Search PubMed⌕ Search

Biomedical subjects

A Barth

Publications and source records attributed to A Barth.

At least 73 records · Page 4Linked to original sources
PubMed1997

Predictors of axillary lymph node metastases in patients with T1 breast carcinoma.

BACKGROUND: Axillary lymph node metastases (ALNM) are the most important predictor of survival in patients with T1 breast carcinoma. Due to a relatively low incidence of axillary metastasis in tumors < or = 2 cm, the role of axillary lymph node dissection for these patients has been questioned. The purpose of this study was to determine the association between the incidence of ALNM and 11 clinical/pathologic factors by univariate and multivariate analysis. METHODS: The authors reviewed data from 918 patients with T1 breast carcinoma who underwent level I/II axillary dissection between 1979 and July 1995. The association between the incidence of ALNM and 11 clinical/pathologic factors (size, lymph/vascular invasion, nuclear grade, S-phase, ploidy, palpability, age, estrogen receptor status, progesterone receptor status, HER-2/neu, and histology) was analyzed by univariate and, when significant, by multivariate analysis. RESULTS: Approximately 23% of the 918 patients with T1 breast carcinoma had ALNM. Multivariate analysis identified four factors as independent predictors of ALNM: lymph/vascular invasion (P < 0.0001), tumor palpability (P < 0.0001), nuclear grade (P = 0.0004), and tumor size (P = 0.01). Among the 117 patients with nonpalpable, nonhigh grade tumors < or = 1 cm without lymph/vascular invasion, the incidence of ALNM was only 3%. However, the 43 patients with T1c tumors with all 3 additional risk factors had a 49% incidence of ALNM. CONCLUSIONS: Clinical and pathologic features of the primary tumor can be used to estimate the risk of ALNM in patients with T1 breast carcinoma. Such a risk assessment might facilitate appropriate management. Routine axillary dissection can be omitted in patients at minimal risk of ALNM, if the treatment decision is not influenced by lymph node status. Axillary lymph node dissection should be performed routinely for all patients with lesions > 1 cm. [See editorial counterpoint on pages 1856-61 and reply to counterpoint on pages 1862-4, this issue.]

Age Factors↗
PubMed1997

Glycine causes increased excitability and neurotoxicity by activation of NMDA receptors in the hippocampus.

Glycine is an inhibitory neurotransmitter in the spinal cord and also acts as a permissive cofactor required for activation of the N-methyl-D-aspartate (NMDA) receptor. We have found that high concentrations of glycine (10 mM) cause marked hyperexcitability and neurotoxicity in organotypic hippocampal slice cultures. The hyperexcitability, measured using intracellular recording in CA1 pyramidal neurons was completely blocked by the NMDA receptor antagonist MK-801 (10 microM), but not by the AMPA receptor antagonist DNQX (100 microM). The neurotoxicity caused by glycine occurred in all regions of hippocampal cultures but was most marked in area CA1. There was significant CA1 neuronal damage in cultures exposed to 10 mM glycine for 30 min or longer (P < 0.01) or those exposed to 4 mM glycine for 24 h compared to control cultures (P < 0.01). The NMDA antagonists MK-801 (10 microM) and APV (100 microM) significantly reduced glycine-induced neuronal damage in all hippocampal subfields (P < 0.01). The AMPA antagonists CNQX, DNQX, and NBQX (100 microM) had no effect on glycine-induced neuronal damage. High concentrations of glycine therefore appear to enhance the excitability of hippocampal slices in an NMDA receptor-dependent manner. The neurotoxic actions of glycine are also blocked by NMDA receptor antagonists.

2-Amino-5-phosphonovalerate↗
PubMed1997

Influence of subchronic administration of oestradiol, ethinyloestradiol and oestradiol sulphamate on bile flow, bile acid excretion, and liver and biliary glutathione status in rats.

