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Biomedical subjects

M Hummel

Publications and source records attributed to M Hummel.

At least 235 records · Page 13Linked to original sources
PubMed1994

[Disseminated peritoneal leiomyomatosis: an exceptionally misleading disease. A case report].

Peritoneal leiomyomatosis disseminata is an exceptional benign disease with characteristic multifocal subperitoneal smooth muscle cell growth. We report and exceptional case associating pelvic endometriosis and mimicking cancer of the ovary. Surgery was performed and was found a posteriori to be excessive in light of the good prognosis of this disease. Positive hormone receptor assays on the surgical specimen favoured ovarian steroid hormone involvement in the aetiopathology of this strange disease.

Diagnosis, Differential↗
PubMed1994

Effects of chronic low level lead exposure on the expression of GFAP and vimentin mRNA in the rat brain hippocampus analysed by in situ hybridization.

In this study we used in situ hybridization to examine the effects of chronic low level lead toxicity during different periods of brain development. Low level lead is known to affect astroglia. GFAP and Vimentin were chosen as glialtypic markers for neurotoxicity. The effects of lead were investigated on male Wistar rats. Animals were divided into four groups: a control group, a permanent group exposed during gestation, lactation and post-weaning (E0-P100), a perinatal group exposed during gestation and postnatally until weaning (E0-P16), and a post-weaning exposed group (P16-P100). All experimental animals were fed a diet containing 750 ppm lead acetate. With respect to Vimentin mRNA no major differences could be detected among the treatment groups. Significant differences in GFAP mRNA levels were detected in the post-weaning group relative to controls. In this group we observed a strong increase of GFAP mRNA in the polymorphic zone of the dentate gyrus and in the CA1 region of the hippocampus. Permanent and perinatal groups showed no overt changes compared to controls. Our findings suggest that an irritation of the mature astrocyte results in a change from the quiescent to the reactive state. The majority of astrocytes that have been exposed during their development and differentiation fail to react even if the exposure is continued to adulthood. This suggests an irreversible insult by low level lead exposure during this period of time.

Animals↗
PubMed1994

[Pelvic actinomycosis: the value of preoperative diagnosis. Apropos of a case].

Pelvic actinomycosis is a chronic suppurative granulomatous disease caused by an anaerobic Gram positive germ, Actinomyces. This rare disease can be severe and life-threatening. A intra pelvic bridge becomes chronic and produces a pseudo-tumoural syndrome of the pelvis with retroperitoneal infiltration or extension to neighbouring organs. Initially, neoplasia is usually diagnosed, leading to mutilating surgical exeresis before the pathology results reveal the presence of pelvic actinomycosis. The most difficult task is to entertain the diagnosis in a patient with an intrauterine device and poor general health, signs of infection and a pelvic syndrome. We observed such a case where the diagnosis was suspected before surgery. Adapted first intention antibiotic therapy led to spectacular recovery and allowed limited surgery without unnecessary ablation of neighbouring organs.

Abscess↗
PubMed1994

Monitoring of the cellular immune system in patients with biventricular assist devices awaiting cardiac transplantation.

Lack of objective parameters to predict the clinical course and outcome are a major problem in managing the patients selected for BVAD-support as a bridge to heart transplantation. This study was intended to assess whether cellular immune parameters have a predictive value for the clinical result of VAD-support. Various cellular immune markers were monitored by multiparameter cytofluorometry in 30 patients who received a VAD system (Berlin Heart). We did not find significant differences in preoperative values of immune parameters between groups of survivors (n = 14) and non-survivors (n = 16). All 9 patients who died of septic multiple organ failure (MOF) had shown increased levels of T-cell activation (CD 71, CD 25, HLA-DR) as well as leukocytosis and 7 patients who died of noninfectious complications (mostly hemorrhage or cerebral complications) had exhibited T-lymphopenia. Seven of 9 patients who died of septic MOF had extremely decreased levels of HLA-DR+ monocytes (< 30%) while all 14 survivors and all 7 patients who died of noninfectious complications showed almost normal monocytic HLA-DR antigen expression, antigen-presenting capacity and cytokine secretion. These observations point to the reduced antimicrobial immunity ("immunoparalysis") in the non-survivors and may explain the fatal course of infection in these individuals. The in vitro results of restitution experiments call for new therapeutic strategies to improve the survival of VAD-patients.

