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Biomedical subjects

J Lowe

Publications and source records attributed to J Lowe.

At least 181 records · Page 10Linked to original sources

Molecular cloning of a novel human leukemia-associated gene. Evidence of conservation in animal species.

We have recently described an 18-kilodalton polypeptide (p18) that is present in much greater abundance in acute leukemic blast cells (myeloid and lymphoid) than in resting or proliferating nonleukemic lymphoid cells or chronic lymphoid and myeloid leukemic cells. In this report we describe the cloning of two different sized full-length cDNAs that code for p18. The two cDNAs differ in their 3'-noncoding regions as a result of alternative polyadenylation. Analysis of the complete nucleotide sequence and the corresponding amino acid sequence did not reveal significant homology to any previously described sequences. We show evidence that this gene is highly conserved in several animal species and low stringency hybridization studies suggest that the p18 gene may be a member of a family of partially homologous genes in the human genome.

Amino Acid Sequence↗

Ubiquitin gene expression in brain and spinal cord in motor neurone disease.

A restriction fragment of the coding region of a human ubiquitin gene has been used in Northern analyses of RNA prepared from human motor cortex and anterior horn region of cervical spinal cord. The analyses show that there is a substantial increase (approximately two-fold) in the expression of a polyubiquitin gene in motor cortex and spinal cord from patients with motor neurone disease compared to these tissues from control cases. Polyubiquitin gene expression in other organisms is associated with physical or chemical cell stresses. The data indicate that the primary stresses which result in the generation of ubiquitinated filamentous inclusion bodies in neurones in motor neurone disease also result in increased transcription of a gene coding for a polyprotein of ubiquitin.

Adult↗

Splanchnic transplantation. An approach to the infant dependent on parenteral nutrition who develops irreversible liver disease.

Two infants with short-bowel syndrome and liver failure associated with obligatory parenteral nutrition received a composite allograft that consisted of en bloc liver, stomach, duodenum, pancreas, jejunum, and ileum. Solutions to the fatal complications in the first case resulted in a functioning composite splanchnic system in the second case. Despite a number of early complications, the small intestine and liver developed near-normal function until a monoclonal, malignant, B-cell lymphoproliferative disorder appeared. The analysis of these two cases supports three summary observations: the operative procedure can be safely performed in a metabolically compromised infant; intestinal allograft rejection, in this model, is controllable with existing immunosuppressive drugs; and this procedure appears to be associated with a uniquely high incidence of lymphoma. Since transplantation is a feasible solution to this devastating infantile disease, further development of this therapy must incorporate means of preventing lymphoma.

Cyclosporins↗

Soluble forms of CD21 and CD23 antigens in the serum in B cell chronic lymphocytic leukaemia.

By using pairs of monoclonal antibodies (MAbs) to different epitopes on CD21 and CD23 antigens, it has been shown that both antigens are readily detectable in cell-free supernates of cultures of B cells expressing these antigens on the cell surface. The antigens remained in the soluble fraction after high speed centrifugation. Sera from normal individuals contained significant amounts of CD21 antigen, whereas little CD23 antigen was detectable. By contrast CD23 but not CD21 antigen was present in urine. Sera from patients with B cell chronic lymphocytic leukaemia (B-CLL) contained increased amounts of both antigens. The levels were related to the surface expression of antigen on the leukaemic cells and the number of cells in the blood. The possible functional role of soluble forms of B cell antigens and the diagnostic potential of their detection in body fluids are discussed.

Antibodies, Monoclonal↗

A phenotypic study of cells from Burkitt lymphoma and EBV-B-lymphoblastoid lines and their relationship to cells in normal lymphoid tissues.

Cells of 7 EBV-B-LCL, 10 Burkitt lines and 13 EBV-B-LCL/Burkitt line hybrids have been phenotyped for antigens of the major B cell clusters and for some other antigens. High levels of CD23 and CD39 and low levels of CD38 (T10) were characteristic of EBV-B-LCL; the converse was true for Burkitt lines. In hybrids the EBV-LCL phenotype was dominant. The phenotype of Burkitt-line cells correlated strongly with that of germinal centre B cells in tonsil sections, but differed markedly from that of marginal zone B cells or follicular mantle cells. The results are discussed in relation to the origin of Burkitt tumours of "sporadic" and "endemic" type, in particular to histopathological evidence that Burkitt lymphomas develop in germinal centres. Recent studies on the location of the breakpoints of Burkitt chromosomal translocations are also considered to be compatible with this concept, even though different regions of the immunoglobulin heavy chain locus are involved in the two types of BL.

ADP-ribosyl Cyclase↗

Microglial cells in human brain have phenotypic characteristics related to possible function as dendritic antigen presenting cells.

The resting human microglia have previously been shown to be cells of dendritic morphology expressing class II MHC antigens and macrophage specific antigens by immunocytochemical techniques. To examine the relationship between the microglia and the family of dendritic antigen presenting cells (APC), normal white matter from eight normal adults with no neurological disease at autopsy was examined by immunocytochemical techniques to localize antibodies to leukocyte common antigen (LCA), HLA-DR, CD1 (T6), CD4 (T4), and glial fibrillary acidic protein. In addition, enzyme histochemical staining for ATPase, non-specific esterase (NSE), and acid phosphatase (ACP) was performed. The normal microglia are ATPase +ve, NSE -ve, ACP -ve, HLA-DR +ve, LCA +ve, CD1 (T6) +ve and weakly CD4 (T4) +ve. This specialized phenotype closely resembles that of Langerhans cells and suggests that microglia are not simply quiescent phagocytes, but may have a primary role as microenvironmentally specialized APC. The finding of weak anti-CD4 (T4) immunoreactivity supports suggestions for a central role for this cell in infection of the central nervous system by human immunodeficiency virus type 1.

