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Biomedical subjects

R Lehmann

Publications and source records attributed to R Lehmann.

At least 127 records · Page 7Linked to original sources
PubMed1997

Capillary electrophoresis in clinical chemistry.

Since its introduction, capillary electrophoresis has diversified, spreading out into different specialized fields covering solutions for almost any analytical questions arising in research laboratories. In the context of clinical chemistry, results must be provided at low costs and in a clinically relevant time frame; however, the attributes which have made capillary electrophoresis such a successful tool in basic research are identical to those attracting clinical laboratories: speed (more efficient, less labor-intensive), low costs (minimal buffer consumption), small sample volume (reduced blood collection volume from patient), increased selectivity (determination of multiple solutes in one run), and versatility (detection of analytes over the wide range of molecular masses and chemical composition). Nevertheless, it should be mentioned that there are still some drawbacks at this stage to be solved in the near future, such as lack of sensitivity for many clinical applications or the constraint to measure in a sequential mode. The aim of this survey is to familiarize clinical chemists, as well as chemists, with a short introduction to capillary electrophoresis, followed by chapters reviewing prominent fields of applications and the latest developments in clinical chemistry.

Body Fluids↗
PubMed1997

Cell migration: don't tread on me.

During directed cell migration, telling cells to avoid certain areas may be as important as attracting them to others. The recently identified wunen gene is involved in the repulsive guidance of migrating primordial germ cells in Drosophila.

Animals↗
PubMed1997

A CCHC metal-binding domain in Nanos is essential for translational regulation.

The Drosophila Nanos protein is a localized repressor of hunchback mRNA translation in the early embryo, and is required for the establishment of the anterior-posterior body axis. Analysis of nanos mutants reveals that a small, evolutionarily conserved, C-terminal region is essential for Nanos function in vivo, while no other single portion of the Nanos protein is absolutely required. Within the C-terminal region are two unusual Cys-Cys-His-Cys (CCHC) motifs that are potential zinc-binding sites. Using absorption spectroscopy and NMR we demonstrate that the CCHC motifs each bind one equivalent of zinc with high affinity. nanos mutations disrupting metal binding at either of these two sites in vitro abolish Nanos translational repression activity in vivo. We show that full-length and C-terminal Nanos proteins bind to RNA in vitro with high affinity, but with little sequence specificity. Mutations affecting the hunchback mRNA target sites for Nanos-dependent translational repression were found to disrupt translational repression in vivo, but had little effect on Nanos RNA binding in vitro. Thus, the Nanos zinc domain does not specifically recognize target hunchback RNA sequences, but might interact with RNA in the context of a larger ribonucleoprotein complex.

Amino Acid Sequence↗
PubMed1997

An Egalitarian-BicaudalD complex is essential for oocyte specification and axis determination in Drosophila.

Genetic experiments suggest that polarization of the oocyte is linked directly to the initial cell fate determination that singles out the oocyte from its 15 sister cells. Specification of oocyte cell fate as well as establishment and maintenance of a polarized microtubule network within the Drosophila oocyte require the activity of the egalitarian (egl) and BicaudalD (BicD) genes. We have isolated the egl gene and show that Egl protein colocalizes with BicD protein at all stages of oogenesis. Immunoprecipitation experiments show that both proteins are part of a protein complex. Egl and BicD proteins localize to the oocyte in three stages that correlate with the stepwise polarization of the oocyte. We propose that the Egl-BicD protein complex links microtubule polarity and RNA transport. During early oogenesis, the complex is required to transport factors promoting oocyte differentiation; during later stages of oogenesis the complex directs the sorting of RNA molecules required for anterior-posterior and dorsoventral patterning of the embryo.

Amino Acid Sequence↗
PubMed1997

[Median facial dysplasia in patients with lip-jaw-palate clefts. Characteristics and problems in interdisciplinary orthodontic-oral surgery treatment].

The diagnosis of median facial dysplasia is made in cases of a typical deficiency of the median facial structures without concomitant abnormalities of the brain, and presence of unilateral or bilateral cleft lip and palate. The identification and description of this type of cleft lip and palate are important because such patients have severe growth disturbances and tissue deficiencies. These make surgical reconstruction and orthodontic treatment difficult. This is demonstrated in two examples. The clinical and roentgenological findings in the mother of one of the demonstrated patients point to a discrete form of the same anomaly.

Adolescent↗
PubMed1997

Control of ocular inflammation after cataract extraction with rimexolone 1% ophthalmic suspension.

