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A Margulis

Publications and source records attributed to A Margulis.

At least 55 records · Page 3Linked to original sources
PubMed1993

Structural and biochemical identity of retinal rod outer segment membrane guanylate cyclase.

Recent molecular cloning reports show that there are at least three membrane guanylate cyclases in vertebrate retina: (1) atrial natriuretic factor receptor guanylate cyclase (ANF-RGC), (2) C-type natriuretic peptide receptor guanylate cyclase (CNP-RGC), and (3) "retinal guanylate cyclase" (RetGC). The specific cellular localization of the first two cyclases is unknown, but RetGC is apparently localized in photoreceptor cells, suggesting that it participates in visual transduction. With the overall objective of identifying the guanylate cyclase that is linked to phototransduction, we compared the structural and regulatory properties of the biochemically characterized 112 kDa bovine rod outer segment membrane guanylate cyclase (ROS-GC) with those of RetGC, ANF-RGC and CNP-RGC. The N-terminal and two internal peptide sequences of purified ROS-GC had about 90% similarity with the corresponding sequences of the RetGC; the sequence identity with natriuretic peptide receptor cyclases was about 30%. A 19 amino acid long sequence from a tryptic peptide of ROS-GC had no corresponding sequence in the other three cyclases. ROS-GC was inhibited by ATP but ANF-RGC and CNP-RGC were activated by ATP in the presence of the respective peptide hormones. These results suggest that ROS-GC represents a new subtype of the membrane guanylate cyclase family that is structurally and biochemically distinct from the other retinal cyclases.

Adenosine Triphosphate↗
PubMed1993

[Extra-abdominal desmoid tumor. Diagnostic, prognostic and therapeutic aspects].

We report the case of a 19 year-old female patient who consulted for a recurrent desmoid tumor of the back which had initially developed during childhood. Its clinical aspect was reminiscent of a localized subcutaneous tumor, but surgical exploration revealed multiple ramified extensions spreading over a wide area deep into the underlying muscular tissue. In spite of two attempts at wide surgery, complete resection was not achieved. EAD tumors are a distinct category between fibromatosis and fibrosarcoma. There is a direct contrast between the benign histological structure and the lack of a metastatic potential, and the fact that they are highly aggressive locally with a great proportion of relapses occurring after resection. Prognosis, which is good in terms of survival, is determinant in the choice of treatment which must remain conservative in the majority of cases. Wide, non mutilating surgery offers the best chances of cure without sequelae. When surgery may be mutilating, 50-60 Gy of radiotherapy (RT) is a good alternative and affords a high rate of complete regression over a long period of time. The value of adjuvant RT after surgical resection has yet to be determined. Hormonotherapy and other drugs are currently being evaluated.

Adult↗
PubMed1992

Effects of lithium on basal and modulated activities of the particulate and soluble guanylate cyclases in retinal rod outer segments.

A large amount of information regarding the kinetics of biochemical reactions involved in visual transduction was derived from electrophysiological studies on dark-adapted rod outer segments. Hodgkin et al. [(1985) J. Physiol. 358, 447-468] observed that when Na was replaced with Li in the perfusion solution bathing the rod outer segment, the dark current slowly declined to zero. This decline was thought to result from a rise in intracellular calcium which was hypothesized to inhibit guanylate cyclase activity and reduce the cyclic GMP concentration. Rod outer segments contain membrane and soluble guanylate cyclase activities, and we show here that Li directly inhibits both types of activities very strongly. Both the basal (at high calcium) and the stimulated (at low calcium) activities of the membrane enzyme were inhibited by Li. Half-maximal inhibition of the stimulated enzyme was at 30 mM Li while for the basal activity it was at 100 mM. Over 80% of the activated enzyme was inhibited at 110 mM Li. The soluble guanylate cyclase activity was stimulated by nitroprusside. One hundred millimolar Li inhibited the basal activity by 20-30%, but the inhibition of the nitroprusside-stimulated (soluble) enzyme was much stronger, resembling that of the activated membrane enzyme. Half-maximal inhibition occurred at 30 mM, and about 80% inhibition was found at 100 mM Li. Stimulation of the soluble enzyme by nitroprusside was independent of calcium in the physiological range. The inhibition of the stimulated enzyme by Li was similarly independent of calcium, except at unphysiologically high concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Nitroprusside-sensitive and insensitive guanylate cyclases in retinal rod outer segments.

