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Biomedical subjects

H Whitwell

Publications and source records attributed to H Whitwell.

9 recordsLinked to original sources
PubMed1996

Concurrent evolution of regions of the envelope and polymerase genes of human immunodeficiency virus type 1 during zidovudine (AZT) therapy.

Nucleotide sequences of regions of the envelope (env) and polymerase (pol) genes of human immunodeficiency virus type 1 (HIV-1) proviral DNA were obtained from sequential blood and autopsy samples from an AIDS patient who had been treated with zidovudine for 9 months. Phylogenetic analyses showed that a reduction in genetic heterogeneity of the env regions of viruses present in the proviral blood population occurred during therapy, and this coincided with an increased pol gene heterogeneity. Differences were observed in different organs obtained post mortem for both the env and pol coding regions. The cardiac blood proviral population consisted mainly of variants which possessed sequences containing mutations at position 215 of the pol gene, associated with drug resistance. By contrast, the brain population consisted entirely of zidovudine sensitive genotypes, and this organ also harboured variants with genetically distinct env sequences. The lymph tissues obtained after death held more diverse proviral env and pol populations, containing both zidovudine sensitive and resistant genotypes.

Amino Acid Sequence↗
PubMed1994

Genomic variation of human immunodeficiency virus type 1 (HIV-1): molecular analyses of HIV-1 in sequential blood samples and various organs obtained at autopsy.

Length polymorphisms and partial nucleotide sequences were determined for the hypervariable regions, V1 to V5, of the human immunodeficiency virus type 1 (HIV-1) env gene obtained from proviral DNA of sequential peripheral blood samples, from viral RNA in plasma, and from proviral DNA obtained from different organs of individuals at autopsy. The lengths of several env regions of HIV-1 proviral DNA differed markedly when obtained from different organs of an individual. Nucleotide sequences of the hypervariable V3 region of HIV-1 obtained from different organs of one patient demonstrated distinct viral variants. Most proviral DNA sequences found in organs were also present in viral RNA obtained from plasma. The majority of HIV-1 V3 variants present in the lymph tissue could be found in the plasma viral population obtained at autopsy and in the sequential blood samples obtained before death, but were absent from the cardiac blood provirus population obtained at autopsy. However, sequence variants found in the brain proviral DNA were not detected in either plasma or the sequential blood samples. Sequence differences were observed at the apex of the V3 loop between HIV-1 variants present in sequential blood samples and in blood lymphocytes and nervous tissue, lymph tissue and plasma obtained post-mortem. The potential effect of lymph tissue on the long-term persistence of different viral variants is discussed. Virus obtained from the two sequential blood samples produced syncytia in primary cultures and was easily transmitted to the continuous JM cell line. Consensus (majority) V3 loop sequences determined for the adapted viruses demonstrated that some, but not all, sequences were represented within the in vivo viral population.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Descriptive epidemiology of primary central nervous system tumours in children: a population-based study.

This study was undertaken to investigate the incidence, outcome and referral patterns of central nervous system tumours in a defined childhood population over a recent 5-year period. The study incorporated pathological review of all available diagnostic material and follow-up assessed survival at a minimum of 5 years from diagnosis. One hundred and forty-seven cases were reviewed, representing an annual incidence of 26.5 per million children aged less than 15 years. The distribution of individual diagnoses by age, sex and anatomical site was similar to comparable data collected previously in the United Kingdom and North America, but the inclusion of 28 cases (19%) without biopsy suggested that the wider use of computed tomography might account for a small increase in incidence over previous estimates. Analysis of referral to the Regional Paediatric Oncology Unit showed that the patients referred were younger than those not referred and were over-represented amongst the diagnoses of medulloblastoma, ependymoma and brain stem glioma, which carry the worst prognosis. Survival for all diagnoses together was 51% at 5 years, ranging from 13% for unbiopsied brain stem gliomas to 100% for juvenile astrocytomas. Referral to the Regional Unit appeared to have some survival advantage for children with medulloblastoma, although this was not statistically significant. Accurately reviewed data such as these are essential in order to assess current workload and treatment success, in addition to enabling investigation of future diagnostic and treatment strategies.

Adolescent↗
PubMed1991

Ubiquitin-immunoreactive intraneuronal inclusions in amyotrophic lateral sclerosis. Morphology, distribution, and specificity.

Antibodies to ubiquitin have been used to search for evidence of abnormal protein degradation in amyotrophic lateral sclerosis--motor neuron disease (ALS). Anterior horn cell ubiquitin-immunoreactive (IR) inclusions were present in all of 31 ALS cases but in none of 23 neurologically normal and in only 1 of 22 neurologically abnormal controls. These inclusions, which were present in familial and sporadic ALS cases, and in cases with dementia, took the form of dense rounded or irregular ubiquitin-IR cytoplasmic inclusions (dense bodies), or loosely arranged bundles ('skeins') of filamentous-appearing material. The presence of ubiquitin-IR inclusions corresponded to the pattern of selective neuronal vulnerability in ALS, although inclusions in pyramidal neurons of the motor cortex were infrequent and were noted in only a minority of cases. Ubiquitin-IR inclusions were more prevalent than Bunina bodies. The latter were present in 67% of ALS cases but were seldom labelled by antibodies to ubiquitin. Intraneuronal inclusions resembling Lewy bodies were present in 23% of ALS cases and were often identified by antibodies to ubiquitin. We conclude that the presence of ubiquitin-IR inclusions in lower motor neurons represents a characteristic pathological feature of ALS in its various clinical forms. Ubiquitin-IR inclusions in ALS differ from ubiquitinated inclusions in other neuronal degenerations in that they are not readily identified by antibodies to cytoskeletal proteins. They may represent accumulations of altered or abnormal neuronal proteins resistant to degradation via the ubiquitin proteolytic pathway.

Adult↗
PubMed1988

Giant cell tumor of the skull: case report.

The case of a 16-year-old girl with giant cell tumor involving the occipital bone is described. The radiological and pathological findings are detailed, followed by a discussion of the literature.

Adolescent↗
PubMed1984

Steroid receptors in human meningioma.

It is well recognised that there is an increased frequency of meningioma in women compared with men and that rapid progression of the disease may occur during pregnancy. Recent studies have demonstrated steroid receptors in human meningioma. In this study we have looked for the presence of nuclear and cytoplasmic estrogen receptor (ER) and cytoplasmic progesterone receptor (PR) in 22 cases of meningioma. Radioreceptor assays using a six-point dextran-coated charcoal procedure failed to demonstrate specific ER, but 17 of 22 meningiomas did have specific PR (range 11-314 fmol/mg cytosol protein). Flat-bed isoelectric focusing in agarose gel was used to confirm the results in a few of these cases. We were not able to correlate the presence of receptor with age or sex of patient, or the site of tumour with receptor content. Of the five PR-negative tumors, one was a poor specimen when the histology was examined and two belonged to the angioblastic group (haemangiopericytic variety), a particularly aggressive tumour with a tendency to be more necrotic. The presence of PR in many of these tumours suggests a possible role for hormone therapy where total resection is not possible.

Adolescent↗
PubMed1984

Coeliac disease presenting with intestinal pseudo-obstruction.

A 22 year old woman presenting with recurrent intestinal pseudo-obstruction is reported. Jejunal biopsy showed subtotal villous atrophy which improved markedly during a period of total parenteral nutrition and with steroid treatment. It did not relapse on a gluten free diet. The reasons why this patient represents a case of coeliac disease with secondary pseudo-obstruction, rather than primary intestinal pseudo-obstruction with secondary bacterial overgrowth, is discussed.

Adult↗