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Biomedical subjects

V Lindner

Publications and source records attributed to V Lindner.

At least 37 records · Page 2Linked to original sources
PubMed2000

Microscopic venous invasion: a prognostic factor in renal cell carcinoma.

OBJECTIVE: Microscopic venous invasion (MVI) is characterized by local destruction of the endothelium by a tumor. The prognostic value of MVI in renal cell carcinoma (RCC) is not well established. MATERIALS AND METHODS: From 1980 until 1990, 255 patients (169 men and 86 women), aged 16-87 (mean 60) years were treated by radical nephrectomy for N0M0 RCC. There were 9 pT1, 163 pT2, 30 pT3a, 34 pT3b, and 19 pT3ab (TNM 1992). The median follow-up time was 74 months. MVI was determined by a double-blind histological study with immunohistochemical staining. RESULTS: MVI was noted in 74 patients (29%). MVI significantly increased metastatic progression (p = 0.003). Only stage and Fuhrman's grade were significant factors for metastatic progression in a multivariate analysis. MVI decreased the actuarial survival rates at 1 year (p = 0.01), but not significantly at 5 and 10 years. MVI and non-MVI survival curves were statistically different with the Peto/Wilcoxon (p = 0.04) and Gehan/Wilcoxon (p = 0.03) tests, but not with the log rank test (p = 0.06). MVI decreased survival in cases with a tumor size of 10 cm or more, capsular invasion, macroscopic venous invasion, stage pT3ab, sarcomatoid cell carcinoma and Fuhrman's grade IV. Only the stage was a significant factor for survival in a multivariate analysis. CONCLUSION: In RCC, MVI is related to cancer progression and survival, but probably not as an independent prognostic factor.

Adolescent↗
PubMed1999

DANCE, a novel secreted RGD protein expressed in developing, atherosclerotic, and balloon-injured arteries.

We have identified and characterized mouse, rat, and human cDNAs that encode a novel secreted protein of 448 amino acids named DANCE (developmental arteries and neural crest epidermal growth factor (EGF)-like). DANCE contains six calcium-binding EGF-like domains, one of which includes an RGD motif. Overexpression studies of recombinant DANCE protein document that DANCE is a secreted 66-kDa protein. DANCE and recently described protein S1-5 comprise a new EGF-like protein family. The human DANCE gene was mapped at chromosome 14q32.1. DANCE mRNA is mainly expressed in heart, ovary, and colon in adult human tissues. Expression profile analysis by in situ hybridization revealed prominent DANCE expression in developing arteries. DANCE is also expressed in neural crest cell derivatives, endocardial cushion tissue, and several other mesenchymal tissues. In adult vessels, DANCE expression is largely diminished but is reinduced in balloon-injured vessels and atherosclerotic lesions, notably in intimal vascular smooth muscle cells and endothelial cells that lose their ability to proliferate in late stage of injury. DANCE protein was shown to promote adhesion of endothelial cells through interaction of integrins and the RGD motif of DANCE. DANCE is thus a novel vascular ligand for integrin receptors and may play a role in vascular development and remodeling.

Amino Acid Sequence↗
PubMed1999

Soluble transforming growth factor-beta type II receptor inhibits negative remodeling, fibroblast transdifferentiation, and intimal lesion formation but not endothelial growth.

Using the rat balloon catheter denudation model, we examined the role of transforming growth factor-beta (TGF-beta) isoforms in vascular repair processes. By en face in situ hybridization, proliferating and quiescent smooth muscle cells in denuded vessels expressed high levels of mRNA for TGF-beta1, TGF-beta2, TGF-beta3, and lower levels of TGF-beta receptor II (TGF-betaRII) mRNA. Compared with normal endothelium, TGF-beta1 and TGF-beta2, as well as TGF-betaRII, mRNA were upregulated in endothelium at the wound edge. Injected recombinant soluble TGF-betaRII (TGF-betaR:Fc) localized preferentially to the adventitia and developing neointima in the injured carotid artery, causing a reduction in intimal lesion formation (up to 65%) and an increase in lumen area (up to 88%). The gain in lumen area was largely due to inhibition of negative remodeling, which coincided with reduced adventitial fibrosis and collagen deposition. Four days after injury, TGF-betaR:Fc treatment almost completely inhibited the induction of smooth muscle alpha-actin expression in adventitial cells. In the vessel wall, TGF-betaR:Fc caused a marked reduction in mRNA levels for collagens type I and III. TGF-betaR:Fc had no effect on endothelial proliferation as determined by reendothelialization of the denuded rat aorta. Together, these findings identify the TGF-beta isoforms as major factors mediating adventitial fibrosis and negative remodeling after vascular injury, a major cause of restenosis after angioplasty.

