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Biomedical subjects

G Wolf

Publications and source records attributed to G Wolf.

At least 235 records · Page 13Linked to original sources
PubMed1998

Expression of hypothalamic peptides in mice lacking neuronal nitric oxide synthase: reduced beta-END immunoreactivity in the arcuate nucleus.

The gas nitric oxide (NO) is an important messenger in brain signaling. Along with many other functions, NO is thought to influence the expression and/or release of various hypothalamic hormones (corticotropin-releasing hormone (CRH), gonadotropin-releasing hormone (GnRH) and vasopressin). To learn more about the role of NO in neuroendocrine mechanisms, we studied in mutant mice lacking neuronal isoform of NO synthase (nNOS) the cellular expression of CRH, neurophysin (the carrier protein of vasopressin/oxytocin) and pro-opiomelanocortin (POMC), as well as of the POMC-derived peptides beta-endorphin (beta-END), alpha-melanocyte-stimulating hormone (alpha-MSH) and corticotropin (ACTH) by use of immunohistochemistry and in situ hybridization. Additionally, the remaining NO-generating capacities of the nNOS minus mice were investigated by NADPH-diaphorase histochemistry and citrulline immunohistochemistry as well as by immunohistochemical localization and Western blot analysis of endothelial NOS (eNOS) and nNOS isoforms. Amongst all hypothalamic peptides under investigation, only beta-END was found to be altered in mutant mice. A morphometric analysis of beta-END producing neurons of the arcuate nucleus revealed that significantly less cells were immunoreactive in mutant mice, whereas the expression of the precursor POMC as well as of other POMC-derived peptides was found to be unchanged. In addition to that, fewer beta-END-immunoreactive fibers were found in the paraventricular nucleus of nNOS minus mice in comparison to wild-type animals. Hence, the reduction of hypothalamic beta-END is probably a posttranslational event that might reflect a disturbed endorphinergic innervation of those hypothalamic neurons which normally express nNOS.

Animals↗
PubMed1998

Link between angiotensin II and TGF-beta in the kidney.

Glomerulosclerosis and tubulointerstitial fibrosis are common morphological correlates of many end-stage kidneys. There is ample evidence that transforming growth factor-beta (TGF-beta) plays a major role in these alterations by directly stimulating synthesis of many extracellular matrix components and reducing collagenase production, finally leading to renal scarring. Although many factors may induce TGF-beta expression in the kidney, one very interesting aspect is the link between angiotensin II (ANG II) and TGF-beta. Originating from observations in vascular smooth muscle cells, there are now several additional studies showing that ANG II stimulates TGF-beta expression in the kidney. Although cell culture studies have convincingly demonstrated that the vasoactive peptide directly stimulates transcription as well as bioactivation of TGF-beta, the in vivo evidence is more indirect. Nevertheless, there are several pathophysiological situations including unilateral ureteral obstruction, chronic cyclosporin A nephrotoxicity, various models of hypertension, and probably diabetic nephropathy in which ANG II-mediated TGF-beta induction has been demonstrated to play an important role in the progression of the disease. The fascinating aspect of this relationship between ANG II and TGF-beta is the fact that hemodynamic changes as well as structural changes are linked together generating a unifying model of progression of chronic renal failure with ANG II as the key player. Angiotensin-converting enzyme (ACE) inhibitor and the more recently introduced AT1-receptor blocker may be potential drugs to interfere with this ANG II-mediated TGF-beta expression. Therefore, these drugs should not only be considered as antihypertensive medications, but should rather be viewed as renoprotective substances influencing renal remodeling by preventing local TGF-beta expression.

Angiotensin II↗
PubMed1998

L-arginine suppresses lipopolysaccharide-induced expression of RANTES in glomeruli.