Aged↗

Pulmonary septic emboli mimicking metastatic rhabdomyosarcoma.

Central venous catheters have proven to be an important aid for the care of pediatric patients with malignancies receiving chemotherapy. A rare complication of such catheters is pulmonary septic emboli. This report describes a 15-year-old white girl with rhabdomyosarcoma who developed pulmonary nodules while on chemotherapy. These lesions appeared to be metastatic rhabdomyosarcoma. However, an excisional biopsy showed the lesions to be septic emboli. The patient was placed on antibiotic therapy and responded well. She was able to continue with her "front-line" therapy because the nodules were confirmed not to be metastatic disease.

Adolescent↗

A study of tolerance to the psychomotor effects of indomethacin in healthy volunteers.

We have examined the effect of single dose indomethacin 50 mg on objective measurements of psychomotor function and whether this effect is altered by pretreatment with indomethacin 25 mg t.i.d. for 7 days in 10 healthy volunteers (5 male, 5 female; age 20-54 y). One hour after a single dose of indomethacin 50 mg there was significant impairment of psychomotor function (critical flicker fusion frequency threshold and choice reaction time) (Wilcoxon p less than 0.05). Pretreatment with indomethacin 25 mg t.i.d. for 7 days prevented this impairment. Thus we conclude that tolerance occurs over the course of a week to the psychomotor effects of indomethacin.

Adult↗

Anti-ubiquitin immunocytochemistry is more sensitive than conventional techniques in the detection of diffuse Lewy body disease.

Brainstem and cortical Lewy bodies in diffuse Lewy body disease show intense immunoreactivity to antibodies against ubiquitin. Quantitative studies show that the novel neuropathological technique of anti-ubiquitin immunocytochemistry is more than twice as sensitive as conventional haematoxylin and eosin stains in detecting cortical Lewy bodies. Anti-ubiquitin immunocytochemistry should be regarded as the method of choice for the diagnosis and quantification of diffuse Lewy body disease.

Antibodies↗

Diffuse Lewy body disease: correlative neuropathology using anti-ubiquitin immunocytochemistry.

Diffuse Lewy body disease is an important pathological substrate of the common syndrome of parkinsonian dementia. The new technique of anti-ubiquitin immunocytochemistry has been used in a correlative quantitative neuropathological study of fifteen cases of diffuse Lewy body disease, showing that the severity of dementia is related to cortical Lewy body density, whilst subcortical abnormalities make a much less significant contribution. Cortical senile plaques also appear to be part of the pathology of diffuse Lewy body disease and should not therefore be used as an isolated diagnostic criterion for Alzheimer's disease. Diagnostic criteria for diffuse Lewy body disease are discussed.

Aged↗

Diffuse Lewy body disease: clinical features in 15 cases.

Fifteen cases of diffuse Lewy body disease were diagnosed on pathological grounds during a single year in one health district. The range and frequency of clinical features contrast strikingly with previous reports. The majority of cases presented with classical levodopa-responsive Parkinson's disease either alone (6 cases) or with mild cognitive impairment (3 cases); the remaining 6 cases presented with cognitive impairment alone. In time almost all patients developed both dementia and Parkinsonism. The dementia was cortical in type, but unusual in that most (12 cases) showed day-to-day fluctuation in severity at some point in their illness. These findings suggest that diffuse Lewy body disease is not rare, and that it presents in a range of ways from dementia with subsequent Parkinsonism to Parkinson's disease with subsequent dementia. The latter mode of presentation suggests that it should be considered as a significant pathological substrate of dementia in Parkinson's disease.

Aged↗

Crush injuries of the foot with compartment syndrome: immediate one-stage management.

Severe crush injuries with compartment syndrome were treated in five patients by an immediate one-stage procedure. This procedure included the assessment of skin flap viability with accurate debridement of devascularized tissues. It was performed according to the split-thickness skin excision technique. Compartment pressures were measured and the fasciotomies were performed through open wounds or separate medial and lateral incisions. The medial incision was extended to release the tarsal tunnel. Fractures were reduced and internally fixed and exposed bones were covered with locally transposed muscles. Skin grafts, taken earlier for the skin viability assessment, were meshed and applied to replace skin loss. All wounds and fractures healed uneventfully with no major functional loss. In multiple trauma, the physician should maintain a high index of suspicion for early diagnosis and treatment of severe foot injuries. Early treatment leads to more desirable results, shorter hospitalization, and faster rehabilitation.

Adult↗

Systemic metastasis from primary intracranial germinoma: a case report and literature review.

A case of systemic haematogenous metastasis occurring post-operatively from a primary suprasellar intracranial germinoma is reported. While local invasion and direct spread associated with surgical incision and shunt procedures are well known, haematogenous metastasis of these tumours is extremely rare. Problems associated with establishing this diagnosis are discussed.

Bone Neoplasms↗