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C Zietz

Publications and source records attributed to C Zietz.

At least 37 records · Page 2Linked to original sources

[HIV-associated non-Hodgkin's lymphomas (HIV-NHL) in the area of the head-neck].

The life span of HIV-infected patients has increased because of anti-retroviral therapy and improved means for treating opportunistic infections. However, HIV infection and subsequent immunosuppression result in an increased risk of high-grade B-cell lymphomas. The purpose of this study was to determine the incidence, localization, clinical features, therapy and survival time of patients with HIV-related lymphomas of the head and neck. Between 1988 and 1995, 280 HIV-infected patients presented with otolaryngologic symptoms. Seventy-two (25.7%) were found to have a neoplastic disease. Fifty-six of these patients (20%) were diagnosed as having Kaposi's sarcoma and 12 (4.3%) had lymphomas. According to the Kiel classification, lymphomas were subdivided into Hodgkin's disease (2 cases) and B-cell lymphomas of high-grade malignancy (10 cases). These latter cases were centroblastic (n = 4), Burkitt's type (n = 4), anaplastic large cell (n = 1) and not classifiable (n = 1). All patients with HIV-related non-Hodgkin's lymphomas (NHL) were men and 8 were homosexuals. The mean age was 36.1 years. In addition to 7 nodal locations, high-grade B-cell lymphomas were found in the oropharynx (n = 2) and palate (n = 1). Four patients underwent chemotherapy, 1 patient underwent radiation therapy and 2 were treated with both methods. Two patients did not receive any treatment and 1 patient underwent laser therapy. The survival time depended on the previous diagnosis of AIDS, the patients' immune status and the karnofsky index. In 2 patients the lymphoma led to the diagnosis of HIV infection. Our findings show that any solitary or enlarging tumors or ulcerating lesions in the head and neck region of HIV patients must be examined histologically to exclude HIV-NHL. We also recommend that young patients with high-grade B-cell lymphomas should undergo HIV screening.

Adult↗

Monocytes in Kaposi's sarcoma lesions are productively infected by human herpesvirus 8.

PCR analysis and serological studies demonstrated a close association between Kaposi's sarcoma (KS)-associated herpesvirus, or human herpesvirus 8 (HHV-8), and the development of Kaposi's sarcoma (KS). The majority of the KS cells were shown to be latently infected by the virus. In this study we investigated which type of cell is productively infected in KS lesions. In situ hybridization was performed with strand-specific RNA probes complementary to the sequences coding for the minor capsid protein (VP23) of HHV-8. The VP23 gene is specifically expressed during the lytic or replicative period of the virus life cycle, and therefore it is a useful marker to detect productively infected cells. By in situ hybridization of KS lesions, a strong hybridization signal was detected only in a small subset of the KS cells of the lesions. Simultaneous application of immunohistochemical staining and in situ hybridization identified the virus-replicating cells to be of monocytic origin. Productively infected monocytes may be an important reservoir for transmission of the virus and for the increase and maintenance of the high load of HHV-8 generally observed in nodular KS lesions during late stages of infection.

Biomarkers↗

Gastrointestinal lymphomas in patients with AIDS.

Non-Hodgkin-lymphoma (NHL)-most frequently high grade B-cell lymphoma-occurs in 5-10% of individuals with HIV-infection. The gastrointestinal tract (GIT) is the most frequent extranodal site of the disease. The optimal therapy for HIV-related lymphoma remains a matter of controversy. In a retrospective analysis we found gastrointestinal lymphoma in ten of 306 HIV-infected patients (3.3%) with a median CD4-count of 92/microliter at time of diagnosis. Median survival for the chemotherapy treatment group was 15 months. The high incidence of gastrointestinal NHL prompted us to commence a prospective survey on diagnostic procedures, therapy and outcome of patients with HIV-infection and gastrointestinal symptoms. 93 of 341 HIV-infected patients with gastrointestinal symptoms were examined by endoscopy. In selected patients we used in addition endoscopic ultrasound (EUS) for visualization and staging before and after chemotherapy. NHL of the GIT was detected in seven of 93 endoscopically examined patients (7.5%). All patients were treated with CHOP initially. Mean survival time was ten months, mean CD4-count at diagnosis 193/microliter (range 0-417). Our results indicate that the diagnosis of gastrointestinal lymphoma should be considered in any HIV-infected patient presenting with unexplained gastrointestinal symptoms. In this group of patients NHL was detected in 7.5% of cases. The use of EUS improves the staging procedure before therapy. Treatment with CHOP resulted in relatively high remission rates and was associated with a low rate of treatment-induced myelosuppression.

