Biomedical subjects

I Langer

Publications and source records attributed to I Langer.

At least 19 recordsLinked to original sources

PubMed2006

Breast cancer sagittal/horizontal plane location influences axillary lymph node involvement.

AIM: To assess the influence of tumour location on axillary lymph node involvement (ALNI) and prognosis in breast cancer by evaluating the significance of the sagittal/horizontal alignment. METHODS: We compared 57 patients with superficially located breast carcinomas up to 3.0 cm with patients having lesions in posterior planes of the breast. Both groups were matched according to age, time of diagnosis, tumour size, grade, hormonal receptor status and tumour site within the frontal plane. Histologic evidence of skin involvement, excluding tumours fulfilling the criteria for pT4b, was defined as inclusion criteria and reference plane for superficial tumour location. RESULTS: Tumours situated in the superficial region of the breast, compared to those located in deeper planes, have an increased risk of ALNI (p=0.023), whereas no difference was observed with reference to disease-specific survival (p=0.203). CONCLUSION: This study shows that ALNI is dependent on sagittal/horizontal as well as frontal tumour location. Clinicians should be aware that tumours lying posteriorly may be at increased risk of occult spread outside axillary lymph nodes.

Adult↗

PubMed2005

Scope and significance of non-uniform classification practices in breast cancer with non-inflammatory skin involvement: a clinicopathologic study and an international survey.

BACKGROUND: The study evaluates the scope of non-uniform classification practices concerning breast carcinomas with non-inflammatory skin involvement. PATIENTS AND METHODS: We compared the clinical course of patients with histologically proven non-inflammatory skin involvement: 119 (65.4%) with clinically obvious 'classical' skin changes (Group A) and 63 (34.6%) with no or only discreet changes (Group B). A questionnaire was circulated to pathology departments in 24 countries to assess the practice concerning the placement of skin- involved breast carcinomas in the TNM classification. RESULTS: Patients in Group B showed a significantly better disease specific survival (P=0.0002). Eighty-six respondents (70.5%) of the survey preferred the 'histological view' and classified tumors with only histological proven skin involvement as T 4 b/stage IIIB. The opposing classification principle ('clinical view'), which dictates that T 4 b breast cancer is a clinical diagnosis and the classical signs must be present, was supported by 31 respondents (25.4%). CONCLUSIONS: A large number of breast cancer patients with non-inflammatory skin involvement are only histologically proven and show, compared with cases exhibiting the classical clinical signs, significant differences in clinical course and prognosis. In general, both subsets were aggregated in one T category/stage (T 4 b/IIIB). This results in a considerable distortion of the reported statistical data.

Adult↗

PubMed2005

Long-term outcomes of breast cancer patients after endoscopic axillary lymph node dissection: a prospective analysis of 52 patients.

BACKGROUND: Reports on long-term outcomes after endoscopic axillary lymph node dissection (ALND) of breast cancer patients are still lacking in the medical literature. The objective of this prospective study was to assess the oncological and functional outcomes in breast cancer patients after endoscopic ALND. METHODS: Fifty-five breast cancer patients were prospectively enrolled, of whom 52 were available for follow-up with a median of 71.9 months (range 11-96). The following oncological and functional endpoints were evaluated during follow-up at several time points: occurrence of local, axillary and distant metastases, seroma or infection, shoulder mobility (range of motion), numbness, pain, presence of lymphoedema as well as restriction in activities of daily living. RESULTS: In 52 patients endoscopic ALND of level I and II was successfully performed. Two port-site metastases (2/52, 4%) occurred, one of which in a patient with negative axillary lymph nodes. The same patient suffered from the only axillary recurrence (1/52, 2%). Three patients (3/52, 6%) developed lymphoedema. No other functional adverse events (shoulder mobility, pain, numbness, hypertrophic scar) were noticed at the end of the observation period. CONCLUSION: The present investigation with long-term follow-up after endoscopic ALND--the first one in the literature--reveals minor morbidity, good functional and cosmetic results. In contrary to conventional surgery, the endoscopic procedure is associated with the occurrence of port-site metastases, not seen in the open approach. Axillary recurrences do not appear more frequently when compared with results after conventional ALND. In the meantime the less invasive sentinel lymph node (SLN) biopsy is the established standard technique in evaluating the axillary lymph node status.

