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Biomedical subjects

J Lehmann

Publications and source records attributed to J Lehmann.

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

Electromyographically evident changes in skeletal muscles during tibial lengthening in dogs using the Ilizarov method.

Twenty-four beagle dogs underwent a lower leg lengthening on the right side of 2.5 cm at a distraction rate of 2 times 0.5 mm per day using a circular fixator system. After a latency phase of 5 days and a distraction phase of 25 days, 12 dogs (30-day dogs) underwent electromyography (EMG) of the gastrocnemius muscle on the lengthened and on the control side. The remaining half of the dogs underwent EMG after a consolidation phase of 25 days following the end of distraction (55-day dogs). During every EMG, at least 20 different muscle potentials were analyzed, and the duration, amplitude, and number of phases were determined of each individual potential. The 30-day dogs had significantly longer potential phases on the lengthened side and insignificantly smaller amplitudes compared with the control side. Furthermore, we observed a slightly larger number of polyphasic potentials on the distraction side. In the 55-day dogs, no significant differences were observed in the various parameters between the lengthened and the control side. Comparing 30- and 55-day dogs, the duration of the potentials on the distraction side was not significantly shorter in the 55-day dogs, and the amplitude significantly higher. These findings could indicate combined neurogenous and myopathic alterations of the muscles during the early distraction phase which will be compensated during the later distraction period and the consolidation phase by reparative and reinnervation processes, leaving no lasting functional damage.

Action Potentials↗
PubMed2000

[Improvement of transrectal ultrasound. Artificial neural network analysis (ANNA) in detection and staging of prostatic carcinoma].

As a result of the enhanced clinical application of prostate specific antigen (PSA), an increasing number of men are becoming candidates for prostate cancer work-up. A high PSA value over 20 ng/ml is a good indicator of the presence of prostate cancer, but within the range of 4-10 ng/ml, it is rather unreliable. Even more alarming is the fact that prostate cancer has been found in 12-37% of patients with a "normal" PSA value of under 4 ng/ml (Hybritech). While PSA is capable of indicating a statistical risk of prostate cancer in a defined patient population, it is not able to localize cancer within the prostate gland or guide a biopsy needle to a suspicious area. This necessitates an additional effective diagnostic technique that is able to localize or rule out a malignant growth within the prostate. The methods available for the detection of these prostate cancers are digital rectal examination (DRE) and Transrectal ultrasound (TRUS). DRE is not suitable for early detection, as about 70% of the palpable malignancies have already spread beyond the prostate. The classic problem of visual interpretation of TRUS images is that hypoechoic areas suspicious for cancer may be either normal or cancerous histologically. Moreover, about 25% of all cancers have been found to be isoechoic and therefore not distinguishable from normal-appearing areas. None of the current biopsy or imaging techniques are able to cope with this dilemma. Artificial neural networks (ANN) are complex nonlinear computational models, designed much like the neuronal organization of a brain. These networks are able to model complicated biologic relationships without making assumptions based on conventional statistical distributions. Applications in Medicine and Urology have been promising. One example of such an application will be discussed in detail: A new method of Artificial Neural Network Analysis (ANNA) was employed in an attempt to obtain existing subvisual information, other than the gray scale, from conventional TRUS and to improve the accuracy of prostate cancer identification.

Adult↗
PubMed2000

Long-term effects of prenatal stress experiences and postnatal maternal separation on emotionality and attentional processes.