Actins↗
PubMed1999

Vascular remodeling in response to altered blood flow is mediated by fibroblast growth factor-2.

Vascular structures adapt to changes in blood flow by adjusting their diameter accordingly. The factors mediating this process are only beginning to be identified. We have recently established a mouse model of arterial remodeling in which flow in the common carotid artery is interrupted by ligation of the vessel near the carotid bifurcation, resulting in a dramatic reduction in vessel diameter as a consequence of inward remodeling and intimal lesion formation. In the present study, we used this model to determine the role of fibroblast growth factor-2 (FGF-2) in the remodeling response by maintaining neutralizing serum levels of a mouse monoclonal antibody against FGF-2 for 4 weeks. Morphometric analysis revealed that intimal lesion formation was not affected by the antibody. However, lumen narrowing was significantly inhibited, resulting in a greater than 3-fold increase in lumen area in anti-FGF-2-treated animals compared with controls. Treatment with anti-FGF-2 antibody significantly inhibited the reduction in vessel diameter (inward remodeling) and shortening of the internal elastic lamina in the ligated vessel. In addition, anti-FGF-2 treatment also caused outward remodeling of the contralateral carotid artery. These findings identify FGF-2 as an important factor in vascular remodeling, and its effects are likely to be mediated by increasing vascular tone. The results are consistent with the recent observation of reduced vascular tone in the FGF-2-deficient mouse.

Animals↗
PubMed1999

Vaccine potential of a recombinant glutathione S-transferase cloned from Schistosoma haematobium in primates experimentally infected with an homologous challenge.

Patas monkeys were twice immunized with a Schistosoma haematobium-derived recombinant glutathione S-transferase (Sh28GST) then challenged with an homologous calibrated challenge. BCG and Freund's Complete Adjuvant (FCA) were used as adjuvants in two distinct protocols. Specific IgG and IgA antibody responses were intense and homogeneous in the animals receiving Sh28GST in the presence of FCA, whereas BCG could only induce moderate and heterogeneous antibody titres. No significant effect on worm burdens was evidenced 36 weeks post-infection in either group of Sh28GST-immunized animals compared to their matched controls receiving an irrelevant protein. Although not significant, 50% reductions in the numbers of eggs located in all tissues (FCA group) and in the urogenital system (BCG group) were noted. Moreover, the total number of excreted eggs was dramatically diminished by 60% and 77% in the BCG and FCA groups, respectively. These reductions reached 75% and 80% in the urines of vaccinated monkeys. Bladder pathology was also reduced in the animals displaying the lowest urinary egg excretions. There was no clear positive or negative correlate between antibody responses and individual levels of protection. Taken as a whole, our results show that Sh28GST was capable of significantly reducing S. haematobium worm fecundity in experimentally infected primates. Although FCA induced higher levels of protection, the efficacy of BCG as an adjuvant appeared sufficient to justify consideration of the future application of this new formulation as a vaccine against human urogenital schistosomosis.

Animals↗
PubMed1999

Isolated renal Aspergillus abscess in an AIDS patient with a normal CD4+ cell count on highly active antiretroviral therapy.

Isolated renal Aspergillus abscess is a very rare complication of HIV infection. It usually occurs in patients with severe immune deficiency. The case of a 29-year-old HIV-infected homosexual male, a nonintravenous drug abuser, who developed a right renal Aspergillus abscess despite normalization of the CD4+ cell count after highly active antiretroviral treatment is described. When antimicrobial treatment failed (amphotericin B followed by itraconazole), he was cured by right nephrectomy and remains in good health 3 months later with no recurrence. In cases of Aspergillus renal abscess in HIV-infected patients, surgery is the treatment of choice, especially in the current era of highly active antiretroviral therapy.

AIDS-Related Opportunistic Infections↗
PubMed1999

Vascular smooth muscle cells express the transcriptional corepressor NAB2 in response to injury.

