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Biomedical subjects

K Engel

Publications and source records attributed to K Engel.

At least 19 recordsLinked to original sources

Identification of MAPKAP kinase 2 as a major enzyme responsible for the phosphorylation of the small mammalian heat shock proteins.

MAP kinase-activated protein kinase-2 (MAPKAP kinase-2) phosphorylates the serine residues in murine heat shock protein 25 (hsp25) and human heat shock protein 27 (hsp27) which are phosphorylated in vivo in response to growth factors and heat shock, namely Ser15 and Ser86 (hsp25) and Ser15, Ser78 and Ser82 (hsp27). Ser86 of hsp25 and the equivalent residue in hsp27 (Ser82) are phosphorylated preferentially in vitro. The small heat shock protein is present in rabbit skeletal muscle and hsp25 kinase activity in skeletal muscle extracts co-purifies with MAPKAP kinase-2 activity throughout the purification of the latter enzyme. These results suggest that MAPKAP kinase-2 is the enzyme responsible for the phosphorylation of these small heat shock proteins in mammalian cells.

Amino Acid Sequence

Dephosphorylation of the small heat shock protein hsp25 by calcium/calmodulin-dependent (type 2B) protein phosphatase.

The dephosphorylation of the mouse small heat shock protein hsp25 within an extract obtained from Ehrlich ascites tumor cells is inhibited by the calcium chelator EGTA and at concentrations of microcystin-LR which are characteristic for inhibition of calcium/calmodulin-dependent (2B type) protein phosphatases. Furthermore, the dephosphorylation of hsp25 in the cell-free system derived from Ehrlich ascites tumor could be increased specifically by addition of the calcium/calmodulin-dependent (2B type) protein phosphatase calcineurin. Dephosphorylation of the heat shock protein hsp25 is also obtained in an in vitro system containing phosphorylated recombinant hsp25, 1 mM Ca2+, calmodulin, and calcineurin specifying hsp25 as the direct substrate for this enzyme. The expression of two isoforms of the catalytic subunit of the mouse calcium/calmodulin-dependent (2B type) protein phosphatases in Ehrlich ascites tumor cells is demonstrated by polymerase chain reaction using specific oligonucleotide primers to the catalytic and calmodulin-binding domain, respectively. Northern blot analysis using the amplified fragments as probes shows that the mRNA of one isoform of the mouse calcium/calmodulin-dependent protein phosphatase is of medium abundance in EAT cells. These data suggest a calcium/calmodulin-dependent dephosphorylation of the small stress protein in EAT cells also in vivo. Since it is known that heat shock increases the intracellular calcium level and that thermotolerance is influenced by calcium chelators, ionophores, and anti-calmodulin drugs, the changes in the degree of hsp25 phosphorylation induced by thermal stress resulting in an altered thermoresistance could be explained at least partially by the calcium/calmodulin-dependent dephosphorylation through protein phosphatases 2B.

Amino Acid Sequence

[Recurrence of vulvar cancer--treatment, experiences and results].

At the University Hospitals of Heidelberg (1970-1988) and Homburg/Saar (1988-1990), 182 patients with vulvar carcinoma were treated. 51 patients had a recurrence of vulvar carcinoma and 21 patients showed a persistence of this tumour. 19 women had a second recurrence of vulvar disease. In these cases, therapy ranged from local surgery to exenteration, depending on the site and tumour extension. 18 patients underwent successful reconstructive surgery. Prognosis was better in cases with local recurrence in comparison to distant sites of metastatic progression (i.e. inguinal nodes or disseminated disease) (p less than 0.001). The five-year survival (after diagnosis of recurrent disease) for patients with early onset of recurrence (less than 20 months after initial therapy) was 28% compared to 68% for patients with late onset of recurrent disease (p less than 0.01).

Female

[Fetomaternal macrotransfusion after successful internal version from breech presentation by moxibustion].

In a primigravida with a fundal/anterior wall placenta, a successful cephalic version was noted at 39 weeks after repeated moxibustion of the point Zhiyin (bl 67). Since routine foetal heart rate monitoring showed a sinusoidal pattern with severe decelerations, immediate Caesarean section was performed. Foetomaternal macrotransfusion of about 300 ml of blood was found. In view of this complication, possible risks of the method are discussed. Moxibustion does not seem to be suitable as self-therapy without close medical follow-up.

