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G Cox

Publications and source records attributed to G Cox.

At least 91 records · Page 5Linked to original sources
PubMed1994

Immunogenicity of the Plasmodium falciparum glutamate-rich protein expressed by vaccinia virus.

The glurp gene of Plasmodium falciparum F32 has been inserted into a vaccinia virus, and the recombinant virus was designated VVG4. Expression of glurp in VVG4-infected Vero cells was analyzed by immunoprecipitation and revealed a primary GLURP product of approximately 220,000 Da; GLURP was detected both intracellularly and in culture supernatants. To study the immunogenicity of vaccinia virus-expressed GLURP, mice were immunized with VVG4 and serum samples were analyzed for antibody reactivity with three polypeptides, covering almost the entire GLURP molecule; these three polypeptides were produced in recombinant form in Escherichia coli. The immune response was primarily directed against a carboxy-terminal repeat region. The mouse anti-GLURP serum recognized authentic GLURP by immunoprecipitation analysis from P. falciparum grown in vitro. These results demonstrate that vaccinia virus-expressed glurp product can induce a humoral immune response against GLURP derived from blood-stage parasites.

Animals↗
PubMed1994

Manganese superoxide dismutase and heat shock protein 70 are not necessary for suppression of apoptosis in human peripheral blood neutrophils.

We have previously shown that granulocyte (G-CSF) and granulocyte/macrophage (GM-CSF) colony-stimulating factors present in human bronchial epithelial cell conditioned medium (HBEC-CM) suppress apoptosis in neutrophils. In this study, we demonstrate that HBEC-CM also induces increased expression of manganese superoxide dismutase (MnSOD) and heat shock protein 70 (HSP70) in neutrophils. However, treatment of neutrophils with recombinant GM-CSF and G-CSF, which suppressed apoptosis to equivalent degrees, did not induce MnSOD or HSP 70. Thus, we conclude that induction of stress proteins is associated with, but not necessary for, suppression of apoptosis.

Adult↗
PubMed1994

Effects of low-dose TRH on cognitive deficits in the ECT postictal state.

A low dose (0.5 mg) of thyrotropin-releasing hormone (TRH), a short-acting tripeptide with known analeptic properties, was administered to eight depressed patients 5 minutes after ECT session 3 or 4 in a double-blind, placebo-controlled crossover design. After TRH infusion the patients displayed selectively better performance on a battery of neuropsychological tests than they did after placebo infusion. Further exploration with pharmacological probes to mitigate ECT postictal cognitive deficits is warranted.

Adult↗
PubMed1994

Symptom severity and utilization of treatment resources among dually diagnosed inpatients.

OBJECTIVE: The author's goal was to determine the clinical characteristics of patients admitted to an acute voluntary psychiatric unit with a dual diagnosis treatment program. METHODS: A total of 104 consecutive patients admitted the unit were divided into three groups based on whether they had a current substance use disorder, a past substance use disorder, or no substance use disorder. On the basis of data derived from extensive structured interviews, the three groups' demographic characteristics, severity of symptoms, and utilization of psychiatric and alcohol and drug treatment services were compared. RESULTS: The dually diagnosed patients in the sample were more likely to have a mood disorder, and the patients without a substance use disorder were more likely to have a diagnosis of schizophrenia or mania. Patients with a current substance use disorder had more severe symptoms and used more treatment resources than patients in other groups. Patients with a past substance use disorder also had increased symptom severity, with measures of severity about halfway between those of patients with current substance use disorder and those of patients with no substance use disorder. CONCLUSIONS: Psychiatric patients with a past substance use disorder, like those with a current substance use disorder, may be at risk for increased symptom severity and increased utilization of treatment resources and may need specialized treatment planning. The needs of dually diagnosed patients with mood disorders as well as those with chronic psychotic conditions should be considered in local and national mental health care planning.

Adult↗
PubMed1993

Identification of BCR/ABL-negative primitive hematopoietic progenitor cells within chronic myeloid leukemia marrow.

