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J Griffin

Publications and source records attributed to J Griffin.

At least 109 records · Page 6Linked to original sources

Effects of interferon-gamma on proto-oncogene expression during induction of human monocytic differentiation.

Activation of the proto-oncogenes c-fos, c-fms, and c-sis has been associated with monocytic differentiation. In the present study, we monitored the relationship of c-myc, c-fos, c-fms, and c-sis expression to interferon-gamma (IFN-gamma)-induced monocytic differentiation of human HL-60 promyelocytic leukemia cells. Treatment of HL-60 cells with 500 U/ml IFN-gamma arrested cell proliferation after 3 days. Appearance of the monocytic phenotype was manifested within 24 hr of IFN-gamma exposure by: increased nitroblue tetrazolium reduction; increased cell surface expression of the HLA-DR, Mo1, and MY4 antigens; and induction of transcripts for the second component of complement (C2) and tumor necrosis factor. In contrast, c-myc expression decreased as a later event after 72 hr of IFN-gamma exposure, and c-fos transcripts remained undetectable until 5 days of treatment. Furthermore, c-fms RNA and transcripts for the macrophage marker apolipoprotein E were induced only after 7 days. Finally, expression of the c-sis proto-oncogene at the RNA and protein levels remained undetectable after induction with IFN-gamma. These findings would thus suggest that declines in c-myc RNA, as well as induction of c-fos, c-fms, and c-sis expression, are not requisite events in the commitment of HL-60 cells to IFN-gamma-induced monocytic differentiation. Expression of c-fos and c-fms, however, is associated with acquisition of markers associated with maturation to macrophages.

Antigens, Surface↗

Spatial segregation of mRNA encoding myelin-specific proteins.

The cellular and subcellular distributions of mRNAs encoding three myelin-specific proteins--myelin basic protein (MBP), proteolipid protein (PLP), and Po protein--were studied in tissue sections of developing rat nervous systems by in situ hybridization. The developmental appearance of these mRNAs closely paralleled the appearance of the proteins they encode as determined by immunocytochemistry. mRNA encoding the extrinsic membrane protein, MBP, was concentrated around oligodendrocyte and Schwann cell nuclei during initial stages of myelination; as myelination proceeded, MBP mRNA became distributed diffusely over myelinated fibers. In contrast, mRNAs encoding the intrinsic membrane proteins, PLP and Po, remained concentrated around oligodendrocyte (PLP) and Schwann cell (Po) nuclei at all stages of myelination. These results establish that myelinating cells spatially segregate certain myelin-specific mRNAs. The presence of MBP mRNA within the cytoplasmic domains of myelin internodes indicates that protein sorting during myelination involves transportation of mRNA to specific subcellular sites.

Aging↗

Seronegative and seropositive rheumatoid arthritis: similar diseases.

A case control study of 50 rheumatoid factor positive (RA+) and 50 rheumatoid factor negative (RA-) patients with rheumatoid arthritis has been carried out. As expected, the RA+ group has significantly more nodules and vasculitis. In terms of clinical joint involvement, the RA- had large-joint involvement. Radiologically, seropositive disease was characterized by more severe involvement of the metacarpophalangeal joints of the thumb and index fingers and in all the metatarsophalangeal joints of the feet. There was no difference either clinically or radiologically between the two groups in terms of symmetry of joint disease or wrist involvement. Of special interest was the finding that the prevalence of HLA-DR4 was elevated to the same degree in both groups but that genetic markers for ankylosing spondylitis and for psoriasis (HLA-B27 and Cw6 respectively) were similar in both groups and not increased above control population levels. It is concluded that the entity defined as RA includes patients with and without rheumatoid factor (RF) in their serum and that this determines differences in disease expression. Whether these differences are the consequences or the cause of RF cannot be concluded on the basis of this study.

Arthritis, Rheumatoid↗

Two-monoclonal-antibody "sandwich"-type assay of human lutropin, with no cross reaction with choriogonadotropin.