Activities of Daily Living↗

PubMed2005

Retroperitoneoscopic living donor nephrectomy: a comparison with the open approach in respect of early postoperative pain management.

INTRODUCTION: We retrospectively compared perioperative donor outcomes and early postoperative pain control after retroperitoneoscopic (RLDN) and standard open (OLDN) living donor nephrectomy. METHODS: One hundred donors included fifty after RLDN (37 women/13 men) and 50 after OLDN (35 women/15 men) were retrospectively analyzed for basic analgesics, for opioid consumption, and for visual analog scale (VAS) to verify the experienced pain. The donors were questioned in the morning and evening of the first through fifth postoperative days. RESULTS: The mean age of both groups was equal. The mean operating time was 149.7 +/- 48.2 minutes (60 to 270) for RLDN and 164.1 +/- 30.3 minutes (60 to 240) for OLDN (P = NS). The mean warm ischemia time was 120 +/- 36 seconds (50 to 240) and 114 +/- 31 seconds (60 to 190) for the RLDN and OLDN groups, respectively (P = NS). The mean evening VAS for RLDN versus OLDN on postoperative days 1 to 5 was: 2.1 versus 2.2 (P = NS), 0.9 versus 1.8 (P = .009), 0.5 versus 1.3 (P = .016), 0.1 versus 0.7 (P = .013), and 0.1 versus 0.7 (P = .013), respectively. In both groups there was a tendency toward a higher VAS score in the morning than in the evening. RLDN donors showed significantly earlier period free of pain (VAS = 0) than those after OLDN. There was a significant difference of being free from any opiate between both groups after surgery. CONCLUSIONS: After RLDN donors experienced less postoperative pain than after OLDN over the early postoperative days. Therefore, postoperative regional anesthesia is not necessary for donors operated by a retroperitoneoscopic approach.

Adult↗

PubMed2004

Changes in bone mineral content after surgical treatment of morbid obesity.

Weight loss reduces bone mass and increases the risk of osteoporosis. This study was undertaken to assess changes of bone metabolism following Roux-en-Y gastric bypass (RYGB) and adjustable silicone gastric banding (ASGB) as compared to nonoperated controls of morbidly obese subjects. Fourteen female and 5 male patients with a mean (+/-SEM) age of 44.3 +/- 1.8 years participated in the 24-month prospective study. Nine patients underwent ASGB, 4 patients RYGB operation, and 6 patients were included in the control group. Bone metabolism was assessed by determination of serum parathyroid hormone (PTH), osteocalcin, urinary deoxypyridinoline, and dual energy x-ray absorptiometry (DXA) before, and 6, 12, and 24 months after intervention. The body mass index (BMI) decreased from 41.0 +/- 1.1 to 34.0 +/- 1.4 kg/m2 in the ASGB group (P = .001), from 42.7 +/- 2.2 to 30.5 +/- 2.2 kg/m2 in the RYGB group (P = .006), and remained unchanged in the control group (from 41.2 +/- 1.2 to 41.4 +/- 1.4 kg/m2) after 24 months. Bone mineral content (BMC) showed no significant change in the ASGB group (from 3,079 +/- 140 to 3,064 +/- 129 g) and in the control group (from 2,945 +/- 130 to 2,940 +/- 111 g), whereas it decreased from 2,968 +/- 111 to 2,621 +/- 139 g in the RYGB group (P = .005). The loss in BMC was accompanied by significant increases in urinary deoxypyridinoline (P < .05) and in serum osteocalcin (P < .01) after RYGB, suggesting both, increased bone resorption and increased bone formation. The authors were aware of the fact that the study groups were small and conclusions need to be regarded as preliminary. However, the RYGB operation resulted in enhanced weight loss and significant net loss of bone mass in comparison to ASGB and obese control subjects. Patients losing large amounts of body weight should be monitored regularly regarding prevention of osteoporosis.

