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Biomedical subjects

H J Altermatt

Publications and source records attributed to H J Altermatt.

At least 109 records · Page 6Linked to original sources

Paraneoplastic anti-neuronal nuclear IgG autoantibodies (type I) localize antigen in small cell lung carcinoma.

Type I anti-neuronal nuclear autoantibodies (ANNA-I, also known as "Hu") are a distinctive serologic marker of small cell lung carcinoma (SCLC) in patients who have peripheral neuropathies or encephalomyeloradiculopathies. A tumor antigen reactive with these antibodies has been identified by other investigators by Western blot analyses, but an antigen has not been localized in SCLC immunohistochemically. We therefore tested, by indirect immunofluorescence, the sera of 49 sequential ANNA-I-positive patients and 30 control subjects for IgG reactive with SCLC. Two tumor cell lines were tested, one established from the primary tumor of a patient with Lambert-Eaton syndrome and the second from the metastatic lesion of a patient without neurologic disease. IgG in all ANNA-I-positive sera bound to both tumors. In most instances, the pattern resembled that seen in neurons, with strong homogeneous nuclear staining, sparing of nucleoli, and faint cytoplasmic staining. A highly significant correlation was noted between endpoint dilutions obtained on SCLC substrates and on central and peripheral neurons (r = 0.863; P less than 0.001). IgG in 3 of 30 control sera bound in low titer to SCLC cells but not to neurons, and 9 control sera contained non-organ-specific anti-nuclear antibodies (ANA). The ANA IgG was absorbed equivalently by homogenates of SCLC or colonic adenocarcinoma cells. In contrast, the reactivity of ANNA-I IgG with cerebellar and myenteric plexus neurons was absorbed only by homogenized SCLC cells. These findings suggest that SCLC antigens account for all neuronal reactivity of ANNA-I. IgG of this specificity may serve as a useful reagent for identifying SCLC cells in surgical pathologic and cytologic specimens.

Aged↗

Photodynamic therapy with chlorins for diffuse malignant mesothelioma: initial clinical results.

Four patients underwent intraoperative photodynamic therapy after surgery with meso-tetra-(hydroxyphenyl)-chlorin (mTHPC-PDT) for diffuse malignant mesothelioma. Preliminary procedures were performed in two patients in order to establish the efficacy of mTHPC-PDT and to optimise its tumoricidal effect. The tumoricidal effect was related to the mTHPC dose, light dose and the time interval between sensitation and activation. 0.3 mg kg-1 mTHPC activated after 48 h with 10 Joules cm-2 of non-thermal laser light at 650 nm resulted in a 10 mm deep tumour infarction, due to tumour vessel necrosis and thrombosis. The mTHPC tissue concentration was up to 14 times higher in the tumour than in normal tissues. Skin photosensitivity was mild, dose dependent and occurred 3 to 10 days after administration of mTHPC. According to the results obtained, intraoperative mTHPC-PDT was performed following pleuropneumonectomy in two, pleurectomy and lobectomy in one and pleurectomy in one patient. Ten Joules cm-2 were delivered to the diaphragm and the costophrenic sulcus and 5 Joules cm-2 to the remaining thoracic cavity. The postoperative course was marked by loss of appetite, fluid retention, hypoproteinemia and severe chest pain. One patient succumbed from aspiration pneumonia. The remaining patients developed no neural or vascular alterations and no bronchial stump insufficiency during follow-up. mTHPC-PDT following surgical tumour resection deserves further evaluation in good risk patients with diffuse malignant mesothelioma.

Combined Modality Therapy↗

[Subependymal giant cell astrocytoma].

Subependymal giant-cell astrocytomas (SEGA) are rare brain tumors. They occur typically in the walls of the lateral ventricles and very seldom in the wall of the third ventricle. In our experience, all patients with SEGA have had tuberous sclerosis. Between January 1950 and May 1990, of our 345 patients with tuberous sclerosis 22 were found to have SEGA. The diagnosis being made histologically in symptomatic cases or by clinical or neuroradiologic methods. The histological, immunohistochemical and ultrastructural features of this unique tumor are discussed. To date, histopathologic methods have not resolved the issue of whether these tumors are exclusively astrocytic or neuronal in nature, or show features of both. Modern immunohistochemical and/or molecular-biological techniques will no doubt elucidate the histogenesis of this highly characteristic, albeit polymorphous tumor.

Adult↗

Paraneoplastic anti-Purkinje and type I anti-neuronal nuclear autoantibodies bind selectively to central, peripheral, and autonomic nervous system cells.

