasodilators, and negative inotropic agents.

Blood Pressure↗
PubMed1991

Post-mortem findings in a fetus with 48,XXY,+21.

A fetus with 48,XXY,+21 was detected on routine amniocentesis at 15 weeks for advanced maternal age. Fibroblast cultures from six different tissues were initiated after termination and each showed the same karyotype without any tissue limited mosaicism. The only phenotypic abnormality detected at post-mortem examination was bilateral clinodactyly of the fifth finger which had been detected on ultrasound. The maternal serum alpha-fetoprotein and the femur length were normal. Maternal age remains an essential criterion for prenatal diagnosis.

Adult↗
PubMed1990

Cytotoxicity of a recombinant ricin-A-chain fusion protein containing a proteolytically-cleavable spacer sequence.

Chimeric proteins composed of ricin toxin A chain (RTA) and staphylococcal protein A (PA) have been produced in E. coli. Constructs consisting of N-terminal RTA and C-terminal PA (RTA-PA) or N-terminal PA and C-terminal (PA-RTA) were capable of binding to immunoglobulin G (via PA) and of specifically depurinating 28 S ribosomal RNA (via RTA). However, neither fusion protein was cytotoxic to antigen-bearing target cells in the presence of an appropriate monoclonal antibody presumably because the RTA could not be released from the PA within the cytosol where the ribosomal substrate of RTA is located. The overcome this, a short amino acid sequence from diphtheria toxin was engineered between the RTA and PA to produce a disulfide-linked loop containing a trypsin sensitive cleavage site. Cleavage of this fusion protein with trypsin converted the RTA-DT-PA to the two chain form consisting of RTA linked by a disulfide bond to PA. The cleaved fusion protein was highly toxic to Daudi cells coated with anti-immunoglobulin antibody suggesting that the RTA could be released from the PA by reduction within the cytosol.

Amino Acid Sequence↗
PubMed1990

Expression in Escherichia coli of an immunoreactive visna virus transactivating protein.

We have cloned the gene encoding the visna 1514 transactivating protein, Tat, into the Escherichia coli lambda pR expression plasmid, pRIT2T. Efficient synthesis of the protein A::Tat fusion protein was obtained in host strains which carried either wild-type or temperature-sensitive (ts) lambda repressors. However, constitutive synthesis of the fusion protein in these host strains resulted in selection against plasmids which synthesized the fusion protein. Efficient repression of the lambda pR promoter was obtained using a ts repressor gene carried on a multicopy plasmid. Synthesis of the fusion protein in this strain was efficient on induction, and reproducible after subculture. Antisera generated against the termini of visna Tat were used to demonstrate that the fusion protein retained the antigenicity of both the N and C termini of the transactivating protein.

Cloning, Molecular↗
PubMed1990

Expansion of immunoregulatory macrophages by granulocyte-macrophage colony-stimulating factor derived from a murine mammary tumor.

Using an immunogenic nonmetastatic murine mammary adenocarcinoma (D1-DMBA-3) induced in BALB/c mice by dimethylbenzanthracene, we have previously shown that splenocytes from tumor bearers have depressed lymphocyte responses to mitogens and antigens, including tumor-associated antigens. In addition, they display decreased natural killer and T-cell cytotoxic activities. Macrophages from tumor-bearing mice appear to be responsible for the suppression of T- and B-cell responses to concanavalin A, lipopolysaccharide, and tumor-associated antigens observed in tumor bearers. The appearance of these macrophages in the spleen tightly parallels the progressive growth of the tumor and the concomitant immunosuppression. Simultaneously high levels of macrophage progenitors were observed in blood, bone marrow, lung, and liver. A significant increase of colony-stimulating activity of the granulocyte-macrophage lineage was detected in the sera from tumor-bearing mice. Higher levels of this colony-stimulating activity (CSA) were detected in tumor cystic fluid as compared with the levels in serum. A tumor cell line established in vitro from the D1-DMBA-3 in vivo tumor produces high levels of a factor with CSA in culture supernatant fluids. Partial purification of the CSA from the tumor cell line supernatants was achieved using CentriCell ultrafiltration and SephacrylS-300 chromatography. These studies revealed that the molecular weight of the colony-stimulating-like factor is 32,000 to 35,000. The morphology of the colonies obtained in cultures using this factor is similar to that of the colonies that develop in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) but not with macrophage colony-stimulating factor (M-CSF). CSA from tumor cell supernatants was neutralized by antiserum to GM-CSF but not with anti-M-CSF or anti-granulocyte colony-stimulating factor (G-CSF). Macrophages from bone marrow or peritoneal exudates from normal mice cultured with tumor supernatant for 2 to 3 days strongly inhibit normal splenocyte responses to concanavalin A and lipopolysaccharide. The data suggest that the tumor releases a GM-CSF that alters the hemopoietic system and induces or expands macrophages, which exert a suppressive function on the immune system of tumor-bearing mice.

