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Biomedical subjects

S Wolf

Publications and source records attributed to S Wolf.

At least 109 records · Page 6Linked to original sources
PubMed1999

Indocyanine green guided laser photocoagulation in patients with occult choroidal neovascularisation.

AIMS: To determine whether indocyanine green (ICG) guided laser photocoagulation of occult choroidal neovascularisations (OCNV) is beneficial for patients with occult choroidal neovascularisation secondary to age related macular degeneration (AMD). METHODS: A prospective pilot study was performed in 21 eyes with OCNV secondary to AMD that could be identified extrafoveolarly or juxtafoveolarly in an early ICG angiographic study. Laser photocoagulation was applied to the neovascular membrane identified in the early ICG angiographic study. RESULTS: Visual acuity ranged from 20/400 to 20/20 (logMAR 0.54 (SD 0.29) before and hand movements and 20/30 (logMAR 0.81 (0.69)) at the last follow up after laser photocoagulation. During the follow up (30 (13) months) vision improved in four eyes (two lines), in seven eyes the initial visual acuity could be stabilised (two lines), in five eyes vision dropped moderately (three to five lines), and in five eyes vision decreased severely (six or more lines). Recurrences (seven patients) or persistent CNV (six patients) was observed in 13 patients. CONCLUSION: This preliminary study of ICG guided laser photocoagulation of occult extrafoveal and juxtafoveal choroidal neovascularisations suggests that this technique may improve the visual prognosis of these patients. Further prospective controlled studies are necessary to confirm these data.

Aged↗
PubMed1999

Direct visual resolution of gene copy number in the human photopigment gene array.

PURPOSE: To visualize by direct fluorescent in situ hybridization the entire human visual pigment gene array on single X-chromosome fibers and to compare the results with values obtained by other molecular techniques. METHODS: The size of the opsin gene array on the X-chromosome in eight male subjects was investigated by (i) direct visual in situ hybridization (DIRVISH) on elongated DNA fibers: (ii) quantitation of genomic restriction fragments after Southern blot hybridization; (iii) quantitation of restriction fragment length polymorphism after PCR amplification (PCR/RFLP), and (iv) sizing of NotI fragments by pulsed field gel electrophoresis and Southern blot detection. Each male subject's color vision was assessed by Rayleigh matches on a Nagel Type 1 anomaloscope. RESULTS: The number of genes resolved by the DIRVISH protocol, which ranges from 1 to 6, agrees exactly with the gene array sizes obtained in the same male subjects from pulsed field gel electrophoresis, but differs from the estimates derived from the commonly used indirect Southern blot hybridization and PCR/RFLP quantitation methods. In particular, the PCR/RFLP method overestimates the copy number in all but the smallest arrays. CONCLUSIONS: Visualization of the X-chromosome opsin gene array by DIRVISH provides a new, direct method for obtaining exact copy numbers and helps to resolve the controversy about the range and the average visual pigment gene number in the human population in favor of smaller average array sizes.

Blotting, Southern↗
PubMed1999

Another source of stem cells.

Blood in umbilical cords contains stem cells, which are used to help fight many diseases. Nurses are in a position to ensure that cord blood is not wasted by letting expectant parents know they can donate it or store it for future use by members of their immediate family.

Blood Banks↗
PubMed1999

Correlation between retinal microcirculation and blood viscosity in patients with hyperviscosity syndrome.

Hyperviscosity syndrome leads to vascular disturbances in different organs. In the retina typical ophthalmoscopic changes can be found including dot and blot hemorrhages, retinal and optic nerve head edema, and increased diameter of retinal veins. In this study we examined the retinal microcirculation in patients with hyperviscosity syndrome. Nineteen patients (14 patients with Waldenstroem's macroglobulinemia, two patients with kryoglobulinemia, three patients with plasmacytoma) were examined. All patients underwent a video fluorescein angiography. In all angiograms the arteriovenous passage time (AVP) and the arm retina time (ART) were quantified. In addition, hematocrit (Hct) and plasma viscosity (ETA) were measured. In patients with hyperviscosity syndrome AVP was significantly prolonged in comparison to healthy volunteers (AVP: 2.5+/-1.3 s vs. 1.5+/-0.4 s; p < 0.01). The ART showed no significant differences. Plasma viscosity was doubled in patients as compared with reference values (ETA: 2.57+/-1.5 mPa s vs. 1.24+/-0.08 mPa s; p < 0.01). In this study we showed an increase in plasma viscosity as well as an increase in arteriovenous passage time. This may result in retinal circulatory disturbances and may cause the typical fundus changes in patients with hyperviscosity syndrome.

