Search PubMed⌕ Search

Biomedical subjects

S Jaffar

Publications and source records attributed to S Jaffar.

At least 19 recordsLinked to original sources
PubMed2000

Loss of nucleus basalis neurons containing trkA immunoreactivity in individuals with mild cognitive impairment and early Alzheimer's disease.

Recent studies indicate that there is a marked reduction in trkA-containing nucleus basalis neurons in end-stage Alzheimer's disease (AD). We used unbiased stereological counting procedures to determine whether these changes extend to individuals with mild cognitive impairment (MCI) without dementia from a cohort of people enrolled in the Religious Orders Study. Thirty people (average age 84.7 years) came to autopsy. All individuals were cognitively tested within 12 months of death (average MMSE 24.2). Clinically, 9 had no cognitive impairment (NCI), 12 were categorized with MCI, and 9 had probable AD The average number of trkA-immunoreactive neurons in persons with NCI was 196, 632 +/- 12,093 (n = 9), for those with MCI it was 106,110 +/- 14,565, and for those with AD it was 86,978 +/- 12,141. Multiple comparisons showed that both those with MCI and those with AD had significant loss in the number of trkA-containing neurons compared to those with NCI (46% decrease for MCI, 56% for AD). An analysis of variance revealed that the total number of neurons containing trkA immunoreactivity was related to diagnostic classification (P < 0.001), with a significant reduction in AD and MCI compared to NCI but without a significant difference between MCI and AD. Cell density was similarly related to diagnostic classification (P < 0.001). There was a significant correlation with the Boston Naming Test and with a global score measure of cognitive function. The number of trkA-immunoreactive neurons was not correlated with MMSE, age at death, education, apolipoprotein E allele status, gender, or Braak score. These data indicate that alterations in the number of nucleus basalis neurons containing trkA immunoreactivity occurs early and are not accelerated from the transition from MCI to mild AD.

Aged↗
PubMed2000

Plasma RNA viral load predicts the rate of CD4 T cell decline and death in HIV-2-infected patients in West Africa.

OBJECTIVE: To examine whether the levels of plasma RNA and DNA provirus predict the rate of CD4 cell decline and patient death. DESIGN: Retrospective analysis of HIV-2 cohort subjects. METHODS: Fifty-two subjects were recruited between January 1991 and December 1992. HIV-2 RNA levels in plasma and DNA levels in peripheral blood mononuclear cells (PBMC) were measured using in-house quantitative PCR assays. The annual rate of CD4 cell decline was calculated using the least-squares method. The survival data on 31 December 1997 were used. RESULTS: The mean percentage of CD4 cells at baseline was 30.7 (SD, 9.5). In a linear regression model, the annual rate of CD4 cell decline was 1.76 CD4% faster for every increase in one log10 RNA copies/ml [95% confidence interval (CI), 0.81-2.7; P = 0.0006; r = 0.46; n = 52] and 1.76 CD4% faster for every increase in log10 DNA copies/10(5) PBMC (95% CI 0.46-3.1; P = 0.01; r = 0.33; n = 42). In a multiple linear regression model, RNA load was related to CD4 decline independently of DNA load (P = 0.02). The overall mortality rate was 7.29/100 person-years. In a Cox regression model, the hazard rate increased by 2.12 for each log10 increase in RNA load (95% CI, 1.3-3.5; P = 0.0023) but only by 1.09 for each log10 increase in DNA load (95% CI, 0.64-1.87; P = 0.8). CONCLUSION: This longitudinal study shows for the first time that a baseline HIV-2 RNA load predicts the rate of disease progression. HIV-2-infected patients with a high viral load may need to be treated as vigorously as HIV-1 patients.

Adolescent↗
PubMed2000

Prior BCG vaccination improves survival of Gambian patients treated for pulmonary tuberculosis.

