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A Margulis

Publications and source records attributed to A Margulis.

At least 37 records · Page 2Linked to original sources
PubMed1998

Identification of effector binding sites on S100 beta: studies with guanylate cyclase and p80, a retinal phosphoprotein.

S100 beta is a calcium-binding protein, which regulates the activities of several enzymes and inhibits the phosphorylation of a variety of protein kinase C substrates in a calcium-dependent manner. The protein was recently found to activate a retinal membrane guanylate cyclase, and in this paper, we report that it inhibits the phosphorylation of an 80 kDa retinal protein (p80). Structurally, S100 beta consists of two EF-hands connected by a hinge region. In view of its small size, wide distribution in a variety of tissues, and regulation of many different proteins, it is of interest to identify the sites on the protein that interact with the effectors, and to determine if the same sites are responsible for interaction with different effectors. We addressed these questions with the use of synthetic peptides with sequences corresponding to different regions of S100 beta and testing their effects on the protein's activation of guanylate cyclase, and inhibition of p80 phosphorylation. Peptides with sequences corresponding to effector interaction sites were anticipated to either block or simulate the effects of S100 beta. The results show that two regions of S100 beta interact with effectors: the C-terminal region of Thr81-Glu91 and the hinge region of Leu32-Leu40. The synthetic peptide containing the latter sequence blocked the S100 beta activation of guanylate cyclase and inhibition of p80 phosphorylation, while the peptide containing the former sequence blocked cyclase activation and simulated S100 beta in inhibiting p80 phosphorylation. By determining the effects of including or excluding dithiothreitol in the assays, we observed that the cysteine residue in the C-terminal region of S100 beta (Cys84) participates in the regulation of guanylate cyclase but not of p80 phosphorylation. We conclude from these results that the C-terminal and hinge regions of S100 beta are important in the regulation of effector proteins and that Cys84 is essential for interaction with only specific effectors.

Amino Acid Sequence↗
PubMed1998

[Microcystic sclerosing adnexal carcinoma: 2 case reports. Diagnostic and therapeutic difficulties].

Microcystic adnexal carcinoma is a recently described malignant neoplasm of adnexal structure. It remains frequently misdiagnosed. These tumors are characterized by their slow progression and by local aggressivity with local recurrences. The best treatment appears to be surgical excision with microscopically controlled margin. We report two cases of microcystic adnexal carcinoma recently observed at Institute Gustave Roussy.

Carcinoma, Skin Appendage↗
PubMed1997

Structural and functional characterization of retinal calcium-dependent guanylate cyclase activator protein (CD-GCAP): identity with S100beta protein.

Calcium-dependent guanylate cyclase activator protein (CD-GCAP) is a low-molecular-weight retinal calcium-binding protein which activates rod outer segment guanylate cyclase (ROS-GC) in a calcium-dependent manner. This investigation was undertaken to determine the protein's structure and identity. Partial amino acid sequencing (72% of the protein), mass spectral analysis, cloning, and immunological studies revealed that CD-GCAP is identical to S100beta, another low-molecular-weight calcium-binding protein whose structure was known. We had shown earlier that the latter protein, which is usually called S100b (S100betabeta or dimer of S100beta), also activates ROS-GC but that the Vmax of activated cyclase was about 50% lower than when stimulated by CD-GCAP. S100b also required about 15 times more calcium (3.2 x 10(-)5 vs 1.5 x 10(-)6 M) for half-maximal stimulation of cyclase. To investigate the possibility that CD-GCAP is a post-translationally modified form of S100b, both proteins were treated with 1 M hydroxylamine which is known to deacylate proteins. After the treatment, CD-GCAP did not activate cyclase while S100b activation remained unaffected suggesting that CD-GCAP could not be a modified form of S100b. Hydroxylamine also broke down CD-GCAP into smaller fragments while leaving S100b intact. It therefore appeared that in spite of identical primary structures, the conformations of the two proteins were different. We then investigated the possibility that the purification procedures of the two proteins, which were quite different, could have contributed to such conformational differences: CD-GCAP purification included a step of heating at 75 degrees C in 5 mM Ca, while S100b purification included zinc affinity chromatography. To test the influence of these treatments on the properties of the proteins, CD-GCAP was subjected to zinc affinity chromatography and purified as S100b (CD-GCAP-->S100b) and S100b was heated in Ca and purified as CD-GCAP (S100b-->CD-GCAP). Cyclase activation, calcium-sensitivity, and hydroxylamine-lability measurements revealed that CD-GCAP-->S100b is identical to S100b and that S100b-->CD-GCAP is identical to CD-GCAP. Taken together the results demonstrate that CD-GCAP and S100b are one and the same protein and that their functional differences are due to different interconvertible conformational states.

