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H C Bauer

Publications and source records attributed to H C Bauer.

At least 19 recordsLinked to original sources
PubMed2005

In search of the astrocytic factor(s) modulating blood-brain barrier functions in brain capillary endothelial cells in vitro.

(1) The blood-brain barrier (BBB) is formed by brain capillary endothelial cells (ECs). There are various cell types, in particular astrocytes, but also pericytes and neurons, located in close vicinity to the capillary ECs which may influence formation and function of the BBB. Based on this consideration, this paper discusses various aspects of the influence of the surrounding cells on brain capillary ECs with special focus on the role of astrocytes. (2) Based on the morphology of the BBB, important aspects of brain EC functions are summarized, such as transport functions and maintenance of low paracellular permeability. Moreover, various facets are discussed with respect to the influence of astrocytes, pericytes, microglia, and neurons on the BBB. Data on the role of glial cells in the ontogenesis of the BBB are presented subsequently. The knowledge on this subject is far from being complete, however, these data imply that the neural/neuronal environment rather than glial cells may be of importance in the maturation of the barrier. (3) The role of glial cells in the induction and maintenance of the BBB is discussed under physiological as well as pathological conditions. Although the literature presents manifold evidence for a great variety of effects induced by astroglia, there are also many controversies, which may result from different cellular models and experimental conditions used in the respective studies. Numerous factors secreted by astrocytes have been shown to induce a BBB phenotype. On the molecular level, increased expression of barrier-relevant proteins (e.g., tight junction proteins) is documented in the presence of astrocyte-derived factors, and many studies demonstrate the improvement of physiological parameters, such as increased transendothelial resistance and decreased paracellular permeability, in different in vitro models of the BBB. Moreover, one has to take into account that the interaction of brain ECs and astrocytes is bi-directional, and that the other cell types surrounding the brain microvasculature also contribute to BBB function or dysfunction, respectively. (4) In conclusion, it is expected that the present and future research focused on molecular mechanisms and signaling pathways will produce new and exciting insights into the complex network of BBB regulation: the cornerstone is laid.

Animals↗
PubMed2003

Oxidative stress in cultured cerebral endothelial cells induces chromosomal aberrations, micronuclei, and apoptosis.

There is evidence accumulating that brain microvasculature is involved critically in oxidative stress-mediated brain damage. Cultured cerebral microvascular endothelial cells were used to demonstrate the cytotoxic and genotoxic effects elicited by hypoxia/reoxygenation and DMNQ treatment in vitro. In addition, the effect of glucose deprivation during oxidative insult was assessed. The parameters determined were: 1) chromosomal aberrations; 2) induction of micronuclei; and 3) apoptosis. Our results indicate that both the exposure of the cerebral endothelial cells to 24 hr of hypoxia followed by 4 hr of reoxygenation, and treatment with the redox cycling quinone DMNQ, increased markedly the occurrence of chromosomal aberrations and micronuclei. It was found that expression of p53 was induced by oxidative stress, particularly when glucose had been omitted from the culture medium. Aglycemic culture conditions in general exacerbated the cytotoxic effects of oxidative insults, as evidenced by the increase in apoptotic cells and the decrease in the mitotic index. Interestingly, neither an elevation of cell lysis nor an increase in necrosis has been observed during our experiments. In summary, our data indicate that oxidative stress exerts considerable genotoxic and cytotoxic effects on cerebral endothelial cells, which might contribute to the progression of tissue damage in the central nervous system.

Animals↗
PubMed2001

Surgical treatment for skeletal breast cancer metastases: a population-based study of 641 patients.

