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Biomedical subjects

D B Jones

Publications and source records attributed to D B Jones.

At least 19 recordsLinked to original sources
PubMed1992

A study of cell proliferation in formalin-fixed, wax-embedded bone marrow trephine biopsies using the monoclonal antibody PC10, reactive with proliferating cell nuclear antigen (PCNA).

We have investigated proliferation in bone marrow trephine biopsies from 32 patients with normal or abnormal haemopoiesis, using the monoclonal antibody PC10, which detects proliferating cell nuclear antigen (PCNA), together with immunohistochemical markers of haemopoietic cell lineage. PCNA immunostaining revealed the pattern of proliferation within individual haemopoietic lineages in normal marrow. Two unexpected observations were made: of erythroid cells, only pro-erythroblasts and occasional early normoblasts reacted, and positivity of megakaryocytes was unrelated to nuclear lobulation or CD61 expression. The pathological cases represented conditions in which haemopoiesis is increased (reactive hyperplasia, chronic granulocytic leukaemia, myeloproliferative and myelodysplastic syndromes, megaloblastic anaemia). Increases in the number, and disturbances of the spatial organization, of PCNA-expressing cells were present to a variable extent in all cases. Sheets of PCNA-positive megaloblastoid erythrocytes were frequently found in myelodysplastic and myeloproliferative tissue, associated with marked disturbances in the spatial organization of all haemopoietic lineages. Cases of megaloblastic anaemia due to vitamin B12/folate deficiency also demonstrated greatly increased erythroid PCNA expression, with positivity in some giant metamyelocytes. In addition to reflecting increased proliferation, elevated PCNA expression in some bone marrow pathologies may be due to altered kinetics of the protein induced by disturbances in growth factor production.

Autoantigens↗
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↗
PubMed1992

Cytogenetic and molecular studies of t(14;18) and t(14;19) in nodal and extranodal B-cell lymphoma.

We have examined 107 cases of B-cell lymphoma for the t(14;18) translocation, characteristically described in follicular lymphoma. B-Cell lymphomas of extranodal origin, and in particular malignancies derived from mucosa-associated lymphoid tissue (MALT), were compared with node-based lymphomas of follicular and diffuse morphology. Cytogenetic techniques were supplemented by molecular analysis using probes which recognize both the major and the minor breakpoint regions of the bcl-2 gene located on chromosome 18 (q21). t(14;18) was detected in 55 per cent of follicular and 27 per cent of diffuse B-cell lymphomas thought to be of follicle centre cell origin. Cytogenetics and molecular analysis proved equally effective in demonstrating the translocation. t(14;18) was not observed in the 36 extranodal lymphomas examined, of which 20 were characterized histologically as lymphomas of MALT, using either technique. In addition, 30 cases demonstrated only a germline band when probed with a bcl-3 probe specific for t(14;19), a translocation observed in chronic lymphocytic leukaemia (CLL). Cytogenetic abnormalities were detected in all cases of extranodal lymphoma, although no consistent abnormality was observed. Numerical abnormalities of chromosomes 3, 6, 16, and 18; structural abnormalities of chromosomes 2, 6, 8, and 9; and small marker chromosomes were frequently seen. This study provides data which suggest that different genetic events are involved in the development of lymphoma of MALT from those giving rise to follicle centre cell lymphomas.

Autoradiography↗
PubMed1992

Pigmented basal cell carcinoma: investigation of 70 cases.

