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Biomedical subjects

A Werner

Publications and source records attributed to A Werner.

At least 73 records · Page 4Linked to original sources
PubMed2000

Chemospecific monofunctionalization of alpha-cyclodextrin in the solid state

[reaction: see text] The properties of the self-assembling aziadamantane inclusion complex with two alpha-cyclodextrin molecules have been exploited to perform a chemospecific monofunctionalization of alpha-cyclodextrin. The insertion of the photochemically generated carbenes takes place chemospecifically into the cyclodextrin's C-3-OH and C-2-OH bonds in 39 and 18% yield, respectively. This model reaction surpasses conventional methods in terms of yield as well as selectivity.

Journal Article↗
PubMed2000

Visualization of pressure distribution within loaded joint cartilage by application of angle-sensitive NMR microscopy.

High-resolution MRI measurements on knee joints show a multilaminar appearance of the cartilage. This intracartilaginar structure, visualized as hypointense zones in T(2)-weighted MR images is based on the dipolar interaction of water molecules within regions of anisotropic arrangement of collagen network. Using the different angle dependence of the MR signal, zones of radially and tangentially oriented network structures can be distinguished. Information equivalent to that from polarization light microscopy can be derived noninvasively. This is demonstrated by polarization light microscopic reference investigations. It is shown that this multilaminar MRI appearance is sensitively influenced by mechanical stress. A model explaining the contrary behavior of loaded tangential and radial network structures is given. Based on this pressure dependence, a noninvasive determination of mechanical properties is possible. Using the variation of size and intensity of the hypointense zones under pressure, dynamic high resolution MRI yields noninvasive information about the intracartilaginar pressure distribution similar to photoelastic measurements. Magn Reson Med 43:884-891, 2000.

Animals↗
PubMed2000

Asymmetries in the time-course of chromatic adaptation and the significance of contrast.

The time-course of chromatic adaptation was determined as a function of the spectral content of the adaptation-light and of image-contrast. The adaptation-lights varied along the chromatic cardinal axes or one of their intermediate axes in an equiluminant plane in colour-space. We found an asymmetry in the initial time-course of adaptation (0.2-10 s) in that adaptation to middle-wavelength light was significantly faster than adaptation to short- and long-wavelength light. The asymmetry was only observed in the presence of a spatially complex pattern. It was fully supported by luminance and chromatic contrast and present under haploscopic stimulus conditions.

Adaptation, Physiological↗
PubMed2000

Pin1-dependent prolyl isomerization regulates dephosphorylation of Cdc25C and tau proteins.

The reversible protein phosphorylation on serine or threonine residues that precede proline (pSer/Thr-Pro) is a key signaling mechanism for the control of various cellular processes, including cell division. The pSer/Thr-Pro moiety in peptides exists in the two completely distinct cis and trans conformations whose conversion is catalyzed specifically by the essential prolyl isomerase Pin1. Previous results suggest that Pin1 might regulate the conformation and dephosphorylation of its substrates. However, it is not known whether phosphorylation-dependent prolyl isomerization occurs in a native protein and/or affects dephosphorylation of pSer/Thr-Pro motifs. Here we show that the major Pro-directed phosphatase PP2A is conformation-specific and effectively dephosphorylates only the trans pSer/Thr-Pro isomer. Furthermore, Pin1 catalyzes prolyl isomerization of specific pSer/Thr-Pro motifs both in Cdc25C and tau to facilitate their dephosphorylation by PP2A. Moreover, Pin1 and PP2A show reciprocal genetic interactions, and prolyl isomerase activity of Pin1 is essential for cell division in vivo. Thus, phosphorylation-specific prolyl isomerization catalyzed by Pin1 is a novel mechanism essential for regulating dephosphorylation of certain pSer/Thr-Pro motifs.

Animals↗
PubMed2000

Unexpected coreceptor usage of primary human immunodeficiency virus type 1 isolates from viremic patients under highly active antiretroviral therapy.

