PubMed Health⌕ Search

Biomedical subjects

M Sacher

Publications and source records attributed to M Sacher.

At least 19 recordsLinked to original sources
PubMed1997

The synaptobrevin-related domains of Bos1p and Sec22p bind to the syntaxin-like region of Sed5p.

SNAREs (soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptors) are cytoplasmically oriented membrane proteins that reside on vesicular carriers (v-SNARE) and target organelles (t-SNARE). The pairing of a stage-specific v-SNARE with its cognate t-SNARE may mediate the specificity of membrane traffic. In the yeast Saccharomyces cerevisiae transport between the endoplasmic reticulum and Golgi complex employs two v-SNAREs, Bos1p and Sec22p, each containing a domain that is related to the neuronal v-SNARE synaptobrevin. Sed5p, which is homologous to syntaxin, is the t-SNARE that functions at this stage of the secretory pathway. Here we report that regions of Bos1p and Sec22p, which are homologous to synaptobrevin, bind to the syntaxin-like domain of Sed5p. Furthermore, we demonstrate that efficient v-SNARE/t-SNARE interactions require the participation of both v-SNAREs, indicating that, unlike post-Golgi membrane traffic, the active form of the endoplasmic reticulum to Golgi v-SNARE is a heteromeric complex.

Binding Sites↗
PubMed1997

Bet1p activates the v-SNARE Bos1p.

Bet1p is a type II membrane protein that is required for vesicular transport between the endoplasmic reticulum and Golgi complex in the yeast Saccharomyces cerevisiae. A domain of Bet1p, that shows potential to be involved in a coiled-coil interaction, is homologous to a region of the neuronal protein SNAP-25. Here, we used in vitro binding studies to demonstrate that Bet1p plays a role in potentiating soluble NSF attachment protein receptor (SNARE) interactions. Mutational analysis points to the coiled-coil region as necessary for Bet1p function, and circular dichroism experiments support this theory. In vitro binding studies were also used to demonstrate that a direct interaction between Bet1p and Bos1p is required for the efficient interaction of the vesicle SNARE with its SNARE target. Genetic studies suggest that the interactions of Bet1p with Bos1p are regulated by the small GTP-binding protein Ypt1p.

Amino Acid Sequence↗
PubMed1997

Renal pyelectasis in fetuses and neonates: diagnostic value of renal pelvis diameter in pre- and postnatal sonographic screening.

OBJECTIVE: Pre- and postnatal pyelectasis detected by sonographic screening is of questionable pathologic importance. Therefore, we defined the natural course and diagnostic value of renal pelvis diameter (RPD) during fetal life and the neonatal period as such dilatation was revealed on routine sonography. MATERIALS AND METHODS: Routine sonography in pregnant women was obtained between gestational weeks 22 and 30. Sonograms were obtained for 1021 fetuses, of which 15 could not be followed up as neonates. The remaining 1006 fetuses also underwent neonatal sonography. All neonates with an RPD larger than 5 mm were followed up sonographically. Neonates with an RPD larger than 9 mm or persistent widening (> 5-9 mm) were examined by voiding cystourethrogram, radionuclide renogram, or both. RESULTS: Thirty fetuses (3%) had an RPD larger than 5 mm. Nine of these fetuses also had an RPD larger than 5 mm as neonates. Of these nine neonates, one had bilateral grade II vesicoureteric reflux (VUR) and two had urinary tract obstructions (one posterior urethral valve and one ureteropelvic junction obstruction). Forty-nine neonates whose results on fetal sonograms had been normal showed an RPD larger than 5 mm on neonatal sonograms. Grade III VUR was found in one boy, and ureteropelvic junction obstruction was found in two boys. The kidneys of 54 neonates who showed an RPD larger than 5 mm without urinary tract obstruction were followed up until an RPD of 0-5 mm was evident. RPD normalized within 1 year of birth, whether VUR was present or not. Symptomatic urinary tract infection was diagnosed in 17 infants who had no renal pelvis dilatation seen on pre-or postnatal screening during the observation period. Seven of the 17 neonates had VUR. Conversely, none of the infants with pre- postnatal dilatation presented with symptomatic urinary tract infection. However, in one neonate an asymptomatic urinary tract infection without VUR was diagnosed by routine urinalysis. CONCLUSION: In our study, we linked renal pelvis dilatation on pre- and postnatal sonograms to obstructive uropathies rather than to vesicoureteric reflux. Prenatal sonography proved less sensitive than postnatal sonography in revealing obstructive uropathies. An RPD smaller than 10 mm on neonatal sonography was of no pathologic significance because renal collecting systems normalized spontaneously in all infants within 1 year of birth. These neonates and infants had no significant risk for urinary tract infection and did not need further evaluation.

