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Biomedical subjects

S Brem

Publications and source records attributed to S Brem.

At least 37 records · Page 2Linked to original sources
PubMed1995

[Leptospira infected rat population as probable cause of a fatal case of Weil's disease].

In the summer of 1992 a patient died of a leptospiral infection which he probably had contracted while he was swimming in an artificial lake in the region of Tübingen/Reutlingen. Regarding the epidemiological role of leptospirosis the rodent population was investigated, because rats and mice were often seen in the surrounding area. 11 rats and 20 mice could be trapped. From their urine or kidneys two leptospiral serovars were isolated: Serovar copenhageni from Rattus norvegicus and serovar saxkoebing from Clethrionomys glareolus. Leptospiral antibody titers were not detected in one of these infected animals. It may be supposed that the Leptospira interrogans serovar copenhageni out of the Serogroup Icterohaemorrhagiae had caused the leptospiral infection of the patient.

Animals↗
PubMed1994

Suramin, an anticancer and angiosuppressive agent, inhibits endothelial cell binding of basic fibroblast growth factor, migration, proliferation, and induction of urokinase-type plasminogen activator.

Suramin, an anticancer agent in current clinical trials, is a prototype of a pharmacological antagonist of growth factors, including basic fibroblast growth factor (bFGF). Suramin inhibited angiogenesis in the chick chorioallantoic membrane assay in a dose-dependent fashion. Suramin, 200 mg/kg i.v., inhibited rat corneal angiogenesis induced by bFGF-impregnated polymers; addition of heparin stimulated angiogenesis and counteracted the inhibition of suramin. The half-maximal inhibitory concentration (IC50) of suramin was determined for key cellular mechanisms that regulate angiogenesis: (a) low and high affinity cellular binding of bFGF to bovine capillary endothelial (BCE) cells with IC50s, respectively, of 24.3 and 71.5 micrograms/ml; (b) spontaneous migration of bovine pulmonary artery endothelial and normal AG 7680 fetal bovine aortic endothelial cells; bFGF-stimulated migration of BCE and transformed GM 7373 fetal bovine aortic endothelial cells with IC50s of 200-320 micrograms/ml; (c) proliferation of bovine pulmonary artery endothelial cells at > 100 micrograms/ml and of BCE cells at > 250 micrograms/ml; and (d) urokinase-type plasminogen activator activity of GM 7373 endothelial cells stimulated by bFGF with an IC50 of 211 micrograms/ml and of BCE cells stimulated by bFGF at > 100 micrograms/ml, but not plasminogen activator activity induced by phorbol 12-myristate 13-acetate. Suramin inhibited multiple control points of angiogenesis, including those stimulated by bFGF. Because tumor growth is angiogenesis dependent, the clinical efficacy of suramin may relate, in part, to angiosuppression.

Animals↗
PubMed1994

Suramin inhibits glioma cell proliferation in vitro and in the brain.

Suramin is a novel anticancer agent that blocks the binding of growth factors, including basic fibroblast growth factor (bFGF), to their receptors. Prior studies showed human and experimental gliomas to upregulate and respond to autocrine stimulation by bFGF, the antiproliferative effects of suramin were therefore studied on glioma cell turnover in vitro and in the brain. Suramin inhibited the growth of rat (C6, 9L) and human (U-118, U-138, A-172, T98G) glioma cell lines in a dose-dependent manner. Suramin significantly reduced the bromodeoxyuridine (BUdR) labeling index of cultured glioma cells at 250 micrograms/ml, P < 0.0001. DNA flow cytometry revealed a significant decrease in the percentage of suramin-treated glioma cells in S-phase, P < 0.01. Using intracerebral rat C6 glioma model in vivo, suramin, 10-60 mg/kg, i.p., produced a dose-dependent reduction of BUdR labeling in both the glioma and endothelial cell subpopulations. Suramin, 200 mg/kg i.v., however, led to intratumoral hemorrhages that reduced survival. Electron microscopy revealed membranous inclusion bodies in the cytoplasm of C6 glioma and endothelial cells, an indication of excess glycosaminoglycans. Moreover, 46% of endothelial cells within the C6 glioma tumor treated with suramin, 60 mg/kg, i.p., developed membrane blebs. Suramin, in clinically relevant doses, significantly inhibits glioma cell growth and cytokinetics. The risk of intratumoral hemorrhage, possibly related to injury of endothelial cells or the accumulation of anticoagulant glycosaminoglycans, constitutes a major side effect and caution should be exercised in consideration of clinical application for intracerebral tumors.

Animals↗
PubMed1994

A diaminoantraquinone inhibitor of angiogenesis.

