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Biomedical subjects

M J Anderson

Publications and source records attributed to M J Anderson.

At least 109 records · Page 6Linked to original sources

Variation of erythroid and myeloid precursors in the marrow and peripheral blood of volunteer subjects infected with human parvovirus (B19).

Infection of normal individuals with human parvovirus (B19) results in a mild disease (erythema infectiosum) but gives rise to aplastic crises in patients with chronic hemolytic anemias. The effects of this disease on hemopoiesis were investigated following intranasal inoculation of the virus into three volunteers. A typical disease ensued with a viremia peaking at 9 d. Marrow morphology 6 d after inoculation appeared normal but at 10 d there was a severe loss of erythroid precursors followed by a 1-2-g drop in hemoglobin, and an increase in serum immunoreactive erythropoietin. Erythroid burst-forming units (BFU-E) from the peripheral blood were considerably reduced, starting at the time of viremia and persisting for 4-8 d depending on the individual. Granulocyte-macrophage colony-forming units (CFU-GM) were also affected but the loss started 2 d later. Both CFU-GM and BFU-E showed a sharp overshoot at recovery. In the marrow, BFU-E and CFU-E were reduced at 6 and 10 d in the individual having the longest period of peripheral progenitor loss. In contrast, there was an increase in BFU-E and CFU-E in the subject with least change in peripheral progenitors. In the third subject, with an intermediate picture, there was a loss at 6 d but an increase at 10 d of erythroid progenitors. It is suggested that the architecture of the marrow might partially isolate progenitors from high titers of virus in the serum and individual variation in this respect might give the results observed.

Adult↗

Isolation of cDNA clones coding for the alpha-subunit of human beta-hexosaminidase. Extensive homology between the alpha- and beta-subunits and studies on Tay-Sachs disease.

The lysosomal beta-hexosaminidases (N-acetyl-beta-glucosaminidase, EC 3.2.1.30) occur as two major isozymes, hexosaminidase A (alpha beta a beta b) and hexosaminidase B (2(beta a beta b)). To facilitate the investigations of the biosynthesis and structure of the enzymes and the nature of mutation in Tay-Sachs disease, we have isolated cDNA clones coding for the alpha-subunit. The polypeptide chains of hexosaminidase A (30 mg) were digested with trypsin, and peptides were isolated by reverse phase high pressure liquid chromatography and their amino acid sequences determined. One of alpha-chain peptides contained a string of seven amino acids from which two sets of oligonucleotides were specified. They were used to screen the SV40-transformed human fibroblast cDNA library of Okayama and Berg. Three cDNA clones, designated pHexA, identified from among 5 X 10(5) clones screened, contained the deduced amino-acid sequences of five alpha-chain peptides. Genomic DNA homologous to pHexA cDNA mapped to human chromosome 15 in somatic cell hybrids, as expected for the pre-alpha-polypeptide. Two of the clones contained identical polyadenylation sites, while the third was polyadenylated about 450 base pairs downstream. The two types of clones were found to correspond to a major 2.0-kilobase pair and a minor 2.3-kilobase pair mRNA species. Blot hybridizations of mRNA and DNA from Tay-Sachs variant fibroblasts revealed absence or reduction of levels of both mRNA species among infantile and juvenile variants, but no observable DNA alterations. Alignment of the pre-alpha- and pre-beta-polypeptides revealed 55% nucleotide and 57% amino acid homology. These data suggest a common origin of the HEXA and HEXB genes and account for the similar substrate specificities of the alpha-dimer subunit, hexosaminidase S, and hexosaminidase B.

Amino Acid Sequence↗

Osteoarticular and pulmonary manifestations of acute leukemia. Case report and review of the literature.

Acute leukemia with bone or joint symptoms of sufficient magnitude to obscure and delay the correct diagnosis has been reported but is rarely mentioned in the recent literature, particularly in adults. The authors report an adult with rapidly fatal acute leukemia and a clinical course dominated by recurrent osteoarticular symptoms; osteoarticular symptoms preceded the diagnosis of leukemia by 3 months and delayed diagnosis and treatment. The correct diagnosis requires awareness of the osteoarticular manifestations of acute leukemia and examination of blood or bone marrow smear by an experienced observer; a biopsy specimen of bone or joint lesions or examination of cytocentrifuged synovial fluid may aid in diagnosis. The immediate cause of death in our patient was respiratory failure with prominent leukemic interstitial pulmonary infiltrates at autopsy; clinically significant leukemic pulmonary infiltrates have only rarely been reported. The authors review the literature on pulmonary and osteoarticular manifestations caused by acute leukemic infiltrates.

Acute Disease↗

Rubella epidemiology in South East England.