Absorptiometry, Photon↗

PubMed2003

Lysine 195 and aspartate 196 in the first extracellular loop of the VPAC1 receptor are essential for high affinity binding of agonists but not of antagonists.

The role in ligand recognition and receptor activation of two adjacent charged residues (lysine 195 and aspartate 196) in the first extracellular loop of the human VPAC(1) receptor was investigated in stably transfected CHO cells expressing the wild type or point mutated receptors.Replacement of lysine 195 by glutamine or of aspartate 196 by asparagine reduced the agonists' ability to stimulate adenylate cyclase activity; VIP behaved like a partial agonist and a partial agonist behaved as an antagonist. The receptor's capacity to recognize agonists was reduced but antagonists' affinity was unaffected. Both results suggesting that the two charged residues are essential for VPAC(1) receptor activation. On the other hand, the double mutant was less severely affected than single mutants suggesting that hydrogen bonds may partially compensate the loss of charged residues. But the inversion of the residues affected receptor recognition and activation more markedly suggesting that the two charged residues do not interact directly.

Adenylyl Cyclases↗

PubMed2003

Peritoneal mesothelioma after environmental asbestos exposure.

Mesothelioma are primary malignant neoplasms of the serous membranes. They usually involve the pleura and rarely the pericardium, the peritoneum and the tunica vaginalis testis. About 90% are associated with exposure to asbestos. The exposure is generally occupational, an environmental inhalation of asbestos and asbestiform fibers in areas in Turkey has been observed and presents a major health problem. This report of a patient from Anatolia with peritoneal mesothelioma after environmental exposure outlines the importance of considering this pathology in the differential diagnosis of a Turkish patient presenting with ascites.

Adult↗

PubMed2003

Diagnosis of malignant hyperthermia susceptibility during CABG surgery.

A 55-year-old man presented for coronary artery bypass graft (CABG) surgery. Malignant hyperthermia (MH) was suspected in his family. This case report describes a diagnostic approach to obtain a definite MH diagnosis by performing an in vitro contracture test at the time of CABG surgery in combination with molecular genetic investigations.

Adult↗

PubMed2002

The genome sequence of Schizosaccharomyces pombe.

We have sequenced and annotated the genome of fission yeast (Schizosaccharomyces pombe), which contains the smallest number of protein-coding genes yet recorded for a eukaryote: 4,824. The centromeres are between 35 and 110 kilobases (kb) and contain related repeats including a highly conserved 1.8-kb element. Regions upstream of genes are longer than in budding yeast (Saccharomyces cerevisiae), possibly reflecting more-extended control regions. Some 43% of the genes contain introns, of which there are 4,730. Fifty genes have significant similarity with human disease genes; half of these are cancer related. We identify highly conserved genes important for eukaryotic cell organization including those required for the cytoskeleton, compartmentation, cell-cycle control, proteolysis, protein phosphorylation and RNA splicing. These genes may have originated with the appearance of eukaryotic life. Few similarly conserved genes that are important for multicellular organization were identified, suggesting that the transition from prokaryotes to eukaryotes required more new genes than did the transition from unicellular to multicellular organization.

Base Sequence↗

PubMed2002

[Malignant transformation of perianal Buschke-Löwenstein tumor. Extensive abdominoperineal rectum excision and reconstruction with transpelvic myocutaneous rectus abdominis muscle flap].

INTRODUCTION: The Buschke Löwenstein tumor (giant condyloma) in its perianal variant is an extremely rare disease caused by human papilloma virus. Although of histologically benign appearance, it infiltrates and destroys the surrounding tissue. There is a high risk of local recurrence and malignant transformation. The treatment of choice is wide surgical resection. CASE: A 56-year-old woman presented with perianal giant condyloma infiltrating the rectum and vagina. The extensive soft tissue defect resulting from wide resection was filled with a transpelvic myocutaneous rectus abdominis flap. Histology showed a squamous cell carcinoma arising in the Buschke Löwenstein tumor with clear resection margins. Therefore, the patient was irradiated locally after uneventful primary wound healing. CONCLUSION: A simultaneous reconstruction of a large pelvinoperineal soft tissue defect with the transpelvic myocutaneous rectus abdominis flap allows primary healing, accelerated rehabilitation, and safe adjuvant radiotherapy without risk of serious radiation damage to the small bowel by preventing it from protruding into the pelvic defect.