Adult↗
PubMed1998

B7.1 is a quantitatively stronger costimulus than B7.2 in the activation of naive CD8+ TCR-transgenic T cells.

Using a TCR transgenic mouse bred onto a recombinase-activating gene-2-deficient background, we have examined the influence of B7.1 and B7.2 on activation of naive, CD8+ T cells in vitro. We found that B7.1 was a more potent costimulus than B7.2 for induction of proliferation and IL-2 production by naive CD8+ T cells. This difference appeared to be quantitative in nature, as determined using transfectants expressing various defined levels of B7.1 or B7.2, or using purified B7.1 or B7.2 fusion proteins. In contrast to the quantitative differences seen in stimulation of naive T cells, B7.1 and B7.2 were comparable in their ability to costimulate responses in T cells previously primed in vitro. In addition, primed, but not naive, T cells were capable of proliferating and producing IL-2 in response to a TCR stimulus alone, apparently in the absence of B7 costimulation. Lastly, we found that B7.1 and B7.2 were equivalently capable of driving differentiation of naive CD8+ T cells into an IL-4-producing phenotype when exogenous IL-4 was added to the primary culture or to an IFN-gamma-producing phenotype in the presence of IL-12. These results indicate that signals generated by B7.1 and B7.2 are qualitatively similar, but that B7.1 is quantitatively stronger than B7.2. Further, our results indicate that the activation state of the responding T cell may influence the efficiency with which the T cell can respond to a costimulatory signal provided by either B7.1 or B7.2.

Animals↗
PubMed1998

Bacterial pro-transglutaminase from Streptoverticillium mobaraense--purification, characterisation and sequence of the zymogen.

The zymogen of bacterial transglutaminase was found during cultivation of Streptoverticillium mobaraense (DSMZ strain) using rabbit antibodies raised against the active enzyme. Ion-exchange chromatography at pH 5.0 yielded a highly purified pro-enzyme. Structure information was obtained by means of Edman degradation and analysis of PCR amplified nucleotide fragments. The data revealed an excess of negatively charged amino acids in the pro-region resulting in a decreased isoelectric point of the zymogen. Additionally, the new sequence gave rise to some modifications to the previously published hypothetical structure of prepro-transglutaminase derived from genomic DNA [Washizu, K., Ando, K., Koikeda, S., Hirose, S., Matsuura, A., Takagi, H., Motoki, M. & Takeuchi, K. (1994) Biosci. Biotechnol. Biochem. 58, 82-87]. Inactive transglutaminase, which carries an activation peptide of 45 amino acids, has a calculated molecular mass of 42445 Da. Its pro-region provides for both suppression of activity and increased thermostability. Furthermore, it could be shown that the micro-organism produces a protease which cleaves pro-transglutaminase at the C-side of Pro45. Rapid transformation of the mature enzyme also occurs by addition of other proteases. During conversion, 43 and 41 amino acid peptides are released by bovine trypsin and dispase from Bacillus polymyxa, respectively. The detection of endogenous substrates in the murein layer makes discussion of the physiological role of bacterial transglutaminases necessary.

Amino Acid Sequence↗
PubMed1998

Interleukin 12-mediated prevention of spontaneous mammary adenocarcinomas in two lines of Her-2/neu transgenic mice.

