Appropriately sized arteries in small animals may be possible models for studying the remodeling process as occurs after arterial balloon injury in humans. Magnetic resonance imaging (MRI) is able to noninvasively image tissue in vivo. To date, small animal angiog raphy models have mostly used research-dedicated instruments and resolution, which are not universally available.Experiments were carried out on a rat aorta model of remodeling in vivo (n=40). Arteries were injured by oversized balloon dilation; control arteries were uninjured. Angiography imaging was performed immediately before sacrifice with an unmodified clinical MRI unit, a 1.5 Tesla MR tomograph with a 20-cm-diameter coil. Longitudinal MRI pictures of the aorta and morphometry of tissue sections to measure luminal and arterial wall areas were analyzed with use of computer-assisted techniques.Comparison of dimensions demonstrated correlation between MRI and histology measurements of the lumen. MRI and morphometry showed a gradual increase in mean luminal area over 6 weeks following injury. The lumen increase correlated with total arterial area and thickness.In this rat aorta model, remodeling documented at histology was followed-up in vivo. The use of such clinical MRI scanners has potential to reduce animal numbers needed to follow-up the remodeling process after therapeutic intervention.

Relapsing polychondritis (RP) is an extremly rare multisystemic disease thought to be of autoimmune origin. In order to assess if RP is associated with anti-phospholipid antibodies (aPL), clinical data and sera of 21 patients with RP were collected in a multicentre study. Concentration of anti-cardiolipin antibodies (aCL) (IgG-, IgM-and IgA-isotypes), anti-phosphatidylserine-antibodies (aPS) (IgG-and IgM-isotypes) and anti-β-2-glycoprotein I-antibodies (aβ2 GPI) were measured by ELISA. In eight patients aCL were found to be elevated. One patient had elevated aPS. No patient had elevated aβ2 GPI. No patient had clinical signs and symptoms of a aPL syndrome. Interestingly, the two RP patients with the highest aPL had concomitant systemic lupus erythematosus (SLE). Therefore the presence of elevated aPL in RP is probably more closely related to an associated SLE than to RP itself. There is no convincing evidence that aPL are associated with RP.

Background and Objectives: We tested dried blood from an ABO bedside test card which had been stored at room temperature for 12 years, to prove that a patient with HIV-1 infection had been infected by blood transfusion. Materials and Methods: Immunoblots for HIV-1 antibodies and threefold PCRs with half-nested primers for the HIV-1 integrase gene were done with eluates from the dried blood spots. Results: HIV-1 antibodies and HIV-1 DNA could be detected in the sample from one unit of blood, but not from the two other units or from the recipient before transfusion. Conclusion: Further studies should be done on the validity of stored dried blood as an alternative to the storage of frozen donor serum for several years for `look-back' studies.

Bei 44 Herztransplantierten wurden präoperativ und bis zu einem und drei Jahre postoperativ psychiatrisch/psychologische Untersuchungen durchgeführt und psychosoziale Daten erhoben. Die Prädiktoren und Kriterien für eine gute Prognose wurden ihrer Rangfolge nach hierarchisiert. Es ergab sich folgende Prädiktorrangfolge: 1. die eindeutige Motivation und der unauffällige psychopathologische Befund, 2. der gute soziale Rückhalt und die vor der Transplantation zum Ausdruck gebrachte positive Berufsperspektive, 3. das Bewußtsein der Geborgenheit durch die Familie und die reife psychologische Verarbeitung der Herzerkrankung und der bevorstehenden Herztransplantation, 4. der fortgeschrittene Schweregrad der Herzerkrankung (Schweregrad IV NYHA), 5. der relativ geringe Fernsehkonsum (weniger als an 4 Abenden), und 6. u. a. noch lebende Eltern und das Vorhandensein von Kindern. Für die 7 prognostischen Kriterien ließ sich folgendeKriterienrangfolge ermitteln: 1. die soziale Reintegration, 2. die Lebenszufriedenheit, 3. die Compliance und der psychopathologische Befund, 4. die berufliche Rehabilitation, und 5. die körperliche Belastbarkeit und der körperliche Zustand. Die Studie zeigt, daß es eine unterschiedliche Gewichtung psychosozialer Faktoren vor und nach der Herztransplantation gibt, und daß die soziale Reintegration der beste Indikator für eine erfolgreiche Herztransplantation ist.

Photosensitivity and induction of skin lesions following UV radiation is a common problem of patients with cutaneous and systemic forms of lupus erythematosus. The detrimental effect of UV radiation to patients with lupus erythematosus was already recognized in the last century. Skin lesions can now be provoked under standardized conditions allowing the diagnosis and classification of patients with photosensitive disorders. The aim of this review is to give an overview on the history, test procedure and test results in patients with lupus erythematosus.

FORPXL is a software interface that provides programs written in Fortran with a convenient and easily expandable access to the versatility of PXL, the C-based Psychological Experiments Library (Irtel, 1992).

