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B Petersen

Publications and source records attributed to B Petersen.

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

Molecular biology of growth-hormone-secreting human pituitary tumours: biochemical consequences and potential clinical significance.

Molecular biological studies have revealed that 30-40% of GH-secreting human pituitary tumours, associated with acromegaly, harbour single-base missense mutations within the Gs alpha gene, termed gsp oncogenes. In addition, a large proportion of GH-secreting tumours inappropriately express the GH-releasing factor (GRF) gene. Gsp-oncogenes result in elevated adenylyl cyclase activity with consequent abnormally high cAMP production. In culture, GH-secreting tumours expressing gsp oncogenes respond more efficiently to the somatostatin analogue, octreotide (SMS), raising the possibility that acromegalics harbouring gsp-positive tumours may be those who optimally benefit from SMS therapy. Inappropriate expression of GRF may result in abnormal presence of a positive autocrine feedback loop, in which secreted GRF acts on the same cells to promote cellular proliferation and GH secretion. Blockade of GRF mRNA translation by means of anti-sense oligonucleotide approaches may prove to be of value in inhibiting tumour function.

Acromegaly↗
PubMed1996

Neuroradiological findings in classical late infantile neuronal ceroid-lipofuscinosis.

We describe a girl aged 5 years, 6 months who began to have seizures at the age of 3 years, 9 months. A cranial CT scan revealed mild, generalized cerebral atrophy. During the next year, she gradually developed ataxia, myoclonic jerks, and bilateral optic nerve atrophy and lost motor skills. A second CT scan performed 12 months after the onset of first symptoms revealed marked progression of cerebral atrophy, especially in the infratentorial area. MRI demonstrated bilateral, periventricular hyperintensities in the T2-weighted images but no changes in the basal ganglia. Electron microscopic investigations of skin biopsies demonstrated curvilinear bodies, confirming the suspected diagnosis of late infantile neuronal ceroid-lipofuscinosis (LINCL). Predominance of cerebral atrophy in the infratentorial area is typical of LINCL. Periventricular white matter lesions may be evident on MRI scans of patients with classical and LINCL-variant disease. In contrast to neuroradiological findings in patients with LINCL-variant disease, findings in patients with classical LINCL revealed no changes in the basal ganglia.

Atrophy↗
PubMed1996

Pituitary adenylate cyclase-activating polypeptide directly stimulates LH and FSH secretion by human pituitary gonadotrophinomas.

The effect of pituitary adenylate cyclase-activating polypeptide (PACAP) on LH and FSH secretion by human pituitary gonadotrophinomas in cell culture was studied. PACAP (1-38 peptide, 0.2-20 nmol/L) dose-dependently stimulated both LH and FSH secretion after 24 hours incubation. Of 11 tumours studied, PACAP (20 nmol/L) stimulated LH and/or FSH secretion by 1.7-4 fold in 9 cases. Two tumours did not respond to PACAP, although LHRH was stimulatory in these. None of the 11 tumours contained gsp mutations, excluding the possibility that these were the cause of the occassionally observed non-responsiveness to PACAP. A combination of PACAP (20 nmol/L) together with TRH (25 nmol/L) resulted in greater stimulatory effects on LH and FSH secretion than exerted by either peptide alone, but this was not observed with LHRH. In 3 tumours tested, PACAP stimulated cAMP production 2-3 fold by cultured human pituitary gonadotrophinomas but had no effect on rate of phosphatidylinositol (PI) turnover. These results indicate that PACAP can directly stimulate LH and FSH secretion by human pituitary gonadotrophs and that PACAP-receptors in gonadotrophin-secreting tumours are coupled with adenylate cyclase but not the PI second messenger system. We conclude that PACAP may play a role in controlling gonadotroph function in the human pituitary gland.

Adult↗
PubMed1996

Basilar artery blood flow during head rotation in vertebrobasilar ischemia.

