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Biomedical subjects

E J Krul

Publications and source records attributed to E J Krul.

16 recordsLinked to original sources
PubMed1999

Different profiles of allelic losses in cervical carcinoma cases in Surinam and The Netherlands.

BACKGROUND: Cervical carcinoma is the second most common malignancy among women worldwide. The highest incidence rates are observed in developing countries. The increased susceptibility to cervical carcinoma in high incidence populations may result from several factors including human papillomavirus exposure and both inherited and acquired genetic traits. Using comparative molecular analysis of cervical carcinomas from Surinam, a high incidence area, and the Netherlands, a low incidence area, distinct molecular genetic profiles were studied in two populations with contrasting risk for the disease. METHODS: In the two populations, the authors compared allelic loss as a marker for the involvement of putative tumor suppressor genes in 40 and 67 carcinoma specimens from Surinam and the Netherlands, respectively. Loss of heterozygosity (LOH) analysis was performed using polymorphic microsatellite markers at sites of known tumor suppressor genes (17p [p53], 13q [Rb, BRCA2], 16q [E-cadherin], and 17q [BRCA1]) and at chromosomes 3p, 6p, 6q, and 11q, which frequently are lost in cervical carcinoma. RESULTS: Remarkable differences in LOH were found between both populations. The most prominent observation was the extremely high frequency of LOH, up to 72%, in the region of the major histocompatibility complex on chromosome 6p in specimens from Surinam. In the group of specimens from the Netherlands, only 45% of LOH was observed at this locus. In addition, LOH was detected significantly more frequently at 6q and 13q in the cases from Surinam whereas LOH was found more frequently at 17p in cases from the Netherlands. CONCLUSIONS: The results of the current study show that heterogeneity exists in tumor-associated somatic genetic alterations between these two populations that may be indicative of the existence of multiple genetic pathways in cervical tumorigenesis.

Adult↗
PubMed1999

HLA and susceptibility to cervical neoplasia.

The association between cervical neoplasia and certain HLA phenotypes observed in different studies has not been consistent. By serological typing, the association between HLA antigens, cervical carcinoma and cervical intraepithelial neoplasia (CIN) was studied in a group of 172 and 116 patients, respectively. We demonstrated an increased frequency of B63 in patients with HPV types other than HPV 16 or 18, and B55 in patients that were negative for all HPV types. The association between cervical carcinoma and DQ3, described in various populations, was not observed in the present study. However, we confirmed other previously observed associations between cervical cancer and class II antigens, i.e., a positive correlation with DR15 irrespective of the HPV status, with DR3 in patients harboring HPV types other than HPV 16 or 18, and with DR11 among HPV 16 positive patients. In contrast, a negative correlation between DR13 and HPV positive cervical cancer was observed which suggests protection of this antigen against HPV-associated cervical cancer. A slight increase of DR15 and DQ4 antigens was observed in CIN patients, suggesting that these specific HLA antigens may be important in determining the risk of CIN.

Carcinoma↗
PubMed1999

Vaccination with HPV16 peptides of patients with advanced cervical carcinoma: clinical evaluation of a phase I-II trial.

A phase I-II clinical trial was performed involving vaccination with HPV16 E7 peptides of patients suffering from HPV16 positive cervical carcinoma which was refractory to conventional treatment. Patients receiving the vaccine were HLA-A*0201 positive with HPV16 positive cervical carcinoma. The clinical trial was designed as a dose-escalation study, in which successive groups of patients received 100 micrograms, 300 micrograms or 1000 micrograms of each peptide, respectively. The vaccine consisted of two HPV16 E7 peptides and one helper peptide emulsified in Montanide ISA 51 adjuvant. 19 patients were included in the study, no adverse side-effects were observed. 2 patients showed stable disease for 1 year after vaccination; 15 patients showed progressive disease of whom 1 died during the vaccination treatment due to progressive disease; and 2 patients showed tumour-regression after chemotherapy following vaccination. A relative low count of lymphocytes before and after vaccination was present in 11/19 patients indicating that these patients were immunocompromised. This study shows that HPV16 E7 peptide vaccination is feasible, even in a group of patients with terminal disease. This paves the way for vaccinating patients with less advanced disease, whose immune system is less compromised by progressive disease.