Autoantibodies provide serologic markers for subacute cerebellar degeneration in the setting of gynecologic or breast cancer (anti-Purkinje cell cytoplasmic antibodies, PCAb), and for encephalomyeloradiculoneuropathies in the setting of small cell lung carcinoma (type I anti-neuronal nuclear antibodies, ANNA-I). PCAb and ANNA-I are not species-restricted in their specificities. The subject of this report is a systematic immunocytochemical investigation of the distribution and types of cells in the mouse central and peripheral nervous system that bind these IgG autoantibodies. Sera used for the study were from two patients with prototypic PCAb reactivity and two with prototypic ANNA-I reactivity, none of whom had evidence of other autoantibodies, and from four age- and sex-matched healthy control subjects. The patients' clinical features were consistent with the classic syndromes that have been reported with PCAb and ANNA-I, respectively. PCAb bound prominently to the cytoplasm of cerebellar Purkinje cells, and also to other large cytoplasm-rich neurons throughout the central nervous system, to neurons in sensory and sympathetic ganglia and myenteric plexus, and to cells of the adrenal medulla. ANNA-I, on the other hand, bound to virtually all neurons in the central and peripheral nervous system, including sensory and autonomic ganglia, myenteric plexus and cells of the adrenal medulla. An unanticipated finding was that immunoreactivity with ANNA-I was enhanced by fixing tissues briefly with formalin. Astrocyte processes were stained by PCAb and by ANNA-I (but not by the control sera). The cytoplasm of sciatic nerve Schwann cells was stained strikingly by PCAb, but ANNA-I did not bind to Schwann cells. Although it has not yet been determined whether or not PCAb or ANNA-I per se are pathogenic, it is apparent that they represent at least a component of an immune response that is initiated by tumor antigens. The distribution of these tumor-related antigens in the nervous system is consistent with the diversity of neurologic manifestations that can occur in individual patients with the associated paraneoplastic syndromes.

Aged↗

Subependymal giant cell astrocytoma: a clinical, pathological, and flow cytometric study.

Of 345 patients with tuberous sclerosis complex evaluated at the Mayo Clinic from 1950 to 1989, 23 were identified as having brain tumors. In 20 of the 23, histological or clinical evidence showed the tumor to be a subependymal giant cell astrocytoma. A search of the Mayo Clinic tissue registry yielded 73 giant cell-containing astrocytomas and intraventricular gliomas exclusive of ependymomas. Reexamination revealed no further examples of subependymal giant cell astrocytoma in patients without features of the tuberous sclerosis complex. Considerable histological variation was observed in the 15 subependymal giant cell astrocytomas subjected to critical microscopic review. It is of note that no correlation was noted between either the histological features, such as atypia, mitoses, endothelial proliferations, necrosis, or the flow cytometric characteristics and the clinical course or the survival time of the patients.

Adolescent↗

Heavy water enhances the antineoplastic effect of 5-fluoro-uracil and bleomycin in nude mice bearing human carcinoma.

The antineoplastic effect of heavy water on the growth of xenotransplanted human carcinoma was compared to that of 2 cytostatic drugs. Seven-week-old BALB/c-nu/nu mice were inoculated subcutaneously with a poorly differentiated oropharyngeal squamous-cell carcinoma, or with variants of carcinoma of the large intestine. After tumor inoculation, 3 subgroups of mice were treated by: (i) moderately deuterated drinking water; (ii) i.p. injections of 5-Fluoro-uracil (5-FU) or Bleomycin; (iii) a combination of deuterated drinking water and of the cytostatic drugs. Control mice were not treated. Heavy water delayed growth of all carcinoma variants. The cytostatic drugs slowed down the growth of the 2 poorly differentiated tumor variants. Conversely, 5-FU did not retard the growth of the moderately well differentiated colon carcinoma. Heavy water combined with either cytostatic drug showed synergistic effects in the 2 poorly differentiated tumor variants. The tumors of treated animals weighed 36% to 90% less than those of control animals. The antineoplastic effects were more conspicuous in poorly than in moderately well differentiated tumor variants. Cytokinetic parameters such as labelling indices following application of 5-125I-Iodo-2'deoxyuridine, and of Ki-67, a monoclonal antibody (MAb) directed against an antigen of proliferating cells, or mitotic indices and tumor volume doubling time, combined with the results of histologic evaluation of the tumors, suggested an underlying deuterium-induced prolongation of tumor-cell cycle times and a reduction of the growth fraction.

Adenocarcinoma↗

[Precancerous and early stage colorectal carcinoma: clinico-pathological implications].