The protection provided by BCG against pulmonary tuberculosis ranges from nil to over 90%. While BCG protects against the more serious forms of tuberculosis, it is not known whether or not it protects patients with pulmonary tuberculosis from death. In a study designed to look at the effects of immunotherapy with M. vaccae as an adjunct to chemotherapy in 285 adult Gambian patients treated for proven pulmonary tuberculosis, we examined the association between the presence or absence of a BCG scar and mortality. The data showed that subjects who had a BCG scar were significantly younger than those who did not, and were less likely to have nutritional oedema. During the course of treatment, none of the 85 patients who had a BCG scar died compared to 35 of 200 patients (17.5%) who did not (P < 0.001). In these Gambian patients with pulmonary tuberculosis, prior vaccination with BCG may have provided substantial protection against death. However, there is the possibility that this finding is the result of confounding by other factors or has arisen from bias. Researchers with similar data need to investigate this question as this association, if true, could have major implications for BCG vaccination.

Adolescent↗
PubMed2000

Season of birth is not associated with delayed childhood mortality in Upper River Division, The Gambia.

There is evidence that season of birth may predict adult mortality from infectious diseases in rural Gambia. Using data collected over a five-year period from the rural, eastern region of the Gambia, we examined whether the season of birth influences mortality in childhood. 26 894 births and 3776 deaths among children under the age of five years were recorded in this region during the period 1989-1993. The estimated 1-4 year population was 95 355. In children aged 1-4 years, the mortality rate per 1000 per year was 16.1 (95% CI 14.9, 17.2) for those born in the 'harvest' season (January to June), which was not significantly different from the rate of 17.9 (95% CI 16.7, 19.0) recorded for those born in the 'hungry' season (July to December) (age-stratified Mantel-Haenszel mortality ratio 0. 91, 95% CI 0.83, 1.01; p = 0.08). Nearly all deaths of 1-4 year olds were attributed to infectious diseases, with malaria accounting for over 40%. None of the cause-specific child mortality rates differed significantly according to the season of birth. These data suggest that beyond infancy, when it is easier to separate the effect of season on cause of death from that of the season of birth, there is no marked difference in the rate of death between Gambian children born in the harvest season and those born in the hungry season.

Birth Rate↗
PubMed2000

Evaluation of clinical pallor in the identification and treatment of children with moderate and severe anaemia.

BACKGROUND: Anaemia from malaria is a common problem in developing countries. Blood transfusion in developing countries is available in few hospitals. Children who are severely anaemic and may require urgent blood transfusion usually present to peripheral first-level health facilities from where they must be referred to hospitals. Since most peripheral facilities do not determine haemoglobin levels, the decision on referral has to be made on clinical grounds. OBJECTIVES: To evaluate the sensitivity and specificity of clinical pallor of the palms, nailbeds, conjunctivae, buccal mucosa or tongue against haemoglobin values and their reproducibility among health workers. METHODS: A total of 2540 children 2 months to 5 years of age presenting to a rural health centre in Ethiopia were enrolled. Clinically detected pallor was compared with measured blood haemoglobin concentrations. RESULTS: Any anaemia (haemoglobin < 11 g/dl) was found in 61% of the children. Severe anaemia (haemoglobin < 5 g/dl) was found in 4%. The presence of any pallor clinically correlated with moderate anaemia (haemoglobin level < 8 g/dl) could be detected with a sensitivity of 95% and a specificity of 64-68% when the palm and nailbeds were used and a sensitivity of 84% and a specificity of 81% when the conjunctivae were used. Severe anaemia was detected clinically as severe pallor in 50-56% of cases (with a specificity of 95-96%). Agreement between physicians was highest for conjunctivae and nailbed pallor (87%) and lowest for palm pallor (73%). Using multivariate analysis, identification of a systolic ejection murmur or altered sensorium, the presence of splenomegaly or malarial parasitaemia were independently predictive of severe and moderately severe anaemia. CONCLUSIONS: Moderate and severe anaemia can be identified clinically in most cases for treatment and referral purposes. A systolic ejection murmur, altered sensorium, the presence of splenomegaly or malarial parasitaemia may be used as additional tools in considering urgent referral for blood transfusion.

