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Biomedical subjects

K Meissner

Publications and source records attributed to K Meissner.

At least 19 recordsLinked to original sources

Inhibition of HIV-1 infection in vitro by murine monoclonal anti-p24 antibodies.

Murine monoclonal antibodies (Mabs) to the major core protein p24 of the human immunodeficiency virus type 1 (HIV-1) were tested for their ability to inhibit the replication and spread of the virus in permanent cell cultures (Molt4/8, K37, H9) and in the culture of II-2 stimulated T cells of healthy donors. After addition of ascitic fluid containing monoclonal anti-p24 antibodies or purified anti-p24 antibodies or the respective control to co-cultures of infected and non-infected cells, HIV-1 replication was evaluated by determining the percentage of infected cells and the activity of reverse transcriptase (RT) in cell-free supernatant. In addition, the supernatant's infectivity was determined. FACS analysis demonstrated p24 antigen in about 40% of unfixed HIV-1 infected cells at the cell membrane. Monoclonal anti-p24 antibodies of different epitope specificity added to the cells but not to the virus delayed the spread of HIV-1 infection in permanent cell culture. Furthermore, anti-p24 Mabs inhibited the release of RT-active virus particles by HIV-1 infected cell lines or II-2 stimulated T-lymphocytes, respectively, up to 60%. The mode of action of anti-p24 antibodies after HIV-1 infection is discussed on the basis of the data obtained.

Animals

Topoisomerase activity in mitochondrial lysates of a higher plant (Chenopodium album L.).

We describe an in vitro system for detection of topoisomerase activity from lysed mitochondria. Mitochondria were isolated from a suspension of cultured Chenopodium album cells. We observed a high activity in relaxation of negatively supercoiled DNA (pBR322). Addition of ATP had no effect on the activity. Topoisomers obtained from negatively supercoiled DNA were identical with topoisomers produced by the topoisomerase I of E. coli. The mitochondrial activity was dependent on the presence of Mg2+ ions and could be inhibited by novobiocin and N-ethylmaleimide. Nalidixic acid and berenil had no influence on the mitochondrial topoisomerase activity. These features characterize the enzyme as a type I topoisomerase.

Cells, Cultured

Fluconazole prophylaxis of recurrent oral candidiasis in HIV-positive patients.

In a randomized, open study, the efficacy of fluconazole as a prophylaxis of recurrent oral candidiasis in patients with advanced stages of HIV-infection (CD4 cell count less than 100/mm3) was studied. For this purpose, the frequency of episodes of oral candidiasis during two different prophylaxis regimens (50 mg/day vs. 100 mg/day) were compared to an untreated control group. Sixty-five HIV-positive patients were included in the study from May, 1989 to January, 1990. Of these, 58 were evaluated over an observation time of 137-215 days. Prophylaxis with fluconazole clearly reduced the occurrence of oral candidiasis. In 20 out of 21 patients in the untreated control group, a total of 60 relapses occurred. In the prophylaxis group receiving 50 mg/day (group 2), two out of 18 patients had four relapses. In the group receiving 100 mg/day (group 3), four out of 19 patients had nine relapses in total. Of 3575 observation days in the control group, treatment due to oral candidiasis was necessary on 393 days (28%). In group 2, on 57 of 3316 days (2%), fluconazole in a higher dosage was administered for treatment. In group 3, relapse treatment with fluconazole 200 mg/day, or treatment with ketoconazole, became necessary in 116 out of 3314 observation days (3%). In all relapses, Candida albicans cfu greater than 10(3)/ml were isolated in the oral wash-outs. As compared to the untreated control group, fluconazole prophylaxis in a daily dosage of 50 as well as 100 mg led to significantly less frequent relapses of oral candidiasis (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome

Successful treatment of primary progressive follicular mucinosis with interferons.

Follicular mucinosis is a primary idiopathic disease or a secondary, lymphoma-associated dermatosis. An effective standard therapy for the benign group is unknown. We describe a patient with primary benign disseminated progressive follicular mucinosis who was successfully treated with recombinant interferon alfa-2b and interferon-gamma. Interferons might act by down-regulation of activated inflammatory cells and/or by induction of enhanced elimination of extracellular mucin via increasing phagocytosis by macrophages.

Adult

[Mycosis fungoides and Sézary syndrome: diagnostic and prognostic relevance of cellular antigen expression].