Postnatal environmental manipulations naturally occur on the background of prenatal experiences. In the laboratory rat, both pre- and postnatal environmental manipulations have been shown to alter adult behaviour. Additionally, it has been demonstrated that the consequences of postnatal manipulations can be altered by previous prenatal stress experience (PS). In the present study, we investigated long-term behavioural consequences of combined PS and postnatal experience, namely repeated maternal separation (MS). PS primarily increases emotionality and fear-related behaviour, while postnatal repeated MS has been previously reported to affect primarily attentional processes. Thus, we tested adult male and female Wistar rats on paradigms involving both emotionality and attention, namely open field, prepulse inhibition (PPI), and latent inhibition (LI) in the active avoidance and the conditioned emotional response paradigms. In line with previous reports, PS decreased open-field locomotion and impaired avoidance learning (increased emotionality), while MS enhanced LI (selective attention) and improved avoidance learning. Further, PS also increased PPI. There was little interaction between the two manipulations: The increased PPI seen after PS was normalised by MS, and the MS-induced enhancement of LI (using the active avoidance paradigm) was not evident in subjects previously subjected to PS. Taken together, these results suggest that the effects of PS and repeated MS are not synergistic in any of the investigated paradigms but can antagonise each other. Thus, in assessing the effects of postnatal manipulations, attention should be paid to the inadvertent occurrence of prenatal stress.

Animals↗
PubMed2000

The capacity to produce IFN-gamma rather than the presence of interleukin-4 determines the resistance and the degree of susceptibility to Leishmania donovani infection in mice.

The immune response against Leishmania donovani infection has been investigated in one resistant mouse strain (C3H/HeJ) and three susceptible mouse strains (C57BL/6, BALB/c, and B10D2/n). In order to correlate the strain-specific course of infection with the individual T cell response phenotype, the ex vivo cytokine secretion patterns of splenic lymphocytes were assessed by ELISA (interferon-y [IFN-gamma], interleukin-4 [IL-4], IL-10) or by bioassay (IL-2). The strain-dependent differences in the course of infection correlated closely with the potency of T cells to produce IFN-gamma. C3H/HeJ mice produced high amounts of IFN-gamma before and during infection, whereas susceptible mice produced low amounts of IFN-gamma early during L. donovani infection. However, C57BL/6 mice, which recovered from the infection rapidly after the acute stage, developed marked IFN-gamma response within the first 30 days of infection. In contrast, in BALB/c and B10D2/n mice, the IFN-gamma production diminished during the acute stage, and this was associated with a delay in recovery and with subsequent switching into the chronic stage. Interestingly, CD8+ T cells contributed significantly to IFN-gamma production during this phase. In contrast to IFN-y, the levels of IL-4 in response to antigen or mitogen ex vivo were always very low. Moreover, neutralization of endogenous IL-4 in vivo by treatment with soluble murine IL-4 receptor did not result in significant decreases in the parasite burdens in spleen and liver but did cause a decrease in the serum IgE level of L. donovani-infected BALB/c mice. These results confirm that in visceral leishmaniasis a Thl-dominated immune response is protective against the L. donovani parasites and, furthermore, that the capacity to produce IFN-gamma rather than the presence of IL-4 determines the efficacy of the immune response in susceptible mice. The data show that CD8+ T cells represent an important source of IFN-gamma during L. donovani infection in susceptible mice, implying a role for this cell type in healing and development of protective immunity.

Acute Disease↗
PubMed2000

Changes in canine peripheral nerves during experimental callus distraction.

In 24 beagles, lengthening of the right tibia was performed by callus distraction after osteotomy and application of a ring fixator. Distraction was started the fifth day after surgery with a distraction rate of 0.5 mm twice per day and ended after 25 days. A control group of six additional dogs underwent tibial osteotomy and external fixation without distraction. Twelve animals with leg lengthening and three animals without leg lengthening were sacrificed immediately after the distraction period of 25 days (Group A), the remaining 15 dogs were sacrificed after an additional consolidation phase of another 25 days (Group B). From the distracted right leg and from the left control side of each animal, the tibial and peroneal nerves were removed and studied by means of morphometric analysis of semithin sections and electron microscopic study. The authors reported only minor alterations of the myelinated nerve fibers consisting in relatively thin myelinated remyelinating nerve fibers, single axon degeneration, or macrophages. There was no axonal sprouting. In contrast, electron microscopic study disclosed signs of late Wallerian degeneration and axonal regeneration of the nonmyelinated axons. Morphometric analysis of the peroneal nerves revealed a significant increase of fiber density and a reduced mean axon and fiber diameter in the consolidation period (Group B). Similar changes were found in the tibial nerves in Group A and disappeared in the consolidation phase (Group B). These features indicate that callus distraction leads to moderate degenerative changes, followed by repair mechanisms, almost complete recovery, and some nerve fiber growth.