Dilatation, Pathologic↗
PubMed1996

Brain perfusion imaging during preoperative temporary balloon occlusion of the internal carotid artery.

UNLABELLED: The main objective of this study was to assess whether 99mTc-HMPAO brain SPECT imaging can identify patients at high risk of developing an infarct following permanent carotid occlusion in the course of brain surgery. METHODS: Test balloon occlusion of the internal carotid artery was performed in 44 patients with a variety of head and neck tumors or aneurysms. Technetium-99m-HMPAO was injected intravenously while the balloon was initiated and a SPECT study was obtained 30 min later. Follow-up CT scans were obtained routinely for all patients at 2 wk and 1 mo following surgery, or earlier when necessary. Thirty patients and five normal volunteers had semiquantitative analysis of cerebral perfusion. RESULTS: Twenty-six patients demonstrated ipsilateral perfusion abnormalities during trial occlusion. Eight patients in this group underwent bypass grafting prior to sacrifice of the artery: two resulting in infarcts. Eighteen patients had symmetric cerebral perfusion during occlusion and four of these patients underwent permanent therapeutic carotid occlusion; three patients had subsequent infarcts and the fourth patient had an impending stroke. CONCLUSION: Patients with symmetric cerebral perfusion measured by 99mTc-HMPAO SPECT may still have a high long-term complication rate following carotid sacrifice. The scan findings in these patients were not predictive of the outcome. Patients with asymmetric cerebral perfusion had alternative therapeutic approach to carotid sacrifice and most of them had good surgical outcomes.

Brain↗
PubMed1996

Rapid differential diagnosis of cerebral toxoplasmosis and primary central nervous system lymphoma by thallium-201 SPECT.

UNLABELLED: This study sought to assess whether 201Tl brain SPECT can significantly reduce the time required for the differential diagnosis of primary central nervous system (CNS) lymphoma and cerebral toxoplasmosis in patients with AIDS. METHODS: Eighteen patients who presented with focal lesions on CT or MRI, or both, underwent 201Tl brain SPECT shortly after admission and before a CT-guided stereotactic brain biopsy. Early and delayed 201Tl uptake ratios were obtained for patients with positive 201Tl study results, and the retention index of 201Tl was calculated. RESULTS: Ten patients had 11 foci of significantly increased 201Tl uptake in regions of corresponding CT/MRI lesions. Five of these patients had biopsy-proven lymphomas, one of them in two separate foci. Another patient was found to have metastatic adenocarcinoma. Three patients had a clinical course and response to radiation therapy consistent with lymphoma, and study results in another patient were considered falsely positive. Of nine patients with no 201Tl uptake in regions of CT/MRI lesions, two had biopsy findings consistent with a benign etiology, and the other seven improved clinically on antitoxoplasmosis medications alone. The overall sensitivity of 201Tl brain SPECT was 100%, and specificity was 90%. The 201Tl retention index in patients with lymphomas was significantly higher than that in patients with adenocarcinomas and nonmalignant lesions (1.35 +/- 0.16 versus 0.24 and 0.56, respectively). CONCLUSION: Thallium-201 brain SPECT is a sensitive and specific method for rapid differential diagnosis of CNS lymphoma and toxoplasmosis in patients with AIDS. The 201Tl retention index is useful in differentiating CNS lymphomas from other malignant and nonmalignant pathologies.

AIDS-Related Opportunistic Infections↗
PubMed1995

Validation and comparison of models predicting survival following intracerebral hemorrhage.

OBJECTIVE: To compare the performance of two previously reported logistic regression models using data independent from those data used to derive the models. DESIGN: Prospective. SETTING: Acute stroke unit of a tertiary care hospital. PATIENTS: One hundred twenty-nine patients with supratentorial intracerebral hemorrhage. MEASUREMENTS AND MAIN RESULTS: Model 1 contains the initial Glasgow Coma Scale score, hemorrhage size, and pulse pressure. The more complex model 2 includes, in addition to those three variables, the presence or absence of intraventricular hemorrhage and a term representing the interaction of intraventricular hemorrhage and Glasgow Coma Scale score. The areas under the receiver operating characteristic curves generated for each model were statistically indistinguishable. CONCLUSIONS: Model 1 predicts 30-day patient status as well as the more complex model 2. Model 1 provides a valid, easy-to-use means of categorizing supratentorial intracerebral hemorrhage patients in terms of their probability of survival.

Cerebral Hemorrhage↗
PubMed1995

First-pass radionuclide cineangiography in diagnosis of coronary artery disease in patients older than 75 years: evaluation of sensitivity.