Adolescent↗
PubMed1993

Synthesis of phosphorylated oligosaccharides in lysozyme is enhanced by fusion to cathepsin D.

Chinese hamster ovary cells transfected with human lysozyme cDNA encoding Asn instead of Gly22 synthesize a mutant lysozyme, [Asn22]lysozyme, with about 60% of the molecules bearing carbohydrate. This carbohydrate is predominantly of the complex type and contains a varied number of lactosamine repeats. In this study we show that the glycosylation of [Asn22] lysozyme fused to human cathepsin D is altered relative to [Asn22]lysozyme alone. The fusion protein is synthesized as a 66-kDa precursor that is cleaved to enzymatically active and antigenically positive cathepsin D and lysozyme. As compared with [Asn22]lysozyme the lysozyme moiety of the fusion protein shows an increased N-glycosylation and a decreased synthesis of lactosamine repeats. Cleavage of the precursor with cathepsin L has revealed that the lysozyme portion of the secreted fusion protein bears a complex type carbohydrate. The intracellularly released lysozyme portion of the fusion protein contains trimmed oligosaccharides. In the presence of NH4Cl the lysosomal targeting of the fusion protein is inhibited. The secreted protein is then enriched in molecules bearing phosphorylated high mannose oligosaccharides in their lysozyme moiety. Our results indicate that carbohydrate processing in [Asn22]lysozyme, including the synthesis of mannose 6-phosphate residues and of lactosamine repeats, is altered by the attached cathepsin D. The phosphorylation of the carbohydrate on the lysozyme portion results in a very efficient lysosomal targeting of the concerned fusion protein molecules.

Animals↗
PubMed1993

Hodgkin's lymphoma-derived tissue serially transplanted into severe combined immunodeficient mice.

Hodgkin (H) and Reed-Sternberg (RS) cells are considered to be the malignant cell population in Hodgkin's disease (HD). To date, their analysis has been hampered by their scarcity in primary tumors, poor growth in vitro, and lack of an animal model. To establish an in vivo system for the characterization of the malignant cells in HD, tumor biopsy samples from 13 HD patients were transplanted beneath the renal capsule or into the liver of severe combined immunodeficient (SCID) mice. HD-derived tissue from three patients gave rise to human tumors in SCID mice. Three different histologic patterns were observed: (1) lymphoproliferative disease (LPD), (2) anaplastic large cell lymphoma (ALCL), (3) Hodgkin-like lesions (HDLL). Immunohistochemical analysis showed that the tumors consisted of activated B cells (CD30+, CD20+). Epstein-Barr virus (EBV)-encoded transcripts were found in 80% to 100% of the tumor cells, although H and RS cells in the primary tumors of two patients were EBV-. All tumors examined (3 of 3) and the majority (6 of 10) of cell lines recultured in vitro had an abnormal karyotype. Southern blot analysis of the human Ig heavy chain gene showed that monoclonal or oligoclonal tumors of different B-cell origin grew in the SCID mice from the same germ line-configurated primary biopsy specimen. Our data suggest that the human cells in the SCID mice have either been derived from EBV superinfected H and RS cells or from EBV-infected bystander cells. If the latter is true, then these bystander cells must be genetically abnormal. The genetic defect would be either aneuploidy or instable euploidy. In either case, the cells might proliferate into malignant aneuploid HDLL or ALCL under the influence of EBV and the special environment encountered in the SCID mice.

Adult↗
PubMed1993

Frequent latent Epstein-Barr virus infection of neoplastic T cells and bystander B cells in human immunodeficiency virus-negative European peripheral pleomorphic T-cell lymphomas.

