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A Timmer

Publications and source records attributed to A Timmer.

28 records · Page 2Linked to original sources
PubMed2000

Comparative genomic and in situ hybridization of germ cell tumors of the infantile testis.

Chromosomal information on germ cell tumors of the infantile testis, ie, teratomas and yolk sac tumors, is limited and controversial. We studied two teratomas and four yolk sac tumors using comparative genomic hybridization (CGH) and in situ hybridization. No chromosomal anomalies were found in the teratomas by any of the methods, not even after CGH on microdissected tumor cells. All yolk sac tumors showed aneuploidy, loss of parts of 4q and 6q, and gain of parts of 20q. Underrepresentation of parts of 8q and overrepresentation of parts of 3p, 9q, 12p, 17, 19q, and 22 were detected in most cases. In addition, one recurrent yolk sac tumor after a sacral teratoma was studied, showing a highly similar pattern of imbalances. While CGH demonstrated loss of 1p36 in one testicular yolk sac tumor, in situ hybridization revealed loss of this region in all yolk sac tumors. High-level amplification of the 12q13-q14 region was found in one yolk sac tumor. MDM2, of which the encoding gene maps to this chromosomal region, was found in all cases using immunohistochemistry, whereas no p53 could be detected. Accordingly, no mutations within exons 5 to 8 of the p53 gene were observed. These data prove the absence of gross chromosomal aberrations in teratomas of the infantile testis and show a characteristic pattern of gains and losses in the yolk sac tumors. Besides confirmation of previously found anomalies, recurrent losses of 1p21-31 and 4q23-33 and gains of 9q34 and 12p12-13 have not been reported before. While genetic inactivation of p53 seems unimportant in the pathogenesis of these tumors, biochemical inactivation by MDM2 might be involved. These data support the existence of three entities of germ cell tumors of the human testis: teratomas and yolk sac tumors of infants, seminomas and nonseminomas of adolescents and young adults, and spermatocytic seminomas of the elderly, each with its own specific pathogenesis.

Aneuploidy↗
PubMed2000

Helping patients with Crohn's disease quit smoking.

Smoking is not only a risk factor for Crohn's disease, but ongoing smoking is associated with a poorer disease course. Therefore, smoking cessation should be an important treatment strategy for Crohn's disease patients who smoke tobacco. Recent improvements in understanding how people quit smoking and the development of pharmacological interventions, such as nicotine patches and bupropion, have improved cessation rates. In this article, we first briefly review the evidence supporting the adverse effects of smoking on the disease course. We next review the current understanding of how people change addictive behaviors, such as smoking. We then describe how the gastroenterologist can aid the patient with Crohn's disease to quit smoking, including appropriate and brief counseling strategies and the use of adjunctive treatments. Given the improvements in smoking cessation strategies, all patients with Crohn's disease should be strongly advised to quit smoking and be aided in doing so.

Administration, Cutaneous↗
PubMed1999

Loss of the Y-chromosome in the primary metastasis of a male sex cord stromal tumor: pathogenetic implications.

The first published chromosomal pattern of the retroperitoneal lymph node metastasis of a malignant gonadal stroma cell tumor of the adult testis is presented. Karyotyping showed structural chromosomal abnormalities and loss of the Y-chromosome. This loss was confirmed in primary tumor and metastasis using fluorescence in situ hybridization (FISH). The characteristic chromosomal abnormality of adult testicular germ cell tumors, an i(12p), was not present. The results are compared with other data of testicular and ovarian sex cord stromal tumors. From the comparison of the male tumors, it is concluded that loss of the Y-chromosome might have a pathogenetic significance.

Chromosome Deletion↗
PubMed1999

Time trends in the incidence and disease location of Crohn's disease 1980-1995: a prospective analysis in an urban population in Germany.

To determine the incidence and clinical pattern of Crohn's Disease in a defined area in Germany, a prospective, population-based study was carried out from 1980 to 1984 and again from 1991 to 1995. All patients newly diagnosed with Crohn's disease within the respective study period who were resident in the study area were included in the study. The results from both study periods were then compared to detect time trends. Altogether 288 (156 and 132, respectively) incident cases were identified yielding an almost unchanged incidence over the years (1980-84: 4.9/10(5); 1991-95 5.2/10(5)). While the peak of incidence is still in the 15-24-year-old group, 1 out of 5 incident patients is now age 50 years and older. Median age at onset of symptoms increased to 30 years (20 years in the former period). Time from onset of symptoms was reduced from a median of 20 months in the 1980s to 5 months. Symptoms did not change significantly, although there seems to be less complicated disease recently. Distal migration of the inflammation in the intestinal tract was observed with significantly more involvement of the sigmoid and rectum in the recent period.

Adolescent↗
PubMed1999

Fatal haemorrhage from Dieulafoy's disease of the bronchus.

A 70 year old woman with a previous history of healed tuberculosis and suspected chronic obstructive pulmonary disease presented with recurrent haemoptysis and respiratory failure from a lobar pneumonia. Massive bleeding occurred when biopsy specimens were taken during bronchoscopy which was managed conservatively, but later there was a fatal rebleed from the same site. Two different Dieulafoy's vascular malformations were found in the bronchial tree at necropsy, one of which was the biopsied lesion in the left upper lobe. This report confirms the possibility that vascular lesions occur in the bronchial tree. It is suggested that, if such lesions are suspected at bronchoscopy, bronchial and pulmonary arteriography with possible embolotherapy should be performed.