Anemia, Iron-Deficiency↗
PubMed2000

Reduction in TrkA-immunoreactive neurons is not associated with an overexpression of galaninergic fibers within the nucleus basalis in Down's syndrome.

Down's syndrome (DS) individuals develop neuropathological features similar to Alzheimer's disease (AD), including degeneration of cholinergic basal forebrain (CBF) neurons. In AD a reduction in CBF/trkA-containing neurons has been suggested to trigger a hyperexpression of galaninergic fibers within the nucleus basalis subfield of the basal forebrain. The present study examined the interrelationship between reductions in CBF/trkA-containing neurons and the overexpression of galaninergic fibers within the nucleus basalis in DS. Within the nucleus basalis stereologic evaluation revealed a 46% reduction in the number of trkA-immunopositive neurons, whereas optical density measurements displayed a nonsignificant 18% reduction in neuronal trkA immunoreactivity in DS as compared with age-matched controls. Western blot analysis also showed a significant reduction in cortical trkA protein levels in DS. A semiquantitative examination of galaninergic fibers in the nucleus basalis revealed only a modest hypertrophy of galaninergic fibers within the nucleus basalis in DS. The present findings indicate a significant reduction in trkA within the nucleus basalis and cortex with only a moderate hypertrophy of galaninergic fibers in DS. These observations suggest that DS may not be an exact genetic model for investigation of changes in the AD basal forebrain.

Aged↗
PubMed2000

Risk factors for mortality among children hospitalized because of acute respiratory infections in Bangui, Central African Republic.

BACKGROUND: Acute respiratory infections are the most common cause of death in children in developing countries. Little information is available on risk factors for mortality among African children presenting with symptoms compatible with acute respiratory infections. OBJECTIVE: To identify risk factors for death among children hospitalized for respiratory complaints who satisfy the WHO clinical definition for pneumonia or severe pneumonia. METHODS: Children <5 years of age who presented with cough and/or difficult breathing and were hospitalized in Bangui during a 1-year period were investigated for risk factors for mortality. The study population consisted of 395 children who satisfied the WHO clinical definition for pneumonia/severe pneumonia. The associations between death and demographic, nutritional, socioeconomic, laboratory and clinical variables were examined. RESULTS: Of the 49 (12.4%) children who died, all but one had had indrawing of the chest which, in univariate analysis, was the risk factor most strongly associated with death [odds ratio, 22.99; 95% confidence interval (CI), 3.81 to 935.2]. In a multivariate model the independent risk factors for death were indrawing of the chest [adjusted odds ratio (AOR) 8.35, CI 1.04 to 66.82], hepatomegaly (AOR 6.72, CI 2.35 to 19.21), age between 2 and 11 months (AOR 6.37, CI 2.18 to 18.59), grunting (AOR 4.53, CI 1.96 to 10.45), a moderate/severe alteration of general status (AOR 3.23, CI 1.17 to 8.94) and acute malnutrition (AOR 2.74, CI 0.96 to 7.78). CONCLUSIONS: These findings could be used in flow charts for the management of children with respiratory complaints to identify children at increased risk of death who need to receive aggressive therapy.

Acute Disease↗
PubMed2000

Safety and immunogenicity of a nonavalent pneumococcal vaccine conjugated to CRM197 administered simultaneously but in a separate syringe with diphtheria, tetanus and pertussis vaccines in Gambian infants.