We investigated 81 cases of peripheral pleomorphic T-cell lymphoma (PMTCL) occurring in human immunodeficiency virus-negative Europeans for the presence of Epstein-Barr virus (EBV)-DNA through polymerase chain reaction (PCR) for the presence of EBV-encoded small nuclear RNAs (EBER) and immediate early mRNAs (Bam H-fragment, lower strand frame [BHLF]) by in situ hybridization (ISH) and for EBV-encoded latent membrane protein (LMP) and nuclear antigen 2 (EBNA2) by immunohistology (IH). EBER-ISH, which could be applied on all cases, showed an overall incidence of EBV-infected cells in 38 of 81 cases (47%) of PMTCL. These data could be confirmed by PCR, which produced congruent results in the cases with amplifiable DNA. By EBER-ISH, the virus was located in the tumor cells in 30 of the 38 EBV-positive cases, with the proportion of the infected cells ranging from 1% to 100%. In 18 of these cases and in the 8 cases without EBV-infected tumor cells, the virus was, respectively, either additionally or exclusively detectable in occasional nonmalignant lymphoid bystander cells. An LMP expression was observed in several of the EBER-expressing tumor cells in 18 cases, whereas EBNA2 was detectable only in one case, which also displayed signs of viral replication. Some nonmalignant EBV-infected B immunoblasts also expressed LMP in several cases. Primary cutaneous and enteropathy-associated PMTCL displayed less frequent EBV infection when compared with other extranodal or nodal manifestations.

Adult↗
PubMed1993

On the appearance of islet associated autoimmunity in offspring of diabetic mothers: a prospective study from birth.

For the first time the incidence of insulin autoantibodies and islet cell antibodies were evaluated in a prospective study from birth. Consecutive neonates (168) from mothers with Type 1 (insulin-dependent) diabetes mellitus (n = 113) and gestational diabetes (n = 55) were included at birth. To date, follow-up sera were obtained from 90 of 168 mother-child-pairs 9 months postpartum and from 39 of 168, 2 years postpartum. At birth, there was a strong correlation between the presence of antibodies in the cord blood of neonates and in maternal circulation [Type 1 diabetic mothers: 20% islet cell antibodies > or = 20 JDF-U (detection threshold of our islet cell antibody assay), 74% insulin antibodies > 49 nU/ml (upper limit of normal range in sera of healthy control subjects aged 0.5 to 46 years); neonates: 21% islet cell antibodies > or = 20 JDF-U, 76% insulin antibodies > 49 nU/ml; gestational diabetic mothers: 11% islet cell antibodies > or = 20 JDF-U, 18% insulin antibodies > 49 nU/ml; neonates: 13% islet cell antibodies > or = 20 JDF-U, 55% insulin antibodies > 49 nU/ml]. This supports transplacental passage of insulin antibodies and islet cell antibodies from diabetic mothers to their offspring. During follow-up, the majority of children lost antibody-positivity after birth. A few offspring, however, exhibited or developed antibodies consistently, whereby insulin autoantibodies preceded islet cell antibodies in each case (antibody-positivity: 9 months: 0% islet cell antibody positive, 3.3% insulin autoantibody positive; 2 years: 2.6% islet cell antibody positive, 7.7% insulin autoantibody positive).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Heart transplantation in Berlin--1993 update.

Heart transplantation has become a routine procedure. Surgical techniques have been standardized and triple-drug immunosuppression has proven to be the most effective posttransplantation medical treatment. A shortage of donor organs has remained the major factor inhibiting extensive application of heart transplantation. Improved techniques of organ protection may eventually contribute to an extension of the donor pool. However, it seems to be more important to develop alternative procedures further (artificial heart, xenotransplantation, extended use of conservative surgical or medical treatment). The patient population undergoing heart transplantation will undoubtedly include more older, severely ill, polymorbid patients who are not suitable for alternative procedures. Pediatric heart transplantation may increase in the coming years and mechanical circulatory support will surely gain in importance for both adult and pediatric patients awaiting heart transplantation.

Adolescent↗
PubMed1993

[Ogilvie's syndrome after cesarean section. Apropos of 3 cases. Review of the literature].