Animals↗
PubMed2000

Surmounting oscillating barriers: path-integral approach for weak noise

We consider the thermally activated escape of an overdamped Brownian particle over a potential barrier in the presence of periodic driving. A time-dependent path-integral formalism is developed which allows us to derive asymptotically exact weak-noise expressions for both the instantaneous and the time-averaged escape rate. Our results comprise a conceptually different, systematic treatment of the rate prefactor multiplying the exponentially leading Arrhenius factor. Moreover, an estimate for the deviations at finite noise strengths is provided and a supersymmetry-type property of the time-averaged escape rate is verified. For piecewise parabolic potentials, the rate expression can be evaluated in closed analytical form, while in more general cases, as exemplified by a cubic potential, an action-integral remains to be minimized numerically. Our comparison with very accurate numerical results demonstrates an excellent agreement with the theoretical predictions over a wide range of driving strengths and driving frequencies.

Journal Article↗
PubMed2000

Retroperitoneal mature teratoma 15 years after initial treatment of testicular mixed germ cell tumor.

We present a patient with a retroperitoneal tumor noted 15 years after treatment of a testicular mixed germ cell cancer. The patient initially underwent right-sided orchiectomy and retroperitoneal lymph node dissection for clinical stage I disease. An early relapse indicated by increasing tumor markers shortly after retroperitoneal lymph node dissection was successfully treated with five cycles of combined chemotherapy. However, 187 months after completion of chemotherapy, a symptomatic right-sided iliac mass was diagnosed. Radical surgical excision of the mass was performed and histologic examination revealed differentiated mature teratoma. This represents the longest time interval reported in the literature for a mature teratoma following treatment of a testicular germ cell tumor.

Adult↗
PubMed2000

Long-term biobehavioral effects of maternal separation in the rat: consistent or confusing?

Over the last decades of research there has been increasing interest in endocrine and behavioral effects of postnatal environmental manipulations. A manipulation procedure that has been widely used to date is that of maternal separation. Many studies have demonstrated that, in the rat, a single or repeated separation of the pups from the mother leads to acute as well as long-term effects on endocrinology and behavior. However, reviewing the literature shows that contrary findings for almost all parameters investigated can be found. A possible explanation for this inconsistency may be the fact that maternal separation has become a collective term for a variety of extremely different experimental manipulations. Therefore, this review aims at evaluating typical effects of maternal separation in the laboratory rat by categorizing different experimental procedures. We concentrate in particular on longterm behavioral effects, although a brief summary of neuroendocrine effects is also provided. In addition, important methodological issues of maternal separation studies are discussed as a possible source for inconsistent findings.

Adaptation, Physiological↗
PubMed2000

[A new live Salmonella enteritidis vaccine for chickens--experimental evidence of its safety and efficacy].

Within the works for the registration of a new live Salmonella Enteritidis vaccine for layers, safety and efficacy of the vaccine strain were tested by experimental studies. After oral administration of the single and the tenfold dose, no incompatibility reactions were seen in day-old chicks. The laying performance and the egg weight were not affected by the vaccination of the chickens during the laying period. There was only a limited period in which the excretion of the vaccine strain and its persistency in organs were seen. Even after the threefold oral vaccination the vaccine strain could not be isolated from eggs and internal organs of slaughtered chickens. Moreover, a high safety for non-target animals (cattle, pigs) could be established. Studies with BALB/c mice proved that a cell-mediated immunity and the development of complement-fixing antibodies is induced by the vaccine. Efficacy studies in target animals were carried out by a proved dependable oral challenge system that reproduces a latent infection with marked S. Enteritidis strains and by means of the seeder-bird method. The test results demonstrate that the vaccination is capable to avert or to reduce an infection significantly.