Tumor growth is dependent upon angiogenesis. There is an intense search for pharmacological inhibitors of angiogenesis as a novel approach to treat angiogenic diseases, e.g., arthritis, diabetic retinopathy or cancer. A series of compounds, originally studied as potential protein kinase C inhibitors, included the diaminoanthraquinone NSC 639366 (1-[[3-(diethylamino)-2-hydroxypropyl]amino]-4-[(2,3- epoxypropyl)amino]-9,10-anthracenedione fumaric acid salt) (SPC-100097), was found to reversibly inhibit bovine endothelial cell growth with an IC50 that ranged between 1 and 4 nM. NSC 639366 reversibly inhibited endothelial cell migration, particularly endothelial cells stimulated by the potent angiogenic molecule, basic fibroblast growth factor. The activity of secreted urokinase-type plasminogen activator and active interstitial collagenase, but not gelatinase, was inhibited by NSC 639366. In vivo, angiogenesis was significantly inhibited by NSC 639366 by using the chick chorioallantoic membrane or the rat corneal bioassay. Two analogs of NSC 639366 did not inhibit endothelial cell growth. These experiments introduce a novel compound that could be clinically useful against angiogenic diseases and encourage further development of compounds that inhibit the plasminogen-plasmin system known to be a key regulator of angiogenesis.

Animals↗
PubMed1993

The prevention of oxyhemoglobin-induced endothelial and smooth muscle cytoskeletal injury by deferoxamine.

The oxidized breakdown products of hemoglobin are important in the pathogenesis of cerebral vasospasm because of their effects on the endothelium and the smooth muscle of the arterial wall. Cytoskeletal changes in cultured vascular cells are sensitive indicators of oxidative injury. Cultured endothelial cells and smooth muscle cells showed a dose-related disruption of the cytoskeleton, particularly the F-actin and vimentin filaments, when exposed to 10(-5) M oxyhemoglobin. The cytoskeletal injury was prevented by the addition of 10(-3) M deferoxamine or 1% albumin. These experiments support a role for deferoxamine in the pharmacological treatment of vasospasm. Furthermore, cytoskeletal studies of cultured arterial endothelial and smooth muscle cells provide a novel in vitro approach by which to study the cellular mechanisms of oxidant injury initiated by the breakdown products of hemoglobin.

Actins↗
PubMed1992

Immunolocalization of basic fibroblast growth factor to the microvasculature of human brain tumors.

BACKGROUND: Microvascular proliferation, a prominent feature of tumors of the central nervous system, is a prime target for anti-cancer therapy. METHODS: Because basic fibroblast growth factor (bFGF) plays a key role in the regulation of angiogenesis, surgical specimens from 52 human brain tumors were examined by immunocytochemical studies with a murine monoclonal antibody to bFGF. Sections from these tumors also were incubated with Ki-67 monoclonal antibody to measure the growth fraction. RESULTS: Immunostaining for bFGF was observed in 45 of 52 (87%) neoplasms, reacting with 97% of the malignant brain tumors and 67% of benign tumors (P < 0.01). The nonreactive tumors were a medulloblastoma and 7 of 21 (33%) benign, noninvasive, slow-growing neoplasms (1 acoustic schwannoma, 3 meningiomas, 2 pituitary adenomas, and 1 cholesteatoma). The indices of proliferation (Ki-67 labeling) were lower for the 21 benign tumors (1.2 +/- 1.1%) than the 31 malignant tumors (10.3 +/- 10.5%; P < 0.001). The bFGF was immunolocalized in the tumor cell nuclei in 23 of 52 tumors (44%) and in the cytoplasm of 8 of 52 (15%) tumors. Immunostaining to bFGF was prominent in the microvascular endothelial compartment in 84% of the malignant tumors and only 52% of benign tumors (P < 0.01). Immunostaining was not present after preabsorption of the antibody with pure human recombinant bFGF. CONCLUSIONS: The presence of bFGF predominantly within the tumor microvasculature indicates a cellular depot for this potent growth factor that mediates angiogenesis and tumorigenesis. These data support a role for bFGF in the transition from the benign to the malignant phenotype.

Blotting, Western↗
PubMed1992

Terson's syndrome: a reversible cause of blindness following subarachnoid hemorrhage.

