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D Bartsch

Publications and source records attributed to D Bartsch.

At least 55 records · Page 3Linked to original sources
PubMed1996

Toward a molecular definition of long-term memory storage.

The storage of long-term memory is associated with a cellular program of gene expression, altered protein synthesis, and the growth of new synaptic connections. Recent studies of a variety of memory processes, ranging in complexity from those produced by simple forms of implicit learning in invertebrates to those produced by more complex forms of explicit learning in mammals, suggest that part of the molecular switch required for consolidation of long-term memory is the activation of a cAMP-inducible cascade of genes and the recruitment of cAMP response element binding protein-related transcription factors. This conservation of steps in the mechanisms for learning-related synaptic plasticity suggests the possibility of a molecular biology of cognition.

Animals↗
PubMed1996

Mxi1 tumor suppressor gene is not mutated in primary pancreatic adenocarcinoma.

Amplification of the c-myc oncogene occurs in a variety of solid tumors, including pancreatic adenocarcinomas. The MXI1 gene, located at 10q24-q25, may serve to negatively regulate c-myc oncogene activity, and potentially has tumor suppressor function. As such, altered MXI1 function might contribute to tumorigenesis. We examined 40 primary human pancreatic adenocarcinomas for MXI1 mutations. Single-strand conformation variant analysis and direct sequencing of the variants revealed a MXI1 polymorphism in 1 of 40 tumors. No MXI1 mutations were identified. Southern blot analyses did not reveal any gross rearrangements of MXI1. These results suggest that MXI1 is unlikely to play a role in human pancreatic adenocarcinoma tumorigenesis.

Adenocarcinoma↗
PubMed1996

Infrequent CDKN2 mutation in human differentiated thyroid cancers.

We examined the frequency of cyclin-dependent kinase (CDK) N2 alterations in differentiated and anaplastic thyroid cancers to assess the involvement of CDKN2 in the development of these cancers. The CDKN2 gene, which encodes the cell-cycle regulator p16, was recently shown to be mutated or deleted in many tumor cell lines. Its role in the genesis of primary tumors is uncertain, however. Tumor and corresponding normal DNAs were prepared by microdissection of paraffin-embedded tissue blocks or from frozen surgical specimens of 15 papillary, 15 follicular, and five anaplastic thyroid carcinomas. The entire CDKN2 coding region was screened by single-strand conformational variant analysis and direct sequencing of variants. The presence of homozygous deletions was evaluated by multiplex polymerase chain reaction (PCR) analysis. Loss of heterozygosity (LOH) in the CDKN2 region was assessed by using flanking polymorphic markers. Two somatic missense mutations were found among the 35 thyroid cancers, one in a follicular tumor and one in an anaplastic tumor. Multiplex PCR suggested the presence of homozygous deletion in one anaplastic tumor and hemizygous deletions in four tumors. LOH studies revealed loss of 9p sequences in four follicular (27%) and two anaplastic (50%) cancers. Our data suggest that alterations in CDKN2 played a role in a minority of thyroid cancers (three of 35). LOH in the region of CDKN2 is seen in a significant proportion of follicular and anaplastic but not papillary cancers. Loss of 9p sequences suggests a role for a tumor suppressor gene in the development of follicular and anaplastic thyroid cancers.

Adenocarcinoma, Follicular↗
PubMed1996

Surgical management of hyperparathyroidism in patients with multiple endocrine neoplasia type 2A.