We have developed a sensitive, specific, noncompetitive sandwich-type assay for human lutropin (hLH). Two monoclonal antibodies are used, and there is no cross reaction with human choriogonadotropin (hCG) or human follitropin (hFSH), and little or none with human thyrotropin (hTSH). There also is no reaction with the free beta chains of hLH and hCG. The detection limit is less than 0.5 int. units of hLH per liter of serum, and the dose-response curve is linear between 0 and 10 int. units/L. The intra-assay CV averaged 5.4% at low doses of hLH; the interassay CV averaged 12.5%.

Antibodies, Monoclonal↗

Subacute sensory neuronopathy secondary to dorsal root ganglionitis in primary Sjögren's syndrome.

Sensory neuropathies, particularly trigeminal neuropathy, have been recognized as neurological complications of Sjögren's syndrome, but the pathogenesis has not been established. We describe a woman with primary Sjögren's syndrome who developed a progressive debilitating subacute sensory neuronopathy. Results of electrophysiological studies were consistent with involvement of the trigeminal and dorsal root ganglia. A thoracic dorsal root ganglion biopsy showed lymphocytic infiltration and degeneration of ganglion cells. We believe that this is the first description of biopsy-documented dorsal root ganglionitis in a subacute sensory neuronopathy associated with Sjögren's syndrome and that the finding suggests an immunopathogenic basis.

Female↗

Effects of subperineurial injections of very-long-chain and medium-chain fatty acids into rat sciatic nerve.

[9,10-3H] palmitic (C16:0) and [1-14C] lignoceric (C24:0) acid dissolved in 10 microL of ethanol were injected subperineurially into the sciatic nerve of rats. Both C16:0 and C24:0 were incorporated into lipids, and in most lipid fractions C16:0 incorporation exceeded that of C24:0. Free ceramide and cholesterol ester were the only lipid moieties in which C24:0 incorporation was equal to or greater than that of C16:0. This finding is of particular interest since the very-long-chain fatty acid excess is by far the most striking in the cholesterol ester fraction in adrenoleukodystrophy. Furthermore, incorporation into cerebroside and sulfatide indicates that at least some of the injected fatty acids were metabolized in the Schwann cell. Subperineurial injections of either very-long-chain fatty acids or medium-chain fatty acids into rat sciatic nerve caused demyelination, and this morphological change does not occur following injection of pure solvent.

Adrenoleukodystrophy↗

Lithium ratio in vitro: familial patterns of illness.

Psychiatric illness in first-degree relatives of psychotic patients with low, intermediate, and high red blood cell (RBC) in vitro lithium ratio (LR) was investigated using the Schedule for Affective Disorders and Schizophrenia and DSM-III. Fewer schizophrenic spectrum disorders were found in the first-degree relatives of high and low LR probands as compared to intermediate LR probands; high LR psychotic probands had families with an increased frequency of depressive spectrum disorder. Alcohol dependence and abuse was particularly prominent in the first-degree relatives of the higher LR probands. High LR may identify a disease that does not belong to the familial-genetic disorders of the schizophrenic spectrum; this illness may bear a closer relationship to disorders of the depressive spectrum.

Adult↗

Differentiation of myeloid cells is accompanied by increased levels of pp60c-src protein and kinase activity.

We have detected a significant increase in the levels of pp60c-src kinase activity associated with the differentiation of myeloid cell lines HL-60 and U-937. The induction of pp60c-src kinase activity becomes apparent approximately 14 hr after the addition of phorbol 12-myristate 13-acetate and increases 20-fold by 72 hr. The enhanced kinase activity can be accounted for by elevated levels of c-src protein in the differentiated cells. When nonleukemic bone marrow cells were examined, myeloid progenitor cells exhibited a low level of pp60c-src kinase activity. As these cells are allowed to differentiate in culture, the resulting adherent monocytes are as high in pp60c-src kinase activity as HL-60 cells induced to differentiate into monocytes. A strong correlation is found between the levels of pp60c-src kinase activity and the degree of monocytic differentiation of the cells from patients with acute myeloid leukemia. Our findings suggest that the activation of pp60c-src kinase activity is a normal physiological event associated with myeloid differentiation.

