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Biomedical subjects

J E McLaughlin

Publications and source records attributed to J E McLaughlin.

At least 37 records · Page 2Linked to original sources
PubMed1995

Distinct HIV-1 long terminal repeat quasispecies present in nervous tissues compared to that in lung, blood and lymphoid tissues of an AIDS patient.

OBJECTIVE: To investigate the phylogenetic relationship of HIV-1 proviral long terminal repeat (LTR) variants present in postmortem samples of lymph node, spleen, lung, dorsal root ganglion and spinal cord as well as in the peripheral blood of an HIV-1-infected patient dying with AIDS. DESIGN AND METHODS: Postmortem tissues were studied by a combination of histology, cell culture and molecular analyses. The patient had a stable CD4 count of 10 x 10(6)/I during the 12 months preceding death. A 540 base-pair fragment of the LTR including U3/R/U5 was amplified using polymerase chain reaction on proviral DNA from the five postmortem tissues and peripheral blood mononuclear cells obtained 2 months prior to death. The population of viral variants was determined by sequencing at least five plasmid clones of the amplicons. The relationship between the variants present in different body sites was investigated using molecular phylogeny methods. RESULTS: HIV-1 was present in all organs analysed and correlated with the presence of abnormal histology. Genetic variation leading to divergence from the consensus sequence was more frequently present in characterized transcription factor binding sites within the LTR (P < 0.0001) although the HIV-1 LTR quasispecies in the different body sites showed similar, relatively low levels of divergence (intra-organ median heterogeneity ranging from 0.0094 to 0.017). Phylogenetic analysis showed that the spinal cord and dorsal root ganglion harboured an LTR population genetically distinct from that present in other organs and more closely related to a previously characterized neurotropic strain of HIV (strain JRcsf). CONCLUSION: The independent clustering of HIV-1 LTR variants present in spinal cord and dorsal root ganglion shows that HIV-1 LTR evolution can occur in a compartmentalized fashion. The data show that the LTR is an important region to analyse in sequence variation studies of HIV since it may play a role in nervous tissue adaptation of HIV-1 and neuropathogenicity. Outgrowth of HIV-1 LTR variants that are most fit for the utilization of tissue-specific transcription factors can occur in the nervous tissue.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Presence of CD3+CD8+Bcl-2(low) lymphocytes undergoing apoptosis and activated macrophages in lymph nodes of HIV-1+ patients.

Infection with human immunodeficiency virus 1 causes profound changes in the lymph nodes of infected patients. In particular, large numbers of CD8+CD45RO+ T cells infiltrate both the paracortex and the germinal centers. These cells contained the cytotoxic granule-associated protein TIA-1 but showed no detectable levels of perforin and shared the same characteristics of the expanded, activated, short-lived CD8+ population found during acute viral infections. These cells expressed low levels of Bcl-2 and are likely to be short-lived in vivo as evidenced by the direct observation of CD8+ apoptotic cells in the paracortical areas of the infected nodes. Changes in the paracortical nonlymphoid populations were also seen. There were reactive changes in the blood vessels, and the macrophage population was expanded and activated. Furthermore, apoptotic bodies were seen in the cytoplasm of the activated CD68+RFD-7+RFD-1+ macrophages pointing to the phagocytic capacity of these cells and their role in the clearance of the apoptotic cells from the tissues. These observations suggest that the persistance of CD8+ population in human immunodeficiency virus 1 infection is not a result of the presence of an abnormal CD8+ population but rather a result of an inappropriate over-stimulation of the CD8+ cells.

Adult↗
PubMed1994

Immunohistochemical study of vascular injury in acute multiple sclerosis.