Ogilvie's syndrome or pseudo-obstruction of the colon shows up as a clinical picture of acute obstruction of the large bowel without an associated pathological lesion as usually occurs in older patients. Three cases of Ogilvie's syndrome following Caesarean section are reported in this work. Caesarean section seems to be the most common operative procedure associated with this syndrome. Up till now 41 cases have been described in the literature. This syndrome is serious because it is possible for the caecum to burst causing faecal peritonitis which carries a heavy mortality. Seventeen cases of perforation of the caecum have been reported in the literature. The diagnosis is made by x-raying the patient's abdomen without any pre-x-ray preparation; if an enema of gastroffin is given it can be shown that there is no organic cause for the obstruction. The pathological cause seems to be disturbance of the autonomic innervation of the colon. The colon should be decompressed rapidly; and the present technique is to do this using a colonoscope with or without epidural anaesthesia. Surgery should be reserved for cases that have complications or that have been refractory to conservative treatment. Of our three cases two were treated successfully by colonoscopic decompression and one with the use of drugs.

Adult↗
PubMed1993

[Endometrioid adenocarcinoma of the uterine isthmus associated with atypical endometrial hyperplasia and polycystic ovaries. Apropos of a case with bicornuate uterus in a 38 year old woman].

A 38 year old patient with multiple known risk factors for endometrial carcinoma (monophasic cycles, obesity, familial prediabetes, nulliparity, polycystic ovaries with diffuse thecal hyperplasia) presented with metrorrhagia caused by an endometrial lesion for which the diagnosis hesitated between atypical endometrial hyperplasia and carcinoma. Hysterectomy was performed because of the presence of a bicornuate uterus, obesity of 130 kg and the patient's lack of desire to have children. Examination of the uterus did not reveal any myometrial invasion in contact with the hyperplastic endometrium. The discovery of an endometrioid carcinomatous metastasis in the lower third of the vagina one year later allowed the retrospective detection of a 3 mm endometrioid carcinoma in the isthmus. No other metastases or recurrence were observed with a follow-up of 5 years.

Adult↗
PubMed1992

Heterogeneous Epstein-Barr virus infection patterns in peripheral T-cell lymphoma of angioimmunoblastic lymphadenopathy type.

In this study, 32 cases of T-cell lymphoma of angioimmunoblastic lymphadenopathy type (AILD-TCL) were investigated for their association with Epstein-Barr virus (EBV). For this purpose, three different approaches were applied: polymerase chain reaction (PCR) for the presence of EBV-DNA, in situ hybridization (ISH) for EBV-encoded small nuclear RNAs (EBER), and immunohistology for EBV-encoded latent membrane protein (LMP). PCR and EBER-ISH produced almost identical results, showing that all but one case of AILD-TCL contained EBV genomes. Three distinctive patterns of EBV infection were observed after immunophenotypical characterization of EBER-positive cells: (1) in 26% of the cases, B and T cells were infected, the majority of which were B cells of immunoblastic morphology located in the remnants of lymphoid follicles; (2) in 42% of the cases, the vast majority of infected cells were neoplastic T cells diffusely distributed in the lymph nodes, but infected B cells were also present; and (3) in 32% of the cases, there were only a few infected small lymphoid cells. Detectable LMP was frequent in cases exhibiting patterns 1 and 2. These findings suggest that in AILD-TCL patients, B cells and especially T cells are highly susceptible to a persistent EBV infection, which often leads to a growth advantage of the infected cells. Thus EBV, in conjunction with genetic abnormalities and selective defects of the immune system, might be involved in the pathogenesis of AILD-TCL.

Base Sequence↗
PubMed1992

Molecular cloning and expression of a new member of the nerve growth factor receptor family that is characteristic for Hodgkin's disease.

In man, Hodgkin's disease (HD) represents the most frequent lymphoma entity whose pathogenesis is still unknown. In order to contribute to the characterization of the molecular mechanisms of this disease, cDNAs coding for the HD characteristic antigen CD30 were cloned from expression libraries of the human HUT-102 cell line using the monoclonal antibodies Ki-1 and Ber-H2. The open reading frame of the cDNA that can be translated from two mRNA species of 2.6 kb, and 3.8 kb, respectively, predicts a 595 amino acid protein with leader, extracellular, single transmembrane, and intracellular domains. When expressed in COS-1 cells, the cDNA presented properties comparable to native CD30 antigen. The CD30 extracellular domain proved to be homologous to members of the nerve growth factor receptor superfamily. Six cysteine-rich motifs could be recognized within the putative ligand-binding domain.

Amino Acid Sequence↗
PubMed1992

Urodilatin: a new peptide with beneficial effects in the postoperative therapy of cardiac transplant recipients.