Adult↗

Adenoma of the middle ear mucosa.

Benign adenomas of the middle ear are rare tumors. To date, approximately 100 cases of adenomatous neoplasms of the middle ear space have been collected in the United States Armed Forces Institute of Pathology, Washington D.C. This report describes two cases of primary adenomatous neoplasms confined to the middle ear cleft seen at the Department of Otorhinolaryngology at Ludwig Maximilians University Hospital, Munich. Although tumors are derived from lining epithelium of the middle ear mucosa, the unique feature of our first case was based on its origin in the epitympanic part of the tympanic membrane. Histopathology was characterized by an adenomatous morphology without atypia or mitoses, proving its benign behavior. No evidence was found for invasion of adjacent tissue. Simple surgical removal afforded excellent prognosis. Clinical behavior, histological appearance, origin of tumors and differential diagnosis are discussed.

Adenoma↗

HIV-related parotid lymphoepithelial cysts. Immunohistochemistry and 3-D reconstruction of surgical and autopsy material with special reference to formal pathogenesis.

Whether lymphoepithelial cysts in the parotid glands in HIV-infected patients develop from pre-existing salivary gland inclusions in intraparotid lymph nodes or from a lymphoepithelial lesion of salivary parenchyma is unclear. To examine their pathogenesis we performed a histological and immunohistochemical study of salivary specimens from 100 AIDS patients in different disease stages. There is a continuous morphological spectrum of changes within the salivary parenchyma, starting with lymphoid stroma infiltration and evolving to characteristic lymphoepithelial duct lesions with a immunohistochemically proven basal cell proliferation and to fully developed ductal cysts. Involvement of myoepithelial cells-postulated in comparable Sjögren-associated duct lesions-is excluded immunohistochemically. Computer-assisted 3-D reconstructions confirm an association of the cysts with the intralobular duct system. Our study disproves the prevailing hypothesis, which suggests that the lymphoid cell compartment of HIV-associated lymphoepithelial cysts stems from pre-existing intraparotid lymph nodes. The results demonstrate that a secondary lymphatic infiltration of salivary parenchyma provokes a lymphoepithelial lesion of striated ducts with basal cell hyperplasia. The frequent progression to a multifocal cystic lymphoepithelial lesion may be supported by ductal compression through a high degree of lymphofollicular hyperplasia in early disease.

Adult↗

[HIV-associated cysts of the parotid glands. An histomorphologic and magnetic resonance tomography study of formal pathogenesis].

BACKGROUND: Multiple and bilateral parotid Lymphoepithelial cysts (LEC) are encountered in 3-6% of HIV-infected patients. The formal pathogenesis of LEC is controversial. They are thought to develop from embryological salivary gland inclusions in intraparotid lymphnodes. METHODS: Seventeen operative parotid specimens from HIV-infected patients were examined histologically and immunohistologically. Findings of magnetic resonance imaging (MRI) were correlated with the histological results. RESULTS: A continuous spectrum of a lymphoepithelial salivary gland lesion is found, developing initially from a lymphoid infiltration of salivary lobules to lymphoepithelial duct lesions with cystic dilatation up to large ductal cysts (diameter up to 3.5 cm) with highgrade parenchymal atrophy. The ductal and cystic lesions demonstrate an intense basal cell hyperplasia without participation of myoepithelial cells. The MRI findings indicate involvement of the entire tissue of both parotid glands. CONCLUSIONS: The preferred hypothesis of a development of HIV-associated Lymphoepithelial cysts from preexisting salivary lymphnode inclusions cannot be verified. Our results demonstrate a continuous development of the cysts from a Sjögren-like cystic lymphoepithelial lesion of parotid glands. The enormous cystic dilatation of the duct lesions presumably is a consequence of ductal obstruction through basal cell hyperplasia of striated ducts and intense intraglandular lymphofollicular hyperplasia.

