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Biomedical subjects

J Lacy

Publications and source records attributed to J Lacy.

At least 37 records · Page 2Linked to original sources
PubMed1991

Granulocyte-macrophage colony-stimulating factor induces transcriptional activation of Egr-1 in murine peritoneal macrophages.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a pleiotropic hematopoietic growth factor that induces both growth and differentiation of tissue macrophages. The subcellular mechanism of action of GM-CSF is unknown. We have examined the effect of GM-CSF on the immediate early response gene, Egr-1, in murine peritoneal macrophages. Our data demonstrate that recombinant GM-CSF (25 units/ml) produces a 12-fold increase in Egr-1 mRNA within 30 min. Pretreatment with cycloheximide (10 micrograms/ml) had no effect on the ability of GM-CSF to increase Egr-1 mRNA. In nuclear runoff studies, GM-CSF increased the transcription rate of Egr-1 by 10-fold at 10 min. The maximal effect on Egr-1 transcription occurred at 25 min (13-fold) and decreased by 45 min. The half-life of Egr-1 mRNA in GM-CSF-treated macrophages is 13-21 min. We were unable to calculate the half-life in control cells, however, because of the short half-life and low level of constitutive expression of Egr-1 mRNA. Endogenous protein kinase C activity in macrophages was depleted by treatment with 12-O-tetradecanoylphorbol-13-acetate for 24 h. GM-CSF increased Egr-1 mRNA in protein kinase C-depleted macrophages, whereas the stimulatory effect of 12-O-tetradecanoylphorbol-13-acetate on Egr-1 was blocked. These data show that GM-CSF rapidly increases transcription of Egr-1 mRNA. The effect of GM-CSF on Egr-1 mRNA does not require de novo protein synthesis or protein kinase C. These findings provide a basis for investigating the molecular mechanism of action of GM-CSF in tissue macrophages.

Animals↗
PubMed1991

Family history of hypertension, gender, and cardiovascular responsivity during stress.

The relationships of family history of hypertension and gender to cardiovascular responses to stress were investigated in this research. One hundred twenty-three subjects were monitored while they rested and performed two tasks, reaction time and Ravens progressive matrices. Positive-family history males exhibited higher levels of systolic blood pressure than the negative male group and higher levels of rate pressure product than the positive-family history female group. Positive-family history males also had heart rate levels as high as the females. Female subjects did not differ from each other based on family history. In addition, subjects were grouped by gender and by high- or low-heart rate reactivity. The results suggest that heart rate reactivity has equally broad effects on cardiovascular function for males and females; for males, this reactivity during rests and tasks also tends to be associated with family history of hypertension.

Adolescent↗
PubMed1991

Conversion of a human B cell lymphoma line by Epstein-Barr virus is associated with increased tyrosine phosphorylation of a 50 kilodalton cytosolic protein.

Infection of human B cells by Epstein-Barr virus (EBV) causes transformation to immortalized lymphoblastoid cells capable of continuous proliferation. To identify biochemical changes induced by EBV infection of B cells, we have utilized isogenic EBV-positive and -negative B cell lymphoma lines as a model to determine whether EBV induces protein tyrosine phosphorylation. By utilizing two different methods, immunoblotting with phosphotyrosine antibodies and phosphoamino acid analysis, it was shown that the presence of EBV in these cells was reversibly associated with increased phosphorylation of a 50 kilodalton cytosolic protein on tyrosine residues. The characteristics of this protein were not consistent with any known EBV-encoded protein that is expressed in latency, and thus it likely represents a cellular protein that is phosphorylated by an endogenous tyrosine kinase. These results suggest that EBV induces protein tyrosine phosphorylation in human B cells, and this may represent an important event in the transformation of B lymphocytes by EBV.

Cell Transformation, Viral↗
PubMed1991

Design and implementation of a new computerized system for intraoperative cardiac mapping.

