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Biomedical subjects

J Welch

Publications and source records attributed to J Welch.

At least 19 recordsLinked to original sources
PubMed1995

Monoclonal antibodies raised against covalently crosslinked complexes of human immunodeficiency virus type 1 gp120 and CD4 receptor identify a novel complex-dependent epitope on gp 120.

The binding of the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein, gp120, to its cell surface receptor, CD4, represents a molecular interaction involving distinct alterations in protein structure. Consequently, the pattern of epitopes presented on the gp120-CD4 complex should differ from those on free gp120. To investigate this concept, mice were immunized with covalently crosslinked complexes of viral HIV-1IIIBgp120 and soluble CD4. Two monoclonal antibodies (MoAbs) obtained from the immunized mice exhibited a novel epitope specificity. The MoAbs were marginally reactive with HIV-1IIIBgp120, highly reactive with gp120-CD4 complexes, and unreactive with soluble CD4. The same pattern of reactivity was seen in solid-phase assays using HIV-1(451)gp120. A similar specificity for complexes was evident in flow cytometry experiments, in which MoAb reactivity was dependent upon the attachment of gp120 to CD4-positive cells. In addition, MoAb reactivity was detected upon the interaction of CD4 receptors with purified HIV-1IIIB virions. Notably, seroantibodies from HIV-positive individuals competed for MoAb binding, indicating that the epitope is immunogenic in humans. The results demonstrated that crosslinked gp120-CD4 complexes elicit antibodies to cryptic gp120 epitopes that are exposed during infection in response to receptor binding. These findings may have important implications for the consideration of HIV envelope-receptor complexes as targets for virus neutralization.

Animals↗
PubMed1995

Intracellular metabolites of mercaptopurine in children with lymphoblastic leukaemia: a possible indicator of non-compliance?

As part of a programme assessing the pharmacokinetics of oral thiopurines given for lymphoblastic leukaemia, we assayed intracellular metabolites of mercaptopurine in children from all over the United Kingdom who were given a standard dose of the drug. The metabolites we measured, thioguanine nucleotides and methylmercaptopurines, are products of two competing metabolic pathways and would be expected to show an inverse correlation. A total of 327 children from 17 centres in the UK were studied. All were on the same therapeutic schedule of mercaptopurine. All had been on an unattenuated full protocol-directed dose (at least 75 mg m-2) for a minimum of 7 days before assay. There was a very wide variation in the concentration of the two metabolites measured; the thioguanine nucleotides ranged from 0 to 1255 pmol per 8 x 10(8) red cells (median 289, lower quartile 210, upper quartile 377) and the methylmercaptopurine metabolites ranged from 0 to 46.3 nmol per 8 x 10(8) red cells (median 5.18, lower quartile 2.31, upper quartile 11.59). The anticipated negative correlation was not apparent, but the ratio between the two was not randomly distributed. No child had both metabolite concentrations in the upper quartiles, but in 32 (10%) children the concentration of both metabolites was in the lower quartile. Of the 32, only one metabolite was detected in four and none at all in six. The most likely explanation for these findings is that a minority of children with lymphoblastic leukaemia fail to take oral mercaptopurine either totally or intermittently. The extent of the problem is unknown, but we suspect it may be clinically important in at least 10% of patients.

Adolescent↗
PubMed1995

Family planning in genitourinary medicine: an opportunistic service?

OBJECTIVE: To evaluate and serve the need for contraception in those not using conventional sources of family planning services. SETTING: South London outpatient genitourinary medicine department at King's College Hospital. DESIGN AND SUBJECTS: Prospective study of 200 women seen consecutively in the clinic by the same doctor (LM) during 1993. Women at risk of unwanted pregnancy were identified, and offered immediate contraceptive provision or referral. RESULTS: 15 women (7.5%) were using no contraception, despite being sexually active and not wishing to conceive; of these two presented with an unwanted pregnancy. A further 23 women (11.5%) were not using their chosen contraception effectively, and another 20 women were unclear about contraceptive methods and wanted advice. Young women were most at risk; 14% of those aged 25 years and under were using no contraception. Eight women wished to defer contraceptive advice; of these four defaulted from follow up. Eighteen women (9%) wanted immediate contraceptive supplies. Ten of 18 returned a follow up questionnaire; all these women were satisfied with the contraceptive advice service received. CONCLUSIONS: Absent or ineffective contraception is common in women attending an inner city genitourinary medicine clinic. Immediate provision of contraceptive education, advice and supplies is welcomed by patients.