Adolescent↗

Vascular endothelial growth factor regulates angiogenesis and vascular permeability in Kaposi's sarcoma.

Abundant vasculature with increased permeability is a prominent histological feature of Kaposi's sarcoma (KS), a multifocal, cytokine-regulated tumor. Here we report on the role of vascular endothelial growth factor (VEGF) in AIDS-KS angiogenesis and vascular permeability. We demonstrate that different cytokines, which were previously shown to be active in KS development, modulate VEGF expression in KS spindle cells and cooperate with VEGF on the functional level. Northern blot analysis as well as studies on single cells using in situ hybridization revealed that VEGF expression in cultivated AIDS-KS spindle cells is up-regulated by platelet-derived growth factor-B and interleukin-1 beta. Western blot and enzyme-linked immunosorbent assay analysis of cell culture supernatants demonstrated that the VEGF protein is secreted by stimulated AIDS-KS spindle cells in sufficiently high amounts to activate proliferation of human dermal microvascular endothelial cells. Basic fibroblast growth factor did not increase VEGF expression but acted synergistically with VEGF in the induction of angiogenic KS-like lesions in a mouse model in vivo. Angiogenesis and cellularity of KS-like lesions were clearly increased when both factors were injected simultaneously into the flanks of mice, compared with separate injection of each factor. A comparable angiogenic reaction as obtained by simultaneous injection of basic fibroblast growth factor and VEGF was observed when cell culture supernatants of AIDS-KS spindle cells were used for these experiments. Finally, analysis of primary human AIDS-KS lesions revealed that high amounts of VEGF mRNA and protein were present in KS spindle cells in vivo. These data provide evidence that VEGF, in concert with platelet-derived growth factor-B, interleukin-1 beta, and basic fibroblast growth factor, is a key mediator of angiogenesis and vascular permeability in KS lesions in vivo.

Animals↗

Consensus-interferon and platelet-derived growth factor adversely regulate proliferation and migration of Kaposi's sarcoma cells by control of c-myc expression.

Platelet-derived growth factor-B (PDGF-B) is a potent paracrine-acting mitogen in Kaposi's sarcoma (KS) lesions. Interferon-alpha is widely used for clinical treatment of KS. Here we show that platelet-derived growth factor-B activates proliferation and migration of cultivated AIDS-KS spindle cells whereas interferon-alpha acts as an inhibitor. At the molecular level, these opposite activities of platelet-derived growth factor-B and interferon-alpha converged onto the adverse regulation of the c-myc gene expression. Platelet-derived growth factor-B induced c-myc mRNA and protein synthesis in cultivated AIDS-KS spindle cells whereas interferon-alpha inhibited these processes. Using c-myc-specific phoshothioate antisense oligodeoxynucleotides, we demonstrated that down-regulation of c-myc expression is sufficient to inhibit proliferation and migration of KS spindle cells in vitro. This indicated that c-Myc protein may be an important regulatory molecule of KS spindle cell proliferation and migration. High amounts of the c-Myc protein were detected in the nuclei of KS spindle cells in histological sections of AIDS-KS biopsies. This suggested that the c-myc gene may also regulate proliferation and migration of AIDS-KS spindle cells in vivo. In this case, c-myc may play an important role in the focus of major pathogenic and therapeutic pathways of KS.

