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Biomedical subjects

B Lotz

Publications and source records attributed to B Lotz.

At least 19 recordsLinked to original sources

Screening for high-grade cervical intra-epithelial neoplasia and cancer by testing for high-risk HPV, routine cytology or colposcopy.

The validity of testing for high-risk types of human papillomavirus (HPV) in cervical cancer prevention programs is undetermined. We compared the performance on primary screening of HPV DNA testing, cytology and colposcopy in detecting cervical intra-epithelial neoplasia (CIN) grade 2 or 3 or cancer. A cohort of 4,761 women, median age 35 years, was screened by routine cytology, routine colposcopy and testing for high-risk HPV by a PCR-based method. Within an 8-month period, women with abnormal findings on cytology or screening colposcopy or in whom high-risk HPV types were detected were referred for colposcopy and biopsy. Women negative on all initial screening tests were followed by a second screening examination. To correct for work-up bias, the true prevalence of CIN 2 or 3 or cancer was estimated by projection from histologically verified subgroups. Cervical biopsies were taken in 364 women (7.6%), of whom 114 (2.4%) showed CIN 2 (n = 34) or CIN 3 (n = 71) or cancer (n = 9). High-risk HPV testing achieved bias-corrected performance measures of 89.4% sensitivity, 93.9% specificity, 35.8% positive predictive value and 99.6% negative predictive value. Bias-corrected rates of true- and false-positives by high-risk HPV testing compared to cytology (colposcopy) were about 4.5 (6.7) and 19.1 (7.4) times higher, respectively. The quality of routine cytology was controlled by computer-assisted review, and the observed number of true-positives more than doubled after adding automated review results. In middle-aged women, testing for high-risk HPV types, particularly when negative, may be used to increase the screening interval in programs for secondary prevention of cervical cancer.

Adult↗

Microdomain patterns from directional eutectic solidification and epitaxy

Creating a regular surface pattern on the nanometre scale is important for many technological applications, such as the periodic arrays constructed by optical microlithography that are used as separation media in electrophoresis, and island structures used for high-density magnetic recording devices. Block copolymer patterns can also be used for lithography on length scales below 30 nanometres (refs 3-5). But for such polymers to prove useful for thin-film technologies, chemically patterned surfaces need to be made substantially defect-free over large areas, and with tailored domain orientation and periodicity. So far, control over domain orientation has been achieved by several routes, using electric fields, temperature gradients, patterned substrates and neutral confining surfaces. Here we describe an extremely fast process that leads the formation of two-dimensional periodic thin films having large area and uniform thickness, and which possess vertically aligned cylindrical domains each containing precisely one crystalline lamella. The process involves rapid solidification of a semicrystalline block copolymer from a crystallizable solvent between glass substrates using directional solidification and epitaxy. The film is both chemically and structurally periodic, thereby providing new opportunities for more selective and versatile nanopatterned surfaces.

Journal Article↗

Detection of high-risk cervical intraepithelial neoplasia and cervical cancer by amplification of transcripts derived from integrated papillomavirus oncogenes.

Cervical cancer emerges from cervical intraepithelial neoplasia (CIN) induced by high-risk HPV (HR-HPV) infections. However, the vast majority of CIN lesions regresses spontaneously, and only a few lesions persist or progress to invasive carcinoma. On the basis of morphological criteria, it is not possible to differentiate high-grade lesions that will regress or persist from those that inevitably will progress to invasive cancers. In most cervical carcinomas, human papillomavirus (HPV) genomes are integrated into host cell chromosomes and transcribed into mRNAs encompassing viral and cellular sequences. In contrast, in early preneoplastic lesions, HPV genomes persist as episomes, and derived transcripts contain exclusively viral sequences. Thus, detection of HPV transcripts derived from integrated HPV genomes may specifically indicate both CIN lesions at high risk for progression as well as invasive cervical cancers. Here, we established a protocol for the amplification of papillomavirus oncogene transcripts (APOT) from cervical specimens that allows us to distinguish episome- from integrate-derived HPV mRNAs. Cervical swab and biopsy samples from 549 patients attending outpatient clinics for cervical dysplasia were screened for the presence of HPV DNA, and 155 samples that were positive for either HPV type 16 (n = 143) or 18 (n = 12) were subjected to the APOT assay. In samples derived from normal cervical epithelia (n = 19) or low-grade cervical lesions (CIN I, n = 10), no integrate-derived HPV transcripts were found. In contrast, in 1 (5%) of 22 samples derived from CIN II lesions, in 10 (16%) of 64 samples from patients with CIN III lesions, and in 35 (88%) of 40 samples from patients with cervical cancer, integrate-derived HPV transcripts were detected. Thus, detection of integrate-derived HPV transcripts in cervical swabs or biopsy specimens by the APOT assay points to advanced dysplasia or invasive cervical cancer.

