PubMed Health⌕ Search

Biomedical subjects

R Dennin

Publications and source records attributed to R Dennin.

13 recordsLinked to original sources
PubMed1997

Expression of complement receptors and regulatory proteins on alveolar CD4+ lymphocytes from human immunodeficiency virus-1 infected individuals.

Several lines of evidence suggest a dysregulation of the complement system in human immunodeficiency virus-1 (HIV-1) infected patients. The aim of this study was to elucidate whether CD4+ alveolar lymphocytes from HIV-1 infected patients show a loss of complement regulatory proteins that would render these cells susceptible to antibody-dependent complement-mediated cytotoxicity. We investigated the expression of complement regulatory (CD46, CD55, CD59) and complement receptor (CR1, CR2, CR3, CR4) proteins on alveolar cells by flow cytometry. Cells were obtained by bronchoalveolar lavage from 17 HIV-1 infected and 12 HIV-1 negative individuals. Expression of adhesion molecules (leucocyte functional associated antigen-1 (LFA-1), intercellular adhesion molecule-1 (ICAM-1)) and CD30 were evaluated in patient subgroups. In addition, interleukin (IL)-1beta, tumour necrosis factor alpha (TNF-alpha), IL-4 and interferon gamma (IFN-gamma) concentrations were measured in supernatants of alveolar cells. We found a significantly reduced expression of CD46 and CD59 on CD4+ alveolar lymphocytes from HIV-1 infected individuals, whereas the expression of CR3, CR4, ICAM-1 and CD30 was increased. IL-1beta and TNF-alpha concentration in supernatants of alveolar cells was augmented in HIV-1 infected patients, but did not correlate with the expression of surface molecules. IFN-gamma concentration was also increased and showed an inverse relationship to the surface expression of CD30 on CD4+. Our data suggest that in human immunodeficiency virus-1 infection an increased level of activation is associated with a diminished expression of complement regulatory proteins on CD4+ alveolar lymphocytes. This phenomenon might contribute to the depletion of CD4+ lymphocytes and the local immunodeficiency in the pulmonary compartment.

Adult↗
PubMed1993

A longitudinal prospective study of cytomegalovirus pp65 antigenemia in renal transplant recipients.

Cytomegalovirus (CMV)-encoded pp65 antigen in peripheral blood leukocytes (CMV antigenemia) was investigated in 1017 serial samples from 64 patients for 16 weeks after renal transplantation in a prospective study. In 110 samples from 24 patients, at least one antigen-positive leukocyte was identified. The median number of stained cells was 4 (range 1-1000) per 4 x 10(5) leukocytes. Twenty-one of 24 patients with serological signs of an active CMV infection were antigen-positive (sensitivity 87.5%), whereas 3 patients with antigenemia did not show serological signs of infection during the observation period (specificity 92.5%). Positive results were obtained 19 days (median) before serological response and 9 days (median) before the onset of CMV syndrome. The sensitivity in defining a CMV syndrome was 100% (n = 8). In all patients who presented with CMV syndrome, antigenemia was present prior to the onset of symptoms or on the same day. In contrast, serological monitoring rendered the diagnosis of CMV infection possible at the onset of clinical symptoms in only two of eight patients. We conclude that (1) insufficient results obtained with the CMV antigenemia assay by other investigators are mainly due to technical problems that can easily be overcome by the protocol presented and (2) the detection of CMV pp65 antigen in peripheral blood leukocytes is an excellent tool for rapid and early diagnosis of CMV infection.

Antibodies, Viral↗
PubMed1993

The long persistence of CMV DNA in the blood of renal transplant patients after recovery from CMV infection.

A total of 30-50% of all renal transplant recipients undergo infections caused by human cytomegalovirus. With the introduction of ganciclovir and foscarnet for specific antiviral therapy there is an increasing demand for diagnostic tools that allow the early and rapid identification of CMV as the causative agent of the observed disease. We and others previously showed the direct detection of pp65 antigen in peripheral blood leukocytes to be an excellent marker for active cytomegalovirus infection. In order to establish whether the detection of CMV DNA by the polymerase chain reaction (PCR) supplies further information in this regard, we compared both methods. In 41 renal transplant patients the PCR assay yielded a sensitivity of 100% compared with 87.5% of the antigenemia assay. Specificities reached 67% and 92.5%, respectively. In 5 patients without both serological signs of infection and antigenemia, CMV DNA was also found. The duration of CMV DNA detection in PBL during active infection was significantly longer than antigenemia. Even after successful treatment of symptomatic CMV disease, DNA was present for a period of weeks without any relapse of disease. In contrast, antigenemia disappeared after antiviral therapy and reappeared only in one patient with relapse of CMV disease. We conclude that PCR offers no advantages over antigen detection in monitoring for CMV infections after renal transplantation.