The early growth response 1 (Egr-1 or NGFI-A) gene product is a zinc finger protein transcription factor which has been implicated in the regulation of genes differentially expressed during the development of vascular disease. Egr-1 activity is regulated by alterations in the amount of protein, as well as protein-protein interactions with positive and negative transcriptional cofactors. NGFI-A-binding protein 2 (NAB2) is an example of a negative transcriptional cofactor capable of binding directly to Egr-1 and repressing Egr-1-mediated transcription. In this study, we show that NAB2 is rapidly and transiently expressed in vascular smooth muscle cells (VSMC) in response to the model agonist phorbol 12-myristate 13-acetate (PMA). This induction occurs at the protein as well as mRNA level, and the time course of induction trails closely behind that of Egr-1. NAB2 expression in VSMC is capable of inhibiting Egr-1 dependent gene expression in response to either PMA or fibroblastic growth factor-2 (FGF-2). In an in vivo model of mechanical arterial injury NAB2 levels also increase transiently in VSMC at a time when Egr-1 is elevated. It is possible that NAB2 is part of a negative-feedback mechanism which serves to down-regulate Egr-1-mediated gene transcription in injured VSMC.

Animals↗
PubMed1999

Cardiac myxoma with glandular component: case report and review of the literature.

A 7 cm diameter tumor of the left atrium is reported in a 78 year-old woman with a past history of pT3N1M0 colonic adenocarcinoma. The histological examination of the atrial tumor disclosed areas of highly vascularized myxoid stroma with cells strongly reactive for vimentin. Multiple mucoid spaces lined by a single layer of goblet cells were scattered among those typical areas of myxoma. No nuclear atypia was observed. Cytoplasm of the glandular cells was immunoreactive for epithelial antisera (keratin, EMA), CEA and CA19.9. Two years later, the patient was doing well, with no local recurrence of the cardiac myxoma and no secondary location of the colonic adenocarcinoma. The histological characteristics, the absence of atypia, the absence of tumoral extension or neoplastic lymphatic vascular thrombi in the pedicle or in the interatrial septum, and the finding of typical myxomatous areas supported the diagnosis of cardiac myxoma with glandular component. To our knowledge, 21 cases of myxoma with glandular mucinous component, focal or prominent, have been previously published in the literature. These myxoma were generally sporadic cases with the same clinical features and prognosis as typical myxoma. Immunoreactivity of these glandular structures was constant for epithelial markers. The positive immunostaining by CEA, and by CA19.9 in our case, reflects the histogenetic endodermal origin.

Aged↗
PubMed1999

Open-labeled long-term study of the efficacy, safety, and tolerability of subcutaneous sumatriptan in acute migraine treatment.

In a multicenter study, a long-term analysis was made of the efficacy, safety, and tolerability of subcutaneous (s.c.) sumatriptan in the acute treatment of migraine attacks over a period of up to 18 months. A total of 2263 patients took part in the study, all able to perform their own acute treatment of migraine attacks at home by s.c. administration of 6 mg of sumatriptan. A headache diary was used by each patient to record the various migraine parameters before the injection and 1 h and 2 h after it. A total of 43,691 attacks were treated and analyzed during the study period from October 1991 to June 1993. Therapy was successful in 89.5% of attacks. Freedom from headache was achieved in 71.0% of cases. In 22.7% of the attacks a second injection was administered on recurrence of the headache; 82.9% of the patients achieved an intraindividual therapy success rate ranging from over 80% to 100%. In the course of treatment there was no change in either the therapy success rate or in the frequency of attacks. Some 4.9% of the patients withdrew from the study because of insufficient efficacy or adverse events. A total of 44.5% of patients reported adverse events, and these were rated serious in the case of 1.7%. S.c. administration of sumatriptan for acute migraine therapy is an effective treatment method, with reliable action, that can be used with good tolerability provided the contraindications are taken into account.

Adolescent↗
PubMed1999

Parathyroid hormone-related protein in rat penis: expression, localization, and effect on cavernosal pressure.

