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Biomedical subjects

H Broholm

Publications and source records attributed to H Broholm.

18 recordsLinked to original sources
PubMed2004

Nitric oxide synthase expression and enzymatic activity in multiple sclerosis.

We used post-mortem magnetic resonance imaging (MRI) guidance to obtain paired biopsies from the brains of four patients with clinical definite multiple sclerosis (MS). Samples were analyzed for the immunoreactivity (IR) of the three nitric oxide (NO) synthase isoforms [inducible, neuronal and endothelial nitric oxide synthase (NOS)], and enzymatic NO synthase activity. MRI guided biopsies documented more active plaques than macroscopic examination, and histological examination revealed further lesions. Inducible NOS (iNOS) was the dominant IR isoform, while reactive astrocytes were the dominant iNOS expressing cells in active lesions. NOS IR expressing cells were widely distributed in plaques, in white and gray matter that appeared normal macroscopically, and on MR. Endothelial NOS (eNOS) was highly expressed in intraparenchymal vascular endothelial cells of MS patients. A control group matched for age and sex showed no such changes. Our data support the hypothesis that NO is a pathogenic factor in MS, and that NOS IR is strongly expressed in brain regions appearing normal by MRI.

Adult↗
PubMed2002

Nitric oxide synthase activity in human pituitary adenomas.

OBJECTIVES: The purpose of the present study was to examine human pituitary adenomas for nitric oxide synthase (NOS) activity by immunohistochemical and enzymatic methods. MATERIALS AND METHODS: Adenomatous tissue from 16 patients were obtained during operation and stained immunohistochemically for hormone production and for the three NOS isoenzymes. Cell types that expressed NOS immunoreactivity (IR) were identified, and the NOS isoform was noted. NOS activity was measured enzymatically by the conversion of L-arginine to L-citrulline in tissue samples. RESULTS: Endothelial cells of pituitary adenomas showed increase of eNOS IR compared with control tissue. The nNOS and iNOS IR were the same in adenomas and controls. There was no correlation between NOS IR and NOS activity measured enzymatically and the endocrine activity of the tumour or other clinical variables. CONCLUSION: The observation of increased eNOS IR in endothelial cells of adenomas may suggest that NO plays a role in the regulation of blood flow in pituitary adenomas.

Adenoma↗
PubMed2000

Immunohistochemical localization of inducible and endothelial constitutive nitric oxide synthase in neoplastic and autoimmune thyroid disorders.

AIM: To investigate the distribution of nitric oxide synthase in tissues derived from patients with autoimmune or neoplastic disorders of the thyroid gland in order to test whether the expression of inducible nitric oxide synthase or endothelial constitutive nitric oxide synthase (two subtypes of EC 1.14.13.39) may be related to the inflammatory activity or degree of neoplasia. EXPERIMENTAL DESIGN: The expression of nitric oxide synthases was examined by immunohistochemistry in tissues from patients with either Hashimoto's thyroiditis (n=6), hyperplastic glands (Graves' disease) (n=7), adenomas (n=8), multinodular goitres (n=7), papillary carcinomas (n=4) or follicular carcinomas (n=5). RESULTS: Expression of inducible nitric oxide synthase was found in 22 of the tissues and was not specific for any of the examined thyroid disorders. Expression of endothelial constitutive nitric oxide synthase was found in some of the epithelial cells in all the tissues. There was no correlation between the intensity and distribution of the immunostaining and the thyroid disorders. CONCLUSION: Demonstration of nitric oxide synthase cannot be used for diagnostic purposes. The expression of endothelial constitutive nitric oxide synthase in all tissues indicates that the enzyme may be of importance for the function or growth of the thyroid epithelial cells.

Adenocarcinoma, Follicular↗
PubMed1998

[Parapharyngeal Burkitt lymphoma in a seven-year-old boy].

The case describes a seven year-old Danish boy who was referred with a short history of nasal obstruction and enlargement of the lymph nodes on the left side of the neck. The ENT examination demonstrated a large parapharyngeal tumour, which was shown by CT-scanning to extend from the level of the zygomatic arch to the superior thoracic aperture. The histological diagnosis was a Burkitt's lymphoma.