Biopsy↗

Dynamical scattering and electron diffraction from thin polymer lamellar crystals - poly(tert-butylethylene sulfide).

Strong violations of Friedel symmetry are observed in hk0 electron diffraction patterns from lamellar crystals of poly(tert-butylethylene sulfide) obtained at 120 kV. These deviations are largely explained by a multislice dynamical scattering calculation based on the crystal structure model. Further improvement is found when a secondary scattering component is added, in keeping with a perfect crystallite thickness less than that of the lamellar thickness. Despite the multiple-scattering perturbations, the frustrated chain packing can still be determined by direct methods followed by Fourier refinement. However, the Friedel-related intensities must be averaged before calculation of normalized structure factors.

Journal Article↗

Uniform distribution of HPV 16 E6 and E7 variants in patients with normal histology, cervical intra-epithelial neoplasia and cervical cancer.

High-risk human papillomaviruses (HPV), particularly HPV 16, are associated with invasive cervical cancer (ICC), and persistent high-risk HPV infection is considered to be a marker for progressive cervical intra-epithelial neoplasia (CIN). However, most high-risk, HPV-infected, pre-cancerous lesions will not progress to invasion. Several reports suggest that specific HPV 16 E6 and/or E7 sequence variations may be associated with a high risk for progression. No data from German patients have so far been reported. Therefore, we analyzed intra-type variations of these oncogenes in women with normal histology or CIN 1 (< or = CIN 1), CIN 2/3 or ICC. Cervical scrapes from 75 patients with normal histology or CIN and biopsies from 37 ICC patients all positive for HPV 16 were analyzed. The open reading frames of oncogenes HPV 16 E6 and E7 were amplified by nested PCR followed by primer cycle sequencing. From each cervical scrape, 2 independent PCR amplicons were generated and sequenced from both orientations. The prototype sequence of HPV 16 E6 and E7 was identified in 33% and 87% of < or = CIN 1, in 62% and 69% of CIN 2/3 and in 43% and 86% of ICC, respectively (not significant). Of all variants identified, the E6 variant 350G (L83V) and the E7 variant 822G were most frequently detected irrespective of histology and showed prevalence rates of 27% to 43% and 7% to 20%, respectively. No statistically significant differences in the prevalence of the E6 or E7 prototype sequences, any variants or multivariants in German women with < or = CIN 1, CIN 2/3 or ICC were found.

Adolescent↗

Distribution of 14 high risk HPV types in cervical intraepithelial neoplasia detected by a non-radioactive general primer PCR mediated enzyme immunoassay.

