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Biomedical subjects

M Heine

Publications and source records attributed to M Heine.

At least 19 recordsLinked to original sources
PubMed1995

Mutation and expression of TP53 in malignant melanomas.

Mutations of the TP53 gene are the most common genetic alterations in human malignancies. Overexpression of the p53 protein has been reported in high frequencies in all types of skin cancer. To determine the role of TP53 in the pathogenesis of malignant melanoma, we investigated the expression of p53 in 12 cell lines and 145 primary and metastatic lesions by immunohistochemistry. Overexpression of p53 was predominantly detected in the cytoplasm of the cells in 96 (66%) tumor and 12 (93%) cell lines. In contrast to findings in other tumor types, in melanomas immunoreactive cells were found in clusters or as scattered single cells. In primary melanomas, the frequency of p53 overexpression did not correlate with tumor thickness. Nucleotide sequencing of TP53 genes of 24 melanoma tumors/cell lines demonstrated point mutations in seven samples, all coding for mutant p53 protein species. The frequency of TP53 alterations of 20%-30% is lower than in other skin tumor types. Notably, immunohistochemistry was not a suitable method to distinguish overexpression of wild-type p53 from mutant species, since cell lines/tumors with TP53 mutations did not show distinctive staining patterns. The mutation pattern in six out of seven lesions was similar to that caused by ultraviolet light damage. This finding may be regarded a further indication for a pathogenetic role of UV light damage in at least a subgroup of malignant melanomas.

Antibodies, Monoclonal↗
PubMed1995

Malignant proliferating trichilemmal cyst.

We report a case of a metastasizing proliferating trichilemmal cyst. A 78-year-old man had multiple common and two proliferating trichilemmal cysts, one of which showed malignant transformation as evidenced by lymph node metastases. Despite surgical removal of the malignant tumor, extensive metastatic disease rapidly occurred. This case exemplifies the difficulties in diagnosis and treatment of these rare tumors and their unpredictable course.

Aged↗
PubMed1995

Expression of p53 protein in malignant melanoma: clinicopathological and prognostic implications.

In the present study, we investigated the expression of the tumour suppressor protein p53 in 113 primary and 43 metastatic malignant melanomas by immunohistochemistry, and correlated the findings with clinicopathological parameters such as histological melanoma subtype, thickness of primary melanomas (Breslow thickness) and patient outcome. In primary melanomas, the polyclonal anti-p53 antibody CM-1 detected immunoreactivity in 70% of the lesions, predominantly in the cytoplasm. Signals were observed in this cellular compartment in 57% of the melanomas, whereas in 32% nuclear p53 over-expression was detected. Immunohistochemistry, using the monoclonal antibody DO-1, revealed lower staining frequencies. However, both antibodies showed congruent results in approximately 80% of the cases. Overall, immunoreactivity was observed in 73% of superficial spreading melanomas, but only in 52% of lentigo maligna melanomas. This difference (P < 0.001) was mainly due to a lower frequency of cytoplasmic immunoreactivity (P < 0.002). There was no difference with respect to cytoplasmic and nuclear immunoreactivity between thin (< 1 mm thickness) and thicker primary melanomas. Staining frequencies detected in metastatic lesions seemed to be lower than in primary tumours. In 103 primary melanomas, follow-up data for at least 5 years were available. In 71% (54 of 76) of the primary melanomas which did not recur, and in 78% (21 of 27) of tumours with subsequent metastases, p53 over-expression was detected by CM-1. However, this difference was not statistically significant. The results of the present study indicate that immunoreactivity to anti-p53 antibodies is a common observation in malignant melanomas, with staining signals predominantly found in the cytoplasm of cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Nucleus↗
PubMed1994

Differential diagnosis of keratoacanthomas and squamous cell carcinomas: diagnostic value of DNA image cytometry and p53 expression.

DNA-cytometry and immunohistochemistry with the anti-p53 antibody DO-1 was performed in 24 keratoacanthomas (KA) and 21 squamous cell carcinomas (SCC) (13 well-differentiated, 8 moderately differentiated) to establish the possible value of these methods for the differential diagnosis of both epithelial tumors. Aneuploidy was detected in 1 (4%) KA and 12 (57%) SCC (p < 0.05). In the latter tumors, histologic grade was associated with an abnormal DNA-content. Six (46%) well and 6 (75%) moderately differentiated SCC were shown to be aneuploid. Over-expression of p53 protein was found in 16 (76%) SCC and 14 (66%) KA (p > 0.05; not significant). However, quantification of p53 expression by evaluating both the intensity of immunostaining and the number of cells with over-expression by means of an immunoreactivity score (IRS) showed significant differences (p < 0.05). There was no correlation of p53 over-expression and aneuploidy in the tumors examined. The analysis of ploidy and immunostaining with anti-p53 antibodies may give useful additional information regarding the differential diagnosis of SCC and KA, if only aneuploidy or a high IRS are considered.