Renal failure after heart transplantation (HTx) still remains a serious problem, especially when cyclosporin A is used for immunosuppression in the early postoperative therapy. To preserve good renal function without reducing immunosuppressive cyclosporin A treatment, we administered urodilatin (CDD/ANP-95-126) in a long-term, low-dose infusion in addition to the usual medication after heart transplantation. From November 1990 to June 1991, 51 patients (46 male and 5 female; mean age 48 years) were treated with a 6-20 ng/kg bw.min infusion for 96 h after HTx. The renal function and hemodynamic parameters of these urodilatin-treated patients were compared in this sequential study with 40 patients (33 male and 7 female; mean age 49 years) who had undergone HTx previously from May to November, 1990, as controls. In this phase IIa study, both groups did not differ significantly with respect to age, sex, indication for HTx, and preoperative renal function. In comparison with controls patients treated with urodilatin had a significantly better renal function: a reduction in the peak plasma creatinine (PC values day 4: 1.5 +/- 0.11 vs. 2.19 +/- 0.19 mg/dl; P = 0.002), a lower peak serum urea (SU values day 4: 109 +/- 8 vs. 154.7 +/- 8.94 mg/dl; P = 0.0036), and a lower incidence of hemodialysis (6% vs. 10%) were observed. Adequate diuresis was maintained in spite of the reduction of furosemide by more than 60% (P = 0.005) on each day of urodilatin infusion in comparison with controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗
PubMed1992

EBV infection patterns in Hodgkin's disease and normal lymphoid tissue: expression and cellular localization of EBV gene products.

The present study was performed to clarify the reported inconsistencies regarding the frequency of the association of Epstein-Barr virus (EBV) and Hodgkin's disease (HD). Biopsies from 102 patients with HD were screened for the presence of EBV-encoded small nuclear RNA (EBER) and latent membrane protein (LMP) by using a non-isotopic in situ hybridization (ISH) and immunohistology (IH), respectively. The results were additionally compared with those obtained by polymerase chain reaction (PCR) for EBV-DNA detection. EBV was detected by EBER-ISH in 67% of the HD cases and in 25% of the control group cases consisting of normal lymph nodes. The results of PCR performed on cases with amplifiable DNA were overall congruent with those obtained by EBER-ISH. With respect to the cellular localization of EBV, four categories of HD could be established: (a) cases with EBV-infected tumour cells (42/102), (b) cases with additional infection of bystander cells (4/102); (c) cases with EBV infection restricted to non-malignant bystander cells (23/102); and (d) cases with neither EBV-infected tumour cells nor bystander cells (33/102). LMP expression was detectable only in the neoplastic cell population of those cases with EBER-positive tumour cells, suggesting a frequent involvement of EBV in the pathogenesis of HD.

Antigens, Viral↗
PubMed1992

Differentiation-induced and constitutive transcription of human papillomavirus type 31b in cell lines containing viral episomes.

The expression of viral genes during the productive life cycle of human papillomaviruses (HPV) is tightly coupled to the differentiation program of epithelial cells. We have examined transcription of HPV as a function of differentiation in an in vitro organotypic raft culture system which allows for epithelial stratification at the air-liquid interface. When CIN612 cells, which contain episomal copies of HPV type 31b (HPV31b), were allowed to stratify in raft cultures, they differentiated in a manner which was histologically similar to that seen in a cervical intraepithelial neoplasia I biopsy lesion. In monolayer cultures of CIN612 cells, two major polycistronic HPV31b transcripts of 1.7 kb which encode (i) E6, E7, E1-E4, and E5 and (ii) E6*, E7, E1-E4, and E5 were identified. These RNAs initiated at a promoter, P97, in the upstream regulatory region of the virus. Following differentiation in raft cultures, the relative abundance of RNAs initiated at P97 was unchanged. In contrast, the expression of a 1.3-kb RNA encoding an E1-E4 fusion protein and E5 was found to increase substantially following differentiation. This transcript was initiated at a novel promoter within the E7 gene (P742). These studies have therefore identified a constitutive viral promoter which is active throughout stratified epithelium as well as a novel promoter which is induced upon epithelial cell differentiation.

Amino Acid Sequence↗