The ability of interleukin (IL)-12 to prevent tumors when administered to individuals with a genetic risk of cancer was studied in two lines of transgenic mice expressing rat HER-2/neu oncogene in the mammary gland. Female BALB/c (H-2(d)) mice carrying the activated HER-2/ neu oncogene show no morphological abnormalities of the mammary gland until 3 wk of age. They then progress through atypical hyperplasia to in situ lobular carcinoma and at 33 wk of age all 10 mammary glands display invasive carcinomas. Adult FVB mice (H-2(q)) carrying the HER-2/neu protooncogene develop mammary carcinomas with a longer latency (38-49 wk) and a lower multiplicity (mean of 2.6 tumors/mice). Treatment with IL-12 (5 daily intraperitoneal injections, 1 wk on, 3 wk off; the first course with 50 ng IL-12/day, the second with 100 ng IL-12/day) begun at 2 wk of age in BALB/c mice and at 21 wk of age in FVB mice markedly delayed tumor onset and reduced tumor multiplicity. Analogous results were obtained in immunocompetent and permanently CD8(+) T lymphocyte-depleted mice. In both transgenic lines, tumor inhibition was associated with mammary infiltration of reactive cells, production of cytokines and inducible nitric oxide synthase, and reduction in microvessel number, in combination with a high degree of hemorrhagic necrosis.

Animals↗
PubMed1998

Carrier-induced, hapten-specific suppression: a problem of antigen presentation?

Prior immunity against a carrier protein has been shown to modulate the serologic response to injected haptens attached to the same carrier. In particular, a carrier/hapten-carrier immunization protocol induces marked suppression for IgG2a anti-hapten Ab production but does not interfere with anti-carrier Ab responses. Although the phenomenon of epitopic suppression has been amply demonstrated, the mechanism underlying the suppression remains unknown. The selective deficiency in IgG2a secretion suggests that IFN-gamma-producing Th1 cells are not properly activated. We and others have shown that the nature of the APCs present during the first encounter with the Ag influences the development of selected Th populations in vivo; dendritic cells (DCs) seem to be required for the induction of primary, Th1-type responses. Since carrier priming induces the clonal expansion of specific B cells that appear to efficiently capture the Ag, we hypothesized that the hapten-carrier conjugate may be presented by B cells in preimmunized animals. Therefore, we immunized mice to the conjugate by injecting syngeneic DCs pulsed in vitro with the Ag. Our data show that an injection of DCs and IL-12 prevents epitopic suppression, suggesting that it may result from defective Ag presentation.

Animals↗
PubMed1998

Expressed sequences as candidates for a novel tumor suppressor gene at band 13q14 in B-cell chronic lymphocytic leukemia and mantle cell lymphoma.

Deletions affecting the interval between the RB1 gene and marker D13S25 at band 13q14 are the most frequent genetic abnormalities of B-cell chronic lymphocytic leukemia (B-CLL) and indicate the presence of a novel tumor suppressor gene in this region. In the current study, a high resolution physical map of fragments spanning one megabasepair (Mb) of genomic DNA at the critical 13q14 segment was constructed. To define the minimal region of loss within the RB1 and D13S25 interval, we screened 322 B-CLLs for deletions at either of the two loci. Thirty mantle cell lymphomas (MCLs) were included in the analysis because we observed a 13q14 deletion pattern similar to B-CLL in this disease. The incidence of 13q14 deletions was 51% in B-CLL and 70% in MCL, respectively. No frequent loss of the BRCA2 gene at band 13q12 was found. Detailed deletion mapping at band 13q14 with probes from the RB1-D13S25 interval lead to the identification of a critical deletion region 400 kb in size. Within this region two segments were most frequently affected, one at D13S272 120 kb in size and another 240 kb distal of D13S272 80 kb in size. From these two segments expressed sequences were identified as candidates for the putative 13q14 tumor suppressor gene involved in the pathogenesis of B-CLL and MCL.

BRCA2 Protein↗
PubMed1998

Characterization of ARC, a divergent member of the AAA ATPase family from Rhodococcus erythropolis.

A gene encoding a AAA ATPase was discovered in the 5' region of the second operon of 20 S proteasome subunits in the nocardioform actinomycete Rhodococcus erythropolis NI86/21. The gene was cloned and expressed in Escherichia coli. The protein, ARC (AAA ATPase forming Ring-shaped Complexes), is a divergent member of the AAA family. The deduced product of the arc gene is 591 residues long (66 kDa). The purified protein possesses a low, N-ethylmaleimide-sensitive ATPase activity and forms rings of six subunits, arranged symmetrically around a central opening or cavity. Two-dimensional crystals grown on lipid monolayers yielded images of the ATPase molecules in "end-on" orientation at 1.9 nm resolution.

Amino Acid Sequence↗
PubMed1998

Ciprofloxacin as a therapeutic modality in pediatric burn wound infections: efficacious or contraindicated?