Cell Division↗

Aortic endothelium in HIV-1 infection: chronic injury, activation, and increased leukocyte adherence.

Clinical and serological studies provide evidence for a pathogenetically relevant vasculopathy in acquired immune deficiency syndrome (AIDS); however, the morphological status of the endothelium under conditions of human immunodeficiency virus (HIV)-1 infection is only sparsely documented. In this study we adapted an en face preparation technique of endothelium for use in immunohistochemistry and investigated the aortic endothelium of pre-AIDS and AIDS patients (n = 32) in comparison with an HIV-negative group (n = 17). The control group showed a regular pattern of evenly distributed aortic endothelial cells, whereas the endothelial cell pattern in the HIV-1-infected patients was clearly disturbed. Simultaneously, the degree of leukocyte adherence on the aortic endothelium increased significantly. These changes were accompanied by an up-regulation of the vascular cell adhesion molecule-1 (VCAM-1) and E-selectin (ELAM-1). The endothelium turnover increased, and one-half of the HIV-1-infected patients exhibited HLA-DR (major histocompatibility complex class II) antigen in the aortic endothelium. Our results provide evidence for a profound and repeated injury with regeneration and activation of the endothelium in HIV-1 infection. Injury as well as activation of the endothelium impairs its normal regulatory properties. This could have consequences for the maintenance of the blood-brain barrier; it might influence the immunologically important interaction of the endothelium with T cells; and it might trigger Kaposi's sarcoma.

Acquired Immunodeficiency Syndrome↗

Identification of interleukin-1 and platelet-derived growth factor-B as major mitogens for the spindle cells of Kaposi's sarcoma: a combined in vitro and in vivo analysis.

By means of a combined in vitro and in vivo analysis we provide evidence that IL-1 beta and PDGF-B, but not OSM (oncostatin M) or IL-6, are major mitogens for the spindle cells of Kaposi's sarcoma (KS) in vivo. PDGF-B and IL-1 beta stimulated proliferation of cultivated KS spindle cells in vitro. Analysis of gene expression in vivo revealed that both factors as well as the PDGF beta-receptor are present in KS lesions. By contrast, IL-6 had no effect and OSM inhibited proliferation of cultivated KS spindle cells. Again, the effect of these factors on cultivated KS spindle cells in vitro was reflected by the gene expression observed in KS lesions in vivo. Neither the expression of IL-6 receptor nor of OSM could be detected in KS lesions by in situ hybridization. Moreover, in situ hybridization revealed an identical pattern of gene expression in cultivated KS spindle cells and KS spindle cells in vivo with respect to the above-mentioned cytokines [PDGF-B, IL-1 beta, IL-1 alpha, IL-6, OSM] and their receptors [PDGF beta-receptor, gp130, IL-6 receptor, leukemia inhibitory factor (LIF) receptor]. This further supported the suitability of cultivated KS spindle cells as an in vitro model in order to determine which cytokines may activate proliferation of KS spindle cells in vivo.

Cell Division↗

[Endoscopy of the upper gastrointestinal tract in HIV disease].

Gastrointestinal (GI) symptoms are part of the most frequent complaints in HIV disease. A methodical effort is required to identify treatable syndromes. Progressive immunodeficiency is associated with increased prevalence of opportunistic or non-opportunistic infections and neoplasms. Dysphagia and odynophagia, in the majority due to candida esophagitis, are best evaluated by endoscopy. In the presence of diarrhea, upper GI endoscopy is indicated if evaluations of stool and endoscopy of the lower GI tract are negative and may uncover proximal small-bowel infection by Cryptosporidium, Microsporidium or Mycobacterium avium. HIV-associated neoplasias (Kaposi's sarcoma, non-Hodgkin lymphomas), not rarely affecting the upper GI tract and sometimes leading to obstruction or bleeding, are reliably diagnosed only by endoscopy. Since visible lesions mostly are nonspecific and normal-appearing mucosa may harbor pathogens, biopsies for pathology and cultures are crucial for correct diagnosis in GI diseases of HIV-infected patients.