Rod outer segments of retina contain guanylate cyclase activity both in the cytosol and membrane fractions. Though the activity in the cytosol is a small fraction of the total activity, it is highly activated by nitroprusside, a nitric oxide generating agent. The membrane guanylate cyclase on the other hand is unaffected by nitroprusside both before and after solubilization. The effects of nitroprusside or nitric oxide on photoreceptor function should therefore be mediated by the cytosolic and not the membrane guanylate cyclase.

Animals↗
PubMed1992

Regression of primary melanoma with metastases.

Seven cases of spontaneous and complete regression of primary melanoma with metastasis are reported. The ages of the patients ranged from 33 to 68 years. There were five men and two women. All patients had had a cutaneous pigmented lesion that underwent a two-stage course: enlargement and darkening, then flattening and depigmentation. Within a few months to 4 years after depigmentation, regional node(s) developed and were removed, confirming the diagnosis of melanoma. An histopathologic examination of the primary sites failed to show residual malignant cells and characteristic features. Primary melanomas that have completely regressed are easily overlooked.

Adult↗
PubMed1992

Effect of lithium on rod photoreceptor rhodopsin-coupled G-protein (transducin).

1. Lithium was known to inhibit both adrenergic and cholinergic agonist-induced activation of G-proteins in cerebral cortex. 2. Doly et al (1989) observed that lithium reduced the b-wave of the electroretinogram and suggested that the effect was due to inhibition of G-protein in photoreceptor cells. 3. This study was undertaken to test this hypothesis directly on photoreceptor cell membranes. Rod disk membranes containing the visual transduction machinery were isolated in the dark and the effect of lithium was tested on (a) activation by bright light of G-protein-mediated cyclic GMP hydrolysis, (b) light sensitivity of the activation, (c) the lifetime of the light-activated receptor, and (d) light activation of GTP-gamma-S binding to the membranes. 4. None of these processes were affected by lithium. It is therefore concluded that the effects of lithium on the b-wave of the electroretinogram should be due to influences on G-proteins in other parts of the retina.

Animals↗
PubMed1992

Randomized trial of thrombolysis versus heparin in unstable angina.

BACKGROUND: The clinical usefulness of intravenous thrombolytic therapy in unstable angina is currently unknown, despite the pathogenetic similarity of this entity to acute myocardial infarction, for which thrombolysis has enjoyed great success. To compare the clinical benefit of intravenous urokinase with that of conventional antithrombotic therapy in preventing the progression of unstable angina to new myocardial infarction, intractable angina, or death within the first 96 hours after hospitalization, 149 patients with unstable angina were randomized to one of two intravenous thrombolytic strategies. METHODS AND RESULTS: Forty-nine patients received 3 million units urokinase i.v. over 90 minutes plus intravenous heparin (group A); 47 patients received unblinded 3 million units urokinase i.v. plus 325 mg aspirin p.o. daily (group B); and 53 patients received placebo thrombolytic infusion plus full-dose heparin (group C). The primary end point of this trial was 96-hour clinical status. There were no significant differences in the baseline characteristics (age, sex, previous myocardial infarction, hypertension prevalence, diabetes, tobacco use, or previous revascularization) among the three groups. Despite an excess of minor untoward reactions for the urokinase groups (chills, 26.5% and 23.4% for groups A and B versus 0% for group C; p < 0.01), there was no significant difference with respect to major bleeds (two, none, and two for groups A, B, and C, respectively; p = NS). At 96 hours after presentation, no significant difference emerged in the incidence of new cardiac events: new myocardial infarctions developed in 10.2% of group A, 6.4% of group B, and 3.8% of group C (p = NS); intractable angina occurred in 6.1% of group A, 10.6% of group B, and 9.4% of group C (p = NS). There were no deaths. All three groups encountered a similar incidence of overall cardiac events: 16.3%, 17.0%, and 13.2% for groups A, B, and C, respectively (p = NS). Although trial enrollment was to extend to 600 patients, interim analysis led to early cessation of enrollment due to a negative trend in respect to outcome after thrombolysis. CONCLUSIONS: High-dose intravenous urokinase followed by either heparin or aspirin can be safely administered to a broad, unselected group of patients with unstable angina. However, this study suggests that no clinical advantage is conferred by urokinase, with either adjunctive antithrombotic therapy over standard heparin therapy alone, when given relatively late (mean, 8.7 hours) after admission for unstable angina. A possible detrimental effect cannot be excluded.

Angina, Unstable↗
PubMed1992

[Lymph node metastasis of melanoma of unknown primary tumor].

