Biomedical subjects

R Lehner

Publications and source records attributed to R Lehner.

At least 19 recordsLinked to original sources

PubMed2001

The cloning and expression of a murine triacylglycerol hydrolase cDNA and the structure of its corresponding gene.

A novel murine cDNA for triacylglycerol hydrolase (TGH), an enzyme that is involved in mobilization of triacylglycerol from storage pools in hepatocytes, has been cloned and expressed. The cDNA consists of 1962 bp with an open reading frame of 1695 bp that encodes a protein of 565 amino acids. Murine TGH is a member of the CES1A class of carboxylesterases and shows a significant degree of identity to other carboxylesterases from rat, monkey and human. Expression of the cDNA in McArdle RH7777 hepatoma cells showed a 3-fold increase in the hydrolysis of p-nitrophenyl laurate compared to vector-transfected cells. The highest expression of TGH was observed in the livers of mice, with lower expression in kidney, heart, adipose and intestinal (duodenum/jejunum) tissues. The murine gene that encodes TGH was cloned and exon-intron boundaries were determined. The gene spans approx. 35 kb and contains 14 exons. The results will permit future studies on the function of this gene via gene-targeting experiments and analysis of transcriptional regulation of the TGH gene.

Amino Acid Sequence↗

PubMed2001

A role for Sp1 in the transcriptional regulation of hepatic triacylglycerol hydrolase in the mouse.

Microsomal triacylglycerol hydrolase (TGH) hydrolyzes stored triacylglycerol in cultured hepatoma cells (Lehner, R., and Vance, D. E. (1999) Biochem. J. 343, 1-10). We studied expression of TGH in murine liver and found both protein and mRNA increased dramatically at 27 days after birth. Nuclear run-on assays demonstrated that this was due to increased transcription. We cloned 542 base pairs upstream of the transcriptional start site of the murine TGH gene. Electrophoretic mobility shift assays demonstrated enhanced binding of hepatic nuclear proteins from 27-day-old mice to the murine TGH promoter, yielding three differentially migrating complexes. DNase I footprint analysis localized these complexes to two distinct regions: site A contains a putative Sp binding site, and site B contains a degenerate E box. We transfected primary murine hepatocytes with a series of 5'-deletion constructs upstream of the reporter luciferase cDNA. Positive control elements were identified in a segment containing site A. Competitive electrophoretic mobility shift assays and supershift assays demonstrated that site A binds Sp1 and Sp3. Transcriptional activation assays in Schneider SL-2 insect cells demonstrated that Sp1 is a potent activator of the TGH promoter. These experiments directly link increased TGH expression at the time of weaning to transcriptional regulation by Sp1.

Animals↗

PubMed2001

Prognostic influence of delays between exploratory and definitive laparotomy in the treatment of malignant ovarian tumors.

BACKGROUND: The aim of this retrospective study was to evaluate whether a delay between a preliminary exploratory laparotomy and a definitive staging laparotomy and interval chemotherapy between the two operations affected the prognosis of ovarian cancer. METHODS: Of 504 patients with malignant tumors of the ovary who were treated at the Department of Obstetrics and Gynecology between 1980 and 1993, there were 24 who had a delayed definitive staging laparotomy. RESULTS: Sixteen patients did not have chemotherapy between their two operations. After definitive laparotomy, 13 patients (54.2%) were free of disease and 11 patients had residual disease (45.8%). CONCLUSIONS: The value of chemotherapy between preliminary and definitive laparotomy in halting tumor growth was not demonstrated by the results of our analysis.

Adult↗

PubMed2001

Localization of telomerase hTERT protein and survivin in placenta: relation to placental development and hydatidiform mole.