Cell Differentiation↗

Low dose ara-C administered by continuous subcutaneous infusion: a pharmacologic evaluation.

Low dose ara-C has been widely used in the treatment of preleukemia and leukemia. These studies have generally utilized either a twice daily, subcutaneous bolus schedule or a continuous intravenous infusion schedule. In order to surmount the logistical problems of long term intravenous infusion while providing prolonged ara-C exposure, we have studied the pharmacology of administering ara-C (20 mg/M2/d) by continuous subcutaneous infusion. The results obtained in eight patients demonstrate that steady state plasma ara-C levels achieved during continuous subcutaneous infusion (24.6-65.6 nM) are not significantly different than those obtained during intravenous infusions (26.2-61.5 nM). Subcutaneous infusions result in prolonged myelosuppression similar to that seen with continuous intravenous infusions. The continuous infusion of low dose ara-C by the subcutaneous route provides a treatment option for some outpatients and offers advantages over intravenous infusions which often require placement of venous catheters or hospitalization.

Adult↗

Plasma fatty acid pattern including diene-conjugated linoleic acid in ethanol users and patients with ethanol-related liver disease.

The level of conjugated dienes (CD) in the serum, conjugated linoleic acid isomer in the phospholipid fraction [18:2(9, 11)], and the fatty acid profile in both the serum and in the separated lipid classes were analyzed in current and previous alcohol abusers and in patients with alcoholic liver disease. None of the subjects consumed alcohol for at least 2-3 days prior to blood collection for analysis of lipids. There was no significant difference in CD or in the absolute level of 18:2(9, 11) among the groups, whereas the 18:2(9, 11)/18:2(9, 12) molar ratio was significantly elevated in patients with liver disease. Fatty acid analysis of the whole plasma extract showed that the absolute level of arachidonic acid increased from 4.8 +/- 3.5 mg/dl (n = 9) in lifelong abstainers to 13.4 +/- 4.0 (n = 8) in current ethanol abusers, and its relative level (related to the total fatty acids) from 1.73 +/- 1.34 to 4.55 +/- 1.01 in the same groups. An increased proportion of linoleic acid in the triglyceride and phospholipid fractions from current abusers and patients with liver disease was also found; the percentage of 18:2 in phospholipids increased from 5.4 +/- 5.0 (n = 8) in lifelong abstainers to 14.3 +/- 3.9 (n = 8) in current abusers and 12.7 +/- 2.2 (n = 10) in patients with liver disease. The percentage of 16:0 was significantly lower in the phospholipids of current abusers as compared to lifelong abstainers.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Two-monoclonal-antibody sandwich-type assay for thyrotropin, with use of an avidin-biotin separation technique.

We have developed a sensitive, specific, noncompetitive, sandwich-type radioimmunoassay for human thyrotropin (hTSH), which can be performed in 30 min. The assay involves two monoclonal antibodies, selected for high affinity and specificity and also for reaction against antigenic sites on hTSH that are distal from each other. One of these antibodies is labeled with 125I; the other is conjugated covalently to biotin. Polystyrene beads were also conjugated covalently to biotin. After conjugation, the beads were incubated with avidin. These beads represent a rapid, simple method for separating hTSH-bound antibody from free antibody. The biotin-antibody-hTSH-125I-labeled antibody complexes bind to the beads and hTSH concentration is directly related to counts per minute. This assay can detect hTSH at a concentration of 0.06 milli-unit/L in serum.

Adult↗

Chronic allopurinol and adenine therapy in Duchenne muscular dystrophy: effects on muscle function, nucleotide degradation, and muscle ATP and ADP content.