The cholestatic effect of the newly developed oestradiol sulphamate (J995) was compared with that of the natural oestrogen oestradiol (E) and of the cholestatic standard oestrogen ethinyloestradiol (EE). Female ovariectomized rats were orally treated for 7 days with oestrogen doses molar equivalent to 0.01, 0.1, 1, and 10 mg E/kg body wt. Bile flow, biliary bile acid and glutathione excretion as well as liver glutathione status were determined after bile duct cannulation under the influence of ketamine anaesthesia. For systemic oestrogen activity, the increase of uterine weight was measured. J995 showed the highest oestrogenic activity followed by EE and E. Impairment of bile flow and biliary glutathione excretion (GSH, GSSG) were found to be in the order E < J995 < EE. As all three oestrogens did not influence bile acid excretion, we postulate that mainly the bile acid-independent fraction of bile flow was inhibited, caused at least partly by impairment of canalicular glutathione transport. Based on the results of these studies, we conclude that a tenfold higher dose of J995 exhibited the same cholestatic effect as EE. Together with higher systemic oestrogenic activity, J995 may be used as a prodrug with reduced hepatic side-effects to replace EE in contraception strategies.

Animals↗
PubMed1997

Peroxidative and glutathione status in uterus and placenta after normal and pathological pregnancy.

In 10 women with disturbed pregnancies without hypertension, reduced (GSH) and oxidized glutathione (GSSG) as well as lipid peroxides as thiobarbituric acid reactive substances (TBARS) were determined in the placenta and in the uterine tissue after unexpected stress-induced Caesarian section (group II). Production of TBARS was also measured in vitro in the 9000 x g supernatant of both tissues. The results were compared with those from women after normal pregnancy and expected Caesarian section (group I). After normal pregnancy higher TBARS and lower GSH with higher GSSG/GSH ratio were found in the placenta in comparison to the uterine tissue, indicating an oxidant/antioxidant imbalance in the placenta. No statistically significant differences were shown between the parameters of groups I and II. The possible oxidant stress associated with disturbed pregnancy and subsequent unexpected Caesarian section in this study was insufficient to alter tissue levels of glutathione nor the peroxidative status of placenta and uterus.

Adult↗
PubMed1996

Time-resolved infrared spectroscopy of the Ca2+-ATPase. The enzyme at work.

Changes in the vibrational spectrum of the sarcoplasmic reticulum Ca2+-ATPase in the course of its catalytic cycle were followed in real time using rapid scan Fourier transform infrared spectroscopy. In the presence of Ca2+, the cycle was induced by the photochemical release of ATP from a biologically inactive precursor (caged ATP, P3-1-(2-nitro)phenylethyladenosine 5'-triphosphate). Absorbance changes arising from ATP binding to the ATPase were observed within the first 65 ms after initiation of ATP release. After ATP binding, up to two subsequent partial reactions of the ATPase reaction cycle were observed depending on the buffer composition (10 mM CaCl2 + 330 mM KCl or 1 mM CaCl2 + 20% Me2SO): (i) formation of the ADP-sensitive phosphoenzyme (kapp = 0.79 s-1 +/- 15% at 1 degrees C, pH 7.0, 10 mM CaCl2, 330 mM KCl) and (ii) phosphoenzyme conversion to the ADP-insensitive phosphoenzyme concomitant with Ca2+ release (kapp = 0.092 s-1 +/- 7% at 1 degrees C, pH 7.0, 1 mM CaCl2, 20% Me2SO). Each reaction step could well be described by a single time constant for all associated changes in the vibrational spectrum, and no intermediates other than those mentioned above were found. In particular, there is no evidence for a delay between the transition from ADP-sensitive to ADP-insensitive phosphoenzyme and Ca2+ release. In 2H2O a kinetic isotope effect was observed: both the phosphorylation reaction and phosphoenzyme conversion were slowed down by factors of 1.5 and 3.0, respectively. The small amplitudes of the observed changes in the infrared spectrum indicate that the net change of secondary structure is very small and of the same order of magnitude for ATP binding, phosphorylation, and phosphoenzyme conversion. Therefore, our results do not support a distinction between minor and major secondary structure changes in the catalytic cycle of the ATPase, which might be expected according to the classical E1-E2 model.

Adenosine Triphosphate↗
PubMed1996

Dipeptidyl-peptidase IV-beta, a novel form of cell-surface-expressed protein with dipeptidyl-peptidase IV activity.

