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Biomedical subjects

S Kaufmann

Publications and source records attributed to S Kaufmann.

At least 37 records · Page 2Linked to original sources

Heterotopic pregnancy obtained after in-vitro fertilization and embryo transfer following bilateral total salpingectomy: case report.

Heterotopic (coexistent ectopic and intra-uterine) pregnancy is common following in-vitro fertilization and multiple embryo transfer. Total bilateral salpingectomy is generally considered to eliminate the risk of ectopic, and hence heterotopic pregnancy. This is, however, not strictly correct as it does not eliminate the risk of interstitial tubal pregnancy. This is the first reported case of a heterotopic pregnancy following total bilateral salpingectomy. The diagnostic pitfalls and a suggested method of avoiding them are discussed.

Adult↗

[Brief narcosis with propofol/ketamine for administering retrobulbar anesthesia].

BACKGROUND: Eye surgery is performed under local anesthesia in more than 90% of the cases. While injecting the local anesthetics a deep sedation is desired. During surgery however the patient should be cooperative, such as to avoid inadvertent movements. We routinely perform local anesthesia (retrobulbar injection and van Lint block) under intravenous anesthesia with propofol (Disoprivan) and ketamine (Ketalar, Ketanest). PATIENTS AND METHODS: To control safety and efficacy of this method a prospective study was performed including 100 consecutive patients. The results were to be compared with an earlier study where 35 Patients received midazolam (Dormicum) and alfentanil (Rapifen) as sedation. The actual protocol included the following points: 1. Personal judgement of the patient. 2. Conditions to perform the retrobulbar injection, 3. Intraoperative conditions and additional sedation, 4. Pulse, blood pressure and blood oxygen concentration, 5. Complications RESULTS: > 95% of the patients had a total amnesia of the injection of local anesthetics. Retrobulbar injection is comfortable (96%), but may be difficult in patients with a narrow orbit and exotropia (4%). Intraoperative conditions were noted as good in 97%. Additional sedation during surgery was necessary in 3%. Blood pressure and pulse remained stable. Blood oxygen concentration showed a tendency to sink during intravenous anesthesia. This could be managed easily by additional oxygen via face mask if necessary. Postoperative emesis was noted in 3%. No further ocular complications occurred that might be related to the anesthetic management. In an earlier study including 35 Patients under comparable conditions we used midazolam and alfentanil for sedation. The results were similar. Midazolam and alfentanil were then used in over 2000 operations. Often the patients were deeply sedated and asleep during surgery which meant a potential risk of a sudden awakening and moving the head inadvertently. Occasionally paradoxical reactions occurred after midazolam. CONCLUSIONS: Using propofol and ketamine while performing the local anesthesia the patients are awake but relaxed and cooperative during surgery. This method has now been used routinely in over 1000 cases. It has proved to be clinically safe and efficient. It offers the surgeon good working conditions and is well tolerated by the patients, reducing their preoperative and perioperative anxieties.

Adult↗

Talin anchors and nucleates actin filaments at lipid membranes. A direct demonstration.

Platelet talin nucleates actin assembly as we show here directly by using rhodamine-phalloidin labelling of actin filaments. Nucleation by talin still occurs after reconstitution into liposomal bilayers. This is also demonstrated directly after protein-lipid double labelling and light microscopic imaging. Talin, thus, is the first actin binding protein for which anchoring and nucleation of actin filament growth at lipid interfaces have been visualized.

Actin Cytoskeleton↗

Probing actin and liposome interaction of talin and talin-vinculin complexes: a kinetic, thermodynamic and lipid labeling study.

Talin purified from human platelets and chicken gizzard smooth muscle is an actin and lipid binding protein. Here, we have investigated the effect of vinculin on (a) talin-nucleated actin polymerization and (b) insertion of talin into lipid bilayers. Calorimetric data show ternary complex formation between talin, vinculin, and actin. Actin-talin, actin-vinculin and actin-(talin-vinculin) binding and rate constants as well as actin polymerization rates for all three protein species have been determined by steady state titration, stopped-flow, and fluorescence assay. In contrast to an increase of the polymerization rate by a factor of less than 2 for actin-talin and actin-(talin-vinculin) when lowering the temperature, we measured a decrease in rates for actin alone and actin-vinculin. The overall equilibrium constants (Keq) in the van't Hoff plot proved linear and were of one-step reactions. Thermodynamic data exhibited signs of van der Waal's binding forces. Using the photoactivatable lipid analogue [3H]PTPC/11, which selectively labels membrane-embedded hydrophobic domains of proteins, we also show that talin partially inserts into the hydrophobic bilayer of liposomes. This insertion occurs in a similar manner irrespective of preincubation with vinculin.