BACKGROUND: Unrelenting high morbidity and mortality have mandated that immunogenic vaccines be used to combat pneumococcal disease in infants. OBJECTIVES: To evaluate the safety and immunogenicity of a nonavalent pneumococcal conjugate vaccine and the antigenic interaction when administered simultaneously with diphtheria, tetanus and pertussis vaccines. METHODS: Two hundred seven infants were randomized to receive three doses of either nonavalent protein conjugate pneumococcal vaccine (PnCV) or inactivated polio vaccine (IPV) at 2, 3 and 4 months of age with routine Expanded Program of Immunization vaccines as scheduled. Vaccinees were visited on Days 1, 2 and 7 to observe local and systemic adverse reactions. Blood was drawn before the first dose and 1 month after the third dose. Antibody concentrations in sera were measured by standardized enzyme-linked immunosorbent assay. Nasopharyngeal carriage of pneumococci was tested at 5 and 9 months of age. RESULTS: No serious reactions were observed. Local induration and tenderness were observed more commonly at the site of administration of diphtheria, tetanus and pertussis vaccines than at the site of administration of IPV or PnCV. Between 79 and 91% achieved >1 microg/ml antibody against specific pneumococcal serotypes. Antibody responses to diphtheria and pertussis antigens were similar in both groups; however, antibody response to tetanus toxoid was significantly lower in infants who received PnCV (geometric mean concentration, 11.1 vs. 17.4; P < 0.001). Nasopharyngeal carriage in PnCV-vaccinated children was reduced but not significantly different from those vaccinated with IPV. CONCLUSION: Simultaneous administration of PnCV with Expanded Program of Immunization vaccines is safe and immunogenic. immune response to the composite antigens is likely to confer protection.

Antibodies, Bacterial↗
PubMed2000

Short-course eflornithine in Gambian trypanosomiasis: a multicentre randomized controlled trial.

OBJECTIVE: A randomized controlled trial was conducted to determine whether 7 days of intravenous eflornithine (100 mg/kg every 6 h) was as effective as the standard 14-day regimen in the treatment of late-stage Trypanosoma brucei gambiense trypanosomiasis. METHODS: A total of 321 patients (274 new cases, 47 relapsing cases) were randomized at four participating centres in Congo, Côte d'Ivoire, the Democratic Republic of the Congo, and Uganda to one of these treatment regimens and followed up for 2 years. RESULTS: Six patients died during treatment, one of whom was on the 7-day regimen, whereas the other five had been on the 14-day regimen (P = 0.2). The response to eflornithine differed markedly between Uganda and other countries. Among new cases in Uganda, the 2-year probability of cure was 73% on the 14-day course compared with 62% on the 7-day regimen (hazard ratio (HR) for treatment failure, 7-day versus 14-day regimen: 1.45, 95% CI: 0.7, 3.1, P = 0.3). Among new cases in Côte d'Ivoire, Congo, and the Democratic Republic of the Congo combined, the 2-year probability of cure was 97% on the 14-day course compared with 86.5% on the 7-day regimen (HR for treatment failure, 7-day vs 14-day: 6.72, 95% confidence interval (CI): 1.5, 31.0, P = 0.003). Among relapsing cases in all four countries, the 2-year probability of cure was 94% with 7 days and 100% with 14 days of treatment. Factors associated with a higher risk of treatment failure were: a positive lymph node aspirate (HR 4.1; 95% CI: 1.8-9.4), a cerebrospinal fluid (CSF) white cell count > or = 100/mm3 (HR 3.5; 95% CI: 1.1-10.9), being treated in Uganda (HR 2.9; 95% CI: 1.4-5.9), and CSF trypanosomes (HR 1.9; 95% CI: 0.9-4.1). Being stuporous on admission was associated with a lower risk of treatment failure (HR 0.18; 95% CI: 0.02-1.4) as was increasing age (HR 0.977; 95% CI: 0.95-1.0, for each additional year of age). DISCUSSION: The 7-day course of eflornithine is an effective treatment of relapsing cases of Gambian trypanosomiasis. For new cases, a 7-day course is inferior to the standard 14-day regimen and cannot be recommended.

Adolescent↗
PubMed1999

Estrogen receptor immunoreactivity within subregions of the rat forebrain: neuronal distribution and association with perikarya containing choline acetyltransferase.