PURPOSE: To assess the efficacy and safety of rimexolone 1% ophthalmic suspension in controlling intraocular inflammation after cataract extraction. SETTING: Twelve independent investigational centers in the United States METHODS: This study comprised 197 patients who had cataract extraction. Postoperatively, patients were randomized to a 2 week regimen of rimexolone 1% ophthalmic suspension or a placebo. Efficacy was analyzed by monitoring total anterior chamber cells and flare, other parameters of inflammation, and treatment failures. Safety was evaluated by monitoring treatment-related adverse events and intraocular pressure (IOP). RESULTS: Rimexolone 1% was clinically and statistically more effective in suppressing cell and flare than the placebo (P < .02). The overall discontinuation rate for treatment-related adverse events was 5.3% in the rimexolone group and 22.2% in the placebo group. There were no between-group differences in IOP. CONCLUSION: Rimexolone 1% ophthalmic suspension was safe and significantly more effective than a placebo in controlling intraocular inflammation after cataract extraction when used four times daily and continued for 2 weeks.

Administration, Topical↗
PubMed1997

Structural consequences of status epilepticus demonstrated with serial magnetic resonance imaging.

OBJECTIVES: To investigate MRI changes during tonic-clonic and focal motor status epilepticus. MATERIAL AND METHODS: Serial MRI-investigations with saggital, coronal and axial spin-echo (SE) T1-weighted 500/15 (repetition time [TR] msec/echo time [TE] msec) with and without application of gadolinium-DTPA, proton-density-SE 2100/30 and SE T2-weighted 2100/90 images. Correlation with seizure frequency and general clinical state and by using constant EEG recordings as well as video-EEG monitoring. RESULTS: Initially, images were normal but several days after onset of status epilepticus focal hyperintensive signal changes on T2-weighted images consistent with focal oedema were seen. The oedema produced a local mass effect as demonstrated with angiography. These changes occurred at a time when there were massive epileptic discharges registered by EEG monitoring in both cases. On subsequent images the oedema resolved but atrophy in combination with a high signal on T2-weighted images suggestive of gliosis were noted in identical regions. In the 1st case it could not completely be ruled out that the signal changes were caused by an encephalitis. However, the signal changes occurred in close time correlation with the epileptic seizure activity rendering the assumption less likely that the signal changes were caused by the encephalitis. In the 2nd case the signal changes could not be attributed to cortical dysplasia or any other condition than the epileptic activity itself. CONCLUSION: Prolonged epileptic seizure activity may cause neuronal damage associated with a typical pattern of MRI signal changes.

Adult↗
PubMed1997

Effects of ketamine sedation on glucose clearance, insulin secretion and counterregulatory hormone production in baboons (Papio hamadryas).

Since the effects of ketamine sedation seem to differ between subspecies of baboons, we assessed the endocrine response to an intravenous glucose tolerance test (IVGTT) in 12 hamadryas baboons. The first phase insulin secretion, basal insulin, and glucose levels, as well as the glucose clearance, were significantly lower in sedated baboons as compared to fully awake animals. Glucagon and cortisol were significantly higher, while growth hormone was lower during ketamine sedation. Papio hamadryas appears to be a promising pre-clinical model for the study of endocrine replacement therapy in insulin-dependent diabetes. However, the data obtained must be interpreted with the knowledge that the anesthetic employed to allow for testing of the animals does have an effect on the parameters described in this report.

Anesthetics, Dissociative↗
PubMed1997

Determinants of radial bone density as measured by PQCT in pre- and postmenopausal women: the role of bone size.

