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G Mohr

Publications and source records attributed to G Mohr.

At least 37 records · Page 2Linked to original sources
PubMed1999

Relationship between O6-methylguanine-DNA methyltransferase levels and clinical response induced by chloroethylnitrosourea therapy in glioma patients.

BACKGROUND: Adjuvant nitrosourea chemotherapy fails to prolong survival significantly as many tumors demonstrate resistance to these drugs. It has been documented in cell lines that O6-methylguanine DNA methyltransferase (MGMT) plays an important role in chloroethylnitrosourea (CENU) drug resistance. METHODS: We evaluated MGMT expression in 22 glioma specimens by using an immunofluorescence assay and compared the results with clinical responses of the patients to CENU-based chemotherapy. RESULTS: Eight tumor samples had no detectable MGMT, whereas other samples had from 9,989 to 982,401 molecules/nucleus. In one group (12 patients), the tumor decreased in size or was stable (effective group), whereas in the other group (10 patients), the tumor demonstrated continuous growth during chemotherapy (progressive group). The Mer- patients (MGMT < 60,000 molecules/nucleus) appeared to have more chance of stable disease or response to CENU therapy than the Mer+ patients (MGMT > 60,000 molecules/nucleus) (X2 = 4.791, p = 0.0286). In patients with glioblastomas multiforme (GBMs), the median time to progression (TTP) of Mer+ patient was shorter than that of Mer- patient (t = 2.04, p = 0.049). As a corollary, the MGMT levels were significantly higher in GBM tumors from the progressive group than those from the effective group (t = 2.26, p = 0.029). However, there was no significant correlation between MGMT levels and either the survival time (r = 0.04, p = 0.8595) or TTP (r = 0.107, p = 0.6444). CONCLUSION: This study suggests that being MGMT positive is indicative of a more aggressive disease that progresses more rapidly with CENU therapy. However, MGMT negative tumors are not always sensitive to CENU agents, suggesting that other factors are also important.

Adult↗
PubMed1999

Endoscopic repair of cerebrospinal fluid rhinorrhea: is it the treatment of choice?

Between 1991 and 1998, 12 patients with cerebrospinal fluid rhinorrhea were operated on using the intranasal endoscopic approach. The procedure was successful in 10 cases. The endoscopic approach failed in two patients who had larger bony defects and herniating meningoencephaloceles. This paper analyzes the case material with respect to the etiology and site of leakage. The value of computed tomography and magnetic resonance imaging for preoperative localization of the leak is discussed. The technique of underlay fascia graft is described and discussion ensues regarding potential pitfalls that may lead to failure of leak closure.

Adult↗
PubMed1999

Intracranial facial nerve reconstruction.

Surgery for tumours of the cerebellopontine angle (CPA) or the internal auditory canal (IAC) is sometimes complicated by the severing of the seventh nerve. Many procedures are available for facial reanimation. Among these, primary intracranial VII-VII reanastomosis is considered as the method of choice. This series reviews all the cases of primary intracranial facial nerve reconstruction that we have performed either directly or with the use of a nerve graft interposition. Functional results are analyzed according to the House-Brackmann grading scale. The advantages and benefits of this technique are discussed as compared with other methods of facial reanimation, namely, the hypoglossal-facial anastomosis.

Adult↗
PubMed1999

Extraneuronal monoamine transporter expression and DNA repair vis-à-vis 2-chloroethyl-3-sarcosinamide-1-nitrosourea cytotoxicity in human tumor cell lines.