Terson's syndrome refers to the occurrence of vitreous hemorrhage with subarachnoid hemorrhage (SAH), usually due to a ruptured cerebral aneurysm. Although it is a well-described entity in the ophthalmological literature, it has been only rarely commented upon in the neurosurgical discussion of SAH. Fundus findings are reported in a prospective study of 22 consecutive patients with a computerized tomography- or lumbar puncture-proven diagnosis of SAH. Six of these patients had intraocular hemorrhage on initial examination. In four patients vitreous hemorrhage was evident on presentation (six of eight eyes). In the subsequent 12 days, vitreous hemorrhage developed in the additional two patients (three of four eyes) due to breakthrough bleeding from the original subhyaloid hemorrhages. The initial amount of intraocular hemorrhage did not correlate with the severity of SAH. Two of the six patients with intraocular hemorrhage died, whereas five of the 16 remaining SAH patients without intraocular hemorrhage died. Of the four survivors with intraocular hemorrhage, three showed gradual but significant improvement in their visual acuity by 6 months. The fourth underwent vitrectomy at 8 months after presentation and had a good visual result. With modern and aggressive medical and microsurgical management, Terson's syndrome should be recognized as an important reversible cause of blindness in patients surviving SAH.

Adult↗
PubMed1991

The cycling pool of cells within human brain tumors: in situ cytokinetics using the monoclonal antibody Ki-67.

Brain tumor growth results from the relative proportion of cells contained in three populations: a) cycling/proliferative; b) quiescent (GO)/static, and c) terminally differentiated/dying. The cycling compartment can be detected by the mouse monoclonal Ki-67 antibody, an available, rapid, safe, sensitive, and specific method for immunostaining of proliferative cells. We report the Ki-67 labeling index (LI) in 48 brain tumors. Malignant brain tumors have elevated LIs, ranging from 6.0% to 56.9%: anaplastic astrocytoma, 8.0 +/- 7.3; glioblastoma multiforme, 10.1 +/- 4.2; germinoma, 11.7; medulloblastoma, 13.1 +/- 6.6; metastases, 40.3 +/- 13.1. By contrast, slow-growing tumors showed lower values (P less than .001), approaching 1%: acoustic schwannoma, 0.4 +/- 0.6; pituitary adenoma, 1.3 +/- 1.9; meningioma, 1.2 +/- 1.2; low-grade astrocytoma, less than 1; pilocytic astrocytoma, 5.6. Human brain tumors can therefore be ranked according to the percentage of cycling cells with the acoustic schwannoma among the least proliferative and the metastatic carcinoma among the most proliferative. Within a given histotype, the Ki-67 LI may have prognostic and therapeutic implications for the individual patient. Already important for neuro-oncology research, the Ki-67 labeling index should be added to the armamentarium of the clinical neuropathologist to complement the standard histopathologic diagnosis with a cytokinetic analysis of cellular proliferation.

Antibodies, Monoclonal↗
PubMed1990

[Leptospira antibody detection in dog serum in the years 1985 to 1988].

In 1985-1988, 993 serum samples of dogs from Southern Bavaria and 408 samples from Northern Bavaria and from several Lands of the Federal Republic of Germany were tested for antibodies against the serovars canicola, icterohaemorrhagiae, grippotyphosa, bratislava, pomona, saxkoebing, sejroe and hardjo by using the microscopic agglutination test (MAT). 683 seras (48.75%) out of altogether 1401 samples showed a reaction against one up to seven serovars. The mostly low canicola- and icterohaemorrhagiae titers, having been proved in over 30% of the samples, can be put down to the fact, that usually the dogs had been vaccinated. Most frequently titers were found with the serovars grippotyphosa and bratislava--in Southern Bavaria 28.3%, in Northern Bavaria and other Lands of the Federal Republic of Germany 18.6%. The prevalence of titers against serovar saxkoebing, with or without a reaction against other serovars out of homologous and heterologous serogroups, reach up to 3.2% in sendings coming from Southern Bavaria and in other sendings up to 6.1%.

Animals↗
PubMed1990

Anticopper treatment inhibits pseudopodial protrusion and the invasive spread of 9L gliosarcoma cells in the rat brain.

The copper ion, a cofactor of angiogenesis, is sequestered in human brain tumors and the adjacent brain. The invasive spread of neoplastic cells has been linked to angiogenesis and involves similar mechanisms of migration and tumor-matrix interaction. In this report, copper depletion inhibited the infiltrative spread of the normally invasive 9L gliosarcoma. Twenty made Fischer 344 rats were each injected with 1 X 10(5) 9L cells; 10 rats were treated with a low-copper diet and penicillamine. In the normocupremic control rats, a "diffuse" invasive pattern was observed in all 10 animals. In the hypocupremic group, a "nodular" pattern, with a discrete border between tumor and brain, was found in 7 of 10 rats (P less than 0.01). In a second experiment, the brains of 16 tumor-bearing rats were studied by electron microscopy. In the 8 normocupremic control rats, cytoplasmic extensions and pseudopodial protrusions, cytological markers of invasive cells, were prominent at the tumor-brain interface. In striking contrast, pseudopodia were absent along the border of the tumors in the 8 hypocupremic rats. These findings suggest a biological role of copper in the neoplastic spread of brain tumor cells. Pharmacological and metabolic alteration of the cellular microenvironment to inhibit invasiveness represents a novel therapeutic approach, especially for tumors of the brain in which malignancy is a function of regional invasiveness.