PATIENTS AND METHODS: Forty-six patients with vertebrobasilar ischemia and 40 control subjects were examined during head rotation using transcranial Doppler ultrasonography. RESULTS: In the control group, no difference in blood flow velocity through the BA was found between the neutral and rotated positions. Based on these data, a blood flow reduction in the BA of more than 20% was considered to be significantly abnormal (p < 0.01). In three of 46 patients no signal was detectable in the BA using TCD. The reduction in blood flow velocity through the BA during head rotation was strongly dependent on the condition of the VA; none of 23 patients without atherosclerotic lesions or hypoplasia of the VA developed a significant reduction in blood flow through the BA. Two of 11 patients with unilateral VA lesions had significantly reduced blood flow in the BA (27% and 31%), although both were asymptomatic. Five of nine patients with bilateral VA lesions showed a significant reduction in blood flow through the BA (mean = 52%, minimum = 30%), and four of these developed clinical symptoms such as vertigo or diplopia during the rotation maneuver. CONCLUSION: These data suggest that patients with uni- or bilateral lesions of the VA are at risk for developing clinically relevant reductions in blood flow through the BA during head rotation. Because not all patients with VA lesions developed reduced blood flow velocity, we conclude that individual vascular mechanisms must play an important compensatory role.

Adult↗
PubMed1996

The mind-body connection.

Fed up with a system oriented more to illness than to wellness and with quick fixes like popping pills, a growing number of health care consumers are turning to non-invasive complementary therapies to help achieve personal well-being.

Canada↗
PubMed1995

Autologous progenitor cell transplantation: prior exposure to stem cell-toxic drugs determines yield and engraftment of peripheral blood progenitor cell but not of bone marrow grafts.

Agents with stem cell-toxic potential are frequently used for salvage therapy of Hodgkin's disease (HD) and high-grade non-Hodgkin's lymphoma (NHL). Because many patients with relapsed or refractory lymphoma are candidates for autologous progenitor cell transplantation, possible toxic effects of salvage chemotherapy on progenitor cells must be taken into account. In a retrospective study, we have analyzed the influence of a salvage regimen containing the stem cell-toxic drugs BCNU and melphalan (Dexa-BEAM) on subsequently harvested bone marrow (BM)- and peripheral blood-derived progenitor cell grafts (PBPC) and compared it with other factors. Progenitor cells were collected from 96 patients with HD or high-grade NHL. Seventy-nine grafts were reinfused (35 PBPC and 44 BM) after high-dose chemotherapy. Compared with patients autografted with BM, hematopoietic recovery was significantly accelerated in recipients of PBPC. For PBPC, the number of Dexa-BEAM cycles ( > or = v > 1) was the predominate prognostic factor affecting colony-forming unit-granulocyte-macrophage (CFU-GM) yield (66 v 6.8 x 10(4)/kg, P = .0001), CD34+ cell yield (6.6 v 1.6 x 10(6)/kg, P = .0001), neutrophil recovery to > 0.5 x 10(9)/L (9 v. 11 days, P = .0086), platelet recovery to > 20 x 10(9)/L (10 v 15.5 days, P = .0002), and platelet count on day +100 after transplantation (190 v 107 x 10(9)/L, P = .031) using univariate analysis. Previous radiotherapy was associated with significantly lower CFU-GM and CD34+ cell yields but had no influence on engraftment. Patient age, patient sex, disease activity, or chemotherapy other than Dexa-BEAM did not have any prognostic impact. Multivariate analysis confirmed that Dexa-BEAM chemotherapy was the overriding factor adversely influencing CFU-GM yield (P < .0001), CD34+ cell yield (P < .0001), and platelet engraftment (P < .0001). BM grafts were not significantly affected by previous Dexa-BEAM chemotherapy or any other variable tested. However, prognostic factors favoring the use of BM instead of PBPC were not identified using joint regression models involving interaction terms between the graft type (PBPC or BM) and the explanatory variables investigated. We conclude that, in contrast to previous radiotherapy or other chemotherapy, exposure to salvage regimens containing stem cell-toxic drugs, such as BCNU and melphalan, is a critical factor adversely affecting yields and performance of PBPC grafts. Marrow progenitor cells appear to be less sensitive to stem cell-toxic chemotherapy. PBPC should be harvested before repeated courses of salvage chemotherapy involving stem cell-toxic drugs to preserve the favorable repopulation kinetics of PBPC in comparison with BM.