AIMS: To examine the vascular changes occurring in three archival cases of acute multiple sclerosis, and to provide immunohistochemical evidence of early endothelial cell activation and vascular occlusion in this condition. METHODS: Central nervous system tissues from three cases of acute active multiple sclerosis and six non-inflammatory controls were stained using the following methods: haematoxylin and eosin, Luxol fast blue, cresyl violet, Bielschowsky's silver, and reticulin. Tissues were also immunostained with specific antibodies against collagen type IV, factor XIIIa, class II antigens, glial fibrillary acidic protein, and fibrinogen. RESULTS: Early vascular endothelial cell activation which may progress to vasculitis and vascular occlusion including class II antigen expression and fibrin deposition were identified. The vascular changes were seen prior to cerebral parenchymal reaction and demyelination, and were not seen in control cerebral tissues. CONCLUSION: It is proposed that vascular endothelial cell activation may be an early and pivotal event in the evolution of multiple sclerosis, and that demyelination may have an ischaemic basis in this condition. The vascular endothelium may contain an early element in the evolution of multiple sclerosis.

Acute Disease↗
PubMed1993

Methyl methacrylate: inhalation developmental toxicity study in rats.

Methyl methacrylate (99.9% pure) was administered by vapor inhalation exposure to five groups (27 rats/group) of presumed pregnant rats (Crl:CD) at concentrations of 0 (control), 99, 304, 1,178, and 2,028 ppm for 6 hr/day on days 6-15 of gestation (G). Maternal body weight, feed consumption, and clinical signs were recorded throughout gestation. Dams were euthanized on day 20 G. Each uterus was weighed and corpora lutea, implantation sites and resorptions were counted. The number of fetuses per litter were counted and their location within the uterus recorded. All fetuses were weighed, sexed and examined for external and skeletal alterations. One half of the fetuses from each litter were examined for visceral alterations. No treatment-related deaths were noted at any concentration tested. Treatment-related effects on maternal body weight and feed consumption were noted at all exposure levels. The decreases in maternal body weight at 99 and 304 ppm were minimal and transient since they returned to control values by the next weighing period. When exposure was discontinued, body weight gain and feed consumption in all exposure groups returned to control values. There were no treatment-related changes in the number of litters produced or in the mean number per litter of corpora lutea, implantations, resorptions, live or dead fetuses, or sex ratio. Fetal body weights were similar between the control and treated groups. There were no treatment-related increases in the type or incidence of external, visceral, or skeletal malformations, developmental variations, or variations indicative of retarded development. Exposure to methyl methacrylate concentrations up to 2,028 ppm resulted in no embryo or fetal toxicity or malformations even at exposure levels that resulted in maternal toxicity.

Administration, Inhalation↗
PubMed1993

Pathological findings correlated with MRI in HIV infection.

MRI forms an important part of the assessment of patients with HIV-related disease presenting with cerebral symptoms. Eleven formalin-fixed brains were studied at 0.5 T using T2- and T1-weighted sequences. In two cases of progressive multifocal leucoencephalopathy and one case each of toxoplasmosis and lymphoma, the extent of white matter abnormality seen on MRI corresponded broadly with that on pathological examination. In general, however, histological changes were more frequent than lesions on MRI. Cases in which abnormalities were not seen with standard MRI included those with multiple tuberculous granulomata, multinucleate giant cells, microglial nodules, perivascular cuffing and cytomegalovirus inclusions. A common finding on MRI was punctate or patchy high signal in the basal ganglia on T2-weighted scans, seen in six cases. Corresponding histological changes included calcification of vessels with widened perivascular spaces, and mineralised neurones.

AIDS Dementia Complex↗
PubMed1993

The value of per-operative smear examination during stereotactic biopsy.

Sixty-two consecutive CT-directed stereotactic biopsies were studied retrospectively to determine the value of the per-operative smear examination. Overall, in 69% of cases the immediate smear result agreed with the definitive histology. However, a smear diagnosis of malignant glioma was more reliable than that of metastasis (with 100% and 55% agreement with the final result respectively). In those cases where the final histological diagnosis was that of malignant glioma, immediate smear preparations taken from the hypodense centre were found to be more reliable than those taken from the enhancing edge.

Biopsy, Needle↗
PubMed1993

A clinico-pathological audit of opportunistic viral infections in HIV-infected patients.

