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Biomedical subjects

A L Jones

Publications and source records attributed to A L Jones.

At least 109 records · Page 6Linked to original sources
PubMed1996

Selective IgA deficiency, hypothyroidism and congenital lymphoedema.

The occurrence of selective IgA deficiency and hypothyroidism with congenital lymphoedema has never previously been documented, although the association of hypogammaglobulinaemia with congenital lymphoedema has previously been reported and can result in recurrent respiratory infections. We report a 34 year old woman with congenital lymphoedema who was found to have symptomatic autoimmune hypothyroidism and asymptomatic selective IgA deficiency.

Adult↗
PubMed1996

Eye drops--the hidden poison.

Eye drops are very commonly prescribed but their potential for systemic absorption and serious toxicity may be forgotten. This paper examines patterns of prescription of eye drops in Scotland by general practitioners. A review of the serious systemic features and toxicity, and their management, of commonly used eye drops is undertaken. Practical recommendations for the monitoring of such effects in clinical practice are made.

Adrenergic beta-Antagonists↗
PubMed1996

Pulmonary B-cell non-Hodgkin's lymphoma associated with autoimmune disorders: a clinicopathological review of six cases.

Because pulmonary B-cell non-Hodgkin's lymphomas are now thought to arise in bronchial mucosa-associated lymphoid tissue (MALT), 45 patients with pulmonary B-cell lymphomas were reviewed to look for aetiological factors in the lung. It was found that six of the 45 lymphomas arose in patients with systemic autoimmune disease, which in three patients involved the lung. These three patients all had cryptogenic fibrosing alveolitis treated with long-term immunosuppressive therapy. Five of the six lymphomas were high grade and one was low grade. The association of pulmonary lymphomas with autoimmune interstitial lung disease is consistent with associations between autoimmune diseases and lymphomas presenting at other mucosal sites, and lends weight to the hypothesis that formation of bronchial mucosa-associated lymphoid tissue precedes the development of lymphoma.

Adult↗
PubMed1996

Design, production and characterization of antibodies discriminating between the phenol- and monoamine-sulphating forms of human phenol sulphotransferase.

1. Phenol sulphotransferases (PSTs) are important enzymes in xenobiotic and endobiotic detoxication, and a key component of the body's chemical defence mechanism. 2. Human phenol-(P-PST) and monoamine-(M-PST) sulphating forms of PST share 93% amino acid sequence identity, and to date the various antibodies produced against PSTs all recognize both enzymes. 3. We have identified two peptides based on the cDNA-derived amino acid sequences of human P-PST and M-PST, which elicited for the first time antibodies capable of discriminating between these highly homologous enzymes. 4. These antibodies represent valuable tools for studying the expression, distribution and function of human phenol sulphotransferases.

Amino Acid Sequence↗
PubMed1995

Discordant expression and variable numbers of neighboring GGA- and GAA-rich triplet repeats in the 3' untranslated regions of two groups of messenger RNAs encoded by the rat polymeric immunoglobulin receptor gene.

An unusual S1-nuclease sensitive microsatellite (STMS) has been found in the single copy, rat polymeric immunoglobulin receptor gene (PIGR) terminal exon. In Fisher rats, elements within or beyond the STMS are expressed variably in the 3' untranslated regions (3'UTRs) of two 'Groups' of PIGR-encoded hepatic mRNAs (pIg-R) during liver regeneration. STMS elements include neighboring constant regions (a 60-bp d[GA]-rich tract with a chi-like octamer, followed by 15 tandem d[GGA] repeats) that merge directly with 36 or 39 tandem d[GAA] repeats (Fisher or Wistar strains, respectively) interrupted by d[AA] between their 5th-6th repeat units. The Wistar STMS is flanked upstream by two regions of nearly contiguous d[CA] or d[CT] repeats in the 3' end of intron 8; and downstream, by a 283 bp 'unit' containing several inversions at its 5' end, and two polyadenylation signals at its 3' end. The 283 nt unit is expressed in Group 1 pIg-R mRNAs; but it is absent in the Group 2 family so that their GAA repeats merge with their poly A tails. In contrast to genomic sequence, GGA triplet repeats are amplified (n > or = 24-26), whereas GAA triplet repeats are truncated variably (n < or = 9-37) and expressed uninterruptedly in both mRNA Groups. These results suggest that 3' end processing of the rat PIGR gene may involve misalignment, slippage and premature termination of RNA polymerase II. The function of this unusual processing and possible roles of chi-like octamers in quiescent or extrahepatic tissues are discussed.

Animals↗
PubMed1995

Human platelet phenolsulfotransferases: cDNA cloning, stable expression in V79 cells and identification of a novel allelic variant of the phenol-sulfating form.

We have isolated cDNA clones encoding phenol- and monoamine-sulfating phenolsulfotransferases, using the reverse transcription-polymerase chain reaction method with human platelet mRNA as template. These cDNAs were stably expressed in the Chinese hamster fibroblast cell line V79 and their substrate specificities towards known sulfotransferase isoenzyme-selective compounds determined. The nucleotide and derived amino acid sequences of the monoamine-sulfating form were identical to those previously identified in human liver and brain, but the cDNA for the human platelet phenol-sulfating form we isolated contained 5 and 2 amino acid changes from the two previously published sequences from human liver and brain, suggesting that we have identified a new allelic variant of human phenol-sulfating phenolsulfotransferase.

