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Biomedical subjects

W M Howell

Publications and source records attributed to W M Howell.

At least 19 recordsLinked to original sources
PubMed1992

T-cell receptor variable (V) gene usage by lymphoid populations in T-cell lymphoma.

A panel of monoclonal antibodies specific for TcR V gene families was used to study TcR V region expression in 28 cases of malignant and reactive T-cell expansions including four cases of mixed cellularity Hodgkin's disease (HD) and five reactive cases. TcR V beta 5 gene products were represented in three cases of lymphoblastic malignancy (V beta 5.1, V beta 5.2) and two cases of peripheral T-cell lymphoma (PTCL) (V beta 5.1). In the PTCL cases, the expanded family was found in the absence of clonal TcR gene rearrangements and in one of these cases with Ig JH and Ck clonal gene rearrangements consistent with the presence of a phenotypically and histologically undetectable clonal B-cell population. In a third PTCL case not investigated for genotype, the TCR V alpha 12 family was overrepresented. Expanded TcR V alpha 2 and V beta 5.1 families were identified in HD and V beta 8 and V beta 5.2/V beta 5.3 families in a reactive lymph node and CD3 and CD8-positive blood lymphocytosis respectively. Further study of PTCL and related entities are needed to establish whether expanded TcR families are common in those cases that fail to exhibit clonal TcR gene rearrangement.

Antibodies, Monoclonal↗
PubMed1991

Is adult-onset coeliac disease due to a low-grade lymphoma of intraepithelial T lymphocytes?

Enteropathy-associated T-cell lymphoma commonly presents with malabsorption, and debate continues as to whether adult-onset coeliac disease (CD) is itself a form of low-grade lymphoma. A 59-year-old man with adult-onset CD required resection of a segment of oedematous jejunum. Histological examination of this tissue revealed an intense intraepithelial lymphocytosis. Immunophenotypic (CD3-, CD4-, CD8-, CD34-, and CD45 RO-) and cytogenetic (deletion of the Y chromosome and chromosome 9) abnormalities were found, together with monoclonal T-cell-receptor gene rearrangements. Some patients with adult-onset CD may have low-grade lymphoma from the outset of their illness.

Biopsy↗
PubMed1991

Variable X-chromosome DNA methylation patterns detected with probe M27 beta in a series of lymphoid and myeloid malignancies.

In this study the X chromosome probe M27 beta was used to investigate DNA methylation at the DXS255 locus and hence X inactivation status and determination of tumour clonality in blood, bone marrow and biopsy tissue involved with morphologically and phenotypically defined lymphoid and myeloid disease from 14 female patients along with uninvolved bone marrow from two control individuals. Thirteen out of 16 individuals (81%) were restriction fragment length polymorphism (RFLP) heterozygous for DXS255. DNA methylation status could not be assessed in the three DXS255 homozygous individuals. In eight DXS255 heterozygous individuals clonality was clearly demonstrated using M27 beta and in six of these cases independent analysis using T cell receptor (TcR) and immunoglobulin (Ig) gene probes confirmed the presence of clonal tumour cell populations. In the two controls, polyclonality was inferred from M27 beta probe analysis. In the remaining three cases (all acute lymphoblastic leukaemia (ALL)) both DXS255 X chromosome sequences appeared to be methylated. Clonality in these cases was demonstrated by TcR or Ig monoclonal gene rearrangements. These data demonstrate the value of the M27 beta probe for determining tumour clonality in a number of cases with lymphoid and myeloid disease but indicate that there may not always be a complete correlation between DNA methylation. X inactivation status and tumour clonality in certain lymphoid neoplasms, restricting the use of this probe in clonality studies. Correlations between DNA methylation, X inactivation status and stage of normal and neoplastic T and B cell development require further investigation.

Antigens, Neoplasm↗
PubMed1991

Detection of IL-2 at mRNA and protein levels in synovial infiltrates from inflammatory arthropathies using biotinylated oligonucleotide probes in situ.

A non-radioactive in situ hybridization method for IL-2 mRNA detection based on the use of four biotinylated oligonucleotide probes, plus appropriate positive and negative control probes was developed and applied to synovial surgical and needle biopsies from rheumatoid arthritis (RA), spondyloarthropathy (SpA), psoriatic arthritis (PsA) and juvenile chronic arthritis (JCA) patients. In eight surgical biopsies (six RA, one SpA, one PsA) this non-radioactive system showed similar sensitivity to that of a previously described 32P-labelled probe system, and in addition detected IL-2 mRNA in five out of seven biopsies from SpA and PsA patients and in two out of two JCA needle biopsies. IL-2 mRNA was found in the absence of IL-2 protein in RA biopsies (six surgical, 12 needle), but variable amounts of IL-2 protein were detected in six out of seven needle biopsies from SpA, PsA and JCA patients, where CD3+ lymphoid infiltrates were present. These data suggest differences in IL-2 regulation and expression in RA and non-RA inflammatory arthropathies.

Adolescent↗
PubMed1991

No association between susceptibility to multiple sclerosis and HLA-DPB1 alleles in the French Canadian population.