BACKGROUND: The surgical management of hyperparathyroidism in patients with multiple endocrine neoplasia type 2A (MEN 2A) is controversial. We report the long-term follow-up, mutational analysis, and surgical outcome in a large group of patients with MEN 2A and hyperparathyroidism. METHODS: Clinical and genetic data for MEN 2A patients with biochemically and pathologically confirmed hyperparathyroidism and a minimum of 5 years of follow-up were analyzed retrospectively, and outcomes after surgical management were compared. RESULTS: Thirty-five (29%) of 119 patients from 14 MEN 2A kindreds had biochemical and pathologic evidence of hyperparathyroidism, with a mean follow-up of 14.7 years. The phenotypic expression of hyperparathyroidism was associated with germline mutations of the RET protooncogene at codons 634 and 618. At initial operation, 21 (62%) patients had a selective resection, eight (24%) had a subtotal resection, five (14%) had total parathyroidectomy with autotransplantation, and one had an inadvertent total parathyroidectomy. Twenty-seven (77%) patients were cured by the first operation. Persistent hyperparathyroidism occurred in three (8.6%) patients, and recurrent hyperparathyroidism occurred in five (14.3%) patients; both occurred only in patients treated with selective or subtotal resection. Permanent postoperative hypoparathyroidism occurred in six (21%) of 29 patients after selective or subtotal resection, in the one patient with inadvertent total parathyroidectomy, and in one (20%) of 5 patients treated with total parathyroidectomy and autotransplantation. CONCLUSIONS: Recurrent or persistent hyperparathyroidism occurs after selective or subtotal parathyroidectomy, as a result of either missed glands or interval development of neoplasia in previously normal parathyroid glands left in situ. Therefore we advocate total parathyroidectomy and heterotopic autotransplantation for patients with hyperparathyroidism and MEN 2A.

Adolescent↗
PubMed1995

Aplysia CREB2 represses long-term facilitation: relief of repression converts transient facilitation into long-term functional and structural change.

The switch from short- to long-term facilitation induced by behavioral sensitization in Aplysia involves CREB-like proteins, as well as the immediate-early gene ApC/EBP. Using the bZIP domain of ApC/EBP in a two-hybrid system, we have cloned ApCREB2, a transcription factor constitutively expressed in sensory neurons that resembles human CREB2 and mouse ATF4. ApCREB2 represses ApCREB1-mediated transcription in F9 cells. Injection of anti-ApCREB2 antibodies into Aplysia sensory neurons causes a single pulse of serotonin (5-HT), which induces only short-term facilitation lasting minutes, to evoke facilitation lasting more than 1 day. This facilitation has the properties of long-term facilitation: it requires transcription and translation, induces the growth of new synaptic connections, and occludes further facilitation by five pulses of 5-HT.

Activating Transcription Factor 2↗
PubMed1995

A VAMP-binding protein from Aplysia required for neurotransmitter release.

Before the fusion of synaptic vesicles with the plasma membrane, a protein complex is thought to form between VAMP--an integral membrane protein of the vesicle--and two proteins associated with the plasma membrane, SNAP-25 and syntaxin. The yeast two-hybrid interaction cloning system has now been used to identify additional proteins from Aplysia that interact directly with VAMP. A 33-kilodalton membrane protein, termed VAP-33 (VAMP-associated protein of 33 kilodaltons), was identified whose corresponding messenger RNA was detected only in the central nervous system and the gill of Aplysia. Presynaptic injection of antibodies specific for VAP-33 inhibited synaptic transmission, which suggests that VAP-33 is required for the exocytosis of neurotransmitter.

Amino Acid Sequence↗
PubMed1995

Clinical and surgical aspects of double adenoma in patients with primary hyperparathyroidism.

The incidence of double parathyroid adenoma in 277 prospectively documented patients suffering from primary hyperparathyroidism was 5.4 per cent (15 patients). Patients with double adenoma were all symptomatic and had a significantly higher parathyroid hormone (PTH) level and tumour weight than those with a solitary adenoma or four-gland hyperplasia. In 11 patients the adenomas were located bilaterally. Bilateral neck exploration must be performed routinely to deal successfully with this condition at initial operation. In six patients one enlarged gland was found in the thymus or posterior mediastinum. These locations should be explored, especially in patients with high PTH levels, in those in whom all four parathyroid glands cannot be detected or if only one small adenoma is found. In all such patients, selective resection of the enlarged parathyroid glands resulted in normocalcaemia (median follow-up 3.5 years). Selective resection of the pathological glands is the treatment of choice.

