[Mucocele of the appendix. A rare differential diagnosis of right-sided adnexa tumor].
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Aged↗
Biomedical subjects
M Weiss
Publications and source records attributed to M Weiss.
Concomitant administration of chlorambucil limits dose intensity of fludarabine in previously treated patients with chronic lymphocytic leukemia.
Fifteen patients with chronic lymphocytic leukemia (CLL) were treated in a phase I-II study of chlorambucil with an escalating dose of fludarabine. The study was designed to identify a maximum tolerated dose (MTD) of fludarabine given in conjunction with a constant dose of chlorambucil. Patients were eligible for study if they had Rai intermediate or high-risk disease which had relapsed from or was refractory to conventional treatment. The initial cohort of patients received fludarabine 10 mg/m2/d days 1-5 and chlorambucil 20 mg/m2 days 1 and 15. Cycles were repeated every 28 days. Unacceptable toxicity was encountered in this cohort. The protocol was then modified to give chlorambucil 20 mg/m2 on day 1 (only). At this chlorambucil dose, cohorts of three patients were treated with fludarabine 10, 15, and 20 mg/m2/d x 5 days. The predominant toxicity was thrombocytopenia with 73% experiencing grade > or = 3 toxicity. The dose-limiting non-hematologic toxicity was infection. We identified an MTD of fludarabine of 15 mg/m2/d x 5 days when given with chlorambucil 20 mg/m2 for this group of patients. One patient achieved a CR and three patients achieved a PR for a total response rate of 27%. We conclude that concomitant administration of chlorambucil limits the dose intensity of fludarabine which can be administered to previously treated patients with CLL.
Aged↗
[Monitoring microvascular osteomyocutaneous flaps by measuring tissue oxygen pressure].
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Bone Transplantation↗
Human granulocyte-macrophage colony-stimulating factor receptor signal transduction requires the proximal cytoplasmic domains of the alpha and beta subunits.
Human granulocyte-macrophage colony-stimulating factor (GM-CSF) controls the production, maturation, and function of cells in multiple hematopoietic lineages. These effects are mediated by a cell-surface receptor (GM-R) composed of alpha and beta subunits, each containing 378 and 881 amino acids, respectively. Whereas the alpha subunit exists as several isoforms that bind GM-CSF with low affinity, the beta common subunit (beta c) does not bind GM-CSF itself, but acts as a high-affinity converter for GM-CSF, interleukin-3 (IL-3), and IL-5 receptor alpha subunits. The cytoplasmic region of GM-R alpha consists of a membrane-proximal conserved region shared by the alpha 1 and alpha 2 isoforms and a C-terminal variable region that is divergent between alpha 1 and alpha 2. The cytoplasmic region of beta c contains membrane proximal serine and acidic domains. To investigate the amino acid sequences that influence signal transduction by this receptor complex, we constructed a series of cytoplasmic truncation mutants of the alpha 2 and beta subunits. To study these truncations, we stably transfected the IL-3-dependent murine cell line Ba/F3 with wild-type or mutant cDNAs. We found that the wild-type and mutant alpha subunits conferred similar low-affinity binding sites for human GM-CSF to Ba/F3, and the wild-type or mutant beta subunit converted some of these sites to high-affinity; the cytoplasmic domain of beta was unnecessary for this high-affinity conversion. Proliferation assays showed that the membrane-proximal conserved region of GM-R alpha and the serine-acidic domain of beta c are required for both cell proliferation and ligand-dependent phosphorylation of a 93-kD cytoplasmic protein. We suggest that these regions may represent an important signal transduction motif present in several cytokine receptors.
Amino Acid Sequence↗
Related signals for endocytosis and basolateral sorting of the asialoglycoprotein receptor.
The major subunit of the human asialoglycoprotein receptor contains signals for efficient endocytosis and specific basolateral expression in polarized Madin-Darby canine kidney cells, both of which are located within its 40-residue cytoplasmic domain. The aromatic residue in this segment, tyrosine 5, which is necessary for efficient clustering into clathrin-coated pits at the plasma membrane, is also necessary for exclusive basolateral delivery. Mutation of this residue to alanine resulted in a nonpolar expression of the protein. Replacement of tyrosine 5 with phenylalanine yielded almost wild-type rates of endocytosis as well as specific basolateral expression, indicating that tyrosine phosphorylation is not essential for either sorting step. The close similarity between the two sorting signals was further corroborated by deletion mutants showing that the amino-terminal 10 residues of the cytoplasmic domain are sufficient for basolateral polarity and efficient endocytosis. The kinetics of appearance of newly synthesized wild-type and mutant receptor protein at the apical and basolateral surfaces indicate that these proteins are sorted intracellularly and are transported directly to the respective domains. Mutants affected in basolateral sorting lost polarity, i.e, appeared to similar extents on both surfaces, indicating that there is no significant apical sorting information elsewhere in the protein. The close correlation between endocytosis and basolateral polarity suggests common recognition mechanisms at the plasma membrane and in the trans-Golgi network.