BACKGROUND: Food and Drug Administration regulations state that ciprofloxacin hydrochloride may cause arthropathies. For this reason, such therapy is contraindicated in the pediatric population. However, several studies in children with cystic fibrosis have found the drug to be efficacious. Our hypothesis was that ciprofloxacin treatment is justified in the case of multiresistant organisms in burn populations. DESIGN: During a 4-year period (January 1, 1993, to December 31, 1997) we treated 56 of our pediatric burn patients with ciprofloxacin when cultures proved resistant to other antibiotics. The burn area was 65% of the total body surface area. The average patient age was 8.4 years. Of the 56 patients who received ciprofloxacin, 50 received the recommended dose. Biopsy specimens were assessed for quantitative bacteriology and antibiotic sensitivity. Radiologic review was conducted to examine for arthropathy. RESULTS: All patients showed unequivocal reduction in quantitative bacterial counts, and susceptibility to ciprofloxacin remained stable without the development of resistance. Of the 56 patients treated, 42 had a major reduction in their quantitative wound biopsies from 10(6) to less than 100 colonies per gram of tissue, while the remaining 14 were observed to have a 2- to 3-log decrease. No arthropathy was detected in any of the 56 patients receiving ciprofloxacin. Review of the patients' charts showed no documented adverse events associated with the use of ciprofloxacin. All patients survived their thermal injury and the complications associated with it without any untoward problems or complications of arthropathy. CONCLUSION: On the basis of these data, ciprofloxacin therapy in the treatment of immunosuppressed pediatric burn patients is efficacious and does not cause arthropathy.

Adolescent↗
PubMed1998

Local tissue properties in bone healing: influence of size and stability of the osteotomy gap.

To characterize the site-specific mechanical and histological properties in fracture repair and to relate these properties to the initial mechanical situation, an experimental fracture model was used in the metatarsus of 42 sheep. The mechanical situation of a transverse osteotomy was described by three gap sizes (1, 2, or 6 mm) and two amounts of strain (7 or 31%). An external fixator that allowed a defined axial movement provided control of these settings. Nine weeks following surgery, the healing area was dissected and tensile and compressive properties were measured in subregions of the fracture gap and the periosteal callus. The central, sagittal section was used for quantitative histology. We found the quality of the tissue along the osteotomy line to be most important for regaining mechanical stability. Increasing the size of osteotomy gaps resulted in poorer mechanical and histological qualities, and the repair process was less complete. Interfragmentary strain did not significantly influence the repair process. The smaller strain levels had already stimulated the secondary repair process, and this stimulatory effect could not be further enhanced by increasing the amount of strain. Our finding that large gaps between bone segments were not as well healed as were smaller gaps suggests that it is advantageous to avoid large gaps in fracture treatment.

Animals↗
PubMed1998

Retinal capillary density in patients with arterial hypertension: 2-year follow-up.

BACKGROUND: Arterial hypertension is known to be an important risk factor for cerebral and cardiovascular disease. Previous studies have demonstrated a decrease of capillary density in the perifoveal network in tandem with decreased capillary flow velocity in patients with essential hypertension. In a prospective study we quantified the retinal microcirculation in order to evaluate the time course of changes in the perifoveal network. METHODS: Thirty-three patients with essential hypertension (mean age 45 +/- 14 years) underwent video-fluorescein angiographic studies at baseline and at 2 years 28 +/- 6 months) thereafter. The angiograms were obtained with a scanning laser ophthalmoscope and were digitally recorded. By means of digital image analysis we quantified off-line the mean area of perifoveal intercapillary areas (PIA) and the mean capillary flow velocity. RESULTS: At baseline, the patients with hypertension showed significantly increased PIA and a significantly decreased capillary flow velocity compared with reference values. During the follow-up period the capillary flow velocity decreased further significantly, whereas the PIA showed no significant change. CONCLUSIONS: The continuous decrease of capillary flow velocity demonstrates a progression of altered microcirculation in patients with essential hypertension whose blood pressure was believed to be well controlled. Further studies with this technique may be useful to determine the influence of antihypertensive therapy and may help to identify patients at risk for cerebrovascular events.

Blood Flow Velocity↗