OBJECTIVE: To find if a difference in telomerase or survivin expression exists between non-neoplastic tissues and hydatidiform moles, and explore expression of those proteins in normal placental development, post-term gestation, and preeclampsia. METHODS: Formalin-fixed placental tissues were selected from collections of the Department of Pathology at the University of Colorado. Five specimens of each trimester, five each of preeclamptic and post-term placentas, and 23 molar pregnancies were selected. The telomerase catalytic protein hTERT was localized in placental tissues using the catalyzed signal amplification system, and survivin was localized by conventional immunoperoxidase method. Staining was graded on a scale of zero to 4. RESULTS: hTERT staining was detected in sections of 42 of 48 specimens (23 of 23 hydatidiform moles, 19 of 25 non-neoplastic placental tissues). The intensity of staining for hTERT was higher in hydatidiform moles (mean 3.3, median 3) compared with levels in non-neoplastic placental tissues (mean 0.92, median 1) (P <.001). Survivin was detected in 39 of 48 specimens (22 of 23 hydatidiform moles, 17 of 25 non-neoplastic placental tissues). Compared with non-neoplastic tissues (mean 0.88, median 1), survivin levels were elevated in hydatidiform moles (mean 1.35, median 1) (P =.031). CONCLUSION: Survivin and telomerase were increased in hydatidiform moles, suggesting that regulation of apoptosis and stabilization of telomere length might be involved in neoplastic transformation of the placenta. The patterns of expression observed for survivin and telomerase in non-neoplastic placental tissues suggest that the control of apoptosis and stabilization of telomeric DNA might also be involved in normal gestational development.

Biomarkers↗

PubMed2001

Expression of survivin in normal, hyperplastic, and neoplastic colonic mucosa.

The regulation of apoptotic cell death may have a profound effect on the pathogenesis and progression of colon cancer. Survivin, a member of the inhibitor of apoptosis gene family, has been detected in fetal tissue and in a variety of human malignancies. In the current study, we investigated survivin expression by an immunohistochemical approach in benign, hyperplastic, premalignant, and malignant lesions of the colon. Survivin was detected in all cases of normal colonic mucosa (20/20), hyperplastic polyps (20/20), adenomatous polyps (20/20), and in both well differentiated and moderately differentiated colonic adenocarcinomas (20/20). In the normal colonic mucosa, survivin expression was mostly restricted to the base of the colonic crypts. All epithelial cells showed uniformly intense staining for survivin in hyperplastic polyps. By contrast, adenomas and adenocarcinomas showed a heterogeneous staining pattern with cell-to-cell, gland-to-gland, and regional variability in the intensity of survivin staining. In contrast to the basal preponderance of staining in normal colonic mucosa, numerous survivin positive cells were present at the luminal surface of hyperplastic polyps, adenomatous polyps, and adenocarcinomas. In conclusion, the expression of survivin is not a specific marker of adenocarcinoma of the colon but does show characteristic and reproducible patterns of expression in non-neoplastic proliferative lesions and in normal colonic mucosa.

Colon↗

PubMed2001

Open Tübingen titanium prostheses for ossiculoplasty: a prospective clinical trial.

OBJECTIVE: The overall purpose of the study was the evaluation of the efficacy of Tübingen titanium prostheses (TTPs) for ossiculoplasty. STUDY DESIGN: A two-part clinical study of 216 patients undergoing ossiculoplasty was performed. The first part was a prospective study using TTPs (n = 114). The second part involved study of historical control patients (n = 102) with gold and ceramic prostheses. INTERVENTIONS: All patients underwent ossiculoplasty. MAIN OUTCOME MEASURES: Measures included median air conduction thresholds and air-bone gaps. RESULTS: All patients were per-protocol patients. When the air-bone gap "gold standard" (i.e., < or =10 dB) was investigated in the main speech spectrum, partial TTPs reached this level at 2 kHz in 44% (n = 22) and at 3 kHz in 38% (n = 19). Gold and ceramics revealed significantly lower values. Similar results were obtained for total prostheses. Differences for TTPs and ceramics were statistically significant (Mann-Whitney U test, alpha = 5%). CONCLUSION: The use of TTPs for ossiculoplasty is an efficient treatment method.

Acoustic Stimulation↗

PubMed2001

Total implantation of the active hearing implant TICA for middle ear disease: a temporal bone study.

