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Biomedical subjects

J Ford

Publications and source records attributed to J Ford.

At least 145 records · Page 8Linked to original sources
PubMed1990

Investigation of spontaneously aborted concepti for microbial DNA: investigation for cytomegalovirus DNA using polymerase chain reaction.

Karyotypic analysis of concepti spontaneously aborted in the first trimester shows approximately 50% of these concepti contain abnormal chromosomes. In order to determine whether cytomegalovirus (CMV) infection may play a role in the early loss of pregnancies with either normal or abnormal chromosomes, we have developed an assay to amplify CMV DNA in DNA extracts from spontaneously aborted concepti using the polymerase chain reaction (PCR). Using PCR, we were unable to detect CMV DNA in any of 350 spontaneously aborted concepti. Viral cultures were also negative when 36 of these were tested. Our results suggest that CMV infection is an unlikely cause of pregnancy loss in the first trimester of pregnancy.

Abortion, Spontaneous↗
PubMed1990

Characterization of an interleukin-2 dependent human leukemic cell line, PER-315, with an immature T cell phenotype which does not express the tac antigen.

Cell line PER-315 was established from a bone marrow sample of a 5-year-old boy diagnosed with acute lymphoblastic leukemia (ALL) of T cell lineage. PER-315 cells express the surface markers present on immature thymocytes, express cytoplasmic CD3, and their growth is dependent on interleukin-2 (IL-2). Hence, this cell line represents a new type of precursor T-ALL, which is IL-2 dependent. Assessment of the T cell receptor rearrangements confirmed the clonal origin of cell line PER-315, and comparison with the patient's leukemia cells revealed an identical pattern. PER-315 cells show strong cytotoxicity against cell lines K562, Daudi, and Molt-4. They do not express the Tac antigen, but bind IL-2 with a Kd of 650 pM. Since PER-315 cells represent immature thymocytes, this new cell line may provide a model to further investigate the IL-2 receptor structure present at this stage of T cell differentiation.

Antigens, Neoplasm↗
PubMed1989

Development of resistance to 1-beta-D-arabinofuranosylcytosine after high-dose treatment in childhood lymphoblastic leukemia: analysis of resistance mechanism in established cell lines.

Cell lines PER-163 and PER-164 are derived from a patient with acute lymphoblastic leukemia who developed resistance to 1-beta-D-arabinofuranosylcytosine (ara-C) after high-dose (HD) therapy. Both lines are highly resistant to ara-C and have maintained stable resistance for more than 18 mo. The resistance in PER-164 cells is the result of a selection process in vivo only, while PER-163 cells have in addition been exposed to ara-C in culture. Comparison with cell line PER-145, which is sensitive to ara-C and was established from the same patient before HDara-C therapy, revealed no differences with respect to surface markers, morphology, cytochemical stains, or requirements for growth in vitro. The leukemic origin of the three cell lines is indicated by the close similarities of all three cell lines to the patient's fresh cells. The analysis of the two resistant cell lines shows that resistance to ara-C is not due to lower ara-C transport capacity nor to cytokinetic reasons, since the percentage of cells in S-phase is similar in all three cell lines. In addition, the resistant cell lines do not show any increased cytidine deaminase activity. PER-164 cells show a markedly reduced deoxycytidine kinase activity, 4.8 nmol/h/mg of protein, compared to PER-145 cells with an enzyme activity of 21.48 nmol/h/mg of protein. In PER-163 cells, no deoxycytidine kinase activity could be detected. Furthermore, the two resistant cell lines show significantly different dCTP levels. The sensitive PER-145 cells generated 97.9 pmol of 1-beta-D-arabinofuranosylcytosine triphosphate (ara-CTP)/10(7) cells during a 45-min incubation period in the presence of 10(-6) M ara-C. This contrasts with 0.16 and 12 pmol of ara-CTP/10(7) cells for PER-163 and PER-164 cells, respectively. These investigations suggest that cell phenotypes with distinct features can be generated after HDara-C treatment and that decreased deoxycytidine kinase activity appears to be one of the major mechanisms of resistance.

Arabinofuranosylcytosine Triphosphate↗
PubMed1989

Substance abuse/mental illness: diagnostic issues.

"Dual diagnoses" of substance abuse and mental illness disorders are common both in psychiatric and substance abuse treatment settings. Recent studies have demonstrated that specific diagnostic categories of mental illness have implications for treatment outcomes of dually disordered patients, but a diagnostic standard has not emerged. The present study compared lay-administered DIS diagnoses with clinical diagnoses of patients in a state hospital treatment program for "dual diagnoses" patients. Categories of DIS diagnoses showed weak association with categories of clinical diagnoses. Several frequent DIS diagnoses were not made clinically and vice versa. Implications for choice of diagnostic instruments to use with this patient population are discussed, as is the potential value of structured assessments in supplementing clinical data.

