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Biomedical subjects

J Lowe

Publications and source records attributed to J Lowe.

At least 199 records · Page 11Linked to original sources
PubMed1989

Two new IgA1-kappa plasma cell leukaemia cell lines (JJN-1 & JJN-2) which proliferate in response to B cell stimulatory factor 2.

Two new cell lines with the phenotype of terminally differentiated B cells have been derived from the presentation bone marrow of a patient with plasma cell leukaemia. They express the same immunoglobulin (A1-kappa) as the original bone marrow cells. JJN-1 is an hypodiploid, slow-growing line with a plasmacytic morphology, which grows in medium with 15-20% fetal calf serum. When JJN-1 was stimulated with a supernatant ('ESG') containing B cell stimulatory factor 2 (BSF-2/IL-6), a hypotetraploid sub-line, JJN-2, was selectively stimulated. JJN-2 is dependent on ESG for survival. The stimulatory effect of ESG can be completely abrogated by an anti-BSF-2 monoclonal antibody. However, purified BSF-2 alone only produces sub-maximal stimulation of the lines. Both lines show complex karyotypic abnormalities, including 14q- and del(6q). JJN-1 and JJN-2 may be useful for the study of late B cell differentiation and for use as immunogens for the generation of anti-plasma cell monoclonal antibodies.

Antigens, Surface↗
PubMed1989

Intermediate filaments and ubiquitin: a new thread in the understanding of chronic neurodegenerative diseases.

We have recently shown that there is a previously unsuspected link between the intracellular inclusions seen in several major chronic human degenerative diseases, including neurodegenerative diseases: the inclusions showing ubiquitin immunoreactivity. The conditions include Parkinson's disease, motor neurone disease, Alzheimer's disease, Pick's disease, and alcoholic liver disease as well as cerebellar astrocytomas and a myopathy. The inclusions found in these diseases are reported to contain intermediate filaments: neurofilaments are associated with Lewy bodies in Parkinson's disease, Pick's bodies in Pick's disease and neurofibrillary tangles in Alzheimer's disease, cytokeratins are found in Mallory bodies in alcoholic liver disease, glial fibrillary acidic proteins and vimentin are found in Rosenthal fibres in astrocytomas, and desmin is found in cytoplasmic bodies in cytoplasmic body myopathy. Therefore five classes of intermediate filaments are found in inclusions which also contain ubiquitin immunoreactivity; we have also shown that ubiquitin immunoreactivity is present in vesicles in some areas of granulovacuolar degeneration in Alzheimer's disease. Protein ubiquitination is considered a signal for extralysosomal protein degradation, (although ubiquitination may have several other important functions). We have recently shown that intermediate filaments are involved in protein sequestration before degradation by lysosomally mediated autophagy: therefore intermediate filament-containing ubiquitinated inclusions may be the hallmarks of cellular attempts to eliminate pathogenic insults by the activation of both extralysosomal and lysosomal mechanisms of intracellular protein degradation. We have recently been able to reproduce, at least in part, some of the clinical observations in tissue culture cells. Ubiquitinated protein conjugates accumulate in lysosomes in fibroblasts treated with the lysosomal cysteine protease inhibitor E-64, which may mimic aspects of granulovacuolar degeneration.

Chronic Disease↗
PubMed1989

Ubiquitin: new insights into chronic degenerative diseases.

Ubiquitin is a 76-amino-acid protein and is perhaps the most conserved gene product in evolution. It modulates degradation of abnormal or damaged proteins and belongs to the class of heat-shock proteins induced in conditions of cell stress. Recent work shows that ubiquitin is involved in several chronic degenerative diseases characterized by the formation of cellular inclusion bodies. The ubiquitin response to cell injury appears to be cytoprotective and particularly important in diseases of the nervous system.

Humans↗
PubMed1989

Intermediate filament-ubiquitin diseases: implications for cell sanitization.

The molecular pathology of chronic degenerative disease is not understood. Generally there must be two related, but opposing, processes: the direct deleterious effects of the pathogenic insult which can be chemical or viral and a cellular cytoprotective response to the insult. We have recently shown that there is a previously unsuspected link between the intracellular inclusions seen in some major chronic degenerative diseases: the inclusions contain ubiquitin immunoreactivity. The conditions include Parkinson's disease, motor neurone disease, Alzheimer's disease and alcoholic liver disease as well as astrocytomas and a myopathy. Protein ubiquitination is considered a signal for extra-lysosomal protein degradation although ubiquitin-protein conjugation may have several other important functions. Intermediate filaments are a component of some of the inclusions in diseased cells; we have previously reported that they are involved in protein sequestration for degradation by lysosomally mediated autophagy. Therefore, intermediate-filament-containing ubiquitinated inclusions may be hallmarks of cellular attempts to eliminate pathogenic insults by activating protein degradation mechanisms. Ubiquitinated inclusions could also be a hallmark of viral infections: they are in polio-virus-infected anterior horn neurones and Epstein-Barr-transformed lymphoblastoid cells. Some of the clinical observations can be reproduced experimentally in tissue culture cells. The implications of the combined clinical and experimental observations for cell sanitization and protein catabolism will be discussed.

