PubMed Health⌕ Search

Biomedical subjects

C J Lacey

Publications and source records attributed to C J Lacey.

At least 19 recordsLinked to original sources
PubMed2005

GABA(B) receptors at glutamatergic synapses in the rat striatum.

Although multiple effects of GABA(B) receptor activation on synaptic transmission in the striatum have been described, the precise locations of the receptors mediating these effects have not been determined. To address this issue, we carried out pre-embedding immunogold electron microscopy in the rat using antibodies against the GABA(B) receptor subunits, GABA(B1) and GABA(B2). In addition, to investigate the relationship between GABA(B) receptors and glutamatergic striatal afferents, we used antibodies against the vesicular glutamate transporters, vesicular glutamate transporter 1 and vesicular glutamate transporter 2, as markers for glutamatergic terminals. Immunolabeling for GABA(B1) and GABA(B2) was widely and similarly distributed in the striatum, with immunogold particles localized at both presynaptic and postsynaptic sites. The most commonly labeled structures were dendritic shafts and spines, as well as terminals forming asymmetric and symmetric synapses. In postsynaptic structures, the majority of labeling associated with the plasma membrane was localized at extrasynaptic sites, although immunogold particles were also found at the postsynaptic specialization of some symmetric, putative GABAergic synapses. Labeling in axon terminals was located within, or at the edge of, the presynaptic active zone, as well as at extrasynaptic sites. Double labeling for GABA(B) receptor subunits and vesicular glutamate transporters revealed that labeling for both GABA(B1) and GABA(B2) was localized on glutamatergic axon terminals that expressed either vesicular glutamate transporter 1 or vesicular glutamate transporter 2. The patterns of innervation of striatal neurons by the vesicular glutamate transporter 1- and vesicular glutamate transporter 2-positive terminals suggest that they are selective markers of corticostriatal and thalamostriatal afferents, respectively. These results thus provide evidence that presynaptic GABA(B) heteroreceptors are in a position to modulate the two major excitatory inputs to striatal spiny projection neurons arising in the cortex and thalamus. In addition, presynaptic GABA(B) autoreceptors are present on the terminals of spiny projection neurons and/or striatal GABAergic interneurons. Furthermore, the data indicate that GABA may also affect the excitability of striatal neurons via postsynaptic GABA(B) receptors.

Animals↗
PubMed2005

Modulation of retino-collicular transmission by Group III metabotropic glutamate receptors at different ages during development.

Group III metabotropic glutamate receptors (especially mGlu4, mGlu7, mGlu8) are thought to be involved in modulating visual processing in the adult superior colliculus, a major termination site of retinal input in the rodent brain. We have investigated this role by making field EPSP recordings in response to optic tract stimulation in superior colliculus slices taken from rats aged from P14 to P180. Application of the Group III agonist L-AP4 at a concentration (10 microM) effective to activate mGlu4 and mGlu8 receptors, but not mGlu7 receptors, resulted in reductions of the field EPSP in all ages, although the effect was greatest in slices taken from P14 rats. Increasing the L-AP4 concentration to 100 microM so as to also activate mGlu7 receptors resulted in further field EPSP reductions. Similar reductions were seen in the combined presence of the GABA antagonists picrotoxin and CGP55845A, indicating a lack of involvement of GABAergic mechanisms in the action of L-AP4. Pairing of optic tract stimuli (20 ms separation) resulted in paired-pulse depression at all ages. L-AP4 was found to reduce paired-pulse depression at both 10 microM and 100 microM in slices from all ages of rat. The results of this study suggest that mGlu4/mGlu8 and mGlu7 receptors modulate retino-tectal transmission via a presynaptic mechanism, and that these effects are greatest in young animals. This is the first demonstration of a functional change in Group III receptor effect with aging, and this would be consistent with developmental regulation of these receptors.

Age Factors↗
PubMed2004

Concurrent granulomatous Pneumocystis carinii and Mycobacterium xenopi pneumonia: an unusual manifestation of HIV immune reconstitution disease.