Carcinoma, Squamous Cell↗
PubMed1994

[Fatal diffuse alveolar damage after gold medication].

We report about the case of a 74-year-old woman who suffered diffuse alveolar damage and consecutive lethal pulmonary failure after gold therapy for rheumatoid arthritis. This is the fourth documented case of fatal pulmonary failure following gold therapy. The clinical findings were dominated by severe dyspnoea that warranted respirator therapy shortly after admission. Chest radiographs showed progressing confluent perihilar patchy infiltrates that suggested interstitial involvement. Steroid therapy had only a short-lasting effect on the respiratory failure, the patient died in prolonged hypoxic circulatory failure. Post-mortem examination showed the organotypical findings of diffuse alveolar damage in proliferative stage with advanced pulmonary fibrosis. With the discontinuation of gold medication and early steroid therapy, this disease which is based on immunological pathomechanisms is usually reversible. Both the knowledge of this entity and early diagnosis are essential for a promising therapeutic intervention.

Aged↗
PubMed1993

Mechanisms of hepatotoxicity caused by dacarbazine in rats.

Possible risks of fatal dacarbazine hepatotoxicity have not been studied systematically. We therefore asked whether dacarbazine hepatotoxicity is influenced by the dose or mode of application, by dacarbazine light-decay products, by prior liver damage or by an induction of dacarbazine metabolism. 22 Sprague-Dawley rats were treated with 4.5 mg and 200 mg dacarbazine/kg bodyweight i.p. and i.v., with dacarbazine light-decay products and with 4.5 mg and 200 mg dacarbazine/kg bodymass after previous galactosamine and ethanol treatment. Serum alanine aminotransferase, cholinesterase and white blood cell and platelet numbers were measured and liver histology was evaluated. Dose-dependent dacarbazine hepatotoxicity could be demonstrated by histology. The mode of application, dacarbazine light-decay products and acute liver damage did not influence dacarbazine hepatotoxicity. However 200 mg dacarbazine/kg bodymass after ethanol pretreatment caused significant serological changes and a significant leucodepression. The increased hepato- and myelotoxicity after induction of hepatic microsomal enzymes should be reason to exclude ethanol and drugs that induce hepatic microsomal enzymes prior to treatment with dacarbazine.

Alanine Transaminase↗
PubMed1993

[Diagnosis of local panarteritis nodosa of the uterine cervix].

A 44-year old woman was referred because of metrorrhagia and asthenia. A diagnosis of uterine malignancy was suspected on the basis of the management of the Cervix uteri and an elevated erythrocyte sedimentation rate. Conisation and hysterectomy were performed, and histological examination revealed necrotising vasculitis affecting the Cervix uteri. Corpus uteri, muscle and fat biopsies showed no Periarteritis nodosa lesions. The incidental finding of necrotising arteritis in a surgical uterine specimen, involves further study to exclude systemic disease. The ability to involve any organ in the body makes it possible for specialists in every branch of medicine to be involved in the management and care of these patients.

Adult↗
PubMed1993

Human and murine dermis contain dendritic cells. Isolation by means of a novel method and phenotypical and functional characterization.

Dendritic cells (DC) comprise a system of cells in lymphoid and nonlymphoid organs that are specialized to present antigens and to initiate primary T cell responses. The Langerhans cell of the epidermis is used as a prototype for studies of DC in the skin. We have characterized a population of DC in human dermis, one of the first examples of these cells in nonlymphoid organs other than epidermis. To identify their distinct functions and phenotype, we relied upon the preparation of enriched populations that emigrate from organ explants of dermis. The dermal cells have the following key features of mature DC: (a) sheet-like processes, or veils, that are constantly moving; (b) very high levels of surface MHC products; (c) absence of markers for macrophages, lymphocytes, and endothelium; (d) substantial expression of adhesion/costimulatory molecules such as CD11/CD18, CD54 (ICAM-1), B7/BB1, CD40; and (e) powerful stimulatory function for resting T cells. Dermal DC are fully comparable to epidermis-derived DC, except for the lack of Birbeck granules, lower levels of CD1a, and higher levels of CD36. DC were also detected in explants of mouse dermis. We conclude that cutaneous DC include both epidermal and dermal components, and suggest that other human nonlymphoid tissues may also serve as sources of typical immunostimulatory DC.