AIM: To evaluate the presence of high risk human papillomaviruses (HPV) in cervical smears showing intraepithelial neoplasia (CIN). METHODS: The presence of 14 high risk HPV was evaluated in 114 cervical smears with CIN of different degrees, by comparing a non-radioactive polymerase chain reaction (PCR) enzyme immunoassay (EIA) with conventional PCR followed by radioactive Southern blot hybridisation. General primer PCR amplicons detecting low risk and high risk HPV were typed for 14 different high risk HPV types (HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68) by a non-radioactive PCR-EIA. Virus load of HPV 16 positive CIN was assessed using the semiquantitative PCR-EIA. RESULTS: Histological evaluation confirmed CIN I in 49 cases (mean age 29.0 years, range 17 to 52), CIN II in 31 cases (mean age 30.8 years, 18 to 54), and CIN III in 34 cases (mean age 31.1 years, 16 to 57). The non-radioactive PCR-EIA showed an overall agreement rate of 90% (kappa value 0.75) when compared with conventional general primer PCR followed by radioactive Southern blot hybridisation. High risk HPVs were detected in 47% of CIN I, 77% of CIN II, and 97% of CIN III (p < or = 0.02). HPV types 39, 51, 56, and 58 were found in CIN I exclusively (between 2% and 8%). HPV 16 and HPV 31 were detected in 12% and 2% of CIN I, 35% and 21% of CIN II, and 74% and 13% of CIN III, respectively (p < or = 0.03 and p < or = 0.04). The virus load estimated by the semiquantitative PCR-EIA of HPV 16 was similar in CIN I, CIN II, and CIN III. CONCLUSIONS: The PCR-EIA has high clinical sensitivity for detecting CIN II/III (90%). There was a significantly higher prevalence rate of HPV 16 and 31 in CIN III than in CIN I and II.

Adolescent↗

Long-term hyperglycemia is related to peripheral nerve changes at a diabetes duration of 4 years. The Wisconsin Diabetes Registry.

OBJECTIVE: To examine longitudinal hyperglycemia and peripheral nerve responses in a population-based incident cohort. RESEARCH DESIGN AND METHODS: A sample from an incident cohort of young people was comprehensively followed from diagnosis of IDDM. Participants were invited to submit blood samples three times per year for central testing of GHb. During their 4th year of diabetes, nerve conduction studies were performed on the median sensory and motor, peroneal motor, and sural sensory nerves. Relationships between mean GHb and nerve latencies, velocities, and amplitudes were explored. RESULTS: GHb was positively related to all nerve latencies and negatively related to all nerve velocities. The relationships between mean GHb and nerve conduction latencies and velocities differed by sex for the peroneal nerve latency (beta = 0.17 male subjects, beta = -0.01 female subjects; P < 0.001). Pubertal participants had lower velocities and longer latencies than prepubertal participants (beta = 0.37; P = 0.05 peroneal latency), after adjustment for GHb, height, and extremity temperature. Sensory and motor nerve amplitudes were related to GHb, and these relationships did not differ by sex. CONCLUSIONS: Our study indicates that sustained hyperglycemia is related to functional changes, at the minimum, in peripheral sensory and motor nerve conduction at a diabetes duration of 4 years. Our findings are consistent with a dying-back neuropathy, and there is some suggestion that chronic hyperglycemia may be more detrimental to nerves in male subjects than in female subjects.

Adolescent↗

Effects of single and repeated doses of theophylline on aspects of performance, electrophysiology and subjective assessments in healthy human subjects.

The effects of both single and repeated doses of theophylline were evaluated on a battery of nine performance tests, the EEG, the EMG and on subjective assessments of mood and side-effects. The subjects were 20 healthy adults who participated in both phases of this randomized, double-blind, placebo controlled, crossover study. The single dose of 400 mg and the repeated doses of 300 mg b.d. for 4 weeks were intended to attain therapeutic serum concentrations. The Sternberg Additive Factors Method for assessing information processing revealed enhanced performance in both phases of this study, while the Horizontal Addition Test showed improved performance in the single dose phase only. The remaining seven performance tests failed to show significant differences between theophylline and placebo. Single doses of theophylline did not significantly alter mood, but marked adverse effects were encountered in the repeated dose phase, possibly related to unpleasant side-effects. Both EEG and EMG findings indicative of stimulation were associated with a single dose of theophylline, but substantial tolerance developed during 4 weeks of therapy. These findings demonstrate CNS stimulation by both single and repeated doses of theophylline with the occurrence of adverse side-effects during repeated administrations.

Adult↗

Electrophysiological indices of central and peripheral nervous system function during theophylline therapy.