Adolescent↗
PubMed1989

Establishment and characterization of a childhood T-cell acute lymphoblastic leukemia cell line, PER-255, with chromosome abnormalities involving 7q32-34 in association with T-cell receptor-beta gene rearrangement.

A human leukemia cell line, PER-255, was established from the bone marrow of a 5-year-old boy with features typical of lymphomatous T-acute lymphoblastic leukemia (T-ALL). The leukemic origin of cell line PER-255 is indicated by its cytochemical and immunologic similarity to the patient's fresh leukemic cells, which correspond to immature cortical thymocytes. Southern blot analysis showed that the IgJH genes were in germline configuration, whereas both alleles of the T-cell receptor-beta (TCR-beta) gene were rearranged in PER-255 cells, with identical rearrangements present in the patient's leukemic cells. Cytogenetic analysis of the cell line revealed a single abnormal clone with the karyotype 46,XY,t(7;10)(q32-34;q24),t(9;12) (p22;p12-13). Reciprocal translocations involving chromosome bands 7q32-36, containing the gene for the TCR-beta chain, have been reported for a number of tumors of T-cell origin. Translocations involving the 7q32-36 region appear to be nonrandomly associated with childhood T-ALL, whereas abnormalities of 9p and 12p have been reported to be nonrandomly involved in ALL but not specifically associated with the T-cell phenotype.

Child, Preschool↗
PubMed1989

Progressive resistance to doxorubicin in mouse leukemia L1210 cells with multidrug resistance phenotype: reductions in drug-induced topoisomerase II-mediated DNA cleavage.

Cells selected for resistance to doxorubicin (DOX) express the multidrug resistance (MDR) phenotype, and resistance has been suggested to be due primarily to enhanced cellular efflux of drug. A progressively DOX-resistant (10- and 40-fold) L1210 mouse leukemia model system, which does not exhibit enhanced DOX efflux as a primary mechanism of resistance, was found to display the MDR phenotype, based on overexpression of P-glycoprotein in western blots and cross-resistance to vinca alkaloids. Cross-resistance to another topoisomerase II inhibitor, etoposide (VP-16), was similar to that of DOX (10- and 40-fold), whereas resistance to N-[4-(9-acridinylamino)-3-methoxyphenyl]methanesulfonamide (m-AMSA) was 5-fold lower. In contrast, no cross-resistance to camptothecin, an inhibitor of topoisomerase I, was observed. Topoisomerase II decatenation activity in nuclear extracts from 10- and 40-fold DOX-resistant cells was 2- and 4-fold lower, respectively, when compared to sensitive cells. In these cells, however, marked reductions in m-AMSA- and VP-16-induced topoisomerase II mediated DNA cleavage were found to exceed decreases in the catalytic activity of the enzyme. Results from this study demonstrated that, in progressively DOX-resistant L1210 mouse leukemia cells with the MDR phenotype, a better relation existed between the degree of resistance and reduced VP-16- and m-AMSA-induced topoisomerase II mediated DNA cleavage, than between increases in P-glycoprotein and concomitant reduction in DOX accumulation.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1988

Paratesticular dermoid cyst in 6-month-old infant.

We describe a 6-month-old male infant with a dermoid cyst of the left paratesticular region. To our knowledge, this represents the youngest patient reported with this rare benign teratoma. We advocate enucleation for this particular type of teratoma based on referenced histopathological criteria.

Dermoid Cyst↗
PubMed1988

Limiting-dilution analysis of T cells extracted from solid human lung tissue: comparison of precursor frequencies for proliferative responses and lymphokine production between lung and blood T cells from individual donors.

This study evaluates the frequency and functions of immunocompetent T cells at the clonal level in solid human lung tissue versus peripheral blood. Enzymatic digestion of slices of histologically normal human lung yielded 18-42 x 10(6) viable mononuclear cells per gram wet weight tissue, of which 60-72% were lymphocytes; based upon these recoveries and the known weight of adult lung, the (median) lung parenchymal lymphocyte population can be estimated as 6 x 10(9), being of the same order as the blood pool and 15-30-fold that recoverable by broncho-alveolar lavage. Flow cytometric analysis indicated that the bulk of these lymphocytes was OKT3+/T11+ (CD3/CD2) T cells. Purified blood and lung T cells from each subject were cultured at limiting dilution in the presence of PHA, irradiated feeder cells and recombinant human IL-2. The mean frequency estimates for PHA-responsive T cells in these populations were 1 in 1.23 (81%) and 1 in 3.22 (31%) for blood and lung, respectively. This difference was seen for T cells from each donor and was highly significant by paired t-test (P less than 0.002). Analysis of surface phenotypes and functions of individual blood and T-cell clones indicated comparable frequencies for OKT4 (CD4) and OKT8 (CD8) expression, TNF production and mitogen-induced cytotoxicity. However, a striking inverse relationship was observed between the overall frequency of IL-2-producing clones (79% for blood versus 47% for lung) and interferon-gamma (IFN-gamma)-producing clones (46% versus 87%). These differences were found for each subject, and both were highly significant (P less than 0.001) by paired t-test. The available literature suggests that the majority of these lung T cells represent transient immigrants derived from the blood. Accordingly, the functional differences we have observed suggest either selective trapping within the lung vascular bed of peripheral blood T cells of certain functional phenotypes or alternatively selection/modulation of T cells by lung-derived factors during their transit through the tissue.