R_Contrast is a program for the rapid assessment of recognition contrast thresholds on the PC.

Two patients with retroorbital pain syndromes with or without paresis of cranial nerves developed weeks after ipsilateral headache resembling chronic paroxysmal hemicrania (CPH) but without autonomic features. These findings might support the hypothesis that CPH may be caused by a pathological process in the region of the cavernous sinus, as has been proposed for the Tolosa-Hunt syndrome (THS).

Phenotyping of cytokeratin (CK) 18-positive cells in bone marrow is gaining increasing importance for future prognostic screening of carcinoma patients. Urokinase-type plasminogen activator receptor (uPA-R) is one example of a potential aggressive marker for those cells. However, a valid and reliable double staining method is needed. Using monoclonal antibodies against uPA-R and CK18, we modified an immunogold/alkaline phosphatase double staining protocol. UPA-R/CK18-positive tumor cell controls exhibited black uPA-R staining in 15–80 of cases and red CK18 staining in almost 100 of tumor cells. Isotype- and cross-matched controls were completely negative. Bone marrow from healthy donors was always CK18-negative. Reproducibility of CK18-positive cell detection was estimated in a series of specimens from 61 gastric cancer patients comparatively stained with the single alkaline phosphatase-anti-alkaline phosphatase (APAAP) and our double staining method (106 bone marrow cells/patient). In four cases, double staining could not reproduce CK18-positive cells. In 34 cases it revealed fewer or equal numbers, and in 23 cases more CK18-positive cells than the APAAP method. Overall quantitative analysis of detected cell numbers (838 in APAAP, range 1–280 in 106; double staining 808, range 0–253) demonstrated relative reproducibility of APAAP results by double staining of 97. Correlation of results between both methods was significant (p<0.001, linear regression). Sensitivity of double staining tested in logarithmic tumor cell dilutions was one CK18-positive cell in 300,000. Specific uPA-R staining was seen on CK18-positive cells in bone marrow from 29 of 61 patients, and also on single surrounding bone marrow cells. To test the specificity of this staining, bone marrow cytospins from 10 patients without tumor disease were stained for uPA-R with the APAAP method. uPA-R expression was confirmed in all 10 cases, with a mean of 6.5 uPA-R-positive cells in 1000 bone marrow cells (SEM 1.2). These results suggest that our double staining protocol is a sensitive, reproducible, and specific method for routine uPA-R phenotyping of disseminated CK18-positive cells in bone marrow of carcinoma patients.

A total of 74 human skin wounds were investigated and collagen types I and VI were localized in the wound area by immunohistochemistry. Collagen type I appeared in the form of ramifying string-like structures after approximately 5–6 days, but positive reactions in the form of a spot-like staining around isolated fibroblasts also occurred in a skin wound aged 4 days. Collagen VI was detectable after a post-infliction interval of at least 3 days showing a strongly positive reacting network associated with fibroblasts in the wound area. Both collagens appeared almost constantly after a wound age of 6–7 clays and could also be found in wounds aged a few months. Therefore, although a positive reaction for collagen type I in the form of string-like and ramifying structures around wound fibroblasts indicates a wound age of at least 5–6 days, a spot-like positive staining for collagen type I cannot exclude a wound age of at least 4 days. A positive staining for collagen type VI represents a post-infliction time of 3 days or more. The almost constant appearance of these collagen types suggests that negative results in a sufficient number of specimens indicate a wound age of less than 6–7 days, but cannot completely exclude longer post-infliction intervals. Since collagen type I and VI are also found in the granulation/scar tissue of lesions with advanced wound age, the immunohistochemical analysis of these proteins provides no further information for an age determination of older skin wounds.

Confirmation of the diagnosis of GH deficiency in adults and children involves provocative testing for human (h) GH. Different commercially available immunoassays yield largely discrepant results in the measurement of GH levels in human serum. These discrepancies result in doubtful relevance of cut-off levels proposed for GH provocative testing. We have developed an immunofunctional assay method that allows quantitation of only those GH forms in circulation that possess both binding sites of the hormone for its receptor and thus can initiate a biological signal in target cells. An anti-hGH monoclonal antibody recognizing binding site 2 of hGH is immobilized and used to capture hGH from the serum sample. Biotin-labeled recombinant GH-binding protein in a second incubation step forms a complex with those hGH molecular isoforms that have both binding sites for the receptor. The signal is detected after a short third incubation step with labeled streptavidin. The assay is sensitive (detection range, 0.1-100 micrograms/L) and has average inter- and intraassay precisions of 10.3% and 7.3% respectively. Endogenous GH-binding protein does not interfere with the hGH result; placental lactogen slows no detectable cross-reaction in this immunofunctional assay. The degree of immunofunctionally active hGH forms in serum samples, calculated by comparison of immunofunctional assay and RIA results, varied between 52-93%. We propose this immunofunctional assay for GH measurement as a new reference method for hGH quantitation in serum. The immunofunction assay translates only hGH forms into an assay signal that are capable of dimerizing GH receptors and, thus, of initiating a biological effect in target cells.

