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Biomedical subjects

J R Neilson

Publications and source records attributed to J R Neilson.

16 recordsLinked to original sources
PubMed2006

Universal features of terahertz absorption in disordered materials.

Using an analytical theory, experimental terahertz time-domain spectroscopy data, and numerical evidence, we demonstrate that the frequency dependence of the absorption coupling coefficient between far-infrared photons and atomic vibrations in disordered materials has the universal functional form, C(omega)=A+Bomega(2), where the material-specific constants A and B are related to the distributions of fluctuating charges obeying global and local charge neutrality, respectively.

Journal Article↗
PubMed2005

A highly unusual cluster of acute promyelocytic leukaemia: an environmental aetiology?

We report three consecutive cases of acute promyelocytic leukaemia (APML) that were diagnosed within a 4-month period. This unexpected sequence of events was made all the more notable following our discovery of co-incidental geographic, social, and occupational factors that linked them together. Our data strongly suggests that environmental agents may play a greater role in the aetiology of APML than is commonly perceived.

Adult↗
PubMed2003

Recurrent paroxysmal cold haemoglobinuria in a 3-year-old child: a case report.

We present the case of a 3-year-old girl who presented on two separate occasions, eight months apart, with typical features of paroxysmal cold haemoglobinuria (PCH). On each occasion, she suffered malaise and fever with dark urine following an upper respiratory tract infection. She developed severe anaemia and required transfusion of red cells on both occasions, although each time she made a quick recovery. She was found to be direct antiglobulin test-positive with anti-C3d, and agglutination was observed on the blood film. A biphasic Donath-Landsteiner antibody was demonstrated. The specificity of the antibody was not identified, although it was not anti-P. As far as we are aware, recurrence of acute PCH in a child has not been previously reported in the literature.

Agglutination Tests↗
PubMed1999

L-type calcium channels and GSK-3 regulate the activity of NF-ATc4 in hippocampal neurons.

The molecular basis of learning and memory has been the object of several recent advances, which have focused attention on calcium-regulated pathways controlling transcription. One of the molecules implicated by pharmacological, biochemical and genetic approaches is the calcium/calmodulin-regulated phosphatase, calcineurin. In lymphocytes, calcineurin responds to specific calcium signals and regulates expression of several immediate early genes by controlling the nuclear import of the NF-ATc family of transcription factors. Here we show that NF-ATc4/NF-AT3 in hippocampal neurons can rapidly translocate from cytoplasm to nucleus and activate NF-AT-dependent transcription in response to electrical activity or potassium depolarization. The calcineurin-mediated translocation is critically dependent on calcium entry through L-type voltage-gated calcium channels. GSK-3 can phosphorylate NF-ATc4, promoting its export from the nucleus and antagonizing NF-ATc4-dependent transcription. Furthermore, we show that induction of the inositol 1,4,5-trisphosphate receptor type 1 is controlled by the calcium/calcineurin/NF-ATc pathway. This provides a new perspective on the function of calcineurin in the central nervous system and indicates that NF-AT-mediated gene expression may be involved in the induction of hippocampal synaptic plasticity and memory formation.

Biological Transport↗
PubMed1999

Subtypes of human immunodeficiency virus type 1 and disease stage among women in Nairobi, Kenya.

In sub-Saharan Africa, where the effects of human immunodeficiency virus type 1 (HIV-1) have been most devastating, there are multiple subtypes of this virus. The distribution of different subtypes within African populations is generally not linked to particular risk behaviors. Thus, Africa is an ideal setting in which to examine the diversity and mixing of viruses from different subtypes on a population basis. In this setting, it is also possible to address whether infection with a particular subtype is associated with differences in disease stage. To address these questions, we analyzed the HIV-1 subtype, plasma viral loads, and CD4 lymphocyte levels in 320 women from Nairobi, Kenya. Subtype was determined by a combination of heteroduplex mobility assays and sequence analyses of envelope genes, using geographically diverse subtype reference sequences as well as envelope sequences of known subtype from Kenya. The distribution of subtypes in this population was as follows: subtype A, 225 (70.3%); subtype D, 65 (20.5%); subtype C, 22 (6.9%); and subtype G, 1 (0.3%). Intersubtype recombinant envelope genes were detected in 2.2% of the sequences analyzed. Given that the sequences analyzed represented only a small fraction of the proviral genome, this suggests that intersubtype recombinant viral genomes may be very common in Kenya and in other parts of Africa where there are multiple subtypes. The plasma viral RNA levels were highest in women infected with subtype C virus, and women infected with subtype C virus had significantly lower CD4 lymphocyte levels than women infected with the other subtypes. Together, these data suggest that women in Kenya who are infected with subtype C viruses are at more advanced stages of immunosuppression than women infected with subtype A or D. There are at least two models to explain the data from this cross-sectional study; one is that infection with subtype C is associated with a more rapid disease progression, and the second is that subtype C represents an older epidemic in Kenya. Discriminating between these possibilities in a longitudinal study will be important for increasing our understanding of the role of specific subtypes in the transmission and pathogenesis of HIV-1.

Base Sequence↗
PubMed1997

High prevalence of hepatitis G virus in bone marrow transplant recipients and patients treated for acute leukemia.

Hepatitis G virus (HGV) is a newly described virus that has been implicated in transfusion-associated hepatitis. The prevalence of HGV in a group of multitransfused patients with hematological malignancy was studied using a reverse transcription polymerase chain reaction technique. Transfusion histories and serum aspartate aminotransferase (AST) levels were recorded. HGV was detected in 29 of 60 (48%) patients. There was no difference in HGV positivity rates between those with normal AST levels and those with raised AST levels. Analysis of patients by treatment type showed that 20 of 33 (61%) patients who received a bone marrow transplantation procedure were HGV positive compared with 9 of 27 (33%) treated with conventional combination chemotherapy (P = .036) despite similar transfusion histories. There was no significant difference in HGV positivity between patients treated before the introduction of United Kingdom blood donor screening for hepatitis C virus antibody:18 of 39 (46%) and those treated after the introduction of screening 11 of 21 (52%). HGV infection appears to be extremely common in these patients; however, the clinical significance of these findings with respect to liver dysfunction is not yet clear.