Adult↗
PubMed1987

Changes in nuclear magnetic resonance (T2) relaxation of limb tissue with bed rest.

Bed rest is used to simulate the effects of weightlessness on human physiology. A spin-echo procedure was used to image the lower leg of 15 normal male volunteers before and after 5 weeks of horizontal bedrest. In addition to noninvasively measuring muscle size changes, accurate T2 images were produced to investigate possible relaxation time changes immediately (2-4 h) and 1-2 days after bed rest. Subcutaneous fat showed no change in T2, bone marrow showed a decrease, and muscle showed no change immediately after bed rest but increased 1-2 days following reambulation.

Adipose Tissue↗
PubMed1987

PER-117: a new human ALL cell line with an immature thymic phenotype.

A new cell line, PER-117, was established from bone marrow cells of an eighteen months old boy with an acute lymphoblastic leukaemia (ALL). The leukaemic origin of cell line PER-117 is indicated by its cytochemical, immunological and cytogenetic similarity to the patient's fresh leukaemic cells. PER-117 carries a marker chromosome which was identified as a translocation between chromosomes 1 and 11. The surface marker analysis revealed that the phenotype of PER-117 is RFB-1+, RFT-1+ (CD5), 3A1+ (CD7), OKT 9+, OKT 10+ and HLA-DR-. Thus, this cell line appears to represent a prothymocyte or stage I thymocyte and preliminary data suggest that it can be induced in vitro to further differentiate.

Antibodies, Monoclonal↗
PubMed1986

An ultrastructural study of acute and long-term lung response to commercial diatomaceous earth.

The acute pulmonary effects of intratracheally instilled particles of calcined diatomaceous earth were found to include a pronounced neutrophil invasion of the bronchioles by 4 h after exposure which remained well developed through 1 day post-exposure. The number of macrophages and neutrophils in the alveoli continued to increase through 1 day post-exposure and remained above control values through 7 days post-exposure. The number of macrophages, many of which contained diatomaceous earth, remained elevated for the duration of the experiment. Most phagocytosis of the particles was carried out by macrophages, with minor participation by neutrophils. Many of the reactive macrophages in the groups with post-exposure periods longer than 2 h showed various types of pathological alterations. A few particles were found in type I epithelial cells. Oedematous changes were observed in some type I epithelial cells and proliferation of type II epithelial cells was evident in some alveoli, particularly those near the respiratory bronchioles. Mild diffuse fibrosis was first observed at 6 months and was still present at 15 months but remained confined to the areas containing the diatomaceous earth.

Animals↗
PubMed1986

Recurrent sterile meningitis caused by a pituitary abscess.

The case of a 21 year old woman who presented with recurrent sterile meningitis and bitemporal hemianopia is described. Computed tomographic scan showed a large low density ring enhancing lesion above and within the pituitary fossa which at operation and on histological examination was found to be compatible with an abscess. The visual field defect recovered completely and the scan appearances returned to normal postoperatively.

Abscess↗
PubMed1986

Efficacy of mevinolin as adjuvant therapy for refractory familial hypercholesterolaemia.

Mevinolin, a potent inhibitor of cholesterol synthesis, was used as a therapeutic adjuvant in patients with refractory familial hypercholesterolaemia for an average period of 13 months. Sustained decreases in serum cholesterol of 23 and 31 per cent were achieved by doses of 20 mg and 40 mg/day respectively in 13 heterozygotes already on cholestyramine or after partial ileal bypass. Administration of 80 mg/day to three patients undergoing plasma exchange reduced peak serum cholesterol levels by 11.5 per cent in two homozygotes and by 17 per cent in a double heterozygote for familial hypercholesterolaemia and type III hyperlipoproteinaemia. The decrease in cholesterol was largely confined to low-density lipoprotein and no significant changes occurred in serum triglyceride or high-density lipoprotein cholesterol. Mevinolin was well-tolerated except in one patient who developed myositic symptoms; asymptomatic, transient elevations of serum enzymes were observed in five others. Short and long Synacthen tests showed no evidence that the drug impaired adrenocortical response to ACTH. These results indicate that mevinolin provides a safe and highly effective means of reducing LDL levels in patients with heterozygous familial hypercholesterolaemia refractory to conventional treatment but is less useful in homozygotes.

Adult↗