Adult

[Effect of surgical procedure and adjuvant therapy on cosmetic results after breast conserving therapy in breast cancer].

A total of 207 patients undergoing breast conserving therapy (BCT, excision of tumour with clear margins, radiotherapy, sequential chemotherapy for node-positive patients) were clinically evaluated after a median follow-up of 11 months (min 2/max 22). The aim of the study was to analyse the impact of various individual factors, surgical techniques and adjuvant therapies on the cosmetic result. In 85.7% of all cases the objective outcome was satisfactory (very good: 48.8%, good: 36.9%) and in 14.3% unsatisfactory (fair: 13%, poor: 1.3%). Objective cosmetic results were rated significantly better by the patients (p = 0.01), in cases with biopsy weights of greater than 100 grms. (large/hyperplastic breast, p = 0.01), non-reconstructed mammary glands (simply closure of subcutis and skin, p = 0.01), non suction drainage of the breast (p - 0.04) and normal healing of the wound (p = 0.01). There was a trend towards better cosmetic results in the premenopause in patients with a tumour localised in the upper outer quadrant, in cases of a curvilinear as compared to a radial incision (upper/outer quadrant) and in small or average-sized breasts with biopsy weights of less than 50 grms. Cosmetic results were unaffected by a "two-step" procedure, standardised postoperative radiotherapy (45-55 Gy) and by sequential chemotherapy (3x CHT/radiotherapy/3x CHT). Unsatisfactory cosmetic short-term results should primarily be regarded as a surgical complication of BCT. Results can be improved by taking into consideration the importance of the relation of breast/biopsy-weight as well as standardising the operative procedure (curvilinear incision, closure of subcutis and skin, drainage without suction, perioperative antibiotic prophylaxis).

Adult

[Breast saving treatment of breast cancer: results, risks, new developments].

In the Departments of Gynaecology and of Gynaecological Radiology of the University of Heidelberg, breast conserving therapy was carried out in 1330 patients with breast cancer between 1975 and 1990. The tumour size was up to 3 cm and 28% showed positive nodes. The median age was 47.6 years, segmental resection was the standard operation and whole breast irradiation with 50 Gy and an additional boost of 10 Gy was the standard irradiation schedule. After 5 years (n = 307), the following results were observed: local failure: 6.8%, regional lymph node recurrence: 2.1%, overall survival: 88.3%, disease-free survival: 81.2%. 5 out of 36 of the cases of mortality died without having had a recurrence. Significant factors for local failure were following: 1. lymphangiosis of more than 1 cm in size around the tumour (p = 0.03) 2. intra-ductal non-invasive cancer of more than 1 cm in size around the primary tumour (p = 0.01) 3. intra-ductal non-invasive cancer reaches the margin of resection (p less than 0.00001) With segmental resection (2 cm margin macroscopically free of tumour), tumour beyond the margins--so-called residuals, showed in 19% histologically. In the other 3 quadrants, additional secondary primaries in 25% (multicentric cancers) of macroscopical size could be confirmed in an additional study. In case of high risk for local failure, more radical surgery as well as more intense irradiation is recommended.

Adult

Three different actin filament assemblies occur in every hair cell: each contains a specific actin crosslinking protein.

The apex of hair cells of the chicken auditory organ contains three different kinds of assemblies of actin filaments in close spatial proximity. These are (a) paracrystals of actin filaments with identical polarity in stereocilia, (b) a dense gellike meshwork of actin filaments forming the cuticular plate, and (c) a bundle of parallel actin filaments with mixed polarities that constitute the circumferential filament belt attached to the cytoplasmic aspect of the zonula adhaerens (ZA). Each different supramolecular assembly of actin filaments contains a specific actin filament cross-linking protein which is unique to that particular assembly. Thus fimbrin appears to be responsible for paracrystallin packing of actin filaments in stereocillia; an isoform of spectrin resides in the cuticular plate where it forms the whisker-like crossbridges, and alpha actinin is the actin crosslinking protein of the circumferential ZA bundle. Tropomyosin, which stabilizes actin filaments, is present in all the actin filament assemblies except for the stereocilia. Another striking finding was that myosin appears to be absent from the ZA ring and cuticular plate of hair cells although present in the ZA ring of supporting cells. The abundance of myosin in the ZA ring of the surrounding supporting cells means that it may be important in forming a supporting tensile cellular framework in which the hair cells are inserted.

