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Biomedical subjects

T Hughes

Publications and source records attributed to T Hughes.

At least 91 records · Page 5Linked to original sources
PubMed1990

The role of alternative splicing patterns of BCR/ABL transcripts in the generation of the blast crisis of chronic myeloid leukaemia.

Three major types of mRNA can be expressed as a result of the Philadelphia translocation, dependent on the position of the break within the BCR gene on chromosome 22. In addition, alternative splicing of the mRNA transcribed from the BCR/ABL fusion gene has been reported and it has been suggested that this may play a role in the generation of the acute phase of Philadelphia positive chronic myeloid leukaemia (CML). We have examined the fusion RNA present in 24 cases of chronic phase CML and 21 cases of patients with CML in blast crisis using the polymerase chain reaction. In no case was it possible to detect the presence of the e1a2 junction which encodes the p190 hybrid protein product. We conclude that the acquisition of the p190 does not play a significant role in the generation of the blast crisis of CML. Neither could we detect a significant difference in the number of cases which simultaneously express both b2a2 and b3a2 junction products in samples isolated from chronic phase and blast crisis. In the series analysed by ethidium bromide stained gels, there was, however, an increase in the percentage of cases expressing the b3a2 junction in the mononuclear cells of blast crisis patients as compared to the white blood cells of patients in chronic phase.

Base Sequence↗
PubMed1990

Bone marrow transplantation for chronic myeloid leukemia: the use of histocompatible unrelated volunteer donors.

We treated 17 patients with chronic myeloid leukemia (CML) by bone marrow transplantation using marrow from human leukocyte antigen (HLA)-matched unrelated donors. Patients were conditioned with a combination of in vivo monoclonal antibodies, chemotherapy with daunorubicin (n = 7) or busulfan (n = 10) and cyclophosphamide, and both total body and total lymphoid irradiation. Donor marrow was depleted of T cells by incubation with monoclonal antibodies of the Campath series. Fourteen (88%) of 16 evaluable patients had sustained engraftment. Four (27%) of the 15 evaluable patients developed acute graft-versus-host disease (GVHD) of grade II or greater, and 4 of 12 evaluable patients developed chronic GVHD. Three patients developed hematological and two developed cytogenetic evidence of relapse. Eight patients (47%) survive at a median follow-up of 32 months (range 10-51 months), giving an actuarial survival of 44%. Five patients remain alive without evidence of hematological or cytogenetic relapse, giving an actuarial disease-free survival of 27%. Pneumonitis caused or contributed to death in six of the nine patients who died. We conclude that T-cell depletion can prevent the severest forms of GVHD but also increases the risk of relapse after transplant with unrelated donors, as it does with HLA-identical siblings. Nevertheless the use of matched unrelated donors should be considered for CML patients who lack HLA-identical siblings.

Adolescent↗
PubMed1989

Aluminium and the human brain.

Aluminium can cause an encephalopathy with a characteristic clinical picture and distinctive histopathology. Evidence associating aluminium with Alzheimer's disease and other dementias is both meagre and inconclusive.

Aluminum↗
PubMed1989

Polymerase chain reaction for detection of residual leukaemia.

The occasional finding of cells positive for the Philadelphia (Ph) chromosome months or years after bone-marrow transplantation for chronic myeloid leukaemia raises the possibility that the Ph-positive clone may never be eradicated. The polymerase chain reaction with probes able to detect the transcript of the bcr/abl hybrid gene at very low levels was used to study marrow cells from seven patients in continuing haematological and cytogenetic remission 5-7 years after allogeneic bone-marrow transplantation for chronic myeloid leukaemia. No evidence of the leukaemic mRNA was found. Thus, it seems that all leukaemic cells were eradicated in these patients and that they are truly cured.

Adolescent↗
PubMed1989

Prediction of graft versus host disease by frequency analysis of cytotoxic T cells after unrelated donor bone marrow transplantation.

HLA "matched" unrelated donor bone marrow transplants are associated with an increased incidence and severity of graft-versus-host disease in comparison with HLA-identical sibling transplants. This is presumably due to HLA and non-HLA histocompatibility differences between donor and recipient. Using a limiting dilution assay, we have previously demonstrated a relationship between cytotoxic T lymphocyte precursor frequency and HLA disparity. In this study we have compared CTL-p frequencies with clinical GVHD, and demonstrate for the first time a significant correlation (P less than 0.005) between high CTL precursor frequency prior to BMT and severity of acute GVHD after HLA A, B, DR "matched" unrelated donor transplants using T cell depleted marrow. This assay system may be of value in the final selection of HLA "matched" unrelated donors for BMT.

Anemia, Aplastic↗
PubMed1988

A prospective study of acute cerebrovascular disease in the community: the Oxfordshire Community Stroke Project 1981-86. 1. Methodology, demography and incident cases of first-ever stroke.

A prospective study of acute cerebrovascular disease in a community of about 105,000 people is reported. The study protocol combined rapid clinical assessment of patients with accurate diagnosis of the pathological type of stroke by CT or necropsy, whether or not they were admitted to hospital. The study population was defined as those people who were registered with one of 50 collaborating general practitioners (GPs). Referrals to the study were primarily from the GPs though, to ensure complete case ascertainment, hospital casualty and admission registers, death certificates and special data from the Oxford Record Linkage Study were also scrutinized. Six hundred and seventy five cases of clinically definite first-ever in a lifetime stroke were registered in four years yielding a crude annual incidence of 1.60/1,000 or 2.00/1,000 when adjusted to the 1981 population of England and Wales. The age and sex specific incidence rates for first stroke showed a steep rise with age for both sexes. The odds of a male sustaining a first stroke were 26% greater than those of a female. Ninety one per cent of patients were examined in a median time of four days after the event by a study neurologist and 88% had cerebral CT or necropsy.