Mycosis fungoides and Sézary syndrome (cutaneous T-cell lymphomas [CTCL]) are recognized, especially in the early stages, as being a potentially difficult diagnostic problem when they have to be histologically differentiated from a series of inflammatory disorders (ID). The diagnostic value of immunophenotyping is controversial; almost all studies have been semiquantitative. The prognostic implications of the antigen expression in CTCL are not known. To acquire more insight into these problems, the expression of differentiation-associated and activation/proliferation-associated antigens was examined in cryostat sections from 35 patients with conclusively diagnosed CTCL and 19 patients with ID. Positive cells were calculated as numbers/mm2 tissue section. The results were analysed statistically. Single antigen expressions were not helpful for differentiation between CTCL and ID. High percentages (89%-96%) of patients with CTCL stages I, II, and III and patients with ID could be classified correctly (discriminant analysis) by combined quantitative assessment of the expression of antigens Ki67 and Ki1/CD30 in the dermis and CD25 in the epidermis. In later stages (IVa, IVb) the note of correct classifications was worse because of the decrease in discriminating properties of the respective antigens. The biological role of antigen expressions was analyzed together with the clinical parameters (age, stage of disease). Stage was the parameter with the most significant influence on patient survival. CD1a-positive epidermal cells (Langerhans cells) were the only cell population that was significantly (P = 0.011) associated with survival. Death resulting from CTCL was significantly (P = 0.003) less frequent in patients with epidermal CD1a-positive cell densities higher than 90 cells/mm2 in comparison with patients with lower numbers.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Epidermal Langerhans' cell densities influence survival in mycosis fungoides and Sézary syndrome.

Because Langerhans' cells (LC) (CD1a-positive epidermal cells) have been discussed to be involved in the pathogenesis of mycosis fungoides and Sézary syndrome, the authors examined the influence of densities of Langerhans' cells and, concurrently, of other phenotypes retrospectively on survival of 35 patients. Cell densities were assessed on cryostat sections (alkaline phosphatase antialkaline phosphatase-technique) of the respective diagnostic biopsy specimens. Additionally, two clinical parameters (age, stage of disease) were evaluated. CD1a-positive epidermal cells were demonstrated to be the only cell population being significantly associated (P = 0.011) with survival. Death resulting from mycosis fungoides and Sézary syndrome was significantly (P = 0.003) less frequent in patients with epidermal CD1a-positive cell densities higher than 90 cells/mm2 (optimal break point) as compared with patients with lower numbers. These results suggest that Langerhans' cells have a significant impact on prognosis of patients with mycosis fungoides and Sézary syndrome. They play an important role in the host defense mechanisms against these lymphomas rather than to favor their progression as proposed recently.

Adult

Study of neu-protein expression in mammary Paget's disease with and without underlying breast carcinoma and in extramammary Paget's disease.

Correlation between neu/c-erbB-2/Her-2 gene amplification and overexpression of the neu gene product has been reported in tumors of glandular origin, especially ductal breast carcinomas. Formalin-fixed and dewaxed sections from 23 cases of mammary (MPD) and 9 cases of extramammary (EPD) Paget's disease were immunohistochemically stained by means of the monoclonal antibody 3B5 directed against an intracellular domain of the neu gene protein. All MPDs exhibited a distinct membrane staining of tumor cells independent of the presence of ductal breast carcinomas found in 18 cases. All these breast carcinomas also were positive for neu staining. In contrast to MPD, all EPDs were negative. Normal epidermis was always negative. Northern blot analysis sustained the immunohistologic findings in that the presence of neu mRNA could be demonstrated in two of three cases with MPD. Negativity in one case was due to dilution effects by nontumor cells. Our results suggest that Paget cells of mammary and extramammary localization, although very similar phenotypically, derive from different genetic accidents. Furthermore neu positivity in all MPDs and all underlying ductal carcinomas suggests common genetic alterations for both tumors. However the finding of five neu protein-positive MPDs without associated ductal breast carcinomas may suggest a somewhat different transformation process.

Breast Neoplasms

[H2-receptor antagonists and the incidence of gastroduodenal ulcer perforation and hemorrhage. An epidemiological study].

