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Biomedical subjects

M Kaufmann

Publications and source records attributed to M Kaufmann.

At least 217 records · Page 12Linked to original sources
PubMed1994

Functional expression of a stably transfected parathyroid hormone/parathyroid hormone related protein receptor complementary DNA in CHO cells.

Chinese hamster ovary (CHO) cells were stably transfected with OK-O complementary DNA encoding the parathyroid hormone/parathyroid hormone related protein (PTH/PTHrP) receptor derived from opossum kidney (OK) cells (Jüppner et al., 1991). A subclone of transfected CHO cells, CHO-E2, presented high affinity binding of 125I-labeled [Tyr36]chickenPTHrP(1-36)amide ([125I]chPTHrP(1-36)) (Kd 1.28 +/- 0.10 nM) similar to that of wildtype OK cells (Kd 2.23 +/- 0.16 nM) (P < 0.01). Photoaffinity labeling of the PTH/PTHrP receptors using N-hydroxysuccinimidyl-4-azidobenzoate modified [125I]chPTHrP(1-36) revealed the same specifically labeled 90 kDa protein in CHO-E2 and OK cells. In CHO-cells, chPTHrP(1-36) stimulated cyclic AMP accumulation in dose-dependent fashion (EC50 0.15 +/- 0.04 nM) and raised peak cytosolic free calcium concentration (EC50 2.90 +/- 0.36 nM) independent of extracellular calcium, and stimulated phosphate uptake (EC50 0.21 +/- 0.07 nM). Both, chPTHrP(1-36) and 12-O-tetradecanoylphorbol-13-acetate stimulated phosphate uptake were suppressed by staurosporine. But, Sp-cyclic adenosine-3',5'-monophosphothioate did not affect phosphate uptake in CHO-E2 cells. In conclusion, a PTH/PTHrP receptor stably expressed in CHO cells is linked to stimulation of phosphate uptake. Receptor coupling presumably occurred through the protein kinase C rather than the protein kinase A pathway.

Alkaloids↗
PubMed1994

[Hysteroscopic endometrium ablation to avoid hysterectomy in "high risk" patients].

Hysteroscopic endometrial ablation under maximal anaesthesiological surveillance was performed in 34 high-risk patients to avoid hysterectomy. It was a collective of patients with heavy thrombo-embolic or thrombotic disease, either under permanent anticoagulation due to residual disease or multiple endoprosthetic treatment, or with endogenous coagulopathy. In all these women, hysterectomy was either a relative or an absolute contraindication. In 22 patients, treatment resulted in complete amenorrhoea or at least hypomenorrhoea (without menometrorrhagia) respectively cyclic spotting. In 6 further patients, amenorrhoea was achieved after a repeat procedure. Endometrial ablation was thus successful in 28 of 34 cases. In these patients, hysterectomy with the risk of major or even lethal complications, could thus be avoided. Hysterectomy, however, had to be performed in 2 women with extensive adenomyosis uteri interna. Within two respectively three years after endometrial ablation, two other patients died from causes unrelated to the surgical intervention (cardiac infarction, cerebral haemorrhage). Follow-up ranged from 1 to 5 years. Hysteroscopic endometrial ablation proved an effective therapeutic option in this selected group of patients. Other indications require further study.

Adult↗
PubMed1994

[Histologic regression of breast cancer after primary (neoadjuvant) chemotherapy].

Primary (neoadjuvant) chemotherapy of locally advanced breast carcinomas is performed to locally reduce the tumour mass and to improve the operability. Recently, the indication for primary chemotherapy has been extended for preoperative treatment in breast conserving surgery. In an ongoing clinical trial we examined the resection specimens of 51 mammary carcinomas after primary chemotherapy. These patients had received a neoadjuvant therapy with epirubicin/cyclophosphamide for size reduction of large (> 3 cm) but operable tumours (pretreatment median tumour size 4.5 cm by mammography). The tumour response was evaluated pathologically and compared with the clinical tumour regression that was observed in over two-thirds of all cases. We classified the regressive changes using a semiquantitative scoring system from 0 to 4 (0 = no effect, 1 = resorption and tumour sclerosis, 2 = minimal residual invasive tumour [< 0.5 cm], 3 = residual noninvasive tumour only, 4 = no tumour detectable). The aim of this study was to evaluate the improvement of operability objectively and to correlate the histology of the primary tumour with the response to treatment. With invasive lobular carcinomas, the tumour size after therapy was reduced less than average and irrespective of the amount of histological tumour cell reduction, largely due to the stromal content of these neoplasms. Invasive ductal carcinomas with extensive or predominant intraductal component also underwent only a slight decrease in tumour size; this was because of the lack of tumour response with the intraductal component. Well differentiated tubular carcinomas were particularly resistant to primary chemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

[Incontinence operation by "Retzius-scopy"? An endoscopic modification of the Marshall-Marchetti-Krantz operation].