Endotoxemia leads to the infiltration of inflammatory cells in glomeruli and the tubulointerstitium of the kidney. The ultimate mechanisms for this infiltration, however, are not entirely clear. In this study, the glomerular formation of the chemokine RANTES (regulated upon activation normal T cell expressed and secreted) was examined in an in vivo model of endotoxemia to evaluate the role the local release of chemokines might play in the regulation of this inflammatory cell infiltrate. Since the beneficial effects of nitric oxide (NO) on immune-mediated tissue injury have been reported, we also examined possible interactions between the chemokine RANTES and the L-arginine/NO pathway. To induce endotoxemia, rats were injected intraperitoneally with lipopolysaccharide (LPS). Glomeruli were isolated over a 24-h time period, and RANTES was assessed by Northern blotting, a chemotactic assay, and a specific enzyme-linked immunosorbent assay. The chemokine release was associated with increased glomerular infiltration of monocytes/macrophages. LPS also stimulated the mRNA expression of inducible NO synthase and increased the release of nitrite into the supernatants of isolated glomeruli. Supplementation of L-arginine intake increased the release of glomerular nitrite and reduced glomerular RANTES expression after the injection of LPS. Inhibition of the L-arginine/NO pathway by the unspecific NO synthase inhibitor N(G)-nitro-L-arginine methylester significantly increased glomerular RANTES mRNA expression and the number of infiltrating glomerular macrophages. These data demonstrate that L-arginine suppresses glomerular RANTES formation and suggest that the chemokine-mediated recruitment of glomerular macrophages in LPS-induced endotoxemia can be modulated by the L-arginine/NO pathway.

Animals↗
PubMed1998

Regulation of glomerular TGF-beta expression in the contralateral kidney of two-kidney, one-clip hypertensive rats.

Previous studies have demonstrated that angiotensin II stimulates expression of transforming growth factor-beta (TGF-beta) in cultured renal cells. To investigate whether similar mechanisms are operative in vivo, glomerular TGF-beta mRNA expression was investigated in two-kidney, one-clip (2-K 1-C) hypertensive rats. Glomerular TGF-beta1 transcripts were elevated in the clipped kidney 6 d, but not 3 d, after surgery. Later, during the course of the disease (21 to 35 d), TGF-beta1 mRNA was upregulated in contralateral kidneys compared with sham-operated control kidneys. There was no difference in plasma TGF-beta1 levels between 2-K 1-C rats and controls. Treatment with the AT1 receptor antagonist losartan, as well as with triple therapy (hydralazine, reserpine, and hydrochlorothiazide), started 1 d after clipping, significantly reduced systolic BP in hypertensive rats at day 21 after clipping. Both treatments were equally effective in preventing the increase in glomerular TGF-beta1 mRNA and protein expression in the contralateral kidney at day 21. In a second set of experiments, interventional treatment with losartan or triple therapy, starting 14 d after surgery, was investigated. This treatment for 3 wk significantly reduced the increase in TGF-beta1 expression in the contralateral kidney. At day 35 after clipping, considerable glomerular damage and sclerosis were present, mainly in contralateral kidneys. Interventional treatment with losartan or triple therapy partly prevented this glomerular damage of the contralateral kidney. The data demonstrate that TGF-beta1 expression in the contralateral kidney in 2-K 1-C rats is regulated by the increase in systemic BP rather than by direct effects of angiotensin II.

Animals↗
PubMed1998

Evaluation of needle size for breast biopsy: comparison of 14-, 16-, and 18-gauge biopsy needles.

OBJECTIVE: The purpose of our study was to compare the quantity and quality of tissue harvested from breast biopsy when using 14-, 16-, and 18-gauge "long-throw" needles. SUBJECTS AND METHODS: We performed a prospective randomized study in 64 patients with 66 breast lesions. Under stereotactic guidance, passes were made in random order with each of the three biopsy needles in each lesion. Samples were measured for tissue area and scored for their quality. All lesions, including benign and malignant lesions and lesions with and without microcalcifications, were analyzed. Findings of the biopsy samples were compared with the final diagnoses made at surgical excision. RESULTS: In all 66 lesions, 14-gauge biopsy needles obtained significantly larger specimens (14-gauge, 13.14 mm2; 16-gauge, 9.6 mm2; 18-gauge, 6.41 mm2; p < .05) and scored significantly better (14-gauge, 8.37; 16-gauge, 7.56; 18-gauge, 7.14; p < .016) than either of the smaller needles. The results for malignant and benign lesions and for lesions with and without microcalcifications were similar but not equal to the overall results. However, benign lesions and areas with microcalcifications seem to be more problematic for both smaller needles than for 14-gauge needles. CONCLUSION: Our results indicate that the quantity and quality of breast biopsy specimens depend on the needle size. Of the three needle sizes tested, only 14-gauge long-throw biopsy needles can be recommended for breast biopsy.