Adenoma↗
PubMed1995

Frequent mutations of CDKN2 in primary pancreatic adenocarcinomas.

The gene encoding the cell-cycle regulatory protein p16, CDKN2, is localized on chromosome band 9p21. CDKN2 is frequently deleted or mutated in a variety of tumor cell lines, including pancreatic cancer cell lines and xenografts, as well as in some primary tumors. We examined 32 primary pancreatic adenocarcinomas for CDKN2 mutations and for loss of heterozygosity of 9p21 sequences to assess the role of CDKN2 in pancreatic carcinogenesis. Single-strand conformation variant analysis (SSCV) and direct sequencing of the variants revealed somatic CDKN2 mutations in 11 of 32 tumors (five frame-shift mutations, five nonsense mutations, and one missense mutation). One tumor appeared to be characterized by homozygous deletion of CDKN2. These results suggest that CDKN2 plays an important role during tumorigenesis or tumor progression in a significant proportion of pancreatic adenocarcinomas.

Adenocarcinoma↗
PubMed1995

Low frequency of CDKN2 mutation in endometrial carcinomas.

The CDKN2 gene on chromosome 9p21 encodes the p16 inhibitor of cyclin D/cyclin-dependent kinase 4 complexes. Mutations and deletions of CDKN2 have been frequently identified in cell lines, whereas most primary tumors have demonstrated a lower frequency of alteration. To assess the role of CDKN2 in endometrial tumorigenesis, 34 tumor samples were examined for loss of heterozygosity at 9p21 and mutation in CDKN2. To identify tumors that had lost 9p21, samples were genotyped with markers flanking the CDKN2 locus. The frequency of CDKN2 mutation in endometrial carcinomas was determined by single-strand conformation variant analysis and direct sequencing of variants. Of the 34 tumors examined, three revealed loss of 9p21 sequences. Two samples were characterized by point mutations in CDKN2, one of which also showed loss of 9p21 sequences.

Alleles↗
PubMed1995

Proteins functioning in synaptic transmission at the sensory to motor synapse of Aplysia.

Over expression of Aplysia synaptotagmin in acutely dissected cholinergic neurons from the buccal ganglia, or in primary co-cultures of glutaminergic sensory neurons and motor neurons, causes a reduction synaptic transmission. Anti-sense oligonucleotide treatment of similar cultures produced an enhancement of synaptic transmission. The interaction between Aplysia VAMP/synaptobrevin and syntaxin is reconstructed using the yeast two hybrid system, and used to identify amino acid residues of VAMP/synaptobrevin that are required for this interaction. Point mutations around residue 50, close to the site of cleavage by botulinum toxins specifically disrupt the interaction with syntaxin. An additional VAMP/synaptobrevin binding protein, VAP33, is identified using the yeast two hybrid system. Intracellular injection of VAP33 specific antisera inhibits synaptic transmission in sensory-motor neuron co-cultures.

Amino Acid Sequence↗
PubMed1995

CD15 and HKN-1 reveal cerebellar compartments with a complex overlap.

The CD15-epitope in the cerebellar cortex is expressed by Bergmann glial fibers which are organized in symmetrical iterative stripes. Their arrangement appears complementary to the pattern described for the organization of compartments demonstrated by any other marker used so far. HNK-1 however, reveals stripes that are not complementary to the general pattern for the organization of compartments.

Animals↗
PubMed1994

Characterization of a Y-Box factor from Aplysia californica.

A cDNA isolated from the marine invertebrate Aplysia californica encodes a protein containing a domain with a high degree of homology to the Y-Box-binding factors. The expression of this gene is unaffected by the facilitatory neurotransmitter, 5-hydroxytryptamine. When expressed in Escherichia coli, the encoded protein is shown to bind RNA in vitro.

Amino Acid Sequence↗
PubMed1994

[Pancreatitis in primary hyperparathyroidism (pHPT) is a complication of advanced pHPT].