BACKGROUND: The objective of this article was to assess the occurrence of symptomatic bone metastases in a defined population of patients with breast carcinoma and to characterize the clinical outcome with reference to surgical treatment for pathologic fracture or neurologic deficit. METHODS: The authors identified all patients in the Stockholm Breast Cancer Database (population base 1.8 million) with a diagnosis of bone metastases during 1989--1994. These cases were linked with the Stockholm County Council Hospital Discharge Diagnosis Registry that includes information on in-patient care and discharge diagnoses. This enabled us to identify patients who had undergone surgical treatment for their bony metastases at any of the six departments of orthopedics in the region, or who had been treated at the one department of neurosurgery. RESULTS: Six hundred forty-one patients with breast carcinoma presented with symptomatic skeletal metastasis during 1989--1994, and 107 (17%) were operated on. Metastases were located in long bones (77), spine (14), and pelvis (6). The median survival postoperatively was 6 months. The total reoperation rate was 0.12. Hip screws and glide-screw plates were associated more often with failure as was location in the distal femur. Pain decreased postoperatively in 77% of the patients, and function improved in 65%. CONCLUSIONS: One in 10 patients with breast carcinoma developed symptomatic bone metastases, and one-fifth of these patients required surgery for pathologic fracture or neurologic deficit. There was a high failure rate in those hospitals in which few patients were operated on.

Adult↗
PubMed2001

Identification and localization of M-CoREST (1A13), a mouse homologue of the human transcriptional co-repressor CoREST, in the developing mouse CNS.

By means of subtractive and differential hybridization techniques we have identified a novel murine gene (1A13) the expression of which is developmentally regulated in the mouse brain. Comparison of the nucleotide and predicted protein sequence revealed closest relationship of 1A13 to human CoREST, a transcriptional co-repressor required for regulation of neural-specific gene expression. Thus, we will refer to 1A13 as M-CoREST. As shown by in situ hybridization and Northern blotting, expression of M-CoREST mRNA is abundant in neural tissue at early embryonic stages but declines significantly towards birth, coincident with the progression of CNS maturation.

Amino Acid Sequence↗
PubMed2001

Immunolocalization of occludin and claudin-1 to tight junctions in intact CNS vessels of mammalian retina.

The distributions of occludin and claudin-1, two tight junction-associated integral membrane proteins were investigated by immunohistochemical analysis of whole-mount preparations of the blood vessels in the myelinated streak of the rabbit retina. Light microscopy revealed that occludin and claudin-1 immunoreactivities were abundant along the interface of adjacent endothelial cells of all blood vessels. Electron microscopy revealed that both proteins were distributed in a regular pattern (at regular intervals of approximately 80 nm) along the length of tight junctions, probably in the regions of tight junction strands. No other structures or cell types expressed either of these two proteins in the myelinated streak. Whereas occludin immunoreactivity was concentrated only at the tight junction interface, claudin-1 immunoreactivity also extended into the cytoplasm of the endothelial cells, suggesting a different structural role for claudin-1 than for occludin at tight junctions. Retinal pigment epithelial cells expressed occludin around their entire circumference, consistent with the function of these cells as a barrier separating the retina from the leaky vessels of the choroid. Also consistent with the association of occludin expression with vessels that exhibit functional tight junctions, this protein was expressed at only a low level in, and showed an irregular distribution along, the vessels of the choroid, a vascular bed that lacks blood-barrier properties. Further, the distribution of occludin was examined during formation and remodelling of the rat retinal vasculature. Occludin expression was evident at the leading edge of vessel formation and was found on all vessels in both the inner and outer vascular plexus. Numerous vascular segments at the early stage of vascular formation and regression lost occludin expression. The biological significance of this transient loss of occludin expression in terms of barrier function remains to be elucidated.

Animals↗
PubMed2001

Diagnosis of skeletal lymphoma and myeloma by radiology and fine needle aspiration cytology.