Biopsy, Needle↗
PubMed1998

Transforming growth factor-beta stimulates urokinase expression in tumor-associated macrophages of the breast.

Recent studies have shown that urokinase (uPA) is an independent prognostic marker in breast cancer. uPA plays a key role in the degradation of tumor matrix and promotes tumor progression. Macrophage expression of uPA appears to be important in this context. Our objective in the present study was to provide evidence that tumor growth factor-beta (TGF-beta) released from breast cancer cells markedly up-regulates uPA expression in tumor-associated macrophages (TAMs). TAMs from 32 breast carcinomas were cultured. Blood monocytes from healthy donors and breast cancer patients as well as tissue macrophages from patients with fibrocystic changes of the breast were also examined. After TGF-beta incubation, uPA levels were tested by ELISA, and uPA mRNA levels were determined by Northern blot analysis. TGF-beta receptor and uPA cell surface fluorescence intensities were determined by flow cytometry; TGF-beta receptors were determined by Western blot analysis. Protein kinase-C dependence was also examined, and immunohistochemical stainings for uPA and TGF-beta were performed. We have demonstrated that TGF-beta markedly up-regulates basal uPA expression (mRNA and protein) in TAMs but only modestly increases uPA production in blood monocytes and tissue macrophages. Exposure of macrophages to TGF-beta1 led to a rapid and sustained increase in uPA mRNA levels, which was independent of de novo protein synthesis and completely inhibited by actinomycin D. H7 markedly reduced the ability of TGF-beta to stimulate uPA expression. Likewise, okadaic acid potentiated the ability of TGF-beta to up-regulate macrophage uPA expression. We suggest that TAMs are more responsive to TGF-beta stimulation than are blood monocytes and tissue macrophages because of different TGF-beta receptor densities. TGF-beta stimulates transcription of the uPA gene, increases uPA-mRNA stability, and activates uPA expression via protein kinase-C-dependent mechanisms. The ability of TGF-beta to induce macrophage uPA expression may provide an indirect mechanism by which this growth factor stimulates angiogenesis. It may be, therefore, that TAMs promote tumor progression and tumor angiogenesis.

Breast Neoplasms↗
PubMed1998

Microscope remote control with an Internet browser.

OBJECTIVE: To develop a telemicroscopy system that is independent of specialized hardware and software for microscope remote control. DESCRIPTION OF THE SYSTEM: An automatic microscope mounted on a CCD camera was connected to a computer that fulfills the function of an internet server. Any internet user can access this server and can control the microscope by use of an internet browser with Java support. The system can be tested at http:@amba.rz.charite.hu-berlin.de/telemic. FUNCTION AND APPLICATIONS: The user can move the microscope stage, change the magnification or execute any other microscope operations by pressing buttons of the downloaded telemicroscopy client program. The new microscope images are transferred automatically. Structures of interest within the images can be highlighted and discussed online with other telemicroscopy clients. Any internet browser with Java support, like Netscape or Microsoft Internet Explorer, makes an internet user a telemicroscopy client and thus a possible consultant for telepathology. CONCLUSION: The internet telemicroscope offers new possibilities for telepathology. This development should promote communication between pathologists and may thus increase the quality of diagnosis.

Computer Communication Networks↗
PubMed1998

Enhanced cellular glutathione peroxidase immunoreactivity in activated astrocytes and in microglia during excitotoxin induced neurodegeneration.

The cellular distribution pattern of cellular glutathione peroxidase (GPx) was analyzed immunocytochemically in the normal rat central nervous system (CNS) and following exposure to the excitotoxin quinolinic acid (Quin). In the normal CNS, GPx was localized predominantly to microglia, identified by staining with isolectin B4 or the monoclonal antibody OX-42. Three days after intrastriatal administration of 90 pmoles Quin, GPx immunoreactivity was increased in activated microglia and also in astrocytes costained for glial fibrillary acidic protein (GFAP). Whereas GPx-positive astrocytes were seen predominantly in the environment of the lesion, most intensive immunoreactivity was located in globular-shaped microglia in the lesion core. GPx staining was generally low in neurons and failed to increase its intensity after lesion. In the case of excitotoxin-induced generation of oxygen-derived free radicals, the elevation of GPx levels in microglia, and likewise in activated astroglia, may provide an important mechanism to withstand oxidative stress.