BACKGROUND: Pigmented basal cell carcinoma (PBCC) is a clinical and histologic variant of BCC. OBJECTIVE: Our purpose was to identify the histologic subtypes of BCC that were most often associated with pigment and to determine whether this correlated with outcome after excision. METHODS: A series of PBCC was identified and the histologic subtype noted. Margins of all excisions were examined for residual tumor. These results were then compared with a series of nonpigmented BCCs. RESULTS: In a series of 1039 consecutive BCCs, 70 (6.7%) contained pigment. The histologic growth pattern most frequently associated with pigment was the nodular/micronodular pattern (12.4%) followed by the nodular (7.7%), superficial (7.2%), micronodular (4.0%), and the nodular/micronodular/infiltrative (3.4%) patterns. Margins were examined for evidence of residual tumor in the 40 cases that were excised. In only one case (2.5%) was the margin positive for tumor. This was statistically significant (p less than 0.05) compared with 388 excisions of nonpigmented BCCs with comparable growth patterns in which 69 (17.7%) showed positive margins. CONCLUSION: PBCC, as a clinical variant, is more frequently excised with adequate margins than are tumors of comparable histologic subtypes that do not contain pigment.

Biopsy↗
PubMed1992

Oncogenes in Hodgkin's disease.

The following manuscript reviews data presented at the Cologne meeting relating to oncogene expression in Hodgkin's disease. Presented data ranged from investigations of oncogene expression in cell lines, where transcripts of unique size were identified and lineage related expressions of transcription factors described to detailed cytogenetic investigations of fresh Hodgkin's biopsy tissue. Particular attention was centred on discrepancies in the described expression of t(14; 18) and the molecular demonstration of translocated bcl-2 breakpoints in Hodgkin's disease. A large volume of data was presented relating to the relative expression of bcl-2 breakpoints by either genomic hybridization or hybridization following DNA amplification, the expression of the bcl-2 protein or the defined cytogenetic presence of the translocation. Certain other cytogenetic abnormalities of interest in Hodgkin's disease were discussed.

Cell Line↗
PubMed1992

Alpha-1 anti-trypsin and CD30 expression occur in parallel in activated T cells.

We have performed an immunohistochemical study of immunoblastic T cell lymphoma and enteropathy-associated T cell lymphoma for alpha-1 anti-trypsin and CD30. Cytoplasmic staining for alpha 1 anti-trypsin is present in the malignant cells in both types of T cell neoplasm which also express CD30, a marker of lymphoid activation. Peripheral blood T lymphocytes on stimulation with mitogen also show granular cytoplasmic expression of alpha 1 anti-trypsin. Time course studies show that this parallels the expression of CD30. Alpha 1 anti-trypsin expression appears therefore to be associated with activation in T cells. Further studies of sub-fractionated T lymphocytes in vitro suggest that the expression of alpha 1 anti-trypsin on activation is not restricted to an individual lymphocyte subset.

Antigens, CD↗
PubMed1992

The expression of the EBV latent membrane protein (LMP-1) is independent of CD23 and bcl-2 in Reed-Sternberg cells in Hodgkin's disease.

A series of 33 cases of Hodgkin's disease was investigated for the presence of the EBV encoded latent gene product LMP-1 and of CD23 using immunohistochemical techniques. The expression of bcl-2 was examined in a subset of cases. LMP-1 was detected in the Reed-Sternberg cells in 15 cases. Although LMP-1 is known to upregulate CD23 and bcl-2, there was no correlation between the expression of LMP-1 and the detection of CD23 and bcl-2 in Reed-Sternberg cells.

Adolescent↗
PubMed1992

The effect of glycosylation trimming enzyme inhibitors on monoclonal antibody recognition of alpha-sialoglycoprotein epitopes.

The human erythrocyte membrane contains four sialoglycoproteins, denoted alpha, beta, gamma and delta (also known as glycophorins A, C, D and B respectively), of which alpha-sialoglycoprotein (alpha-SGP) is the most predominant species. The extracellular portion of alpha-SGP is heavily glycosylated with approximately 15 O-linked carbohydrate side-chains and a single N-linked group. We have used inhibitors of carbohydrate trimming enzymes to investigate the contribution of this single N-glycan moiety towards the recognition of a range of antibody binding sites on alpha-SGP. Two erythromyeloid cell lines, K562 and HEL, were cultured in the presence of these inhibitors and altered binding of antibodies to epitopes adjacent to the N-glycan was observed. Digoxigenin-coupled lectins were used to stain cytocentrifuge preparations and Western blots of cell lysates in order to confirm that modification of N-linked carbohydrate side-chains had been achieved. We suggest that the N-glycan side chain of alpha-SGP has a role in conferring conformational stability upon epitopes which lie in its vicinity.