Recently, combinations of antiretroviral drugs (highly active antiretroviral therapy [HAART]) have led to a dramatic reduction of human immunodeficiency virus type 1 (HIV-1)-related clinical symptoms. Success of treatment is defined as almost complete suppression of plasma viremia, although in a sizable fraction of patients this goal is not achieved. We characterized primary HIV-1 isolates from 2 cohorts of patients in which HAART failed in terms of viral suppression. One cohort showed clinical benefit and stable or increasing CD4+ T cell numbers despite high viral load. The second viremic cohort had no CD4+ T cell recovery and exhibited typical AIDS-related symptoms. Primary isolates from HAART patients with minor clinical symptoms used CXCR4 as the most relevant receptor on primary cells. Thus, for the first time, it is shown that patients improving clinically under HAART harbor relatively high viral loads with viruses preferring CXCR4 as coreceptor.

Amino Acid Sequence↗
PubMed2000

Aging and baroreflex control of RSNA and heart rate in rats.

Aging is associated with altered autonomic control of cardiovascular function, but baroreflex function in animal models of aging remains controversial. In this study, pressor and depressor agent-induced reflex bradycardia and tachycardia were attenuated in conscious old (24 mo) rats [57 and 59% of responses in young (10 wk) Wistar rats, respectively]. The intrinsic heart rate (HR, 339 +/- 5 vs. 410 +/- 10 beats/min) was reduced in aged animals, but no intergroup differences in resting mean arterial blood pressure (MAP, 112 +/- 3 vs. 113 +/- 5 mmHg) or HR (344 +/- 9 vs. 347 +/- 9 beats/min) existed between old and young rats, respectively. The aged group also exhibited a depressed (49%) parasympathetic contribution to the resting HR value (vagal effect) but preserved sympathetic function after intravenous methylatropine and propranolol. An implantable electrode revealed tonic renal sympathetic nerve activity (RSNA) was similar between groups. However, old rats showed impaired baroreflex control of HR and RSNA after intravenous nitroprusside (-0.63 +/- 0. 18 vs. -1.84 +/- 0.4 bars x cycle(-1) x mmHg(-1) x s(-1)). Therefore, aging in rats is associated with 1) preserved baseline MAP, HR, and RSNA, 2) impaired baroreflex control of HR and RSNA, and 3) altered autonomic control of resting HR.

Aging↗
PubMed2000

The shrinkage-activated Na(+) conductance of rat hepatocytes and its possible correlation to rENaC.

At moderate cell shrinkage, activation of Na(+) channels is the most prominent mechanism of regulatory cell volume increase in rat hepatocytes. The amiloride sensitivity of these channels suggests a relation to the family of epithelial Na(+) channels (ENaCs). The present study was performed to determine the pharmacological profile of shrinkage-activated Na(+) channels and to test for ENaC expression in primary cultures of rat hepatocytes; in addition, the influence of the cell volume regulated serine/threonine kinase hSGK on activity and pharmacological profile of rENaC was examined in Xenopus oocytes. Conventional electrophysiology in hepatocytes reveals that the shrinkage-activated Na(+) channel is inhibited by amiloride and EIPA with IC(50) values of 6.0 and 0.12 micromol/l, respectively. Western blots and RT-PCR demonstrate that rat hepatocytes do express all three subunits (alpha, beta, gamma) of ENaC. Coexpression of hSGK with rENaC in Xenopus oocytes reveals that the kinase stimulates ENaC by a factor of 4. Moreover, hSGK decreases the affinity to amiloride (increase of IC(50) from 0.12 to 0.26 micromol/l) and increases the affinity to EIPA (decrease of IC(50) from 250 to 50 micromol/l). In conclusion, rat hepatocytes express ENaC, which is activated by the cell volume-sensitive kinase hSGK. ENaC may contribute to the Na(+) channels activated by osmotic cell shrinkage in hepatocytes, whereby the relatively low amiloride and high EIPA sensitivity of the channel could at least be partially due to modification by SGK, which decreases the amiloride and increases the EIPA sensitivity of ENaC.