Animals↗
PubMed2000

Traumatic scapulothoracic dissociation.

Scapulothoracic dissociation is an infrequent injury with a potentially devastating outcome. The diagnosis is based on clinical and radiographic findings of forequarter disruption. These include massive soft tissue swelling of the shoulder, displacement of the scapula and neurovascular injuries (brachial plexus, subclavian artery and osseous-ligamentous injuries). The mechanism of injury appears to be the delivery of severe rotational force sheering the shoulder girdle from its chest wall attachments around the scapula, shoulder joint and at the clavicle. Early recognition of the entity and aggressive treatment are crucial. Outcome is not dependent on management of the arterial injury, but rather on the severity of the neurological deficit.

Accidents, Traffic↗
PubMed1999

Peripheral benzodiazepine receptors in cerebral cortex, but not in internal organs, are increased following inescapable stress and subsequent avoidance/escape shuttle-box testing.

Stress-induced alterations in peripheral benzodiazepine receptor (PBR) density have been reported in humans and in rats. However, the PBR response is highly specific, and its function remains largely unexplained. The aim of the present study was to investigate the relationship between behavior in the two-way active avoidance paradigm (2WAA) and post-test PBR densities in adrenal, testis, kidney, and cerebral cortex. Adult male Wistar rats were tested in the 2WAA either in the naive state (AA) or 24 h following shock preexposure (PE), known to interfere with avoidance/escape response acquisition, and decapitated immediately after testing. Control subjects were decapitated without experimental experience. The stressful characteristic of the experiment was validated by significantly increased post-test corticosterone levels in AA and PE subjects compared with controls, with a trend towards higher corticosterone levels in PE relative to AA rats. Similarly, PE compared with AA subjects tended to show retarded acquisition of the escape/avoidance response. PBR densities in adrenal, kidney, and testis and central benzodiazepine receptors (CBR) in the cerebral cortex remained unaffected by avoidance testing. Cerebral cortex PBR density was significantly increased in PE subjects. These findings suggest that avoidance testing, although stressful to the animals, led to changes confined to cerebral cortex PBR, indicating that the hypothalamic-pituitary-adrenal (HPA) response occurs independently of the PBR response in peripheral organs, and also suggest that the opportunity for coping alters the impact of the stressor on the subject and prevents the expression of PBR response in peripheral organs.

Adrenal Glands↗
PubMed1999

NO-Donors, part 3: nitrooxyacylated thiosalicylates and salicylates - synthesis and biological activities(#).

Organic nitrates release nitric oxide when incubated with thiosalicylic acid. S-Nitrooxyacylated esters and amides of thiosalicylic acid, together with the corresponding salicylates, were synthesized in order to perform a first in vitro evaluation of these new nitrate-thiol-hybrid prodrugs. These prodrugs might release NO in vivo after biotransformation without the use of endogenous reductives. None of these prodrugs released NO spontaneously when dissolved in buffer solution, but they did activate soluble guanylyl cyclase and induced vasodilatation of phenylephrine-pretreated male Wistar rat aorta in a potency range between that of isosorbiddinitrate and glycerole trinitrate.

Journal Article↗
PubMed1999

Estimation of cell damage in bench- and pilot-scale affinity expanded-bed chromatography for the purification of monoclonal antibodies.