Chronic myeloid leukemia (CML) is a malignant disorder of the hematopoietic stem cell. It has been shown that normal stem cells coexist with malignant stem cells in the bone marrow of patients with chronic-phase CML. To characterize the primitive hematopoietic progenitor cells within CML marrow, CD34+DR- and CD34+DR+ cells were isolated using centrifugal elutriation, monoclonal antibody labeling, and flow cytometric cell sorting. Polymerase chain reaction analysis of RNA samples from these CD34+ subpopulations was used to detect the presence of the BCR/ABL translocation characteristic of CML. The CD34+DR+ subpopulation contained BCR/ABL(+) cells in 11 of 12 marrow samples studied, whereas the CD34+DR- subpopulation contained BCR/ABL(+) cells in 6 of 9 CML marrow specimens. These cell populations were assayed for hematopoietic progenitor cells, and individual hematopoietic colonies were analyzed by PCR for their BCR/ABL status. Results from six patients showed that nearly half of the myeloid colonies cloned from CD34+DR- cells were BCR/ABL(+), although the CD34+DR- subpopulation contained significantly fewer BCR/ABL(+) progenitor cells than either low-density bone marrow (LDBM) or the CD34+DR+ fraction. These CD34+ cells were also used to establish stromal cell-free long-term bone marrow cultures to assess the BCR/ABL status of hematopoietic stem cells within these CML marrow populations. After 28 days in culture, three of five cultures initiated with CD34+DR- cells produced BCR/ABL(-) cells. By contrast, only one of eight cultures initiated with CD34+DR+ cells were BCR/ABL(-) after 28 days. These results indicate that the CD34+DR- subpopulation of CML marrow still contains leukemic progenitor cells, although to a lesser extent than either LDBM or CD34+DR+ cells.

Adult↗
PubMed1993

Negative reciprocity and communication in couples with a violent husband.

To better understand the relationship dynamics of couples experiencing husband-to-wife violence, the interaction patterns of 29 domestically violent (DV), 15 distressed but nonviolent (DNV), and 13 happily married (HM) couples were examined using the Marital Interaction Coding System and lag sequential analyses. DV spouses were generally more often aversive and less often facilitative than nonviolent couples. DV couples were significantly more likely to engage in negative reciprocity than their DNV or their HM counterparts. DV wives were as likely as their husbands to reciprocate negative behavior. Furthermore, no support was found for a negative reinforcement hypothesis that husbands' aversiveness was shaped or maintained by wives' capitulation.

Adult↗
PubMed1993

Induction of heat-shock protein 70 in neutrophils during exposure to subphysiologic temperatures.

The expression of heat-shock protein (HSP) 70, a marker of cellular stress, was evaluated in neutrophils. In cells isolated by conventional method, expression of both the inducible HSP72 and the constitutive HSP73 forms of HSP70 was found. This was observed when cells were isolated at room temperature or at 4 degrees C. When autologous plasma was used during the isolation procedure and the entire procedure was done at 37 degrees C, there was no expression of HSP72. Omission of plasma from the isolation procedure done at 37 degrees C also resulted in increased expression of HSP72. These studies demonstrate that the expression of HSP70 in neutrophils is induced by isolation at low temperatures and in the absence of plasma. These observations may be important for studies of the regulation of HSP expression and for other studies that relate to neutrophil activation.

Adult↗
PubMed1993

Cytokines and pulmonary fibrosis.

Chronically inflamed and fibrotic tissue of the respiratory tract can be shown to actively express the genes and products of a number of powerful growth and differentiating factors. The initial activation of lung inflammatory cells, including alveolar macrophages, is presumed to result in the release of early acting cytokines such as IL-1 and TNF. Subsequent activation and possible phenotype alteration of the structural cells results in release of other growth factors and accumulation of blood derived inflammatory cells. These cells, once they have entered the tissue and become further activated, may begin to release their own autocrine factors and "feed back" some of the similar signals to the tissue cells in a paracrine manner, further inducing differentiation and phenotype change. These internal tissue cell and cytokine cascades could account for the chronic nature of the inflammation. Therapeutic intervention must therefore take into account the inflammatory component as well as the nature of the cytokines and structural cells involved in the propagation of the disease.

Cytokines↗
PubMed1993

Effects of weight cycling in rats allowed a choice of diet.

We examined the effects of weight cycling, produced by bouts of weight loss and regain, on body weight, body composition, dietary fat intake, and energy efficiency. Three groups of adult female Wistar rats were followed for 116 days: control rats (n = 10) were allowed ad libitum access to three mixed diets with protein as a constant proportion of energy and fat provided at 10, 30, and 50% of energy; cycled rats (n = 10) had four bouts of food restriction (50% of baseline intake for 10 days) and refeeding (18-20 days of ad libitum access to the 3 mixed diets); maturity controls (n = 10) were treated identically to controls during the first two cycles and identical to cyclers during the final two weight cycles. At the end of the experiment, we could identify no negative effects of weight cycling on any of the measures taken, and in fact body weight and percentage body fat were lower in cyclers than controls. Dietary fat intake was not altered by weight cycling. In summary, weight cycling did not promote body weight or body fat gain.