The sensitivity of first-pass radionuclide cineangiography in the detection of coronary artery disease was evaluated in 60 patients subdivided equally according to age younger than or older than 75 years. The mean age of group 1 (age > or = 75 years) was 80.2 years +/- 5.3, and the mean age in group 2 (age < 75 years) was 62.0 years +/- 6.4. Disease prevalence in group 1 was 87% versus 80% in group 2. Group 1 had higher prevalence of hypertension (67% vs 33%) and lower prevalence of typical angina pectoris (23% vs 55%). Overall sensitivity of first-pass radionuclide cineangiography in group 1 was 93% versus 97% in group 2. Older patients had significantly lower maximal heart rates, workloads, and exercise durations, and age correlations were significant for exercise heart rate, workload, and exercise duration. Failure to achieve an adequate exercise endpoint had significant effect on testing sensitivity only in the younger subjects (98% vs 60%), indicating that sensitivity of first-pass radionuclide cineangiography is age independent.

Age Factors↗
PubMed1995

Avid uptake of technetium-99m-HMPAO by an intracranial plasmacytoma during carotid balloon test occlusion.

A 56-yr-old woman was evaluated for removal of a tumor at the base of the skull. A test to determine the risk of carotid artery sacrifice was performed prior to surgery using carotid balloon occlusion of the left internal carotid artery and 99mTc-HMPAO perfusion scintigraphy during the occlusion. An unusual intense focus of increased uptake was seen at the site of the primary tumor in the left cavernous sinus. The tumor, found to be plasmacytoma at surgery, demonstrated only mild washout from 30 min to 2 hr after administration of 99mTc-HMPAO, with a tumor-to-cerebellum ratio of 1.6 and 1.5, respectively, and a tumor-to-contralateral cranial ratio of 2.5 and 2.4, respectively. Intracranial plasmacytoma shows good response to radiation therapy, and the differentiation of this tumor from other neoplasms is pertinent to the mode of treatment and surgical approach. Technetium-99m-HMPAO SPECT imaging may be a useful tool in distinguishing these tumors from other neoplasms at the base of the skull.

Brain Neoplasms↗
PubMed1994

Postoperative changes on brain SPECT imaging after aneurysmal subarachnoid hemorrhage. A potential pitfall in the evaluation of vasospasm.

Serial brain SPECT imaging was performed on patients after subarachnoid hemorrhage and surgical clipping of intracranial aneurysms. A total of 20 HMPAO scans were performed on 9 patients in whom clinical vasospasm did not develop. Areas of diminished regional cerebral blood flow (rCBF) were found near the operative site in 17 of 20 studies, which did not correlate with the patients' neurologic condition and were suggestive of postoperative edema. Brain SPECT imaging has a potentially valuable role to play in the evaluation of postoperative patients susceptible to vasospasm; however, it is important to be aware of postoperative changes in rCBF that are not related to vasospasm.

Brain↗
PubMed1993

Emergency treatment of bronchospastic attacks in an emergency medicine department: effects of a quality improvement project.

New insights have recently changed the therapeutical approach to bronchospastic attack (BA). In this paper we present the results of a quality assurance study devised to: (1) verify the extent to which these new insights are put into practice in our Emergency Medicine Department (EMD); (2) evaluate changes in EMD medical staff behaviour faced with BA after discussion and distribution of medical practice guidelines on the treatment of BA (a document produced by a group of experts in pulmonary medicine working in the EMD on the basis of current literature and personal experiences); (3) assess the impact of such guidelines on quality care. A retrospective analysis demonstrated an incorrect treatment of BA in the EMD. After the introduction of the guidelines we observed: (1) an improvement in physician behaviour that completely agreed with guidelines in 56% of instances after discussion and distribution of the document, in 8% before; (2) an improvement in the outcome of patients treated for BA in the EMD (13 versus 36% relapses for patients treated in the EMD and discharged).

Bronchial Spasm↗
PubMed1992

The energy cost of walking or running on sand.

