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Biomedical subjects

W May

Publications and source records attributed to W May.

At least 37 records · Page 2Linked to original sources

Human lymphocyte-specific pp52 gene is a member of a highly conserved dispersed family.

For a better understanding of genes that potentially function in B lymphocyte cell signaling, we isolated the human genomic counterpart of the murine pp52 or LSP1 gene. We unexpectedly found that the human pp52 gene is one of four closely related loci. Representative cosmids from each of the four family members were isolated and chromosomally localized by fluorescence in situ hybridization. Nucleotide sequence was obtained from an exon common to each locus and demonstrated very close similarity among all four loci. Two of the four loci harbored dysfunctional frameshift mutations or premature translation stop sites. The exon of one locus was flanked by an 80-bp perfect inverted repeat, suggesting that it may have originated through a looped intermediate DNA structure. Through a series of cDNA hybridization studies and nucleotide sequence analyses we were able to unambiguously link the lymphocyte-expressed gene to the locus mapped to chromosome 11p15.5. This same chromosomal band has been involved in tumor-related chromosomal translocations found in chronic lymphocytic leukemia.

Animals↗

Isolation and chromosomal mapping of the human immunoglobulin-associated B29 gene (IGB).

The B29 gene encodes a B-cell-specific membrane protein in the immunoglobulin antigen receptor complex. B29 is a crucial member of this receptor complex and is believed to function as an effector of signal transduction in a manner analogous to that of the CD3 components of the T cell antigen receptor. We have isolated a full-length human B29 cDNA clone by using a murine B29 cDNA probe. We show that there is an extremely high degree of evolutionary conservation between the human and mouse proteins, particularly in the transmembrane and intracytoplasmic regions, where the identity is 96%. In addition, the intracytoplasmic region in both proteins contains an identical peptide motif that is present in a number of molecules involved in lymphocyte activation. Genomic Southern blot analysis of human cell lines hybridized with both murine and human B29 cDNAs gives patterns consistent with a single-copy gene occupying a small region of the genomic sequence. Using human B29 cosmid DNA, we have localized the B29 gene to human chromosome 17q23 via fluorescence in situ hybridization. B29 is the first gene localized to this area of the genome. Interestingly, a subset of human B cell chronic lymphocytic leukemias (CLL) has translocations in this locus on chromosome 17.

Amino Acid Sequence↗

Early childhood hepatocerebral degeneration misdiagnosed as valproate hepatotoxicity.

Four unrelated children were thought to have valproate-associated hepatotoxicity. They presented with recurrent partial secondarily generalized status epilepticus and epilepsia partialis continua followed by mental and motor regression. Despite treatment with multiple antiepileptic medications, they continued to have seizures. After initiation of valproic acid (VPA), all 4 manifested liver failure within 3 months. Two of these children each had 1 sibling who was not exposed to VPA, but who developed the same clinical picture including liver failure. At the time of autopsy, all 6 children had similar neuropathological findings with focal areas of spongiosis and neuronal loss, diffuse gliosis, and Alzheimer type II cells. One VPA-treated patient underwent a successful liver transplantation only to die from relentlessly progressive neurological deterioration. We propose that many of the reported patients with VPA-associated hepatotoxicity represent undiagnosed patients with early childhood hepatocerebral degeneration, the Huttenlocher variant of Alpers' syndrome. This disease manifests by obstinate partial seizures, recurrent partial secondarily generalized status epilepticus, epilepsia partialis continua, psychomotor deterioration, and hepatic dysfunction that is exacerbated by VPA administration. The accelerated demise from liver failure in the nontransplanted patients before the central nervous system pathology fully evolves makes the diagnosis of this rare condition difficult. The occurrence of disease in the unexposed siblings suggests recessive inheritance.

Brain↗

Evaluation of automated urinary iodine methods: problems of interfering substances identified.

We evaluated automated methods for measurement of urinary iodine (UI) over a range expected in iodine-replete and iodine-deficient populations. Results obtained with Technicon AutoAnalyzer II systems, based on either dialysis or acid digestion, were compared with those obtained by a manual alkaline ashing technique. Results of automated dialysis were consistently higher than those obtained by the other methods. The apparently higher concentrations of UI we measured were due to interfering substances crossing the dialysis membrane and participating in the catalytic reaction. Thiocyanate (SCN) was one endogenous substance contributing to the increased measurement of UI. For urinary SCN concentrations of 5 to 15 mg/L, the amount of overestimation in the UI measurement attributable to SCN ranged from 21.8 to 61 micrograms/L. However, SCN may account for only 40-50% of the apparent increase in UI. In samples with lower UI (less than 50 micrograms/L), interfering substances produced a 100% error in results. We conclude that the automated dialysis system should not be used to assess iodine-deficient populations. This leaves a major dilemma for researchers wanting to assess the iodine status of populations, because the automated digestion method is no longer commercially available.