AIDS-Related Opportunistic Infections↗

Expression of adhesion molecules, platelet-activating factor, and chemokines by Kaposi's sarcoma cells.

The present study was designed to investigate whether cells cultured from Kaposi's sarcoma (KS), a vascular tumor with a prominent leukocyte infiltration, express molecules important for the recruitment and activation of leukocytes. KS cells expressed intercellular adhesion molecule-1, which was augmented by exposure to IL-1 beta or TNF-alpha. Unlike endothelial cells, resting or cytokine-activated KS cells did not express appreciable levels of intercellular adhesion molecule-2, vascular cell adhesion molecule-1, and E-selectin on their surface. Weak expression of vascular cell adhesion molecule-1 mRNA was detectable by Northern blot analysis and, most clearly, by PCR analysis. Upon exposure to inflammatory cytokines, KS cells produced the attractant/activating lipid platelet-activating factor. KS cells expressed appreciable levels of the chemotactic cytokines, monocyte chemotactic protein-1 (MCP-1) and IL-8, as determined by Northern blot analysis, immunoassay, or bioassay. Chemokine production was augmented by IL-1 beta or TNF-alpha. MCP-1 expression was also detected in KS lesions by in situ hybridization. The set of molecules identified in the present study is probably important in determining the prominent leukocyte infiltration observed in KS. Tumor-associated leukocytes may amplify autocrine/paracrine circuits that sustain KS proliferation and contribute to recruitment of host vascular cells.

Base Sequence↗

Absence of HIV-1 DNA in cartilage from HIV-positive patients.

Human immunodeficiency virus (HIV) infections are mainly transferred by blood, semen or organ transplantations. Since allogenic transplants have an established place in reconstructive surgery, the possibility of transferring HIV with such transplants has been a subject of much concern. Postmortem cartilage samples were obtained from eight HIV-infected patients and examined using the polymerase chain reaction in order to detect proviral HIV-1 DNA (gag, pol, env). Blood, brain and spleen samples were also obtained and used as positive controls. Results showed that no cartilage sample contained any HIV-DNA, whereas proviral sequences were clearly demonstrated in perichondrium from six patients. These findings indicate that HIV is not present in cartilage of HIV-infected patients, making HIV transmission through cartilage grafting improbable when transplants from HIV-negative donors are used.

Adult↗

[Immunohistochemical study of the neuroanatomy of the nasal turbinate in man. Innervation pattern of the blood vessels].

The complex vasculature of the human nasal mucosa plays an important role in the protection of the lower respiratory airways. It has to react to different external and internal stimuli and is under control of the autonomic nervous system. The aim of our study was to detect the precise localisation of neural structures in human nasal mucosa vessels under physiological conditions. Silver impregnation and histochemical staining techniques only allowed a partial aspect of autonomic innervation. Modern immunostaining methods with antibodies to neuron-specific enolase (NSE) and S-100 protein proved to be better for the demonstration of nerve structures. Tissue samples were taken from inferior turbinates received at mucotomy in 42 patients. After fixation the samples were embedded in paraffin wax and cut into serial sections. Additionally frozen sections were performed. The immunocomplexes were visualised by the avidin-biotin-complex (ABC) or by the alkaline phosphatase anti-alkaline phosphatase (APAAP) technique. A high density of S-100 and NSE immunoreactivity of neuronal and glial components of autonomic innervation could be demonstrated in the vessels of human nasal turbinates. Branching off relatively thick nerve bundles of the lamina propria fibres extended to the adventitia of the arteries near the periost and formed a periarterial nerve plexus. Fibres of this plexus supplied the smooth muscle tissue of the tunica media. Around veins only a few single nerve fibres could be demonstrated. By using immunocytochemical techniques it is possible to correlate the localisation of the classical neurotransmitters and multiple vasoactive neuropeptides with the corresponding innervation structures of the complex vasculature in human nasal mucosa.

