PubMed Health⌕ Search

Biomedical subjects

S Reimer

Publications and source records attributed to S Reimer.

At least 19 recordsLinked to original sources
PubMed2005

Resistance to interference in complex negative patterning.

Resistance to interference was examined in rats that received a complex negative patterning discrimination in which XA and XB were followed by food reinforcement and XAB was not Retention of the discrimination was evident after separate reinforcement of both A and B (Experiment 3), but not after reinforcement of either AB (Experiments 1 and 3) or XAB (Experiments 2 and 3). These data suggest that complex negative patterning discriminations are acquired configurally and that the relative similarity of the original discrimination and subsequent interference trials dictates the final degree of retention observed.

Animals↗
PubMed2004

Elevated expression and release of tissue-type, but not urokinase-type, plasminogen activator after binding of autoantibodies to bullous pemphigoid antigen 180 in cultured human keratinocytes.

In bullous pemphigoid (BP), the binding of BP180-specific antibodies to their hemidesmosomal target antigen is not sufficient for blister formation, but must be accompanied by the release of proteases. Using plasminogen activator (PA) knock-out mice, the PA system has previously been shown to be a prerequisite for blister formation in experimental murine BP. Here, we found elevated levels of plasmin and tPA, but not of uPA, in blister fluid from BP patients (n = 7) compared to blisters from patients with toxic epidermal necrolysis (n = 4) and suction blisters in healthy controls (n = 7). Subsequently, we addressed the question whether keratinocytes release PA in response to the binding of anti-BP180 antibodies. Treatment of cultured normal human keratinocytes with BP IgG, but not with control IgG, led to both increased protein and mRNA levels of tPA, but not of uPA, as determined by ELISA and RT-PCR, respectively. The specificity of this finding was confirmed using BP180-deficient keratinocytes from a patient with generalized atrophic benign epidermolysis bullosa, where no tPA release was observed after stimulation with BP IgG. Our results show the elevated expression and release of tPA from normal human keratinocytes upon stimulation with antibodies to human BP180. Keratinocytes, by secreting tPA, may thus play an active role in blister formation of BP.

Autoantibodies↗
PubMed2001

Antibodies to desmogleins 1 and 3, but not to BP180, induce blisters in human skin grafted onto SCID mice.

Pemphigus and bullous pemphigoid (BP) are blistering skin diseases associated with IgG autoantibodies to desmosomal and hemidesmosomal components. When autoantibodies to desmogleins 1 and 3 from patients with pemphigus foliaceus (PF) and pemphigus vulgaris (PV) or rabbit antibodies against the murine hemidesmosomal component BP180 are passively transferred into neonatal mice, they induce blisters in the skin of the mice. To develop an animal model that would duplicate the findings in the skin of the patients more closely, full-thickness human skin from healthy volunteers was grafted onto SCID mice. Injection of the purified IgG fraction from the serum of PF and PV patients led to subcorneal and suprabasal splits in the human grafts and human IgG was deposited intercellularly in the upper and lower layers of the epidermis, respectively. Interestingly, anti-BP180 autoantibodies purified from the serum of BP patients and from a rabbit immunized with recombinant human BP180 strongly bound to the basement membrane zone of the grafts (n=32), fixed murine complement, led to the recruitment of neutrophils to the upper dermis of the graft, but did not induce subepidermal blisters. We report a novel experimental model for PF and PV which should greatly facilitate further studies to dissect the immunopathological mechanisms in these diseases. Specifically, this model can be used to identify pathogenically relevant epitopes on human desmogleins 1 and 3 and to develop novel strategies for the treatment of pemphigus.

Animals↗
PubMed2001

The IL-8 release from cultured human keratinocytes, mediated by antibodies to bullous pemphigoid autoantigen 180, is inhibited by dapsone.