Amino Acid Sequence↗
PubMed1997

Endogenous ADP-ribosylation of a G(alpha i) protein in bovine ciliary body is stimulated by nitric oxide.

Five ciliary body membrane proteins were labeled when incubated with (adenylate-32P)NAD. Nitric oxide donors stimulated the labeling of 64, 40, and 29-30 kDa proteins and inhibited that of 58 and 56 kDa proteins. The greatest influence of nitric oxide was on the 40 kDa protein: a 17-fold stimulation. Western blotting and immunoprecipitation with specific antibodies identified this protein as the alpha-subunit of G(i-1). Studies with inhibitors showed that the protein was mono-ADP-ribosylated. Treatment of (32P)NAD-labeled G(i-1) with Hg and analysis of the released radioactive material showed that the protein was ADP-ribosylated on a cysteine residue.

Adenosine Diphosphate Ribose↗
PubMed1997

Radical resection of radiation-induced sarcoma of the chest wall: report of 15 cases.

BACKGROUND: Surgical management of radiation-induced sarcoma of the chest wall remains difficult because of its impressive local aggressiveness. METHODS: Between 1987 and 1995, 15 patients (median age, 58 years) underwent radical resection of radiation-induced sarcoma of the chest wall. This type of tumor was defined as a metachronous, histologically different neoplasm in the irradiated field of the original tumor. Ten patients had a history of primary breast cancer and 5 patients, Hodgkin's disease. The median delivered radiation dose to the primary tumor area was 45 Gy, and the median interval between radiotherapy and diagnosis of sarcoma was 14 years. Seven tumors were located on the sternum, three on the lateral chest wall, and five in the thoracic outlet. Four total and three partial sternectomies, three lateral chest wall resections and five resections of tumors in the thoracic outlet (three first-rib resections) were performed. Seven patients required stabilization of the chest wall with prosthetic material. Soft tissue reconstruction was carried out with either muscle flaps and skin advancement in 9, musculocutaneous flaps in 4, or skin flaps alone in 2 patients. RESULTS: One patient died 3 months after total sternectomy of respiratory failure. Two patients (13.3%) had a local complication: sepsis after sternectomy in 1 and cutaneous necrosis in 1. Local recurrence occurred in 7 patients after a median interval of 10 months. Two of them died, and 4 underwent a repeat resection, 3 of whom are still alive. Four patients died of systemic recurrence. With a median follow-up of 30 months, overall 5-year survival and 5-year disease-free survival rates were 48% and 27%, respectively. CONCLUSION: Despite poor long-term disease-free survival, radical resection of radiation-induced sarcoma of the chest wall is justified on the basis of low postoperative morbidity and the lack of other available therapies.

Female↗
PubMed1997

Basal cell carcinoma of the face: surgery or radiotherapy? Results of a randomized study.