1-Deoxynojirimycin↗
PubMed1992

Cell-stroma interactions in monocytopoiesis.

We have used immunohistochemistry to distinguish monocytes from early granulocyte precursors in trephine biopsies, in order to determine the distribution of monocytopoiesis within bone marrow. Developing granulocytes and monocytes have extensively overlapping immunophenotypes, but differential expression of calgranulin by monocytes and granulocytes during their maturation permitted the use of this antigen as a marker of bone marrow monocytes. In addition to morphologically normal bone marrow biopsies, in which monocyte numbers are relatively low, we studied pathological conditions in which either monocytopoiesis or granulopoiesis is selectively increased. By contrast with the highly zonal distribution of developing granulocytes, we found that monocytes were dispersed singly throughout the bone marrow. There was no evidence of preferential localisation of monocytes to particular stromal compartments. We hypothesise that developing monocytes are highly mobile within the bone marrow stroma and are relatively independent of physical stromal contacts for differentiation signals.

Bone Marrow↗
PubMed1992

An oral health survey of Head Start children in Alaska: oral health status, treatment needs, and cost of treatment.

The purpose of this study was to obtain information on the oral health status, treatment needs, and cost of treatment for Head Start children in Alaska. Twenty communities, representing five regions within the state, were selected for participation. The study consisted of three distinct parts: a caries status exam, a sociodemographic questionnaire, and a treatment needs examination. A total of 544 children between three and five years old were examined. The mean dmft and dmfs scores were 3.91 and 8.73, respectively. When stratified by race, the Alaska Native children had significantly higher mean dmft and dmfs scores. When stratified by community of residence, those children residing in the rural communities had higher rates of dental caries than the urban children. Forty-five percent of the total sample was in need of dental restorative treatment, excluding examinations, radiographs, and preventive services. The proportion of rural children needing care was much higher than the urban children (59% vs 27%). On average, each urban child needed treatment on 0.7 teeth, while each rural child needed treatment on 2.8 teeth. When all treatment factors including sedation and transportation costs are considered, the potential cost of treatment for the 1,475 children enrolled in the Alaska Head Start programs was $601,624.

Age Factors↗
PubMed1992

CD43 expression in B cell lymphoma.

AIMS: To determine the expression of CD43 in frozen sections in a range of B cell lymphomas. METHODS: The monoclonal antibody WR14, clustered provisionally in the Fourth Leucocyte Typing Workshop as a CD43 reagent, was investigated by epitope blocking studies on formalin fixed reactive lymph node tissue, using the established CD43 antibody MT1, to validate its use as a CD43 reagent. CD43 expression was studied in 131 immunophenotypically defined B cell lymphomas, including lymphocytic lymphoma (Lc, n = 13), centrocytic lymphoma (Cc, n = 14), and a range of follicle centre cell lymphomas (FCC) including centroblastic/centrocytic follicular (CbCcF, n = 48), centroblastic diffuse (CbD, n = 39), centroblastic/centrocytic diffuse (CbCcD, n = 4), centroblastic follicular and diffuse (Cb FD, n = 3) and centroblastic/centrocytic follicular and diffuse (CbCc FD, n = 1). Nine lymphomas of mucosa associated lymphoid tissue (MALT) were also examined. RESULTS: Epitope blocking studies showed that WR14 is a CD43 reagent that binds to an epitope identical with or close to that recognised by MT1. Eleven of 13 (84%) cases of Lc and 11 of 14 (78%) cases of Cc expressed CD43; 87 of 95 (91%) cases of FCC did not. All eight low grade lymphomas of MALT were negative. One high grade lymphoma, transformed from a low grade MALT lymphoma, was positive for CD43. The expression of CD43 by tumours of B cell lineage was associated with the expression of CD5 (p < 0.001) although either antigen could occasionally be found in the absence of the other. CONCLUSION: CD43 reagents can be used in conjunction with CD5 antibodies for the immunophenotypic discrimination of follicle centre cell lymphomas from non-follicle centre cell lymphomas.