Animals↗
PubMed1992

[Extraction of an artery in rectal biopsy].

A biopsy of a rectal carcinoma has led to the extraction of a 2.5 cm arterial specimen, followed by an arterial bleeding. The cause of this exceptional complication was the presence of atypical vessels reaching the rectal lumen due to tumor ulceration.

Adenocarcinoma↗
PubMed1992

Prostaglandin photoaffinity probes: synthesis and binding affinity of C-18 substituted PGF2 alpha prostanoids bearing a perfluorinated aryl azide.

C-18 Phenoxy analogs of prostaglandin F2 alpha (PGF2 alpha) that possessed a perfluorinated aryl azide and an aryl iodide substituent were synthesized and evaluated as potential photoaffinity probes for PGF2 alpha. Prior studies indicated that only hydrophobic modifications in the omega-side chain of PGF2 alpha were compatible with high binding affinity, and this finding excluded the use of a hydroxyl-substituted C-18 phenoxy group as an activated aryl ring capable of radioiodination. Consequently, an alternate means of introducing the iodine substituent using an ipsosubstitution of a trimethylsilyl arene was developed. Although this strategy was successful from a synthetic perspective, the potential PGF2 alpha photoaffinity probe, (15S)-18-[3'-((4''-azido-2'',3'',5'',6''-tetrafluorophenyl)- methoxy) methyl-5'-iodophenoxy]-19,20-bisnorprostaglandin F2 alpha, exhibited only marginal competitive binding with [3H]-PGF2 alpha to ovine luteal cells and to plasma membranes of bovine corpora lutea. The hydrophobic but bulky C-18 substituent was presumably incompatible with effective receptor binding.

Affinity Labels↗
PubMed1992

Prostaglandin photoaffinity probes: synthesis and binding affinity of aryl azide-substituted C-1 esters of prostaglandin F2 alpha.

In seeking prostaglandin F2 alpha (PGF2 alpha) photoaffinity probes possessing both an efficient, photoactive cross-linking substituent and a radiolabel of high specific activity, the synthesis and binding affinity of PGF2 alpha C-1 esters in which the alcohol component possessed either an aryl azide or a perfluorinated aryl azide was investigated. These derivatives showed great promise due to their ability to compete for the binding of [3H]-PGF2 alpha in both a luteal membrane binding assay and in a whole luteal cell binding assay. Identification of the C-1 site in PGF2 alpha as a site for modification of the PGF2 alpha molecule with photoactive alcohol derivatives represented a logical step toward the goal of developing a useful PGF2 alpha photoaffinity probe.

Affinity Labels↗
PubMed1991

Gram-negative bacterial pneumonia with secondary aspergillosis in an AIDS patient.

A 40-year-old, HIV-infected female patient received antibiotic treatment for a urinary tract infection. After the initial success of therapy and a symptom-free period, she developed pneumonia with septic shock and adult respiratory distress syndrome (ARDS). In spite of intensive care and respirator therapy with positive end-expiratory pressure (PEEP), she died of infectious toxic shock. Autopsy findings showed relapsing, gram-negative, bacterial pneumonia (morphologically compatible with Klebsiella pneumonia) and secondary, invasive aspergillosis. The pathogenesis and epidemiology of these unusual complications of AIDS are discussed.

AIDS-Related Complex↗
PubMed1991

[Multilocular angiosarcoma with involvement of the heart].

A thyroid tumour, initially diagnosed as an anaplastic carcinoma of the thyroid, was removed in a 66-year-old woman. Further examination, other than ultrasonography of the abdomen (normal), were refused, 26 months later a painful swelling was noted in the right buttock: a fist-sized haematoma, without evidence of malignancy was removed at another hospital. Computed tomography revealed a cystic tumour in the left upper abdomen, about 8 x 11 cm, not clearly related to any organ. Echocardiography, performed because of atrial fibrillation, demonstrated a space-occupying lesion, 42 x 38 mm, in the left atrium with central necroses and originating broad-based from the interatrial septum and the aortic root. The retroperitoneal upper-abdominal tumour encircling the root of the aorta and a gluteal tumour in the area of the previous haematoma could not be completely removed. Histologically they and the previously removed (and again examined) thyroid tumour were angiosarcomas. Removal of the atrial tumour was not attempted. Six months later it had penetrated the entire atrial septum and grown into the right atrium. The patient had lost 25 kg and three months later died of respiratory failure. Autopsy was refused. The findings suggest a left-atrial angiosarcoma which may well have been the primary tumour site. In case of angiosarcomatous tumours echocardiography should be performed as a staging examination.

Aged↗