A rapid, portable, yet inexpensive and expandable computer-based system utilizing current technology has been developed from experience in the operating room. An efficient operating system well suited for surgery is defined. New technology recording arrays fabricated from multielectrode flexible Kapton strips were developed and found to be easy to use and highly reliable. Novel arrays are created easily for research or special clinical applications. The system displays all incoming data in real time and transfers 16-s epochs to disk on command. After the user defines a beat for analysis, the computer determines the activation time for each channel, rejects unsatisfactory channels, and displays the results for review and modification before plotting the isochronal map on the monitor. The average time to recall data and produce a map is 16 s; if manual review of 120 channels is included, mapping time is less than 4 min. Clinical data recorded during surgery are discussed. The speed and operational ease demonstrated in the operating room make this computer/electrode system valuable both for surgery and for elucidating basic mechanisms of arrhythmias.

Algorithms↗
PubMed1990

Macrophage colony-stimulating factor production by murine and human keratinocytes. Enhancement by bacterial lipopolysaccharide.

CSF have a broad range of effects on differentiated cells outside the bone marrow. Site-specific elaboration of these factors may influence local immune reactions. Keratinocytes have been demonstrated to produce a number of immunoactive cytokines, including factors capable of modifying macrophage function. We have previously identified at least two products of keratinocytes that induce DNA synthesis by elicited peritoneal macrophages; one factor has been identified as granulocyte-macrophage CSF. In the present study, the second keratinocyte product has been characterized and identified as macrophage-CSF (M-CSF). Conditioned media from cultures of normal human keratinocytes and the transformed murine keratinocyte cell line PAM 212 induce formation of macrophage colonies in soft agar as well as dose-dependent proliferation of the M-CSF-dependent cell line BAC1.2F5. The bioactivity in both assays is blocked by neutralizing anti-M-CSF antibody. Western blot analysis of cell lysates from both PAM 212 and normal human keratinocytes demonstrates multiple molecular mass forms of M-CSF (45 to 98 kDa). Northern blot analysis (PAM 212 cells) and in situ hybridization (normal keratinocytes) demonstrate expression of M-CSF mRNA. Stimulation of keratinocytes with LPS increases M-CSF synthesis as measured both by bioactivity and level of mRNA expression. Thus, both murine and human keratinocytes produce M-CSF in vitro. Furthermore, production of keratinocyte-derived M-CSF is increased by bacterial LPS. CSF production by keratinocytes may play an important role in regulating the cutaneous immune response.

Animals↗
PubMed1990

Interleukin 6 is an autocrine growth factor for mesangial cells.

Interleukin 6 (IL-6) induces the acute phase response, differentiation of B cells, proliferation of T cells, thymocytes, hematopoietic progenitors, hybridoma and plasmacytoma cells. Monocytes, T cells, fibroblasts, epithelial and endothelial cells secrete IL-6. Since IL-6 responsive cell-types may participate in the pathogenesis of glomerular inflammation, we studied the secretion of IL-6 by rat MCs, using the IL-6 dependent hybridoma cell line B9. The results of our studies indicate that MCs secrete IL-6 with a molecular weight of 17-42 kDa and isoelectric point of 4.0 to 5.3 MC-IL-6 activity could be blocked by a polyclonal antimurine-IL-6 antibody. MC express IL-6 mRNA as determined by Northern blot. Furthermore, our data demonstrate that IL-6 acts as an autocrine growth factor for MC. Incubation of subconfluent MC with recombinant IL-6 results in a dose-dependent increase of 3H-thymidine incorporation and number of MCs. Moreover, reverse phase HPLC fractions of MC-CM containing IL-6 activity increase 3H-thymidine incorporation by MC. In addition to its possible paracrine role in mediating the immune response in the glomerulus, MC-IL-6 may also be one of the autocrine signals leading to mesangial cell proliferation in vivo.

Animals↗
PubMed1990

Rat tracheal epithelial cells produce granulocyte/macrophage colony-stimulating factor.