Adult↗
PubMed1996

Cervical carcinoma in Surinam. Incidence and staging of cervical carcinoma between 1989 and 1994.

BACKGROUND: Epidemiologic data show a high incidence of cervical cancer throughout the world and a high mortality, particularly in developing countries. The aim of this study was to describe the incidence and stages of cervical carcinoma in Surinam. Results were compared with data from The Netherlands (used as representative of western European countries) because of a medical and patient exchange program. METHODS: Data for Surinamese patients analyzed in this study were based on the files from the Department of Pathology at the University of Surinam from 1989 through 1994. Cumulative and incidence rates standardized to the World Standard Population were calculated and compared with rates in other South American countries and in The Netherlands. Age distribution and stage of disease (according to the International Federation of Gynecology and Obstetrics) among Surinamese and Dutch women were compared. Furthermore, differences in incidence rates among the multiple ethnicities of the Surinamese population were evaluated. RESULTS: Age standardized incidence rates for Surinam and The Netherlands were 26.7 and 6.2 per 100,000 women, respectively. The cumulative rate up to age 74 years was 2.9 in Surinam versus 0.6 in The Netherlands. Incidence in Surinam rose sharply with age. More than 40% of the Surinamese women presented with Stage IIB disease or higher compared with 12% in The Netherlands. In Surinam, low stage of disease was highest in the youngest group (48%), whereas only 18% of women 65 years or older presented with Stage I disease. Incidence rates in Surinam varied by ethnic group. Amerindians and Javanese were more likely to develop cervical cancer than were other ethnicities. CONCLUSIONS: Cervical carcinoma in Surinam was characterized by high incidence rates and relatively advanced stage of disease at presentation. Moreover, incidence was not equally distributed among the different ethnic groups. This may reflect a greater exposure to risk factors and differential access to diagnostic and treatment services.

Adult↗
PubMed1994

The expression of histocompatibility-related leukocyte antigens in the pathway to cervical carcinoma.

The major histocompatibility complex probably plays a crucial role in the efficacy of the cellular immune response against virally infected cervical diseases. Therefore, the allele-specific histocompatibility-related leukocyte antigens (HLA) class I and II expression on normal (n = 10), premalignant (n = 25), and malignant cervical tissue (n = 30) was investigated. No alterations in monomorphic or locus/allele-specific HLA class I or II expression were observed in normal and premalignant epithelial tissue. In cervical carcinomas, however, a reduced expression of HLA class I antigens was present in 70% of the cases, comprising a monomorphic class I loss in 20%, and an allele-specific loss in 50% of HLA-A2-, 66% of A3-, 56% of Bw4-, and 37% of Bw6-positive patients. De novo expression of class II antigens was observed in 80% of the cervical carcinomas, with the sublocus products being expressed in the order HLA-DR > HLA-DQ > HLA-DP. The authors' results show that alteration in HLA expression is a process confined to malignant cells, which may allow tumors to evade immune surveillance. In addition, these findings have to be considered as new strategies of immunotherapy using cytotoxic T lymphocytes are developed.

Alleles↗
PubMed1994

Cytokine regulation of parathyroid hormone-related protein messenger ribonucleic acid levels in mouse spleen: paradoxical effects of interferon-gamma and interleukin-4.