Diagnosis of skeletal lymphoma and myeloma by radiology and fine needle aspiration cytology From 1986 to 1998, all patients referred to Karolinska Hospital because of a skeletal destruction of unknown origin routinely underwent radiographic examination and fine needle aspiration cytology (FNAC). Among these, there were 83 patients with solitary lesions of the bone diagnosed and treated for myeloma (plasmacytoma) or non-Hodgkin's lymphoma. Review of the series showed that myeloma could not be distinguished radiographically from lymphoma. Nor could low and high grade lymphoma lesions be discriminated by radiographic appearance. The diagnostic utility of plain radiography in the two conditions seems to be confined to the mere detection of a destructive bone lesion and visual guidance for FNAC. The latter aspect, however, is crucial for the application of FNAC to bone lesions. Review of the cytologic specimens obtained by FNAC showed that they allowed a conclusive diagnosis in all 40 myeloma cases and in 41 of 43 lymphoma cases. In 32 of the 40 myeloma cases, the FNAC material could be used for immunocytochemistry, which disclosed kappa or lambda light chain restriction, corroborating the cytomorphological diagnosis. Thirty-eight lymphomas were characterized immunologically and in 35, a light chain restriction could be demonstrated. Our results show that the use of FNAC in the diagnosis of primary myeloma and lymphoma of bone obviates the need for other diagnostic modalities, including open biopsy. A combined approach based on radiology and FNAC, performed as an out-patient procedure, offers rapid and accurate diagnosis of myeloma and lymphoma among patients with radiographically unclassified destructive bone lesions.

Adolescent↗
PubMed2001

Monitoring referral and treatment in soft tissue sarcoma: study based on 1,851 patients from the Scandinavian Sarcoma Group Register.

This report is based on 1.851 adult patients with soft tissue sarcoma (STS) of the extremities or trunk wall diagnosed between 1986 and 1997 and reported from all tertiary referral centers in Norway and Sweden. The median age at diagnosis was 65 years and the male-to-female ratio was 1.1:1. One third of the tumors were subcutaneous, one third deep, intramuscular and one third deep, extramuscular. The median size was 7 (1-35) cm and 75% were high grade (III-IV). Metastases at presentation were diagnosed in 8% of the patients. Two thirds of STS patients were referred before surgery and the referral practices have improved during the study. The preoperative morphologic diagnosis was made with fine-needle aspiration cytology in 81%, core-needle biopsy in 9% and incisional biopsy in 10%. The frequency of amputations has decreased from 15% in 198688 to 9% in 1995-1997. A wide surgical margin was achieved in 77% of subcutaneous and 60% of deep-seated lesions. Overall, 24% of operated STS patients had adjuvant radiotherapy. The use of such therapy at sarcoma centers increased from 20% 1986-88 to 30% in 1995-97. Follow-up has been reported in 96% of the patients. The cumulative local recurrence rate was 0.20 at 5 years and 0.24 at 10 years. The 5-year metastasis-free survival rate was 0.70.

Adolescent↗
PubMed2001

Local recurrence of deep-seated, high-grade, soft tissue sarcoma: 459 patients from the Scandinavian Sarcoma Group Register.

This study was based on 459 adult patients with deep, high-grade, soft tissue sarcoma of extremities or trunk wall reported to the Scandinavian Sarcoma Group Register (1986-1993). All patients had their definitive surgery for primary tumor at a sarcoma center. The median follow-up was 7.5 (3-12) years. 204 patients are still alive. 68 patients had amputations and 391 underwent limb-sparing surgery. Among 183 patients with intralesional or marginal margins after limb-sparing surgery, 65% had postoperative radiotherapy and 9% of the 198 patients with wide margins. The local recurrence rate after limb-sparing surgery was 26%. The rate with an intralesional or marginal margin was 39% without postoperative radiotherapy versus 24% when radiotherapy was given. It was 25% after a wide margin, and no recurrences were noted among the 10 patients with a compartmental surgical margin. Among patients with a wide margin, a subset fulfilling criteria for a myectomy was defined. The local recurrence rate was 26% among these 62 and there was no advantage of myectomy over other wide margins. More radical surgical margins would improve the local recurrence rate, but this can hardly be achieved in center-operated patients without increasing the amputation rate. Instead, increased use of radiotherapy in all patients with inadequate margins, and to a larger extent in those with wide margins will improve local control.