Bullous pemphigoid (BP) is a subepidermal blistering disease associated with autoantibodies to the hemidesmosomal 180 kD BP autoantigen (BP180). However, the binding of autoantibodies to BP180 alone is not sufficient for blister formation in this disease and the infiltration of neutrophils into the skin is required. Dapsone and nicotinamide inhibit neutrophil chemotaxis and are used effectively in treating BP. IL-8 is a known chemoattractant for neutrophils and has been implicated in the inflammatory process of both human and experimental murine BP. We have recently shown that antibodies to BP180 mediate a dose and time-dependent release of IL-6 and IL-8 from cultured normal human epidermal keratinocytes (NHEK). In the present study, we addressed the question whether dapsone or nicotinamide influence this cytokine release. We demonstrate that dapsone, but not nicotinamide, in its pharmacological range, inhibits the IL-8, but not the IL-6 release from NHEK, induced by anti-BP180 IgG, in a dose-dependent fashion as detected by ELISA. IL-8 mRNA levels, as determined by RT-PCR, were the same in cells treated with BP IgG alone compared to cells treated with BP IgG plus dapsone. This observation suggests that dapsone inhibits the BP IgG-induced IL-8 release from cultured NHEK by mechanisms at the post-transcriptional level. Our findings contribute to the understanding how dapsone leads to a reduced influx of neutrophils into BP lesions and, finally, to the cessation of blister formation in this disease.

Animals↗
PubMed2000

Autoantibodies to BP180 associated with bullous pemphigoid release interleukin-6 and interleukin-8 from cultured human keratinocytes.

Bullous pemphigoid is an inflammatory subepidermal blistering disease that is associated with auto- antibodies to the keratinocyte surface protein, BP180. In addition to the binding of autoantibodies, the infiltration of inflammatory cells is necessary for blister formation. Cytokines, including interleukin-6 and interleukin-8, have been implicated in the disease process of both human and experimental murine bullous pemphigoid. This study was aimed at testing the hypothesis that the binding of anti-BP180 antibodies to their target antigen triggers a signal transduction event that results in the secretion of these pro-inflammatory cytokines. Consistent with this hypothesis, treatment of cultured normal human epidermal keratinocytes with bullous pemphigoid IgG, but not control IgG, led to increased levels of interleukin-6 and interleukin-8, but not interleukin-1alpha, interleukin-1beta, tumor necrosis factor-alpha, interleukin-10, or monocyte chemoattractant protein-1, in the culture medium. This effect was concentration- and time-dependent and was abolished by depleting the bullous pemphigoid IgG of reactivity to two distinct epitopes on the BP180 NC16A domain. Upregulation of interleukin-6 and interleukin-8 was found at both protein and mRNA levels. In addition, bullous pemphigoid IgG did not induce the release of interleukin-6 and interleukin-8 from BP180-deficient keratinocytes obtained from a patient with generalized atrophic benign epidermolysis bullosa. These data indicate that bullous pemphigoid-associated autoantibodies to the human BP180 ectodomain trigger a signal transducing event that leads to expression and secretion of interleukin-6 and interleukin-8 from human keratinocytes.

Autoantibodies↗
PubMed1999

Different gene expression of MDM2, GAGE-1, -2 and FHIT in hepatocellular carcinoma and focal nodular hyperplasia.

Overexpression and/or mutations of oncogenes, tumour suppressor genes and tumour rejection genes have been observed in several human malignancies. Their analyses might be of diagnostic importance. Therefore, malignant hepatocytes derived from hepatocellular carcinoma (HCC) tissue as well as non-malignant hepatocytes derived from focal nodular hyperplasia (FNH) were studied. Samples containing normal human hepatocytes (HC) served as controls. Cellular material was obtained by fine-needle aspiration biopsy guided by ultrasound. Cells were analysed for expression and mutation of the oncogene MDM2, the genes GAGE-1, -2 coding for tumour-associated antigens and the candidate tumour suppressor gene FHIT. Different patterns of non-mutant FHIT transcripts including precise deletion of exons were found in 7/10 HCC, 2/10 FNH and 2/10 HC. However, expression of non-mutant GAGE-1, -2 RNA was demonstrated exclusively in 6/10 HCC samples. Further genetic features specific of HCC were point mutations in a zinc-finger motif of MDM2 (3/10 HCC samples). Neither GAGE-1, -2 expression nor MDM2 mutations were observed in the FNH samples, or in normal hepatocytes. Our findings suggest that occurrence of variable FHIT transcripts is not restricted to hepatic malignant tumours. In contrast, MDM2 mutations and GAGE-1, -2 expression were associated with HCC specimens. Therefore, the RT-PCR assays for GAGE-1, -2 and MDM2 might be useful adjuncts in cytodiagnosis of liver neoplasms.