Adult↗

Hepatic microsomal enzyme induction and adrenal crisis due to o,p'DDD therapy for metastatic adrenocortical carcinoma.

Two cases are described in which metastatic adrenocortical carcinoma associated with Cushing's syndrome was treated with mitotane (o,p'DDD). The first patient had initially been treated by bilateral adrenalectomy and, whilst responding to mitotane biochemically and by remission of metastases, experienced repeated episodes of adrenal crisis requiring a substantial increase in steroid therapy. The second patient failed to respond to the drug, but evidence of hepatic enzyme induction was noted during its administration. It is suggested that hepatic microsomal enzyme induction can occur in association with treatment with mitotane and that this can lead to an increased destruction of exogenous steroid with clinical consequences.

Addison Disease↗

AIDS and related conditions. One year's experience in St. Vincent's Hospital, Sydney.

Fifty-six patients were referred in 1983 for assessment in connection with AIDS and related disorders. Clinical and immunological classification of patients was carried out according to the NHMRC criteria. The presence of antibodies to an AIDS-associated retrovirus (ARV) was determined in some patients. Of the 32 patients who could be categorized, three patients had AIDS, and all three had serum antibodies to ARV. Fifteen patients had lymphadenopathy syndrome with impaired T-cell immunity. Ten of 12 patients tested had antibodies to ARV. Symptomatic illnesses resembling lymphadenopathy syndrome, but without immune defects, occurred in nine patients. By contrast, five patients who had no symptoms had impaired immunity, and in seven patients no clinical and immunological abnormalities were found. The classification proposed by the NHMRC was found to be useful in delineating several major clinical and immunological patterns of response to infection with the AIDS-associated retrovirus.

Acquired Immunodeficiency Syndrome↗

Contact tracing in the acquired immune deficiency syndrome (AIDS). Evidence for transmission of virus and disease by an asymptomatic carrier.

The sexual contacts of a patient with acquired immune deficiency syndrome were traced, and clinical, immunological, and serological evidence was obtained and evaluated. It was determined that the patient acquired the disease from a homosexual man who had no symptoms, but in whom laboratory evidence of immunodeficiency and serological evidence of exposure to the AIDS-associated retrovirus was found.

Acquired Immunodeficiency Syndrome↗

Preparation and properties of immobilized rubredoxin.

Rubredoxin, one of the three protein components of the epoxidation/hydroxylation system of Pseudomonas oleovorans was immobilized by attachment to CNBr-activated agarose (Sepharose 4B). Since this represents the first reported example of the preparation of a water-insoluble derivative of an enzyme of this type, the electron transfer and physical properties of the conjugate were examined in order to allow comparison with those of the soluble enzyme. Immobilized rubredoxin exhibits all of the major spectral properties of the soluble enzyme above 300 nm, but some distortion in the 280 nm abosrbance band was observed. The immobilized enzyme accepts electrons from dithionite or form NADPH in the presence of spinach ferredoxin-NADP reductase, and upon reduction the visible absorbance is bleached. Immobilized rubredoxin mediates the reduction of cytochrome c in the presence of NADPH and spinach reductase, although it is less efficient in this role than soluble rubredoxin. The oxidation-reduction potential of immobilized rubredoxin was determined and found to be similar to that of the soluble enzyme. In the presence of 2.5 m guanidine HCL, the immobilized enzyme is considerably more stable than soluble rubredoxin toward denaturation. After anaerobic reduction, iron was readily removed from immobilized rubredoxin by washing in 0.5 m Tris base, PH 9.5 containing 0.07 M mercaptoethanol, and the resulting immobilized apoenzyme could then be reconstituted to give back a conjugate with the original iron content, as judged from its absorbance at 497 NM. Reptition of the entire reduction-dissociation-reconstitution cycle gave the same results as were obtained after the initial reconstitution.

Anaerobiosis↗