Burkitt Lymphoma↗
PubMed1997

Tracheobronchopathia osteochondroplastica.

A case of tracheobronchopathia osteochondroplastica (TO) was diagnosed in a 68-year-old male with prolonged cough. A bronchoscopy revealed multiple nodular excrescences along the anterolateral wall of the trachea and main bronchi. Tissue specimens showed pronounced change of bronchial cartilage with massive mineralization diagnostic for TO. The literature on the subject is reviewed here. The aetiology and pathogenesis is unknown. The severity of TO range from no symptoms to severe dyspnoea, haemoptysis or pneumonitis. Treatment is seldom necessary. However, in severe cases, bronchoscopic removal of obstructing excrescences and surgery has been performed with therapeutic effect. Differential diagnosis of nodular excrescences includes amyloidosis, endobronchial sarcoidosis, calcificating lesions of tuberculosis, papilomatosis and tracheobronchial calcinosis. Awareness of the condition as a differential diagnosis to neo-plasms is important, to avoid unnecessary surgery or chemotherapy.

Aged↗
PubMed1997

Gliomatosis cerebri--an appropriate diagnosis? Case reports.

PURPOSE: To evaluate the premises for the diagnosis gliomatosis cerebri in relation to diffuse astrocytomas. MATERIAL AND METHODS: CT, MR images and pathological analyses were used to assess the cases of 4 patients with diffusely infiltrating astrocytic tumours that radiologically, clinically and pathologically resembled gliomatosis cerebri. RESULTS AND CONCLUSION: Some astrocytomas have an immense potential for diffuse infiltration and they would seem to be more frequent than recognized hitherto. The definition of gliomatosis cerebri as a separate entity is questionable, and a diagnosis of diffusely infiltrating astrocytoma is recommended in such cases.

Adult↗
PubMed1997

Comparison of the reproducibility of the WHO classifications of 1975 and 1994 of endometrial hyperplasia.

In a blinded, randomized design, six histopathologists with an interest in gynecological pathology examined the inter- and intraobserver variation of the histopathological diagnosis of endometrial hyperplasia according to the World Health Organization (WHO) classification of 1975 and the new WHO classification of 1994. On four occasions, the pathologists assessed hematoxylin/eosin-stained slides from 128 cases originally diagnosed and coded in the Snomed system as endometrial hyperplasia. In the first and third rounds, the slides were classified according to the 1975 classification and in the second and fourth rounds according to the 1994 classification. The overall interobserver agreement in the two rounds where the 1975 classification was used was 0.47 and 0.51, and the kappa values 0.24 [95% confidence interval (CI) 0.21-0.27] and 0.30 (95% CI 0.27-0.33). The overall interobserver agreement in the two rounds using the 1994 classification was 0.45 and 0.41 and the kappa values 0.25 (95% CI 0.23-0.28) and 0.20 (95% CI 0.17-0.22). Reducing the classification to two categories with clinical significance (atypical endometrial hyperplasia versus others in the 1975 classification, and atypical endometrial hyperplasia, complex versus others in the 1994 classification) increased the overall agreement of the 1975 classification in both rounds to 0.91 and of the 1994 classification to 0.92 and 0.90. The kappa values increased to 0.54 (95% CI 0.49-0.58) and 0.49 (95% CI 0.45-0.54) in the 1975 classification and to 0.59 (95% CI 0.54-0.63) and 0.42 (95% CI 0.37-0.46) in the 1994 classification. The intraobserver overall agreement for the 1975 classification ranged from 0.80 to 0.55 and the kappa values from 0.70 (95% CI 0.58-0.81) to 0.28 (95% CI 0.17-0.39). The intraobserver overall agreement for the 1994 classification ranged from 0.71 to 0.46 and the kappa values from 0.60 (95% CI 0.51-0.70) to 0.20 (95% CI 0.09-0.30). It is concluded that there is considerable inter- and intraobserver variation using both the 1975 and the 1994 classifications of endometrial hyperplasia. We propose that there is need for a specification and for a simplification of the classification.

Double-Blind Method↗
PubMed1996

Immunocytochemical localisation of tumor necrosis factor alpha in thyroid tissues from patients with neoplastic or autoimmune thyroid disorders.