Although PTH-related protein-(1-36) [PTHrP-(1-36)] is known to be expressed in smooth muscle and to exert potent myorelaxant effects, its tonic effects on cavernosal smooth muscle has not yet been explored. Using the RT-PCR technique, the present study establishes that PTHrP messenger RNA is present in microdissected corpus cavernosa in the rat. In immunohistochemical studies using affinity-purified antibodies to middle regions of PTHrP, immunostaining was localized throughout the penile structures, including vessels, cavernosal smooth muscle, and trabecular fibroblasts. Strong immunostaining for PTHrP was also detected in the dorsal nerve bundles. In anesthetized rats, intracavernosally injected boluses of increasing doses of PTHrP-(1-36) (0.3-30 pmol in 100 microl saline) had little effect on intracavernosal pressure. However, they markedly potentiated the dilatory response to papaverine (8-800 nmol), increasing the papaverine-induced intracavernous pressure by 2.5-fold, close to the mean arterial pressure. In conclusion, the cavernosal expression of PTHrP messenger RNA, the distribution of immunoreactive PTHrP throughout the structuro-functional components of the erectile apparatus and its strong potentiating action on papaverine-induced cavernosal relaxation, collectively suggest that PTHrP participates in the control of cavernosal tone.

Animals↗
PubMed1999

[Congenital generalized dropsy and intrapericardial fetal teratoma. Report of a case of prenatal diagnosis].

Intrapericardial teratomas are rare tumors usually occurring in early infancy. Such a case was diagnosed in a 20 week old fetus, with a lethal outcome. About fifteen cases of intrapericardial teratoma have been reported in the fetal period. They are usually symptomatic, with a more or less severe pericardial effusion, sometimes complicated by cardiac compression and/or hydrops fetalis. Prognosis of the prenatally diagnosed pericardial teratomas is more related to the occurrence of hydrops fetalis than to the behavior of the tumor itself. The main interest of sonographic ante-natal diagnosis consists of the possible improvement of hemodynamic consequences through in utero pericardiocentesis. Macroscopic and microscopic features of this cardiac tumor are similar to those of extrapericardial teratomas. Most tumors discovered in fetal period are mature and histologically benign lesions. Only one case showed immature components. The coexistence of a malignant component (germ cell or non germ cell tumor) has been described in the postnatal and adulthood.

Adult↗
PubMed1999

[Retroperitoneal mucinous cystadenoma].

The authors report an unusual case of retroperitoneal mucinous cystadenoma in contact with the isthmus of a horseshoe kidney and associated with congenital absence of the left ovary. The retroperitoneal site is very unusual, as only about twenty cases have been reported in this site. The pathogenesis of these tumours remains unclear and the authors discuss the various hypotheses proposed to date.

Cystadenoma, Mucinous↗
PubMed1999

[Ovarian metastasis of colorectal adenocarcinomas. A clinico-pathological study of 41 cases].

We report a series of 41 ovarian metastases from colorectal adenocarcinomas. The patients'mean age was 57.1 years at the time the metastasis was discovered, and 55.8 years at the time the primary carcinoma was found. The diagnosis of the primary tumour was anterior to the metastasis in 25 cases (mean interval 21 months), simultaneous in 13 and posterior in 3 others. The metastases formed cystic and solid masses with a mean weight of 330 g. The endometrioid architectural type was the most frequent, either pure (71%, 29/41) or associated with a mucinous component (17%, 7/41). Pure mucinous or other architectural types were rare. The endometrioid type was characterized by glands with a garland pattern, and intraluminal dirty tumoral necrosis. Immunohistochemistry helped to distinguish the metastases of endometrioid type from serous or endometrioid primary ovarian carcinoma; 71% of the former were CK7(-)/CK20(+), and 100% of the latter had the reverse profile CK7(+)/CK20(-).

Adenocarcinoma↗
PubMed1998

Increased expression of Axl tyrosine kinase after vascular injury and regulation by G protein-coupled receptor agonists in rats.

Axl is a receptor tyrosine kinase originally identified as a transforming gene product in human myeloid leukemia cells. Cultured rat vascular smooth muscle cells also express Axl, where it has been proposed that Axl may play a role in cell proliferation. In the current study, we tested the hypotheses that Axl expression would parallel neointima formation in balloon-injured rat carotid, and that Axl expression would be regulated by growth factors present at sites of vascular injury. Ribonuclease protection assay showed dynamic increases in Axl mRNA in vessels, with peak expression 7 and 14 days after injury. Immunohistochemical analysis confirmed these results and demonstrated that Axl protein expression was localized primarily to cells of the neointima after injury. Northern blot analysis indicated increased mRNA expression for the secreted Axl ligand, Gas6, in injured carotids, with a time course paralleling that of Axl upregulation. Axl and Gas6 expression were temporally correlated with neointima formation, suggesting a role for Axl signaling in this process. Other studies, performed in cultured rat vascular smooth muscle cells, revealed positive regulation of Axl mRNA expression by thrombin or angiotensin II but not by basic fibroblast growth factor, platelet-derived growth factor-BB, or transforming growth factor-ss1. Western blot analysis confirmed these results, showing that Axl protein expression was specifically increased by thrombin or angiotensin II. Our results implicate Axl as a potential mediator of vascular smooth muscle migration and proliferation caused by vascular injury and G protein-coupled receptor agonists.