Base Sequence↗
PubMed1992

Phase I trial of murine monoclonal antibody L6 in combination with subcutaneous interleukin-2 in patients with advanced carcinoma of the breast, colorectum, and lung.

PURPOSE: A phase I trial was undertaken to determine the toxicity and biologic effects of a combination of murine monoclonal antibody L6 (MoAb L6) plus subcutaneous (SC) interleukin-2 (IL-2). PATIENTS AND METHODS: Fifteen patients with refractory adenocarcinoma (five breast, five lung, five colorectal), received L6 at 200 mg/m2 intravenously (IV) daily on days 1 to 7, followed by a 1-week rest period. IL-2 was given at either 2, 3, or 4.5 x 10(6) U/m2 daily doses times 4 days for a total duration of 3 weeks. RESULTS: Side effects of L6 consisted of mild fever and chills along with a rash and serum sickness in one patient. One patient developed dyspnea and urticaria, that resolved with antihistamines. Maximum-tolerated dose (MTD) of SC IL-2 was 3 x 10(6) U/m2, with dose-limiting toxicities that consisted of grade 4 fatigue and dyspnea. Significant decreases in complement levels along with increases in absolute lymphocyte count and eosinophil count were observed. Mean antibody-dependent cellular cytotoxicity from mononuclear cells taken from patients who received IL-2 was elevated significantly compared with baseline in all patients independent of IL-2 dose (P less than .05). Serum IL-2 levels were elevated in 13 of 14 patients (range, 0.9 to 100 U/mL). Human antimouse antibody (HAMA) titers were elevated in nine of 14 (64%) patients who were tested between 3 and 8 weeks after L6 infusion. One patient with breast cancer had a transient mixed response, and one patient with colorectal cancer had a partial response. CONCLUSIONS: L6 and SC IL-2 were well tolerated in the majority of patients when given in the outpatient setting. In view of the clinical efficacy of this combination, more phase II trials are warranted.

Adult↗
PubMed1991

Administration of interleukin-2 (IL-2) results in increased plasma concentrations of IL-5 and eosinophilia in patients with cancer.

Peripheral eosinophilia is almost invariably observed during the course of interleukin-2 (IL-2) therapy and is frequently accompanied by the development of a capillary leak syndrome characterized by edema, weight gain, and oliguria. We studied five patients with advanced malignancy treated with IL-2. Eosinophilia was not present initially but developed in all patients late in the course of therapy, with counts ranging from 2,328/mm3 to 15,958/mm3. In all patients, there was a temporal relationship between the infusion of IL-2 and the appearance of elevated plasma concentrations of IL-5, a growth factor for eosinophils. Granulocyte-macrophage colony-stimulating factor was not detectable in plasma. IL-4 and gamma-interferon plasma levels were variably elevated. Plasma concentrations of major basic protein, a toxic eosinophil granule protein, began increasing before eosinophil counts increased. By the time of the third IL-2 infusion, high concentrations of major basic protein were present in all five patients (up to 5,600 ng/mL) and skin biopsies showed major basic protein deposition in the dermis. Four patients developed significant capillary leak syndrome and all of these patients showed markedly elevated major basic protein levels. The lowest peak plasma concentration of major basic protein (1,751 ng/mL) was observed in the one patient who did not develop edema and weight gain. These results suggest that IL-2 induces IL-5 leading to marked peripheral eosinophilia and extravascular eosinophil degranulation. The release of toxic eosinophil products at extravascular sites and in the circulation may contribute to the pathogenesis of the capillary leak syndrome complicating IL-2 therapy.

Aged↗
PubMed1989

Multiple infections in cases of cervical cancer from a high-incidence area in tropical Africa.

The presence of several infections was determined in tissue and serum samples from 34 cases and 23 controls seen in 1984-85 at Mulago Hospital in Kampala, Uganda. When assessing single infections, association with cervical cancer could be shown for 5 agents, namely by Southern blot assay for human papillomavirus types 16 and 18 (HPV), and by serological tests at varying levels of antibody titres, for herpes simplex virus type I and/or 2 (HSV), cytomegalovirus (CMV), Epstein-Barr virus, viral capsid antigen (EBV-VCA), and Chlamydia trachomatis (CLT). Due to interaction, HSV and CMV were associated with cervical cancer only when infection by both of these agents was demonstrable. In the assessment of the simultaneous presence of these 5 infections, moderately high antibody titres were taken as the cut-off point for infection by HSV, CMV, EBV-VCA, and CLT. This showed that 3 and 4 infections at a time were seen in the majority of the cases in contrast to the controls with essentially no more than 2 such infections. A linear trend in the rise of risk for cervical cancer was noted with increasing number of infections.