3T3 Cells↗
Comparative evaluation of bicycle and dobutamine stress echocardiography with perfusion scintigraphy and bicycle electrocardiogram for identification of coronary artery disease.
In 66 patients with suspected coronary artery disease (CAD), exercise electrocardiography (ECG), exercise echocardiography, dobutamine stress echocardiography (dosage, 5 to 40 micrograms/kg/min), single-photon emission computed tomography (SPECT) using methoxy-isobutyl-isonitrile (MIBI) and coronary angiography were performed prospectively to compare methods for detecting CAD. CAD was defined as 70% luminal area stenosis in at least 1 coronary artery at coronary angiography. Significant CAD was present in 50 patients. Compared with exercise ECG, exercise echocardiography, dobutamine stress echocardiography and MIBI-SPECT had a significantly higher sensitivity (52% vs 80, 79 and 89%; p < 0.01, p < 0.01 and p < 0.001, respectively). There were no significant differences in sensitivity between exercise echocardiography, dobutamine stress echocardiography and MIBI-SPECT. Specificity of MIBI-SPECT was lowest (71%), whereas exercise ECG, exercise and dobutamine echocardiography had higher specificities (93, 87 and 81%, respectively). Significance, however, was not achieved. Differences in overall accuracy between exercise echocardiography (82%), dobutamine stress echocardiography (80%) and MIBI-SPECT (85%) were not significant. Comparison with accuracy of exercise ECG (62%) was significant (p < 0.05, p < 0.05 and p < 0.01, respectively). In 1-vessel disease, exercise ECG had a lower sensitivity (45%) than exercise and dobutamine echocardiography and MIBI-SPECT (79, 78 and 84%; p < 0.02, p < 0.02 and p < 0.01, respectively). Regarding the 24 patients with false-negative exercise ECG results, 67% had positive exercise echocardiography findings, 71% positive dobutamine echocardiography results and 84% positive technetium-99m MIBI-SPECT results.(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗
Evidence of L-arginine/nitric oxide pathway in endothelium and smooth muscle of human internal mammary artery.
UNLABELLED: The L-arginine-nitric oxide (NO) pathway was investigated in human internal mammary artery (HIMA) in vitro. HIMA rings were mounted in organ bath, and then incubated in Krebs buffer for 1 to 8 hrs, relaxing agents were tested. Under these conditions, L-arginine (0.1 microM - 1 mM) elicited only minor relaxation after 2 hr incubation, whereas with increased incubation time (4, 6, 8 hrs), the concentration-dependent relaxation to L-arginine increased significantly in endothelium-intact and -denuded vessels. NG-nitro-L-arginine (100 microM) or NG-monomethyl-L-arginine (100 microM) or methylene blue (2.7 microM) partially inhibited L-arginine relaxation. In endothelium-intact HIMA and in both types of rings A23187 (10 microM) and L-arginine (100 microM), respectively, increased the concentration of NO in medium and cGMP content of vascular tissues. These increases were partially inhibited by NG-nitro-L-arginine (100 microM) or methylene blue (2.7 microM). CONCLUSION: in smooth muscle of HIMA L-arginine-NO conversion is calcium independent, which is different from that in endothelium.
Acetylcholine↗
[Magnesium therapy of acute heart infarct--has its time come?].
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Humans↗
Spatiotemporal expression of pregnancy-specific glycoprotein gene rnCGM1 in rat placenta.
As a basis towards a better understanding of the role of the pregnancy-specific glycoprotein (PSG) family in the maintenance of pregnancy, detailed investigations are described on the expression of a recently identified rat PSG gene (rnCGM1) at the mRNA and protein levels. Using specific oligonucleotide primers, rnCGM1 transcripts were identified after reverse transcription, polymerase chain reaction, and hybridization with a radiolabelled, internal oligonucleotide. Transcripts were only found in significant amounts in placenta. In situ hybridization visualized rnCGM1 transcripts at day 14 post coitum (p.c.), in secondary trophoblast giant cells and in the spongiotrophoblast. Only those secondary giant cells lining the maternal decidua were positive. In contrast, primary giant cells did not contain rnCGM1 mRNA. At day 18 p.c., rnCGM1 transcripts were almost exclusively detectable in the spongiotrophoblast. No rnCGM1 transcripts were found in rat embryos of these two developmental stages. Rabbit antisera were generated against the amino-terminal immunoglobulin variable-like domain and against a synthetic peptide containing the last 13 carboxy-terminal amino acids of rnCGM1. Both antisera recognized a 124 kDa protein in day 18 rat placental extracts as identified by Western blot analysis. The anti-peptide antiserum recognized a 116 kDa protein in the serum of a 14 day p.c. pregnant rat that is absent from the sera of non-pregnant females. Taken together, these results confirm exclusive expression of rnCGM1 in the rat trophoblast, but unlike human PSG, negligible or no expression is found in other organs, such as fetal liver or salivary glands, indicating a more specialized function of rnCGM1. Its spatiotemporal expression pattern is conducive with a potential role of PSG in protecting the fetus against the maternal immune system and/or in regulating the invasive growth of trophoblast cells.