OBJECTIVE: To determine the prevalence of opportunistic viral infections in multiple tissues at postmortems of HIV-infected patients, and to relate these findings to their antemortem clinical course. DESIGN: A study of viral infections in 16 tissues of HIV-positive postmortem cases, by a combination of histology and cell culture (virus isolation). Clinical details were abstracted retrospectively from patient records. PATIENTS: Forty-seven consecutive autopsies, performed between 1985 and 1992. SETTING: Autopsies were conducted by a single pathologist in a single London teaching hospital. RESULTS: Opportunistic viral infections were detected in 72% of all cases, comprising cytomegalovirus (CMV, 66%), herpes simplex virus (11%), JC virus (6%) and adenovirus (2%). The most commonly infected tissues were lung, adrenal, gastrointestinal tract and central nervous system, although all tissue sites sampled could potentially support viral replication. Of 464 tissues tested by both histology and cell culture, histology alone detected CMV in 45 tissues and cell culture alone detected CMV in 31 tissues. We determined that CMV detection in postmortem gastrointestinal tissues and central nervous tissue was significantly associated with antemortem undiagnosed diarrhoea and encephalitis, respectively. CONCLUSION: There is a high prevalence of opportunistic viral infections in late-stage HIV disease, which is best detected postmortem by the use of both histology and cell culture. Many of these infections correlate with undiagnosed symptoms antemortem. The ability of sensitive methods for virus detection to alert the clinician to such cases antemortem should be critically evaluated, as should attempts to influence the natural history of these infections by antiviral drugs. Continuing clinico-pathological audit is important for AIDS patients in order to monitor the impact of known opportunistic viral infections and to identify others which may emerge as immunosuppression becomes more profound.

AIDS-Related Opportunistic Infections↗
PubMed1993

Bacteriological evaluation of a down-draught necropsy table ventilation system.

AIMS: To evaluate the microbiological efficacy of a down-draught necropsy table ventilation system (which surrounds the cadaver with a "curtain" of air under continuous extraction) during post mortem procedures. METHODS: Air sampling was carried out both in the presence and absence of staff and cadaver and during a full post mortem procedure, with functioning and non-functioning table air extraction. The penetration of the air "curtain" was also examined during the use of an oscillating bone saw by means of a tracer organism, Bacillus subtilis var niger, painted on to the skull. RESULTS: There was little difference between bacterial counts obtained in the presence of staff only, staff plus cadaver, or during a post mortem examination. With all counts obtained, however, there was a two to three-fold reduction when the ventilation was in operation compared with when the extract duct was occluded. Using the tracer organism, a two to three log reduction in counts was shown when the "curtain" was in operation during the use of the oscillating bone saw. CONCLUSIONS: These results suggest that the system provides potential protection for post mortem room staff against airborne infections.

Air Conditioning↗
PubMed1992

Primary cerebral lymphoma: a study of 47 cases probed for Epstein-Barr virus genome.

AIMS: To determine the prevalence of Epstein-Barr virus genome in primary cerebral lymphomas occurring in the absence of immune suppression. METHODS: Forty eight consecutive patients with lymphomas restricted to the central nervous system were identified, all of whom had had neurosurgical biopsies performed at the National Hospitals for Neurology and Neurosurgery, London. Only five patients had some form of underlying immune deficiency; 43 were apparently normal. The tumours were studied with immunohistochemical markers and by in situ hybridisation, using a biotinylated probe to the internal repeat region of Epstein-Barr virus. RESULTS: All the lymphomas were B cell in origin. Tumours from the five immunosuppressed patients all showed hybridisation, as did two of the "spontaneous" tumours. CONCLUSIONS: This is the largest series of cerebral lymphomas so far probed for Epstein-Barr virus genome: as more are examined, it is suggested that a small proportion of the tumours from immunocompetent patients will also contain the virus.

B-Lymphocytes↗
PubMed1990

Pancreatic pseudocyst causing portal vein thrombosis and pancreatico-pleural fistula.

Portal vein thrombosis and pancreatico-pleural fistula are unusual complications of chronic pancreatitis. We describe a patient with chronic alcoholic pancreatitis in whom erosion of the splenic vein led to portal vein thrombosis and to the development of a pancreatico-pleural fistula. We suggest that fistula formation may occur over a considerable time period as the portal vein thrombosis was diagnosed three years before the amylase-rich pleural effusions.

Adult↗
PubMed1989

Neuropathology of the brain in HIV infection.