Acute Disease↗
PubMed1997

Deletions at 11q identify a subset of patients with typical CLL who show consistent disease progression and reduced survival.

Eighty-four patients with typical chronic lymphocytic leukemia (CLL) (by morphological and immunophenotypic criteria) on whom karyotypes were available were studied. Binet stage at diagnosis and follow-up were defined. Survival was calculated from diagnosis. Fifty-one percent of patients had a karyotypic abnormality, the commonest being abnormalities at 13q14 (16%); these patients did not have significantly different survival from patients with normal karyotype. The second commonest abnormality was del(11q) (13%); these patients had significantly worse survival when compared both with patients with normal karyotype (P < 0.0001) and with other patients with karyotypic abnormality (P = 0.0012). All patients with del(11q) had progressed to stage C at follow-up while only 20% of the other patients had shown any disease progression (P < 0.0001). Del(11q) may identify a subset of patients with typical CLL who have worse survival and consistent disease progression and in future may help define a group of patients with CLL who could benefit from earlier or more intensive therapy.

Adult↗
PubMed1996

Role of non-transferrin bound iron in iron overload and liver dysfunction in long term survivors of acute leukaemia and bone marrow transplantation.

AIMS: To determine whether nontransferrin bound iron is present in the serum of long term survivors of acute leukaemia and bone marrow transplantation who have liver dysfunction as indicated by consistently raised serum aspartate aminotransferase (AST) activities. METHODS: Thirty eight patients, who were at least three years from the end of treatment, were studied. Serum samples were analysed for hepatitis C, hepatitis B, AST, ferritin, and non-transferrin bound iron. A bleomycin based assay was used to detect non-transferrin bound iron. Patient and blood bank records were examined to determine the number of units of transfused blood received by each patient. RESULTS: Ten patients had consistently raised serum AST activities. Of these, two had evidence of hepatitis C infection, one had chronic hepatitis B infection and one had chronic graft versus host disease affecting the liver. None of these four patients had detectable non-transferrin bound iron. The remaining six patients had no obvious reason for raised AST activities, but four had non-transferrin bound iron detectable in their serum as compared with only two out of 28 patients with normal AST activities. Patients with abnormal AST activities had higher serum ferritin concentrations than those with normal AST, though serum ferritin was raised in 21 of 28 patients without liver dysfunction. CONCLUSION: Non-transferrin bound iron may be found in this group of patients, suggesting that iron overload is the cause of the observed liver dysfunction. Non-transferrin bound iron may also be a more specific indicator of iron overload than the serum ferritin concentrations.

Adult↗
PubMed1996

Chronic hepatitis C in long term survivors of haematological malignancy treated in a single centre.

AIMS: To investigate the impact of hepatitis C virus (HCV) infection in long term survivors of haematological malignancy treated before the introduction of blood donor screening in September 1991. METHOD: Patients were tested for evidence of HCV infection by third generation enzyme linked immunosorbent assays, a recombinant immunoblot assay and reverse transcriptase polymerase chain reaction. Serum aspartate aminotransferase activities were measured. The number and type of blood component units received by each patient were recorded. RESULTS: Forty two patients were studied who had received a total of 7143 blood component units. Two patients (4.8%) were found to have HCV infection, both had histological evidence of chronic active hepatitis, and one is now receiving treatment with alpha-interferon. Both of these patients had been missed by the ongoing look-back programme which aims to detect recipients of all known HCV infected blood components. CONCLUSION: Although HCV infection affects a minority of long term survivors of haematological malignancy, infected patients may benefit from alpha-interferon treatment. The screening of all patients treated for haematological malignancy before September 1991 is advocated.

Adult↗
PubMed1995

Leukaemic mantle cell lymphoma with t(11;14) and trisomy 12 showing clinical features of state A0 B cell chronic lymphocytic leukaemia.

The precise diagnosis of lymphoma usually requires the histological examination of lymph nodes or involved tissues. Mantle cell lymphoma is a form of intermediate grade non-Hodgkin's lymphoma in which typical morphological immunophenotypic and cytogenetic features have been recognised. A case of leukaemic mantle cell lymphoma with the characteristic reciprocal translocation t(11;14) together with trisomy 12, a chromosomal abnormality usually associated with B cell chronic lymphocytic leukaemia (CLL), is presented. This combination of cytogenetic abnormalities has not been reported previously. The lack of lymphadenopathy and hepatosplenomegaly in this patient is more in keeping with stage A0 CLL. This case demonstrates the close clinical and biological relationship between mantle cell lymphoma and CLL.

Journal Article↗
PubMed1994

Polycythaemia rubra vera transforming to acute lymphoblastic leukaemia with a common immunophenotype.

Lymphoblastic transformation of polycythaemia rubra vera is an extremely rare phenomenon. A case of a 76 year old man with polycythaemia rubra vera who developed acute lymphoblastic leukaemia (ALL) 16 years after his initial diagnosis is reported. Membrane markers showed a CD10 positive (common ALL) immunophenotype. To our knowledge this association has not been previously recorded. The rare occurrence of ALL in polycythaemia rubra vera may indicate that in a minority of patients clonal expansion of an abnormal pluripotent haemopoietic stem cell is responsible for the polycythaemia rubra vera disease phenotype.

Aged↗