The only curative treatment to proximal bile duct cancers with involvement of both hepatic ducts is liver transplantation. A curative resection with wide lateral clearance is limited due to the neighbourhood of vital anatomic structures in the liver hilum. The majority of patients with bile duct cancers is over 60 years of age and due to concomitant disease, they do not fulfill the requirements for liver transplantation. Our treatment strategy in adequate cases is palliative tumor resection and reconstruction of bile passage by sutureless biliodigestive anastomosis as proposed by Rodney Smith. We treated 11 patients with this method, in 5 patients an additive combined radiotherapy by percutaneous radiation and intraluminal after-loading therapy was performed. Our results indicate that this strategy leads to effective palliation in cases provided that only microscopic residual tumor is left in situ (R1-resection). Our observed survival times compare favorably to survival times after liver transplantation (average survival time 11.5 months median survival time 10 months).

Adult

[Acute cholecystitis in cholelithiasis: importance of early surgery (a comparative study)].

The results of early surgery (ES) for acute calculous cholecystitis obtained in 74 patients operated on between 3/78 and 12/87 were compared with relevant data obtained in 74 sex- and age-matched patients with a history of acute cholecystitis operated on for biliary colic or jaundice during the same period. Operative procedures, incidence of jaundice and common bile duct calculi, duration of operation, number of patients requiring blood transfusions, surgical and general complications and mortality showed no significant difference. Only operative blood loss was significantly higher in the ES group, but this was of no practical relevance. ES precludes the sequelae of emergency surgery in the delayed surgery group not infrequently necessary for failure of conservative treatment of acute cholecystitis, which necessarily precedes planned delayed surgery, and thus renders a significant reduction of over-all risk. This forms the rationale for ES as treatment concept.

Acute Disease

Intermittent incomplete intestinal obstruction: a frequently mistaken entity. Ultrasonographic diagnosis and management.

Intermittent incomplete intestinal obstruction (IIIO) was diagnosed by sonography in 81 patients during the course of a study conducted from January 1984 to July 1988. The clinical presentation, history and characteristic sonographic findings are described. Successful conservative therapy was instituted in all patients based upon clinical and sonographic treatment response observations. Twenty-seven percent of patients returned with complete obstruction, necessitating surgery between 13 and 36 months later. Although conservative treatment uniformly renders relief from IIIO, elective surgery is indicated in patients whose IIIOs recur at progressively shorter intervals.

Abdomen

[Reactive acalculous cholecystitis: a bland and asymptomatic course--incidence of a classical stress disease].

A systematic search for reactive acalculous cholecystitis (RAC) performed from 11/85 until 11/87 rendered an incidence of 9 in 1272 patients recovering from surgery and 1 in 930 patients treated conservatively for various diseases. 8 patients presented with typical but discrete clinical symptoms whereas 2 remained asymptomatic. Abdominal sonography proved to be the most useful diagnostic procedure. The ratio of classic fulminant disease to cases presenting with lesser severity was calculated to be 1:50. All patients in this series were managed nonoperatively in respect to RAC. The pathoanatomic and pathogenetic context is reviewed and the author's impression corroborated that relevant cases may frequently go by unnoticed by clinicians.

Adult

[Experimental ultrasound analysis of the appendix. Contribution to improving the diagnosis of acute inflammation in routine clinical practice].

Sonographic investigations of fresh operative specimens - 50 non-infected, 50 chronic and 50 acute inflammatory appendices - and also of 335 pertinent operated patients with "typical" appendiceal disorders were performed. All other entities, mimicking acute or perforated appendicitis were excluded from this study. Under experimental conditions, negative, chronic and acute or phlegmonous appendices appeared as "cockade" or "pseudokidney sign" with reflecting wall and echoless lumen. The application of a 5 Mz linear transducer made the differentiation of three wall layers feasible, in negative appendices as well as in dilated acute appendicitis, whereas in chronic inflammation and in obliterating acute appendicitis a wall layer stratification was not possible. In clinical application of 335 operated patients we only could demonstrate cases of acute or perforated appendicitis (n = 182/220), but no cases of non-infected appendix. In 57% of pertinent cases the objectivation of lumen dilatation, in 35% a wall layer stratification was feasible. Acute, phlegmonous or perforated appendicitis was proven by demonstrating an immobile "pseudotumor mass" with dominating constant hypodense reflex property. The pertinent diameters as measured in clinical acute appendicitis exceeded significantly the diameters observed in experimental sonography of negative appendices with a differential intact mobility. Intraluminary coproliths and hyperdense reflecting attached omental segments facilitated a sonographic diagnosis. In 101/115 patients correct negative diagnosis was established. On the basis of these criteria, a sensitivity of 83%, a specificity of 88% and a diagnostic accuracy of 85% related to the diagnosis of acute or perforated appendicitis was obtained in this study.