The operative treatment of stress incontinence with the Marshall-Marchetti-Krantz procedure has proved effective. A new, endoscopic modification of this procedure is presented here, based on the principle of vesico-urethral suspension with fibrin glueing. Open abdominal surgery is replaced by retziusscopy and a minimal invasive endoscopic intervention in the Retzius' cavity.

Female↗
PubMed1994

[The positive "vocal fremitus" in malignant breast tumors in color MEM ultrasound imaging--an exciting artifact in confirming the diagnosis?].

In the experimental phase of application of a new Non-Doppler technology (MEM system, Acoustic Imaging, Phoenix; Dornier Medizintechnik) we observed, that in patients, who spoke during colour imaging of a breast tumour, artifacts appeared in or around the lesion: the colour artifacts were seen regularly inside the tumour in cases of malignancies, and exactly surrounding benign tumours. Postoperative histological findings served as an objective criterion of classification/differentiation. To examine this phenomenon, we performed a study in 71 patients. These women with a sonographically detectable tumour (37 malignant, 34 benign) were examined on the day before surgery. We observed, that if patients uttered the number "99" with a relatively low voice or alternatively hummed a deep sound, the artifacts could be regularly visualized. In 66/71 patients (93%) status evaluation by artifact generation due to vocal fremitus examination was correct. In 3 patients the tumour was erroneously described as malignant, histology showing a proliferative mastopathy. In 2 cases the tumour was classified as benign, whereas histology revealed a malignancy, in both patients a large ductal-invasive carcinoma (> 3 cm). This phenomena could, however, not be reproduced with other colour techniques. A possible explanation is: Thoracic vibrations during speech can be registered by the MEM technique. These vibrations are not perpetuated into the benign lesion characterised by a displacing growth, due to which the vibrations are "barred off" at the borders of the tumour. Infiltrating growth typical of a malignancy causes transmission of these vibrations into the center of the tumour.(ABSTRACT TRUNCATED AT 250 WORDS)

Artifacts↗
PubMed1994

Restraint reduction: can it be achieved?

This article describes a step-by-step process for implementing restraint reduction programs in two skilled nursing facilities. The combination of using standardized guidelines, customizing others, and involving direct-care staff in facing challenges led to success. A research-practice partnership enabled a formal evaluation of the program. A pre- and posttest study design revealed significant reductions in physical restraints without increasing staff. This project demonstrates that frail, elderly people in nursing homes need not be physically restrained to receive effective care, but that alternatives can include more dignified options.

Accidental Falls↗
PubMed1994

Apical and basolateral parathyroid hormone receptors in rat renal cortical membranes.

Brush border (BBM) and basolateral membranes (BLM) of rat renal cortical cells separated by free flow electrophoresis revealed two distinct peaks of BBM-specific leucine aminopeptidase and Na+/K(+)-ATPase for BLM. PTH/PTH-related protein (PTHrP) receptors were identified in BBM and BLM. Specific binding of 125 pM [125I]chicken [Tyr36]-PTHrP-(1-36)amide [chPTHrP-(1-36)] to individual fractions of membranes separated by free flow electrophoresis overlapped with the leucine aminopeptidase and Na+/K(+)-ATPase profiles. Binding to pooled BBM was 53 +/- 5% (mean +/- SEM) of that to BLM (P < 0.01). In BBM and BLM, half-maximal inhibition of binding was obtained with 0.4-0.9 nM chPTHrP-(1-36) and 0.2-0.6 nM rat PTH-(1-34). Guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S; 100 microM) lowered chPTHrP-(1-36) binding to 50% of control levels, and half-maximal inhibition of binding was obtained with 480 and 8 nM GTP gamma S in BBM and BLM, respectively. Cross-linking of the PTH/PTHrP receptors with [125I]chPTHrP-(1-36) modified with N-hydroxysuccinimidyl-4-azidobenzoate revealed indistinguishable doublets of 83 and 73 kilodaltons in both BBM and BLM. Adenylyl cyclase was stimulated 6- and 10-fold by chPTHrP-(1-36) and GTP gamma S, respectively, in BLM and 1.3- and 1.9-fold in BBM. In conclusion, PTH receptors were recognized in both the basolateral and brush border membranes. Different receptor coupling to G-proteins and minimal cAMP stimulation in BBM provide evidence for PTH/PTHrP receptor isotypes and/or different postreceptor activation in BBM and BLM.