It is disputed to what extent tumor necrosis factor-alpha is present in the thyroid follicular epithelial cells and/or in the interstitial cells in different disorders of the thyroid gland. We describe the immunohistochemical detection of tumor necrosis factor-alpha using formaldehyde fixed and paraffin embedded tissue and a polyclonal anti-serum with high tumor necrosis factor-alpha neutralising activity. We examined the distribution of tumor necrosis factor-alpha in interstitial cells and follicular epithelial cells in thyroid carcinomas, adenomas, non-toxic multinodular goiters and autoimmune thyroid diseases. Tumor necrosis factor-alpha was demonstrated in thyroid follicular epithelial cells, most frequently in non-toxic multinodular goiters (six of seven patients) and less frequently in adenomas (three of nine patients), papillary carcinomas (two of five patients), follicular carcinomas (one of five patients), Hashimoto's disease (one of six patients) and Grave's disease (one of seven patients). Tumor necrosis factor-alpha producing interstitial cells were found in two thirds of patients with all six thyroid diseases.

Adenocarcinoma, Follicular↗
PubMed1995

Proliferating cell nuclear antigen and Ki-67 immunohistochemistry of oligodendrogliomas with special reference to prognosis.

BACKGROUND: The biologic behavior of oligodendrogliomas is somewhat unpredictable. A supplementary prognostic factor is, therefore, desirable. METHODS: Thirty-two pure supratentorial oligodendrogliomas were investigated using proliferating cell nuclear antigen (PCNA) and Ki-67 immunohistochemical analyses. The correlation of PCNA and Ki-67 labeling index (LI) with prognosis were studied, and the correlation of LI with clinical data was evaluated. RESULTS: The PCNA LI had a range of 0-17% (mean, 5.27%; standard deviation [SD] = 4.65), and the Ki-67 LI had a range of 0-29% (mean, 4.19%; SD = 5.66). In general, the PCNA LI seemed to be higher than the Ki-67 LI. The mean survival time was 4.4 years, and 5- and 10-year survival rates were 38% and 19%, respectively. Ki-67 and PCNA staining indicated that patients with a high LI (> 3% and > 4%, respectively) had a significantly higher mortality, with mean survival time of 23.5 months and 26.2 months, respectively. No significant correlation between LI (or survival) and tumor size, cerebral localization, radiation, resection/biopsy, sex, age, or cytologic atypia was found. CONCLUSIONS: The use of Ki-67 and PCNA LI higher than 3% and 4%, respectively, appears reliable as prognostic factors when investigating pure supratentorial oligodendrogliomas.

Adolescent↗
PubMed1995

Immunocytochemical localisation of interleukin-1 alpha and interleukin-6 in thyroid tissues from patients with neoplastic or autoimmune thyroid disorders.

We describe the distribution of interleukin-6 and interleukin-1 alpha in thyroid tissues obtained from patients with autoimmune diseases or neoplastic thyroid disorders employing immunohistochemistry in sections from paraffin embedded tissue blocks. Interleukin-6 was found in thyroid follicular epithelial cells (TFEC) from papillary carcinomas (four of five patients) but not in follicular carcinomas (five patients). Interleukin-6 was also detected in non-toxic multinodular goiters (four of seven patients), in patients with Graves' disease who did not have an early recurrence of hyperthyroidism after surgery (three of four patients), in follicular adenomas (five of nine patients), in Hashimoto's thyroiditis (two out of six patients, both belonging to a group of three with an early stage of the disease), and in paraadenomatous tissues (in three of nine patients). Interleukin-1 alpha positive TFEC were found less frequently than interleukin-6, and only in tissues with interleukin-6 positive TFEC. Only few interleukin-6 and interleukin-1 alpha positive interstitial cells were found, even in the lymphocyte infiltrates (in both the autoimmune, benign or malignant disorders). In conclusion, both interleukin-6 and interleukin-1 alpha could be demonstrated in TFEC from patients with autoimmune diseases, benign neoplasms or papillary carcinoma, whereas follicular cancer tissues were without interleukin-6 and interleukin-1 alpha. In contrast with previous studies, interleukin-6 and interleukin-1 alpha were demonstrated in TFEC from patients with both Graves' disease and Hashimoto's thyroiditis, and the presence of these cytokines was related to the stage of the autoimmune process.