Alleles↗
PubMed1995

Expression and identification of the strA-strB gene pair from streptomycin-resistant Erwinia amylovora.

Deletions in either of the genes in the strA-strB gene pair of Erwinia amylovora plasmid pEa34 resulted in a dramatic decrease in streptomycin resistance (SmR), but SmR was restored to high levels by complementation. When strA and strB were cloned separately on a lacIq/Ptac-based expression vector in Escherichia coli, only the protein encoded by strA was produced. When a strong Shine-Dalgarno sequence was introduced and the start codon was located outside the double-stranded region of the stable stem-loop, the protein encoded by strB was produced. Biochemical analysis of the respective phosphorylated products demonstrated that strA and strB encoded aminoglycoside-3"-phosphotransferase (APH(3")-Ib) and aminoglycoside-6-phosphotransferase (APH(6)-Id), respectively. These data suggest that the high-level SmR in bacteria containing strA and strB is due to the combined action of the two enzymes.

Base Sequence↗
PubMed1995

Reduced platelet phenolsulphotransferase activity towards dopamine and 5-hydroxytryptamine in migraine.

OBJECTIVE: The sulphation of the neurotransmitters dopamine and 5-hydroxytryptamine, and of the prototypical xenobiotic 4-nitrophenol, by phenolsulphotransferases was measured in platelet homogenates prepared from a group of migraine sufferers and a group of control subjects. RESULTS: The activity of the M form of phenolsulphotransferase, responsible for the sulphation of dopamine and 5-hydroxytryptamine was significantly reduced in the migraine population, by 28% with dopamine as substrate and by 20% with 5-hydroxytryptamine. The activity of the P form of the enzyme towards 4-nitrophenol was the same in both groups. We also report that the selective inhibition of P form phenolsulphotransferase by red wine is much more potent than previously thought, with a 2000-fold dilution of dealcoholised red wine having the ability to inhibit sulphation by this enzyme by 50%. CONCLUSION: Our findings suggest that a reduced capacity for sulphation and inactivation of biogenic amines and catecholamines may be related to susceptibility to migraine.

Adult↗
PubMed1995

The effect of nitric oxide synthase inhibition on portal pressure and azygos blood flow in patients with cirrhosis.

It has been proposed that the hyperdynamic circulation found in cirrhosis is mediated by nitric oxide released through the induction of nitric oxide synthase. To investigate this the effect of the nitric oxide synthase inhibitor, NG-monomethyl-L-arginine (L-NMMA), was studied upon the portal circulation. After a 30-min infusion of 3 mg/kg of L-NMMA there was a significant fall in heart rate from 83.2 +/- 4.4 to 74.2 +/- 3.9 bpm (p = 0.005), and a significant rise in mean arterial pressure from 91.6 +/- 2.2 to 103.7 +/- 3.2 mmHg, p = 0.004). There was, however, no change in hepatic venous pressure gradient (16.7 +/- 1.5 to 16.1 +/- 1.7 mmHg, p = 0.477) nor in azygos venous blood flow (366 +/- 126 to 368 +/- 145 ml/min, p = 0.683). On subgroups analysis by Child-Pugh grade, significant changes occurred in heart rate and mean arterial pressure only in grade A and B patients (p = 0.0061 and p = 0.0068, respectively). Regional peripheral blood flow was studied using hand thermography. All patients who had an isothermic hands (relatively cold fingers compared to palmar temperature) at the start of the study developed an isothermic pattern after the L-NMMA infusion. This study demonstrates a significant systemic effect of nitric oxide synthase inhibition in patients with cirrhosis but no effect upon the portal or portosystemic collateral circulations at this dose.

Adult↗
PubMed1995

Portal and systemic haemodynamic response to acute and chronic administration of low and high dose isosorbide-5-mononitrate in patients with cirrhosis.

Oral isosorbide-5-mononitrate (Is-5-Mn) was given in doses of 10 and 40 mg acutely and chronically (twice daily for four weeks), allowing a nitrate free interval to 25 patients with cirrhosis. Both 10 mg and 40 mg Is-5-Mn reduced the hepatic venous pressure gradient acutely and chronically, without evidence of tolerance. This was achieved by a reduction in the wedged hepatic venous pressure. The effect on mean azygos blood flow was variable with no significant mean change seen acutely or after chronic use with either dose. The variability was dependent not on the dose used but on the initial azygos flow; the flow in patients with initially low values increased and those with high azygos flows decreased after nitrate challenge. The development of the porto-collateral flow seems an important parameter in predicting haemodynamic response to Is-5-Mn.

Adult↗
PubMed1995

Long-term outcome of state hospital patients discharged into structured community residential settings.