Adenylyl Cyclases↗
PubMed1994

Calcitonin inhibits phosphate uptake in opossum kidney cells stably transfected with a porcine calcitonin receptor.

Calcitonin (CT), and PTH and PTH-related protein (PTHrP) stimulated urinary excretion of phosphate is brought about through inhibition of Na/P04 cotransport in proximal renal tubules. PTH/PTHrP receptors linked to inhibition of phosphate uptake have been characterized in a renal tubular cell line from the American opossum (OK). Specific binding of [125I]salmon CT (sCT) to OK cells was not recognized, but 1 microM sCT stimulated cAMP accumulation 10-fold and reduced phosphate uptake by 7 +/- 2% (P < 0.05). The responses were amplified in OK cells stably transfected with a cloned CT receptor from a porcine LLC-PK1 kidney cell line. The transfected cells expressed 20,000 CT receptors per cell with a Kd of 0.05 nM and an EC50 of cAMP accumulation of 6.2 nM; maximal cAMP stimulation in response to 1 microM sCT was 259-fold (P < 0.01). Phosphate uptake was inhibited by 35 +/- 4% in response to 1 microM sCT and by 34 +/- 3% to 1 microM chicken PTHrP(1-36) (P < 0.01). Half-maximal inhibition was obtained with 0.63 +/- 0.30 nM sCT and with 1.39 +/- 0.67 nM chicken PTHrP(1-36). The inhibition of [125I]sCT binding by nonlabeled human amylin required about 5000-fold higher concentrations than those of sCT, and human calcitonin gene-related peptide-I (CGRP) at up to 1 microM did not affect [125I]sCT binding. The rank order of potencies with respect to stimulation of cAMP accumulation and inhibition of phosphate transport of sCT, amylin and CGRP was the same. This is the first report linking a cloned CT receptor to inhibition of phosphate transport in a renal proximal tubular cell.

Animals↗
PubMed1994

Cerebral vasomotor responsiveness to carbon dioxide is preserved during propofol and midazolam anesthesia in humans.

Carbon dioxide reactivity, as measured by transcranial Doppler ultrasonography, was determined during total intravenous anesthesia with propofol or midazolam in comparison with an awake control group. Thirty ASA physical status I neurosurgical patients undergoing lumbar laminectomy participated in the study. In randomized order they were subjected to a CO2 reactivity challenge, either under an intravenous anesthesia technique or in the awake state. CO2 reactivity was calculated in each study group as a relative change in middle cerebral artery (MCA) flow velocity per mm Hg change in end-tidal CO2 (PETCO2) (%/mm Hg). The cerebrovascular response to changes in CO2 was preserved during intravenous anesthesia. There was a significant difference (P < 0.05) in the reactivity slopes between the awake and the anesthetized patients with a small but not significant difference between the propofol and the midazolam group. We conclude that hypocarbia is effective in reducing cerebral blood flow velocity (CBFV) during intravenous anesthesia, either with propofol or midazolam.

Adult↗
PubMed1994

[The bipolar needle electrode in surgical laparoscopy. Initial technical experimental and clinical results].

To date the tremendous spread of operative laparoscopic procedures associated with monopolar high-frequency techniques has lead to an increase in complications caused by monopolar leakage currents. Experimental-surgical measurements on minipigs have shown no significant leakage currents in clinical relevant power range during laparoscopic application of a bipolar needle electrode as compared to monopolar electrodes. Practicability and safety of the bipolar electrode was proven in 100 operative laparoscopies for organ preserving or reconstructive surgery. In summary, with the new laparoscopic bipolar needle electrode a secure surgical instrument is available, with which finest tissue handling and minimal thermal damage feasible.

Electrodes↗
PubMed1993

Comparison of parathyroid hormone receptors in rat osteosarcoma cells and kidney.