Adolescent↗
PubMed2001

Pre-operative radiotherapy in soft tissue tumors. Assessment of response by static post-contrast MR imaging compared to histopathology.

PURPOSE: To evaluate if static post-contrast MR imaging was adequate to assess tumor viability after pre-operative radiotherapy in soft tissue sarcoma. MATERIAL AND METHODS: Post-contrast MR imaging of 36 soft tissue sarcomas performed 0-54 days (median 13 days) after pre-operative radiotherapy, were retrospectively reviewed and compared to post-operative histopathology reports. The contrast enhancement of the tumor was visually graded as minor, moderate or extensive. From the post-operative histopathology reports, three types of tumor response to radiotherapy were defined: Poor, intermediate or good. The size of the tumors before and after radiation was compared. RESULTS: Even if most viable tumors enhanced more than non-viable tumors, there was major overlapping and significant contrast enhancement could be seen in tumors where histopathological examination revealed no viable tumor tissue. Based on histopathology, there were 12 good responders; 8 of these showed minor, 3 moderate and 1 extensive contrast enhancement on MR imaging. Sixteen tumors had an intermediate response; 3 showed minor, 8 moderate and 5 extensive enhancement. Eight tumors had poor response; none showed minor enhancement, 3 moderate and 5 extensive enhancement. Both increase and decrease in tumor size was seen in lesions with a good therapy response. CONCLUSION: Static post-contrast MR imaging cannot reliably assess tumor viability after pre-operative radiotherapy in soft tissue sarcoma. In tumors with no viable tumor tissue, moderate and extensive contrast enhancement can be seen.

Adolescent↗
PubMed2000

Surgical margins, local recurrence and metastasis in soft tissue sarcomas: 559 surgically-treated patients from the Scandinavian Sarcoma Group Register.

The prognostic importance of surgical margins on local recurrence rates and metastasis-free survival (MFS) was studied in 559 patients with soft tissue sarcoma of the extremities and trunk wall. The patients were all surgically treated, but received no adjuvant treatment. The median follow-up for the survivors was 7.4 (range: 0.1 - 12.5) years. Independent prognostic factors for MFS were analysed by Cox models. The overall 5-year MFS was 0.72 (95% confidence intervals (CI) 0.68 - 0.76). High histopathological malignancy grade (relative risk (RR) 3.0; 95% CI 1.5 - 6.3) and an inadequate surgical margin (RR 2.9; 95% CI 1.8 - 4.6) were independent risk factors for local recurrence. High histopathological malignancy grade and large tumour size (> 7 cm) were the most important risk factors for metastasis. Local recurrence was associated with an increased risk of metastasis (RR 4. 4; 95% CI 2.9-6.8), but an inadequate surgical margin was not a risk factor for metastasis (RR 1.1; 95% CI 0.8-1.7). This study confirms that, as regards metastasis, tumour-related risk factors (malignancy grade and tumour size) are more important risk factors than treatment-related factors. Local recurrence was associated with an increased metastasis rate, whereas inadequate surgical margin was a risk factor for local recurrence but not for metastasis. Hence, the proposed causal association between local recurrence and metastasis is doubtful, and if it exists is a weak association.

Adolescent↗
PubMed2000

Neural induction of the blood-brain barrier: still an enigma.