The brains of 26 patients infected with the human immunodeficiency virus (HIV) were examined post mortem. All patients were men, aged 20-67 years (mean 38.8). 13 (50%) were homosexual, 3 (12%) were bisexual, 8 (31%) were haemophiliac, 1 was both an intravenous drug addict and homosexual, and 1 denied belonging to any risk group. Only 3 (12%) brains were normal, whereas 23 (88%) showed abnormalities that varied in severity and complexity. 11 were affected by more than one disease. In addition to neoplasms, opportunistic infections, and vascular lesions, 6 cases of HIV encephalitis were found, characterised by multinucleate giant cells which indicate the presence of HIV. Microglial-macrophage nodules (nodular encephalitis) occurred in 5 cases. Cerebral pathology differed between risk groups: all 6 patients with HIV encephalitis were homosexuals, whereas vascular lesions were more common in haemophiliacs. These observations have fundamental implications for clinical practice and indicate the importance of neuropathological examination in AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1985

An immunohistological approach to persistent lymphadenopathy and its relevance to AIDS.

Recent evidence has shown that not only AIDS but also the majority of 'unexplained' persistent, generalized lymphadenopathy (PGL) are related to HTLV-III/LAV infections. The early detection how these changes may proceed to AIDS then become a prime interest. Eleven patients with PGL (10 homosexual males and one heterosexual haemophiliac) have been studied by immunohistology using monoclonal antibodies to dendritic reticulum cells of the germinal centre, T and B lymphocyte subsets, plasma cells and factor VIII, as an endothelial marker. In six cases only follicular and paracortical hyperplasia was detected, while in five other cases destruction of the dendritic reticulum cell network was seen with this sensitive method. This early destruction may explain the release of activated B cells into the circulation and prove to be an ominous prognostic sign, as it appears to correlate with 'prodromal' symptoms. In four out of 11 cases the depletion of T4+ cells in the paracortex was not as severe as in the blood, indicating that T4+ cells may preferentially settle in tissues at the time of T4 lymphopenia. In addition, germinal centres contained an additional patchy infiltration of T8+ cells. A patient with Kaposi's sarcoma did not show germinal centre destruction but did reveal extensive plasma cell infiltrates. Immunohistology may contribute to the definition of prognosis and analysis of disease progression in patients with PGL.

Acquired Immunodeficiency Syndrome↗
PubMed1982

Inhibition of leucocyte motility and prevention of immune-complex experimental colitis by hydroxychloroquine.

The inhibitory effects of hydroxychloroquine on leucocyte motility have been compared with those of prednisolone. It has been shown to have similar potency to prednisolone as an inhibitor of human neutrophil and monocyte motility. Hydroxychloroquine has then been compared with placebo in the prevention of an immune-complex experimental colitis in rabbits. Rectal biopsies were taken from rabbits 24 hours after initiation of colitis, coded, and graded histologically. The summated gradings for acute inflammation and goblet cell depletion had worsened more in the control rabbits (mean grade +6.7) than in the treated rabbits (mean grade +1.8) P less than 0.05. There was no difference in the mononuclear cell infiltrate between the two groups. Hydroxychloroquine, which is a potent inhibitor of leucocyte motility, effectively prevents the acute inflammatory infiltrate in this experimental colitis model and therefore merits trial in human ulcerative colitis.

Animals↗
PubMed1982

Father absence and cognitive performance in a large sample of six- to eleven-year-old children.

The effects of father absence on educational achievement and intellectual development of 6-11-year-old children were investigated by employing a nationally representative sample of 5,493 father-present and 616 father-absent children from the Health Examination Survey of the National Center for Health Statistics. Scores on the WISC and the WRAT were significantly depressed for father-absent white children. Father-absent black children evidenced a decreased test performance only on measures of achievement. All decrements were small and accounted for approximately 1% of the variance. Following statistical control for SES, we associated no decrements with the father's absence/presence, and in some instances, small but significant increments were found to be associated with children from fatherless families. The role of SES in father absence is discussed, and the request for a paradigmatic shift in research in the area of father absence is reiterated.

Achievement↗