This report of concurrent granulomatous Pneumocystis carinii pneumonia (GPCP) and Mycobacterium xenopi pneumonia (MXIP) in a patient with advanced HIV disease 3-5 weeks after commencing antiretroviral therapy (ART) fits the syndrome of HIV immune reconstitution/restoration disease (IRD). It may also be a unique window into the immunology of granulomatous inflammation.

AIDS-Related Opportunistic Infections↗
PubMed2001

The treatment of human papillomavirus lesions of the lower genital tract.

Anogenital warts are caused by human papillomavirus types 6 and 11 infection, and are the most common clinical manifestation of lower genital tract human papillomavirus infection. They are the most frequently recognized sexually transmitted disease in the developed world, occurring at an incidence rate of 0.5-1.2% in young men and women aged 18-25 years. Many therapies for genital warts have been described, none being ideal in that all therapeutic modalities fail to clear the warts in a proportion of patients, and the recurrence of warts after successful treatment is seen with all treatments. The current knowledge base of the therapy of genital warts is flawed by a lack of good natural history data either with treatment or without treatment over longer periods of time, in that most trials report comparisons of monotherapies over a short time and there is a lack of structured trials addressing consecutive therapies over longer durations, as occurs in real-life clinical situations.

Adolescent↗
PubMed2001

The interrelation of HIV, cervical human papillomavirus, and neoplasia among antenatal clinic attenders in Tanzania.

OBJECTIVES: To determine the prevalence and interrelation of cervical human papillomavirus (HPV) genotypes, squamous intraepithelial lesions (SIL), HIV, and other reproductive tract infections (RTIs) among urban antenatal clinic attenders in Mwanza, Tanzania. METHODS: Genital swabs were collected from 660 pregnant women and tested for a range of RTIs and for cervical cytology. Cervical HPV-DNA was detected by PCR and genotyped. HIV and syphilis serologies were performed. RESULTS: HPV prevalence was 34% (209/612 women). Of the 144 typeable samples, 83% were high risk (HR-HPV) oncogenic strains (56% HPV 16 related types). SIL was detected in 43 women (7%), with high grade SIL in 3%. There was a high prevalence of HIV (15%), and of any RTI (83%). Genital warts were detected in 20 women (3%). HPV infection was associated with some behavioural factors (short duration of relationship, single status, not using condoms) and gonorrhoea. There was no overall association between HPV and HIV (OR=1.02, 95% CI 0.6-1.6), but a non-significant trend towards a stronger association with HR-HPV in women aged 15-19 (OR=2.79, 95% CI 0.8-9.5) and women aged > or =30 (OR=3.20, 95% CI 0.7-15). SIL was associated with HPV (OR=3.66, 95% CI 1.9-7.0), but not significantly with HIV (OR=1.54, 95% CI 0.7-3.4). Prevalence of SIL was higher among women dually positive for HPV/HIV compared to HPV infection only (21% v 12%), although this difference was not statistically significant (p=0.17). CONCLUSIONS: HPV infection was highly prevalent in this young antenatal population. The association of HIV with HR-HPV types in older women may suggest that the principal HIV/HPV interaction in this population is for HIV to upregulate HPV persistence, leading to subsequent development of SIL.

Adolescent↗
PubMed2000

Prospects for control of herpes simplex virus disease through immunization.

Herpes simplex viruses (HSVs) can cause a variety of infections, including genital herpes. Despite effective antiviral therapy, HSV infections remain a significant worldwide public health problem. Vaccines offer the best hope for controlling spread and limiting HSV disease. This article discusses the pathogenesis and immunobiology of mucocutaneous HSV infections, summarizes the spectrum of diseases caused by HSV, and provides a review of the field of HSV vaccine research. This article also discusses what might be realistically expected of a vaccine intended for control of genital herpes and explores the question of whether a vaccine that is effective in controlling genital HSV disease might also be effective in controlling nongenital HSV disease. The efficacy of such vaccines for the full spectrum of HSV disease will eventually determine the timing and targeting of immunization, ranging from selective immunization in preadolescence to universal childhood immunization as part of the routine childhood regimen.

Female↗
PubMed2000

European course on HPV associated pathology: guidelines for primary care physicians for the diagnosis and management of anogenital warts.