Antibodies, Monoclonal↗
PubMed1992

Alpha-1 antitrypsin gene exon use in stimulated lymphocytes.

AIMS: To investigate the expression of mRNA transcripts containing exon A or B in lymphocyte cultures. METHODS: An in situ hybridisation technique, using synthetic, biotinylated oligonucleotide probes was deployed to allow the demonstration of exon A, exon B, or the normal hepatocyte message containing exon C. RESULTS: Lymphocytes used the same alternative splicing technique as monocytes in the generation of their alpha-1 antitrypsin message. They also provided data on the frequency of exon A and B expression in cells from different subjects. Most circulating granulocytes failed to show the alpha-1 antitrypsin message, suggesting that this protein is synthesised in the marrow and represents a stored protein component in polymorph and circulating nuclear lymphocytes. CONCLUSIONS: In situ hybridisation is a sensitive technique for the detection of individual gene exon use in cell populations. Lymphocytes show the same promoter use as that described for monocytes.

Antisense Elements (Genetics)↗
PubMed1992

Vascular endothelial cell antibodies in diabetic patients. Association with diabetic retinopathy.

OBJECTIVE: To determine the incidence of antiendothelial cell antibodies in diabetic patients with and without retinopathy. RESEARCH DESIGN AND METHODS: The study consisted of 70 insulin-dependent diabetic (IDDM) subjects, 36 non-insulin-dependent diabetic (NIDDM) subjects, and 40 nondiabetic control subjects. Blood samples were obtained from diabetic patients and control subjects and patients with background and proliferative retinopathy were identified. RESULTS: Vascular endothelial cell (VEC) antibodies were examined in the sera of 36 NIDDM subjects, 70 IDDM subjects, and 40 nondiabetic control subjects by indirect immunofluorescence. VEC antibodies were present in 5 of 40 (12%) control subjects, 7 of 23 (30%) newly diagnosed IDDM patients, 6 of 17 (35%) IDDM patients without retinopathy, 12 of 18 (67%) IDDM patients with background retinopathy (P less than 0.05), and 9 of 12 (75%) IDDM patients with proliferative retinopathy (P less than 0.01). Three of 13 (23%) NIDDM patients with retinopathy and 6 of 23 (26%) without retinopathy were VEC antibody positive. No associations were observed between the presence of VEC antibodies and either the quality of glycemic control or the duration of diabetes. A significant association between VEC antibodies and large-vessel disease was found in IDDM patients with retinopathy (P less than 0.05). CONCLUSIONS: Antibodies directed against vascular endothelial cells may play a role in the development of microvascular, and possibly macrovascular, disease in diabetes.

Adult↗
PubMed1992

Effects of exogenous emulsifiers and fat sources on nutrient digestibility, serum lipids, and growth performance in weanling pigs.