Acid Anhydride Hydrolases↗
PubMed1998

The in situ polymerase chain reaction for detection of chlamydia trachomatis.

The in situ polymerase chain reaction (PCR) is a technique that has important applications in the diagnosis of viral and bacterial diseases. This study investigated an in situ PCR assay established to detect the presence of Chlamydia trachomatis in endocervical swabs. In addition, histological sections of endocervical squamous cell carcinoma were analyzed because previous studies had revealed a significant association with C. trachomatis. A total of 20 cervical neoplasms (squamous cell carcinoma in situ; n = 10; invasive squamous cell carcinoma; n = 10) and endocervical smears taken from five patients with and without inflammatory changes were analyzed by conventional PCR. Chlamydial DNA was found in 10 histological samples (six carcinomas in situ, four invasive carcinomas) and in one endocervical swab from a patient with known C. trachomatis infection. Positive specimens were used for establishing an in situ PCR assay (IS-PCR). After IS-PCR, these samples showed dense cytoplasmic staining of endocervical cells (smears) and non-neoplastic epithelial cells (cervical neoplasms). The other tumor samples and smears did not demonstrate positive PCR reaction. The results indicate that in situ PCR is an effective technique for localizing C. trachomatis in target cells because IS-PCR detection of chlamydial DNA correlated with histological and cytological features.

Adult↗
PubMed1997

Point mutations and nucleotide insertions in the MDM2 zinc finger structure of human tumours.

This study investigates the human oncoprotein MDM2, which interferes with regulation of cell division and apoptosis. Fifteen mixed-type follicular non-Hodgkin's lymphomas, ten leukaemias, two hepatocellular carcinomas, one osteosarcoma, and ten normal cell lines (fibroblasts, osteoblasts, mesothelium, peripheral lymphocytes) were tested for MDM2 expression and MDM2 gene mutation by reverse transcriptase-polymerase chain reaction (RT-PCR), immunocytochemistry, and nucleotide sequence analysis. Two follicular lymphomas, three leukaemias, both hepatocellular carcinomas, and the osteosarcoma sample showed transcription of the activated MDM2 gene. These samples lacked amplified MDM2 genes and carried mis-sense, non-sense and frame-shift mutations in a zinc finger region of MDM2, altering the amino acid sequence or causing premature termination of transcription. The mis-sense mutations were found in tumour cells that showed significant accumulation of MDM2 and lack of nuclear p53. Non-sense mutations and frame-shift mutations were found in tumours lacking MDM2 proteins. The mutations may affect the biological properties of MDM2 proteins.

Amino Acid Sequence↗
PubMed1997

Automated molecular genetic DNA analysis for detecting B-cell non-Hodgkin's lymphoma in cytologic specimens.

OBJECTIVE: In fine needle aspiration cytology, conventional morphologic and immunocytologic criteria are often insufficient for distinguishing the mixed type of follicular lymphoma (NHL) from reactive lymphoid hyperplasia (RLH). For improving cytodiagnosis, we adapted computer-assisted polymerase chain reaction (PCR) assays on cytologic specimens. These novel techniques aim at fluorescence-based sequencing and sizing of PCR products that result from NHL-specific markers, such as the chromosomal t(14;18) (q32;q21) translocation and the CDR3 regions of expanded B-cell neoplasia. STUDY DESIGN: Aspirates from eight cases with mixed-type follicular NHL and from nine cases with a cytologic finding of RLH were investigated by PCR and with an automated laser scanning system. RESULTS: PCR detected the t(14;18) translocation in 5/8 B cell NHL samples and 1/9 RLH samples. By means of automated DNA sequencing, two of the five positive probes in the group of NHLs were identified as false positive. The CDR3 regions of expanded B-cell clones were found in four of eight NHL aspirates by means of PCR and computer-assisted analysis. CONCLUSION: This study proved the reliability of automated genetic assays for diagnosing low grade B-cell NHLs in aspirates since false positive results are excluded.

Biopsy, Needle↗
PubMed1994

[Anesthesia with jet injection. Use of Medi-Jector EZ dermojet for anesthesia in minor surgery].

The local anaesthetic procedure is often painful to the patient. During a period of 21 weeks, jet injection was used as the anaesthetic procedure in 55 cases of minor surgery in a single general practice. The application is discussed, giving a variety of examples. The method provides a simple and almost pain-free anaesthetic procedure in the majority of minor surgical operations. The amount of anaesthetic is reduced. The method is particularly suitable for anaesthetizing sensitive areas like the finger of a child or verrucas.