Anal Canal↗

PubMed2002

Two tyrosine residues in the first transmembrane helix of the human vasoactive intestinal peptide receptors play a role in supporting the active conformation.

1: We investigated the human vasoactive intestinal polypeptide (VIP) receptors VPAC(1) and VPAC(2) mutated at conserved tyrosine residues in the first transmembrane helix (VPAC(1) receptor Y146A and Y150A and VPAC(2) receptor Y130A and Y134A). 2: [(125)I]-Acetyl-His(1) [D-Phe(2), K(15), R(16), L(27)]-VIP (1-7)/GRF (8-27) (referred to as [(125)I]-VPAC(1) antagonist) labelled VPAC(1) binding sites, that displayed high and low affinities for VIP (IC(50) values and per cent of high affinity binding sites: wild-type, 1 nM (57+/-9%) and 160 nM; Y146A, 30 nM (40+/-8%) and 800 nM; Y150A, 4 nM (27+/-8%) and 300 nM). [R(16)]-VIP behaved as a "super agonist" at both mutated VPAC(1) receptors and the efficacies of VIP analogues modified in positions 1, 3 and 6 were significantly decreased. 3: VIP was less potent at the Y130A and Y134A mutated VPAC(2) receptors (EC(50) 200 and 400 nM, respectively) than at the wild-type VPAC(2) receptor (EC(50) 7 nM). Furthermore, [hexanoyl-His(1)]-VIP behaved as a "super agonist" at the two mutated VPAC(2) receptors, and VIP analogues modified in positions 1, 3 and 6 were less potent and efficient at the mutated than at wild-type VPAC(2) receptors. However, the Y130A and Y134A mutants could not be studied in binding assays. 4: Our results suggest that the conserved tyrosine residues do not interact directly with the VIP His(1), Asp(3) or Phe(6) residues (that are necessary for receptor activation), but stabilize the correct active receptor conformation.

Adenylyl Cyclases↗

PubMed2002

A small sequence in the third intracellular loop of the VPAC(1) receptor is responsible for its efficient coupling to the calcium effector.

The stimulatory effect of vasoactive intestinal peptide (VIP) on the intracellular calcium concentration ([Ca(2+)](i)) has been investigated in Chinese hamster ovary cells stably transfected with the reporter gene aequorin, and expressing human VPAC(1), VPAC(2), chimaeric VPAC(1)/VPAC(2) or mutated receptors. The VIP-induced increase in [Ca(2+)](i) was linearly correlated with receptor density, and was higher in cells expressing VPAC(1) receptors than in cells expressing a similar density of VPAC(2) receptors. The study was performed to establish the receptor sequence responsible for this difference. VPAC(1)/VPAC(2) chimaeric receptors were first used for broad positioning: those receptors having the third intracellular loop (IC3) of the VPAC(1) or the VPAC(2) receptor behaved, in this respect, phenotypically like VPAC(1) and VPAC(2) receptors respectively. Replacement in the VPAC(2) receptor of the sequence comprising residues 315-318 (VGGN) within IC3 by its VPAC(1) receptor counterpart (residues 328-331; IRKS) and the introduction of VGGN instead of IRKS into VPAC(1) was sufficient to mimic VPAC(1) and VPAC(2) receptor characteristics respectively. Thus a small sequence in the IC3 domain of the VPAC(1) receptor is responsible for the efficient agonist-stimulated increase in [Ca(2+)](i).

Amino Acid Sequence↗

PubMed2001

Two basic residues of the h-VPAC1 receptor second transmembrane helix are essential for ligand binding and signal transduction.