Angiotensin II↗
PubMed1998

Increased expression of estrogen receptor-beta mRNA in male blood vessels after vascular injury.

Estrogen exerts direct effects on vascular endothelial and smooth muscle cells that are important for vascular protection. Estrogen receptor-alpha (ERalpha) is expressed in vascular cells from males and females and may mediate some of the effects of estrogen on vascular tissue. However, we recently found that estrogen is able to protect against vascular injury in ovariectomized female ERalpha knockout mice. These mice express the newly described estrogen receptor-beta (ERbeta) in their aortas, suggesting that ERbeta may also mediate some of the direct effects of estrogen on the vasculature. In this study, the level of expression of ERalpha and ERbeta mRNA in male rat aortas was examined before and after vascular injury using en face (Häutchen) preparations and in situ hybridization. Little or no change in ERalpha expression was observed after vascular injury in either vascular endothelial or smooth muscle cells at any time point. In contrast, ERbeta mRNA was found to be expressed markedly after balloon injury. In endothelial cells, ERbeta was increased by 2 days after injury, and high levels of expression were maintained at 8 and 14 days. Furthermore, ERbeta expression was high in luminal smooth muscle cells at 8 and 14 days after injury and had decreased to low levels by 28 days after injury. These data demonstrate the presence of ERbeta in male vascular tissues and the induction of ERbeta mRNA expression after vascular injury, supporting a role for ERbeta in the direct vascular effects of estrogen.

Animals↗
PubMed1998

Prenatal diagnosis of Walker-Warburg syndrome in three sibs.

Walker-Warburg syndrome (WWS) is an autosomal recessive condition characterized by diffuse neurodysplasia, resulting in brain and eye abnormalities. We report on 3 prenatally diagnosed cases of this syndrome born to a consanguineous couple. An ultrasonographic examination showed hydrocephalus at the 27th week of the first pregnancy. Amniocentesis documented a normal male karyotype. The couple opted for termination of the pregnancy but declined an autopsy. Seven months later, hydrocephalus was observed at 20 weeks of the second pregnancy. Termination of pregnancy was performed at the 22nd week. Autopsy of this male fetus showed dilated ventricles, thin cortex, and type II lissencephaly with microscopic evidence of chaotic architecture. Eye examination showed retinal dysplasia. Notwithstanding the lack of demonstrable muscle change, the diagnosis of Walker-Warburg syndrome was made. Ten months later, hydrocephalus was discovered in the third fetus, a female, at 13 weeks of gestation. Termination of pregnancy was performed at 20 weeks. At autopsy, brain, eye, and muscular findings were similar to those of the previous case. In addition, cystic changes and a stenosis of the pyelo-ureteral junction were found in the right kidney. Type II lissencephaly and retinal dysplasia are characteristic of WWS. Muscular dystrophy has been pointed out as an additional abnormality in postnatal cases. By contrast, the lack of demonstrable muscle changes in the fetal period must be emphasized. Those cases illustrate practical problems in the ultrasound and pathologic diagnosis of WWS in the fetal period.

Abnormalities, Multiple↗
PubMed1998

[Acute therapy of episodic and chronic cluster headache with sumatriptan s.c. Results of a one-year long-term study].

The aim of the open prospective study was to investigate the efficacy, safety and tolerability of subcutaneous sumatriptan in the acute treatment of cluster headache. Self-treatment with 6 mg sumatriptan subcutaneously was monitored over a period up to 1 year. Headache parameters were documented by the patients with a headache diary. A total of 2031 attacks in 52 patients were investigated. Treatment with sumatriptan was effective in 88% of the attacks and 57% of the patients were pain-free within 15 min after injection; 42% of the patients became painfree within 15 min after at least 90% of their attacks. During long-time treatment the efficacy remained unchanged. Of the patients 10% withdrew from the study due to lack of efficacy or adverse events. In total, 62% of the patients reported adverse events, which were serious in 3.8% of the cases. Subcutaneous self-treatment of cluster headache is both highly effective and well tolerated.

Acute Disease↗