The aim of the present study was to examine the influence of anthropometric, hormonal, and geometric factors on the variability of radial bone mineral density (BMD) in women. In 583 healthy pre- and postmenopausal females (aged 40-60 years) radial total (BD) and trabecular BMD (TBD) was measured by peripheral quantitative computerized tomography at the nondominant distal forearm. In addition, 29 women who had suffered a Colles' fracture after minor trauma were also evaluated. There was no age-dependent change in radial BD and TBD before menopause. We found a negative correlation between BMD and age and years since menopause (YSM) in postmenopausal women (BD = 422.73 - 2.342 age - 6.308YSM; r = 0.36, p = 0.0001, n = 128). The variation of YSM, body mass index (BMI), and age accounted for 20% of the variability of BD in postmenopausal women. In contrast, in premenopausal women, only 3% of the variability could be explained by anthropometric variables. Bone mineral content (BMC) and bone area, but not BMD at the distal radius, were significantly correlated to grip strength (r = 0.25, p = 0.006 for BMC, r = 0.26, p = 0.003 for area). The cross-sectional bone area of the CT slice showed a significant increase with aging (y = 263.02 + 1.25x; r = 0.14, p = 0.0009). There was a strong negative correlation between bone area and BD and TBD (y = 516.04 - 0.668x; r = -0.57, p < 0.0001 for BD). If BMD is normalized for BA, variation is reduced by 32% (for BD) and 10% (for TBD), respectively. Women with Colles' fracture had a significantly lower TBD normalized for BA (fracture group [-0.71 +/- 0.88] vs. normals (0.03 +/- 0.99]; p = 0.00009). Our results show that YSM and BMI are predictors of postmenopausal BMD. However, radial BMD is influenced strongly by geometric variables such as cross-sectional bone area.

Absorptiometry, Photon↗
PubMed1997

Long-term function (6 years) of islet allografts in type 1 diabetes.

Eight type 1 diabetic patients, ages 29-41 years, with mean diabetes duration of 23 years (range 18-29 years) received islet transplants from 1 to 5 donors. Seven patients had stable kidney allografts 1-11 years before the islet transplant, and one patient had a simultaneous islet-kidney allograft. Patients' blood glucose control was poor as reflected by the mean +/- SD HbA1c of 9.1 +/- 1.7% before transplant. Of the first three patients, two (1 and 3) achieved insulin independence for 36 and 38 days, respectively. Two recipients rejected their islet grafts within 1 month (2 and 8) and therefore were excluded from analysis. The HbA1c and insulin requirement of the six remaining patients who had persistent islet function for more than 60 days was significantly reduced from 9.3 +/- 1.9 to 6.4 +/- 1.0% (P = 0.002) and from 0.75 +/- 0.15 to 0.35 +/- 0.12 U x kg(-1) x day(-1) (P < 0.001), respectively. The two patients with the longest graft survival (4 and 6) achieved a normalization or near-normalization of their HbA1c levels during 6 years in the absence of severe episodes of hypoglycemia. As demonstrated by a decline in C-peptide response during Sustacal challenge tests over a 6-year period, there was a diminution of islet allograft function over time, despite persistence of normal or near normal HbA1c. We concluded that transplantation of allogeneic islets with an islet mass comparable with whole or segmental pancreas transplants in type 1 diabetic patients can result in long-term islet allograft function; further, we concluded that, in conjunction with small dosages of exogenous insulin, a functioning islet allograft can result in near-normalization of blood glucose levels and significant improvement in HbA1c. The occurrence of severe hypoglycemic episodes observed for patients in the Diabetes Control and Complications Trial was not observed in recipients with functioning islet transplants, despite the continuous need for exogenous insulin therapy to sustain normal HbA1c over the 6-year follow-up. The significant improvement in metabolic control observed for the patients described in this study, and the potential to significantly decrease or halt the progression of diabetic complications, support the continued application of islet allotransplantation as a treatment modality for type 1 diabetic patients.

Adult↗
PubMed1997

Improved human islet isolation using a new enzyme blend, liberase.

Enzymatic digestion of donor pancreases is a vital step in human and large mammalian islet isolation. The variable enzymatic activities of different batches of commercially available collagenase is a major obstacle in achieving reproducibility in islet isolation procedures. In the present work, the effectiveness of Liberase, a standardized mixture of highly purified enzymes recently developed for the separation of human islets, was compared with that of a traditional collagenase preparation (type P). The results of 50 islet isolations using Liberase enzyme were compared with those of 36 isolations with collagenase, type P. No significant differences in donor age, cold ischemia time, digestion time, or weight of the pancreases were observed between the two groups. Islet yield was significantly higher in the group where the Liberase enzyme was used. All parameters examined (islet number, islet number per gram of tissue, islet equivalent number, and islet equivalent number per gram of tissue) were significantly improved when Liberase enzyme was used. Different lots of Liberase enzyme were tested, and no difference was observed. Islets isolated with Liberase enzyme were also of larger size and were much less fragmented, suggesting a gentler enzymatic action and better preservation of anatomical integrity. Islets isolated with Liberase enzyme, assessed both in vitro and in vivo, revealed a functional profile similar to that of islets separated with collagenase. Liberase enzyme appears, therefore, to represent a new powerful tool for improving the quality of human islet isolation.

Adult↗