Adolescent↗
PubMed1987

Association between O blood group and occurrence and severity of diarrhoea due to Escherichia coli.

During studies of diarrhoea due to Escherichia coli in 316 adult volunteers, ABO and Rh blood group determinations were done to look for differences in the occurrence or severity of illness in association with certain blood groups. In studies using heat-labile enterotoxin-producing E. coli, volunteers with O blood group had a significantly higher attack rate for diarrhoea than persons with other blood groups. In contrast, in studies with enteropathogenic or heat-stable enterotoxin-producing E. coli, no association was found between occurrence of diarrhoea and ABO group. These studies, and previous studies finding a similarly increased susceptibility to cholera in persons with O blood group, suggest that the mechanism of increased risk involves an interaction between blood group substances and the similar enterotoxin produced by E. coli and Vibrio cholerae.

ABO Blood-Group System↗
PubMed1985

Hypothalamic monoaminergic activity and pituitary function in male rats with estrogen-induced pituitary hyperplasia.

The mechanism by which estrogen enhances prolactin (PRL) secretion and induces hyperplasia of lactotrophs is not defined clearly. The objective of this study was to examine hypothalamic monoaminergic PRL regulatory systems and pituitary hormone secretion in the early and later stages of estrogen-induced hyperprolactinemia and pituitary hyperplasia. Dopamine (DA) and serotonin (5-HT) turnover were determined in microdissected brain regions 3 and 30 days after a single subcutaneous dose of estradiol (2 mg) to male ACI rats. Plasma samples were collected in animals with indwelling intra-atrial cannulae. 3 days after estrogen there was a significant increase in plasma PRL, pituitary PRL and growth hormone (GH), and DA turnover in the median eminence and arcuate nucleus. Plasma concentrations and pituitary content of PRL increased at 30 days. The responsiveness of PRL to thyrotropin-releasing hormone (TRH) was enhanced at both times. Concentrations of DA decreased considerably in the median eminence and arcuate nucleus by 30 days, and turnover decreased in the median eminence. 5-HT turnover was not affected in the early stages of hyperprolactinemia. Plasma GH increased and TSH was unchanged, even though pituitary content of both hormones decreased at 30 days. Estrogen had no effect on plasma corticosterone. These findings support the hypothesis that estrogen induces pituitary hyperplasia by antagonizing DA inhibition of PRL-secreting cells and by enhancing their responsiveness to TRH.

Animals↗
PubMed1984

Characterization of high density lipoprotein binding activity in rat adrenocortical cells.

Rat adrenocortical cells take up high density lipoprotein cholesterol for use as steroidogenic substrate. To better understand this unique uptake process, we have first characterized HDL binding. Infusion of human 125I-labeled HDL into rats pretreated with 4-APP demonstrated that the adrenal and ovary accumulate HDL in a saturable fashion in vivo. Subsequent studies using isolated rat adrenocortical cells demonstrated that cellular uptake of HDL is comprised of two events. One event is characterized by reversible membrane binding and is complete by 60 min (t1/2 = 20 min). The second event is marked by irreversible apoprotein accumulation which continues for at least 3 hr. Reversibly bound material exhibits the same apoprotein distribution as unincubated HDL. Irreversible accumulation could not be attributed to internalization or lysosomal accumulation inasmuch as it also occurred with partially purified plasma membranes and was not enhanced by addition of chloroquine. Reversible binding of human HDL3 exhibited a saturable dependence on concentration (Kd = 27 micrograms protein/ml; N = 3.0 X 10(6) sites/cell) similar to that previously reported for rat liver, ovary, and testis. Cell accumulation of HDL decreased by over 80% at 4 degrees C compared to 37 degrees C, did not require calcium, and was not diminished by prior cell treatment with trypsin or pronase. These results indicate that rat adrenocortical cells possess plasma membrane recognition sites for HDL with different properties than those of the LDL receptor. Moreover, adrenal accumulation of HDL apoproteins does not lead to secondary lysosome formation.

Adrenal Cortex↗
PubMed1981

New laparoscopic sterilization with exteriorization of tubes (cauterization, ligation): a preliminary report.

The fallopian tube's remarkable mobility and inherent length makes possible its exteriorization from the abdominal cavity to perform any kind of tubal sterilization. We offer a new laparoscopic technique utilizing (1) exteriorization of the tube and the performance of either (a) tubal ligation (Pomeroy technique); or (b) unipolar cauterization, or (2) intraabdominal in-sleeve cauterization in case of failure to exteriorize the tube. Our approach, on the one hand, was to avoid laparotomy but still preserve the advantages of tubal ligation, and on the other hand, to avoid possible bowel burn but still retain the beneficiary effect of electrical cauterization. To accomplish this, a simple second puncture uninsulated trocar-sleeve and grasping forceps were designed. With this technique, 325 patients have had voluntary interval sterilization at Olive View Medical Center-UCLA Campus (1977-1980). No bowel burn or pregnancies have occurred. No laparotomies have been necessary. Complications were minor and compared favorably with those cases in which other techniques were used.

Adult↗