Alzheimer Disease↗
PubMed1989

Ubiquitin-protein conjugates: clinical and experimental findings.

Ubiquitin has been extensively studied as a protein which is a cofactor in extralysosomal protein degradation, particularly in reticulocyte lysates. Ubiquitin is also found conjugated to nuclear histones and surface receptors in somatic cells. Until recently the occurrence of stable cellular ubiquitin-protein conjugates in physiological and pathological states had not been considered and studied. Recently we have shown that ubiquitin-protein conjugate immunoreactivity is a clinical feature in several ostensibly unrelated chronic human degenerative diseases as well as in some viral diseases. The consistent observation is the occurrence of intracellular extralysosomal inclusions containing intermediate filaments and ubiquitin conjugates as determined by immunohistochemical methods. These diseases are therefore part of a family of intermediate filament-ubiquitin diseases. The involvement of intermediate filaments with ubiquitin, a protein of known significance in protein degradation, ties in with separate evidence for a close role between intermediate filaments and protein degradation. We have previously shown that intermediate filaments may be involved in protein sequestration for degradation in the lysosomal system. Clinical immunohistochemical observations suggest that elements of the lysosomal degradation system and the ubiquitin-dependent extralysosomal system are involved in the molecular pathogenesis of some diseases. To underpin these clinical observations, we have recently shown that ubiquitin-protein conjugates accumulate in lysosome-related multivesicular bodies in cells in which lysosomal degradation is impaired. This phenomenon may result from increased ubiquitin protein-conjugate formation in cells with a compromised lysosomal system followed by chance uptake into multivesicular bodies. Alternatively, ubiquitination may normally serve as a signal for protein uptake into the lysosomal system, ubiquitinated protein-conjugates may therefore accumulate in cells with a functionally impaired lysosomal system.

Cell Compartmentation↗
PubMed1989

Young children's understanding of counting and cardinality.

4-year-old's knowledge of counting and cardinality--the last count word reached represents the numerosity of the set--was tested in 2 experiments. Experiment 1 investigated the nature of early cardinality responses by presenting different forms of the cardinality question before, after, and before and after the child counted. Both type and time of question has large effects. Experiment 2 examined whether children of this age could recognize errors in 4 counting procedures and whether they would reject a cardinality response arrived at through a mistaken counting procedure. The children were very good at recognizing a standard counting procedure as correct. They had only limited success at treating procedures that violated the stable order of count words or violated the one-one correspondence between count word and object as incorrect. They lacked an understanding of the order irrelevance in that they judged valid, nonstandard counting orders as incorrect. The children did not seem to link their evaluation of a cardinality response with their evaluation of the counting procedure used to reach that response. The results do not indicate that counting principles initially govern the child's acquisition of counting knowledge. They are consistent with the suggestion that early cardinality responses are last-word responses.

Child, Preschool↗
PubMed1988

A filamentous inclusion body within anterior horn neurones in motor neurone disease defined by immunocytochemical localisation of ubiquitin.

Using an immunocytochemical method to localise antibodies to ubiquitin, filamentous inclusion bodies were seen in spinal anterior horn neurones in cases of motor neurone disease (MND) but not in any control cases. These inclusion bodies appeared to be closely associated with classical Bunina bodies and immuno-electron microscopy suggested that they were based on arrays of straight 10-15 nm filaments together with some granular material. These observations link the protein ubiquitin with a chronic neurodegenerative disease and extend previous observations of a close association between filamentous inclusion bodies and ubiquitin. Ubiquitin-filament inclusions should be regarded as a new hallmark in the histological diagnosis of MND.

Adult↗
PubMed1988

Ubiquitin is a component of neurofibrillary tangles in a variety of neurodegenerative diseases.

Ubiquitin has been shown to be a component of neurofibrillary tangles in Alzheimer's disease. We now show immunocytochemically that it is also a component of neurofibrillary tangles in several other neurodegenerative diseases of diverse aetiology, including Down's syndrome, dementia pugilistica and postencephalitic parkinsonism, and in normal ageing. Ubiquitin immunoreactivity is not, however, generally found in the neurofibrillary tangles of progressive supranuclear palsy. These findings show that while associated ubiquitin is not a feature unique to the tangles of Alzheimer's disease, it is not simply a non-specific response to the presence of an inclusion body within the cell. The observations suggest that ubiquitin may have an important role in the formation of neurofibrillary tangles in a variety of neurodegenerative diseases.