Three experiments were conducted to determine whether emulsifiers improve utilization of fat from diets for early-weaned pigs. In Exp. 1, 96 weanling pigs (17 d old) were used in metabolism cages, with main effects of fat source (soybean oil, tallow, lard, and coconut oil) and emulsifier treatment (no emulsifier, lecithin, and lysolecithin as 10% of the added fat). Soybean oil and coconut oil were more digestible than tallow and lard (P < .001). Tallow was more digestible when lecithin and lysolecithin were added (P < .007), and pigs fed lecithin had lower serum triglycerides and cholesterol than pigs fed lysolecithin (P < .03). In Exp. 2, 270 weanling pigs (21 d old) were used in a growth assay. Treatments were 1) control diet; 2) Diet 1 with soybean oil; 3) Diet 1 with tallow; 4, 5, and 6) Diet 3 with lecithin replacing 5, 10, and 30% of the tallow, respectively; and 7, 8, and 9) Diet 3 with lysolecithin replacing 5, 10, and 30% of the tallow, respectively. At d 14 of the experiment, digestibility of tallow was improved more by lecithin than lysolecithin (P < .008). For the total experiment (d 0 to 35), the control pigs had poorer gain:feed ratio than did the pigs fed the fat sources (P < .002). In Exp. 3, 420 weanling pigs (21 d old) were used. Treatments were 1) control diet with soybean oil; 2) Diet 1 with tallow; and 3, 4, and 5) Diet 2 with 10% of the added fat as soybean oil, lecithin, or monoglyceride, respectively. Adding soybean oil, lecithin, and monoglyceride to tallow increased digestibility of total fat (P < .07). From d 0 to 14, pigs fed soybean oil gained weight faster than pigs fed the other treatments (P < .06), and pigs fed tallow without emulsifiers had the lowest ADG. Considering all experiments, addition of emulsifiers increased digestibility of nutrients but had minimal effect on growth performance.

Animal Feed↗
PubMed1992

Criteria for the definition of Epstein-Barr virus association in Hodgkin's disease.

There is a clear association between the Epstein-Barr virus (EBV) and Hodgkin's disease (HD). EBV is not, however, detectable within the affected tissues of all cases. The proportion of positive cases varies from 15-79% depending on the assay used to detect EBV. The techniques utilised vary not only in sensitivity but in their ability to detect viral DNA, RNA, or protein and in their ability to demonstrate the cellular localisation of the virus. Thus, the biological significance of a positive result will vary depending on the method of analysis. In the present study, four different methods of detecting EBV were compared. RNA in situ hybridization was found to be the most practical method of detecting EBV in tumour cells. Using this assay EBV was detected in the Reed-Sternberg cells of 33% and 45% of the two series of HD cases examined in this study. We believe that these cases should be considered EBV-associated.

Adolescent↗
PubMed1991

X-linked recessive nephrolithiasis with renal failure.

BACKGROUND AND METHODS: Nephrolithiasis may occur as a consequence of a number of hereditary disorders. We describe a large kindred from northern New York with hereditary nephrolithiasis accompanied by urinary concentrating defects, nephrocalcinosis, renal insufficiency, and renal wasting of potassium, phosphate, calcium, and uric acid. The pattern of inheritance was established by examining the patients and their records and interviewing family members. Selected members of the family were evaluated in detail, with measurements of erythrocyte cation fluxes and carbonic anhydrase (carbonate dehydratase) activity. RESULTS: The kindred consisted of 162 family members from six generations. All nine affected persons were male and appeared to have inherited the disease from their mothers. No affected man transmitted the gene to a son, but the daughters of affected men were carriers. The patients presented in childhood with calcium nephrolithiasis and proteinuria, with progression to nephrocalcinosis, urinary concentrating defects, and renal insufficiency. Renal biopsies revealed tubular atrophy, interstitial fibrosis, and glomerulosclerosis; the characteristic features of other forms of hereditary nephritis were absent. Abnormalities in the renal excretion of calcium, phosphate, potassium, and uric acid were found only in the adult members of the kindred, although renal biopsies were abnormal even in younger members. In one patient who has had a renal transplant for seven years, the disease has not recurred. CONCLUSIONS: This kindred manifested an X-linked recessive nephrolithiasis with renal failure, a new form of hereditary renal disease. Most of the identifiable physiologic abnormalities occurred after the development of nephrolithiasis and renal insufficiency and may not be of pathogenetic importance.

Adult↗
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↗