Adolescent↗
PubMed1995

Intramural hemorrhage of the thoracic aorta. Diagnostic and therapeutic implications.

BACKGROUND: Intramural hemorrhage (IMH) was recently identified at necropsy and anecdotally in vivo as a unique aortic syndrome (without entry and with no flap-like intraluminal component, such as overt aortic dissection). However, little is known about diagnosis, prognosis, and outcome of IMH. METHODS AND RESULTS: Between 1983 and 1993, 360 patients from two medical centers with clinical indications of aortic dissection were prospectively evaluated; they presented to the emergency department a median of 3.5 hours after onset of back or chest pain or other suggestive symptoms. Among 195 patients with aortic syndromes, 25 patients (12.8%) were diagnosed to have IMH of the thoracic aorta with no evidence of a primary intimal tear, flap, or overt dissection by multiple noninvasive imaging modalities, including magnetic resonance imaging (n = 12), contrast-enhanced computed tomography (n = 14), and transesophageal echocardiography (n = 3) in random order. There were 16 men and 9 women with a median age of 56 +/- 13 years (range, 15 to 80 years). Arterial hypertension was present in the majority (84%), and Marfan's syndrome was present in 3 patients (12%). IMH was diagnosed within 4 days of hospital admission (median, 2.5 hours). IMH involved the ascending aorta (type A) in 12 cases (48%), the aortic arch in 2 (8%), and the descending aorta (type B) in 11 cases (44%); imaging results were validated by crossmatching with intraoperative, pathomorphological, and/or angiographic findings. IMH was 8.5 +/- 5 cm in length and 2.0 +/- 1.2 cm in aortic wall thickness. Aortic regurgitation and pericardial and mediastinal effusion were present in 5 of 12 patients (42%) with type A IMH and 2 of 11 patients (18%) with type B IMH. IMH progression to overt dissection, rupture, and/or acute tamponade occurred in 8 of 25 patients (32%) within 24 to 72 hours, indicating the need for urgent intervention. The 30-day mortality rate of IMH afflicting the ascending aorta was 80% (4 of 5 cases) with medical treatment (sedation and blood pressure control) versus no mortality in 7 cases with early surgical repair (P < .01); after 1 year, 71.4% of surgically treated patients were alive versus 20% in the medical group (P < .05). IMH of the aortic arch resulted in an early mortality of 50% (1 of 2 patients) with medical treatment. In IMH confined to the descending thoracic aorta, survival with medical treatment was not different from surgical therapy; there was 1 early death among 6 patients with medical therapy and none out of 5 patients with surgery (P = NS). At 1-year follow-up, medical and surgical therapy groups had survival rates of 80% and 83%, respectively (P = NS). CONCLUSIONS: IMH is associated with a clinical profile and prognosis similar to classic dissection and may be considered an ominous precursor of overt aortic dissection. Tomographic noninvasive imaging ensures rapid, nontraumatic diagnosis of IMH. The outcome of IMH of the ascending aorta appears favorable only with immediate surgical repair.

Adolescent↗
PubMed1995

The growth hormone secretagogue, L-692,429, induces phosphatidylinositol hydrolysis and hormone secretion by human pituitary tumors.