With regard to the clinical implication and importance of carcinoma prevention, the histogenesis and pathobiology of the precancerous lesions and conditions of the colorectum are described. Polyps, dysplasia (with and without ulcerative colitis), adenomas and polyposis syndromes are defined, and their potential as markers for an increased risk for colorectal cancer is estimated. For the time being, the prevention of colorectal cancer is only possible by interrupting the multistage carcinogenesis in due course, i.e. during the precancerous stages. The exact knowledge of the latter is the rational of the clinical procedures.

Adenomatous Polyposis Coli↗

[Lyophilized allogeneic costal cartilage as reconstruction material in middle-ear surgery].

From 1.1. 1983 to 31.3. 1983 we used lyophilised allogenic costal cartilage as reconstruction material in middle ear surgery in 53 patients. Reconstructions of the posterior bony canal wall were performed in cholesteatoma surgery in 89% of the cases. Lyophilised cartilage was also used for the restoration of a traumatic defect in the posterior bony canal wall, for the reconstruction of an atretic ear and an old radical cavity, for closing of a bony defect in the roof of the mastoid, and shaping a cartilaginous columella, or modiolus. Lyophilised cartilage fulfills its function completely in 87% of the cases. 5 reconstructions of the posterior bony canal wall were moderately sunk in. The ears were however dry and free of an inflammation. Both the ear canal and the drum were easy to survey. In 2 cases of a recurrent cholesteatoma, the lyophilised cartilage was extensively destroyed. There were no problems, such as incompatibility, host-versus graft reaction, infection or distortion of the cartilage. With regard to our results, we recommend lyophilised allogenic costal cartilage as reconstruction material in circumscribed defects of the bony ear canal and in bony defects of the skull base of the ear, if larger and thicker pieces of cartilage, as can obtained from the patient's ear, are necessary.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

The epithelium of the human endolymphatic sac: immunohistochemical characterization.

A panel of monoclonal and polyclonal antibodies has been used to study the epithelium of the extraosseous part of the human endolymphatic sac (ES) by immunohistochemistry. The ES epithelium reacted with several epithelial markers such as Lu-5, different anticytokeratins, antiepithelial membrane antigen, and anticarcinoembryonic antigen. Unexpectedly, all epithelial cells also revealed a strong positive reaction for the mesenchymal marker vimentin and for S-100 protein. 'Neuroendocrine', a neurosecretory antigen, and neuron-specific enolase reactivity was detected in a few epithelial cells. The results support the assumption that the ES epithelium is metabolically active and capable of secretion and resorption. These findings are in keeping with results of functional experiments in animals. The demonstration of neurosecretory antigen and neuron-specific enolase in some cells indicate that the epithelium may also have paracrine functions.

Antibodies, Monoclonal↗

Human endolymphatic sac: evidence for a role in inner ear immune defence.

In an immunohistochemical study, monoclonal and polyclonal antibodies have been used to identify cells and structures in the extraosseous part of endolymphatic sacs (ES) which were removed at autopsy from 30 persons. Intraluminal, intraepithelial, intravascular and perisaccular cells expressed the leukocyte common antigen. Immunostaining with antibodies against the CD4 and CD8 antigens revealed the predominance of CD4-positive T lymphocytes in the ES. A few lymphoid cells were found to express the major histocompatibility antigen class II. Interdigitating cells of the Langerhans type were rarely found in the epithelial layer. B lymphocytes were present in the lumen and the stroma of the ES and IgA- or IgG-containing cells in the stroma only. IgA, secretory component and the J chain were detected within epithelial cells and in the lumen of the ES. Macrophages were observed in the lumen and the stroma. Our findings are in accordance with previously published data in animals and man and give further evidence of an important role of the ES in inner ear immune defence.

Antibodies, Monoclonal↗

[Differential diagnosis of atypical plasma cells in the cerebrospinal fluid].

2102 samples of lumbar cerebrospinal fluid (CSF) were examined by qualitative cytology for atypical plasma cells. Samples from seven patients contained such cells. Retrospective investigation of these patients revealed that four of them had had neuroborreliosis, one had multiple sclerosis, one herpes zoster and one malignant non-Hodgkin lymphoma. It is concluded that in a case of unexplained meningoradiculitis with lymphoplasmocytic reaction in the CSF, morphological analysis of the plasma cells can provide important diagnostic pointers.

Adult↗

[Immunoreactive somatostatin in the peripheral olfactory system and nasal mucosa of the human].

Immunohistochemically, the cyclic retradecapeptide somatostatin was demonstrated in periglomerular cells and fibres of the glomerular layer (Fig. 3) of the human olfactory bulb as well as in the superficial granule layer and fibres (Fig. 2) of the olfactory tract. Additionally, somatostatin was found in endothelial cells of subepithelial arterioles and capillaries of the regio olfactoria (Fig. 4a, b) and superior turbinate. We assume that somatostatin has a paracrine transmitter function in the peripheral olfactory system and a regulative function on the blood flow of the superior nasal mucosa.

