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Biomedical subjects

G Ludwig

Publications and source records attributed to G Ludwig.

At least 19 recordsLinked to original sources

Clinical, physiologic, and pathologic evidence for vagus dysfunction in a case of traumatic brain injury.

A trauma victim with locked-in syndrome demonstrated severely decreased bowel sounds, intact response to suppository, and elevated, but unchanging pulse. Absent cardiac response to tracheal suctioning, high gastric residual volumes, and pulmonary edema in response to a urecholine challenge demonstrated dysfunction in the automatic system. Symptoms persisted for 2 1/2 years until death. At autopsy, asymmetric bilateral involvement of the dorsal motor nucleus of the vagus and of the nerve tract in the medulla were demonstrated. In contrast, a control subject with locked-in syndrome caused by a stroke did not demonstrate these phenomena. In trauma patients with delayed gastric emptying, measurement of the heart rate response to deep suctioning may lead to the diagnosis of this vagus dysfunction syndrome.

Adult

Enhancement of protective immune responses to Venezuelan equine encephalitis (VEE) virus with microencapsulated vaccine.

Venezuelan equine encephalomyelitis (VEE) virus is a mosquito-borne arbovirus of major human health significance in the New World. Currently two forms of VEE virus are used for immunization of humans and horses, i.e. a live attenuated and a formalin-inactivated vaccine. Clinical evidence suggests that these vaccines are not fully efficacious and may produce certain undesirable side-effects. In the present study, microspheres composed of biocompatible and biodegradable poly (DL-lactide-co-glycolide) (DL-PLG) were evaluated for their effectiveness as a delivery system of whole, inactivated VEE virus vaccine for the induction of protective immune responses. Mice receiving 50 micrograms VEE virus in microspheres composed of an equimolar ratio of DL-lactide and glycolide (50:50 DL-PLG) exhibited a primary circulating IgG antibody response which was approximately 32-times higher than the response induced with the same dose of unencapsulated (free) virus. A similar difference in responses was seen with antigen doses ranging from 3.1 to 50 micrograms. A rapid increase in antibody activity was seen after the secondary immunization (day 50). Formalin fixation of inactivated VEE virus was important for immunogenicity since the circulating anti-VEE virus antibody response induced with microencapsulated nonformalin-fixed virus vaccine was lower than that induced with microencapsulated formalin-fixed virus vaccine. Furthermore, at low antigen concentrations, DL-PLG microsphere vaccines prepared with the solvent methylene chloride induced higher antibody responses than those prepared using ethyl acetate as the solvent. Microencapsulated vaccine also induced higher VEE virus neutralization titers than did free virus vaccine. Finally, the microencapsulated virus was more effective than the free virus in inducing immune responses protective against systemic challenge with virulent VEE virus. These results demonstrate that DL-PLG microspheres containing formalin-fixed, inactivated VEE virus were effective in augmenting circulating IgG antibody levels and neutralization titers to the VEE virus following systemic immunization and in affording enhanced protection against systemic challenge with virulent VEE virus. The effects of antigen form and the microsphere processing solvent on the immunogenicity of the vaccine are discussed.

Adjuvants, Immunologic

Sclerosis of the skin in the GEMSS syndrome. An overproduction of normal collagen.

BACKGROUND: We describe a recently observed set of autosomal dominant GEMSS (glaucoma, lens ectopia, microspherophakia, stiffness of the joints, and shortness) syndrome in a 47-year-old woman and her 23-year-old son. In addition, sclerosis of the skin, from which both patients suffered, is investigated in detail. OBSERVATIONS: The histologic examination of skin biopsy specimens obtained from the upper aspects of the backs of both patients revealed a markedly thickened dermis. Immunohistochemical examination of the dermal collagen bundles showed a collagen pattern similar to systemic sclerosis and normal control skin. In situ hybridization showed a markedly enhanced gene expression of transforming growth factor beta 1. CONCLUSION: The sclerotic skin changes in GEMSS syndrome are the result of an abnormally increased production of normal collagen that might be attributable to the enhanced in situ production of transforming growth factor beta 1.

Abnormalities, Multiple

XDJ1, a gene encoding a novel non-essential DnaJ homologue from Saccharomyces cerevisiae.

The gene encoding a novel DnaJ-like protein, termed Xdj1, has been identified by amplification of Saccharomyces cerevisiae genomic DNA. An open reading frame of 1380 bp was detected. Disruption of XDJ1 did not yield any detectable new phenotype. A double-deletion strain containing a disruption of both XDJ1 and YDJ1, another gene coding for a DnaJ-like protein, was still viable. Under a variety of growth conditions, no XDJ1 transcripts could be detected by Northern blot analysis and no translation product was found by immunoblotting with antibody against Xdj1 produced in Escherichia coli. Thus, XDJ1 is either expressed only under very specific conditions or represents a silent gene.

Amino Acid Sequence

Frequency response of PVDF needle-type hydrophones.