Prompted by the controversy on the efficacy of allopurinol in Duchenne muscular dystrophy and by our observations of an abnormal adenine nucleotide turnover in this disease, we conducted an 18 month, double-blind clinical trial with allopurinol and adenine in 14 Duchenne boys paired according to age and functional activity. Detailed clinical evaluation was performed trimonthly. Muscle ATP and ADP content was measured before and after 1 year of treatment. The effect of therapy on adenine nucleotide turnover was determined. No significant difference was observed between the treated and placebo groups, but both showed a significant deterioration (p less than 0.05) in most clinical parameters. Muscle ATP was reduced in Duchenne dystrophy (p less than 0.02) but did not change with therapy, and no correction of the abnormal adenine nucleotide degradation was observed.

Adenine Nucleotides↗

The effect of insulin treatment on insulin secretion and insulin action in type II diabetes mellitus.

We have studied the effects of 3 wk of continuous subcutaneous insulin infusion (CSII) on endogenous insulin secretion and action in a group of 14 type II diabetic subjects with a mean (+/-SEM) fasting glucose level of 286 +/- 17 mg/dl. Normal basal and postprandial glucose levels were achieved during insulin therapy at the expense of marked peripheral hyperinsulinemia. During the week of posttreatment evaluation, the subjects maintained a mean fasting glucose level of 155 +/- 11 mg/dl off insulin therapy, indicating a persistent improvement in carbohydrate homeostasis. Adipocyte insulin binding and in vivo insulin dose-response curves for glucose disposal using the euglycemic clamp technique were measured before and after therapy to assess the effect on receptor and postreceptor insulin action. Adipocyte insulin binding did not change. The insulin dose-response curve for overall glucose disposal remained right-shifted compared with age-matched controls, but the mean maximal glucose disposal rate increased by 74% from 160 +/- 14 to 278 +/- 18 mg/m2/min (P less than 0.0005). The effect of insulin treatment on basal hepatic glucose output was also assessed; the mean rate was initially elevated at 159 +/- 8 mg/m2/min but fell to 90 +/- 5 mg/m2/min in the posttreatment period (P less than 0.001), a value similar to that in control subjects. Endogenous insulin secretion was assessed in detail and found to be improved after exogenous insulin therapy. Mean 24-h integrated serum insulin and C-peptide concentrations were increased from 21,377 +/- 2766 to 35,584 +/- 4549 microU/ml/min (P less than 0.01) and from 1653 +/- 215 to 2112 +/- 188 pmol/ml/min (P less than 0.05), respectively, despite lower glycemia. Second-phase insulin response to an intravenous (i.v.) glucose challenge was enhanced from 170 +/- 53 to 1022 +/- 376 microU/ml/min (P less than 0.025), although first-phase response remained minimal. Finally, the mean insulin and C-peptide responses to an i.v. glucagon pulse were unchanged in the posttreatment period, but when glucose levels were increased by exogenous glucose infusion to approximate the levels observed before therapy and the glucagon pulse repeated, responses were markedly enhanced. Simple and multivariate correlation analysis showed that only measures of basal hepatic glucose output and the magnitude of the postbinding defect in the untreated state could be related to the respective fasting glucose levels in individual subjects.(ABSTRACT TRUNCATED AT 400 WORDS)

Adipose Tissue↗

Effects of 1-beta-D-arabinofuranosylcytosine and phorbol ester on differentiation of human K562 erythroleukemia cells.

We have previously demonstrated that 1-beta-D-arabinofuranosylcytosine (ara-C) induces hemoglobin synthesis in human K562 erythroleukemia cells. The present study extends these findings by demonstrating that ara-C treatment of K562 cells results in both increased heme synthesis and accumulation of alpha-, gamma-, epsilon-, and zeta-globin RNA. The results also demonstrate that ara-C enhances K562 cell surface expression of glycophorin. Furthermore, we demonstrate that phorbol ester (12-O-tetradecanoylphorbol-13-acetate; TPA) inhibits the effects of ara-C on heme production, accumulation of globin RNA, and glycophorin expression. The inhibitory effect occurs maximally when K562 cells are treated with TPA before undergoing ara-C-induced commitment to erythroid differentiation. These findings suggest that TPA inhibits an early step in the process required for ara-C to enhance expression of genes involved in the erythroid program.

Cell Differentiation↗