Adolescent↗
PubMed1994

Effects of minor groove binding drugs on the interaction of TATA box binding protein and TFIIA with DNA.

TBP (TATA box binding protein), a general transcription factor required for proper initiation of gene expression by RNA polymerase II, and minor groove binding drugs (MGBs) both interact with DNA within the minor groove at AT sites. This study has evaluated MGBs as inhibitors of DNA/TBP complex formation by gel mobility shift assays. Our results demonstrate that reversible MGBs (DAPI, distamycin A, Hoechst 33258, and netropsin) are effective inhibitors of the formation of DNA/TBP complex and that distamycin A is the most potent (0.16 microM inhibits TBP complex formation by 50%). CC-1065, a drug that covalently binds to DNA in the minor groove, is even more active than distamycin A (0.00085 microM inhibits TBP complex formation by 50%). Significantly more CC-1065 (0.009 microM) is required to break up preformed DNA/TBP complex compared to the drug concentration needed to prevent complex formation. In comparison, the order of drug addition has little influence on the ability of reversible MGBs to disrupt DNA/TBP complex. In the presence of TFIIA, a factor that enhances TBP association with DNA, greater drug concentrations (distamycin A and CC-1065, respectively) are needed to disrupt a preformed complex of DNA/TBP/TFIIA. In comparison to MGBs, drugs capable of binding to DNA by intercalation are generally weaker at blocking TBP complex formation except for hedamycin, which can intercalate and irreversibly bind to DNA and is as effective as reversible MGBs.

Base Sequence↗
PubMed1994

Setting up regional audit in genitourinary medicine and HIV: the south east Thames experience.

Audit at regional level is a useful complement to local audit, especially in small specialties. Regional audit can reduce professional isolation and lead to the development of uniformly high standards in the care given by a variety of providers. The development of regional audit in genitourinary medicine in South East Thames (UK), and of HIV medicine in South Thames, is described. Meetings are held quarterly, and concentrate on standard setting and development of guidelines. Information about the practice of individual units is collected by questionnaire, the results presented, and guidelines developed. Participation in completing questionnaires and attending the meetings is good. Regional guidelines in eleven topics have been produced, and methods of auditing changes in practice are now being assessed. A regional common data-set is being developed to assist in the audit process.

Ambulatory Care↗
PubMed1994

Clozapine-induced seizures and EEG changes.

Clozapine, an atypical antipsychotic drug, is widely used in refractory schizophrenia. At New Hampshire Hospital, 7 of the first 35 patients treated (20%) had convulsions. Patterns were tonic-clonic (5), complex partial (2), and myoclonic (3). Seizures were dose-related and may be anticholinergic in etiology. EEG changes are frequent with clozapine, particularly as dosage is increased. Twenty-six of 35 patients (74%) had EEG abnormalities at some time during clozapine treatment. EEG is a sensitive means of detecting clinical toxicity. When EEG abnormalities (slowing, dysrhythmia, or paroxysmal discharges) are detected, immediately lowering the dose by at least 25-50 mg per day and adjusting weekly until EEG returns to baseline can reduce the incidence of seizures.

Adult↗
PubMed1993

Moving beyond the Patient Self-Determination Act: educating patients to be autonomous.

This article explores the limitations of the Patient Self-Determination Act. We need to think of advance directives as a process of understanding, reflecting, and discussing, not just a written document. Further, health care professionals must initiate the process of advance directive education in the outpatient setting. Our dialysis unit has successfully integrated this view into daily care of patients and families.

Advance Directives↗
PubMed1992

Neglect and visual recognition.