Actin Cytoskeleton

Generation of antibodies against human hsp27 and murine hsp25 by immunization with a chimeric small heat shock protein.

A hybrid protein containing the N-terminal part of the murine stress protein hsp25 (amino acids 1 to 110) and the C-terminal part of the human stress protein hsp27 (amino acids 111 to 208) was expressed in E. coli using a T7 polymerase/promoter system. The recombinant hybrid protein was purified and used for immunization of rabbits. In contrast to immunization experiments using hsp25 and hsp27 alone, immunization with the hybrid protein hsp25/27 leads to antibodies which can be used for detection of both hsp25 and hsp27.

Amino Acid Sequence

[Prognostic factors for long-term survival in anorexia nervosa].

This work describes the results of a long-term follow-up (mean duration = 13.5 years) of 105 female anorexia nervosa patients, for 93.3% of whom (n = 98) we were able to obtain information. Our objective was to identify factors affecting the long-term prognosis in these cases. Weight gain and a stable partnership after treatment as well as high body weight on termination of treatment were shown to be especially important for long-term recovery. This suggests the following for treatment of anorexia nervosa: besides restoration of normal body functions, the patient should attempt to leave her parents' home and enter a partner relationship. Further weight gain should not be neglected during this process.

Anorexia Nervosa

[Therapy of patients with severe anorexia (summary of a report on a research project)].

From 1981 to 1983 a special project on anorexia nervosa was granted within "Sonderforschungsbereich 115" (Hamburg--West Germany). We want to give a review of those aspects of our studies which led us to a therapeutic concept for severely affected inpatients. Starting in the diagnostic field with problems of motivation and alexithymia we turn to psychodynamic subgroups, mention the studies of endocrinology, the Self-structure and the father-types, continue with epidemiologic studies as a device of interpreting pathologic phenomena. Concerning our therapeutic investigations--basing on a long-term follow-up--we report on therapeutic elements, results, follow-up and a hierarchy in prognostic factors of our in-patient treatment. In a critical survey of the results we finally discuss therapeutic recommendations.

Affective Symptoms

[Testing of a liquid, ready-to-use, breast milk substitute in the county of Funen].

A newly developed liquid ready-to-use cow's milk based formula (BD) was used as the sole nutrient in 314 healthy term infants below the age of 28 weeks--except for supplementary feeding introduced at an average age of 142 days. The incidence of dyspeptic problems (constipation, diarrhea, vomiting), the parents' and visiting nurses' comments on the product, and the causes of "BD failure" (termination of BD feeding because of suspected cow's milk allergy, dyspepsia, etc.) were recorded as were rates of weight gain and linear growth. It is concluded that BD is a valuable alternative to existing powdered milk formulas and that the growth of the infants compared satisfactorily with published reference values.

Animals

[The pH and acidity of feces in colorectal neoplasms].

The pH and faecal titratable acidity in fresh faeces were measured in patients with colo-rectal carcinoma or adenoma and in normal individuals. Significantly higher pH values and lower acidity were found in patients with cancer than in normal individuals. Patients with cancer had pH greater than 6.90 more frequently than normal. Patients with adenomata did not differ significantly from normal individuals. These results support performance of intervention trials with lowering of the pH in the colon with the object of cancer prophylaxis even although the causal connection is obscure.

Adenoma

[The extent of radical axillary lymph node excision].

A study on histological findings in 1047 patients who underwent total axillary lymph node dissection (topographical levels I-III), was conducted. A mean of 20.3 lymph nodes (LN) was assessed; LN metastases were detected in 492 cases. Retrospective analysis showed that, by mere dissection of LNs level I, 10 of the 492 nodal positive cases (2.0%) would have been classified false negative. Additionally, according to the number of positive LNs detected in stage I, 85 of the 492 patients (17%) would have been assigned to a group with a better prognosis (prognostic groups 1-3, 4-9, greater than or equal to 10 pos. LNs). By mere dissection of LNs levels I and II, only 1 of 492 (0.2%) patients would have been categorized false negative and only 24 patients (5%) would have been included in a group with a better prognosis, on the basis of the number of positive LNs dissected. Thus dissection of LNs stages I and II provides sufficient prognostic information. Since, however, in 145 nodal positive cases (14% of the entire collective e.g. 29.5% of all patients with positive lymph nodes), metastases were detected in level III, these LNs should be removed as well, in order to prevent axillary recurrences. One could only dispense with dissection of level III, if LN metastases levels I and II could be excluded during the operation.