A subpopulation of hearing-impaired patients has conductive hearing loss that cannot be improved by classic tympanoplasty. Other patients have a mixed hearing loss and cannot be helped by present forms of ear surgery or by hearing aids. Possible help for some patients may come from current implantable hearing devices if these are modified for the patient's specific anatomic situation. The TICA LZ 3001 is a hearing implant for total implantation used to treat moderate to severe sensorineural hearing loss. Most patients who use it have a normal ossicular chain that allows coupling of the implant to the incus. The present temporal bone study demonstrates that the TICA can also be used in patients with an interrupted ossicular chain. If the incus long process shows a defect, the TICA may be coupled to the incus body, and connection between the stapes and the long process of the incus can be achieved with a commercially available titanium-angle prosthesis or liquid ionomeric cement. In cases of an absent incus, the coupling axis of the transducer may be coupled to the stapes head via a modified coupling element. With an absent stapes, the coupling axis may be coupled directly to the perilymph by a coupling element similar to a gold stapes prosthesis.

Ear, Middle↗

PubMed2000

Ectopic pregnancy.

Ectopic pregnancy is a implantation occurring elsewhere than in the cavity of the uterus, whereas ninety-nine percent of extrauterine pregnancies occur in the fallopian tube. The incidence of extrauterine pregnancy has increased from 0.5% thirty years ago, to a present day 1-2%. The most frequent cause of tubal pregnancy is previous salpingitis. Mortality rates for tubal pregnancies used to be approximately 1.7% in the 1970s but dropped to 0.3% in 1980s. DIAGNOSIS: Using transvaginal ultrasound it is possible to obtain positive evidence of an ectopic pregnancy at a very early stage. In cases of hCG titers>2,000 IU/l, intrauterine pregnancy can be diagnosed with certainty. The most important differential diagnosis of ectopic pregnancy is early intrauterine pregnancy. CLINICAL MANAGEMENT AND THERAPY: Regardless of the therapeutic strategy selected by the physician, informing the patient is a major aspect of the management of ectopic pregnancy. If surgery is considered appropriate, the patient must be informed about the nature, side effects and complications of the procedure. However, it should be remembered that in some cases, the actual chances of cure first become apparent at surgery. In asymptomatic patients with a serum hCG titer <1,000 IU/l that is falling, it is appropriate to wait and watch. In clinically stable patients with an unruptured tubal pregnancy and steady hCG levels, systemic treatment with methotrexate might also be considered. In unruptured tubal pregnancy with a hCG titer between 1,000 and 2,500, a further therapeutic alternative is intratubal injection of prostaglandins, hyperosmolar glucose of NaCl. Generally speaking, the currently widespread laparoscopic surgical treatment of the fallopian tube hardly influences the risk of recurrence. If the gestational mass is larger, the serum hCG titer higher than the approximate limit of 2,500 mU/ml and/or the tube already ruptured, surgery is usually required. PREVENTION: The most effective prevention is to avoid tubal inflammation or, in cases of preexisting inflammation, to administer effective therapy.

Chorionic Gonadotropin↗

PubMed2000

Human studies of a piezoelectric transducer and a microphone for a totally implantable electronic hearing device.

OBJECTIVE: For the surgical treatment of patients with moderate and severe sensorineural hearing loss, the authors have developed a totally implantable hearing device, the totally integrated cochlea amplifier (TICA). To evaluate the effectiveness of transducer and microphone of this device, three separate human studies were conducted. STUDY DESIGN: The first study using transducer prototypes involved self experiments in investigators with normal hearing. The second study used the transducer prototypes in patients with hearing loss, and the third study involved the temporary implantation of the final transducer prototype and microphone in patients undergoing otologic surgery. PATIENTS: In routine middle ear surgery, transducer prototypes were coupled to the ossicular chain of 28 patients. In addition to the transducer, in 5 patients the microphone was placed beneath the skin of the auditory canal, allowing the skin to cover the microphone membrane completely. RESULTS: The piezoelectric transducer reached an equivalent sound pressure level of 145 dB SPL < or =10 kHz. The dynamics for music reached 32 dB, which was identical with the results of the preoperative investigations using high-fidelity headsets (33 dB). The low nonlinear distortions of <0.1% and the frequency range of 10 kHz are reflected in the positive evaluation of the sound quality by 84% of the patients involved. When phonetically balanced speech material and music were presented under free field conditions at a sound level of 65 dB SPL, understanding of the phonetically balanced speech material was 100%. Most patients judged the presentations of music as clear and undistorted with all broadband components. CONCLUSIONS: Data in humans on the performance of the two main components of the TICA implant, the transducer and the microphone, are reported.