Adenoma↗
PubMedDate not supplied

Vascular endothelial growth factor (VEGF) receptor neuropilin-1's distribution in astrocytic tumors.

Neuropilin-1 is a VEGF165- and semaphorin receptor expressed by endothelial cells and tumor cells. The specific function of neuropilin-1 is not fully known, but in the developing nervous system neuropilin, as a semaphorin receptor, has been shown to influence neuronal guidance. The expression of neuropilin-1 was studied in low-grade and high-grade astrocytic tumors, the latter characterized by extensive angiogenesis. We examined 20 low-grade astrocytomas (WHO grade II) and 46 glioblastomas (WHO grade IV) immunohistochemically for neuropilin-1, p53 and EGFR. The glioblastomas were according to the p53 and EGFR expression classified as 35 primary--de novo--glioblastomas, 9 secondary glioblastomas, and 2 uncertain cases. Furthermore, the presence of mast cells was evaluated to search for any potential function in angiogenesis. The glioblastomas expressed neuropilin-1 in the endothelial cells of the proliferating vessels and the majority of the glioblastomas had immunoreactive neoplastic astrocytes, with no difference between the glioblastoma subgroups. Six out of twenty of the low-grade astrocytomas were negative in the endothelial cells and 8 out of 20 in the tumor cells for neuropilin-1. Mast cells were observed in the collagen matrix around larger vessels in the leptomeninges, but not adjacent to malignant tumor vessels or as part of the tumor process itself. Increased expression of neuropilin-1 is shown in endothelial cells and in neoplastic astrocytes of glioblastomas. Less neuropilin-1 expression is found in about half of the low-grade astrocytomas in both neoplastic astrocytes and endothelial cells. The results suggest a correlation between neuropilin-1 and vascularity in human astrocytic tumors and a possible role for neuropilin-1 as a receptor for VEGF-induced angiogenesis.

Astrocytoma↗
PubMedDate not supplied

Acardiac twin with preserved brain.

The fatal acardiac syndrome is a rare complication of monochorionic twinning and is reported in 1 of 35,000 births. It is caused by arterioarterial and venovenous placental anastomoses leading to circulatory predominance of 1 twin. The donor 'pump' twin provides circulation for itself and for the recipient acardiac twin. The acardiac twin is usually grossly abnormal with severe reduction anomalies of the upper part of the body. We report a twin pregnancy, where a recipient twin initially by ultrasound was misdiagnosed as dead. In the third trimester the supposedly dead twin presented as an edematous acardiac twin without peripheral reduction defects and a nearly normally developed brain. An acardiac twin with a nearly normal external appearance and an almost normally developed brain, nourished by a surviving twin brother, has not previously been described in the literature.

Adult↗
PubMedDate not supplied

Immunohistochemical investigation of p53 and EGFR expression of oligodendrogliomas.

The biological behavior of oligodendrogliomas is somewhat unpredictable. A supplementing prognostic factor is, therefore, desirable. Thirty-two supratentorial pure oligodendrogliomas were studied immunohistochemically by exposing the tumors to a monoclonal antibody towards the p53 protein, and a polyclonal antibody against the epidermal growth factor receptor (EGFR). A mean p53 labeling index (% of tumor cells stained) of 8.6% and a weak EGFR expression in 18 of the oligodendrogliomas were found. Univariate analysis showed no correlation between p53, EGFR expression and prognosis. Multivariate analysis showed that age was a prognostic factor for survival.

Adolescent↗
PubMedDate not supplied

Nitric oxide synthase expression of oligodendrogliomas.