Basal cell carcinomas (BCCs) are very frequent cutaneous cancers, often located on the face. Cure rates with surgery and radiotherapy are high, but these treatments have never been compared prospectively. A randomized trial was initiated in 1982 to compare surgery and radiotherapy in the treatment of primary BCC of the face measuring less than 4 cm. The primary end point was the failure rate (persistent or recurrent disease) after 4 years of follow-up. The secondary end point was the cosmetic results assessed by the patient, the dermatologist and three persons not involved in the trial. In the course of the trial, 347 patients were treated. Of the 174 patients in the surgery group, 71% had local anaesthesia and 91% frozen section examination. Of the 173 patients in the radiotherapy group, 55% were treated with interstitial brachytherapy, 33% with contactherapy and 12% with conventional radiotherapy. The 4-year actuarial failure rate (95% CI) was 0.7% (0.1-3.9%) in the surgery group compared with 7.5% (4.2-13.1%) in the radiotherapy group (log-rank P = 0.003). The cosmetic results assessed by four of the five judges were significantly better after surgery than after radiotherapy. Eighty-seven per cent of the surgery-treated patients and 69% of the radiation-treated patients considered the cosmetic result as good (P < 0.01). Thus, in the treatment of BCC of the face of less than 4 cm in diameter, surgery should be preferred to radiotherapy.

Adult↗
PubMed1997

Intratumoral oxygen tension in metastatic melanoma.

Tumour hypoxia can lead to a decrease in the biological effectiveness of radiation and alkylating agents. Few data are available on oxygen tension (PO2) in melanoma. In 20 patients with past history of melanoma, PO2 was evaluated in normal tissues and suspected metastatic lesions (nodes and skin metastases). Oxygen tension was measured using a needle probe technique (KIMOC-6650 histograph, Eppendorf, Germany), the day before the surgical removal of the suspected metastatic lesion. Histological confirmation of the malignant origin of the removed lesion was obtained in 18 cases. In two cases invasion by the known melanoma was not seen histologically. The median PO2 for normal tissues was 40.5 mmHg. For tumours, the median PO2 was 11.6 mmHg, and it was 17.1 mmHg in nodes and 6.7 mmHg in skin metastases. Very low values (< 2 mmHg) accounted for 20% of the recorded values in nodes and 15% in skin metastases. When analysed according to the node size (< or > or = 3 cm in diameter), the median PO2 was 10.4 mmHg in large nodes (six patients) and 53.3 mmHg in small nodes (six patients). For the two non-tumoral lesions, the median PO2 values were 20.9 and 25.1 mmHg, with no values below 10 mmHg. Thus a decrease in PO2 values, probably corresponding to tumour hypoxia, was found in most of the metastatic tumours when compared with normal tissues. The prognostic value of these PO2 measurements in melanoma remains to be demonstrated in the tumour response to radiotherapy or alkylating agents. However, tumour hypoxia can already be investigated as a target for new treatment modalities in metastatic melanoma.

Adult↗
PubMed1996

Activation of bovine photoreceptor guanylate cyclase by S100 proteins.

S100 proteins are acidic calcium-binding proteins present in high concentration in the brain and at lower concentrations in peripheral tissues. Their function remains to be elucidated in many tissues. In this report we show for the first time that S100 proteins stimulate the bovine photoreceptor membrane guanylate cyclase. The extent of stimulation varied between the different S100 proteins with the S100b exhibiting the highest level of influence. The stimulation by all S100 proteins was calcium dependent, with the half-maximal stimulation occurring at about 35-40 microM calcium. These results suggest that in some cells S100 proteins can mediate calcium signals via cyclic GMP.

Animals↗
PubMed1995

A novel calcium-dependent activator of retinal rod outer segment membrane guanylate cyclase.

The membrane guanylate cyclase in retinal rod outer segments (ROS-GC) is known to be negatively regulated by calcium; when the calcium concentration is reduced below the dark-adapted level of about 500 nM, the enzyme is activated by a soluble protein. We now report that the enzyme is also positively regulated by calcium; a novel soluble protein is identified and purified from bovine retina which activates ROS-GC, with half-maximal activation occurring at 2-5 microM calcium. The activation is dose-dependent, and at its maximum, cyclase is stimulated up to 25-fold. The activator has a molecular mass of about 40 kDa and is a multimer of a 6-7 kDa peptide.