Alzheimer Disease↗
PubMed1988

Ubiquitin is a common factor in intermediate filament inclusion bodies of diverse type in man, including those of Parkinson's disease, Pick's disease, and Alzheimer's disease, as well as Rosenthal fibres in cerebellar astrocytomas, cytoplasmic bodies in muscle, and mallory bodies in alcoholic liver disease.

Polyclonal antibodies were raised which have a high affinity for conjugated ubiquitin. Immunocytochemistry was performed on paraffin sections of tissues showing well-characterized inclusion bodies. Ubiquitin was found as a component of the intermediate filament inclusion bodies characteristic of several major diseases including Lewy bodies of Parkinson's disease, Pick bodies of Pick's disease, Mallory bodies of alcoholic liver disease, cytoplasmic bodies of a specific myopathy, and Rosenthal fibres within astrocytes. Ubiquitin was also present in the three histological lesions characteristic of Alzheimer's disease. These observations suggest a fundamental role for ubiquitin in the formation of intermediate filament inclusion bodies in man, and have implications regarding the pathogenesis of these important diseases.

Alzheimer Disease↗
PubMed1988

Split-thickness skin excision in severe open fractures.

Split-thickness skin excision can be used as a one-stage procedure for the accurate diagnosis of flap viability and the immediate treatment of friction-avulsion injuries in severe open fractures. After cleaning the wound, the avulsed flap is temporarily sutured back to its original bed and a split thickness graft is taken from it and meshed to a 1:3 ratio. Surface dermal capillary bleeding then serves as an indicator of viability, clearly displaying a line for the excision of devascularized skin and correlating well with a concomitant fluorescein test. The wounds are re-opened and, after fixation of the fracture, the viable part of the flap is returned to its original bed and the remaining defects are covered with the meshed graft. We have treated 16 patients with extensive degloving injuries in this way, 15 needing only the single surgical procedure. All retained flaps survived, no other donor sites were needed and the split-thickness grafts took with 90% to 100% success.

Adolescent↗
PubMed1987

Cerebral vasculitis associated with hairy cell leukemia.

Hairy cell leukemia was diagnosed in a 74-year-old man. He was followed for 5 years when he developed confusion and focal neurological signs. Despite investigation and treatment he died. Postmortem study revealed isolated primary necrotizing vasculitis affecting the cerebral arteries. No leukemic infiltration of the central nervous system was found. There is a recognized association between hairy cell leukemia and generalized necrotizing vasculitis of polyarteritis type, however, this is the first case report of isolated cerebral vasculitis associated with this condition. The importance of excluding infective (mycotic) arteries in this type of case is emphasized.

Aged↗
PubMed1987

ELISA measurement of IgG subclass production in culture supernatants using monoclonal antibodies.

Specific and sensitive ELISA to quantitate the human IgG subclasses in cell culture supernatants are described. These assays detect a minimum of 5 ng/ml IgG1, 90 ng/ml IgG2, 8 ng/ml IgG3 and 8 ng/ml IgG4 and can generally measure IgG subclasses in lymphocyte cultures containing a minimum of 200 ng/ml of total IgG. The isotype specificity of these ELISA is demonstrated and each individual ELISA shown to react with a number of paraproteins of the relevant subclass independently of their light chain type or their (major Caucasian) allotype. These assays have been used to determine the IgG subclass response of normal human lymphocytes to pokeweed mitogen in vitro.

Antibodies, Monoclonal↗
PubMed1987

Unusual combination of Monteggia, Colles', and navicular fractures.

A rare combination of an ulnar fracture with posterior dislocation of the head of the radius and intraarticular fracture of the distal radius concomitant with an ipsilateral navicular fracture is presented. To the best of our knowledge, no such case has been reported. The mechanism of this fracture combination is discussed with respect to its role in producing the Monteggia type II fracture. Treatment consisted of a combination of closed and open reduction with external fixation.

Adult↗
PubMed1987

Spondylolysis in the upper lumbar spine. A study of 32 patients.

Reports of spondylolysis in vertebrae other than those of the lower lumbar spine are rare. We report 32 patients with upper lumbar spondylolysis who have been studied clinically, radiologically and scintigraphically. Twenty patients had bilateral lesions, and seven of those with unilateral lesions had structural changes or anomalies in the opposite posterior arch. Positive scans were found to be associated with a short clinical history, and indicated stress-related lesions. Our findings suggest that mechanical factors may play a role in the aetiology of spondylolysis in the upper lumbar spine similar to that which they play in the lower lumbar spine, and that local structural anomalies may contribute to abnormal loading of these vertebrae.