1. The study of the blood-brain barrier and its various realms offers a myriad of opportunities for scientific exploration. This review focuses on two of these areas in particular: the induction of the blood-brain barrier and the molecular mechanisms underlying this developmental process. 2. The creation of the blood-brain barrier is considered a specific step in the differentiation of cerebral capillary endothelial cells, resulting in a number of biochemical and functional alterations. Although the specific endothelial properties which maintain the homeostasis in the central nervous system necessary for neuronal function have been well described, the inductive mechanisms which trigger blood-brain barrier establishment in capillary endothelial cells are unknown. 3. The timetable of blood-brain barrier formation is still a matter of debate, caused largely by the use of varying experimental systems and by the general difficulty of quantitatively measuring the degree of blood-brain barrier "tightness." However, there is a general consensus that a gradual formation of the blood-brain barrier starts shortly after intraneural neovascularization and that the neural microenvironment (neurons and/or astrocytes) plays a key role in inducing blood-brain barrier function in capillary endothelial cells. This view stems from numerous in vitro experiments using mostly cocultures of capillary endothelial cells and astrocytes and assays for easily measurable blood-brain barrier markers. In vivo, there are great difficulties in proving the inductive influence of the neuronal environment. Also dealt with in this article are brain tumors, the least understood in vivo systems, and the induction or noninduction of barrier function in the newly established tumor vascularization. 4. Finally, this review tries to elucidate the question concerning the nature of the inductive signal eliciting blood-brain barrier formation in the cerebral microvasculature.

Animals↗
PubMed2000

Use of genetically modified glial cells overexpressing laminin alpha1-chain peptides in neurite outgrowth studies.

1. C6 glioma cells were transfected with two constructs carrying C-terminal laminin alpha1-chain sequences of 117 and 114 bp length, respectively. These sequences are specifically known to code for peptides which have neurite-promoting activity. 2. The stable expression and secretion of the two peptides was detected by Northern and Western blot analysis. 3. Primary neuronal cultures derived from embryonic mouse forebrain were cocultured with these transfected cells and exhibited a substantial increase in neurite outgrowth and in survival time. Conditioned media from the transfected cells generated similar effects. 4. Organotypic cultures from embryonic mouse brain were used as a second system as being closer to the in vivo situation. Again, coculture of brain slices with transfected cells or treatment with laminin peptide-containing media increased neuronal outgrowth.

Animals↗
PubMed2000

Growth factor-induced morphological, physiological and molecular characteristics in cerebral endothelial cells.

The capacity of vascular endothelial cells to modulate their phenotype in response to changes in environmental conditions is one of the most important characteristics of this cell type. Since different growth factors may play an important signalling role in this adaptive process we have investigated the effect of endothelial cell growth factor (ECGF) on morphological, physiological and molecular characteristics of cerebral endothelial cells (CECs). CECs grown in the presence of ECGF and its cofactor heparin exhibit an epithelial-like morphology (type I CECs). Upon removal of growth factors, CECs develop an elongated spindle-like shape (type II CECs) which is accompanied by the reorganization of actin filaments and the induction of alpha-actin expression. Since one of the most important functions of CECs is the creation of a selective diffusion barrier between the blood and the central nervous system (CNS), we have studied the expression of junction-related proteins in both cell types. We have found that removal of growth factors from endothelial cultures leads to the downregulation of cadherin and occludin protein levels. The loss of junctional proteins was accompanied by a significant increase in the migratory activity and an altered protease activity profile of the cells. TGF-beta1 suppressed endothelial migration in all experiments. Our data provide evidence to suggest that particular endothelial functions are largely controlled by the presence of growth factors. The differences in adhesiveness and migration may play a role in important physiological and pathological processes of endothelial cells such as vasculogenesis or tumor progression.

Actins↗
PubMed2000

Consequences of local recurrence of soft tissue sarcoma: 205 patients from the Scandinavian Sarcoma Group Register.