Animals↗
PubMed1998

[Results of stereotactic guidance of breast excisional biopsy versus stereotactic core biopsy in occult breast lesions].

Interventional procedures, whether markings or core biopsies, are very important for clarifying non-palpable breast lesions. Both at present as well as in future--in the age of breast screening--such methods must be used more and more. Although breast screening is not carried out on an organized basis in our country, it is gaining importance. Currently there is a covert screening in progress and women are availing this facility to an increasing extent. Various organisations including the press and audio-visual media have arisen the interest of the population. An increase in diagnostic studies is being flanked by an increase in surgical activity. As a result, on the one hand a larger number of small carcinomas as well as benign lesions are being operated. This has brought the cost-bearers, i.e. all of us, to the limits of what can be done. Surgery costs money. One solution to the problem is preoperative marking which is used in all patients suspected of carcinoma, and the other is core biopsy which is used in lesions that appear benign on X-rays. Radiologically benign lesions are not histological diagnoses. Although a well trained radiologist will make the correct diagnosis in 95 to 98% of cases, the possibility of error is still 2 to 50%. In the light of this knowledge, it would appear logical to operate all apparently benign lesions. However, a more intensive use of bioptic procedures is a solution to this problem. To compare costs: Surgery for clarification of a lesion involves a hospital stay of about 3 days while bioptic studies can be carried out on an outpatient basis. Besides, surgery costs 2 to 3 times more than bioptic studies, depending on the hospital and the bioptic material used. A core biopsy needle costs about two-thirds the price of a rotating cannula. However, it should be emphasized that core biopsy is not a method of treatment and will never be one. It should remain a diagnostic procedure, although small lesions may well be aspirated by this method. The ABBI systems is intended to be a therapeutic method. At present, no final statement can be made about the utility of this procedure.

Biopsy↗
PubMed1998

[Computer-assisted diagnosis in mammography: the R2 ImageChecker System in detection of spiculated lesions].

Because of the rapid development of computer systems for digitalization and image analysis, they play an increasing important role in computer-assisted diagnosis (CAD). Especially in the field of mammography, the early signs of malignancy are relatively uniform and therefore more easily detected by a computer algorithm. In this study, we tested one of the few commercially available systems for the detection of both microcalcifications and suspicious, spiculated solid lesions on 40 cases of proven breast carcinomas. These mammograms were analyzed by three independent observers with and without knowledge of the computer results, respectively. Depending on the time of their radiologic experience, the sensitivity of the observers alone was 92.4%, 86.1% and 82%. With knowledge of the computer interpretation, sensitivity of all three observers rose significantly to 100%, 92.7%, and 95%, respectively. However, due to a high number of false positive results of the computer algorithm (0.4 markers per image), the positive predictive value of the interpretations worsened from 100%, 92.7%, and 95.5% to 86.4%, 97.3%, and 91.1%, respectively. It can be expected that future developments will soon overcome this problem and CAD will become an effective tool in screening mammography.

Adult↗
PubMed1998

[Ultrasound-controlled stereotactic breast biopsy--description and initial clinical results of a new breast biopsy device].

UNLABELLED: The aim of this prospective study was first to describe a new dedicated 3D-ultrasound guided stereotaxic breast biopsy unit and second its specificity, sensitivity, accuracy and positive predictive value (concerning malignant and benign lesions). Technical considerations are noted and discussed. SUBJECTS AND METHODS: 45 women (aged between 20 and 77 years; mean age: 49.73 years) with sonographically suspect breast lesions were assigned to the new biopsy device (Sonopsy, NeoVision Corporation, Seattle). All biopsies were performed by an experienced radiologists (G. Wolf) and the results compared to the surgical biopsies. RESULTS: Sensitivity and accuracy was 93.3%, specificity 100%, the positive predictive value (concerning malignant lesions) 95.4% and (concerning benign lesions) 97.8%. In 9/45 biopsies (20%) complications were noted (1 hematoma, 2 collapses, 5 vasovagale reactions). In 13/45 Cases (28.9%) the suspect lesions were more distinctively, respectively more clearly defined on the conventional/dedicated sonography unit. CONCLUSION: This dedicated unit combines all advantages of sonographic and stereotaxic guided core biopsies. Our results show that this technique is a promising new method for breast biopsy.