HLA-DPB1 typing was performed using polymerase chain reaction DNA amplification and sequence-specific oligonucleotide probing (PCR-SSOP) which permitted identification of 17 distinct DPB alleles using 15 oligonucleotide probes. The accuracy of this approach was confirmed in an initial study of 26 human B-lymphoblastoid cell lines which demonstrated close agreement between PCR-SSOP and PLT assigned types. A cohort of 47 adult French Canadians was then studied to provide an estimate of DPB1 allelic frequencies in an ethnically homogeneous population. DPB1*0401 was the most frequent phenotype (61.5%) and only DPB1*0101, 0301 and 0402 were also present at frequencies greater than 10%. HLA-DPw4 has been reported to be associated with multiple sclerosis (MS) but our PCR-SSOP analysis of 52 French Canadian MS patients showed no association with either the DPB1*0401 or DPB1*0402 splits of DPw4 or with any other DPB1 allele.

Alleles↗
PubMed1991

HLA DPB1 alleles and susceptibility to rheumatoid arthritis.

HLA-DPB1 genotypic and phenotypic frequencies were investigated in a series of 35 adult rheumatoid arthritis (RA) patients and 42 controls. No significant associations between DPB1 alleles and susceptibility to RA were demonstrated, although some non-significant differences in DPB1*0301 and 0401 allele frequencies between patients and controls were observed.

Alleles↗
PubMed1991

An investigation of T-cell subset phenotype and function in the rheumatoid synovium using in situ hybridization for IL-2 mRNA.

Cryostat sections of synovial biopsy tissue from patients with active rheumatoid arthritis (RA), spondyloarthritis (SpA) and osteoarthritis (OA) have been investigated for interleukin-2 (IL-2) mRNA and protein production. In situ hybridization using 32P-labelled oligonucleotide probes based on IL-2 gene sequences coded by exon 1 and exon 3 of the IL-2 gene revealed IL-2 mRNA over lymphoid aggregates in RA and SpA tissue. No IL-2 mRNA was detected in OA tissue and reflected the absence of lymphoid infiltrates in these tissues. Total mRNA, as detected by a 32P oligo dT probe, was found in all tissue examined. IL-2 protein product was detected by monoclonal antibody staining in SpA but not in RA or OA tissue. This is the first report of in situ studies of lymphoid function in the microenvironment of the RA synovium. Whether these data reflect the function of normal CD3+ CD4+ CD45RO+ T-cell subsets in the diseased joint remains to be resolved.

Aged↗
PubMed1979

Chromosome core structure revealed by silver staining.

Chromosomes were subjected to either prolonged hypotonic solution pretreatment or aging. Both conditions greatly loosened and dispersed the overlying epichromatin from the central chromosome core structure. This was followed by silver staining and examination with bright-field microscopy. The chromosome core selectively reduced the silver and stained black while the surrounding epichromatin stained yellow. A single core was seen extending the length of each chromatid. Nucleolus organizer regions appeared to be attached to the core, while kinetochores seemed to be specialized regions of the core itself. Cytochemical tests indicated that the core component(s) responsible for silver staining was non-histone protein(s).

Adenocarcinoma↗
PubMed1978

A rapid technique for producing silver-stained nucleolus organizer regions and trypsin-giemsa bands on human chromosomes.

A simple and rapid technique is described whereby the nucleolus organizer regions (NORs) of human chromosomes can be differentially stained with silver. This staining is followed by trypsin-Giemsa banding on the same metaphase chromosomes. The metaphases simultaneously exhibit silver-stained NORs and G bands, allowing for the unequivocal identification of all chromosomes and greatly facilitating studies involving the NOR-bearing acrocentrics.

Azure Stains↗
PubMed1978

Silver stain reveals nucleolus organizer regions on a satellited Yq chromosome.

Chromosomes from a patient with a satellited Yq were stained with a silver procedure that differentially stains nucleolus organizer regions. The Yqs stained heavily in all cells examined, indicating the presence of ribosomal cistrons at this region. The Yqs also entered into satellite associations with the D and G group chromosomes at a frequency greater than would be expected through chance.

Azure Stains↗
PubMed1977

Visualization of centriole-bodies using silver stain.

Duplicate staining of human metaphase chromosomes, first with Giemsa followed by silver, revealed the presence of two small silver-stained bodies not seen in the Giemsa stained metaphases. Similar bodies were subsequently found in the metaphases of several animal groups. The size, structure, spatial relationships to the nucleus, behavior throughout the cell cycle, and apparent universal presence of these bodies suggest that they are either centrioles or associated centriolar structures. These centriole-bodies can be seen throughout the cell cycle, even in hypotonically spread C-metaphase chromosome plates. The silver stain procedure allows enough resolution to distinguish parent and daughter centriole-bodies at interphase, thus permitting visualization of the replication, maturation and separation stages of these bodies with the light microscope.

Animals↗
PubMed1977

Visualization of ribosomal gene activity: silver stains proteins associated with rRNA transcribed from oocyte chromosomes.

Cricket oocyte chromosomes were stained with silver at pachytene when certain chromosome regions are active in rDNA amplification and rRNA transcription. The silver preferentially stained the known locations of 18S + 28S ribosomal cistrons. Cytochemical tests revealed that the silver binds neither to the rDNA nor transcribed rRNA, but rather to proteins which rapidly associate with the freshly-transcribed rRNA. As rRNA transcription proceeds, the quantity of silver stainable proteins progressively increases. The silver procedure can be used to visualize gene activity at the rDNA sites with conventional light microscopy.

Animals↗