The first step in downstream processing of mammalian cell culture includes the separation of the cells without cell damage to avoid the release of intracellular enzymes, which could potentially cause proteolytic degradation of the target protein and may increase the impurities for further chromatographic steps. This especially includes the reduction of host DNA for therapeutic proteins. The aim of this investigation was to examine the extent of cell damage at the bench and pilot scale using a stabilized fluidized bed (expanded bed) for direct recovery of IgG from cell culture broth. For this purpose, Streamline-25 and -200 columns containing 75 mL and 5 L of rProtein A matrix, respectively, were used. The repeated batch cultivations resulted in high cell viabilities of about 90% prior purification. The pH was gently adjusted to pH 8 before the broth was applied to the gel. In bench scale, 1 to 6 L of unclarified feed was applied to the Streamline-25 column. In pilot scale, up to 95 L was processed using the Streamline-200 column. The antibodies from 95 L of unclarified feed were recovered after approximately 1.5 h. The possible cell damage, caused either by the equipment or by the cells' passage through the expanded bed, was detected by the following assays: microscopic count of the cells using trypan blue dye exclusion to determine viability; monitoring of intracellular components (i.e., DNA concentration); activity of lactate dehydrogenase (LDH); and, finally, the particle load in the flow through and the eluate. Despite the sensitivity of hybridoma cells to shear forces, neither the high flow rate (300 to 450 cm/h) nor the passage of the cells through the expanded bed caused any relevant cell damage or clogging of the gel. Excellent DNA depletion was observed.

Animals↗
PubMed1999

Resolution of newly synthesized racemic dihydropyridines with different chiral selectors by means of capillary electrophoresis.

The racemates of newly synthesized 4-aryl-1,4-dihydropyridine derivatives attracting interest in the treatment of coronary insufficience were resolved via the formation of diastereomeric salts. In order to check the quality of the preparative resolution, capillary electrophoresis using neutral cyclodextrins (CDs) was developed. In particular, the alpha-CD was found to be a powerful discriminator of the enantiomers. Additionally, taking amlodipine and nicardipine into consideration, a mechanism of the chiral recognition with alpha-CD could be proposed.

Amlodipine↗
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

Improvement in coronary flow reserve determined by positron emission tomography after 6 months of cholesterol-lowering therapy in patients with early stages of coronary atherosclerosis.

BACKGROUND: Early stages of coronary atherosclerosis are characterized by a mainly functional impairment of coronary vasodilator capacity under the impact of such risk factors as hypercholesterolemia. The goal of this study was to determine whether 6-month cholesterol-lowering therapy improves coronary flow reserve in patients with angina, reduced flow reserve despite minimally diseased coronary vessels or even normal angiogram, and mild to moderately elevated LDL levels on average. METHODS AND RESULTS: We noninvasively investigated 23 consecutive patients (18 men, 5 women; mean age, 56+/-7.6 years) with a mean LDL level of 165+/-34 mg/dL at baseline by PET for myocardial blood flow measurement with [13N]ammonia at rest and under dipyridamole stress (0.56 mg/kg) before and after lipid-lowering therapy with simvastatin for 6 months. Between baseline and the 6-month follow-up, total cholesterol concentration fell from 241+/-44 to 168+/-34 mg/dL, and the LDL level decreased from 165+/-34 to 95+/-26 mg/dL (P<0.001). Overall, coronary flow reserve increased from 2.2+/-0.6 to 2.64+/-0.6 (P<0.01). Maximal coronary flow increased significantly from 182+/-36 to 238+/-58 mL/minx100 g (P<0.001) at follow-up. Minimum coronary resistance declined significantly from 0. 51+/-0.12 to 0.40+/-0.14 mm Hg. mL-1. minx100 g (P<0.001). Concomitantly, a regression of anginal symptoms was observed in most patients. CONCLUSIONS: Our results suggest that cholesterol-lowering therapy with simvastatin may improve overall coronary vasodilator capacity assessed noninvasively by PET in patients with mild to moderate hypercholesterolemia. Consequently, intensive lipid-lowering therapy is considered a vasoprotective treatment for selected patients in very early stages of coronary atherosclerosis with the potential of preventing further disease progression.

Adult↗