Adult↗
PubMed1998

[Stereotactic breast biopsy: comparison of vacuum punch biopsy versus high speed core biopsy].

Since few years a new vacuum-assisted biopsy is used in addition to the common gun-needle biopsy in suspicious lesions of the mamma. Aim of our study was to compare these two techniques in regard to their histological outcome. Retrospectively, 149 of the 1997 performed biopsies and the corresponding operation specimens were evaluated. The biopsied lesions were divided in star-like densities, roundish opacities and different forms of microcalcifications. We found both stereotactical methods very accurate. In vacuum-assisted biopsies more representative material could be obtained in cases of microcalcifications. The better quality of the tissues made the histological result more reliable. In concern to other lesions in the mammogram there was no difference between the two techniques at all. In summary, both stereotactical methods revealed comparable and valuable results whereas in any form of microcalcifications we suggest to apply the vacuum-assisted method.

Biopsy↗
PubMed1998

Angiotensin II is involved in the progression of renal disease: importance of non-hemodynamic mechanisms.

Several recent studies have provided clear evidence that angiotensin-converting enzyme (ACE)-inhibitors slow the progression of renal disease. These effects are mainly independent from a comitant reduction in systemic blood pressure. Thus, angiotensin II (Ang II) exerts other effects on the kidney which are involved in the loss of renal function. Ang II induces proliferation of cultured mesangial and glomerular endothelial cells. Our group was the first to demonstrate that Ang II stimulates hypertrophy of cultured proximal tubular cells. Ang II stimulates bioactivation and expression of transforming growth factor-beta (TGF-beta) in tubular MCT cells. This Ang II-mediated expression of TGF-beta is due to an increase in transcriptional activity. A neutralizing anti-TGF-beta antibody attenuates the Ang II-induced increase in protein synthesis in MCT cells suggesting that the hypertrophy is mediated by synthesis and activation of endogenous TGF-beta. Proximal tubular cells undergoing Ang II-mediated hypertrophy are arrested in the G1-phase of the cell cycle and express typical G1-phase-associated genes. Induction of such G1-phase-associated early growth response genes have been also described in vivo after infusion of Ang II into the renal artery. This G1-phase arrest depends on the induction of the cyclin-dependent kinase (CdK) inhibitor p27Kip1. p27Kip1 expression is stimulated after incubation of LLC-PK1 cells with Ang II or TGF-beta and binds to cyclin D1-CdK4 complexes, inhibits their kinase activity, and hampers G1-phase exit. Ang II stimulates transcription of collagen type IV in MCT cells. In addition to the classical a1 (IV) chain, a3 (IV) collagen, which has normally a restricted localization in the kidney, is also induced. This stimulation is mediated by endogenous synthesis and autocrine action of TGF-beta because a neutralizing anti-TGF-beta antibody as well as TGF-beta antisense oligonucleotides attenuate Ang II-induced collagen type IV transcription and synthesis. In addition, Ang II exerts immunomodulatory effects on the kidney through the induction of chemokines such as MCP-1 and RANTES. In conclusion, Ang II has emerged as a multifunctional acting as a growth factor and a profibrogenic cytokine, and even having inflammatory properties.

Angiotensin II↗
PubMed1997

Differential expression of neuronal and endothelial nitric oxide synthase in blood vessels of the rat brain.

Constitutively expressed isoforms of nitric oxide synthase in the brain comprise the neuronal (nNOS) and the endothelial (eNOS) enzyme. However, they show striking differences in terms of their preferred histological compartments: nNOS is found predominantly in neurons, eNOS preferentially in endothelia. Our study demonstrates, by means of in-situ hybridization, that nNOS mRNA also localizes to the endothelia of pial vessels but not to those of capillaries. eNOS, however, is expressed in brain capillaries and, as shown by immunohistochemistry, likewise in larger blood vessels, but never in neurons or glia. The endothelial expression of nNOS and eNOS was also confirmed by RT-PCR. The differential distribution of NOS isoforms in brain vessels might be explained with their different mode of activation by stimuli affecting only one particular NOS isoform.

Animals↗