Animals↗
PubMed1995

A new clinical classification for hospital prognosis of unstable angina pectoris.

Unstable angina represents a heterogeneous spectrum of clinical entities between chronic stable angina and acute myocardial infarction. To facilitate prognostication of in-hospital outcome, we prospectively tested on a priori unstable angina classification scheme based on information available at the time of acute presentation. Prospective database enrollment at the time of emergency room presentation was performed and patients were classified into 1 of the following categories: class IA, acceleration of previous exertional angina without electrocardiographic (ECG) changes; class IB, acceleration of previous exertional angina with ECG changes; class II, new-onset exertional angina; class III, new-onset rest angina; class IV, protracted rest angina with ECG changes. The study consisted of 1,387 consecutive patients with unstable angina. Baseline demographics and aggregate in-hospital major cardiac event rates were recorded (myocardial infarction, refractory angina, and death). There was a significant increasing trend in cardiac events from class I to IV (p < 0.0001). Class IA patients had the lowest aggregate event rate at 2.7% (p = 0.0005). Paired chi-square tests of adjacent categories showed no differences in event rates for class IB and II (p = 0.3). A significantly higher rate of adverse events was seen for class III patients (20.1%, p < 0.0001). Class IV patients demonstrated the highest rate of in-hospital adverse events (42.8%, p < 0.0001). We conclude that this easily deduced, universally applicable categorization of unstable angina is highly prognostic of in-hospital adverse cardiac events and hence could have potential use for triage decisions regarding hospital admission and intensity of therapy.

Aged↗
PubMed1995

Prolonged urokinase infusion for chronic total native coronary occlusions: clinical, angiographic, and treatment observations.

Prolonged intravascular infusion of urokinase has proven beneficial in reestablishing patency of chronically occluded peripheral arteries and saphenous vein grafts. This study was performed to assess the efficacy and safety of prolonged urokinase infusion as a prelude to angioplasty in chronically occluded native coronary arteries, that had failed standard angioplasty techniques. Twenty-five patients with objective evidence for ischemia in the distribution of a chronic coronary occlusion were referred for percutaneous intervention. Patients were assessed for any potential exclusions from lytic therapy. Urokinase infusion through both a SOS wire and a stable guiding catheter was continued at 100,000-240,000 units/hr for 8-25 hr; patients then underwent attempted balloon angioplasty. Mean duration of urokinase infusion was 20.6 +/- 7.7 hr (total dose 163,000 +/- 52,447 units/hr). Fibrinogen levels dropped slightly with this (300 +/- 129 to 203 +/- 81 mg/dl, P = 0.02). Angiography posturokinase showed improvement in 7 (28%) with regard to coronary flow (> or = 1 TIMI-grade). Angioplasty was successful in 13 (52%), with final angiographic result revealing thrombus in 5 (20%), or dissection 8 (32%). The infusions were well-tolerated with a low incidence of chest pain, 2 (8%) or ischemic ECG response, 2 (8%); myocardial infarction, 2 (8%); or significant bleeding 2 (8%). All patients survived the procedure, with a length-of-hospital stay = 5.1 +/- 4 days. Use of prolonged preangioplasty intracoronary urokinase infusion can be done safely with success in roughly one-half of patients with chronic total native coronary occlusions who have failed prior attempts at percutaneous intervention.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

The bovine rod outer segment guanylate cyclase, ROS-GC, is present in both outer segment and synaptic layers of the retina.