We mutated the vasoactive intestinal peptide (VIP) Asp(3) residue and two VPAC(1) receptor second transmembrane helix basic residues (Arg(188) and Lys(195)). VIP had a lower affinity for R188Q, R188L, K195Q, and K195I VPAC(1) receptors than for VPAC(1) receptors. [Asn(3)] VIP and [Gln(3)] VIP had lower affinities than VIP for VPAC(1) receptors but higher affinities for the mutant receptors; the two basic amino acids facilitated the introduction of the negatively charged aspartate inside the transmembrane domain. The resulting interaction was necessary for receptor activation. 1/[Asn(3)] VIP and [Gln(3)] VIP were partial agonists at VPAC(1) receptors; 2/VIP did not fully activate the K195Q, K195I, R188Q, and R188L VPAC(1) receptors; a VIP analogue ([Arg(16)] VIP) was more efficient than VIP at the four mutated receptors; and [Asn(3)] VIP and [Gln(3)] VIP were more efficient than VIP at the R188Q and R188L VPAC(1) receptors; 3/the [Asp(3)] negative charge did not contribute to the recognition of the VIP(1) antagonist, [AcHis(1),D-Phe(2),Lys(15),Arg(16),Leu(27)] VIP ()/growth hormone releasing factor (8-27). This is the first demonstration that, to activate the VPAC(1) receptor, the Asp(3) side chain of VIP must penetrate within the transmembrane domain, in close proximity to two highly conserved basic amino acids from transmembrane 2.

Adenylyl Cyclases↗

PubMed2001

Characterization of functional VIP/PACAP receptors in the human erythroleukemic HEL cell line.

The presence of VIP/PACAP receptors was investigated on the human erythroleukemic cell line HEL. Specific binding of [125I]-PACAP or [125I]-VIP on HEL cells or membranes was very low and did not allow to perform competition curves. At 37 degrees C PACAP transiently increased cAMP levels in the presence of the non-specific phosphodiesterase inhibitor IBMX, suggesting rapid desensitization. Kinetic studies revealed that optimal conditions to measure the EC(50) of PACAP(1-27) were 10 min at 20 degrees C. Under those conditions, PACAP-related peptides increased cAMP levels with EC(50) in agreement with the pharmacological profile of the VPAC(1) receptor subtype: PACAP = VIP > [K(15), R(16,) L(27)]VIP(1-7)/GRF(8-27) = [R(16)]ChSn (two VPAC(1) agonists) >> helodermin = secretin. RO 25-1553, a selective activator of VPAC(2) receptor was inactive at 1 microM. Dose-response curves of VPAC(1) agonist molecules (PACAP, VIP, [K(15), R(16), L(27)]VIP(1-7)/GRF(8-27), [R(16)]ChSn) were shifted to the right by the VPAC(1) receptor antagonist [AcHis(1), D-Phe(2), Lys(15), Leu(17)]VIP(3-7)/GRF(8-27), with a K(i) of 3 +/- 1 nM (n = 3). The presence of VPAC(1) receptor mRNA was confirmed by RT-PCR. Preincubation with PACAP or PMA showed that VPAC(1) receptors underwent homologous and heterologous desensitization. This study provides the first evidence for the expression of functional VPAC(1) receptors undergoing rapid desensitization in HEL cells.

Base Sequence↗

PubMed2001

Mutational analysis of the human vasoactive intestinal peptide receptor subtype VPAC(2): role of basic residues in the second transmembrane helix.

1. We investigated the role of two conserved basic residues in the second transmembrane helix arginine 172 (R172) and lysine 179 (K179) of the VPAC(2) receptor. 2. Vasoactive intestinal polypeptide (VIP) activated VPAC(2) receptors with an EC(50) value of 7 nM, as compared to 150, 190 and 4000 nM at R172L, R172Q and K179Q-VPAC(2) receptors, respectively. It was inactive at K179I mutated VPAC(2) receptors. These results suggested that both basic residues were probably implicated in receptor recognition and activation. 3. The VPAC(2)-selective VIP analogue, [hexanoyl-His(1)]-VIP (C(6)-VIP), had a higher affinity and efficacy as compared to VIP at the mutated receptors. 4. VIP, Asn(3)-VIP and Gln(3)-VIP activated adenylate cyclase through R172Q receptors with EC(50) values of 190, 2 and 2 nM, respectively, and through R172L receptors with EC(50) values of 150, 12 and 8 nM, respectively. Asn(3)-VIP and Gln(3)-VIP behaved as partial agonists at the wild type receptor, with E(max) values (in per cent of VIP) of 75 and 52%, respectively. In contrast, they were more efficient than VIP (E(max) values of 150 and 150% at the R172Q VPAC(2) receptors, and of 400 and 360% at the R172L receptors, respectively). These results suggested that the receptor's R172 and the ligand's aspartate 3 are brought in close proximity in the active ligand-receptor complex. 5. The K179I and K179Q mutated receptors had a lower affinity than the wild-type receptors for all the agonists tested in this work: we were unable to identify the VIP amino acid(s) that interact with K179.