Analyses of data collected in a large survey (sample size greater than 3000) of rubella antibody in South East England, finely stratified according to age, reveal age-dependent changes in the pattern of virus transmission. The rate or force of infection changes from low in the young children to high in the 5- to 15-year-olds and back to low again in the adult age classes (there is a 50% reduction between the 5- to 15-year-olds and the 20+-year-olds). Raised levels of immunity are recorded in the teenage and young adult female segments of the population as a consequence of the UK rubella immunization programme. Mean antibody concentrations show a decline with age and are, on average, lower in vaccinated females when compared with unvaccinated males of the same age. The interpretation of horizontal cross-sectional serological data and future research needs are discussed.

Adolescent↗

Nerve-induced remodeling of muscle basal lamina during synaptogenesis.

To identify mechanisms that regulate the deposition of the junctional basal lamina during synaptogenesis, immunocytochemical experiments were carried out on cultured nerve and muscle cells derived from Xenopus laevis embryos. In some experiments successive observations were made on individual muscle cells after pulse-labeling with a fluorescent monoclonal antibody specific for a basal lamina proteoglycan. In others, old and new proteoglycan molecules were differentially labeled with antibody conjugated to contrasting fluorochromes. These observations revealed that surface deposits of antibody-labeled proteoglycan remain morphologically stable for several days on developing muscle cells. Over the same period, however, new sites of proteoglycan accumulation formed that contained primarily those antigenic sites recently exposed at the cell surface. When muscle cells became innervated by cholinergic neurites, new proteoglycan accumulations were induced at the developing neuromuscular junctions, and these too were composed almost exclusively of recently deposited antigen. In older muscle cultures, where many cells possessed relatively high background concentrations of antigen over their surfaces, developing neuromuscular junctions initially showed a markedly reduced proteoglycan site-density compared with the adjacent, extrajunctional muscle surface. Much of this perineural region eventually became filled with dense, nerve induced proteoglycan plaques at later stages of synapse development. Motoneurons thus appear to have two, superficially paradoxical effects on muscle basal lamina organization. They first cause the removal of any existing, extrajunctional proteoglycan from the path of cell contact, and then induce the deposition of dense plaques of recently synthesized proteoglycan within the developing junctional basal lamina. This observation suggests that the proteolytic enzyme systems that have already been implicated in tissue remodeling may also contribute to the inductive interaction between nerve and muscle cells during synaptogenesis.

Animals↗

Aplastic and hypoplastic episodes in sickle cell disease and thalassaemia intermedia.

Aplastic and hypoplastic crises are well recognised complications of sickle cell disease. Recent evidence has shown that most of these crises are caused by parvovirus infection. Five cases of aplastic or hypoplastic crises in patients born and living in this country were studied. Three patients had clear evidence of parvovirus infection, while in two evidence of parvovirus infection was lacking. One patient had evidence of concurrent parvovirus and Mycoplasma pneumoniae infection. Recurrent crises may occur, and reticulocyte monitoring during infection in patients with chronic haemolytic states is therefore important.

Adolescent↗

Parvovirus infection associated with aplastic crisis in a patient with HEMPAS.

An aplastic crisis associated with parvovirus infection occurred in a patient suffering from hereditary erythrocytic multinuclearity associated with a positive acidified (Hams) test (HEMPAS). This case emphasises that any patient who has a shortened red cell survival is susceptible to an aplastic crisis induced by parvovirus.

Adult↗

Human serum parvovirus associated vasculitis.

A 48 year old man had a severe symmetrical arthritis of knee and ankle joints accompanied by an extensive purpuric rash of both legs and several areas of skin necrosis. No other system was clinically involved. Human serum parvovirus-specific IgM was present in a blood sample taken 2 weeks after the onset of the clinical illness indicating recent infection with this virus. The patient was treated with complete bed rest, and the application of saline soaks to both legs. He had a recurrence of the rash 5 weeks after onset, but otherwise made a complete recovery. Purpura with skin necrosis has not previously been reported in association with this virus.

Arthritis↗

Self-organization of ependyma in regenerating teleost spinal cord: evidence from serial section reconstructions.

Multiple ependymal structures have been observed in regenerating spinal cord of the teleost Apteronotus albifrons. Evidence is presented for two modes of formation of the secondary ependymas: budding off from the primary ependyma, and de novo origin of a tube-like ependymal structure within a group of undifferentiated cells. Serial sections of regenerated cord provide evidence that undifferentiated cells not in immediate contact with the main ependymal layer can organize and differentiate into an ependymal structure in the regenerating spinal cord. These findings suggest that a significant amount of morphological organization can take place independent of the normal developmental sequence and environment.

Animals↗

An erythema infectiosum-like illness caused by human parvovirus infection.

In the spring of 1980, an epidemic of an illness that resembled erythema infectiosum occurred in Manitoba, Canada. We initiated prospective epidemiologic, clinical, and microbiologic studies of this illness among elementary-school children and their families. Initial microbiologic studies failed to identify the cause of the exanthem. After a similar illness associated with serologic evidence of human parvovirus infection occurred in London, stored specimens of 12 patients with exanthem were investigated for parvovirus infection. Eleven patients had parvovirus-specific IgM antibody, as did two family contacts and a teacher with nonexanthematous illnesses, and two asymptomatic family members. None of 28 children with measles or rubella had serologic evidence of recent parvovirus infection. Human parvovirus was detected by DNA hybridization and immune electron microscopy in the serum of one patient who later had a rash and in one unaffected family contact. Parvovirus DNA was also detected in the pharyngeal specimen of the teacher who was ill but did not have a rash. We conclude that human parvovirus infection can be asymptomatic or cause a variety of clinical manifestations, including nonexanthematous illness and an illness resembling erythema infectiosum.