Adolescent↗
PubMed1992

Differential dopaminergic regulation of proenkephalin and prodynorphin mRNAs in the basal ganglia of rats.

Proenkephalin and prodynorphin mRNA levels in the caudate-putamen and in the nucleus accumbens of rats were measured by in situ hybridization 2, 4 and 8 weeks following unilateral lesion of the medial forebrain bundle by 6-hydroxydopamine (6-OHDA). After 2 weeks a 60% increase of the levels of proenkephalin mRNA in the ipsilateral caudate-putamen was observed which declined to 20% above control after 8 weeks. A smaller increase in the levels of proenkephalin mRNA of about 20% was observed in the nucleus accumbens after 2 weeks and no significant alteration could be observed 4 and 8 weeks after lesioning. The levels of prodynorphin mRNA in the ipsilateral caudate-putamen decreased 20% below control and returned to control levels 4 and 8 weeks post-lesion. In contrast, in the nucleus accumbens a persistent ipsilateral decrease of prodynorphin (20-30%) was found 2, 4 and 8 weeks post-lesion. These findings indicate, that lesions of the mesostriatal dopamine (DA) system differentially influences opioidergic gene expression in distinct areas of the caudate-putamen. The lesions cause an increase in proenkephalin mRNA levels which was higher in the caudate-putamen than in the nucleus accumbens and tend to be reversible. Conversely, the lesion caused a persistent decrease in the levels of prodynorphin mRNA in the nucleus accumbens and a small and transient decrease in the caudate-putamen.

Animals↗
PubMed1991

GABAergic regulation of striatal opioid gene expression.

Peptides derived from prodynorphin and preproenkephalin are located in GABAergic striatal projection neurons. We have used nucleic acid hybridization techniques to investigate the role of GABA in the regulation of striatal opioid peptide gene expression. Rats were treated with the GABA-transaminase inhibitors aminooxy acetic acid, ethanolamine O-sulphate and gamma-vinyl-GABA for one week. The GABA levels in the striatum were significantly elevated after each treatment. The GABA-transaminase-inhibitors decreased the striatal levels of the opioid peptides met-enkephalin and dynorphin(1-8) and concomitantly decreased the concentrations of the mRNAs coding for proenkephalin and prodynorphin. These findings indicate that GABA exerts an inhibitory influence on prodynorphin and proenkephalin gene expression in the striatum. The mechanisms underlying these inhibitions are discussed.

4-Aminobutyrate Transaminase↗
PubMed1990

Nigrostriatal dopamine mediates the stimulatory effects of corticotropin releasing factor on methionine-enkephalin and dynorphin release from the rat neostriatum.

This study examined the effects of corticotropin-releasing factor (CRF) on the in vitro release of methionine-enkephalin (Met-enkephalin) and dynorphin in neostriatal slices taken from rats with unilateral 6-hydroxydopamine (6-OHDA)-induced lesions of the nigrostriatal DA pathway. In neostriatal slices from control saline-infused animals and in those from the contralateral hemisphere of 6-OHDA-lesioned animals, CRF (10(-10) M) administered as a 90-min pulse exerted potent stimulatory effects on both Met-enkephalin and dynorphin release. In the neostriatal slices of 6-OHDA-lesioned striata, both the basal release and tissue content of Met-enkephalin were significantly (P less than 0.01) higher (2-fold) than those of control animals and the contralateral hemisphere of 6-OHDA-lesioned animals; however, neither the basal release nor the tissue content of dynorphin in 6-OHDA-lesioned striata was significantly different from control striata. In response to CRF (10(-10) M) the release of both Met-enkephalin and dynorphin were significantly diminished in slices of 6-OHDA-lesioned striata. These data support previous studies suggesting that nigrostriatal DA itself may exert a tonic inhibitory action on the activity of striatal Met-enkephalin neurones; however, DA may not have the same influence on striatal dynorphin neurons. However, the results of this study demonstrate that the action of CRF on Met-enkephalin as well as dynorphin release from the rat neostriatum is DA dependent. The data suggest that CRF receptors in the rat neostriatum may be localized on nigrostriatal/nigropallidal DA terminals/collaterals.

Animals↗