Amiloride↗
PubMed2000

Pancreas picture of the month. Pancreatic manifestation of cystic fibrosis.

The Magnetic Resonance Cholangio Pancreatography (MRCP) provides within a few seconds complete information on cystic degeneration of the pancreas in patients with cystic fibrosis. The authors present a case report of cystic fibrosis with a pathognomonic magnetic resonance cholangio pancreaticography image of the pancreas.

Adolescent↗
PubMed1999

Functional characterization of a Na+-phosphate cotransporter (NaPi-II) from zebrafish and identification of related transcripts.

1. We report the molecular identification of a Na+-Pi (inorganic phosphate) cotransport system of the NaPi-II protein family from zebrafish intestine. Following a PCR-related strategy, a DNA fragment from intestine-derived RNA was isolated. Rapid amplification of cDNA ends (3'- and 5'-RACE) resulted in the complete sequence (2607 bp) containing an open reading frame of 1893 bp. 2. The NaPi-II-related protein was expressed in Xenopus laevis oocytes and the resulting transport activity was analysed by electrophysiological means. The apparent Km for Pi was 250 microM (96 mM Na+, -60 mV), and voltage-dependent binding of Na+ exhibited a Km of 67.1 mM (1 mM Pi, -60 mV). 3. Interestingly, the overall transport activity was almost insensitive to changes in the holding potential. The apparent affinity for Na+ decreased under hyperpolarizing conditions, whereas Pi binding showed no voltage dependence. Transport activity was inhibited at low pH, which is characteristic for renal NaPi-II isoforms. 4. The expression of the NaPi-II-related isoform was addressed by reverse-transcription PCR. The mRNA could be detected in intestine, liver, eye and kidney. Unexpectedly, a second NaPi-II-related isoform was identified and found to be expressed in kidney, intestine, liver, brain, eye and prominently in testis. In addition, a shorter amplicon was demonstrated to be an antisense transcript related to the NaPi-II intestinal isoform.

Amino Acid Sequence↗
PubMed1999

Cancer risk following radiotherapy for infertility or menstrual disorders.

A cohort of 968 Israeli women treated with radiotherapy for infertility was followed up for cancer incidence. The majority of the subjects were irradiated to both the ovaries and the pituitary gland. Mean doses to the brain, colon, ovary and bone marrow were 0. 8, 0.6, 1.0 and 0.4 Gy, respectively. More than 10 years after radiation treatment, 60 cancers were observed compared with 74.5 expected based on national cancer incidence rates (standardized incidence ratio 0.81, 95% confidence interval 0.61-1.04). No statistically significant excess or deficit was seen for any individual type of cancer; however, a non-significant 60% increased risk of colon cancer was observed. Risk of colon cancer was higher among women with 2 or more treatments and increased with length of follow-up. A decreased risk of breast cancer was suggested. Neither age at exposure nor attained age modified subsequent cancer risk. No clear excess of any cancer site was observed among women at organ doses above the median compared with subjects at doses below the median, except a slight increase in colon cancer. No significant excess incidence of cancer was demonstrated in this small cohort of patients treated with radiotherapy for infertility. Our results are consistent with those from an earlier study of cancer mortality among women receiving radiotherapy for infertility conducted in New York City. Int. J. Cancer 82:795-798, 1999. Published 1999 Wiley-Liss, Inc.

Adult↗
PubMed1999

Integrin family of cell adhesion molecules in the injured brain: regulation and cellular localization in the normal and regenerating mouse facial motor nucleus.