The T-cell activation antigen CD26, is a type II membrane glycoprotein with intrinsic dipeptidyl-peptidase IV (DPP IV) activity, characterized by its capacity to cleave off N-terminal dipeptides containing proline as the penultimate residue. Independent of its catalytic activity, CD26 has also been characterized as adenosine deaminase binding protein. By using CD26 negative human C8166 cells, here we describe the existence of another cell-surface protein which manifests CD26-like DPP IV activity. For convenience, this protein will be referred to as DPP IV-beta. Consistent with the cell-surface expression of DPP IV-beta, intact C8166 cells manifested a high level of DPP IV, whereas, they manifested poor activity against substrates of DPP II known to have an intracellular localization. A partially purified preparation of CD26 from human MOLT4 cells, and the DPP IV-beta expressed on intact cells were found to possess similar catalytic activity and pH optimum. In addition, cell-surface CD26 and DPP IV-beta on intact MOLT4 and C8166 cells, respectively, resisted digestion by proteolytic enzymes such as trypsin and proteinase K. However, adenosine deaminase activity was not detectable on the surface of C8166 cells in contrast to CD26 positive MOLT4 cells. In accord with this, 125I-labeled adenosine deaminase which binds CD26 was found not to bind DPP IV-beta. Gel-filtration experiments using 0.5% Triton X-100 extracts from C8166 and MOLT4 cells, revealed that the apparent molecular mass of DPP IV-beta is 82 kDa, whereas that of CD26 is 110 kDa as expected. Taken together, our results suggest that DPP IV-beta is a CD26-like protein which could be characterized by distinct properties.

Adenosine Deaminase↗
PubMed1996

bFGF enhances the protective effects of MK-801 against ischemic neuronal injury in vitro.

The neuroprotective activity of basic fibroblast growth factor (bFGF) in combination with the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 was evaluated in organotypic hippocampal slice cultures. Oxygen/glucose deprivation produced neuronal damage which was assessed using propidium iodide fluorescence. Treatment with increasing doses of bFGF demonstrated significant neuroprotection that was optimal at 10 ng ml-t. This effect was diminished at higher concentrations. MK-801, at the optimal concentration of 30 microM, demonstrated greater neuroprotective efficacy than bFGF. However, bFGF significantly enhanced the protection conferred by MK-801 alone. These results suggest that neurotrophic factors such as bFGF may augment the neuroprotective effects of NMDA antagonists against ischemic neuronal injury.

Animals↗
PubMed1996

A new mechanism in serine proteases catalysis exhibited by dipeptidyl peptidase IV (DP IV)--Results of PM3 semiempirical thermodynamic studies supported by experimental results.

Herein we present results of semiempirical molecular orbital calculations employing the PM3 molecular model. The compounds studied are related to substrates of the serine protease dipeptidyl peptidase IV (DP IV). Our goal was the thermodynamic characterization of the DP IV-enzyme-catalyzed reaction pathway. A new mechanism of serine proteases catalysis is presented. We found that a tetrahedral intermediate can be stabilized by the formation of an oxazolidine ring with the nonscissile P2-P1 peptide bond. In this way, the negative charge of the tetrahedral intermediate around the scissile bond is transferred to the carbonyl oxygen atom of the preceding peptide bond. This negative charge can be compensated by a proton transfer from the positively charged N-terminus to this oxygen atom. It is shown that the positively charged N-terminus is the driving force in this particular serine protease mechanism of catalysis. The mechanism is supported by observed secondary hydrogen isotope effects on the C alpha proton for an alanine residue in the P2 position. We suggest a trans-cis isomerisation around the P2-P1 peptide bond in the final step of the acylation and cleavage of the substrates. The results obtained by our theoretical calculations are compared with several experimental findings supporting the suggested mechanism.

Binding Sites↗
PubMed1996

Combination therapy with MK-801 and alpha-phenyl-tert-butyl-nitrone enhances protection against ischemic neuronal damage in organotypic hippocampal slice cultures.