Amino Acid Sequence↗
Instant therapy of acquired agranulocytosis and sepsis by recombinant granulocyte-macrophage colony-stimulating factor in a polytrauma patient.
Recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) was given to an intensive-care patient with polytrauma in a life-threatening situation with acquired agranulocytosis and sepsis. Mature granulocytes reappeared in the blood 2 days after initiation of rhGM-CSF therapy; granulocyte precursors peaked at 43% after 5 days. Bone marrow examination performed 7 days after the beginning of rhGM-CSF therapy revealed complete regeneration of granulopoiesis. The functional analysis of these blood leukocytes in vitro showed regular production of reactive oxygen radicals. Clinically, the patient recovered without any serious side effects due to the rhGM-CSF therapy. These results suggest that rhGM-CSF accelerates granulocyte recovery from acquired agranulocytosis with the presence of their functional activity.
Adult↗
Bedside manners: paradoxes of physician behavior in grand rounds.
This paper explains some of the routine of grand rounds in a major Israeli teaching hospital. It focuses on paradoxical behavior of physicians and others who participate in grand rounds. Behaviors are explained as boundary marking mechanisms meant to redefine statuses in the hospital and defend the physician from threats to his status. These paradoxical behaviors also function to permit the physician to enter and depart from the more culturally marginal territories of human experience, those which people try to deny or mask in everyday life. In particular, paradoxical behavior arises when dealing with death, waste, and sex. Paradoxical behavior is seen as a means of making a space in which everyday reality is masked and turned into play, creating a boundary between the medical reality and the social world. Paradox and other aspects of the grand rounds serve to restratify and counteract structural breakdown created by the physician's entry into states of pollution.
Adaptation, Psychological↗
Tracheal allograft replacement. An unsuccessful method.
Replacement of the tracheal conduit remains a difficult and unresolved surgical problem. We present an experimental study of 20 pigs undergoing replacement of the cervical trachea using glutaraldehyde (n = 5), glycerol (n = 5), lyophilized (n = 5) and cryopreserved (n = 5) pretreated allogenic grafts (AGs). In the lyophilized group, a stainless steel spiral endoprosthesis was used as stent. A segment of native trachea measuring 3.2 +/- 0.3 cm (range: 1-5 cm) in length and 1.4 +/- 0.02 cm in diameter was resected and replaced with AGs measuring 3.8 +/- 0.2 cm in length and 1.4 +/- 0.2 cm in diameter. Neither immunosuppressive agents nor steroids were given. Animals were followed up with weekly bronchoscopy, and trachea and chest roentgenography. Those receiving glutaraldehyde AG (21.6 +/- 6.4 days) and lyophilized AG (19.5 +/- 7.8 days) had a longer survival than those receiving glycerol AG (6.8 +/- 0.3 days) and cryopreserved AG (5 +/- 0.5 days). At postmortem, grafts were examined grossly and with light microscopy. The cause of death was always airway obstruction, and the underlying processes were: 1) collapse due to cartilaginous microscopic necrosis in cryopreserved and glycerol AGs; 2) necrosis of allograft which crossed the spiral stent for lyophilized AGs; 3) granulation formation, tissue necrosis and anastomosis leakage in glutaraldehyde AGs. Results demonstrate that passage of necrotic tissue across the grafts represent the common failure denominator, making the different AGs studied unsuitable for long-segment tracheal replacement.
Animals↗
Capillary deposition of C4d complement fragment and early renal graft loss.
Clinical outcome of kidney grafts that are affected by the complex syndrome of 'early graft dysfunction' is uncertain and rather unpredictable. In this study, an individual prognosis for dysfunctioning allografts (N = 93) is attempted by the immunohistological assessment of vascular classical complement activation in graft biopsies. Thus, capillary deposition of complement fragment C4d was observed in the majority (N = 51) of early dysfunctioning grafts. In 43 biopsies, abundant deposition of fragment C4d was present in all capillaries, whereas in eight specimens a segmental distribution of capillary C4d was observed. In 42 grafts with early dysfunction no capillary C4d was detectable. Eighteen subsequent graft losses within one year (16 early losses) were recorded in the subgroup with C4d in all capillaries, and three early losses in the group with segmentally distributed C4d. Only four graft losses (3 early losses) were recorded in the C4d-negative group (P = 0.0027; Pearson's chi square test). The resulting one-year graft survival rates (72% for the study group) differed markedly between the subgroups. Grafts with generalized or segmental capillary deposition of C4d had 57% and 63% survival, respectively, contrasted by 90% survival in the C4d-negative group. It is of note, however, that also three of the four grafts that were finally lost within the C4d-negative group, showed distinct capillary deposition of C4d in second biopsies. Vascular deposition of complement fragment C4d therefore represents a clinically relevant factor that contributes to early graft dysfunction. Its assessment is helpful for an individual graft prognosis.