Axilla

[Guideline for the assessment of therapeutic success in the treatment of anorexia].

Several different empirical studies dealing with the field of intrafamily relations, long term prognostic factors and the differentiation of living and deceased allowed us to postulate a guiding criterion for the evaluation of anorexia-treatment: The success of treatment depends on the quality and development of social relations (object relationships). In this case the development of new relationships, that do not belong to the old pathogenous field, are extremely important.

Adult

Perioperative systemic antibiotics for prophylaxis of infections in breast surgery: sulbactam/ampicillin versus mezlocillin/oxacillin.

In a prospective, randomized, open trial, efficacy of one dose of sulbactam/ampicillin (1 g:2 g) was compared to three doses of mezlocillin/oxacillin (2 g:1 g), starting with induction of anesthesia in 80 breast surgery patients with an increased risk of postoperative infection. No infections at the site of operation were seen in either group. Fever due to postoperative pulmonary complications occurred in one patient in the sulbactam/ampicillin group. The only side effect was a moderate exanthema observed in one patient in the mezlocillin/oxacillin group. In this study of the prophylaxis of patients with an increased risk of postoperative infections having the potential to jeopardize the results of surgery, a single dose of sulbactam/ampicillin was as effective as a short term course of three doses of mezlocillin/oxacillin.

Adult

[Side effects and complications in breast-saving therapy of breast cancer].

From 1975 to June 1987, a total of 664 women underwent breast-conserving therapy for invasive carcinoma at the University Hospital for Women, Heidelberg, FRG (562 patients: surgical procedure/radiotherapy, 102 patients: only radiotherapy). A subgroup of 203 nonselected patients was prospectively followed up for complications and side effects. The population examined was representative of the entire series with reference to age distribution, tumor stage and localisation. The mean follow-up period was 28.9 months after primary therapy. Complications of breast-conserving therapy (surgery, post-operative radiotherapy, adjuvant chemotherapy for node-positive patients) were assessed by one investigator including evaluation of a standardized patients' questionnaire. The most frequent and serious single complication was lymphedema (LE) of the arm. The incidence of severe LE (greater than or equal to 3 cm difference in circumference) was 6.4%. A total of 25.1% of all patients reported some degree of swelling of the arm. The overall LE-rate was 23.1% according to the newly introduced LE-score combining the degree of difference in circumference, individual handicap and need for physiotherapy. The LE-rate was significantly increased in patients with adjuvant chemotherapy (40.1%, p less than 0.01). General impairment of arm function was reported frequently (65.6%). Shoulder mobility was severely restricted (abduction of arm less than or equal to 90 degrees) in 3.6%. Further complaints were related to impairment of fine motor function (4.5%), shielding of the arm (15.4%), reduction in absolute force (22.1%) and/or rapid tiring of the arm (37.4%). Radiotherapy related toxicity accounted for cutaneous edema (50.3%) and fibrosis of the breast (slight: 33.8%, pronounced: 9.7%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Empirical coverage of psychodynamic configurations of anorexia nervosa.

For the last several years, the clinical picture of anorexia nervosa has been covered at the following three levels: (1) symptomatology (including partner and family relations); (2) psychodynamics; (3) narcissistic level. As far as the psychodynamic level is concerned, this paper presents the pertinent theory in its operationalized form for a clinical rating. The convergent validity of the five psychodynamic configurations is tested by a comparison of clinical rating, a questionnaire (IATAN) and a standardized interview (SIAN); divergent validity is tested by verifying the mutual differences of the five configurations.

Adolescent

An interaction model of anorexia nervosa.

Noticeable similarities were found in the psychosocial field by a comparison of a group of anorexia nervosa patients with a representative sample of normal controls. In particular, no confirmation could be found of the mother dominance coupled with the weak and frequently absent father, as postulated under the interactional model of anorexia nervosa. Empirical discriminate analyses of the role of individual family members are necessary.

Adolescent