L-692,429 is a non-peptidyl GH secretagogue. We examined the effects of L-692,429 on cultured human pituitary tumors removed from patients with acromegaly. Dose-dependent stimulation of GH secretion was observed, with 1 mumol/L leading to 2 or 3-fold increases. Prolactin (PRL) secretion by a mixed somatotrophic-lactotrophic tumor was also stimulated. The effects of L-692,429 were abolished by phloretin and W7 but not Rp-cAMPS. Rate of phosphatidylinositol turnover was markedly increased up to 3-fold by L-692,429. These results show that L-692,429 increases hormone secretion by human pituitary cells via a protein kinase C and Ca2+ dependent mechanism.

Acromegaly↗
PubMed1995

Glycan modification of a thermostable recombinant (1-3, 1-4)-beta-glucanase secreted from Saccharomyces cerevisiae is determined by strain and culture conditions.

High level biosynthesis and secretion of the thermostable hybrid (1-3, 1-4)- beta-glucanase H(A16-M) has been achieved in Saccharomyces cerevisiae by means of the yeast vacuolar endoprotease B promoter (PRB1P) and the Bacillus macerans (1-3, 1-4)-beta-glucanase signal peptide. The N-glycans present on the yeast-secreted H(A16-M), denoted H(A16-M)-Y, were released by endoglycosidase H, and identified by proton NMR spectroscopy to be a homologous series of Man8-13GlcNAc2, although only traces of Man9GlcNAc2 were found. Therefore, processing of N-glycans on H(A16-M)-Y is similar to that on homologous proteins. Most of the N-glycans (88%) were neutral while the remainder were charged due to phosphorylation. Site-directed mutagenesis of Asn to Gln in two of the N-glycosylation sequons, and subsequent analysis of the N-glycans on the yeast-secreted proteins together with analysis of the N-glycans from the individual sites of H(A16-M)-Y suggest the presence of steric hindrance to glycan modification by the glycans themselves. H(A16-M)-Y produced under control of either the yeast protease B or the yeast 3'-phosphoglycerate kinase promoter, each in two different Saccharomyces strains revealed a dependence of N-glycan profile on both strain and culture conditions. The extent of O-glycosylation was found to be nine mannose units per H(A16-M)-Y molecule. An attempt to identify the linkage-sites for the O-glycans by amino acid sequencing failed, suggesting non-stoichiometric or heterogeneous O-glycosylation. The possible modes in which N-glycans might contribute to resistance of H(A16-M)-Y to irreversible thermal denaturation are discussed with respect to structural information available for H(A16-M)-Y.

Bacillus↗
PubMed1995

Determination of lactate dehydrogenase activity and urea content in milk by dry chemistry.

Comparison of the new technique of dry chemistry (EKTACHEM 700-XR, Eastman Kodak Co., USA) with conventional wet chemistry (HITACHI 717, Boehringer Mannheim, Germany) for quantitations of lactate dehydrogenase activity and urea content in bovine milk resulted in correlation coefficients of more than 0.9 even when measuring fresh raw milk by dry chemistry.

Animals↗
PubMed1995

Biochemical characteristics of human pituitary somatotropinomas with and without gsp mutations: in vitro cell culture studies.

Gsp oncogenes are present in about 40% of somatotropinomas. They result in excessive cAMP production and have been proposed to be the cause of increased GH secretion. We have used in vitro cell culture to compare the biochemical characteristics of somatotropinomas with and without gsp oncogenes (gsp-positive and gsp-negative tumors, respectively). Of 30 somatotropinomas examined, 10 proved to be gsp positive, as determined by sequence analysis of DNA generated by the polymerase chain reaction. The somatostatin analog, octreotide, powerfully inhibited GH secretion by gsp-positive somatotropinomas, but had no effect on 8 of 13 gsp-negative tumors. Five of 20 gsp-negative and 4 of 10 gsp-positive tumors failed to respond to GHRH, whereas stimulatory effects ranging from 37-500% increases in GH secretion occurred in the remainder. However, strong stimulation (> 4-fold) occurred only in 5 of the gsp-negative tumors. The basal phosphatidylinositol turnover rate was elevated in about 25% of gsp-negative somatotropinomas. These results demonstrate similar and highly variable effects of GHRH on both types of somatotropinoma, whereas the absence of gsp oncogenes is often associated with resistance to octreotide. The phosphatidylinositol turnover data suggest that defects within this second messenger system may be present in a subset of somatotropinomas without gsp oncogenes.