Antibodies, Viral↗
PubMed1984

[Risk of chickenpox during pregnancy and the neonatal period].

A newborn fell ill from congenital chickenpox eight days after delivery, a chickenpox rash having been noted in the mother two days before delivery. Administration of zoster-hyperimmune serum to the mother at the onset of the rash and to the child immediately after birth had no demonstrable effect on the course of the disease. Autopsy, the baby having died on the eleventh day post-partum, revealed focal necrotizing pneumonia of all the lobes. Varicella-zoster virus was isolated from lung material. On the basis of present knowledge the risk of varicella infection in the fetus and neonate is 1-7 maternal cases per 10 000 pregnancies. Transplacental passage of the virus can occur at any time during pregnancy. A congenital varicella syndrome is very rare in the first two thirds of pregnancy, but bland infection of the fetus is also likely. Illness of the mother at the end of pregnancy leads to clinically manifest varicella in about a quarter of neonates. The death-rate of congenital varicella is up to 30% if the mother falls ill between the fourth day before and the second day after delivery. Neonatal varicella acquired post-partum takes a relatively mild course. The most important prophylactic measure, in addition to the administration of zoster-hyperimmune serum to the mother within three days of incubation, is to delay delivery past the critical period.

Adult↗
PubMed1984

[Prevention of infection in sonography].

The instruments and surroundings of five ultrasound diagnostic departments were tested for bacteria, antimicrobic characteristics, and prevalence of Hbs Ag in commercial contact medium (cellulose) and were also analysed after contamination in vitro. Facultative pathogenic bacteria as well as normal skin bacteria were found on the ultrasound equipment. It was established that cellulose and oils taken from wide- mouthed containers and applied manually or with a brush, were often contaminated. However, no contamination was evident in contact medium that was still in its original packing or stored in small containers and subsequently refilled daily. No antimicrobic activity on the part of preservative agents in the cellulose could be demonstrated after artificially contaminating some contact medium with Staph. aureus and E. coli. Elimination of artificially added Hbs Ag in the contaminated contact medium could not be proven. It is postulated that transfer of bacteria or Hepatitis B infection during an ultrasound diagnosis is possible. It is therefore recommended that appropriate prophylactic hygienic measures be taken, especially with patients susceptible to infection.

Bacterial Infections↗
PubMed1983

Cell and virus sensitivity studies with recombinant human alpha interferons.

The cell sensitivity of recombinant human alpha interferons (rIFN-alpha) of greater than 95% purity (A,D and the hybrid A/D) and crude nature (B and F) was studied in human (WISH, HeLa, AG1732), bovine (MDBK, BT), monkey (Vero), mouse (L), rabbit (RK-13), and hamster (BHK-21) cells. Based on an activity of 100% in WISH cells, the other cells responded to rIFN-alpha A as follows: AG1732 (90%), HeLa (94%), and MDBK and BT cells (170-190%). Rabbit, mouse, and hamster cells had a relative sensitivity of less than 1%. rIFN-alpha B and F were essentially equivalent to rIFN-alpha A in terms of cell sensitivity, but MDBK and BT cells were about 20 times more sensitive to rIFN-alpha D than were WISH cells and rIFN-alpha D was 1/5 to 1/10 as active on L cells as on WISH cells. The activity of the hybrid IFN A/D on bovine, mouse, and human cells was similar. The inhibitory dose50 (U/ml) of rIFN-alpha A, B, D, and F against virus infections in WISH cells were: vesicular stomatitis virus (1-4), rhinovirus types 1 and 42 (2-18), and herpes simplex virus (HSV) type 2 (45-70). Type 1 HSV, Semliki Forest (SFV) and encephalomyocarditis (EMC) viruses were tested against only rIFN-alpha A and D where SFV and EMC were the most sensitive to both IFNs (ID50-SFV, 0.2 U/ml, EMC, 1.2 U/ml) while 13 U/ml of rIFN-alpha A and D inhibited Type 1 HSV. The various rIFN-alpha s did not exhibit different antiviral spectra in vitro. When tested in mice rIFN-alpha A did not protect against infections with SFV, EMC, HSV, or influenza viruses. rIFN-alpha D and A/D protected mice infected with EMC, SFV, or HSV.

Animals↗
PubMed1982

[Heck's focal epithelial hyperplasia].

Three patients with focal epithelial hyperplasia Heck are presented. In two cases biopsies were made and investigated biochemically and by electron microscopy. In one case typical papillomavirus and HPV 1-DNA could be demonstrated, in the other the attempts of isolation failed. Virologic results and epidemiologic considerations suggest a viral etiology of focal epithelial hyperplasia Heck, but they are not sufficient to prove this.

Adult↗