It is unknown whether local resident cells of the upper airway are able to regulate the number and function of phagocytic cells by the secretion of cytokines. We undertook to determine if tracheal epithelial cells (TEC) produce the potent cytokine granulocyte/macrophage colony-stimulating factor (GM-CSF) and how TEC-derived GM-CSF might be regulated. Conditioned media (TEC-CM) from 7- to 21-day-old primary cultures of rat TEC contained material with bioactivity similar to GM-CSF. This bioactivity was increased in conditioned medium from lipopolysaccharide (LPS)-treated (1 microgram/ml) TEC. Molecular characterization of bioactivity revealed a molecular weight of 27 to 44 kD by gel-filtration high performance liquid chromatography (HPLC), and elution at 44 to 50% acetonitrile by reverse-phase HPLC, similar to that of authentic GM-CSF. The biologic activity of TEC-CM was completely blocked by a goat polyclonal anti-GM-CSF antibody. With in situ hybridization using a murine GM-CSF cDNA probe, more than 95% of the adherent TEC population expressed GM-CSF transcripts, and the number of transcripts was significantly increased by LPS (1 microgram/ml, 48 h). TEC appear to produce a cytokine that is functionally, biochemically, and antigenically indistinguishable from GM-CSF. The ability of TEC to produce GM-CSF suggests that these cells may play a role in modulating the inflammatory response in the airway.

Animals↗
PubMed1989

Post-transcriptional mechanisms of deregulation of MYC following conversion of a human B cell line by Epstein-Barr virus.

By utilizing an Epstein-Barr virus (EBV)-negative Burkitt's lymphoma line (BJAB) and several EBV-positive sub-lines derived from it by in vitro infection, it has been shown previously that the presence of the EBV genome in this B cell line is reversibly associated with deregulation of MYC expression. Specifically, the decline in the level of MYC transcripts observed in the EBV-negative BJAB line as cells approach stationary phase of growth is abrogated in the presence of the virus. In the studies described herein, the mechanism of deregulation of MYC in EBV-converted BJAB cells was examined. It was shown that the presence of EBV in BJAB cells was not associated with changes in the rate of transcription from exons I, II or III of MYC as cells approached stationary phase of growth. In contrast, the stability of MYC mRNA was altered in EBV-positive BJAB cells. Specifically, the half-life of MYC mRNA increased from less than 36 to greater than 70 min in EBV-positive BJAB lines as cells progressed from early to late exponential phase of growth. This alteration in stability of MYC transcripts was reversibly associated with the presence of the virus, since an EBV-negative revertant BJAB line did not display an increase in stability of MYC transcripts in late exponential phase of growth. In addition, progression from early to late exponential phase of growth in two EBV-immortalized lymphoblastoid lines derived from normal human B cells was also associated with prolongation of the half-life of MYC.(ABSTRACT TRUNCATED AT 250 WORDS)

B-Lymphocytes↗
PubMed1989

Rat mesangial cells produce granulocyte-macrophage colony-stimulating factor.

Because inflammatory processes in renal glomeruli may involve monocyte-macrophages (MPs) and T-lymphocytes, we have investigated whether products of glomerular mesangial cells (MCs) can stimulate the proliferative activity of these effector cells. We found that cultured rat MCs (subcultures 2-15), maintained under serum-free conditions, secrete a soluble factor into the supernate [MC-conditioned medium (CM)], which supports growth of the T-helper cell-derived line HT-2. Moreover, MC-CM increased [3H]thymidine incorporation by thioglycollate-elicited peritoneal MPs but did not induce growth of the interleukin 2 (IL-2)- or interleukin 4 (IL-4)-dependent cell line CTLL-2. Further functional, serological, and biochemical analysis of MC-CM revealed that rat MCs secrete a cytokine that, by all of the techniques used, is indistinguishable from granulocyte-macrophage colony-stimulating factor (GM-CSF). Both northern blot and in situ hybridization with a specific cDNA probe for murine GM-CSF showed that MCs express GM-CSF mRNA transcripts. The present findings indicate that cultured rat MCs produce GM-CSF. Release of GM-CSF by MCs in vivo may play a role in the interaction of MCs with MPs, T-cells, and neutrophils in glomerular disease.

