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Biomedical subjects

J Andersson

Publications and source records attributed to J Andersson.

At least 217 records · Page 12Linked to original sources
PubMed1992

Lipopolysaccharide induces human interleukin-1 receptor antagonist and interleukin-1 production in the same cell.

A new member of the interleukin-1 (IL-1) family has recently been described. Human IL-1 receptor antagonist (IL-1ra) is structurally related to IL-1 alpha and IL-1 beta but binds to IL-1 receptors on various target cells without demonstrable agonist activity. Understanding the mechanisms of regulation of IL-1ra production may clarify the biology of this unique cytokine as well as elucidate its possible role as a natural anti-inflammatory protein. The effects of lipopolysaccharide (LPS) on IL-1 alpha, IL-1 beta and IL-1ra production was studied at a single-cell level by use of cytokine-specific antibodies and indirect immunofluorescence technique. The peak synthesis of IL-1ra and IL-1 alpha/beta occurred in peripheral blood monocytes obtained from healthy blood donors within 4 and 6 h of cell stimulation, respectively. By double-staining procedure all IL-1ra-positive cells were also IL-1 alpha and/or beta positive. Thus, endotoxin induced simultaneous synthesis of the IL-1 gene family in the same cells. Only monocytes contributed to the production of IL-1 alpha, beta and IL-1ra during the 96 h of cell culture. The maximum number of IL-1ra-producing monocytes was 48 +/- 16% as compared to peak production of IL-1 alpha and beta which occurred in 75 +/- 9% and 80 +/- 12% (p < 0.001), respectively, of all peripheral blood monocytes. The incidence of IL-1 alpha- and beta-containing cells was not only significantly higher but also occurred for a longer time period, 72 h as compared to 24 h for IL-1ra localized in the Golgi organelle. However, IL-1ra-containing cells with a diffuse cytoplasmic appearance were also evident (20%-30%) at a later stage, 12 to 72 h after stimulation. Blocking IL-1 surface receptors by addition of exogenous recombinant IL-1 beta before stimulation could not inhibit the diffuse cytosolic localization. This indicates that the "late" staining pattern did not reflect IL-1ra being secreted and internalized after binding to extracellular receptors. Thus, perhaps IL-1ra modulates IL-1 effector mechanisms by receptor interactions both inside and outside the cell.

Adult↗
PubMed1992

Immunoglobulin G subclasses and lymphocyte stimulatory responses to cytomegalovirus in transplant patients with primary cytomegalovirus infections.

The early activation of T- and B-cell responses to cytomegalovirus was studied in immunosuppressed patients. Primary lymphocyte stimulation to cytomegalovirus (CMV) antigen, a measure of T-helper activity, and anti-CMV IgG subclass responses were analyzed. Ten patients suffering from primary CMV infection following renal transplantation were studied. Of the ten, nine became positive for CMV induced lymphocyte proliferation 5-40 weeks after transplantation. Nine showed an almost simultaneous appearance of anti-CMV IgG1 and three at 3-32 weeks after transplantation, while one patient synthesized only low levels of anti-CMV IgG1. The lymphocyte proliferation assays have limited diagnostic value for primary CMV infection in renal transplant patients. The humoral and cellular immune responses seemed to be independent of each other.

Adolescent↗
PubMed1992

Effectiveness of low-dose cotrimoxazole prophylaxis against Pneumocystis carinii pneumonia after renal and/or pancreas transplantation.

We retrospectively examined the effectiveness of prophylaxis with cotrimoxazole in preventing Pneumocystis carinii pneumonia in recipients of kidney and combined kidney-pancreas transplants between 1985 and 1989. Cotrimoxazole prophylaxis (480 mg daily or 300 mg/m2), when used, was started within 2 months after transplantation and usually continued until 6 months after surgery. Eight (3.7%) of the 214 patients who were not given prophylaxis were infected with Pneumocystis carinii, and there were 4 fatalities (50% mortality). There were no cases among the 161 patients given prophylaxis (P less than or equal to 0.03). No serious adverse effects were noted in the prophylaxis group. It is concluded that prophylaxis against Pneumocystis carinii infection is well tolerated and should be given as soon as possible to all organ transplant recipients for at least 6 months.