We previously found that 2-chloroethyl-3-sarcosin-amide-1-nitrosourea (SarCNU), a new chloroethylnitrosourea analogue presently in phase I clinical trials, is a selective cytotoxin that enters cells via the extraneuronal transporter for monoamine transmitters (EMT). In this study, we assessed whether EMT expression correlates with SarCNU cytotoxicity by determining EMT expression in 23 human tumor cell lines with reverse-transcription PCR. Western blot analysis was used to measure protein levels of the DNA repair genes, O6-methylguanine-DNA methyltransferase (MGMT), and excision repair cross-complementing rodent repair deficiency gene 2 (ERCC2). SarCNU cytotoxicity was determined by the sulforhodamine B colorimetric anti-cancer-drug screening assay and correlated with gene expression. Almost all of the cell lines screened were positive for EMT expression. However, seven cell lines (MGR-1, MGR-2, T98-G, SKI-1, SKNSH, 297, and GBM) expressed low levels of EMT. Although there was no linear correlation between SarCNU cytotoxicity and EMT expression, SarCNU cytotoxicity significantly correlated with ERCC2 protein levels, and MGMT-rich (Mer+) cell lines (MGMT protein level >0.1) were more resistant to SarCNU than MGMT-poor (Mer-) cell lines (MGMT protein level <0.1). Moreover, multiple regression analysis indicated that the best correlation with SarCNU cytotoxicity was attainable with EMT plus MGMT and ERCC2 expression. This study suggests that in human tumor cell lines both EMT and DNA repair factors, specifically, MGMT and ERCC2, are important determinants of SarCNU activity. Because EMT is expressed in a wide variety of human tumors, SarCNU should be a more widely effective alternative chemotherapeutic agent.

Antineoplastic Agents↗
PubMed1998

Group II intron mobility in yeast mitochondria: target DNA-primed reverse transcription activity of aI1 and reverse splicing into DNA transposition sites in vitro.

The retrohoming of the yeast mtDNA intron aI1 occurs by a target DNA-primed reverse transcription (TPRT) mechanism in which the intron RNA reverse splices directly into the recipient DNA and is then copied by the intron-encoded reverse transcriptase. Here, we carried out biochemical characterization of the intron-encoded reverse transcriptase and site-specific DNA endonuclease activities required for this process. We show that the aI1 reverse transcriptase has high TPRT activity in the presence of appropriate DNA target sites, but differs from the closely related reverse transcriptase encoded by the yeast aI2 intron in being unable to use artificial substrates efficiently. Characterization of TPRT products shows that the fully reverse spliced intron RNA is an efficient template for cDNA synthesis, while reverse transcription of partially reverse spliced intron RNA is impeded by the branch point. Novel features of the aI1 reaction include a prominent open-circular product in which cDNAs are incorporated at a nick at the antisense-strand cleavage site. The aI1 endonuclease activity, which catalyzes the DNA cleavage and reverse splicing reactions, is associated with ribonucleoprotein particles containing the intron-encoded protein and the excised intron RNA. As shown for the aI2 endonuclease, both the RNA and protein components are used for DNA target site recognition, but the aI1 protein has less stringent nucleotide sequence requirements for the reverse splicing reaction. Finally, perhaps reflecting this relaxed target specificity, in vitro experiments show that aI1 can reverse splice directly into ectopic mtDNA transposition sites, consistent with the previously suggested possibility that this mechanism is used for ectopic transposition of group II introns in vivo.

DNA, Fungal↗
PubMed1998

Clinical response of O(6)-methylguanine-DNA methyltransferase levels to 1,3-(2-chloroethyl)-1-nitrosourea chemotherapy in glioma patients.

Adjuvant nitrosourea chemotherapy fails to prolong patient survival significantly as many tumors demonstrate resistance to these drugs. It has been documented in cell lines that O(6)-methylguanine-DNA methyltransferase (MGMT) plays an important role in chloroethylnitrosourea (CENU) drug resistance. The authors evaluated MGMT expression in 22 glioma specimens by using an immunofluorescence assay and compared the results with clinical response of the patients to CENU-based chemotherapy. The patients were treated with CENU after evidence of progressive disease following surgery and radiotherapy. Eight tumor samples had no detectable MGMT, whereas other samples had from 9989 to 982,401 molecules/nucleus. In one group (12 patients), the tumor decreased in size or was stable (effective group), whereas in the other group (10 patients), the tumor demonstrated continuous growth during chemotherapy (progressive group). The median time to progression (TTP) was 6.7 months with a median survival of 13 months. The Mer(-) patients (MGMT < 60,000 molecules/nucleus) appeared to have more chance of stable disease or response to CENU therapy than the Mer(+) patients (MGMT > 60,000 molecules/nucleus) (chi-square = 4.791, p = 0.0286). In patients with glioblastomas multiforme (GBMs), the TTP of Mer(+) patients was shorter than that of Mer(-) patients (t = 2.04, p = 0.049). As a corollary, the MGMT levels were significantly higher in GBM tumors from the progressive group than those from the effective group (t = -2.26, p = 0.029). The TTP and survival time in the effective GBM group were also longer than those in the progressive GBM group. However, there was no significant correlation between MGMT levels and either the survival time (r = 0.04, p = 0.8595) or TTP (r = 0.107, p = 0.6444). Results from this study suggested that MGMT positivity is indicative of more aggressive disease that progresses more rapidly when exposed to CENU therapy. However, MGMT-negative tumors are not always sensitive to CENU agents, suggesting that other factors may also be important.