Amplifiers, Electronic↗

PubMed2000

Alcohol consumption during methadone maintenance treatment.

Alcohol consumption during methadone maintenance treatment (MMT) often becomes a problem. We investigated a group of 68 patients undergoing MMT in our care. Mean duration of MMT was 50 months. A set of risk factors for problematic alcohol use ('alcohol indicators') was set up consisting of patients' account and laboratory parameters. 52% of patients were positive for these 'alcohol indicators' and 32% of patients fulfilled more severe criteria for alcohol abuse. There was exactly the same proportion of patients with 'alcohol indicators' at the start of MMT as at follow-up examination. In 79% of these patients 'alcohol indicators' were found on both occasions, testifying that alcohol problems were a stable trait. While patients without 'alcohol indicators' showed an improvement of liver parameters over time, those with 'alcohol indicators' suffered a considerable deterioration, indicating that the amount of alcohol consumption had increased.

Adult↗

PubMed1999

Cloning and expression of a cDNA encoding a hepatic microsomal lipase that mobilizes stored triacylglycerol.

A microsomal triacylglycerol hydrolase (TGH) was recently purified from porcine liver [Lehner and Verger (1997) Biochemistry 36, 1861-1868]. To gain further insight into the function of TGH, we have cloned a cDNA encoding TGH from a rat liver cDNA library and generated McArdle RH7777 rat hepatoma cell lines that stably express the rat TGH. The putative protein derived from the cDNA sequence contains a cleavable signal sequence and a catalytic site serine residue present within a pentapeptide motif (GXSXG) that is conserved in all known lipases. TGH-transfected cells showed a 2-fold increase, compared with control cells, in the rate of depletion of prelabelled triacylglycerol stores. Thus, TGH is capable of hydrolysis of stored triacylglycerol. In contrast, the rate of turnover of labelled phosphatidylcholine was similar in both the vector- and TGH-transfected cells. Studies in TGH-transfected cells demonstrated that utilization of intracellular triacylglycerol pools for secretion was approx. 30% higher than in vector-transfected cells. Whereas phosphatidylcholine secretion was essentially the same in control and TGH-transfected cells, TGH-transfected cells also secreted an approx. 25% greater mass of triacylglycerol into the medium and had increased levels of apolipoprotein B100 in the very-low-density lipoprotein density range compared with control cells. The results suggest that the microsomal TGH actively participates in the mobilization of cytoplasmic triacylglycerol stores, some of which can be used for lipoprotein assembly.

Animals↗

PubMed1999

Subcellullar localization, developmental expression and characterization of a liver triacylglycerol hydrolase.

The mechanism and enzymic activities responsible for the lipolysis of stored cytosolic triacylglycerol in liver and its re-esterification remain obscure. A candidate enzyme for lipolysis, a microsomal triacylglycerol hydrolase (TGH), was recently purified to homogeneity from pig liver and its kinetic properties were determined [Lehner and Verger (1997) Biochemistry 36, 1861-1868]. We have characterized the enzyme with regard to its species distribution, subcellular localization, developmental expression and reaction with lipase inhibitors. The hydrolase co-sediments with endoplasmic reticulum elements and is associated with isolated liver fat droplets. Immunocytochemical studies localize TGH exclusively to liver cells surrounding capillaries. Both TGH mRNA and protein are expressed in rats during weaning. The enzyme covalently binds tetrahydrolipstatin, an inhibitor of lipases and of triacylglycerol hydrolysis. The enzyme is absent from liver-derived cell lines (HepG2 and McArdle RH7777) known to be impaired in very-low-density lipoprotein (VLDL) assembly and secretion. The localization and developmental expression of TGH are consistent with a proposed role in triacylglycerol hydrolysis and with the proposal that some of the resynthesized triacylglycerol is utilized for VLDL secretion.