Human observers were trained to criterion in classifying compound Gabor signals with sym- metry relationships, and were then tested with each of 18 blob-only versions of the learning set. General- ization to dark-only and light-only blob versions of the learning signals, as well as to dark-and-light blob versions was found to be excellent, thus implying virtually perfect generalization of the ability to classify mirror-image signals. The hypothesis that the learning signals are internally represented in terms of a 'blob code' with explicit labelling of contrast polarities was tested by predicting observed generalization behaviour in terms of various types of signal representations (pixelwise, Laplacian pyramid, curvature pyramid, ON/OFF, local maxima of Laplacian and curvature operators) and a minimum-distance rule. Most representations could explain generalization for dark-only and light-only blob patterns but not for the high-thresholded versions thereof. This led to the proposal of a structure-oriented blob-code. Whether such a code could be used in conjunction with simple classifiers or should be transformed into a propo- sitional scheme of representation operated upon by a rule-based classification process remains an open question.

A severe vasculitis, probably therapy related, in a sixty-four-year-old man being treated for possible subacute bacterial endocarditis, was associated with the development of transverse myelitis. It is hypothesized that the vasculitis affected the small vessels to the spinal cord in the same way that systemic vasculitis can also cause a transverse myelitis.

Nongenomic in vitro effects of aldosterone on the sodium-proton antiport and intracellular second messengers have been described in human mononuclear leukocytes, vascular smooth muscle cells, and endothelial cells. To test the potential physiological relevance of these effects, an in vivo 31P magnetic resonance spectroscopy study on the human calf at rest and during exercise was performed in 10 healthy volunteers receiving either 1 mg aldosterone or placebo iv in a double blind, randomized, cross-over trial. Spectra were analyzed for phosphocreatine, ATP, phosphomonoesters, inorganic intracellular phosphate, and intracellular pH. Resting values remained unchanged by aldosterone. After isometric contraction of the calf (50% body weight for 3 min), phosphocreatine recovered to significantly higher levels after application of aldosterone compared with placebo. Other parameters were not significantly changed by aldosterone. Effects appeared immediately after isometric contraction and, thus, occurred within 8 min of aldosterone administration. They are, therefore, likely to represent the first contemporary evidence of nongenomic in vivo effects of aldosterone in man. These findings also point to an involvement of aldosteron in the acute stress adaptation of cellular oxidative metabolism in human muscle physiology.

Autosomal recessive mutations in the 17 beta-hydroxysteroid dehydrogenase 3 gene impair the formation of testosterone in the fetal testis and give rise to genetic males with female external genitalia. Such individuals are usually raised as females, but virilize at the time of expected puberty as the result of increases in serum testosterone. Here we describe mutations in 12 additional subjects/families with this disorder. The 14 mutations characterized to date include 10 missense mutations, 3 splice junction abnormalities, and 1 small deletion that results in a frame shift. Three of these mutations have occurred in more than 1 family. Complementary DNAs incorporating 9 of the 10 missense mutations have been constructed and expressed in reporter cells; 8 of the 9 missense mutations cause almost complete loss of enzymatic activity. In 2 subjects with loss of function, missense mutations testosterone levels in testicular venous blood were very low. Considered together, these findings strongly suggest that the common mechanism for testosterone formation in postpubertal subjects with this disorder is the conversion of circulating androstenedione to testosterone by one or more of the unaffected 17 beta-hydroxysteroid dehydrogenase isoenzymes.

1 Contrary to established metabolic pattern, a recent investigation of NNK metabolism produced in rat urine higher levels of 4-(methylnitrosamino)-1-(3-pyridyl)-1- butanone (NNK) and 4-(methylnitrosamino)-1-(3-pyri dyl)-1-butanol (NNAL) than their N-oxides, suggesting that reconversion of N-oxides could occur after urine formation. 2 To verify the possible role of bacteria in the reduction of NNK-N-oxide and NNAL-N-oxide to their respective parent compounds, NNK and NNAL, in smokers with urinary tract infection (UTI), the N-oxides were isolated from the urine of rats treated with 5-3HNNK and individually incubated at 37°C with ten bacterial species in sterile human urine under different pH regimens. After incubation with the bacteria, aliquots of culture media were analyzed by high pressure liquid chromatography (HPLC) with radiochemical detection. 3 Escherichia coli, Enterobacter cloacae, Klebsiella pneumoniae and Proteus mirabilis possessed varying capacity to regenerate NNK and NNAL from their N- oxides while others showed no detectable reductive capability within 24 h. 4 This result constitutes the first experimental evidence that in tobacco users with concomitant UTI, bacterial regeneration of the procarcinogenic NNK and NNAL from their N-oxides could occur in the bladder leading to increased carcinogen burden in these individuals.