Parathyroid hormone/parathyroid-hormone-related peptide (PTH/PTHrP) receptors have been characterized with chicken parathyroid hormone related protein [Tyr36]chPTHrP(1-36)amide (chPTHrP(1-36)) as radioligand in rat UMR-106 osteosarcoma (UMR) cells and in rat renal cortical membranes (RCM). Binding of 125 pM [125I][Tyr36]chPTHrP(1-36) was displaced by chPTHrP(1-36) with ID50 values of 2.6 +/- 0.22 nM (mean +/- S.E.) and 0.9 +/- 0.03 nM in UMR cells and RCM, respectively. ID50 values in membranes from UMR cells and RCM were the same in the presence and absence of 10 microM guanosine-5'-O-(3-thiotriphosphate). Rat [Nle8,18] PTH(1-34) was 5-fold more potent than chPTHrP(1-36) in RCM, but not in UMR cells. Hill coefficients derived from binding inhibition were 0.93 and 0.35 in UMR and RCM, respectively. For affinity labeling, N-hydroxysuccinimidyl-4-azidobenzoate-modified [125I]chPTHrP(1-36) was used. Specifically-labeled PTH/PTHrP-binding proteins had a molecular mass of 83 kDa in UMR cells and RCM. Treatment with N-endoglycosidases lowered the molecular mass of chPTHrP binding proteins to 54 kDa in UMR and RCM. In conclusion, skeletal UMR-106 cells and renal cortical membranes of the rat reveal PTH/PTHrP receptors with no apparent tissue specific differences in molecular mass of the polypeptide backbone and polysaccharide chains. Higher affinity of rat PTH(1-34) binding and lower Hill coefficients in kidney compared to bone are consistent with tissue specific receptor-ligand interactions.

Animals↗
PubMed1993

Characterization of binding sites for a GnRH-agonist (buserelin) in human breast cancer biopsies and their distribution in relation to tumor parameters.

Gonadotropin-releasing hormone analogs (GnRH-A) have been added to the armentarium in the therapy of hormone-dependent breast cancer in premenopausal women. The effect of chronic GnRH-A-treatment in premenopausal women is based on the suppression of the hypothalamus-pituitary-ovarian axis and the reduction of sex-steroid serum levels. In addition, a number of experimental and clinical data have been accumulated indicating a direct action of GnRH-A on breast cancer cells and tissue. In this study we analyzed 235 human breast cancer biopsies for specific GnRH-A-binding. We demonstrate high affinity GnRH-A binding sites in human breast cancer tissues. The evaluation of clinical data showed no correlation of the level of GnRH-A-binding with classical tumor parameters.

Amino Acid Sequence↗
PubMed1993

Human breast tumors containing non-DNA-binding immunoreactive (67 kDa) estrogen receptor.

Evidence to date indicates that structurally abnormal estrogen receptor (variant ER) can be detected in some human breast tumors. Based on in vitro ability to bind DNA sequences containing the cognate estrogen response element (ERE), these variant receptors may be categorized into DNA-binding ER (Type-1 variants) and non-DNA-binding ER (Type-2 variants). To look for Type-2 variants of normal size (67 kDa ER) that lack the ability to form immunoreactive ER-ERE complexes, a panel of 40 cryopreserved primary breast tumors were extracted and analyzed by enzyme immunoassay (ER-EIA), gel-shift, and Western blot techniques. For the 33 tumor extracts containing > or = 10 fmol/mg ER (by ER-EIA), the amount of 67 kDa ER detectable by D75 anti-ER monoclonal antibody under fully denatured and reduced assay conditions (Western blotting) did not correlate well with the presence or intensity of D75 immunoreactive ER-ERE bands seen under native conditions by gel-shift assay. Overall, 30% (10 of 33) of these extracts containing 67 kDa ER failed to produce immunoreactive ER-ERE complexes, with this frequency varying from over 40% in tumor samples with lower ER content (10-49 fmol/mg) to 11% in tumor samples with the highest ER content (> 100 fmol/mg). These results indicate that Type-2 variant receptors characterized as non-DNA-binding 67 kDa ER may be present in a significant fraction of ER-positive primary breast tumors; preliminary evidence suggests that further study of abnormalities in ER tertiary or quaternary structure, such as those produced by intracellular oxidation of ER thiol groups, is warranted.

Blotting, Western↗