B.Q., a right-handed woman who had suffered a stroke affecting the right parietal region, showed visuospatial neglect and problems in recognizing seen objects and faces. Investigation of her visual recognition problems revealed a striking inability to identify the left sides of chimaeric objects and faces. Often, B.Q. would deny that the stimulus was chimaeric at all, and she was remarkably poor (though above chance) at discriminating chimaeric from normal faces. Even when left-sided details had been accurately traced or described, they were often either ignored in reporting the identities of the constituent parts of a chimaeric or assimilated in some way to the information from the right side. Neglect of the left side was more pronounced for chimaerics which approximated an individual face or object. It occurred regardless of the chimaeric's position in B.Q.'s field of vision, and was found with brief (200 ms) presentations of stimuli confined to her (perimetrically intact) right visual field. When chimaeric faces were inverted, B.Q. continued to neglect the side of the chimaeric falling to her left, which implies that the neglect did not operate in entirely object-centered coordinates. However, left-sided information could be used if it was critical in determining the identity of an object or a face. We suggest that this could explain B.Q.'s lack of neglect of individual words, for which left-sided (initial) letters are often crucial to successful recognition. An account of her deficit is proposed, involving an interaction between moderately defective pick-up of left-sided information in an object-based coding system and preserved access to stored representations of familiar visual stimuli.

Attention↗
PubMed1991

Inflammatory pseudotumors of the spleen.

Inflammatory pseudotumors are uncommon benign lesions that have been found in numerous organ systems. However, their appearance within the spleen is decidedly rare. Grossly, pseudotumors appear as well-circumscribed, encapsulated masses, while microscopic examination reveals a polymorphous inflammatory cell infiltrate occurring variably with granulomatous reaction, fibrosis, and cell necrosis. Because they often present either as unexplained, asymptomatic masses or with vague constitutional symptoms, splenic inflammatory pseudotumors can raise suspicion for a primary splenic neoplasm, such as lymphoma. Splenectomy is the treatment of choice.

Female↗
PubMed1991

Disentangling neglect and hemianopia.

In this paper we report findings which question the diagnosis of a hemianopia in B.Q., a 66-year-old lady who shows unilateral spatial neglect following a lesion to the right parietal lobe. The presence of a hemianopia has been indicated following two independent assessments of B.Q.'s visual fields. We examined B.Q.'s performance on a visuo-spatial task in which single or double stimuli were displayed left and right of a central fixation point. B.Q. failed to report left stimuli when the fixation point was continuously displayed (OVERLAP CONDITION). This performance is consistent with the suggestion of a left hemianopia as indicated by perimetric field testing. In a further condition the fixation point was extinguished prior to stimuli onset (GAP CONDITION). B.Q. consistently responded to left stimuli in the gap condition and also showed improved performance to right stimuli. Eye movements were recorded on a separate testing session, in which B.Q. showed a normal saccadic response to left targets in the gap condition, but not during the overlap condition. These results suggest that B.Q.'s failure to report left stimuli during field plotting is due to her neglecting left stimuli and not because she has a visual field defect. By using a testing procedure which reduces the severity of neglect B.Q. is able to respond to left stimuli. Reducing the severity of B.Q.'s neglect also abolishes the apparent hemianopia. Standard field plotting techniques which use a consistently displayed fixation point may not be appropriate for the testing of neglect patients' visual fields.

Aged↗
PubMed1991

Head circumference and intellectual performance of patients with Duchenne muscular dystrophy.

The head circumferences of 64 patients with Duchenne muscular dystrophy were measured and found to be greater than those of a normal population. The patients had relative, and in 12 cases, absolute macrocephaly. 47 of the 64 patients underwent intelligence testing and were found to be significantly intellectually impaired, particularly in verbal and language skills. There was no correlation between head circumference or absolute macrocephaly and intellectual performance. The cause of macrocephaly in these patients is unknown and its relevance to the aetiology of intellectual impairment in Duchenne muscular dystrophy is not yet clear.

Adolescent↗