Animals↗
PubMed1988

Treatment of diabetic foot infections: Wagner classification, therapy, and outcome.

A total of 850 cases of septic diabetic foot infections were reviewed in 355 patients. Age, sex, other chronic diseases, site, etiology, Wagner grade, treatment, and results were analyzed. One third of the patients were in their sixth decade of life. There were 180 women and 175 men. Chronic diseases included hypertension, congestive heart disease, and renal failure. Staphylococcus aureus was the most common bacteria. Treatment was considered to meet protocol standards if Wagner's algorithms and infectious disease principles were followed. Thirty-nine Wagner grade 0 infections were seen: only one was not treated appropriately. Eighty-eight percent treated per protocol healed and the one not treated appropriately failed. In grade 1, 79% of the 154 evaluable patients were treated appropriately with a 86% success rate versus a 53% success rate for those not treated per protocol. Of three quarters of the 64 patients with grade 2 infections treated according to protocol, 73% healed. One of those in grade 2 who was not treated according to protocol healed. In grade 3, 64% of the 251 patients were treated per protocol with a 79% success rate versus a 12% success rate for those who were not treated per protocol. Most of the 189 patients with grade 4 cases were treated according to protocol with 88% success; the 20 not treated per protocol had a 15% success rate. Thirty of the 32 grade 5 patients were treated per protocol and all but one healed. Protocol therapy had a statistically significant effect by chi 2 test in the treatment of all groups.

Adult↗
PubMed1987

Amplification and deregulation of MYC following Epstein-Barr virus infection of a human B-cell line.

In Epstein-Barr virus (EBV)-positive Burkitt lymphoma (BL) the role of EBV in the translocation and deregulation of the MYC oncogene remains unknown. By utilizing an EBV-negative BL (BJAB) and several EBV-positive sublines derived from it by in vitro infection, it was possible to show that the presence of the virus was associated with altered expression and copy number of MYC. In the EBV-negative BJAB line, the level of MYC transcripts declined progressively as cells approached the stationary phase of growth. In contrast, in EBV-infected BJAB cells MYC expression remained elevated as cells entered stationary phase. This effect on MYC expression was reversibly linked to the presence of the virus. Furthermore, following EBV infection of BJAB cells by two different strains of EBV, amplification of MYC in association with the appearance of a homogeneously staining region on chromosome 8 at the mapped location of MYC had occurred. These studies suggest that both the deregulation of MYC transcription and the chromosomal rearrangement in the region of the MYC locus in this B-cell line may have occurred as a result of EBV infection.

Antigens, Viral↗
PubMed1987

Molecular cloning and chemical synthesis of a region of platelet glycoprotein IIb involved in adhesive function.

Membrane glycoprotein (GP) IIb-IIIa is a component of a platelet adhesive protein receptor. A region of the heavy chain of GPIIb, defined by the monoclonal antibody PMI-1, is involved in adhesion receptor function. We have localized and chemically synthesized this region of GPIIb. A cDNA clone that directs the synthesis of a fusion protein reactive with the PMI-1 antibody was isolated from a phage lambda gt11 expression library constructed with mRNA from an erythroleukemia (HEL) cell line. The deduced amino acid sequence of this clone indicates that it spans the light-heavy chain junction of GPIIb and contains a portion of the carboxyl terminus of the heavy chain and the amino terminus of the light chain. The PMI-1 epitope was found to be contained within a 9-kDa staphylococcal V8 protease fragment of GPIIb, and such a fragment was predicted within the putative heavy-chain sequence. A computerized antigen prediction program identified a single sequence with a high probability of containing a continuous epitope. A synthetic 17-residue peptide containing this sequence binds PMI-1 and inhibits PMI-1 binding to GPIIb-IIIa. The peptide-antibody complex has an approximate Kd of 1.2 microM, which compares to a Kd of 0.95 microM for PMI-1 binding to GPIIb. The region containing the PMI-1 epitope shows no similarity to corresponding regions of two other adhesion receptors, indicating that this portion of GPIIb may function in activities unique to the platelet receptor.