Base Sequence↗
PubMed1995

[Intramural hemorrhage of the thoracic aorta as a precursor of dissection].

Aortic dissection without entry and blood-flow in a false lumen was recently identified at necropsy and in vivo as intramural hemorrhage in the aortic wall (IMH). It was the purpose of the study to elucidate clinical signs and prognosis in this rare and poorly understood condition. Among 360 prospectively evaluated patients with clinical suspicion of aortic dissection, 195 patients presented with evidence of aortic disease. Of these, 25 patients (13.2%) had IMH of the thoracic aorta with no primary intimal tear, flap or overt dissection as shown by MRI (n = 12), contrast enhanced CT (n = 14) and TEE (n = 3). IMH was confirmed intraoperatively or at necropsy. There were 16 men and 9 women of ages 56 +/- 13 years; arterial hypertension was associated in 84% and Marfan's syndrome in 12%. IMH involved the ascending aorta in 12 (48%), the arch in 2 (8%), and the descending aorta in 11 cases (44%). IMH occupied 8.5 +/- 5 cm in length and 2.0 +/- 1.2 cm in aortic wall thickness. Both aortic regurgitation and pericardial/mediastinal effusion was present in 42% of type A and in 18% of type B IMH. IMH progression to overt dissection, rupture and/or acute tamponade occurred in 8/25 cases (32%) within 24 to 72 h, indicating the need for urgent surgical repair. The 30-day mortality of IMH inflicting the ascending aorta was 80% (4 of 5) with medical treatment in contrast to none (of 7) with early surgical treatment (p < 0.01). One-year survival was 71% in surgically treated patients and 20% with medical treatment (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

[A comparison of 2 new rapid methods for determination of HbA1C concentration in patients with diabetes mellitus].

We have evaluated a new immunoturbidimetric assay (DCA 2000 HbA1c system, Bayer, Denmark) for determination of HbA1c. The aim of the study was to evaluate accuracy, precision and feasibility for the DCA 2000 method when employed in a diabetes centre by a technical assistant and at a general practitioner's by non lab staff. The results were compared with a high performance liquid chromatographic method (HPLC, AUTO A1C, Kyoto Daiichi Kagaku Co., Kyoto, Japan) which is the current laboratory method, and therefore used as reference. Assay time for the DCA 2000 method was nine minutes, while the HbA1c result was displayed within four minutes by HPLC. Blood samples were drawn after informed consent from 118 patients during a period of two months at the out-patient clinic of the Dept. of Paediatrics, Glostrup Hospital (n = 67) and at a general practitioner's (n = 51). Each sample was analyzed twice by each method on two consecutive days. In the HbA1c range from four to 14% (n = 67) the average within-assay precision (SD) for the HPLC method was 0.13%, whilst it was 0.23% for the DCA 2000 method (p < 0.001). The within-assay precision was low and acceptable, and for both methods it was independent of the current HbA1c concentration. For the DCA method precision was almost similar (p > 0.07) when carried out by a technical assistant (SD: 0.20%) and by non lab staff (SD: 0.25%). Interbatch variations for HbA1c results investigated with two different batches of reagents within a month were SD 0.30% (HbA1c range: 4.9-5.9%, n = 30) and SD 0.44% (HbA1c range: 10.5-12.1%, n = 30) for these two preparations.(ABSTRACT TRUNCATED AT 250 WORDS)

Chromatography, High Pressure Liquid↗
PubMed1994

Variable regulation by insulin of insulin gene expression in HIT-T15 cells.

