Biomedical subjects

Jan-Olaf Gebbers

Publications and source records attributed to Jan-Olaf Gebbers.

7 recordsLinked to original sources

PubMed2005

Role of the different isoforms of cyclooxygenase and nitric oxide synthase during gastric ulcer healing in cyclooxygenase-1 and -2 knockout mice.

Traditional NSAIDs, selective cyclooxygenase (COX)-2 inhibitors, and inhibitors of nitric oxide synthase (NOS) impair the healing of preexisting gastric ulcers. However, the role of COX-1 (with or without impairment of COX-2) and the interaction between COX and NOS isoforms during healing are less clear. Thus we investigated healing and regulation of COX and NOS isoforms during ulcer healing in COX-1 and COX-2 deficiency and inhibition mouse models. In this study, female wild-type COX-1(-/-) and COX-2(-/-) mice with gastric ulcers induced by cryoprobe were treated intragastrically with vehicle, selective COX-1 (SC-560), COX-2 (celecoxib, rofecoxib, and valdedoxib), and unselective COX (piroxicam) inhibitors. Ulcer healing parameters, mRNA expression, and activity of COX and NOS were quantified. Gene disruption or inhibition of COX-1 did not impair ulcer healing. In contrast, COX-2 gene disruption and COX-2 inhibitors moderately impaired wound healing. More severe healing impairment was found in dual (SC-560 + rofecoxib) and unselective (piroxicam) COX inhibition and combined COX impairment (in COX-1(-/-) mice with COX-2 inhibition and COX-2(-/-) mice with COX-1 inhibition). In the ulcerated repair tissue, COX-2 mRNA in COX-1(-/-) mice, COX-1 mRNA in COX-2(-/-) mice, and, remarkably, NOS-2 and NOS-3 mRNA in COX-impaired mice were more upregulated than in wild-type mice. This study demonstrates that COX-2 is a key mediator in gastric wound healing. In contrast, COX-1 has no significant role in healing when COX-2 is unimpaired but becomes important when COX-2 is impaired. As counterregulatory mechanisms, mRNA of COX and NOS isoforms were increased during healing in COX-impaired mice.

Animals↗

PubMed2005

Gastrin-releasing peptide receptors in normal and neoplastic human uterus: involvement of multiple tissue compartments.

CONTEXT: Bombesin-like neuropeptides including gastrin-releasing peptide (GRP) and their corresponding receptors, mediate multiple physiological actions and have biological significance in cancer. However, information about the function of these neuropeptides and the incidence, distribution, density, and subtype of their receptors in human uterine tissues is scarce. OBJECTIVE: The objective of the study was to investigate normal and neoplastic human uterine tissues for their bombesin receptor status. DESIGN: In vitro subtype-specific bombesin receptor autoradiography was used in this study. PATIENTS: The following tissue samples were taken immediately after surgery: myometrium (n = 41), endometrium (n = 29), leiomyomas (n = 26), leiomyosarcomas (n = 6), endometrial adenocarcinomas (n = 28), and carcinosarcoma (n = 1). RESULTS: Normal uterine tissues expressed GRP receptors (GRP-Rs) in the myometrium, in subsets of secretory endometrial glands, and in subsets of endometrial blood vessels of the late proliferative and the secretory phase. Most leiomyomas (20 of 26) expressed GRP-R but not the leiomyosarcomas. GRP-Rs were also detected in 10 of 28 adenocarcinomas, one of one carcinosarcoma, and in blood vessels surrounding the adenocarcinomas. No other bombesin receptor subtypes (neuromedin B receptors and bb3) were detected. CONCLUSIONS: These findings may be of physiological and pathophysiological significance. The expression of GRP-R in glands and vessels during specific phases of the cycle suggests a timely precise physiological action of GRP in these targets; in certain uterine neoplasms, the GRP-R overexpression may contribute to tumor development because GRP is a potent growth factor. Furthermore, these findings may be diagnostically and therapeutically relevant. The expression of GRP-R in leiomyomas may allow distinguishing them from receptor-negative leiomyosarcomas; GRP-R in leiomyomas, in a subset of endometrial adenocarcinomas, carcinosarcomas, and in peritumoral vessels may be candidates for receptor targeting in vivo.

Adenocarcinoma↗

PubMed2005

Immunohistochemical analysis reveals high frequency of PMS2 defects in colorectal cancer.

BACKGROUND & AIMS: Germline mutations in the DNA mismatch repair (MMR) genes MSH2, MSH6, or MLH1 predispose to colorectal cancer (CRC) with an autosomal dominant inheritance pattern. The protein encoded by PMS2 is also essential for MMR; however, alterations in this gene have been documented only in extremely rare cases. We addressed this unexpected finding by analyzing a large series of CRCs. METHODS: Expression of MSH2, MSH6, MLH1, and PMS2 was studied by immunohistochemistry in 1048 unselected, consecutive CRCs. Where absence of MMR proteins was detected, microsatellite instability and cytosine methylation of the respective gene promoter were analyzed. The DNA of patients presenting with PMS2-deficient cancers was examined for germline and somatic alterations in the PMS2 gene. RESULTS: An aberrant pattern of MMR protein expression was detected in 13.2% of CRCs. Loss of expression of MSH2, MSH6, or MLH1 was found in 1.4%, 0.5%, and 9.8%, respectively. PMS2 deficiency accompanied by microsatellite instability was found in 16 cases (1.5%) with a weak family history of cancer. The PMS2 promoter was not hypermethylated in these cases. Despite interference of the PMS2 pseudogenes, we identified several heterozygous germline mutations in the PMS2 gene. CONCLUSIONS: PMS2 defects account for a small but significant proportion of CRCs and for a substantial fraction of tumors with microsatellite instability. However, the penetrance of heterozygous germline mutations in PMS2 is considerably lower than that of mutations in other MMR genes. The possible underlying causes of this unorthodox inheritance pattern are discussed.