The European Course on HPV Associated Pathology (ECHPV) was founded in 1990 by a group of clinicians, pathologists, and virologists to teach important principles for the practice and management of human papillomavirus (HPV) disease to gynaecologists, dermatologists, and other medical disciplines. These guidelines are intended to assist the practice of primary care physicians for diagnosis and treatment of anogenital warts.

Adjuvants, Immunologic↗
PubMed1999

Phase IIa safety and immunogenicity of a therapeutic vaccine, TA-GW, in persons with genital warts.

A fusion protein vaccine consisting of human papillomavirus 6 L2E7 with Alhydrogel was developed for the treatment of genital warts. Twenty-seven subjects with genital warts received 3 immunizations over 4 weeks in an open-label study. The vaccine was well-tolerated, and all subjects made serum IgG antibodies, predominantly IgG1, against L2E7. Nineteen of 25 tested persons made antigen-specific T cell proliferative responses to L2E7, and peripheral blood mononuclear cells when cultured with L2E7 in vitro produced both interferon-gamma and interleukin (IL)-5, although IL-5 predominated after the final vaccination. Five subjects completely cleared warts within 8 weeks. Subjects whose warts were not cleared by 8 weeks were offered conventional therapy. Recurrence of warts was not seen in any of the 13 persons whose warts cleared by vaccine alone or with conventional therapy. While these preliminary results of the use of this therapeutic immunogen are encouraging, proof of efficacy will require randomized double-blind trials.

Adult↗
PubMed1997

Analysis of the sociodemography of gonorrhoea in Leeds, 1989-93.

OBJECTIVE: To investigate the epidemiology of gonorrhoea in an urban area in the United Kingdom. DESIGN: Analysis of all cases of gonorrhoea with regard to age, sex, ethnic group, and socioeconomic group with 1991 census data as a denominator. SETTING: Leeds, a comparatively large urban area (population around 700,000) in the United Kingdom. SUBJECTS: All residents of Leeds with culture proved cases of gonorrhoea during 1989-95. MAIN OUTCOME MEASURE: Relative risk of gonorrhoea. RESULTS: Sex, age, race, and socioeconomic group and area of residence were all independently predictive of risk of infection. Young black men aged 20-29 were at highest risk, with incidences of 3-4% per year. Black subjects were 10 times more likely than white subjects to acquire infection, and subjects from the most deprived socioeconomic areas were more than four times more likely than those from the most affluent areas to acquire infection. CONCLUSIONS: Different ethnic and socioeconomic groups vary in their risk of infection with gonorrhoea within an urban area. Targeted interventions and screening to reduce the incidence of sexually transmitted disease are now priorities.

Adolescent↗
PubMed1996

Use of terbinafine in HIV-positive subjects: pilot studies in onychomycosis and oral candidiasis.

Study 1. Eighteen HIV-positive Caucasian homosexual men with initial positive fungal microscopy were recruited into this prospective, dual-centre, open-label study. They received a once-daily oral dose of 250 mg terbinafine for 12 weeks. Eight were subsequently excluded after screening cultures proved negative. The mean CD4 count of the 10 evaluable subjects was 302/mm3. All 10 positive fungal cultures were confirmed as Trichophyton rubrum. Using an intention-to-treat analysis, healthy unaffected nail growth increased from a mean of 1.6 mm at baseline to 5.2 mm after 12 weeks' treatment. Clinical response after treatment was 6.4 mm at 36 weeks and 8.0 mm at 48 weeks. Three of the 10 toenail infections were cured mycologically. This 30% cure rate was maintained over 48 weeks' follow-up, despite three patients discontinuing the study. One withdrew following a terbinafine-induced drug rash. Two others stopped treatment during HIV-related illnesses, but without terbinafine side-effects. Study 2. Ten HIV-positive subjects, nine culture-positive for Candida albicans and one for Candida albicans and Candida glabrata, were recruited into this pilot study. They received 250 mg oral terbinafine daily for 14 days. Their average CD4 count was 131/mm3. All patients remained culture-positive throughout the study. Slight improvements in signs and symptoms were seen in one or two patients but this might well have been attributable to improved oral hygiene. Oral terbinafine at this dosage was therefore not thought an effective treatment for this indication in HIV-positive patients. The drug was well tolerated and no serious treatment-related adverse events were reported.