Journal Article↗
PubMed1998

On the independence of modality effects and end-term and distance effects in episodic comparative judgement: dissociations of errors and reaction times.

The experiments reported in this paper explore the effect of modality variations on end-term and distance effects in an episodic comparative judgement task. In each experiment, subjects were to store serial orders of objects on a size dimension. Memory was tested after a brief retention interval by a comparative judgement task, in which subjects were presented with two elements of an order and had to point to the formerly larger one. Regarding the response times, we hypothesized that modality variations affect speed of stimulus identification and code access processes. We further hypothesized that distance variations and end-term variations affect processing components that are independent of the component affected by the modality variation. Finally, we assumed that end-term and distance effects interact in a predictable way, because they mirror competing response selection strategies. The latency data clearly support these hypotheses. As regards the accuracy data, we argued that modality and end-term effects, if they show up within the accuracy data, very likely have a different basis than the effects within the latency data. Again, the data support this assumption showing clear dissociations of accuracy and latency data. With respect to the stimulus modality variation, the whole data pattern shows that explanations which rely on modality-specific codings are not justifiable.

Adult↗
PubMed1998

Intracranial aneurysms and sickle cell anemia: multiplicity and propensity for the vertebrobasilar territory.

OBJECTIVE: We describe a case of sickle cell anemia and multiple intracranial aneurysms and review the English-language-reported cases of sickle cell disease associated with intracranial aneurysms proven angiographically or by autopsy, to assess whether there are associations with aneurysm multiplicity and sites of aneurysm occurrence. CLINICAL PRESENTATION: A 28-year-old woman with sickle cell disease and a subarachnoid hemorrhage underwent successful clipping of three intracranial aneurysms. RESULTS: Among 44 reviewed cases, 57% of patients demonstrated multiple aneurysms, and aneurysms from patients with multiple aneurysms comprised nearly 80% of the total number of aneurysms. There were, on average, three aneurysms per patient for patients with multiple aneurysms. There was a predominance of female patients (female/male ratio, 1.6:1), although there existed no significant differences in age or gender for patients with single or multiple aneurysms. None of the patients with multiple aneurysms was older than 40 years of age at the time of presentation. Patients with multiple aneurysms and sickle cell disease showed a significant difference in the distribution of the aneurysm sites, with a significantly large number occurring in the vertebrobasilar axis. Multiple aneurysms associated with sickle cell disease showed a higher rate of simultaneous occurrence in the posterior and anterior circulation, compared with multiple aneurysms in the general population. CONCLUSION: There are strong statistical associations for aneurysm multiplicity and sites of aneurysm occurrence among reported patients with sickle cell disease. Patients with sickle cell anemia and neurological symptoms should undergo magnetic resonance angiography or four-vessel angiography to detect potentially harmful, but neurosurgically treatable, pathological conditions.

Adolescent↗
PubMed1998

Excision repair cross-complementing rodent repair deficiency gene 2 expression and chloroethylnitrosourea resistance in human glioma cell lines.