Integrins are a large family of heterodimeric glycoproteins that play a crucial role in cell adhesion during development, inflammation, and tissue repair. In the current study, we investigated the localization of different integrin subunits in the mouse facial motor nucleus and their regulation after transection of the facial nerve. In the normal mouse brain, there was clear immunoreactivity for alpha5-, alpha6-, and beta1-integrin subunits on blood vessel endothelia and for alphaM- and beta2-subunits on resting parenchymal microglia. Facial nerve transection led to an up-regulation of the beta1-subunit on the axotomized neurons and an increase in the alpha4-, alpha5-, alpha6-, beta1-, alphaM-, alphaX-, and beta2-subunits on the adjacent, activated microglia. Quantification of the microglial integrins revealed two different expression patterns. The subunits alpha5 and alpha6 showed a monophasic increase with a maximum at day 4, the alphaM-subunit a biphasic regulation, with an early peak at day 1 and an elevated plateau between day 14 and 42. At day 14, there was also an influx of lymphocytes immunoreactive for the alpha4beta1- and alphaLbeta2-integrins, which aggregated at sites of neural debris and phagocytotic microglia. This finding was accompanied by a significant increase of the alpha5beta1-integrin on blood vessel endothelia. In summary, facial axotomy is followed by a strong and cell-type-specific expression of integrins on the affected neurons and on surrounding microglia, lymphocytes, and vascular endothelia. The presence of several, strikingly different temporal patterns suggests a selective involvement of these molecules in the different adhesive events during regeneration in the central nervous system.

Animals↗
PubMed1999

[Breaking of bad news. Practical advice to physicians for successful communication with patients].

BACKGROUND: In the more and more complex world of modern medicine, communication skills become increasingly important. Many physicians are however unaware of their difficulties in giving information in a clear and comprehensible way. This is especially true for breaking bad news. Keys for good communication consist in: careful preparation of the physical context of the interview; finding out how much the patient knows or suspects; giving the information in small amounts and a balanced way; responding to the patient's feelings and finally making a contract for the future.

Communication Barriers↗
PubMed1999

Cultivation and characterization of a new immortalized human hepatocyte cell line, HepZ, for use in an artificial liver support system.

The new human hepatocyte cell line HepZ was investigated with regard to use it for a mass cell cultivation. The cells were originally derived from a human liver biopsy and immortalized through lipofectamine-mediated transfection of albumin-promotor-regulated antisense constructions against the negative controlling cell cycle proteins Rb and p53 (pAlb asRb, pAIb asp53). Furthermore, plasmids including genes coding for the cellular transcription factor E2F and D1 cyclin (pCMV E2F, pSV2neo D1) were cotransfected to overcome the G1-restriction point. Cell cultivation was performed in a 2-liter bioreactor with a working volume of 1 liter. With CultiSpher G microcarriers used in a concentration of 3 g/l a maximal density of 7.1 x 10(6) cells/ml was achieved in a cultivation period of 20 days. The cells exhibited a maximal specific growth rate of 1.0 per day in the first 4 days. After 9 days of cultivation the stationary growth phase was reached with an average cell density of 5.5 x 10(6) cells/ml. The viability status of the culture was determined indirectly by measuring of the lactate dehydrogenase activity (LDH) at 37 degrees C. During the growth phase the activity rose slightly up to a value of 200 U/l. The cells were flat after first attachment on the gelatine microcarriers and spherical after growing into the three-dimensional inner matrix--both of which characteristics were verified by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The liver-specific cytochrome P450 activity was challenged with a pulse of 7 micrograms/ml lidocaine at a cell density of 4.5 x 10(6) cells/ml. After an induction period of 3 days with 50 micrograms/ml of phenobarbital, 26 ng/ml MEGX were generated within one day compared to 5 ng/ml without induction. The new cell line HepZ has proven to retain liver-specific qualities and to be appropriate for mass cell cultivation for bioartificial devices.

Albumins↗
PubMed1999

Calcium-induced structural changes of cartilage proteoglycans studied by H NMR relaxometry and diffusion measurements.

1H transverse nuclear magnetic relaxation times (T2) and self-diffusion coefficients (SDCs) of water were measured in isolated proteoglycan aggregates from pig articular cartilage. The influence of varying osmotic pressure, as well as of different calcium concentrations, on the samples was investigated. Due to a structural transition of the proteoglycans that results from changed electrostatic interactions at higher calcium concentrations, an additional fraction of water protons is observable. These protons are characterized by a very long T2 value and low, restricted diffusion. Additionally, electron microscopic elemental analyses and XFA investigations were performed to estimate the amount of calcium taken up by the proteoglycans. A model for the calcium-mediated structural transition of the cartilage proteoglycans is proposed that explains the experimental results. The investigations suggest the ability of proteoglycans to act as a calcium-concentrating agent and suggest their important role in the calcification process of articular cartilage.