Glucose and insulin are generally considered to express opposite effects on insulin synthesis and secretion from pancreatic islets. For the most part this generalization has arisen from short-term experiments. Our studies focused on the chronic, long-term effects of variable insulin concentrations on insulin gene expression and secretion in cultures of HIT-T15 cells. From passage 70, HIT cells were split and passed weekly for 25 weeks in media containing either (A) 11.1 mmol/l glucose with no insulin added; (B) 11.1 mmol/l glucose with insulin added to maintain a level of approximately 4,000 microU/ml; (C) 0.8 mmol/l glucose with no insulin added; (D) 0.8 mmol/l glucose with insulin added to maintain a level of approximately 4,000 microU/ml; and (E) 0.8 mmol/l glucose with progressively less insulin added over time to mimic the gradual decrease in media insulin levels found in condition A. Our data indicate that during chronic passing of HIT cells, addition of exogenous insulin led to preserved levels of insulin mRNA, insulin content and insulin secretion in cells cultured in media containing 11.1 mmol/l glucose concentration. However, in media containing 0.8 mmol/l glucose concentration, addition of insulin diminished the levels of insulin mRNA, insulin content and insulin secretion. Nonetheless, in all cases exogenously added insulin sustained greater levels of insulin mRNA, insulin content and insulin secretion than the instance wherein media containing a high concentration of glucose only was used.(ABSTRACT TRUNCATED AT 250 WORDS)

Actins↗
PubMed1994

Distinct morphological and mito-inhibitory effects induced by TGF-beta 1, HGF and EGF on mouse, rat and human hepatocytes.

TGF-beta 1 is known as a potent inhibitor of proliferation of rat and human hepatocytes. In this study we show that the effects of TGF-beta 1 are quite different on mouse hepatocytes. In rat and human hepatocytes, TGF-beta 1 inhibited DNA synthesis and also inhibited the morphological changes induced by growth factors in rat and human hepatocytes. In contrast, addition of TGF-beta 1 to mouse hepatocytes resulted in pronounced alterations in morphology of these cells. These changes were similar to those induced by HGF and EGF. The induction of structural changes by TGF-beta 1 was noted only in mouse hepatocytes. Mouse hepatocytes were also much more resistant to the mito-inhibitory effect of TGF-beta 1. These findings suggest profound differences in hepatocyte growth regulation between these species and may relate to observed differences in susceptibility to carcinogenesis.

Alkaloids↗
PubMed1994

Rapid determination of antifungal activity by flow cytometry.

We have developed a rapid assay of antifungal activity which utilizes flow cytometry to detect accumulation of a vital dye in drug-damaged fungal cells. Results of these studies suggest that flow cytometry may provide an improved, rapid method for determining and comparing the antifungal activities of compounds with differing modes of action.

Antifungal Agents↗
PubMed1994

Human acoustic neuromas secrete interleukin-6 in cell culture: possible autocrine regulation of cell proliferation.

Interleukin-6 (IL-6) secretion by cell cultures of human acoustic neuromas was examined. Secretory rates varied from 0.02 to 5.4 ng/10(5) cells per 4 days, depending on the tumor. The IL-6 immunoreactivity eluted from a Sephadex G-100 column in a major peak corresponding to an M(r) of 30,000 and a lesser peak corresponding to an M(r) of 50,000. Western blot analysis revealed three IL-6 immunoreactive bands with M(r)s corresponding to 53,000, 29,000, and 24,000. Tumor necrosis factor-alpha, interleukin-1-beta, and cholera toxin all stimulated IL-6 secretion. An antisense phosphorothioate oligonucleotide against IL-6 messenger RNA inhibited both [3H]thymidine uptake and IL-6 secretion by acoustic neuroma cells in culture. In addition, [3H]thymidine uptake was inhibited by a specific polyclonal antibody against IL-6. We conclude that human acoustic neuroma cells produce and secrete IL-6, which may act in an autocrine manner to stimulate cellular proliferation.

Adult↗