OBJECTIVE: This longitudinal study examined various dimensions of the lives of patients with chronic mental illness immediately before and again several years after their discharge from a state hospital into well-staffed structured community residential settings. METHODS: Fifty-three patients with chronic mental illness and long histories of hospitalization were evaluated shortly before their state hospital discharge using a comprehensive structured assessment of nine dimensions of functioning and symptomatology. A follow-up assessment was undertaken a mean of 7.5 years after discharge into four structured group home settings. RESULTS: At follow-up, 57 percent of the patients continued to live in structured community residential settings, 28 percent had moved on to independent living, and 16 percent had returned to an institutional setting. Fifty-five percent needed hospital readmission, but the total sample spent only 11 percent of the time after discharge in the hospital. At follow-up, patients showed significant improvements in cognitive and social functioning, and 94 percent expressed a preference for life in the community. CONCLUSIONS: Many patients discharged to structured community residential settings seem to prefer them to the state hospital, are able to graduate to independent settings, and show improvement in important dimensions of functioning after several years in the community. Other dimensions seem resistant to change despite the structure and support afforded by residential settings.

Activities of Daily Living↗
PubMed1995

Soluble adhesion molecules and interleukin-2 receptor concentrations in patients with autoimmune chronic hepatitis.

OBJECTIVE: To test the hypothesis that elevated serum levels of intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), (s)E-selectin, (s)P-selectin and soluble interleukin-2 receptor (sIL-2R) occur in patients with biochemically inactive autoimmune hepatitis (AICH) compared with controls. Such a finding would suggest continued immune activation, which in the long-term would contribute to the development of cirrhosis in such patients. METHODS: sICAM-1, sVCAM-1, sE-selectin, sP-selectin and sIL-2R were measured in serum from 50 patients with AICH, divided into two groups according to whether their serum alanine aminotransferase (ALT) levels were normal (below 40 IU/l) or increased (above 40 IU/l). Fourteen healthy subjects served as controls. Eight patients were followed after the induction of remission with increased immunosuppressive therapy. RESULTS: Elevated levels of sICAM-1, sVCAM-1 and sE-selectin were found in patients with AICH compared with controls, independent of their ALT concentration. Only sICAM-1 was significantly elevated in the patients with active disease compared with patients with inactive disease. sIL-2R concentrations were significantly higher in patients with active disease (ALT above 40 IU/l) compared with controls. sP-selectin concentrations were similar in controls and patients with AICH. In patients with clinical and biochemical relapse, increased steroid therapy was followed by a significant reduction in sICAM-1, sVCAM-1 and sIL-2R. The response of sE-selectin was more variable. sICAM-1 remained elevated in five of the eight patients treated with increased steroid therapy despite normalization of their transaminase levels, sIL-2R, sE-selectin and sVCAM-1 levels. In 52% of patients with biochemically inactive AICH (ALT below 40 IU/l), sICAM-1 was above the control range. CONCLUSIONS: These data suggest that patients with AICH have ongoing immune activation despite biochemically inactive disease. This may result in low grade hepatic inflammation and may explain the progression to cirrhosis in patients with AICH despite immunosuppressive therapy.

Adult↗
PubMed1994

The Royal Marsden Hospital pilot tamoxifen chemoprevention trial.

A pilot randomised placebo controlled trial using tamoxifen in healthy women at increased risk of developing breast cancer, has been undertaken in order to evaluate the problems of accrual, acute symptomatic toxicity, compliance, and safety as a basis for subsequent large national multicentre trials designed to test whether tamoxifen can chemoprevent breast cancer. From October 1986 until June 1993, 2012 healthy women with an increased risk of developing breast cancer, usually because of a strong family history, were randomly allocated to receive tamoxifen 20 mgs/day or placebo for up to 8 years if possible. Accrual remained high in spite of extensive informed consent regarding potential risk. Acute symptomatic toxicity was low for participants on tamoxifen or placebo and compliance remained correspondingly high with a predicted 77% of women on tamoxifen and 82% of women on placebo continuing medication at 5 years. There was a significant increase in hot flushes (34% versus 20%) mostly in premenopausal women (p < 0.005), vaginal discharge (16% versus 4%, p < 0.005), and menstrual irregularities (14% versus 9%, p < 0.005). The requirements for hormone replacement therapy for women on tamoxifen or placebo were the same. Safety monitoring indicates no adverse anti oestrogenic effects of tamoxifen. There was no obvious effect of tamoxifen on bone mineral densities (single photon radial absorption). The fibrinogen and antithrombin III were both lowered, resulting in no observed detrimental effect on the ratio of these clotting factors. There was a significant reduction in the serum cholesterol maintained out to 5 years. Annual pelvic assessment using transvaginal ultrasound indicates an increased incidence of uterine fibromata and benign ovarian cysts.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Sulfation of endogenous compounds and xenobiotics--interactions and function in health and disease.

Sulfation is a major detoxication mechanism for endogenous compounds and xenobiotics performed by a family of sulfotransferase isoenzymes. Understanding the normal cellular functions of these different sulfotransferases and the way in which endogenous and exogenous factors are able to influence their activity and expression will provide us with the information necessary to develop novel therapeutic strategies for conditions where sulfation may be implicated. This concept is discussed and is illustrated by examples including adverse drug reactions, fetal development and cancer.

Amino Acid Sequence↗