Adolescent↗
PubMed1992

Endotoxin and Staphylococcus aureus enterotoxin A induce different patterns of cytokines.

The effects of Staphylococcus aureus enterotoxin A (SEA) and lipopolysaccharide (LPS) in cytokine production were assessed at the single cell level in cells obtained from healthy blood donors. Cytokine production was studied with UV-microscopy of fixed and permeabilized cells stained with cytokine specific monoclonal antibodies. The cytokines evaluated included tumour necrosis factor (TNF)-alpha, interleukin (IL)-1 alpha, IL-1 beta, IL-6, IL-8, IL-10, IL-2, IL-4, interferon (IFN)-gamma and TNF-beta. LPS exhibited marked production of IL-1 alpha, IL-1 beta, TNF-alpha, IL-6 and IL-8. After LPS stimulation IL-1 alpha, IL-1 beta, TNF-alpha and IL-8 were the dominating products, all peaking at or before 4 hours after cell stimulation. In addition, IL-10 production was evident after 12 hours of cell stimulation. The T-lymphocyte-derived cytokines TNF-beta, IL-2, IFN-gamma and IL-4 were never detected in the cultures. All cytokine production, except IL-8, was downregulated at 96 hours. In contrast, peak production of IL-1 alpha, IL-1 beta and IL-8, which were the dominant products, occurred after 12 hours in the SEA-stimulated cultures. Further, a significant T-lymphocyte production of TNF-beta, TNF-alpha, IFN-gamma and IL-2 was found with peak production 12-48 hours after initiation. Only low amounts of IL-6 were evident. The two types of cytokine pattern and kinetics found may correspond to the different clinical conditions after invasive Gram-negative Escherichia coli vs Gram-positive Staphylococcus aureus infections in humans, with a much more rapid onset of disease after E. coli infections.(ABSTRACT TRUNCATED AT 250 WORDS)

Cytokines↗
PubMed1992

On the origin of natural IgM in immunoglobulin transgenic mice.

Surface transgenic IgM was expressed by > 95% of small resting splenic B cells but only by 50% of CD5+ and CD5- peritoneal B cells from the mu-transgenic mouse line M54. Transgenic male M54 were crossed with female CBA/N mice carrying the Xid defect. Offspring F1 animals carrying the transgene were analysed for the presence of transgenic and endogenous IgM expressed both in the serum as well as on the surface of splenic and peritoneal B cells. We found that the levels of serum IgM coded for by the transgene were similar in both F1 male, which lack CD5 B cells, and female transgenic mice, which have CD5 B cells. Thus, the Xid defect does not influence the expression of the transgene at the level of naturally activated plasma cells, a finding substantiated by the fact that both male and female naturally activated splenic plasma cells express the transgene at the same frequency. F1 hybrid mice, like transgenic C57BI/6 M54 mice, have naturally activated splenic plasma cells that overexpress endogenous IgM coded for by the VH gene family Q52. The data indicate that normal serum IgM is not derived from CD5+ B cells and that the serum IgM coded for by the mu-transgene from M54 is produced at normal levels even in the male F1 mouse which lacks CD5+ B cells.

Animals↗
PubMed1992

Effects of FK506 and cyclosporin A on cytokine production studied in vitro at a single-cell level.