Adult↗

Isolation and characterization of CAB-63, a novel calcium-binding protein.

A novel calcium-binding protein named CAB-63 (formerly called calregulin) has been purified from bovine liver 100,000 X g supernatant. The purified protein has been characterized with respect to its physical, chemical, and calcium-binding properties. It has an apparent molecular weight of 63,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and 55,000 by sedimentation equilibrium centrifugation under nondenaturing conditions. It is an asymmetric molecule with a frictional coefficient of 1.69 and a Stokes radium of 44.2 A. Amino acid analysis has revealed 34.0% acidic residues, 14.0% basic residues, and 4.0% tryptophan. The acidic nature of the molecule is further confirmed by its isoelectric point of 4.65. In the presence of 3 mM MgCl2 and 150 mM KCl, CAB-63 binds 3.0 mol of calcium/mol of protein with an apparent Kd = 0.1 microM. Immunoblotting and Ouchterlony double-diffusion procedures have identified CAB-63 in a variety of bovine tissues. Immunocytochemical staining of both fibroblasts and cryotome-sectioned bovine liver further indicates that CAB-63 immunoreactivity is restricted to an elaborate system of perinuclear membranous vacuoles and cisternae indistinguishable from immunocytochemical staining of the endoplasmic reticulum. It is concluded that CAB-63 represents a major calcium-binding protein whose subcellular organization suggests a possible role in the function of the endoplasmic reticulum.

Amino Acids↗

Diagnosis of human parvovirus infection by dot-blot hybridization using cloned viral DNA.

The human parvovirus can be detected in serum by the immunological techniques of immune electron microscopy (IEM), counterimmunoelectrophoresis (CIE), and radioimmunoassay (RIA). A portion of the genome of this virus has been cloned in pAT153 and used as a 32P-labelled probe in dot-blot hybridization assays to detect parvovirus DNA in serum specimens. This test proved a highly sensitive means of detecting virus in microlitre volumes of serum, giving positive results for samples containing 0.5 pg viral DNA, equivalent to 10(4) virus particles. Unlike CIE and RIA the test is not affected by the presence of parvovirus-specific antibody in serum specimens, and has permitted virus to be detected in specimens obtained up to 11 days after the onset of clinical symptoms of aplastic crisis.

Anemia, Hemolytic↗

Retrograde labeling of regenerated electromotor neurons with HRP in a teleost fish, Sternarchus albifrons: relation to cell death.

Back-labeling of regenerated electromotor neurons in the teleost Sternarchus albifrons was performed to test the hypothesis that, in regenerated spinal cord, incorrectly located electromotor neurons are eliminated because their axons do not reach the correct target area (electric organ). In each cross section examined, all of the regenerated electromotor neurons ipsilateral to the implantation site were labeled with horseradish peroxidase, including those ectopic cells located at the edge of the cord, which are later eliminated by selective cell death. Retrograde labeling of these ectopic neurons demonstrates that their axons do extend into the correct target area (the regenerated electric organ). Thus total misdirection of the axons cannot be the cause of their subsequent cell death. We conclude that selective neuronal death in this system does not reflect the absence of axonal projection to the correct target area.

Afferent Pathways↗

Generation of electromotor neurons in Sternarchus albifrons: differences between normally growing and regenerating spinal cord.

This study examines the regulation of the number of electromotor neurons during postnatal growth of the spinal cord in the gymnotiform teleost Sternarchus albifrons. It specifically asks whether a large overproduction of electromotor neurons and a wave of cell death, similar to those occurring during spinal cord regeneration in this species, play a role in the on-going growth at the caudal tip of the normal spinal cord. Neurons are produced from ependymal precursors at the caudal end of the spinal cord during both normal growth in the adult and regeneration of the spinal cord in this species. Previous studies have demonstrated that during spinal cord regeneration after amputation of the tail in Sternarchus, there is an initial massive (up to fivefold) overproduction of electromotor neurons, followed by a wave of cell death which reduces the number of these neurons to the normal level. In the present study, transverse sections through the caudalmost spinal segment of normal adult Sternarchus were examined. Proceeding rostrally from the caudal tip of the cord, the number of electromotor neurons increases monotonically to reach the normal number at a site 4-5 mm rostral to the caudal tip. Neither a massive overproduction of electromotor neurons nor a wave of neuronal death are observed during on-going growth of the normal spinal cord. The mechanisms by which the neuronal number is modulated are therefore different in the on-going normal growth of spinal cord versus regeneration of spinal cord in this species.

Animals↗