This paper examines the factors governing the frequency response of ultrasonic polyvinylidene fluoride (PVDF) polymer needle-type hydrophones, in particular the sensitivity variations in the lower frequency range of 1-6 MHz. A theoretical model was used to analyze the influence of the hydrophone's diameter, the metal electrodes, thickness, PVDF material properties, the adhesive layer acoustical characteristics and the backing material, on the frequency response of the hydrophone. The results of the theoretical modelling differ by less than +/- 0.5 dB from those obtained experimentally from the reciprocity calibration in the frequency range 1-20 MHz. It is shown that the needle hydrophone's diameter and backing material are the main reasons for the sensitivity variations observed in the frequency range below 6 MHz.

Acoustics

The influence of spatial polarization distribution on spot poled PVDF membrane hydrophone performance.

The influence of spatial polarization distribution on spot poled PVDF membrane hydrophone performance was calculated and then experimentally verified using a one-dimensional model based on acoustic wave propagation through a layered medium. It is shown that the sensitivity of the hydrophone is markedly dependent on the spatial polarization distribution. It is also shown that there can be a significant difference between the voltage sensitivities measured in the same hydrophone probe depending on which electrode is actually facing the acoustic source. The measurements carried out in the frequency range 1-20 MHz indicate that this difference, while negligible below 2 MHz, may exceed 1.6 dB at higher frequencies. The model developed can also be used to determine the "effective" piezoelectric constant d33 of the PVDF material as a continuous function of frequency. Moreover, the model predicts the existence of a negative slope in the frequency response of the spot poled membrane hydrophone. The experimental confirmation of this prediction underscores the importance of using swept frequency methods during calibration measurements.

Electricity

Evaluation of conservative therapeutic approaches to Peyronie's disease (fibrotic induration of the penis).

Conservative approaches to the treatment of Peyronie's disease are limited. Irradiation is of no value because the efficacy has not been proven and it may cause tissue damage requiring or hampering subsequent surgery. Vitamin-E therapy is ineffective and is also not recommended. p-Aminobenzoate treatment has to be discontinued because of intolerance in one third of the cases, and the response rate is not superior to that of a placebo. Local infiltration of the plaques with orgotein (Peroxinorm) results in a marked improvement in just under 50% of cases and is therefore a justified approach in the early stages of the disease. It is, however, unclear how great the placebo effect and the spontaneous remission rate are. Surgery suited to the individual case must be considered in patients with severe angulation of the penis rendering introitus impossible, calcium deposits, or worsening of the condition despite injections of Peroxinorm.

4-Aminobenzoic Acid

Androgen dependence and tissue specificity of renin messenger RNA expression in mice.

Testosterone, a steroid hormone which increases blood pressure by hitherto unknown mechanisms, is known to induce renin synthesis in the submandibular gland (SMG) of mice. Since renin as well as all other components of the renin-angiotensin system are present in organs important for cardiovascular control, e.g. the kidney, heart, adrenal gland and brain, it is of interest to study the effect of testosterone on renin gene expression in these organs. Renin messenger (m) RNA concentrations were measured by a solution hybridization assay using a 32P-labeled mouse SMG renin complementary (c) RNA as a radioactive probe (detection limit: 1 pg renin mRNA). Measurements were performed after 2 h and after 2, 7, 14 and 21 days of dihydrotestosterone (DHT) treatment in female NMRI mice. Renin mRNA concentration (values are expressed as pg renin mRNA/ micrograms total RNA) in the SMG was significantly increased after 7 days (108 +/- 22 in controls versus 630 +/- 101 in DHT-treated mice), after 14 days (83 +/- 15 in controls versus 743 +/- 83 in DHT-treated mice) and after 21 days (107 +/- 30 in controls versus 579 +/- 76 in DHT-treated mice), but did not reach levels found in untreated male NMRI mice (1021 +/- 84). In the kidney, a decrease was observed within 21 days, from 43 +/- 4 and 40 +/- 4 to 29 +/- 2 and 22 +/- 1.7 pg/micrograms in controls and DHT-treated groups, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands

[Diagnostic imaging in male reproductive medicine].

Imaging methods are essential in the diagnosis of erectile dysfunction. With sonography the penile cavernous tissue and the deep arteries can be shown. This visualization is optimized by high-resolution ultrasonography with pulsed Doppler spectrum analysis or angiodynography. Pharmacocavernosonography combined with pharmacocavernosometry is the method of choice to verify pathologic venous leakage from the penis. Phalloarteriography is absolutely necessary before surgery for revascularization of the penis. In investigations of fertility sonography of the scrotum only plays a subordinate role, as an occlusion of the epididymis cannot be diagnosed in this way. In contrast, good visualization of any small intraparenchymous tumor of the testicle is possible. Transrectal sonography allows the best assessment of the vesicular glands. A persisting varicocele is visualized by retrograde phlebography of the internal spermatic vein. Antegrade phlebography of the spermatic vein with Valsalva maneuver is used by some workers in preference to the above-mentioned method, but has not yet been fully evaluated. Scrotal thermography can visualize a varicocele in a satisfactory manner. Obstacles to ejaculation can sometimes be visualized with retrograde urethrography and/or voiding urethrography. Focused x-rays of the sella turcica are necessary if there is any suspicion of a prolactinoma. Mammography will help to differentiate between gynecomasty and alimentary pseudo-gynecomasty. CT and NMR are used to diagnose tumors of the adrenal and pituitary glands; these methods are rarely used to diagnose abdominal cryptorchidism. Radiologic representation of the ductus deferens with contrast medium (vasography) now has to be rejected as harmful and obsolete.