Adolescent↗
PubMed1987

Modulation of the murine immune response to human IgG by complexing with monoclonal antibodies. I. Antibody responses to determinants on the constant region of light chains and gamma chains.

Complexing a human IgG lambda paraprotein with a monoclonal antibody (McAb) to a lambda-chain determinant markedly depressed the anti-lambda response of immunized mice. No anti-lambda was found in the serum after two or four injections of the complex, whereas high titres of anti-lambda chain antibody were found in the sera of mice immunized with the IgG paraprotein complexed with any single anti-gamma chain McAb or with a pool of anti-gamma chain McAbs. Responses to the highly immunogenic Fc gamma portion of the molecule were not suppressed by complexing with a single anti-gamma chain McAb and were only slightly suppressed after complexing with a pool of anti-gamma chain McAbs. Some anti-Fc gamma antibody was produced by all animals receiving a single injection of the immunogen complexed to any McAb, but free immunogen did not generate a primary response. Complexing the IgG with an anti-Fc gamma McAb enhanced the response to to the poorly immunogenic C gamma 1 domain but no anti-C-gamma 1 was produced by mice receiving the IgG complexed with an anti-C-gamma 1 McAb. In immunizations with 'free' (Bence-Jones) lambda chain, all the antibody produced was directed against 'free'-specific determinants. Complexing the Bence-Jones protein with McAbs to 'free' or 'general' determinants on the lambda chain did not enhance or suppress the response. It is concluded that the response to weakly or moderately immunogenic, but not to strongly immunogenic, regions of the molecule may be suppressed by complexing the immunogen with a McAb of appropriate specificity. Possible reasons for this result are discussed.

Animals↗
PubMed1987

Modulation of the murine immune response to human IgG by complexing with monoclonal antibodies. II. Antibody responses to idiotopes of the human IgG paraprotein and of the mouse monoclonal antibodies.

Anti-idiotope antibodies produced by mice immunized with a human IgG paraprotein complexed with various mouse monoclonal antibodies (McAbs) have been measured. All animals receiving more than one injection of the paraprotein (free or complexed with a mouse McAb) produced antibodies to the idiotypes of the paraprotein. Complexing with a McAb, especially an anti-Fc-gamma McAb, enhanced the response. Antibodies to the idiotopes of mouse McAbs were more difficult to produce and their production was very dependent on the mode and schedule of the immunization. The best antisera were produced by mice receiving a course of injections of pre-formed complexes of the IgG paraprotein and McAbs. Four of five mice produced antibodies to the idiotopes of an anti-light chain McAb (C4) after a course of immunization (one primary plus four boosts) of an IgG-C4 complex. Two of the six mice receiving a similar course of injections of the paraprotein complexed with an anti-gamma McAb (A55) produced high titres of antibodies to A55 idiotypes. Responses were enhanced when complexes were prepared with a pool of McAbs. It is probable that the formation of large multi-cross-linked complexes containing the McAb under study is important in generating the response. Once a response is initiated, very high titres may be achieved.

Animals↗
PubMed1986

Sequence analysis in the E1 region of adenovirus type 4 DNA.

Adenovirus type 4 (Ad4) is the sole member of adenovirus group E based on overall DNA sequence homology, restriction endonuclease cleavage patterns, and the size of capsid proteins. We cloned the BamHI-F fragment from the left end of Ad4 in pUC13-1 between the SalI and BamHI sites in order to carry out the structural analysis of the E1A region of Ad4. The complete sequence of the BamHI-F fragment (2042 bp) has been determined. From the DNA sequence, the splice sites for the putative 12 S and 13 S mRNAs, encoded by the E1A region of Ad4 were deduced. If protein synthesis initiates at the first available AUG triplet (position 575), these 12 S and 13 S mRNAs would code for polypeptides containing 226 and 257 amino acids, respectively. Comparison of Ad4- and Ad7-13 S mRNA-coded polypeptides indicates that there is 57% homology, whereas the homology is only 38% with Ad12 and 31% with Ad2-13 S mRNA-coded polypeptides. The structural analysis in the E1 region of Ad4 also includes the coding region for the E1B 19-kDa protein. Ad4 and Ad7 shows 65% homology in the coding regions for E1B 19-kDa protein. Comparison of the DNA sequence of Ad4 with those of Ad2, Ad7, and Ad12 by using a dot matrix computer program and by Southern hybridization revealed that Ad4 bears a stronger homology with Ad7 than with Ad2 and Ad12 in this region. Hydropathy plots and alignments of the putative polypeptides coded by this region in Ad4 with those from the corresponding regions of different serotypes to reveal the highly conserved domains also support the above conclusion.

Adenovirus Early Proteins↗