Administration of the neuroactive steroid hormone estrogen has been shown to effect cholinergic basal forebrain neuronal function. Antibodies directed against the estrogen receptor alpha (ERalpha) revealed dark (type 1) and light (type 2) nuclear positive neurons within the islands of Calleja, endopiriform nucleus, lateral septum, subfields of the cholinergic basal forebrain, bed nucleus of the stria terminalis, striohypothalamic region, medial preoptic region, periventricular, ventromedial, arcuate and tuberal mammillary nuclei of the hypothalamus, reuniens and anterior medial thalamic nuclei, amygdaloid complex, piriform cortex and subfornical organ. In contrast, only a few scattered ERalpha labeled neurons were found in cortex and hippocampus. ERalpha stained cell bodies were not seen in the striatum. Counts of ERalpha labeled neurons in intact female rats revealed significantly more type 2 neurons within the basal forebrain subfields. Quantitation of ERalpha immunoreactive neurons revealed a significant decrease in the relative number of type 1 neurons within the medial septum (MS), horizontal limb of the diagonal band (HDB) and substantia innominata/nucleus basalis (SI/NB) following ovariectomy. Quantitation following choline acetyltransferease (ChAT) immunohistochemistry revealed a significant decrease in the number of ChAT positive neurons within the MS, HDB and SI/NB, but not VDB following ovariectomy. Following ovx, the percentage of double labeled cholinergic basal forebrain neurons also declined significantly within the MS, VDB, HDB and SI/NB. These observations suggest that estrogen effects a subpopulation of cholinergic basal forebrain neurons and may provide insight into the biologic actions of this steroid in Alzheimer's disease.

Animals↗
PubMed1999

Preparation for a pneumococcal vaccine trial in The Gambia: individual or community randomisation?

In preparation for a large phase-3 trial of pneumococcal polysaccharide/conjugate vaccine among infants in The Gambia, the relative merits of community and individual randomisation were considered. The impact of vaccination might be enhanced in a community randomised trial if there was a substantial 'herd' effect. This might occur if those vaccinated comprise a substantial proportion of potential transmitters of infection. However, there are few data on the sources of pneumococcal infections in The Gambia and with the high degree of mobility of people in The Gambia, it seems unlikely that any herd effect would be strong. In the absence of a herd effect, a community-randomised trial would have lower power for the mortality end-points compared to an individually randomised trial of the same size. In addition, a community-randomised trial might not provide sufficient control against potential confounders and blinding might be difficult to sustain if the vaccine has a strong effect. An individually randomised trial seems a better strategy under the conditions prevailing in The Gambia.

Bacterial Vaccines↗
PubMed1999

Dopamine transporter-immunoreactive neurons decrease with age in the human substantia nigra.

Unbiased disector stereologic cell counting was applied to sections from the human substantia nigra that were immunostained by using a monoclonal antibody against the dopamine transporter (DAT). This antibody was found to penetrate the full thickness of the stained section. Quantification of the number of DAT immunostained neurons was performed in human cases stratified into three age groups, young (ages 0-49 years), middle aged (ages 50-69 years), and aged (ages 70-85 years). The number of DAT-immunoreactive nigral neurons was normalized for each case by constructing a ratio of the number of DAT-containing neurons to total number of neuromelanin-containing cells in each subject's sample. Three types of DAT nigral neurons were seen: type 1, intensely stained; type 2, lightly stained; and type 3, DAT-immunonegative neuromelanin-containing perikarya. By 50 years of age, the number of type 1 neurons decreased significantly (P < 0.0001), whereas the number of type 2 neurons increased with age (P < 0.0001). Type 3 neurons also increased with age (P < 0.01), although less robustly than type 2 neurons. Type 1 neurons decreased by 11.2% per decade, and the total number of nigral neurons (types 1-3) decreased by 6.7% per decade. Relative to the young group, there were 75% and 88% reductions in type 1 neurons in the middle-aged and aged groups, respectively. This contrasts with the 35% and 41% reductions in total number of neuromelanin-containing neurons seen in middle-aged and aged groups, respectively. The young group had significantly more type 1 neurons and fewer type 2 neurons compared with middle-aged and aged participants. Post-hoc analyses indicated that the young group had significantly fewer type 3 neurons compared with middle-aged and aged participants. These findings demonstrate an age-related reduction in the number of substantia nigra DAT-immunoreactive neurons. Therefore, insight into the mechanisms regulating the rate of DAT synthesis may aid in our understanding of the decline of DATs with aging and its functional significance.