Mononuclear cells obtained from human blood were mitogen or antigen activated in vitro in the presence or absence of FK506 or cyclosporin A (CsA). Cytokine production was studied at a single-cell level by ultraviolet (UV) microscopy of fixed permeabilized cells using cytokine-specific monoclonal antibodies (mAb). Phenotypic characterization of the monokine-producing cells was achieved by two-colour immunofluorescent staining. Cytokine production after antigen activation with Staphylococcus aureus enterotoxin A (SEA) was significantly reduced. FK506 or CsA inhibited SEA-induced tumour necrosis factor-alpha (TNF-alpha) production both in monocytes (P less than 0.01) and in lymphocytes (P less than 0.001), at a drug concentration of 1-25 ng/ml for FK506 and 100-500 ng/ml for CsA. Lymphocyte synthesis of interleukin-2 (IL-2), interferon-gamma (IFN-gamma) and TNF-beta after SEA activation was also significantly reduced by either of the drugs. In contrast, endotoxin-induced monokine production (TNF-alpha and IL-6) after lipopolysaccharide (LPS) stimulation was unaffected by FK506 or CsA even when added in concentrations as high as 1000 ng/ml. When the cells were stimulated by phorbol ester (phorbol 12-myristate 13-acetate, PMA) plus calcium ionophore (ionomycin), FK506 and CsA inhibited, in a dose-dependent manner, the production of IL-2, IL-4, IL-5, IFN-gamma and TNF-alpha. The 50% inhibitory concentration (IC50) for FK506 or CsA on the cellular synthesis of the various cytokines varied between 0.6 and 1.0 ng/ml and 20 and 60 ng/ml, respectively. Further stimulation by addition of anti-CD28 mAb to the cultures resulted in an augmented IL-2 and IFN-gamma production which was resistant to both FK506 and CsA. This report delineates extensive similarities between the two drugs in mechanisms of immunosuppression by blockade of identical interleukin production. Depending on the mode of cell activation the two drugs inhibited not only cytokine production in lymphocytes but also antigen-induced monokine (TNF-alpha) production in macrophages, although the optimal immunomodulatory effect of FK506 was achieved at a concentration approximately 50-fold lower than that of CsA.

Antigens, CD↗
PubMed1991

Ribavirin treatment for chronic hepatitis C.

We evaluated oral ribavirin as therapy for chronic hepatitis C infection in a pilot study including 10 patients. Patients (7 men, 3 women; mean age 40 years, range 23-54) all had biopsy-proven chronic non-A, non-B hepatitis and were repeatedly positive for antibodies to hepatitis C virus. Treatment was with oral ribavirin 1000-1200 mg per day in two divided doses for 12 weeks. The median serum alanine aminotransferase concentration for all patients at enrollment was 3.15 mu kat/l (range 1.22-7.79) and decreased significantly (p less than 0.005) to 1.25 mu kat/l (0.78-2.04) after 12 weeks of treatment. Within 6 weeks of the end of treatment the median serum alanine aminotransferase concentration was not significantly different from that before treatment. Side-effects were mild and fully reversible after cessation of therapy. We conclude that ribavirin is the first drug to offer a potentially effective oral treatment for chronic hepatitis C. It should be further evaluated in controlled trials, possibly in combination with interferon alpha.

Administration, Oral↗
PubMed1991

Development of intrapancreatic abscess--a consequence of CMV pancreatitis?

Cytomegalovirus (CMV) pancreatitis was diagnosed in eight out of 124 pancreatic transplant recipients. Five of the eight patients developed intrapancreatic abscesses and four of the grafts were lost, but one is still functioning. In the three additional cases of pancreatitis, antiviral treatment with foscarnet or ganciclovir was given as soon as signs of CMV pancreatitis were detected. No such grafts were lost during the acute phase. CMV infection was diagnosed in cells from pancreatic juice, by virus isolation, detection of CMV antigen in cells from pancreatic juice or by CMV serology. The signs and symptoms of CMV pancreatitis included fever, general malaise, abdominal pain, diarrhoea, localized peritonitis, hyperamylasaemia, leukopenia and hyperglycaemia. It is recommended that rapid diagnostic procedures for CMV should be carried out when early signs of pancreatitis develop in pancreatic graft recipients. Antiviral treatment should be given when CMV pancreatitis is suspected or diagnosed in order to prevent the development of intrapancreatic abscesses and graft loss.

Abscess↗
PubMed1991

Waveform pattern recognition--a new semiquantitative method for analysis of fetal aortic and umbilical artery blood flow velocity recorded by Doppler ultrasound.