Acute Disease

Cutaneous T cell lymphoma: immunocytochemical study on activation/proliferation and differentiation associated antigens in lymph nodes, skin, and peripheral blood.

The expression of activation/proliferation antigens (CD 25, CD 30, Ki 67, transferrin receptor) in lymph nodes and skin were compared in nine patients with mycosis fungoides (MF) with patients with erythroderma not related to MF, and patients with reactive lymphofollicular hyperplasias (a total of 14 patients). A panel of differentiation antigens was analyzed in addition. Reactivities were revealed by the APAAP technique. Activation/proliferation antigen scores in lymph nodes were related to the clinical stages of MF in most instances (low scores in cases of MF stage I/II, high scores in 3/4 cases of MF stage III/IV). They differed markedly in cases of non-MF-erythrodermia with the exception of one patient, and in all cases of reactive lymphofollicular hyperplasia. Expression of activation/proliferation antigens in lymph nodes were different in most cases from those in skin and peripheral blood. For diagnostic use, the activation/proliferation antigen scores were superior to the cell differentiation antigen profiles. Among cellular differentiation antigens, only the extent of CD1+ cells provided some diagnostic information, since the number of these cells were markedly increased in all cases of dermatopathic lymphadenitis with/without MF when compared with reactive lymphofollicular hyperplasia. In the diagnosis of MF, immunohistochemistry of activation/proliferation or differentiation antigens cannot replace routine paraffin histology, but may provide supplement any data in equivocal cases.

Adult

Severe clostridium infection following perforation of the uterus in a patient with an ectopic pregnancy.

Twenty-eight hours after CO2 insufflation and curettage in a 26 year old, haemolysis, jaundice and anuria developed. As an ectopic pregnancy was also suspected, a diagnostic laparoscopy was done and was followed by a hysterectomy and left salpingo-oophorectomy before Clostridium perfringens was grown on culture. The survival of the patient despite clostridial infection is probably due to immediate surgical treatment and intensive post-operative care.

Adult

Quantitative analysis of T6-positive Langerhans cells in human skin cancers.

Epidermal Langerhans cells (LC) are required for antigen-presentation and for stimulating antigen-specific T cell activation. Similar functions may be important in the immune response to malignant skin tumours. Monoclonal anti-T6 antibody was used to examine LC population in basal and squamous cell carcinomas. Positive control labeling was performed with monoclonal anti-HLA-DR antibody. The number of T6-positive LC per mm2 of section was significantly decreased (p less than 0.01) in the tumour group in comparison with a sex and age-matched control group. The number of sun-exposed and covered regions was taken into consideration in each respective group. Within the tumours, LC were found more frequently in the tumour periphery and in most differentiated tumour areas (horn pearls) than in the rest of the tumour mass. T6-positive LC were rarely found in the dermis. Moreover, LC exhibited morphological changes in specimens from tumours. Staining with anti-HLA-DR antibody revealed less numerous positive cells within tumour nests than labeling with OKT6. A relationship between T6-positive LC quantities and extent of HLA-DR-positive infiltrates around tumours could not be established. These results suggest that immunological surveillance of neoantigen-bearing tumour cells may be impaired in skin cancer. A reason for the reduced LC number may be an altered microenvironment in tumour tissue.

Aged

GP37 expression in normal and diseased human epidermis: a marker for keratinocyte differentiation.

An antiserum prepared against a glycoprotein (GP37) extracted from the upper epidermal layers, was used to stain frozen sections of human oral mucosa, normal and abnormal skin by an indirect immunofluorescence technique. On normal human epidermis, this antiserum mainly reacted with the cytoplasm of granular cells, whereas on buccal mucosa the recognized antigen was observed as scattered dots limited to the upper epithelial layers. In epidermal diseases, alterations in the staining pattern were observed. In psoriasis, the labelling was markedly diminished; in contrast, in lichen planus it was intense and present on the 3-6 uppermost cellular layers. Basal cell epitheliomas were almost negative, except around horn cysts. In Bowen's disease dyskeratotic cells were strongly labelled. In squamous cell carcinomas a clear-cut staining was observed in squamous nests. On cultures, GP37 expression could be induced by growing epidermal cells in vitamin A-depleted medium. The biological significance of the observed staining patterns remains to be precised. Nevertheless, GP37 represents a sensitive marker of epidermal differentiation and may be useful in skin pathology and in in vitro studies.

Animals