Animals↗

PubMed1999

Contraceptive knowledge and behavior of conventionalists, careerists, idealists, bouncers, desperadoes, and outsiders.

The aim of the survey was to determine the contraceptive behavior and knowledge on contraceptive methods of adolescents. We defined six clusters according to personality, leisure activities, and sociodemographic characteristics: conventionalists, careerists, idealists, bouncers, desperadoes, and outsiders. 1010 Austrian adolescents aged 14-24 years participated in the survey. 96%-100% indicated that they were familiar with the condom and the contraceptive pill. The two most popular contraceptive methods cited were the condom (39%) and OC (34%). Whereas 40% of conventionalists reported that OC were their preferred method of contraception, 53% of idealists indicated that they preferred the condom. 66% of the desperadoes indicated that they considered the pill expensive. 85% of conventionalists and careerists believe that OC offer the best protection against pregnancy. Clusters with higher self-esteem and those with a higher educational level were more likely to believe that this method is unreliable. The results obtained indicate that outsiders, desperatoes, and bouncers show deficits in sex education; only careerists and idealists appeared to be better informed. Research on adolescent contraceptive behavior should drop the traditional stratifying criteria and appreciate the diversity of adolescent populations in order to be better able to classify adolescents according to their contraceptive attitudes.

Adolescent↗

PubMed1998

Unsuspected primary tubal carcinoma during operative laparoscopy.

OBJECTIVE: To evaluate the possible risk of dealing with an unsuspected primary carcinoma of the fallopian tube during laparoscopic surgery. METHODS: We performed a countrywide survey in Austria concerning laparoscopic procedures in cases of primary carcinoma of the tube. The questionnaire consisted of questions regarding the pre-, intra-, and postoperative management. RESULTS: Of 18,435 laparoscopies in cases of an adnexal mass, 5 cases were reported, when laparoscopy was performed on an unsuspected carcinoma of the tube. Therefore, the risk of detecting this malignancy during laparoscopy after preoperative evaluation is 1 in 3687 cases (0.028%). CONCLUSION: The risk of encountering an unsuspected primary carcinoma of the fallopian tube during laparoscopy in Austria is an extremely rare situation. In case of a malignancy, a staging or debulking laparotomy should be performed immediately or as soon as possible.

Aged↗

PubMed1998

[Cold deformation elements for attaching an implantable hearing aid transducer to ear ossicles or perilymph].

Development and short-term implantation results of the Tübingen implantable hearing aid (TI = Tübingen implant) have been presented. The TI is designed for patients with sensorineural hearing loss due to a malfunction of the cochlear amplifier. This can be identified by the presence of positive recruitment and the absence of TEOAE (transitory evoked otoacoustic emissions). The Tübingen implant functions in two ways: it allows electronic amplification of the auditory signal and electromechanical signal transduction into a micromechanical vibratory stimulus. There are two paths by which vibratory stimulus reaches the cochlea: (1) directly through a perforation in the stapes foot plate into the perilymph or (2) via the ossicular chain. Made of pure titanium, the casing of the helium-tight welded transducer includes the piezoelectric actuator. An implantable manipulator device is designed for transducer positioning and anchoring in the mastoid cavity. Usually, the transducer probe tip is directly coupled to the body of the incus. This functions without a special coupling device by utilization of an Erbium-YAG laser. Special anatomical situations or the loss of incus and/or stapes suprastructure, however, requires coupling of the vibratory signal to other points of the ossicular chain or to the perilymph. A major problem, however, was an intraoperative, irreversible link between the titanium probe tip and coupling elements. To overcome this problem, the coupling elements were made of gold. A crimp technique was developed, allowing the surgeon to induce cold deformation of the gold. The cold deformation technique (crimp) results in an irreversible coupling between the titanium probe tip and the golden coupling element.

Cochlear Implantation↗

PubMed1998

[Value of Schüller conventional roentgen diagnosis and computerized tomography of the temporal bone in preoperative diagnosis of the Tübingen implantable cochlear amplifier].