Adolescent↗
PubMed1999

Clinical predictors of hypoxaemia in Gambian children with acute lower respiratory tract infection: prospective cohort study.

OBJECTIVES: To determine clinical correlates and outcome of hypoxaemia in children admitted to hospital with an acute lower respiratory tract infection. DESIGN: Prospective cohort study. SETTING: Paediatric wards of the Royal Victoria Hospital and the hospital of the Medical Research Council's hospital in Banjul, the Gambia. SUBJECTS: 1072 of 42 848 children, aged 2 to 33 months, who were enrolled in a randomised trial of a Haemophilus influenzae type b vaccine in the western region of the Gambia, and who were admitted with an acute lower respiratory tract infection to two of three hospitals. MAIN OUTCOME MEASURES: Prevalence of hypoxaemia, defined as an arterial oxygen saturation <90% recorded by pulse oximetry, and the relation between hypoxaemia and aetiological agents. RESULTS: 1072 children aged 2-33 months were enrolled. Sixty three (5.9%) had an arterial oxygen saturation <90%. A logistic regression model showed that cyanosis, a rapid respiratory rate, grunting, head nodding, an absence of a history of fever, and no spontaneous movement during examination were the best independent predictors of hypoxaemia. The presence of an inability to cry, head nodding, or a respiratory rate >/= 90 breaths/min formed the best predictors of hypoxaemia (sensitivity 70%, specificity 79%). Hypoxaemic children were five times more likely to die than non-hypoxaemic children. The presence of malaria parasitaemia had no effect on the prevalence of hypoxaemia or on its association with respiratory rate. CONCLUSION: In children with an acute lower respiratory tract infection, simple physical signs that require minimal expertise to recognise can be used to determine oxygen therapy and to aid in screening for referral. The association between hypoxaemia and death highlights the need for early recognition of the condition and the potential benefit of treatment.

Acute Disease↗
PubMed1999

Proviral load and immune function in blood and lymph node during HIV-1 and HIV-2 infection.

Proviral load as well as lymphocyte phenotype and function were compared in peripheral blood and lymph node compartments of 17 HIV-1, 12 HIV-2 and three dually infected patients with lymphadenopathy. The mean percentage (95% confidence interval (CI)) of CD4+ cells was higher in lymph node mononuclear cells (LNMC) than in peripheral blood mononuclear cells (PBMC) in both infections, being 26.7% (21. 1%, 32.3%) and 15.3% (10.4%, 20.2%), respectively, for HIV-1-infected patients (P = 0.0001) and 32.3% (22.7%, 41.9%) and 22. 1% (13.6%, 30.6%), respectively, for HIV-2-infected patients (P = 0. 02). In both types of infection, proviral load adjusted for number of CD4+ cells was higher in LNMC than in PBMC: the geometric mean (95% CI) was 8937 (4991; 16 003) and 4384 (2260; 8503), respectively, for HIV-1 patients (P = 0.02) and 1624 (382; 6898) and 551 (147; 2058) DNA copies, respectively, for HIV-2 patients (P = 0.05). Proviral load in both compartments was closely correlated (HIV-1, r = 0.60, P = 0.01; and HIV-2, r = 0.83, P = 0.0003). In both infections, proliferation and interferon-gamma (IFN-gamma) production in response to purified protein derivative (PPD) was lower in LNMC than in PBMC, both of which, in turn, were lower than in healthy controls. These results indicate that in HIV-2 as in HIV-1 infection, infected cells have a tropism for the lymph nodes resulting in higher viral load in this compartment and lower lymphocyte responses to the recall antigen PPD which may increase susceptibility to tuberculosis.