Animals↗
PubMed1990

Progressive induction of mRNA synthesis for androgen-responsive genes in mouse kidney.

A number of mRNAs present in kidney are selectively induced by the administration of androgen to mice. Using a pulse-labelling method to measure in vivo rates of mRNA synthesis, seven androgen-responsive mRNAs were tested. The time courses of induction following testosterone treatment indicated that androgen-responsive mRNA synthesis increases progressively. Depending on the mRNA examined, it took 2-10 days after the start of hormone administration for synthesis rates to reach a maximum. Even the fastest of these inductions is slow compared to response times in other steroid-responsive systems, and is very slow compared to the time required for androgen-receptor complex to accumulate in the nucleus. We conclude that gene activation in response to androgen is a prolonged and incremental process rather than a single event. Two alternative models are proposed: (1) these genes are actually responding to intermediate transcription factors that accumulate progressively in response to androgen; (2) the androgen-responsive genes contain multiple binding sites that have a cumulative effect on transcription as the number of receptor complexes bound increases.

Actins↗
PubMed1990

Characterisation of Chlamydia psittaci isolated from a horse.

This paper describes the isolation and characterisation of a strain of Chlamydia psittaci obtained from a nasal swab taken from a horse with serous nasal discharge. Initial isolation was achieved in cycloheximide-treated McCoy cell monolayers. Chlamydial inclusions stained by immunofluorescence either with a rabbit antiserum raised against C. psittaci or with a monoclonal antibody directed against the genus-specific lipopolysaccharide antigen were single and compact. They did not stain with iodine or with a monoclonal antibody reactive against Chlamydia trachomatis. The agent was re-isolated in the yolk sacs of embryonated hens eggs and designated N16. Identification of the agent was confirmed by electron microscopy. Unique plasmid DNA was prepared from a purified suspension of chlamydial elementary bodies (EBs), and analysed by electrophoresis through 1.0% agarose gels stained by ethidium bromide. This strain of C. psittaci grew relatively slowly in cycloheximide-treated McCoy cells, and the yield of elementary bodies during the course of one growth cycle was relatively low.

Animals↗
PubMed1990

The development of a laser for stone fragmentation and its place in the management of stones in the era of extracorporeal lithotripsy.

The parameters of a laser which govern stone fragmentation are the pulse duration, wavelength and fibre diameter. The pulse duration is the most important parameter governing fibre transmission. The shorter the pulse duration the less tissue damage and the easier the plasma production at the stone surface but the greater the difficulty to transmit the laser energy through the fibre. At 1 microsecond pulse duration the laser wavelength is highly significant because it governs the degree of absorption at the stone surface necessary for plasma production. Transmission of this laser energy through 200 micron core fibres is straightforward. Fragmentation is achieved by placing the fibre in contact with the stone surface. There is negligible tissue injury. A miniaturised ureteroscope has been developed specifically for the laser. This appears to be easier to use and carries less risk of instrumentational injury to the ureter.

Adolescent↗