Adult↗

[Cystic lymphoepithelial lesions in the head and neck area in HIV-infected patients].

Benign lymphoepithelial cysts (BLC) are rare disorders of salivary glands (0.6%). In patients infected by HIV, they are seen more often. In comparison to sporadic BLC, the patients are younger, the diameter of the cysts is up to 5 cm and they are often located bilaterally. At the Department of ENT, Head and Neck Surgery of the Ludwig-Maximilians-University, Munich, ten HIV-infected patients (two females) showed lymphoepithelial cysts (six times bilaterally). One of these revealed a metastasis of a small cell neoplasma near the cysts, another patient showed a non-Hodgkin's lymphoma of low grade malignancy (MALT-type), and one patient additionally had bilateral Warthin's tumours. The BLCs were mostly located in the parotid tail. In three cases, the cysts were found on the inferior border of the parotid and once at the submandibular gland. The age ranged from 27 to 71 years (medium 45.7 years). The mode of HIV infection was homosexuality five times, drug abuse twice, heterosexuality once, and blood products once. In two cases, the channel of transmission was unknown. The majority of the patients showed minor HIV illness (CDC II [n = 2]/CDC III [n = 4]); the rest had advanced immunodeficiency (CDC IV [n = 4]). All the cysts were examined by ultrasonography and NMR. According to the clinical findings and the general stage of health, BLCs were either enucleated (n = 8) or a superficial parotidectomy (n = 5) and selective biopsy of lymph nodes (n = 3) suspected to be malignant were performed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Differential diagnosis of benign middle ear tumors].

Adenomas of the middle ear are quite rare tumours of the ear and of recent recognition. Two cases of adenomatous neoplasms confined to the middle ear are presented. Usually these tumours are located on the promontorium or in the hypotympanon. The unique feature of the first described case is based on its origin in the epitympanic pouch of the tympanic membrane. The second case originated from the mucosa in the hypotympanon. The third case is a tumour-like lesion which was not distinguishable on clinical grounds from a jugulo-tympanic paraganglioma or a middle ear adenoma. The adenomas of the middle ear are histopathologically characterised by differentiated glandular structures within fibrous tissue and recurrences are rarely observed. Surgical removal by the endaural route gives an excellent prognosis as shown by the literature and our own clinical cases.

Adenoma↗

[HIV-associated Kaposi sarcoma in the head and neck area: a clinical, morphologic and therapeutic review].

Since 1987 233 HIV-infected patients have been treated at the Department of Otorhinolaryngology, Head and Neck Surgery of the Ludwig-Maximilians-University of Munich. 70% of these patients had advanced immunodeficiency disease (ARC and AIDS). 46 presented a Kaposi's sarcoma (KS) in the head and neck region. 91% were homosexual men. KS was most often located in the mouth (67%), oropharynx (65%) and skin (39.1%), while the larynx (10.9%), hypopharynx (8.7%), lymph nodes (6.5%) and nasopharynx (4.3%) were rarely involved. In 15 patients, a KS of the head and neck region was the initial symptom for the HIV-infection. Although the clinical features of this disease are typical, histological examination is required because differential diagnosis can show other rare diseases, such as bacillary angiomatosis, which are easily cured. The morphology of early plain or elevated KS exhibits more irregular vascular components while the nodular KS is dominated by sarcomatous cell lines. Immunohistochemical studies with antibodies to viral components revealed no reactivity to HIV-, HPV-, HSV-, EBV- and CMV-antigens. The best local treatment proved to be CO2- or ND:YAG-laser therapy. Cutaneous lesions were treated with camouflage or by fractionated radiotherapy. Advanced disease showed best response to systemic chemotherapy. Despite the advanced stage of immunodeficiency syndrome, an adequate local or systemic therapy can obviously improve the quality of life in HIV-infected patients.

Adult↗