Amino Acid Sequence↗
PubMed1986

Induction of c-myc expression in human B lymphocytes by B-cell growth factor and anti-immunoglobulin.

Purified human B lymphocytes were examined for transcriptional expression of c-myc in response to mitogenic stimulation by the method of in situ hybridization using 35S-labeled DNA probes. The level of c-myc expression increased 10- to 20-fold within 2 hr after the addition of anti-mu, formalinized Staphylococcus aureus Cowan strain I, or B-cell growth factor, as compared to resting B cells. After 72-96 hr of mitogenic stimulation, c-myc expression remained elevated 5-fold, but expression among individual cells had become more heterogeneous than at early time points. To determine whether c-myc expression in human B lymphocytes is phase specific within the cell cycle, mitogen-stimulated cells were sorted by DNA content into populations of cells in G0/G1, S, and G2/M phases of the cell cycle. Examination of c-myc expression in phase-specific cells revealed that c-myc expression was elevated in all phases of the cell cycle, but it appeared to be maximally expressed in S phase. These studies suggest that c-myc expression in normal human B lymphocytes is cell-cycle dependent and remains elevated in all phases of the cycling cell.

Antibodies, Anti-Idiotypic↗
PubMed1985

Effects of diacetyl diamines on in vitro activation and proliferation of human B lymphocytes.

N,N'-Diacetylputrescine (tetramethylenebisacetamide [TMBA]) and its six carbon analog, hexamethylenebisacetamide (HMBA), inhibited the proliferative response of human B lymphocytes to anti-mu and formalinized Cowan I strain Staphylococcal aureus (SAC) stimulation. In contrast, B cell growth factor-stimulated proliferation of human B cells was minimally inhibited by TMBA or HMBA. The antiproliferative effect of these diamine derivatives was specific for anti-mu (or SAC) activation of normal B cells, because the proliferation of PHA-stimulated human T cells and transformed human B cells was not affected by the presence of TMBA or HMBA. The inhibitory effect of diacetyl diamines on anti-mu (or SAC)-induced B cell activation was dose dependent and persisted after removal of the diamine derivatives from the culture media. These studies show that diacetylated derivatives of polyamines modulate human B cell activation in vitro by specific abrogation of anti-mu or SAC activation.

Acetamides↗
PubMed1977

Coronary atherosclerosis in valvular heart disease.

To evaluate the usefulness of routine coronary arteriography in patients undergoing cardiac catheterization for the evaluation of valvular heart disease, we performed coronary arteriographic studies routinely in a series of 201 patients primarily catheterized for such evaluation. Coronary artery obstructive lesions in excess of 50% of the lumen were present in 45 of the 201 patients. In 18 of the 45 there was no history of chest pain. Three of the 18 had three vessels involved while 2 had two vessels involved. A total of 27 patients (13.4%) had luminal obstruction greater than 70%, and 9 of these had no pain. In 35 of the 201 patients, classic angina pectoris existed in the absence of radiographically significant disease. Severe coronary disease was found to coexist with hemodynamically severe valvular heart disease and was not predictable noninvasively.

Adolescent↗
PubMed1975

A novel actinomycete from sugar-cane bagasse: Saccharopolyspora hirsuta gen. et. sp. nov.

A new species of nocardioform actinomycete isolated from spontaneously heated sugar-cane bagasse is described as Saccharopolyspora hirsuta gen. et sp. nov. It has affinities with species of both Nocardia and Actinomadura but can be distinguished from both genera by its morphology, sporulation, wall and lipid analyses, antibiotic resistance, degradation and carbon utilzation tests.

Actinomycetaceae↗