Adolescent↗

Preparation of human temporal bone for immunohistochemical investigation.

Successful treatment of progressive sensorineural hearing loss with corticosteroids and cyclophosphamide has promoted the notion of a new entity 'autoimmune hearing loss'. In this context, we have examined sera of patients suffering from idiopathic sensorineural hearing loss, in order to study the binding of humoral antibodies to structures of the normal human inner ear. Investigations were carried out with indirect fluorescence techniques on temporal bones obtained at autopsy. To minimize the possibility of artifacts, we suggested that indirect immunofluorescence with the patients' sera should yield a reproducible positivity on sections of at least three normal temporal bones. In this study, we describe a method for removal and preparation of human temporal bone which ensures reproducible immunohistochemical results.

Adolescent↗

[Adenoid basalioma of the axilla].

Basal cell carcinoma is the most common malignant skin tumor in the elderly. It occurs predominantly in the head and neck region. As is well known, skin exposed to sunlight is the most frequent location, but basal cell carcinoma can arise elsewhere. This report describes a 81-year old woman who developed a basal cell carcinoma of the adenoid subtype in the axilla. Before surgical excision, the lesion was diagnosed cytologically. This diagnosis was confirmed by histology. Cytologic examination of skin lesions whose size and location allow this procedure appears to be the sole conservative means of achieving a presurgical diagnosis. The technique is simple. The morphologic differential diagnosis of basal cell carcinoma is discussed.

Aged↗

Multiple hamartomas of the breast.

We report the unusual case of two distinct hamartomas in one of the breasts of a 20-year-old woman. Hamartoma (adenolipoma, fibroadenolipoma, lipofibroadenoma) of the breast, a rare benign lesion, occurs in females. It is unilateral and displays an organoid structure. It is composed of lactiferous ducts, mammary glands, and connective and fatty tissue, surrounded by a pseudocapsule. It causes enlargement of the breast, usually without localized lesion on palpation. Mammographic and intraoperative findings, however, are characteristic. As the microscopic features of hamartoma are similar to those of other related benign lesions of the breast, diagnosis may be difficult by histologic examination alone; in addition, knowledge of radiologic, surgical and clinical findings may be required.

Adult↗

[Otosclerosis. A paramyxovirus-induced inflammatory reaction].

Despite intensive investigation the cause of otosclerosis remains unknown. Recent immunohistochemical and electron microscopic studies of otosclerotic stapes have revealed a possible viral aetiology. Therefore we investigated the histology, ultrastructure and immunohistochemistry of fragments of otosclerotic footplates. Immunoglobulins G (IgG) and A (IgA) were found in plasma cells, oseocytes, chondrocytes and connective tissue of the active lesions. Polyclonal and monoclonal antibodies against paramyxovirus and rubella virus antigens produced reproducible reactions with these antigens at different sites of otosclerotic stapes, especially in the epithelial cells of the overlying middle ear mucosa. Using specific T-lymphocyte and B-lymphocyte markers about 80% of the lymphocytes present in the otosclerotic footplate proved to be T-lymphocytes. There was neither deposition of immunoglobulins nor any expression of viral antigens in non-otosclerotic footplates which were investigated as controls. Our results indicate that otosclerosis is an inflammatory reaction of the otic capsule initiated or caused by paramyxovirus and/or rubella virus. The silent progress of the disease and its onset under certain conditions, e.g. endocrine upsets, show similarity to slow viral infections.

Adult↗

Heavy water delays growth of human carcinoma in nude mice.

Deuterium-enriched water has an antiproliferative effect on transplantable mouse tumors without toxic side effects. Since the response to treatment of human carcinomas growing in nude mice is deemed to be a good indicator of the potential clinical behavior of these tumors, we studied the influence of this stable isotope of hydrogen on the growth of xenotransplanted human carcinomas of various histologic types, grades, and primary sites. Seven-week-old Balb/c-nu/nu mice were inoculated subcutaneously, either with oropharyngeal squamous cell carcinomas or with carcinomas of the large intestine. After tumor inoculation, the mice were given drinking water containing 30 atom% D2O. Heavy water effectively retarded the growth of the human carcinomas. At the end of the experiment, the weight of the tumors was reduced to values ranging from 22% to 65% of the control values. The reproducible antiproliferative effect was more conspicuous in poorly differentiated carcinomas than in moderately well-differentiated variants. Since animals in both groups, kept under identical conditions, drank the same amount of water and had similar body weights, the difference in tumor growth can be attributed to the moderate deuteration of the hosts.

Aged↗