Cyclic-GMP, which plays a pivotal role in visual transduction in the vertebrate retina, is synthesized by guanylate cyclase. The purpose of this study was to localize a rod outer segment-derived particulate guanylate cyclase (ROS-GC) to the retina of several species that have different populations of rods and cones. A rabbit antibody was raised against a synthetic peptide, corresponding to the sequence A107-L125 of bovine ROS-GC. Western blot analysis showed a single immunoreactive band at about 115 kDa with bovine rod outer segments but not with human rod outer segments. Light microscopic immunocytochemistry of tissue sections revealed immunoreactivity in the outer segment layer and in the outer and inner plexiform layers. The rod-rich rat retina showed uniform immunolabeling of outer segments; the cone-containing cat retina showed heavily labeled cone outer segments and lighter labeling of rod outer segments; the cone-rich chicken retina showed a uniformly and intensely labeled outer segment layer. Preincubation of the primary antibody with the peptide completely blocked antibody binding. Electron microscopic immunocytochemistry of the cat retina confirmed the presence of guanylate cyclase in photoreceptor outer segments and demonstrated its association with disk and plasma membranes. These data support a concept in which guanylate cyclase is much more concentrated in the outer segments of cones than rods. The immunolabeling of the plexiform layers suggests that the particulate guanylate cyclase is not unique to the photoreceptor outer segments, and may also play a role in transduction processes of retinal synapses.

Amino Acid Sequence↗
PubMed1995

Melanoma arising de novo in childhood: experience of the Gustave-Roussy Institute.

Between January 1956 and December 1990, 17 patients younger than 17 years with available pathological screens of de novo cutaneous melanoma, and with no other risk factors (xeroderma pigmentosum, giant congenital naevi, congenital melanoma or a proven family history of dysplastic naevus syndrome) were seen at the Gustave-Roussy Institute. The median age was 9 years and 9 months (range 2 years and 3 months-16 years and 9 months). The primary disease was located in the lower extremities in 10 cases, the trunk in five cases, and the upper extremities or head and neck in one case. The disease was localized for 10 patients at presentation (stage I), six had proven nodal metastasis (stage II) and one patient had nodal and breast metastases. The median thickness of the primary lesion was 2.89 mm (range 0.64-10). Five tumours were at level III on Clark's index, eight at level IV and four at level V. Six cases were classified as superficial spreading, two as unclassified radial growth, three nodular, three with Spitzoid cells, and three were unclassified. Two patients presented local recurrence with an initial unclassified melanoma, with a thickness greater than 2.5 mm. At a median follow-up time of 7 years, two patients had died from recurrent disease, and one patient had died from a second malignancy.

Adolescent↗
PubMed1995

Comparison between familial and nonfamilial melanoma in France.

BACKGROUND AND DESIGN: Five percent to 10% of cutaneous malignant melanomas (CMMs) occur in a familial setting. Clinical, epidemiologic, and genetic studies of familial CMM in different regions of the world have led to various results. To assess the characteristics of familial CMM in France, the clinical, histologic, and epidemiologic characteristics of 295 patients with CMM were recorded, and a comprehensive familial investigation was performed for each case. Patients with a family history of CMM were compared with nonfamilial cases. RESULTS: Cutaneous malignant melanoma occurred as a familial cancer in 22 (8%) of 295 patients. Among the multiple variables studied, those significantly associated with the familial occurrence of CMM were red hair, inability to tan, and presence of clinically atypical moles. When these variables were considered together in a multivariate analysis, only the association with red hair (P = .001) and atypical moles (P < .05) remained significant. In addition, the patients with familial melanoma exhibited the following tendencies: a younger age at diagnosis, a higher number of moles, and the development of multiple primary melanomas, but these results did not reach statistical significance. Factors relating to UV light exposure, histologic features of CMM, course of the disease, and occurrence of nonmelanoma cancers showed a similar distribution between familial and nonfamilial cases. CONCLUSION: A familial investigation should be performed for each patient with CMM in France, particularly when he or she exhibits phenotypic risk factors for CMM such as red hair and atypical moles.

Adult↗
PubMed1994

Emergent percutaneous cardiopulmonary bypass in patients having cardiovascular collapse in the cardiac catheterization laboratory.