Electrophysiological parameters including the EEG, somatosensory evoked potentials (SEP), F waves, long loop reflexes and peripheral nerve conduction velocities were assessed during the 15th week of theophylline therapy, with serum levels maintained in the low therapeutic range, in young, healthy male volunteers (n = 7). Recordings were repeated 1 week after vitamin B6 supplementation and finally 6-7 weeks after the cessation of medication. Alpha amplitudes were significantly lower during theophylline therapy compared to the posttreatment baseline recording. The SEP findings failed to reveal any significant differences between the three recordings, as was the case with peripheral nerve conduction velocities and long loop reflexes. The average F wave latencies during theophylline therapy were significantly shorter, and the percentage F waves recorded was higher, compared to the baseline recordings. These findings suggest that relatively long-term theophylline therapy has stimulatory effects on aspects of electrical activity in the brain and spinal cord. These effects appeared to be unchanged after vitamin B6 supplementation for 1 week.

Adult↗

Posterior tibial and sural nerve somatosensory evoked potentials in dystrophia myotonica.

Somatosensory evoked potentials (SEPs) were recorded in a group of 18 patients with dystrophia myotonica and in 28 control subjects after stimulating the right and left posterior tibial (SEP-PT) and sural (SEP-S) nerves at the ankles. Recording electrodes were placed in the popliteal fossae, overlying the L3 spinal vertebrae, and at the appropriate scalp sites. In all control subjects and dystrophia myotonica subjects SEP-PT latencies were shorter than equivalent SEP-S latencies, probably reflecting conduction along group I muscle afferents and along slower conducting cutaneous afferents, respectively. Intergroup comparisons revealed prolonged absolute and interpeak latencies in the dystrophia myotonica group, showing both peripheral and central somatosensory pathway involvement. Individual abnormal latencies which exceeded the control group mean plus 3 standard deviations were found in 66% of the dystrophia myotonica group, mainly due to prolonged peripheral conduction times. Results pointed to the concomitant involvement of both the posterior tibial and sural nerve somatosensory pathways in dystrophia myotonica.

Adolescent↗

Poly (d trp-L Leu), poly (D Phe-L Leu) and poly (D Val-L Val-D Val-L Ala) as model polymers for the elucidation of the gramicidin a conformation.

From infrared observations it is concluded that the conformation of poly (D Trp-L leu), poly (D Leu-L Trp), poly (D Phe-L leu) and poly (D val-L Val-D Val-L Ala) wich are model polymers of Gramicidin A is the same as one species of the antibiotic. Diffraction investigations indicate that poly-(D Phe-L Leu) and poly (D Val-L Val-D Val-L Ala) have a helical conformation which is most probably the pi DL 8 helix.

Gramicidin↗

The chemical structure and the crystalline structures of Bombyx mori silk fibroin.

Some recent data (i.e. published in the last ten years) on the chemical and crystalline structures of B. mori silk are reviewed. The main emphasis is put on the crystallizable portion of silk fibroin, including its chemical constitution and its molecular conformation (at the crystallographic unit-cell level) in the two crystalline modifications : the beta pleated sheet and the silk I structures. The structural aspects are based on a discussion of X-ray and electron diffraction data, and on conformational energy analyses of a model (Ala-Gly)n polypeptide of silk fibroin.

Amino Acid Sequence↗

[Enzyme induction in Streptomyces hydrogenans, VI. Studies on the induction of 20beta-hydroxysteroid dehydrogenase, using immunological methods].

Antiserum against crystallized 20beta-hydroxysteroid dehydrogenase from Streptomyces hydrogenans was used for various immunodiffusion and immunoprecipitation tests to show an increase of the de novo synthesis of 20beta-hydroxysteroid dehydrogenase by Streptomyces hydrogenans after cultivation of the cells in the presence of 11beta,21-dihydroxy-4,17(20)-pregnadien-3-one. Half lives of mRNA for 20beta-hydroxysteroid dehydrogenase in induced cells and of total mRNA in non-induced cells were calculated to be 126 s and 66 s, respectively. In vivo, 20beta-hydroxysteroid dehydrogenase appears to consist of four equal subunits. The monomers, molecular weight of 27 300, show a high tendency to form dimers and tetramers in the absence of dissociating agents. The aggregation is completely reversible in the presence of increasing concentrations of sodium dodecylsulfate.

Animals↗