A semiquantitative computerized waveform pattern recognition system for analysis of the fetal descending aortic and umbilical artery Doppler flow velocity waveforms is presented. Based on empirically and manually selected clinical recordings from both vessels, 11 computerized and normalized standard curves for the aorta (type curves A to K), and 10 curves for the umbilical artery (type curves a to j) were constructed. The best match between the normalized waveform and the standard curve was based on either the degree of absent diastolic flow or, in cases with positive diastolic flow, on the calculation of the least square sum of the difference. The pattern recognition was tested against conventional waveform indices and our older semiquantitative Blood Flow Class (BFC) system in 472 clinical consecutive Doppler recordings. A good correlation was found. This new relatively simple computer-based method for waveform analysis is now prospectively applied in clinical studies.

Aorta, Thoracic↗
PubMed1991

Combined treatment of symptomatic human immunodeficiency virus type 1 infection with native interferon-alpha and zidovudine.

Patients with advanced human immunodeficiency virus type 1 (HIV-1) infection who had p24 antigen despite treatment with zidovudine (AZT) for 4-28 months received 3 x 10(6) IU of native interferon-alpha (IFN-alpha) daily for 3 months. Infectious HIV was detected in the plasma of all patients, in most cases at high titers, before IFN-alpha treatment. There was no correlation between HIV titers and p24 antigen levels. Antiviral activity, as measured by significantly decreased levels of infectious virus or p24 antigen, was observed in six of eight completely treated but in only one of nine incompletely treated patients. After termination of IFN-alpha treatment, there was a significant rise of p24 antigen levels. During IFN treatment, absolute CD4 cell counts showed a tendency toward an increased rate of decline. The side effects were unexpectedly severe. Despite its anti-HIV effect in vivo, IFN-alpha in the dosages used does not seem to be a viable additional treatment for severely immunodeficient patients in ongoing AZT therapy.

Adult↗
PubMed1991

Endogenous VH gene family expression in immunoglobulin-transgenic mice: evidence for selection of antibody repertoires.

VH gene family expression in single cells of the emergent, available and actual B cell repertoires of C57BL/6 mice was compared to that of two immunoglobulin (Ig)-transgenic B6 lines (B6-Sp6 and M54). We found that less than 5% of bone marrow cells of transgenic mice express endogenous VH genes and that the vast majority (95%) of the peripheral, mature B cell repertoire in these animals is composed of cells expressing the VHJ558 transgenic family. Unimmunized transgenic mice, however, diversify VH gene family usage by 'background' Ig-secreting cells in the spleen, greater than 50% of which express endogenous VH genes. The pattern of endogenous VH gene family expression in the actual repertoire of B6-Sp6 mice is indistinguishable from that of normal B6 mice. In contrast, actual repertoires of M54 mice differ by a 4- to 5-fold higher representation of the VHQ52 family. These results demonstrate a powerful positive selection of B cells into the secretory compartments of unimmunized animals, show that actual and available repertoires differ very markedly, and suggest that V region interactions participate in the selection of 'natural antibody' repertoires.

Animals↗
PubMed1991

Maternal blood volume in placenta of the rhesus monkey measured in vivo by positron emission tomography.

The relative volume of the intervillous space of the placenta of the rhesus monkey was measured in vivo using positron emission tomography (PET), a noninvasive tracer technique. 11CO-Hb and 68GaCl3 were both used in three experiments and 68Ga-EDTA in two. The tracers were administered intravenously as bolus doses to 6 pregnant monkeys during 7 different pregnancies. Measurements with 11CO-Hb gave a volume of 48.0% of the total placental volume. Transplacental transfer of 11CO to the fetal circulation is probably a minor problem due to the small fetal blood volume and the prolonged time before the same concentration is reached in the maternal and fetal blood. Measurements with 68GaCl3, which binds to transferrin, gave an intervillous space volume of 55.6% of the placental volume. The concentration of radioactivity in the placenta did not attain a steady state, indicating a clearance of the tracer from the blood only to a small extent. Measurements with 68Ga-EDTA displayed a volume of 60.4% of the placental volume. Transplacental transfer and the additional distribution of radioactivity to fetal and maternal extracellular spaces, including the placenta, when 68Ga-EDTA was used will make this tracer unsuitable in measurements of the blood volume of the placenta with PET.

Animals↗