Oxygen uptake (VO2) at steady state, heart rate and perceived exertion were determined on nine subjects (six men and three women) while walking (3-7 km.h-1) or running (7-14 km.h-1) on sand or on a firm surface. The women performed the walking tests only. The energy cost of locomotion per unit of distance (C) was then calculated from the ratio of VO2 to speed and expressed in J.kg-1.m-1 assuming an energy equivalent of 20.9 J.ml O2-1. At the highest speeds C was adjusted for the measured lactate contribution (which ranged from approximately 2% to approximately 11% of the total). It was found that, when walking on sand, C increased linearly with speed from 3.1 J.kg-1.m-1 at 3 km.h-1 to 5.5 J.kg-1.m-1 at 7 km.h-1, whereas on a firm surface C attained a minimum of 2.3 J.kg-1.m-1 at 4.5 km.h-1 being greater at lower or higher speeds. On average, when walking at speeds greater than 3 km.h-1, C was about 1.8 times greater on sand than on compact terrain. When running on sand C was approximately independent of the speed, amounting to 5.3 J.kg-1.m-1, i.e. about 1.2 times greater than on compact terrain. These findings could be attributed to a reduced recovery of potential and kinetic energy at each stride when walking on sand (approximately 45% to be compared to approximately 65% on a firm surface) and to a reduced recovery of elastic energy when running on sand.

Adult↗
PubMed1991

Effects of order of presentation of exercise intensities and of sauna baths on perceived exertion during treadmill running.

Thirteen male subjects performed a running test on the treadmill consisting of four standard exercise intensities [65%, 75%, 85%, 95% maximal O2 uptake (VO2 max)] presented in ascending, descending or random order. At the end of each exercise intensity, O2 consumption, heart rate (fc), venous blood lactate concentration [( Ia]b) and perceived exertion were assessed. This last variable was determined according to the Borg nonlinear CR-20 scale. The same variables were also determined during exercise at a standard intensity (65% or 95% VO2 max) performed before and after a Finnish sauna bath. Ratings of perceived exertion showed a good test-retest reliability (r = 0.77); they were the same when the exercise intensity was expressed in relative (%VO2 max) or absolute (speed) terms, and were independent of the order of presentation of the exercise. The latter had no effect on fc either but it did, however, influence [Ia]b, which was significantly higher in the descending, as compared to the ascending or random modes of presentation. The sauna bath increased fc at a given exercise intensity, but left perceived exertion and [Ia]b unchanged. It was concluded that at least under the present experimental conditions, fc and venous [Ia]b do not play a major role as determinants of perceived exertion.

Adult↗
PubMed1991

Intracranial chordoma in a preadolescent. Case report.

Chordomas are rare tumors derived from notochord remnants occurring primarily in the sacrum, clivus, and cervical regions. Exceptionally, these tumors occur in children, though usually in the sacrum. Eight cases of clivus chordoma have been described in preteenagers. In this report, a clival chordoma with unusual radiologic features is described in an 11-year-old boy. The literature regarding this entity is reviewed.

Brain Neoplasms↗
PubMed1991

Spinal Charcot arthropathy.

Charcot joints of the spine are well-documented clinical entities most commonly associated with tabes dorsalis. Spinal neuropathic joints, however, may be produced by other disease processes including syringomyelia. In this review, the authors discuss the cause and treatment of spinal Charcot arthropathy with emphasis on surgical therapy and results.

Arthropathy, Neurogenic↗
PubMed1991

Acute atraumatic subdural hematoma associated with moyamoya disease in an African-American.

A 57-year-old black woman with an atraumatic subdural hematoma was treated for congestive heart failure and was found to have moyamoya disease. The association of these two lesions is rare and has never been described in an African-American. High cerebral venous pressures and changes in cerebral perfusion caused by congestive heart failure and the loss of cerebrovascular autoregulation in moyamoya disease may explain the spontaneous occurrence of a subdural hematoma. Recommendations for management are discussed.

Female↗
PubMed1990

Identification of cytochrome P450IA2 as a human autoantigen.

Autoantibodies occurring in a patient with idiopathic autoimmune type chronic active hepatitis (CAH) were found to react with purified rabbit cytochrome P450IA2 and to a much lesser extent with P450IA1. Both cytochrome P450s are known to be inducible by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the rabbit, and the expression of the microsomal protein recognized by the patient serum was induced in adult rabbit livers after treatment with TCDD. This protein is only weakly detected in liver microsomes from neonatal rabbits exposed to TCDD in utero, which is consistent with the age-dependent induction of P450IA2 by TCDD. The serum specifically reacted with a protein of similar size in microsomes prepared from COS-1 cells transfected with an expression vector containing the full length human P450IA2 cDNA. This reactivity was not detected in the cells transfected with the vector alone, indicating that the antibody recognizes human P450IA2. In addition, the serum extensively inhibited 7-ethoxyresorufin O-deethylation catalyzed by isolated human liver microsomes. This catalytic activity is associated with class IA P450s in other species. A screen of sera from patients with various hepatic and nonhepatic diseases indicates that the autoantibody to P450IA2 occurs rarely in CAH. Cytochrome P450IA2 becomes the third P450 identified as an autoantigen in inflammatory liver diseases.

Adult↗