In the central nervous system, nitric oxide (NO) has a variety of biological functions including vasorelaxation and neurotransmission. The synthesis of NO is catalyzed by NO synthases (NOS) existing in 3 isoforms, neuronal NOS (nNOS), inducible NOS (iNOS) and endothelial NOS (eNOS). NO synthase has implications in the pathophysiology of primary glial brain tumors with enhanced expression of nNOS and eNOS in high-grade astrocytic tumors, WHO grades III and IV. Only minor groups of pure oligodendrogliomas have been investigated. The aim of the investigation was to study the expression of the 3 NOS isoforms in this genetically divergent group of primary gliomas and to correlate the findings with tumor grade and expression pattern for the major group of gliomas--the astrocytomas. We examined the NOS expression in 35 oligodendrogliomas, WHO grade II, and 7 anaplastic oligodendrogliomas, WHO grade III, by immunohistochemical methods using formalin-fixed paraffin-embedded material. We observed only a minor expression of nNOS and sparse expression of eNOS in the tumor cells, but a vivid expression of eNOS in the vascular endothelial cells in both the tumor and the surrounding tissue. The rich expression of eNOS in oligodendroglioma vessels independent of tumor grade may suggest that blood flow and angiogenesis in these richly vascularized tumors are modified by NO. Interestingly, enhanced expression of inducible NOS was observed in the oligodendroglial tumor cells in 19 of 35 oligodendrogliomas (54%) and in 2 of 7 anaplastic oligodendrogliomas (29%). This is diverging for iNOS expression in astroglial tumors and the data could be indicative of iNOS exerting anti-tumor activity which may protract the progression from low-grade oligodendrogliomas to more anaplastic types.

Brain Neoplasms↗
PubMedDate not supplied

Papillary glioneuronal tumor--a new tumor entity.

Glioneuronal neoplasms of the CNS comprises a heterogeneous group of generally low-grade tumors expressing glial and neuronal cells of varying differentiation. Recently, a new variant of the glioneuronal tumors has been identified. We present a case of a glioneuronal tumor located in the left frontal lobe of a 16-year-old boy who developed seizures 6 months after brain concussion. MR scan demonstrated an irregular, but well circumscribed, mixed cystic and solid tumor with contrast enhancement in the solid part. Histology showed a papillary glioneuronal tumor. The tumor is indolent with no sign of recurrence after gross total resection.

Adolescent↗
PubMedDate not supplied

Nitric oxide synthase expression and enzymatic activity in human brain tumors.

Nitric oxide (NO) is synthesized by NO synthases (NOS), existing in 3 isoforms. NO influences a great variety of vital functions including vascular tone and neurotransmission. Under conditions of excessive formation, NO emerges as an important mediator of neurotoxicity in a variety of disorders of the central nervous system (CNS). Inhibitors of NOS are available that may modify the activity of all isoforms, which may be of clinical relevance. The expression of the 3 NOS isoforms nNOS, iNOS and eNOS and NOS enzymatic activity was examined in 40 patients with primary CNS tumors (gliomas WHO grades I - IV and meningeomas WHO grades I - III) and in 13 patients with metastases from adenocarcinomas or malignant melanomas. A polyclonal antibody directed against nNOS and monoclonal antibodies directed against iNOS and eNOS were used for immunohistochemical staining. NOS enzymatic activity, measured by labeled arginine to citrulline conversion, was assessed in tissue specimens obtained from the same tumors. NOS data were compared with clinical variables and the degree of edema as judged from MR scanning. nNOS expression was increased in tumor cells of glial neoplasms and most pronounced in high-grade tumors, WHO grades III and IV, and in the carcinoma and melanoma metastases. Low-grade gliomas, WHO grades I and II and meningeomas expressed no or only little nNOS. iNOS was only expressed in a few tumors. eNOS was expressed sporadically in the tumor cells while the expression was increased in vascular endothelial cells in both the tumor itself and the peritumoral area of glial neoplasms, and in metastases. eNOS expression was sporadic in endothelial cells of meningeomas. NOS enzymatic activities were heterogeneous among tumor types (0 - 13.8 pmol/min/mg of protein) without correlation to the NOS expression found by immunohistochemical techniques. Likewise, NOS activity and expression was not correlated to the clinical scores or brain edema. In conclusion, nNOS expression may be a putative useful indicator of brain tumor differentiation and malignancy. The enhanced expression of eNOS in vascular endothelial cells of glial neoplasms and metastases raises the possibility that NO production in tumor endothelial cells may contribute to tumor blood flow regulation and possibly brain edema.

Adenocarcinoma↗