Animals↗
PubMed1999

Molecular signals for glial activation: pro- and anti-inflammatory cytokines in the injured brain.

Injury to the central nervous system leads to cellular changes not only in the affected neurons but also in adjacent glial cells. This neuroglial activation is a consistent feature in almost all forms of brain pathology and appears to reflect an evolutionarily-conserved program which plays an important role for the repair of the injured nervous system. Recent work in mice that are genetically-deficient for different cytokines (M-CSF, IL-6, TNF-alpha, TGF-beta 1) has begun to shed light on the molecular signals that regulate this cellular response. Here, the availability of cytokine-deficient animals with reduced or abolished neuroglial activation provides a direct approach to determine the function of the different components of the cellular response leading to repair and regeneration following neural trauma.

Animals↗
PubMed1999

Stenting for atherosclerotic occlusive disease of the subclavian artery.

The purpose of this study was to evaluate the results of stenting subclavian artery pathologic lesions. Between July 1991 and December 1995, 69 patients (36 males: mean age 67 years, range 34-87 years) underwent intraluminal balloon dilatations followed by stent implantations in 70 subclavian arteries to treat primary atherosclerotic stenoses > 70%. Twenty-three patients (34%) were treated for vertebrobasilar insufficiency (VBI), 25 patients (36%) were treated for upper limb ischemia (ULI), and 10 patients (15%) were treated for both VBI and ULI. Other indications included symptomatic subclavian steal phenomenon (SSS), protection of dialysis arteriovenous fistula, coronary steal syndrome, protection of axilloaxillary bypass, distal embolization, and protection of left internal mammary artery (LIMA)-coronary bypass. Fifty-three cases (78%) were treated for stenosis and 17 cases (22%) for total occlusion of the origin of the subclavian artery. The results of this series indicate that stenting of subclavian artery stenosis appears safe and feasible with good short and mid-term patency, improving at those intervals the initial disappointing reports of balloon angioplasty alone. However, its long-term durability is at present unknown.

Aged↗
PubMed1999

Development of endoscopic dissection of perforating veins and fasciotomy for treatment of chronic venous insufficiency.

As the subfascial endoscopic perforator vein surgery (SEPS) has become increasingly popular, it becomes important to trace the development of this procedure first initiated in 1985. (Improvements in the technique and modifications of initial instrumentation have occurred. These changes are based on experience with greater than 1000 patients treated since 1980 at Krankenhaus der Barmherzigen Brüder in Munich, Klinikum Merheim in Cologne, and the Weilheim Hospital. Results obtained in 96 patients (140 legs) were examined retrospectively and are presented as well as the prospective evaluation of 39 patients with 56 operated legs. (Hauer G, Vasa 1985, 14:59-61; Hauer G, Barkun J, Wisser I, Deiler S, Surg Endosc 1988, 2:5-12; Schneidemann B, Inaug Diss, 1985). This report details the fact that in using our own instruments, including a specially designed videoscope, it has been possible to approach perforating veins of the medial anterior and posterior compartments. This can be done through a 2 cm incision in the proximal calf. Using these instruments, it has been possible to perform a fasciotomy under direct vision. This summary emphasizes that it is not necessary to locate perforating veins preoperatively, and that wound infection and recurrent ulcerations do not occur. This allows application of the method to patients with open ulcers. Further, this report emphasizes that patients with combined arterial and venous ulceration require arterial reconstruction rather than perforator vein interruption. The SEPS operation is relatively contraindicated if there is widespread necrosis and infection of the fascia, especially in combination with ankle ankylosis. In addition, this is the method of choice in patients with multiple incompetent perforating veins with or without open venous ulceration.

Dissection↗