OBJECTIVE: Nitrosoureas are the standard chemotherapeutic agents for malignant brain tumors. However, their anticancer effects are limited because many tumors are resistant to these agents. Nucleotide excision repair can repair bulky deoxyribonucleic acid adducts, including deoxyribonucleic acid damage induced by ultraviolet light and some chemotherapeutic agents, and may be implicated in nitrosoureas resistance. In this study, we compared excision repair cross-complementing rodent repair deficiency Gene 2 (ERCC2), an important component of the nucleotide excision repair system, with 1 ,3-bis-(2-chloroethyl)-1-nitrosourea or (2-chloroethyl)-3-sarcosinamide-1-nitrosourea resistance in human glioma cell lines. METHODS: ERCC2 expression was evaluated by using established quantitative reverse-transcription polymerase chain reaction. 1,3-Bis-(2-chloroethyl)-1-nitrosourea and (2-chloroethyl)-3-sarcosinamide-1-nitrosourea cytotoxicity were determined by a modification of the sulforhodamine B colorimetric anticancer drug screening assay. RESULTS: A significant correlation between ERCC2 expression and 1 ,3-bis-(2-chloroethyl)-1-nitrosourea or (2-chloroethyl)-3-sarcosinamide-1-nitrosourea cytotoxicity was determined (r=0.737, P=0.0226 and r=0.789, P=0.0113, respectively). CONCLUSION: Our results suggest that nucleotide excision repair, specifically ERCC2, may play an important role in nitrosoureas drug resistance in human gliomas.

Brain Neoplasms↗
PubMed1998

Exophytic primitive neuroectodermal tumor of the spinal cord.

We present a case of an exophytic spinal primitive neuroectodermal tumor that, radiologically, simulated an extramedullary nerve sheath tumor, meningioma, or metastatic tumor deposit. MR imaging provided discrete anatomic localization of the tumor, enabling exclusion of multicentricity in the brain and spinal cord.

Adult↗
PubMed1997

A bacterial group II intron encoding reverse transcriptase, maturase, and DNA endonuclease activities: biochemical demonstration of maturase activity and insertion of new genetic information within the intron.

The Lactococcus lactis group II intron Ll.ltrB is similar to mobile yeast mtDNA group II introns, which encode reverse transcriptase, RNA maturase, and DNA endonuclease activities for site-specific DNA insertion. Here, we show that the Lactococcal intron can be expressed and spliced efficiently in Escherichia coli. The intron-encoded protein LtrA has reverse transcriptase and RNA maturase activities, with the latter activity shown both in vivo and in vitro, a first for any group II intron-encoded protein. As for the yeast mtDNA introns, the DNA endonuclease activity of the Lactococcal intron is associated with RNP particles containing both the intron-encoded protein and the excised intron RNA. Also, the intron RNA cleaves the sense-strand of the recipient DNA by a reverse splicing reaction, whereas the intron-encoded protein cleaves the antisense strand. The Lactococcal intron endonuclease can be obtained in large quantities by coexpression of the LtrA protein with the intron RNA in E. coli or reconstituted in vitro by incubating the expressed LtrA protein with in vitro-synthesized intron RNA. Furthermore, the specificity of the endonuclease and reverse splicing reactions can be changed predictably by modifying the RNA component. Expression in E. coli facilitates the use of group II introns for the targeting of specific foreign sequences to a desired site in DNA.

Bacterial Proteins↗
PubMed1997

Quantitation of ERCC-2 gene expression in human tumor cell lines by reverse transcription-polymerase chain reaction in comparison to northern blot analysis.

Excision repair cross-complementing rodent repair deficiency genes (ERCC) are human genes implicated in nucleotide excision repair. ERCC-2 has been implicated in the repair of DNA damaged by chemotherapeutic agents, and may thus play an important role in anticancer drug resistance. ERCC-2 gene expression is low in primary tumor samples rendering it difficult to quantitate. We have developed a semiquantitative method to measure ERCC-2 gene expression utilizing reverse transcription-polymerase chain reaction (RT-PCR). Total RNA extracted from established human tumor cell lines was reverse-transcribed to obtain cDNA. Serially diluted reference ERCC-2 DNA fragment was amplified by PCR to obtain a 617-bp fragment. A standard curve was then created using densitometry readings of the 617-bp bands on agarose gel. A fixed amount of sample cDNA from each cell line was amplified at the same time and the resultant PCR product was read by densitometer. Using the standard curve, ERCC-2 gene expression in a given amount of total RNA was quantitated and normalized to beta-actin expression. There was minimal variation in three repeated experiments with PCR amplification. ERCC-2 gene expression determined by this semiquantitative PCR was also correlated to ERCC-2 quantitation by Northern blot analysis, with a significant concordance (r = 0.912, P = 0.0002). We also successfully applied this sensitive method to quantify five clinical glioma samples.