Under normal physiological conditions, PTH-related protein (PTHrP) is produced in a wide variety of tissues and is thought to act locally in an autocrine or paracrine fashion more analogous to cytokines than to classic hormones such as PTH. In addition, we have recently shown that, like cytokines, PTHrP is induced in the spleen during the response to sublethal doses of endotoxin [lipopolysaccharide (LPS)] an effect that is mediated by tumor necrosis factor (TNF). As complex cytokine cascades are induced in response to infectious or inflammatory stimuli, the effects of other prototypical inflammatory [interferon-gamma (IFN gamma)] or antiinflammatory [interleukin-4 (IL-4)] cytokines on PTHrP gene expression were studied. Paradoxically, IFN gamma (50 micrograms), a cytokine that usually synergizes with TNF, inhibited LPS induction of splenic PTHrP messenger RNA (mRNA) levels in LPS-sensitive C3H/OuJ (OuJ) and LPS-resistant C3H/HeJ (HeJ) mice. The stimulation of splenic PTHrP mRNA levels caused by the administration of TNF alpha or interleukin-1 beta was similarly inhibited by IFN gamma, a type II interferon. In contrast, IFN alpha (50 micrograms), a type I interferon, stimulated splenic levels of PTHrP mRNA. IL-4, a prototypical antiinflammatory cytokine, also had a paradoxical effect on LPS induction of splenic PTHrP mRNA levels. Instead of inhibiting LPS induction of splenic PTHrP mRNA levels in OuJ or HeJ mice, IL-4 (200 ng) actually stimulated PTHrP mRNA levels. These complex cytokine interactions suggest that the expression of PTHrP in response to infectious or inflammatory stimuli depends on the counterbalancing effects of the specific cytokine networks induced by each stimulus.

Animals↗
PubMed1993

Endotoxin increases parathyroid hormone-related protein mRNA levels in mouse spleen. Mediation by tumor necrosis factor.

Parathyroid hormone-related protein (PTHrP) causes hypercalcemia in malignancy. However, the role and regulation of PTHrP in normal physiology is just beginning to be explored. PTHrP is found in the spleen and has several other features common to cytokines. Since endotoxin (LPS) causes many of its effects indirectly by inducing cytokines, studies were undertaken to determine whether LPS might also induce splenic PTHrP expression. LPS (100 ng/mouse) increased splenic PTHrP mRNA levels 3.6-fold in C3H/OuJ mice. This effect was maximal at 2 h and returned to baseline by 4 h. PTHrP peptide levels also increased 3.3-fold in splenic extracts in response to LPS (1 microgram/mouse). Murine TNF-alpha and human IL-1 beta, cytokines that mediate many of the effects of LPS, also increased splenic PTHrP mRNA levels. LPS-resistant C3H/HeJ mice, which produce minimal amounts of TNF and IL-1 in response to LPS, were resistant to LPS induction of splenic PTHrP mRNA, while TNF-alpha and IL-1 beta readily increased PTHrP mRNA levels in C3H/HeJ mice. Anti-TNF antibody blocked LPS induction of splenic PTHrP mRNA in C3H/OuJ mice by 68%, indicating that TNF is a mediator of the LPS induction of PTHrP levels. In contrast, an IL-1 receptor antagonist (IL-1ra) was ineffective. The increase in PTHrP in the spleen during the immune response suggests that PTHrP may play an important role in immune modulation, perhaps by mediating changes in lymphocyte proliferation and/or function.

Animals↗
PubMed1993

Effect of endotoxin on cholesterol biosynthesis and distribution in serum lipoproteins in Syrian hamsters.

Infection and inflammation increase serum triglyceride and cholesterol levels in rodents and rabbits. Endotoxin (LPS) has been used as a model of infection and its effects on triglyceride metabolism have been previously characterized. In the present study we demonstrate that both low (100 ng/100 g body weight) and high dose (100 micrograms/100 g body weight) LPS increase serum cholesterol levels in hamsters. The increase in serum cholesterol is first observed 16 h after LPS and persists for at least 24 h. This increase is primarily due to an increase in low density lipoprotein (LDL) cholesterol. High density lipoprotein (HDL) cholesterol levels decrease after LPS treatment. Both low and high dose LPS increase hepatic cholesterol synthesis (low dose 85%, high dose 205%) and total HMG-CoA reductase activity (low dose 2.97-fold, high dose 9.96-fold). However, the proportion of HMG-CoA reductase in the active form is reduced by LPS treatment. Additionally, the mass of HMG-CoA reductase protein in the liver, measured by Western blotting, is increased after LPS. Moreover, LPS increases hepatic HMG-CoA reductase mRNA levels (low dose 3.1-fold, high dose 14.2-fold). The increase in hepatic HMG-CoA reductase mRNA levels is first seen 4 h after LPS and persists for at least 24 h. In contrast, LPS had only minimal effects on hepatic LDL receptor protein and mRNA levels. These results suggest that LPS increases serum cholesterol levels by increasing hepatic cholesterol synthesis. LPS administration decreases apoE mRNA levels in the liver while having no effect on apoA-I mRNA levels. These results suggest that HMG-CoA reductase is a member of a group of hepatic proteins that are positively regulated by inflammatory stimuli (acute phase proteins) while apoE can be considered a negative acute phase protein in hamsters. It is possible that increases in hepatic HMG-CoA reductase provide cholesterol that allows for the increased production of lipoproteins and elevations in serum lipid levels that may be beneficial to the body's host defense.