Animals↗
PubMed1992

Inhibition of human immunodeficiency virus-1 proliferation by liposome-encapsulated sense DNA to the 5' tat splice acceptor site.

A liposome formulation containing a distearoylphosphatidylethanolamine analog was developed that was endocytosed by both lymphocytes and monocytes. This formulation was used to encapsulate sense and antisense 20-mer oligodeoxynucleotides to the 5' tat splice acceptor site of human immunodeficiency virus type 1. At a DNA concentration of 140 nM, the liposome-encapsulated sense DNA inhibited p24 production by as much as 84% in human peripheral blood leukocytes infected with "wild-type" virus. This treatment also reduced the number of peripheral blood leukocytes producing intracellular viral antigen by 71%. Of interest, no reduction in either parameter was observed for the antisense-containing liposomes. The results demonstrate the promise of a new liposomal delivery vehicle to inhibit human immunodeficiency virus replication by an entrapped oligodeoxynucleotide.

Antiviral Agents↗
PubMed1992

Bronchial epithelial cell-derived cytokines (G-CSF and GM-CSF) promote the survival of peripheral blood neutrophils in vitro.

Neutrophil accumulation in the respiratory tract occurs in a variety of inflammatory disorders, particularly those associated with cigarette smoking. We examined whether bronchial epithelial cells could contribute to this accumulation through the production of factors that increased the survival of neutrophils. Pure primary cultures of human bronchial epithelial cells (HBEC) were used to generate conditioned medium (CM), and the effect of this CM on the survival of neutrophils in vitro was examined. When neutrophils were cultured in control medium, survival was 8.7 +/- 1.7% at 72 h. In contrast, culture of neutrophils in CM resulted in a dose-dependent increase in survival: 22.6 +/- 5.5, 43.6 +/- 4.2, and 64 +/- 3.8% in 1, 10, and 50% CM respectively (mean +/- SEM; P < 0.05). As evidenced by the examination of neutrophil DNA, this prolongation of survival was associated with suppression of apoptosis. Cytokines with known actions on neutrophil biology identified in the CM included granulocyte colony-stimulating factor (G-CSF), granulocyte/macrophage colony-stimulating factor (GM-CSF), and interleukin-8. Through the use of specific neutralizing antibodies, G-CSF and GM-CSF were identified as promoting neutrophil survival. Neutrophil survival was prolonged in the presence of either recombinant human (rh) G-CSF or rhGM-CSF alone in a dose-dependent fashion. In contrast to the response of eosinophils to HBEC-CM, steroid treatment did not prevent the increase in neutrophil survival induced by HBEC-CM. In summary, we show that bronchial epithelial cells markedly increase the survival of human neutrophils in vitro via the release of G-CSF and GM-CSF.(ABSTRACT TRUNCATED AT 250 WORDS)

Apoptosis↗
PubMed1992

Visceral leishmaniasis: a model for infection-induced cachexia.

Parasitic infections and malnutrition coexist in many tropical and subtropical areas. Studies of Leishmania donovani and of experimentally infected Syrian hamsters have provided important insights into the complex interrelationships between malnutrition and this parasitic disease. Malnutrition, which adversely affects cell-mediated immunity, is associated with the development of visceral leishmaniasis (kala-azar) in children living in endemic areas. In turn, L. donovani can cause wasting as well as hepatosplenomegaly, fever, and anemia. Syrian hamsters infected with L. donovani develop a disease that is comparable to that of humans with kala-azar. Weight loss in infected hamsters is associated with splenic macrophage secretion of potentially catabolic cytokines as measured by the D10.G4.1 assay for interleukin-1 and the L929 cytotoxicity assay for tumor necrosis factor/cachectin. Although decreased food intake contributes to wasting in infected hamsters, studies of skeletal muscle function indicate that it is not the sole factor. Leishmania donovani-infected hamsters have also been used to study drugs with the potential to prevent or reverse cachexia.

Adipose Tissue↗
PubMed1992

Synoviocyte derived granulocyte macrophage colony stimulating factor mediates the survival of human lymphocytes.