Pancreatitis occurred in 13 (5.6%) of 234 patients (76 men, 158 women; mean age 63 [2-83] years) who were operated on for primary hyperparathyroidism (pHPT) between 1987 and 1992. The pancreatitis patients had a significantly higher median level of parathormone (340 pg/ml), of serum calcium (3.2 mmol/l) and of thyroid weight (1.7 g) than the remaining 221 patients (135 pg/ml; 2.9 mmol/l; 1.0 g, respectively: P < 0.05 for each). In ten patients pHPT had been diagnosed during an attack of pancreatitis: pancreatitis had been the diagnostic clue to pHPT. After conservative treatment of the pancreatitis and parathyroidectomy seven of the ten patients were free of symptoms during the follow-up. In one patient pancreatitis recurred postoperatively and two patients died of the consequences of haemorrhagic necrotizing pancreatitis. Cholelithiasis, as another possible causative factor for pancreatitis, was present in five of the 13 patients (38%). None of the patients was an alcoholic. These data indicate that there is a positive correlation between advanced pHPT and pancreatitis. Pancreatitis may be the expression of much advanced hyperparathyroidism which has been diagnosed too late.

Acute Disease↗
PubMed1994

[Laparoscopic cholecystectomy in morbid obesity. Indications or contraindications?].

In early reports on the experience with laparoscopic cholecystectomy severe obesity was considered a contraindication for this procedure. The prospectively documented data of 370 consecutive patients undergoing laparoscopic cholecystectomy were analysed to investigate, whether this point of view is still justified. 35 of these 370 patients were classified as being severely obese (body-mass-index greater than 33 kg/m2). Median operation time was significantly longer in these patients than in the remaining patients (p < 0.05). In selected cases the operative technique had to be slightly modified due to extreme abdominal wall thickness. Dissection of Calot's triangle was not more difficult than in non-obese patients. There was no statistically significant difference concerning conversion rates between severely obese patients (11.4%) and the other group of patients (15.5%). Also, the number of complications was not increased in the obese patients. Since the higher complication rate in severely obese patients after conventional abdominal surgery is mainly due to the incision, laparoscopic cholecystectomy is the preferable procedure to treat symptomatic gallstone disease in these patients.

Adolescent↗
PubMed1993

[Laparoscopic adrenalectomy].

Between June and September 1993, laparoscopic adrenalectomy was indicated in five patients (three women, two men; aged 25-50 years). Three had a phaeochromocytoma, two had an adenoma (Conn's syndrome). Four of the five tumours were localized to the right adrenal gland, one to the left. Tumour diameter ranged from 3 to 5 cm. The laparoscopic procedure was successful in four of the patients (three right, one left). In the fifth case the operations had to be completed by conventional surgery, because of non-controllable haemorrhage. Duration of operation ranged between 165 and 360 min for right adrenalectomy and was 135 min for the left one. Rapid convalescence, lower dose of pain-killing drug required, short hospital stay and good cosmetic results characterized the postoperative course after the laparoscopic procedure. This technique thus opens up new perspectives for adrenal surgery.

Adrenal Gland Neoplasms↗
PubMed1993

[Broad use of laparoscopic cholecystectomy in the teaching clinic. Experiences and results of 300 operations].

Laparoscopic cholecystectomy (LC) was integrated early in surgical training according to the concept "observe, assist and then operate under the assistance of an experienced surgeon". 300 LC's were performed by 27 different surgeons (8 board certified surgeons, 19 residents in the year 2-6 of training). 60.3% of all LC's and 73% of LC's performed for acute cholecystitis were done by residents. Our results including an overall complication rate of 5.3% shows, that LC can be performed by residents without additional complications or unacceptable length of operations, provided the threshold for conversion is low and the surgeon is assisted by an experienced laparoscopist. We therefore suggest that the early integration of LC in surgical training is justified.

Cholecystectomy↗