Actins↗

Severe insulin resistance and diabetes mellitus in mandibuloacral dysplasia.

Mandibuloacral dysplasia (MAD) is a syndrome with onset in midchildhood. The predominant characteristics of MAD include flexion contractures; mandibular hypoplasia; loss of body fat; atrophic, speckled skin; and progressive osteolysis of the clavicles. We studied three males with MAD. Each had lipodystrophy of the extremities, with sparing of the face and neck. All had moderate hyperlipidemia. In response to oral glucose, each had a diabetic response, with peak insulin levels between 2870 and 22,960 pmol/L. Insulin-stimulated glucose disposal was determined in two patients with MAD. At an insulin infusion rate of 120 mU/m2 per minute, glucose disposal was less than 25% of that measured at similar levels of insulinemia in nondiabetic control subjects, indicating marked insulin resistance in patients with MAD. The insulin resistance occurred without obesity, excessive levels of counterregulatory hormones, or anti-insulin-receptor antibodies. We suggest that MAD is a previously undescribed form of lipodystrophic insulin-resistant diabetes mellitus.

Abnormalities, Multiple↗

Talin binds to actin and promotes filament nucleation.

Platelet talin binds to actin in vitro and hence is an actin binding protein. By four different non-interfering assay conditions (fluorescence, fluorescence recovery after photobleaching, (FRAP), dynamic light scattering and DNase-I inhibition) we show that talin promotes filament nucleation, raises the filament number concentration and increases the net rate of actin polymerization but has no inhibitory effect on filament elongation. Binding of talin to actin occurs at a maximal molar ratio of 1:3 as determined by fluorescencetitration under G-buffer conditions. The overall binding constant was approximately 0.25 microM.

Actins↗

Insulin-resistant diabetes mellitus and hypermetabolism in mandibuloacral dysplasia: a newly recognized form of partial lipodystrophy.

Mandibuloacral dysplasia (MAD) is a syndrome characterized by partial lipodystrophy and a distinct phenotype, which includes progressive osteolysis of the mandible and clavicles, cutaneous atrophy, joint contractures, and diabetes mellitus. We now describe the results of hyperinsulinemic glucose clamps performed in conjunction with indirect calorimetry in two subjects with MAD. At a glucose level of 5 mmol/L and insulin concentration of over 6.5 x 10(4) pmol/L, glucose disposal rates were less than 20% of maximum insulin-stimulated glucose disposal in five nondiabetic controls. Basal hepatic glucose output was elevated in the two patients and was incompletely suppressed by a 1200 mU/m2.min infusion of insulin. Glucose and lipid oxidation rates were inappropriately elevated, reflecting marked hypermetabolism. Pharmacological concentrations of insulin failed to normally suppress lipid oxidation, diminish FFA levels, or adequately suppress glucagon levels. In summary, MAD is a unique form of lipodystrophic diabetes characterized by typical somatic features, extreme insulin resistance, and marked hypermetabolism.

Adolescent↗

Trends in classification usage in the mental retardation literature.

Trends in classification usage were analyzed through examination of all issues of Mental Retardation, American Journal of Mental Deficiency, and American Journal on Mental Retardation from 1980 through 1989. The research was undertaken to determine whether the recommendations by Taylor (1980) and MacMillan, Meyers, and Morrison (1980) regarding subject description had been implemented. Results indicated that the system of the American Association on Mental Retardation (previously the American Association on Mental Deficiency) was used in over 50% of the articles, whereas the American Educators system was used in only 10%. A further analysis regarding the use of various classification systems as a function of the age of the subjects was also conducted. Implications of these results were discussed.

Adolescent↗

Immunogenetic associations of scleroderma-related antinuclear antibodies.