Actins↗
PubMed1997

Uterine artery embolization: an underused method of controlling pelvic hemorrhage.

Transcatheter arterial embolization has recently emerged as a highly effective percutaneous technique for controlling acute and chronic genital bleeding in a wide variety of obstetric and gynecologic disorders. Benefits for the patient and health care system have included low complication rates, avoidance of surgical risks, fertility preservation, and shorter hospitalizations. In this article the current indications for pelvic embolotherapy, types of embolotherapy, technical considerations, immediate success rates, causes of failure, complications, and outcome expectations are discussed. Our comprehensive literature review and clinical experience suggest that embolization should be used before surgical treatment of nonmalignant pelvic bleeding in many clinical settings, including postpartum, postcesarean, and postoperative bleeding. It is our strong belief that this form of therapy is underused, and the primary purpose of this article is to emphasize its developing role as a highly effective, relatively noninvasive method of treating genital bleeding.

Arteries↗
PubMed1997

Radiosurgery and accelerated radiotherapy for patients with glioblastoma.

OBJECTIVE: To assess the feasibility, toxicity, and local control of stereotactic radiosurgery followed by accelerated external beam radiotherapy (AEBR) for patients with glioblastoma multiforme. MATERIALS AND METHODS: Six males and eight females, with a median age of 67.5 years (range 45-78 years), entered the study. Karnofsky performance status was 90 for five, 80 for six, and 60 for three patients. Following surgery, the patients were left with a residual mass 4 cm. Radiosurgery was delivered with a single dose of 20 Gy to the 90% isodose surface corresponding to the contrast-enhancing edge of the tumour. A total AEBR dose of 60 Gy in 30 fractions was delivered using a concomitant boost technique over four weeks. RESULTS: Median survival time was 40 weeks (range 17-80 weeks). Actuarial survivals at 12 and 18 months were 43% and 14%, respectively. The median time to progression was 25 weeks (range 2-77 weeks). One patient developed a seizure on the day of stereotactic radiosurgery. Two patients experienced somnolence at 47 and 67 days post-radiotherapy. Eight patients remained steroid-dependent. Radiological evidence of leukoencephalopathy was observed in one patient, and brain necrosis in two additional patients at 30 and 63 weeks. One of these two patients with brain necrosis developed complete loss of vision in one eye, and decreased vision in the contralateral eye at 63 weeks. CONCLUSION: Stereotactic radiosurgery followed by AEBR was feasible but was associated with late complications. The use of such radiosurgical boost for patients with glioblastoma multiforme should be reserved for those patients entering controlled clinical trials.

Adult↗
PubMed1997

Acromegaly with normal basal growth hormone levels.

BACKGROUND: The most common cause of acromegaly is excess of growth hormone (GH) secretion. METHODS: We report a 42-year-old male patient, who had become acromegalic over the past 5 years. There were no visual changes or change in sexual function, no gynaecomastia or galactorrhoea. Both CT and MRI scans showed a large mass measuring 2.5 x 2.5 x 3.5 cm, originating from the sella turcica and extending into and totally filling up the sphenoid sinus with diffusely invasive features. RESULTS: Basal serum GH level was within normal range, but insulin-like growth factor 1 (IGF-1) was elevated with slightly increased prolactin (PRL) and impaired GH secretory regulation as well. A pituitary adenoma was partially removed through transsphenoidal microsurgery. Pathology confirmed a mammo-somatotrophic adenoma but immunocytochemistry study of the tumour showed only positivity for PRL but not GH. CONCLUSIONS: When acromegaly occurs without GH level elevation, one should pay attention that: 1) IGF-1 might be the cause of the clinical feature of acromegaly; 2) The tumour might undergo morphological transformation; and 3) Hyperinsulinemia or GH receptor antibody formation could also be the cause of the acromegalic appearance.