From the Scandinavian Sarcoma Group Register, information on 1,224 surgically-treated patients with soft tissue sarcoma (STS) of the extremity or trunk wall, diagnosed between 1987 and 1995, was collected. 205 patients, one third of whom were referred to a center with a local recurrence, had a total of 284 local recurrences. This analysis describes the treatment for these local recurrences, complications and risk of further recurrences. 169 patients were surgically treated for their first local recurrence. An intralesional or marginal margin was achieved in 110 of these patients, 59 of whom were also given radiotherapy. 54 of the 169 patients had a second local recurrence. The second local recurrence rate was 0.50 if the first local recurrence had been treated with only surgery with a marginal margin, compared to 0.28 if treated with surgery with a marginal margin and radiotherapy or with a wide margin (p = 0.0008). In extremity STS, the crude amputation rate for local recurrences was 0.22 (31 of 142)-i.e., higher than for primary tumors 0.09 (96 of 1065) (p < 0.0001). A high local recurrence rate after treatment outside of sarcoma centers has earlier been shown. We conclude that the consequences of local recurrence in terms of morbidity and costs justifies referral of STS patients for multidisciplinary evaluation and multimodality treatment.

Adult↗
PubMed2000

Zinc protects against apoptosis of endothelial cells induced by linoleic acid and tumor necrosis factor alpha.

BACKGROUND: Zinc requirements of the vascular endothelium may be increased in inflammatory conditions, ie, atherosclerosis, in which apoptotic cell death is prevalent. OBJECTIVE: We hypothesized that zinc deficiency may potentiate disruption of endothelial cell integrity mediated by fatty acids and inflammatory cytokines by enhancing pathways that lead to apoptosis and up-regulation of caspase genes. DESIGN: Endothelial cells were maintained in low-serum medium or grown in culture media containing selected chelators, ie, diethylenetriaminepentaacetate or N,N,N', N'-tetrakis(2-pyridylmethyl)-ethylenediamine (TPEN), with or without zinc supplementation. Subsequently, cells were treated with linoleic acid, tumor necrosis factor alpha (TNF-alpha), or both. We studied the effect of zinc deficiency and supplementation on the induction of apoptosis by measuring caspase-3 activity, cell binding of annexin V, and DNA fragmentation. RESULTS: Our results indicated that linoleic acid and TNF-alpha independently, but more markedly in concert, up-regulated caspase-3 activity and induced annexin V binding and DNA fragmentation. Zinc deficiency, especially when induced by TPEN, dramatically increased apoptotic cell death induced by cytokines and lipids compared with control cultures. Supplementation of low-serum- or chelator-treated endothelial cells with physiologic amounts of zinc caused a marked attenuation of apoptosis induced by linoleic acid and TNF-alpha. Morphologic changes of cells observed during zinc deficiency were prevented by zinc supplementation. Media supplementation with other divalent cations (eg, calcium and magnesium) did not mimic the protective role of zinc against apoptosis. CONCLUSIONS: Our data indicate that zinc is vital to vascular endothelial cell integrity, possibly by regulating signaling events to inhibit apoptotic cell death.

Animals↗
PubMed2000

Cytological diagnosis of skeletal lesions. Fine-needle aspiration biopsy in 110 tumours.

We have previously shown that cytological diagnosis based on fine-needle aspiration biopsy (FNAB) is a safe and efficient method for the discrimination between benign, primary malignant and metastatic bony lesions. We have now studied metastatic lesions to assess the diagnostic accuracy and to ascertain whether FNAB allows identification of the primary lesion. Between 1990 and 1997, 447 patients were referred for diagnosis of skeletal lesions of unknown type. Of these 119 proved to have metastatic disease, either myeloma or lymphoma. Nine were excluded leaving 110 consecutive patients with metastatic carcinoma (80), myeloma (16) or lymphoma (14). FNAB gave a correct diagnosis in 102 of the 110 patients (93%). In eight it was inconclusive. It correctly diagnosed 15 of 16 patients with myeloma, 12 of 14 with lymphoma, and 75 of 80 with metastatic carcinoma. Furthermore, the site and type of malignancy were correctly suggested in two-thirds of patients with metastatic carcinoma. Overall, only seven open biopsies were carried out. We conclude that time-consuming and costly investigations can be reduced by choosing FNAB as the initial diagnostic method for skeletal lesions of unknown origin. The choice of radiological examinations, laboratory tests and surgical biopsies can be determined by using FNAB.

Adolescent↗