Acylation↗

PubMed2001

Vasoactive intestinal peptide (VIP) stimulates [Ca2+]i and cyclic AMPin CHO cells expressing Galpha16.

The stimulatory effect of vasoactive intestinal peptide (VIP) and analogues on [Ca2+]i has been investigated in chinese hamster ovary (CHO) cells stably transfected with the reporter gene aequorin, and expressing either the human VPAC1or VPAC2 receptor in absence or in presence of the Galpha16. In cells that were not transfected with Galpha16 and expressed a similar density of receptors, the VIP induced [Ca2+]i ncrease was higher in VPAC1 than in VPAC2 receptor expressing cells. In aequorin/Galpha16 cotransfected cells, the VIP-induced response was higher, reaching 70 to 80% of the maximal calcium response, obtained after digitonin treatment, in response to both VPAC1 and VPAC2 receptor stimulation. The results suggest that in hematopoietic cells, which express both VIP receptors and Galpha16, the signalling pathway of VIP could be mediated through both cyclic AMP and [Ca2+]i increase.

Adenylyl Cyclases↗

PubMed2001

Advanced breast biopsy instrumentation for the evaluation of impalpable lesions: a reliable diagnostic tool with little therapeutic potential.

OBJECTIVE: To assess the potential of advanced breast biopsy instrumentation (ABBI) to clarify the diagnosis of impalpable mammographic lesions and to remove the entire malignant lesions with clear margins. DESIGN: Prospective assessment in a consecutive series of patients. SETTING: University hospital, Basel, Switzerland. SUBJECTS: 139 patients presenting with 144 impalpable microcalcifications or solid nodular densities evident on screening and follow-up mammograms that were suspicious of malignancy. MAIN OUTCOME MEASURES: Feasibility, sensitivity, efficiency in obtaining definitive diagnoses in an outpatient clinic under local anaesthesia, feasibility of complete removal of a primary malignancy, and intervention-related morbidity. RESULTS: The ABBI procedure was successful in 135/144 (94%); an accurate diagnosis was made in 129/130 patients followed up (99%), sensitivity for malignant lesions was 31/32 (97%) and there were 2 complications (2%). Margins of the biopsy cylinder contained a malignant lesion in 26/31 (84%). CONCLUSIONS: Excisional biopsy using the ABBI system is a reliable diagnostic tool with a low morbidity. As in other published series margins were often not clear of tumour and therefore the therapeutic use of the ABBI procedure is limited.

Adult↗

PubMed2000

Eriochrome Black T inhibits endothelial cell growth through S-phase blockade.

We used human umbilical vein endothelial cells (HUVEC) cultures to investigate in vitro the antiproliferative effects of suramin and of its analogue, Eriochrome Black T. The cell cycle phases of interest were characterised with specific immune sera raised against cyclin D(1), cyclin E and proliferating nuclear cell antigen (PCNA). Simultaneous detection of two cell cycle markers was ensured by double colour immunofluorescence. Both compounds inhibited the endothelial cell growth while Eriochrome Black T was more potent than suramin. Suramin induced HUVEC to accumulate in G1-phase as an increase of the number of cells expressing both cyclin D(1) and PCNA was observed. Eriochrome Black T preferentially blocked them in the early S-phase, as it increased the proportion of cyclin E positive cells. These results suggest that in addition of its more potent antiproliferative effect on endothelial cell growth, Eriochrome Black T acts at another molecular level than suramin.

Azo Compounds↗