Adaptor Proteins, Signal Transducing↗

PubMed2004

Bacterial translocation in the normal human appendix parallels the development of the local immune system.

Experimental modes and pathological conditions may result in bacterial translocation (BT), that is, the passage of indigenous bacteria colonizing the intestine through the intestinal mucosa to mesenteric lymph nodes. Yet no data are available on BT in the normal human gut. We determined the occurrence of BT and its extent in histologically normal, incidentally removed human vermiform appendices (VA) from individuals of different ages and correlated the findings with the development with age of associated lymphatic tissue. BT appears to pertain to normal antigen-sampling processes of the GALT in the VA. It also parallels the development of the GALT and its maintenance during adulthood. In the first two weeks after birth, when bacterial colonization of the gut evolves and when the VA lacks the protection of secretory IgA, BT was not detected. Thereafter, BT occurs along with development of the local GALT, which is fully built up after the first year. A physiological uptake of, or invasion by, bacteria may be instrumental (1) for tolerance induction against the indigenous flora and (2) for the stimulation and normal development of the GALT.

Adolescent↗

PubMed2003

Ingested probiotics reduce nasal colonization with pathogenic bacteria (Staphylococcus aureus, Streptococcus pneumoniae, and beta-hemolytic streptococci).

BACKGROUND: As a bacterial reservoir, the nose may harbor potentially pathogenic bacteria (PPB: Staphylococcus aureus, Streptococcus pneumoniae, beta-hemolytic streptococci, and Haemophilus influenzae). In patients carrying PPB, antiseptic regimens could be crucial for infection control after major operations on or injuries of the head, nasal sinuses, or lungs. Such regimens may also be important for diabetic patients and persons receiving hemodialysis, in intensive care units, or with impaired immunity due to various other causes. OBJECTIVE: We tested a possible effect of the ingestion of probiotics on the bacterial flora of the nose. DESIGN: In an open, prospective trial, 209 volunteers were randomly assigned to consume either a probiotic, fermented milk drink [65 mL with Lactobacillus GG (ATCC 53103), Bifidobacterium sp B420, Lactobacillus acidophilus 145, and Streptococcus thermophilus; n = 108] or standard yogurt (180 g; n = 101) daily for 3 wk. Nasal microbial flora were analyzed on days 1, 21, and 28. The microbial examination was blinded to the source of the samples. RESULTS: We found a significant reduction (19%; P < 0.001) in the occurrence of nasal PPB in the group who consumed the probiotic drink but not in the group who consumed yogurt. The effect was mainly on gram-positive bacteria, which decreased significantly (P < 0.05). CONCLUSIONS: The results indicate that regular intake of probiotics can reduce PPB in the upper respiratory tract. The results also indicate a linkage of the lymphoid tissue between the gut and the upper respiratory tract.

Adult↗

PubMed2003

Cytopathology of the nasal mucosa in chronic exposure to diesel engine emission: a five-year survey of Swiss customs officers.

The simple and cheap technique of nasal cytology was used to assess possible adverse effects of chronic exposure to diesel engine emission (DEE) on respiratory mucous membranes. Brush cytology probes were taken from the noses of 194 male, nonsmoking customs officers twice a year (January and July) over a period of 5 years. The study group of 136 officers was solely occupied with clearing of diesel trucks (8.4 hr/day, 42 hr/week). Measured DEE concentrations varied between 31 and 60 microg/m3) and of benzo[a]pyrene concentrations were between 10 and 15 ng/m3). The control group of 58 officers worked only in the office. Over the 5-year period, similar results were obtained in summer and winter. In contrast to those not exposed to DEE, those who were had clear goblet cell hyperplasia with increased metaplastic and dysplastic epithelia and an increase in leukocytes. We found no evidence of progression of the cytopathologic changes. The findings may be described as a chronic inflammation of the nasal mucous membrane in the presence of chronic DEE exposure (chemical-induced rhinitis). Additionally, the findings of metaplastic and dysplastic nasal epithelia in the exposed subjects may indicate a genotoxic effect of chronic DEE exposure in humans.

Benzo(a)pyrene↗

PubMedDate not supplied

Local pathogenic bacteria in allergic rhinitis: a novel concept of its pathogenesis.

BACKGROUND: It is still unclear to what extent microorganisms are involved in the pathogenesis of allergic rhinitis. OBJECTIVE: Therefore, we examined the mucosal colonization with potential pathogenic bacteria (PPB) of the nasal cavity in allergic and nonallergic subjects. METHODS: In an open prospective study of 389 office workers (297 men, mean age 42.5 years, and 92 women, mean age 36.7 years), bacterial swabs were taken selectively from both nasal cavities. Standard skin tests for various aeroallergens and negative control tests were conducted in parallel in these subjects. RESULTS: In the 389 subjects, we found positive skin tests in 58 (15%); 37 of these revealed a high level of sensitivity, whilst the other 21 persons had low to moderate levels. Ninety percent of the 58 sensitive persons had PPB in their nasal cavity while only 36% (119) of the remaining 331 subjects with negative skin tests were shown to have PPB in nasal cultures (p < 0.001). Sixty-four percent of the sensitized subjects with PPB were found to have more than 2 PPB species and a positive correlation with the intensity of the skin reaction. In contrast, only 18% (22) of the 119 nonallergic test persons with PPB had more than 1 PPB species. CONCLUSIONS: This finding of an unusually high frequency of nasal PPB in subjects with positive skin tests to aeroallergens may indicate an involvement of PPB in the pathogenesis of allergic rhinitis. Yet, further data are still lacking to support this novel concept.

Adult↗