Synoviocytes have been shown to be effector cells capable of synthesizing and secreting a variety of cytokines and growth factors. We demonstrate here that synoviocyte derived conditioned medium has immunoregulatory properties as it enhances human peripheral blood lymphocyte survival in a dose dependent manner in vitro. The effect elicited by synoviocyte derived conditioned medium from patients with rheumatoid arthritis (RA) was greater than that induced by synoviocyte derived conditioned medium from patients with osteoarthritis. Granulocyte-macrophage colony stimulating factor (GM-CSF) was found in synoviocyte derived conditioned medium with significantly higher levels present in synoviocyte derived conditioned medium from patients with RA. Recombinant human GM-CSF induced survival of human lymphocytes in vitro and a monoclonal antibody to human GM-CSF fully abrogated synoviocyte derived conditioned medium induced survival. Our results demonstrate that synoviocyte derived GM-CSF may be important in the retention of lymphocytes, which is a central pathological characteristic of the rheumatoid joint.

Arthritis, Rheumatoid↗
PubMed1991

Sequence-specific DNA-binding proteins within the Mbcr on the Ph1 chromosome.

The Philadelphia1 (Ph1) chromosome results from a reciprocal translocation between chromosome 9 and chromosome 22, which fuses a portion of the ABL oncogene to the BCR gene, forming the BCR/ABL fusion gene. This produces a fusion protein with a greatly increased protein tyrosine kinase activity in comparison to that of the normal ABL protein. The BCR/ABL gene is transcribed from the promoter of the normal BCR gene, but little is known about the regulation of its expression. In this study, we asked whether there are sequence-specific DNA-binding proteins (DBP) that bind to the breakpoint cluster region (bcr, or Mbcr) within the BCR gene. Sequence-specific DBP located within the Mbcr could have a transcription-regulating effect, and they could participate in the recombination that generates BCR/ABL. Our data show that there are sequence-specific DBP that bind within the Mbcr.

DNA, Neoplasm↗
PubMed1991

Role of herniography in the diagnosis of occult hernias.

Twenty-two patients with groin or incisional pain and normal physical examinations underwent herniography. Eight patients were found to have 11 unsuspected hernias. Seven were direct, two indirect, and two incisional. Six of nine groin hernias were recurrent. Exploration confirmed the herniographic findings in all patients. Follow-up evaluation of patients undergoing herniorrhaphy revealed resolution of symptoms. Ten of the 14 patients with normal herniograms were asymptomatic 3 months after herniography. In these 22 patients, herniography resulted in a savings of $31,000. We conclude that herniography is cost-effective and useful in patients with abdominal wall pain of obscure etiology.

Adolescent↗
PubMed1991

Structural cell-derived cytokines in allergic inflammation.

Based on observations of fluctuations in progenitors for inflammatory cells during allergic responses, we have proposed that a primary determinant of allergic inflammation involves microenvironmental influences on hemopoietic cell differentiation and phenotype; in addition, as a corollary of this, inflammatory cell burden is proposed as an important indicator of the severity and pattern of the inflammatory process in allergy. The studies outlined here focus on the effects of epithelial-cell- and fibroblast-derived cytokines on granulocytic and monocytic cell differentiation and activation in models involving allergic reactions in the upper and lower airways. Pure cultures of nasal or bronchial epithelial cells or fibroblasts are observed to give rise to cytokines important in inducing the differentiation of basophils, eosinophils, neutrophils and monocyte/macrophages. Gene expression, production and secretion of granulocyte/macrophage-colony-stimulating factor, interleukin-6 (IL-6) and IL-8 can be demonstrated in vitro and in vivo. Up-regulation of gene expression and production of these cytokines, which are important in inducing basophil, eosinophil and neutrophil/macrophage differentiation in several assays, is seen with IL-1 and the neuropeptide substance P; conversely, inhibition of cytokine production by structural cells is observed after pretreatment with corticosteroids in vitro, paralleling in vivo effects. Other modulatory effects also examined include: antiallergic compounds, which may affect posttranscriptional events in cytokine production, and heavy metal ions, which can also induce changes in gene expression. Structural-cell-derived extracellular matrices appear also to be important both in mast cell differentiation and in macrophage cytokine gene expression, both of which potentially feedback upon chronic allergic inflammatory processes, leading to their perpetuation.(ABSTRACT TRUNCATED AT 250 WORDS)

Bronchi↗