Patients selected for the presence of scleroderma-related antibodies (anti-DNA-topoisomerase I [anti-topo I; n = 43], anticentromere antibody [ACA; n = 63], or anti-Pm-Scl [n = 12]) were studied for class I and class II major histocompatibility complex antigens, as well as for Gm and Km allotypes. Anti-topo I was associated with HLA-DR5 (70% of patients versus 30.6% of controls; Pcorr = 0.0018, relative risk [RR] = 5.3). All patients with anti-Pm-Scl were positive for HLA-DR3 (versus 23.5% of controls; Pcorr less than 0.001); 6 of these patients were DR3/4 heterozygous (50% versus 3.5% of controls; Pcorr less than 0.001, RR = 27.3). Patients with ACA were frequently positive for HLA-DR1, DR4, or DRw8, with 73.7% demonstrating at least 1 of these alleles (versus 41.2% of controls; Pcorr = 0.0152, RR = 4.0). This group of ACA-positive patients who had DR1, DR4, and/or DRw8 consisted mainly of a subgroup of patients with rheumatoid arthritis. We conclude that different class II major histocompatibility complex antigens influence the formation of anti-topo I and anti-Pm-Scl. Important clinical differences between these patient groups and the immunogenetic heterogeneity support the notion of different antibody-defined scleroderma subsets.

Antibodies, Antinuclear↗

Nocturnal melatonin levels are unaltered by ovarian suppression in girls with central precocious puberty.

Girls with central precocious puberty were utilized as a model in which to study the melatonin secretory response to ovarian suppression. Eight girls with central precocious puberty documented by clinical and endocrine characteristics, including sleep-entrained augmentation of luteinizing hormone (LH) pulsatility, were investigated. Nocturnal (6:00 P.M. to 9:00 A.M.) plasma melatonin levels were measured hourly by a sensitive and specific radioimmunoassay before and after gonadotropin-ovarian downregulation with gonadotropin-releasing hormone (GnRH)-agonist. Although nocturnal melatonin elevations varied widely between girls, patterns within the same individual were remarkably reproducible and unaltered before and after treatment. Although estrogens have been shown to modulate melatonin synthesis and secretion, in this model, reduction of estrogen levels was not associated with alterations in plasma melatonin concentrations.

Child↗

Type 3 protein kinase C localization to the nuclear envelope of phorbol ester-treated NIH 3T3 cells.

We have examined the immunocytochemical localization of protein kinase C (PKC) in NIH 3T3 cells using mAbs that recognize Type 3 PKC. In control cells, the immunofluorescent staining was similar with mAbs directed to either the catalytic or the regulatory domain of PKC. Type 3 PKC localized in a diffuse cytoplasmic pattern, while the nuclei were apparently unstained. Cytoskeletal components also were Treatment of the cells with phorbol 12-myristate 13-acetate (PMA) resulted in a redistribution of PKC with a specific increase in nuclear PKC. Compared to control cells, the staining with the anticatalytic domain mAbs changed markedly, covering the entire cell surface. In contrast, the staining by the antiregulatory domain mAb did not cover the cell surface and the nuclei remained unstained; these results suggest that PKC activation leads to a conformational change of the regulatory domain such that the epitope recognized by the antiregulatory domain mAb is not readily accessible. We have demonstrated by three criteria that PMA treatment specifically increased PKC in the nucleus: (a) immunofluorescent staining in isolated nuclei increased; (b) Western blots showed that our mAbs detected only one protein, the 82-kD PKC, whose level increased in nuclear lysates from PMA-treated cells; and (c) PKC activity increased in nuclear lysates. In fractionation studies we demonstrated that PKC specifically localized to the nuclear envelope fraction. These results demonstrate that PMA activation leads to a rapid redistribution of Type 3 PKC to the nuclear envelope, and suggests that this isozyme may play a role in mediating PKC-induced changes in gene expression.

Animals↗

Comparison of the acute metabolic effects of 22,000-dalton and 20,000-dalton growth hormone in human subjects.