Adult↗
PubMed1999

Retinal manifestations of HIV-1 and HIV-2 infections among hospital patients in The Gambia, west Africa.

BACKGROUND: In developed countries, 50-75% of AIDS patients develop retinal complications and about 20-40% acquire cytomegalavirus (CMV) retinitis. We conducted a cross-sectional survey to determine prevalence of these in The Gambia where both HIV-1 and HIV-2 infection are present and the prevalence of HIV-1 is rising. METHOD: All patients attending hospital whose percentage CD4+ cells (CD4%) was below 14, the level associated typically with an AIDS diagnosis, and one half of those whose CD4% was 14 or above were asked to join the study. Fifty-six HIV-1, 52 HIV-2 and 12 dually infected patients were recruited. Photographs of the fundi were taken and interpreted independently. The findings were related to the patients' percentage CD4+ cells. RESULTS: The CD4% was < 14 in 40 patients and < 7 in 17 patients. Thirty-six patients were male. No cases of CMV retinitis were found. Four patients whose CD4% were 4, 5, 11 and 23 had cotton wool spots ranging in number from 1 to 14 for any one patient. The prevalence of cotton wool spots was 8% (95% CI, 0-16%) among patients with CD4% below 14 and 12% (95% CI, 0-27) among patients with CD4% below 7. One of the 4 patients had associated microaneurysm and blot haemorrhages typical of more advanced HIV microvasculopathy. CONCLUSION: CMV retinitis is less common in The Gambia than in developed countries. Non-infectious retinopathy may also be less common.

AIDS-Related Opportunistic Infections↗
PubMed1998

m2 muscarinic acetylcholine receptor-immunoreactive neurons are not reduced within the nucleus basalis in Alzheimer's disease: relationship with cholinergic and galaninergic perikarya.

The distribution of profiles containing the m2-muscarinic acetylcholine receptor within the aged human basal forebrain and its relationship to cholinergic and noncholinerigc neurons and alterations in Alzheimer's disease (AD) was investigated by using an m2-specific monoclonal antibody (Levey et al. [1995] J. Comp. Neurol. 351:339-356). Immunocytochemistry revealed that the m2 receptor protein is expressed primarily in noncholinergic multipolar neurons (mean+/-S.E.M.; 355.7+/-15.4 microm2) located primarily outside the cholinergic nucleus basalis subfields. Dual-stained sections from the septal/diagonal band complex revealed that m2 was detected in only 14% of choline acetyltransferase-labeled neurons, whereas only 13% of m2-stained neurons colocalized choline acetyltransferase. Within the nucleus basalis, choline acetyltransferase was found in 35% of the m2-labeled neurons, whereas only 6% of choline acetyltransferase-stained perikarya were dual labeled for m2. Although we did not visualize colocalization of m2+/choline acetyltransferase-immunonegative neurons and the inhibitory neuropeptide galanin, galaninergic fibers coursed in close apposition to m2+ cells. Cell counts demonstrated that 90% of choline acetyltransferase-labeled striatal neurons expressed the m2 receptor. Despite the extensive reduction in cholinergic basal forebrain neurons, cell counts of the relative number ofm2-immunoreactive neurons within the nucleus basalis complex from aged controls and AD patients revealed that the m2 neurons are spared. Finally, our findings suggest that most m2 receptors in the cholinergic basal forebrain are located on noncholinergic structures; therefore, they are not the major source of m2 receptors in the cortex. Thus, the reduced levels of the m2 receptor seen in AD cortex probably reflect changes in other neuronal populations.

Aged↗