Diagnosis, Differential

How safe is the treatment of impotence with intracavernous autoinjection?

Intracavernous administration of papaverine and phentolamine has become an essential and indispensible element in the diagnosis and treatment of erectile dysfunction. This paper assesses the frequency and meaning of the main side effects of intracavernous injections (prolonged erections, fibrosis, etc.). It is concluded that the benefit from this new method definitely exceeds the possible risks. However, for the safe implementation of this method, close and intensive cooperation between the physician and his patient is a condition that has to be guaranteed. Each patient carrying out autoinjection therapy has to be examined at reasonable intervals to evaluate the to date unknown effects of long-term therapy.

Drug Combinations

Angiotensinogen gene expression in extrahepatic rat tissues: application of a solution hybridization assay.

Angiotensin II has numerous biological effects in a hitherto unsuspected variety of tissues. The generation of angiotensin in tissue requires the local presence of its high molecular weight precursor angiotensinogen and is best tested by investigating angiotensinogen gene expression. A quantitative solution hybridization assay for rapid and sensitive measurement of angiotensinogen mRNA was therefore established to study the extrahepatic expression of the angiotensinogen gene. We used a 714 bases BamHI angiotensinogen cDNA fragment cloned into vector pSPT18 and developed a sensitive and rapid assay with a detection limit of 0.5 pg RNA. Quantification of angiotensinogen mRNA from male Sprague-Dawley rats resulted in the following tissue levels (n = 10 for all tissues, except pituitary where n = 5), was expressed as fg mRNA per microgram total RNA, in descending order: liver (9950), hypothalamus (6050), midbrain (4450), brainstem (3950), total brain (2325), aorta (625), kidney (338), adrenal gland (170), and heart atrium (140). The high sensitivity of the assay in addition also allowed for the first time measurement of angiotensinogen mRNA in the low gene expression tissues pituitary (70), heart ventricle (30), and testis (30). This assay will allow detailed studies on the regulation of tissue angiotensinogen and the pathophysiological role of the tissue renin angiotensin systems.

Adrenal Glands

Quantification of renin mRNA in various mouse tissues by a novel solution hybridization assay.

A new solution hybridization assay was established for the measurement of renin mRNA. The assay makes use of a radioactively labelled renin complementary RNA as hybridization probe and allows rapid and sensitive detection of renin mRNA in amounts as low as 0.5 pg. With this assay it was possible to quantify renin mRNA in tissues with low-gene expression such as brain and heart as well as in testis, kidney and the submandibular gland (SMG) of mice. The concentrations in these organs were 0.03, 0.07, 1, 5.2 and 164 pg renin mRNA/micrograms RNA, respectively. These results are in agreement with Northern blotting experiments. The general applicability and ease of the solution hybridization assay described here should greatly improve the rapidity of mRNA measurements in future functional studies.

Animals

Measurement of mRNA by solution hybridization with 32P-labelled single stranded cRNA probe ("SP6 test"). Comparison with a 32P-labelled single stranded cDNA as hybridization probe ("S1 test") for measurement of AVP mRNA.

Radioactively labelled cRNA for the rat AVP gene exon C was synthetized from a pSP64-vector and used for solution hybridization measurement of AVP mRNA ("SP6 test"). For comparison hybridization was carried out with a gel-purified radioactively labelled cDNA probe synthetized by primer extension of AVP gene exon C cloned into an M13mp9 phage vector DNA ("S1 test"). Both tests had a comparable sensitivity of up to 0.2 pg AVP mRNA. Under optimal hybridization conditions kinetics were similar in both tests. The fast and easy preparation of large amounts of labelled cRNA probe and simple determination of absolute amounts of mRNA by saturation kinetics without need of a mRNA standard makes the "SP6 test" an attractive alternative to the known "S1 test". The "SP6 test" should be applicable for a wide variety of genes.

Animals

Renin gene expression in rat tissues: a new quantitative assay method for rat renin mRNA using synthetic cRNA.

A genomic renin exon 9 fragment was subcloned into vector pSPT18 and used for in vitro transcription to obtain 32P-labeled rat renin cRNA. Using this cRNA, we established quantitative solution hybridization and specific Northern blotting assays for renin mRNA. We were able to detect renin mRNA in the kidney, heart ventricle and atrium, brain, testis, and adrenal gland of male rats in the concentrations of 430 +/- 8.1, 110 +/- 1.9, 43 +/- 0.9, 64 +/- 1.1, 47 +/- 0.9 and 11 +/- 0.2 pg mRNA/mg of total RNA, respectively.

Animals