Acromegaly↗
PubMed1997

Evidence for nucleotide excision repair as a modifying factor of O6-methylguanine-DNA methyltransferase-mediated innate chloroethylnitrosourea resistance in human tumor cell lines.

We examined the O6-methylguanine-DNA methyltransferase (MGMT) protein as well as MGMT activity levels and the excision repair cross-complementing rodent repair deficiency gene, ERCC2 (XPD), protein levels in 14 human tumor cell lines not selected for chloroethylnitrosourea (CENU) resistance. These results were compared with 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU) cytotoxicity and UV light sensitivity. MGMT protein correlated significantly with MGMT activity (r = 0.9497, p = 0.0001). There was no significant linear correlation between BCNU cytotoxicity and MGMT content as determined by both Western analysis (r = 0.139, p = 0. 6348) and activity assay (r = 0.131, p = 0.6515). However, MGMT-rich cell lines were found to be more resistant than MGMT-poor cell lines to BCNU (t = 2.2375, p = 0.0225) but not to UV (t = 1.1734, p = 0.1317). Furthermore, the most BCNU-sensitive cell lines were all MGMT-poor. UV sensitivity was significantly correlated to BCNU cytotoxicity (r = 0.858, p = 0.0001). Significant correlations were found between ERCC2 protein levels and BCNU cytotoxicity (r = 0.786, p = 0.0009) or UV sensitivity (r = 0.874, p = 0.0001). Our results confirm that MGMT plays an important role in CENU resistance, but not in UV resistance. The correlation of UV sensitivity with BCNU cytotoxicity suggests that nucleotide excision repair is an important modifying factor of MGMT-mediated innate CENU resistance in human tumor cell lines, especially in highly resistant cell lines. ERCC2 may be implicated in this process.

Antineoplastic Agents, Alkylating↗
PubMed1996

A tyrosyl-tRNA synthetase suppresses structural defects in the two major helical domains of the group I intron catalytic core.

The Neurospora crassa mitochondrial tyrosyl-tRNA synthetase, the CYT-18 protein, functions in splicing group I introns by promoting the formation of the catalytically active structure of the intron RNA. The group I intron catalytic core is thought to consist of two extended helical domains, one formed by coaxial stacking of P5, P4, P6, and P6a (P4-P6 domain) and the other consisting of P8, P3, P7, and P9 (P3-P9 domain). To investigate how CYT-18 stabilizes the active RNA structure, we used an Escherichia coli genetic assay based on the phage T4 td intron to systematically test the ability of CYT-18 to compensate for structural defects in three key regions of the catalytic core: J3/4 and J6/7, connecting regions that form parts of the triple-helical-scaffold structure with the P4-P6 domain, and P7, a long-range base-pairing interaction that forms the guanosine-binding site and is part of the P3-P9 domain. Our results show that CYT-18 can suppress numerous mutations that disrupt the J3/4 and J6/7 nucleotide-triple interactions, as well as mutations that disrupt base-pairing in P7. CYT-18 suppressed mutations of phylogenetically conserved nucleotide residues at all positions tested, except for the universally conserved G-residue at the guanosine-binding site. Structure mapping experiments with selected mutant introns showed that the CYT-18-suppressible J3/4 mutations primarily impaired folding of the P4-P6 domain, while the J6/7 mutations impaired folding of both the P4-P6 and P3-P9 domains to various degrees. The P7 mutations impaired the formation of both P7 and P3, thereby grossly disrupting the P3-P9 domain. The finding that the P7 mutations also impaired formation of P3 provides evidence that the formation of these two long-range pairings is interdependent in the td intron. Considered together with previous work, the nature of mutations suppressed by CYT-18 supports a model in which CYT-18 helps assemble the P4-P6 domain and then stabilizes the two major helical domains of the catalytic core in the correct relative orientation to form the intron's active site.

Bacteriophage T4↗