The acute metabolic effects of 20,000-dalton human growth hormone (hGH20K) in man have not previously been tested. We compared changes in concentrations of free fatty acids (FFA), glucose, and insulin in nine growth hormone deficient children following injection of 22,000-dalton intact human growth hormone (hGH22K) and the smaller variant, hGH20K. There was a significant decline (37%) in the mean FFA concentration from baseline to 1/2 hour post-injection and from baseline to 1 hour post-injection (36%) in the children given hGH22K, but no such decline was seen after injection of hGH20K. No significant differences in mean insulin or glucose concentrations were noted between the two treatment groups, and glucose and insulin concentrations did not acutely change after injection of either hormone. The results of this study indicate that hGH20K has a diminished activity for suppression of FFA as compared to hGH22K. This suggests that GH residues 32-46, missing in hGH20K, constitute all or part of the region of hGH22K producing this response, or that the different primary structures of the two hormones result in tertiary structural differences and altered biological activity.

Adolescent↗

Inhibition by prednisone of growth hormone (GH) response to GH-releasing hormone in normal men.

Glucocorticoids increase GHRH-stimulated GH secretion when added in vitro to cultured monkey, rat, and human pituitary cells and when injected in vivo into anesthetized rats. Yet, in man glucocorticoids inhibit linear growth and GH secretion. To clarify this apparent disparity and to determine if glucocorticoid stimulation can augment GH release in man after direct pituitary stimulation with GHRH, we administered 1 microgram/kg GHRH dosage to seven normal men before and after a 4-day course of prednisone (20 mg, orally, three times daily). The second GHRH test was done 12 h after the last dose of prednisone was given. Prednisone significantly inhibited the mean maximal increase in serum GH after GHRH treatment [20.7 +/- 4.5 (+/- SE) vs. 6.3 +/- 2.4 micrograms/L; P less than 0.01] as well as the GH value obtained by summing and averaging the individual means of the 15, 30, 45, 60, 75, and 90 min serum GH concentrations (11.1 +/- 1.2 vs. 4.3 +/- 0.9 micrograms/L; P less than 0.05). The mean serum insulin-like growth factor I and plasma glucose concentrations were not significantly altered by prednisone administration. These results together with previous in vitro findings imply that glucocorticoid-induced inhibition of GH secretion in man does not occur at the level of the pituitary gland, but, rather, at the hypothalamus or above.

Adrenocortical Hyperfunction↗

Immunotherapy of cancer: experimental approach with activated macrophages proliferating in culture.

Murine macrophages isolated from the peritoneal cavity or from the lung were continuously grown and expanded in vitro on a confluent layer of "mesothelial or endothelial" feeding cells. These cell lines could be obtained from C57B16 or BalbC mice and were nontumorogenic in nude mice. The macrophages were characterized by their capacity to phagocytose yeasts and by the presence of nonspecific esterases, of Fc receptors, and of specific antigens (MAC1 ...). In vitro, these macrophages were fully activated and were tumoricidal against different tumor cell lines. In vivo, adoptive transfer of the expanded macrophages to mice bearing EMT6 sarcoma or 3LL metastasizing carcinoma inhibited the growth of the primary tumors and the development of metastases. Local injection in the vicinity of the primary tumor and i.v. transplantation were effective. The adoptive transfer of expanded macrophages could lead to a new kind of immunotherapy of neoplastic diseases combining selective amplification with effective activation of macrophages as key effector cells.

Animals↗

Towards new leprosy and tuberculosis vaccines.

Leprosy and tuberculosis are chronic infectious diseases causing major global health problems, for which no effective control by vaccination has been achieved. Recent advances in biotechnology may facilitate the design of a new vaccine generation. In this paper the need for, and the potential of, leprosy and tuberculosis vaccines are discussed.

Bacterial Vaccines↗

[Recurrent angioedema with eosinophilic dermatitis--minus variants of the hypereosinophilic syndrome].

Recurrent angio-oedema with eosinophilic dermatitis is characterized by the following symptoms: persistent hypereosinophilic, episodes of angio-oedema, urticarial papular and papulo-pustular exanthema, episodes of fever, as well as increased IgE and IgM levels. Eosinophilic dermatitis with subcorneal pustulation can be seen on histological examination. This disease should be distinguished from the classical hypereosinophilic syndrome because of the absence of internal symptoms and because the prognosis is apparently favourable. Internal corticosteroids are the therapy of choice.

Adolescent↗