Animals↗
PubMed1991

Cognitive function after spinal or general anesthesia for transurethral prostatectomy in elderly men.

Cognitive functions in 53 elderly men who underwent a transurethral prostatectomy were assessed pre-operatively and 4 days and 3 months post-operatively. Thirteen patients had a preference for one particular type of anesthesia, and the remaining 40 were randomly allocated to receive either spinal or general anesthesia. Cognitive function was not different between the groups receiving different types of anesthesia at either time point and did not decrease post-operatively. No pre- or perioperative variable could distinguish the subgroup of patients who had a post-operative decrease of 2 points or more on the Mini-Mental State Examination. No difference in post-operative performance was found in the patient groups with pre-operative Mini-Mental State Examination scores above or under their age-specific norm. It is concluded that neither hospitalization nor the two forms of anesthesia investigated cause a decrease in cognitive function in elderly men.

Aged↗
PubMed1986

Continuous venous access in children for long-term chemotherapy by means of an implantable system.

Between June 1983 and December 1984, 42 Port-a-Cath (PAC) systems have been implanted to establish continuous venous access in 42 children (aged 1 to 16 years) undergoing long-term chemotherapy. The PAC is a totally implantable closed system. Absence of permanent skin penetration decreases the risk of infection. The PAC gives more freedom and less discomfort to the child than a percutaneous system. The complication rate seems acceptable in comparison with that of other methods.

Adolescent↗
PubMed1986

[Experiences with a completely implantable intravenous system in children].

A totally implantable system for venous access has been implanted in 65 children with chronic disease requiring repeated or/and prolonged intravenous therapy. The experiences are described. They indicate that the use of wide catheters (internal diameter greater than or equal to 0.76 mm) and a position of the catheter in the vena cava superior/right atrium rarely give complications, besides a relatively low incidence of sepsis. The children accept the use of the system very well and the easy venous access decreases their emotional stress during a long period of intensive therapy.

Catheterization↗
PubMed1985

Mesoblastic nephromas: a study of 29 tumours from the SIOP nephroblastoma file.

In a series of 889 Wilms' tumours we found 29 pure mesoblastic nephromas. The age of the patients varied from newborn to 22 months, but only five were older than four months. Two histologic types were recognized--leiomyomatous (9) and cellular (20) with a fibrohistiocytic appearance. The leiomyomatous type was almost invariably in stage I, smaller and present in younger infants. At operation half of the cellular type has ruptured or infiltrated the renal pelvis or perirenal tissue. Two patients died of postoperative complications. All others are alive after four years and free from disease.

Female↗
PubMed1983

[Dyspnea caused by tracheal stricture following operative treatment of esophageal atresia].

This report describes eight children with esophageal atresia who developed 'dyspnea spells' during feeding. These spells were caused by a combination of tracheomalacia and tracheal compression. One patient in addition had a vascular ring. Common characteristics in these patients were: low birth weight, other congenital abnormalities and a short esophagus. The diagnosis was confirmed endoscopically. Operative therapy consisted of hemithymectomy and aortopexy. In six patients the symptoms disappeared completely, the two other children improved. The operation appears an effective means of dealing with severe dyspnea spells in children after correction of esophageal atresia.

Aorta, Thoracic↗