Aged↗
PubMed1999

Incidence of ulcerative colitis, 1980-1995--a prospective study in an urban population in Germany.

A prospective, population-based study was carried out from 1980 to 1984 and again from 1991 to 1995 to determine the incidence of ulcerative colitis in an urban area in Germany. Patients with proctitis were excluded from this analysis. 74 (1980-84) and 76 (1991-95) patients newly diagnosed with ulcerative colitis were identified. A slight rise in the age- and sex-standardized incidence rate from 2.4/10(5) in 1980-84 (95% CI 1.8/10(5) to 3.0/10(5)) to 3.0 (95% CI 2.4/10(5) to 3.7/10(5)) in 1991-95 was primarily due to a significant increase of the disease in young woman. A male preponderance in the earlier time period was hereby leveled out. There were no differences in the extent of the disease and the severity of symptoms. However, the time from onset of symptoms to diagnosis was reduced from a median of nine months in the 1980s to two months in the more recent period.

Adolescent↗
PubMed1998

Oral contraceptive use and smoking are risk factors for relapse in Crohn's disease. The Canadian Mesalamine for Remission of Crohn's Disease Study Group.

BACKGROUND & AIMS: Lifestyle factors have been shown to influence prognosis in Crohn's disease. The purpose of this study was to prospectively assess the effects of smoking and oral contraceptive use on clinical relapse rates. METHODS: Placebo-treated patients formed a prospective cohort, followed up for 48 weeks or until relapse. The influence of smoking and the use of oral contraceptives on relapse risk was examined by life-table analysis (log rank tests) and Cox proportional hazards modeling, taking into account demographic and disease characteristics. RESULTS: Of 152 patients, 61 (40%) had a relapse. Univariate analysis showed unfavorable outcomes for women (P = 0.05), current smokers (P = 0.005), and use of oral contraceptives (P = 0.001). Recent surgery was associated with a decreased risk of relapse (P = 0.02). The Cox model retained current smoking vs. never smoking (hazard ratio, 2.1; 95% confidence interval, 1.1-4.2), oral contraceptive use (hazard ratio, 3.0; 95% confidence interval, 1.5-5.9), and medical compared with surgical induction of remission (hazard ratio, 2.1; 95% confidence interval, 1.0-4.2) as predictors of relapse. Ex-smokers did not have an increased risk. Finally, sex, age, time in remission, disease location, and disease duration were not significant predictors. CONCLUSIONS: Oral contraceptive use and smoking are associated with an increased risk of relapse in patients with Crohn's disease.

Adult↗
PubMed1994

The tumor microenvironment: possible role of integrins and the extracellular matrix in tumor biological behavior of intratubular germ cell neoplasia and testicular seminomas.

In the present study, we examined the distribution of integrin subunits and extracellular matrix proteins in normal testis, intratubular germ cell neoplasia (ITGCN), and primary and metastatic seminomas. Compared to normal testis in ITGCN, Sertoli cells showed increased expression of alpha 3, alpha 6, and beta 1 integrin subunits. Malignant intratubular germ cells stained for alpha 3, alpha 6, and beta 1 integrin subunits. Progression of ITGCN to invasive seminoma was associated with loss of alpha 3 integrin subunit expression by tumor cells. Consequent to this loss, it can be speculated that the strong expression on ITGCN may be related to the noninvasive character of the lesion as is also known from other noninvasive tumors. All tumors showed a strong expression of alpha 6 and beta 1 integrin subunits. The alpha 5 integrin subunit was weakly expressed in primary seminomas in all stages. No differences were observed in integrin expression between primary and metastatic tumors. The distribution of extracellular matrix proteins was heterogeneous and revealed clear architectural differences between seminomas that may reflect different stages of tumor stroma formation. To our knowledge, the results presented in this study provide the first information on the possible role of tumor-extracellular matrix interactions in the biological behavior of ITGCN and testicular seminomas.

Extracellular Matrix Proteins↗
PubMed1993

cis-diamminedichloroplatinum(ii) resistance in vitro and in vivo in human embryonal carcinoma cells.

In the embryonal carcinoma cell line Tera and its 3.7-fold cis-diamminedichloroplatinum(II) (CDDP)-resistant subline, Tera-CP, parameters were studied that might have changed in relation to induction of CDDP resistance. Phenotypes of both lines were embryonal carcinoma. Karyotypes were related with a decreased mean number of chromosomes and fewer copies of the short arm of chromosome 12 in Tera-CP. Tera-CP showed cross-resistance for melphalan and 4-hydroperoxycyclophosphamide and had an 1.4-fold increased glutathione (GSH) level, a 1.5-fold increased glutathione S-transferase (GST) activity, and a 1.4-fold increased GST pi expression compared to Tera. Tera-CP was cross-resistant to 5-fluorouracil, but thymidylate synthase activity was not increased. Topoisomerase I and II activities and c-myc RNA and protein expression were the same in both lines. Platinum accumulation was equal in both lines, and platinum-DNA binding was lower in Tera-CP than in Tera. Both cell lines were xenografted into nude mice and tumors showed marked differentiation. Tera-CP tumors were 2.8-fold resistant to CDDP compared to Tera tumors. In new cell lines derived from xenografts of Tera and Tera-CP CDDP sensitivity, GST activity and GSH level corresponded with their sensitivity and resistant origin. Tera-CP is a model of in vitro and in vivo CDDP resistance with the GSH/GST detoxifying system as an important mechanism. CDDP resistance could be induced without a concomitant increase in differentiation.

Animals↗