Antifungal Agents↗
PubMed1995

Neutrophil enzymes in urine for the detection of urethral infection in men.

OBJECTIVES: To determine if assaying the neutrophil enzymes, neutrophil elastase (NE) and myeloperoxidase (MPO) in the urine of men attending a genitourinary medicine clinic could identify those with Neisseria gonorrhoeae or Chlamydia trachomatis infections, and those with urethritis (with or without an identified infection with either organism), and to compare the new assays with the performance of the leucocyte esterase test (LET). METHOD: 100 men had urethral specimens taken for Gram-stained urethral smear, culture for N gonorrhoeae, and for C trachomatis testing by enzyme immunoassay. First-voided urines were tested for leucocyte esterase by commercial dipstick (positives were defined as greater than "trace") and then frozen at -20 degrees C prior to being assayed for NE and MPO. RESULTS: Five patients had gonorrhoea, six had chlamydia and none had both. Evidence of urethritis (> 5 polymorphonuclear leucocytes in four x 1000 fields) was found in 29 men. The results of the urine assays showed MPO levels to be non-discriminatory; however NE levels were significantly elevated in patients with proven infection or urethritis or both. Using NE values from men with no infection or urethritis an upper limit for normal was defined. Utilising this, the sensitivity of the elastase assay was calculated and found to be superior to the sensitivity of LET for detecting proven infection (64% vs 36%) and urethritis (52% vs 31%). CONCLUSIONS: Further studies of neutrophil elastase in the pathogenesis, diagnosis and treatment of urethritis are indicated.

Adolescent↗
PubMed1993

Characterization of Encephalitozoon hellem (Microspora) isolated from the nasal mucosa of a patient with AIDS.

A microsporidium of the genus Encephalitozoon was isolated into culture from the nasal epithelium of a patient with AIDS. It was compared with in vitro isolates of Encephalitozoon cuniculi and the type isolate of Encephalitozoon hellem by SDS-PAGE and by Western blotting with murine antisera raised to E. cuniculi, E. hellem and the nasal isolate, monoclonal antibodies raised to E. cuniculi and sequential sera from the patient. All tests showed similarities between E. hellem and the nasal isolate but differences between these two isolates and E. cuniculi. Minor protein differences between E. hellem and the nasal isolate were not considered sufficient to separate them at the specific level. The new isolate is named the Wainwright isolate of E. hellem. The ultrastructure of the Wainwright isolate in vitro was similar to that of the parasite in vivo but there was a greater tendency for disruption of the parasitophorous vacuoles. The deposition of the electron-dense surface coat on the sporogonic stages of E. hellem, as a uniform layer which later thickens, is in contrast to its deposition as broad bands, which later join up, in E. cuniculi. This may be a useful character in distinguishing the species without recourse to analysis of protein profiles.

AIDS-Related Opportunistic Infections↗
PubMed1993

Lack of detection of human papillomavirus DNA in male urine samples.

OBJECTIVES: To evaluate polymerase chain reaction (PCR) methodology for the detection of urethral human papillomavirus (HPV) infection by examining urinary sediment from males. SETTING: Department of Genitourinary Medicine, Leeds General Infirmary. SUBJECTS: 73 male patients attending for treatment of sexually transmitted diseases, including 14 patients with genital warts which did not involve the urethral meatus. METHODS: Urinary sediment was tested for HPV DNA and human beta globin gene DNA by PCR methodology. A consensus primer set capable of detecting a wide range of HPV types was used. PCR product was analysed by gel electrophoresis and ethidium bromide staining. RESULTS: HPV DNA was not detected in any of the specimens. Human beta globin gene DNA was identified in 40 of the 73 specimens (55%). CONCLUSIONS: Screening urinary sediment for HPV DNA by PCR methodology with analysis of PCR product by gel electrophoresis and ethidium bromide staining is probably unhelpful for studying the prevalence of urethral HPV infection in men.

Base Sequence↗