Recently, the transducer and microphone of a cochlea amplifier implant (CAI) for the treatment of sensorineural cochlear hearing loss have been developed further for implantation into the mastoid cavity. At present, the University of Tuebingen implantable cochlea amplifier consists of an implantable microphone and an implantable piezoelectric transducer. It has been implanted into the first patients. Successful future application of this new implant depends on the suitable fit of the CAI within a patient's mastoid cavity. Using conventional X-ray and CT scans, we analyzed 50 cadaver specimens of the temporal bone before total mastoidectomy. After total mastoidectomy, the volume of the mastoid cavity was measured using CT scans and water volume determination. Finally, the CAI was implanted into those temporal bones that were large enough to house it. Our results demonstrate that the degree of pneumatization in the conventional Schüller X-ray is already a good parameter for preoperative evaluation.

Cochlear Implantation↗

PubMed1998

[An osseointegrated micromanipulator as anchor for implantable hearing aid transducers. 1: Fitting to the surgical anatomy of the temporal bone and surgical technical properties].

The first electronic implantable hearing aids for patients with hearing loss are coupled to the ossicular chain or perilymph during implantation and are now available. Our new Tübingen implant designed for sensorineural hearing loss (SNHL) is the combination of an implantable microphone and piezotransducer. To avoid hearing losses during implantation, the Tübingen piezotransducer will be (1) fixed to the mastoid cavity and (2) positioned to one of the ossicular target points. This can be done with a micromanipulator which will be implanted together with transducer and microphone in the mastoid cavity. The manipulator weights 0.7 g. With four degrees of freedom, it allows highly secure and safe positioning of the transducer's probe tip to the ossicular chain under close to stereotactic conditions. The main advantages of the present micromanipulator are (1) easy handling during surgery, (2) the transducer's precise positioning to the ossicular target point with sufficient degrees of freedom, and (3) the transducer's stable fixation in the mastoid cavity in the final position. Following integrated safety as the leading principle, ossicular or inner ear injuries caused, e.g., by the patient's head movement or unintentional manual contact by the surgeon, are minimized. The micromanipulator is, as it were, the surgeon's vibration-free "artificial hand". The manipulator's development and its optimization to the mastoid cavity by test implantation in 50 human temporal bones are shown in detail. While coupling the transducer to the body of the incus, transducer, microphone, and micromanipulator can be implanted into 76% of all mastoid cavities without protrusion. In the case of transducers coupling to the long process of the incus, the protrusion-free implantation rate of the above-mentioned three implant modules is 78%.

Bone Plates↗

PubMed1998

[A micromanipulator for intraoperative vibratory hearing assessment with an implantable hearing aid transducer].

First concepts of implantable hearing aids to be coupled to the ossicular chain are available for patients with combined or sensorineural hearing loss (SNHL). To ensure that hearing can be improved intraoperative coupling of a test transducer to the ossicular chain is mandatory for allowing surgical anatomy to be checked and vibratory hearing tests to be performed. To achieve this, the test transducer has to be held and positioned securely in situ for some minutes, avoiding risks for middle or inner ear structures. This is not possible using conventional surgical instruments. Thus, a micromanipulator to hold the test transducer during intraoperative hearing tests was developed. This surgical device allows the surgeon safe, risk-free, and controlled coupling of the test transducer to the ossicular chain with one axial and three rotational degrees of freedom. With the aid of a conventional ear retractor (2x2 prongs), the manipulator is fixed at the patient's ear. In conjunction with a piezoelectric test transducer, the manipulator was used in nine patients during local anesthesia. The test transducer is part of an electronic hearing implant (Tübingen implant) specifically designed for SNHL that may be coupled to a middle ear ossicle or the perilymph of the cochlea. The micromanipulator was easy to handle. It allowed accurate positioning of the test transducer in the ear and the desired coupling of the transducer's probe tip to the ossicular chain during auditory tests. According to the principles of integrated safety, the intraoperative risk of ossicular or inner ear injuries caused, for instance, by the patient's head movement is minimized. The design of the manipulator system is universal, also allowing its use for other electronic hearing implants or minimal invasive surgery after minor modifications.

Ear Ossicles↗