Percutaneous cardiopulmonary bypass (PCB) was instituted in 30 initially stable patients who developed either cardiac arrest refractory to resuscitation (n = 7) or cardiogenic shock (mean arterial blood pressure < 50 mm Hg unresponsive to fluid resuscitation or vasopressors) (n = 23) after a catheterization laboratory complication. Events leading to collapse included abrupt closure during percutaneous transluminal coronary angioplasty (PTCA) (n = 22), complications from diagnostic cardiac catheterization (n = 6), left ventricular perforation during mitral valvuloplasty (n = 1), and right ventricular perforation during pericardiocentesis (n = 1). PCB was initiated within 20 minutes of cardiovascular collapse in 83% of patients (arrest: 21 +/- 13 minutes [range 10 to 50]; and shock: 17 +/- 6 minutes [range 10 to 30]). Mean arterial blood pressure increased on PCB from 0 to 56 mm Hg in patients with cardiac arrest and from 37 to 63 mm Hg in those with cardiogenic shock at mean PCB flow rates of 2.5 to 5.0 liters/min. Subsequent therapy on PCB included emergent cardiac surgery (n = 14), PTCA (n = 13) and medical therapy (n = 3). Six patients (20%) survived to hospital discharge (3 with cardiac surgery, 2 with PTCA, and 1 with medical therapy). All 7 patients with refractory cardiac arrest died despite further interventions on PCB, whereas 6 of 23 (26%) with cardiogenic shock survived to hospital discharge. Thus, in response to cardiovascular collapse in the catheterization laboratory, PCB does not salvage patients who do not regain a stable cardiac rhythm. PCB can stabilize patients who develop cardiogenic shock for further interventions which are lifesaving in only a minority of patients.

Aged↗
PubMed1994

Chest wall reconstruction following resection of large primary malignant tumors.

Reconstructive procedures following radical resection of large primary malignant chest wall tumors (PMCWT) continue to evolve. Between 1982 and 1993, 32 consecutive patients (18 males/14 females) with a median age of 47 years (range, 12-77) underwent radical resection for large (median 10 +/- 5.4 cm) PMCWTs arising either from the bone (n = 15) or soft tissues (n = 17) of the chest wall. Nine (28%) had previous surgical resection before referral. Sixteen (50%) required extensive skin excision. Twelve sternectomies (5 total and 7 partial) and 20 lateral chest wall resections were performed. In this latter group, 16 patients (80%) had at least three ribs resected. Resection extended to the lung (10 wedge resections, 2 lobectomies and 1 pneumonectomy) in 13 patients, diaphragm in 3, abdominal wall in 2, brachiocephalic and subclavian vessels in 5, superior vena cava in 1 and upper limb in 1. Stability of the chest wall was obtained with prosthetic material in 27 patients, including Marlex (n = 21), polytetrafluoroethylene (PTFE) (n = 4) and polyglactin (n = 2) meshes. After sternectomy, six patients had a methyl methacrylate mesh reinforcement while soft tissue reconstruction was carried out using the pectoralis major muscle (PM), either alone with skin advancement (n = 8) or as a myocutaneous flap in three males (unilateral n = 2, bilateral n = 1) and by a latissimus dorsi (LD) myocutaneous flap in one female. Muscle transposition was used to reconstruct defects of the lateral chest wall and included 10 LD, 6 PM and 2 serratus anterior (SA) muscles, with associated advancement of the diaphragm in two cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

[Late recurrence of melanoma beyond 10 years].

Late recurrence phenomenon in the course of melanoma (i.e. first recurrence after a 10 years or more disease free interval) is often ignored. Eleven cases and a literature review are presented. Main conclusions are: --lack of clinical or pathological criteria predicting the risk for a given patient, --possible underevaluation of the number of patients affected by these late recurrences, due to a premature follow up cessation, --advantages of prolonged clinical follow up over ten years aimed at early diagnosis of locoregional metastasis which may benefit from successful surgical treatment.

Adult↗