Animals↗
PubMed1989

Rapid in situ cellular kinetics of intracerebral tumor angiogenesis using a monoclonal antibody to bromodeoxyuridine.

The application of a monoclonal antibody to bromodeoxyuridine (BUdR) provides a rapid, reproducible, nontoxic, immunohistochemical method to measure cellular kinetics of intracerebral tumor angiogenesis. The rabbit brain tumor model of angiogenesis consists of tumor and endothelial cell populations with high proliferative rates that demonstrate the close interdependence between microvascular and neoplastic growths as well as topographic gradients, heterogeneity, and regional microdomains of cell proliferation. The labeling index (LI) of endothelial cells was 25.8% at the tumor periphery, compared to 1.7% in the tumor center (P less than 0.001). Concomitant with an increased turnover of neoplastic cells at the tumor periphery. LI was 26.6% with a LI of 7.7% in the center (P less than 0.01). Furthermore, labeled tumor cells tended to be organized around proliferating capillaries, with less DNA synthesis farther from the nearest blood vessel. The established normal microvessels of the brain, e.g., in the opposite tumor-free hemisphere, were mitotically inactive with a LI of less than 0.001%. Quantitation of vascular cytokinetics should be useful in further studies of the pathophysiology of brain tumor angiogenesis and the development of pharmacological approaches directed toward the microvasculature.

Animals↗
PubMed1989

Angiogenesis and blood-brain barrier breakdown modulate CT contrast enhancement: an experimental study in a rabbit brain-tumor model.

Because of the crucial role played by tumor neovascularization in contrast enhancement, we studied the CT imaging findings in a transplantable rabbit brain tumor, the VX2 carcinoma that induces angiogenesis and the breakdown of blood-brain barrier associated with contrast enhancement. Tumor detection by contrast enhancement followed the peak of angiogenesis. Inhibition of angiogenesis, by copper depletion and penicillamine, led to avascular tumors that lack contrast enhancement. Furthermore, there was no contrast enhancement in brain adjacent to the tumor of normocupremic rabbits or within the hypocupremic tumor, despite the breakdown of the blood-brain barrier, without the concomitant presence of angiogenesis. We conclude that contrast enhancement of intracranial tumors is dependent primarily on the proliferation of the microvasculature.

Animals↗
PubMed1989

Angiogenic activity of the atherosclerotic carotid artery plaque.

Neovascularization is observed in complicated atherosclerotic plaques associated with cellular proliferation, plaque hemorrhage, and thrombosis. The angiogenic activity of 278 plaque fragments was tested; the fragments were taken from 12 patients with cerebral ischemia who underwent carotid endarterectomy. Angiogenesis, determined by the sustained ingrowth of new vessels in the rabbit cornea, was induced in 125 (45%) of these fragments. By contrast, angiogenesis was found in only two (2.4%) of 80 control tissues (p less than 0.001): in none of 22 samples of boiled atherosclerotic plaque; in two of 26 samples of normal rabbit carotid artery; and in none of 32 samples of nonatherosclerotic human uterine artery. Histological evaluation revealed that the cellular zones (composed mainly of smooth-muscle cells) were highly angiogenic, with 97 (76%) of 127 samples showing angiogenesis compared with 23 (17%) of 132 acellular fragments that consisted of amorphic, necrotic, calcific, lipid-laden material (p less than 0.001). These results indicate that angiogenesis in vivo is a function of the cellular component of the advanced atherosclerotic plaque, and is not expressed in the normal, stable arterial wall. The fragile new vessels could promote the growth of the plaque or be a source of hemorrhages, microinfarcts, and plaque fissures that convert a stable, silent lesion to an expanding, ulcerated, thrombotic, symptomatic plaque.

Aged↗
PubMed1988

Neovascularization and tumor growth in the rabbit brain. A model for experimental studies of angiogenesis and the blood-brain barrier.

A model for the study of tumor angiogenesis within the rabbit brain is presented. Implantation of the VX2 carcinoma provides a reproducible tumor accompanied by angiogenesis. The authors report the sequential growth, histology, tumor neovascularization, and vascular permeability of this tumor following its intracerebral implantation. Tumor angiogenesis correlates with the rapid and logarithmic intracerebral tumor growth. The proliferation of blood vessels in the tumor and the organization of tumor cells around tumor vessels are described. Breakdown of the blood-brain barrier (detected by Evans blue leakage) starts in the early stages of tumor development and becomes prominent as the tumor vasculature and size increase. This model is useful for experimental studies of angiogenesis.

Animals↗