In vitro combinations of MK-801, an NMDA receptor antagonist, and alpha-phenyl-tert-butyl-nitrone (PBN), a free radical scavenger, have been tested for possible additive neuroprotective effects against anoxia/hypoglycemia (Ax/Hg)-induced neuronal damage. Rat organotypic hippocampal slice cultures were exposed to Ax/Hg for different lengths of time to vary the severity of the insult. Cell death (CD) was assessed using propidium iodide fluorescence and expressed as a percentage of the total neuronal cells present. Pretreatment with PBN alone (500 microM) provided significant protection against moderate ischemic injury and reduced CD from 65% in controls to 2% in the treated group (P < 0.003). A longer ischemic exposure time caused more neuronal damage, which was only slightly reduced by PBN, but significantly reduced by MK-801 (30 microM) (4% CD with MK-801 vs 75% CD in controls; P < 0.0003). With a further increase in the time of ischemic exposure, MK-801 was still protective (33% CD with MK-801 vs 90% CD in controls; P < 0.002), although the combination MK-801 + PBN was more efficient (7% CD with combination, P < 0.01 compared to MK-801 alone). With yet a further increase in the ischemic exposure, PBN or MK-801 alone was not protective; however, a combination of the two still provided significant protection (64% CD with combination vs 100% CD with MK-801 alone; P < 0.01). PBN was protective when administered up to 2 h after Ax/Hg (66% CD in controls vs 36% CD with PBN 500 microM; P < 0.007). The combination MK-801 + PBN was able to increase the therapeutic window up to 3 h (61% CD in controls vs 41% with PBN alone vs 7% with MK-801 + PBN; P < 0.002 compared to PBN alone). In conclusion, the combination of MK-801 and PBN increases both the efficacy and the time window of protection against ischemia.

Animals↗
PubMed1996

Noninvasive differentiation of meningiomas from other brain tumours using combined 111Indium-octreotide/99mtechnetium-DTPA brain scintigraphy.

We have studied prospectively 47 patients with CNS tumours including 16 meningiomas and 33 other tumours using combined 111In-octreotide and 99mTc-DTPA brain scintigraphy. 111In-octreotide scintigraphy was used to image somatostatin receptors (SSR) and 99mTc-DTPA scintigraphy was used to assess the integrity of the blood-brain barrier (BBB). A total of 32 tumours (65%) were detected. All SSR positive tumours also had positive 99mTc-DTPA scans and all SSR negative tumours were negative on 99mTc-DTPA scans. Among the tumours located outside the BBB, all meningiomas and two out of six schwannomas were positive on combined SSR/99mTc-DTPA scintigraphy. Among the tumours located inside the BBB, seven out of nine gliomas grade I-III were negative, whereas all glioblastomas were positive. Other positive tumours included one malignant non-Hodgkin lymphoma and two cerebral metastases. SSR scintigraphy alone was non-specific in the diagnosis of meningiomas, as 16 non-meningiomatous tumours also had positive SSR scans probably due to a breakdown of the BBB (excluding the malignant lymphoma). Measuring the tumour-to-background ratio on SSR scans improved specificity, but sensitivity was decreased below 70% because some meningiomas were only slightly positive. Only the ratio of SSR scintigraphy to conventional 99mTc-DTPA brain scintigraphy (SSR-to-BS index) allowed a reliable differentiation of meningiomas from other CNS tumours, most notable from schwannomas (sensitivity: 94%; specificity: 100%). Our results support the usefulness of combined SSR and conventional brain scintigraphy in the noninvasive pre-operative diagnosis of meningiomas.

Adolescent↗
PubMed1996

Mechanism for transition from initial to stable cell-cell adhesion: kinetic analysis of E-cadherin-mediated adhesion using a quantitative adhesion assay.

A centrifugal force-based adhesion assay has been used to quantitatively examine the kinetics of formation of cell-cell contacts mediated specifically by expression of E-cadherin under the control of a glucocorticoid-inducible promoter in mouse fibroblasts. Analysis of cells expressing maximal or minimal levels of E-cadherin showed that the strength of E-cadherin-mediated adhesion developed in a single exponential step over a short time (half-maximal adhesion, 13-17 min). At 37 degrees C, adhesion strength increased rapidly in the first 20 min without an apparent lag phase. After 90 min, adhesion strength reached a plateau. Differences in final strengths of adhesion were commensurate with the level of E-cadherin expression. Strengthening of adhesion was temperature dependent. At 19 degrees C, strengthening of adhesion was delayed and subsequently developed with a slower rate compared to adhesion at 37 degrees C. At 4 degrees C, adhesion was completely inhibited. Strengthening of adhesion was absolutely dependent on a functional actin cytoskeleton since adhesion did not develop when cells were treated with cytochalasin D. Together, our current and previous (McNeill et al., 1993.J. Cell Biol. 120:1217-1226) studies indicate that the rate of initial strengthening of E-cadherin-mediated adhesion is neither dependent on the amount of E-cadherin expressed nor on long-range protein diffusion in the membrane to the adhesion site. However, initial strengthening of adhesion is dependent on temperature-sensitive cellular activities that may locally couple clusters of E-cadherin to the actin cytoskeleton.