Animals↗
[Hermaphroditism verus: clinical aspects, diagnosis and therapy in adulthood].
A 20-year old woman, who underwent an intersex operation during infancy, was presented for evaluation of the gonads because of suspected true hermaphroditism. The phenotype was female with regular menstruations. Examination revealed an ovarian tumour of 8 cm on the left side and a normal right ovary. During the operation, the tumour was revealed as an endometriosis cyst, which could be excised whilst preserving the ovarian tissue. The right gonad was an ovotestis. The testicular part was removed because of a 4% risk of malignancy. The different combinations of ovary/testis and ovotestis are described. Diagnosis and therapy of true hermaphroditism should be performed as early as possible to obtain an adequate gonadal function and an undisturbed psychosexual development.
Adult↗
[Pelviscopic surgery without pneumoperitoneum? A new method and its effects on anesthesia].
New developments in the field of pelviscopic surgery enable us to perform more extensive, time-consuming and difficult operations. Prolonging the increased intraabdominal pressure carries the risk of dangerous complications, especially in high-risk patients. We introduce a new technique to perform prolonged pelviscopic operations without or with only slightly increased intraabdominal pressure. The abdominal wall is suspended from a fixation frame. Negative effects on anaesthesia caused by prolonged increased intraabdominal pressure can be compensated. Many different pelviscopic operations can be performed using this simple and inexpensive technique, particularly in surgical procedures of the adnexae. This new technique is advantageous especially in high-risk patients, who can no longer be excluded from extensive pelviscopic surgery.
Anesthesia, General↗
["Inflammatory" disk degeneration. Magnetic resonance tomographic clinical picture].
Disc degeneration, if it appears relatively early, progresses rapidly with inadequate bone compensation for stabilisation of the area, or in the presence of anatomic variation of the vertebrae with short sagittal diameters, there may be tissue proliferation and edema in the bone marrow and vascular granulations within the disc. We demonstrated these changes in 17 patients by means of MRT which shows edema of the bone marrow and contrast enhancement within the disc. All these patients had severe symptoms. There were no significant neurological findings since in general there was no disc prolapse. The MRT characteristics of this condition are described and correlated with the clinical and radiological features. The use of Gd-DTPA and subtractive spin-echo and gradient-echo sequences in the differential diagnosis from infective discitis is discussed.
Adult↗
HNF4 and HNF1 as well as a panel of hepatic functions are extinguished and reexpressed in parallel in chromosomally reduced rat hepatoma-human fibroblast hybrids.
Rat hepatoma-human fibroblast hybrids of two independent lineages containing only 8-11 human chromosomes show pleiotropic extinction of thirteen out of fifteen hepatic functions examined. Reexpression of the entire group of functions most often occurs in a block, and except for one discordant subclone, correlates with loss of human chromosome 2. The extinguished cells and their reexpressing derivatives have been examined for the expression of seven liver-enriched transcription factors. C/EBP, LAP, DBP, HNF3, and vHNF1 expression are not systematically extinguished in parallel with the hepatic functions. However, HNF1 and HNF4 show a perfect correlation with phenotype: these factors are expressed only in the cells showing pleiotropic reexpression. Since recent evidence indicates that HNF4 controls HNF1 expression, it can be proposed that the HNF4 gene is the primary target of the pleiotropic extinguisher.
Albumins↗
Benzodiazepines and their solvents influence neutrophil granulocyte function.
We have examined the effects of commercially available preparations and drug-free solvents of diazepam (Valium, Diazepam-Lipuro) and midazolam (Dormicum) by N-formylmethionyl-leucylphenylalanine (FMLP)- and zymosan-induced polymorphonuclear cell (PMN) chemiluminescence and in a cell-free chemiluminescence system. In the case of Valium, drug-free solvent and diazepam suppressed PMN chemiluminescence. With Diazepam-Lipuro, the solvent stimulated and diazepam inhibited PMN chemiluminescence. With midazolam (Dormicum), only the active drug depressed PMN chemiluminescence. FMLP-induced PMN chemiluminescence was depressed 10-100 fold more by diazepam and midazolam than zymosan-induced chemiluminescence.
Diazepam↗