Actins↗
PubMed1996

Synthetic wound dressings--evaluation of interactions with epithelial and dermal cells in vitro.

Comparative testing of seven wound dressings (WD) has been performed with human HaCaT keratinocyte and mouse 3T3 fibroblast cultures. To assess biocompatibility, morphologic examinations were combined with cell counting. Supernatants were subjected to measurements of tissue peptide antigen (TPS), soluble intercellular adhesion molecule 1 (ICAM-1), and interleukins (IL-1 alpha, -1 beta, -6). Furthermore, monoxygenation, the reduced glutathione/oxidized gluthathione (GSH/GSSG) ratio and lipid peroxides were determined. Initial morphologic events were noted within the first day of exposure to WD. After 72 h, inhibition of cell growth was observed in the presence of hydrocolloids and hydrogels. The cytochrome-P-450-dependent ethoxyresorufin 0-deethylation rate and the GSH/GSSG ratio were not altered by WD in HaCaT cells. Lipid peroxide generation, IL-1 and ICAM-1 were scarcely detectable. TPS and IL-6 release indicate the presence of an 'activated stage' of keratinocytes and fibroblasts exposed to WD. Peptide release in vivo may contribute to the beneficial effects of modern dressings in the treatment of superficial cutaneous wounds.

3T3 Cells↗
PubMed1996

[Primary therapy of advanced ovarian carcinoma: current status and perspectives].

Standard therapy of advanced ovarian cancer includes staging laparotomy with aggressive debulking, possibly pelvic and para-aortic lymphadenectomy, and postoperative chemotherapy. Until present, combination chemotherapy with cis-/carboplatin and cyclophosphamide has been standard. Due to the positive results emerging from recent clinical trials, paclitaxel in combination with platinum might soon emerge as a new standard for patients with advanced ovarian cancer. The role of high-dose chemotherapy is currently under investigation. Pretherapeutic chemosensitivity testing, using a third-generation assay, is studied in randomized trials. Since the cost/benefit ratio is increasingly playing an important role, a cost comparison of the six most commonly used chemotherapy protocols is presented.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

Isolated infarcts of the pons.

We studied 36 patients with MRI-proven isolated acute pontine infarct. Corresponding to the constant territories of intrinsic pontine vessels, infarcts followed a predictable distribution, enabling us to delineate three main syndromes. Twenty-one patients had a ventral pontine infarct. Motor involvement varied from mild hemiparesis (ventrolateral pontine syndrome) to severe hemiparesis with bilateral ataxia and dysarthria (ventromedial pontine syndrome). In addition, three-fourths of the patients had clinical evidence for usually mild tegmental dysfunction. Eleven patients had a tegmental pontine infarct, presenting tegmental signs (eye movement disorders, cranial nerve palsies, sensory disturbances), and mostly mild motor deficits (tegmental pontine syndrome). Only four patients had alternating deficits, and these never corresponded to any of the so-called classic pontine syndromes. Infarcts in the medial and the extreme lateral tegmental territory were never observed in isolation, being always associated with cerebellar or larger (and multiple) infarctions in the posterior circulation. Four patients with a bilateral ventrotegmental pontine infarct presented with acute pseudobulbar palsy, bilateral motor deficits, and tegmental signs. The results of etiologic work-up emphasize the concept of basilar artery branch disease, which was the most common presumed cause of stroke (16/36, 44%). Basilar artery branch disease was particularly associated with large ventral infarcts, severe clinical symptomatology, progressive or fluctuating course, and local recurrence. Presumed small-artery disease (9/36, 25%) was usually associated with small ventral or tegmental infarcts and rapidly improving lacunar syndromes. Large-artery stenosis (8/36, 22%) and cardioembolism (1/36, 3%) were less common than in series of posterior circulation infarcts that include simultaneous pontine and extrapontine lesions. Recovery was good in two-thirds of the patients, the worse outcome being associated with large ventral infarcts.

Adult↗