Sixteen patients with clinical stage II melanoma of unknown primary site (regional lymph node metastasis) were followed up between 1978 and 1988. The 5-year survival rate was 47%. These results seem to parallel those for stage II disease with known primary tumor sites, as has been observed in other data from the literature. The hypotheses put forward to explain such lesions are the spontaneous regression of the primary tumor, and the onset of primary malignant melanoma in the lymph nodes.

Adult↗
PubMed1991

Tumor-infiltrating CD3- NK cells are more effective than CD3+ T cells in killing autologous melanoma cells.

We have studied the phenotype and functional activity of tumor-infiltrating lymphocytes (TIL) derived from eight human melanomas cultured for up to 60 d in the presence of recombinant IL-2. In the early period of the cultures, TIL were predominantly T cells of CD8+ phenotype and contained 10-30% of CD3- cells. Four of the five early TIL cultures tested in a cytotoxicity assay displayed a degree of MHC-unrestricted lysis on a series of autologous and allogenic melanoma cell lines as well as the K562 natural killer-sensitive target. With longer periods of time in culture, all TIL lines showed a decrease in lytic activity that was associated with the loss of CD3- cells. Thus, most of the killing of short-term TIL cultures appeared to be mediated by CD3- natural killer cells, whereas CD3+ T cells were found to be weak anti-tumor effectors. Even though the CD3+ T cells were not cytotoxic on K562 targets, their lytic activity (even weak) against melanoma cells appeared to be non-MHC restricted, and was blocked by anti-CD3 antibodies. In addition, cytotoxicity of the CD3+ TIL cultures was compared to that of a CD3-/NKH1+ cell line purified from peripheral blood. It was found that natural killer cells were much more potent than CD3+ TIL on the melanoma cell lines tested.

Antibodies, Monoclonal↗
PubMed1979

Cyclophosphamide, methotrexate, 5-fluorouracil (CMF) in advanced gastrointestinal cancer.

The effectiveness of the cyclophosphamide + methotrexate + 5-fluorouracil schedule (CMF) in 28 patients with advanced gastrointestinal cancer has been studied. No complete remission was obtained; partial remission and objective improvement constituted 56%. The median response period is calculated at a minimum of 12 months, without significant differences between the group of patients previously subjected to palliative canalization surgery and the group of patients not subjected to this operation. The overall median survival time is 10.8 months. On the basis of the data given, the authors conclude by stressing that the CMF combination should be studied more fully in relation to its use in gastrointestinal forms of cancer.

Aged↗
PubMed1979

Indications and results of omental pedicle grafts in oncology.

Sixty omental grafts were performed in our department. Sixty-two percent concerned breast cancer patients. Other grafts were undertaken for other cancers: head and neck, gynecologic urologic and intestinal, skin and soft tissue tumors. These grafts were indicated for radionecrosis or chemonecrosis in 33 cases and for cancer recurrence in 26 cases (among whom 24 were previously irradiated). Only one graft was performed for lymphoedema treatment. Overall, fifty four patients (83.5%) had successful grafts, and six (16.5%) had graft failures. According to the treated lesion we obtained 82% of successful treatment among patients treated for radio or chemonecrosis, and 92% for patients treated for recurrences.

Adolescent↗
PubMedDate not supplied

Influence of dopamine on cyclic nucleotide enzymes in bovine retinal membrane fractions.

Dopamine is a major neurotransmitter and neuromodulator in vertebrate retina. Although its pharmacological and physiological actions are well understood, the biochemical mechanisms of its signal transduction are less clear. Acting via D1 receptors, dopamine was shown to increase cyclic AMP levels in intact retina and to activate adenylate cyclase in retinal homogenates. The action via activation of D2 receptors is controversial: it was reported to decrease cyclic AMP levels in intact retina but inhibition of cyclase could not be demonstrated in retinal homogenates; also it was reported to activate rod outer segment cyclic GMP phosphodiesterase in vitro but did not decrease cyclic GMP levels in aspartate-treated retinas. We made an attempt to fractionate bovine retinal membranes and to investigate the effects of dopamine, via D1 and D2 receptors, on the synthesis and hydrolysis of cyclic AMP and cyclic GMP. Activation of cyclic AMP synthesis was noted in all fractions, but no effects were evident on cyclic nucleotide hydrolysis or cyclic GMP synthesis in any fraction. Also, D2 agonist did not inhibit cyclic AMP synthesis. These observations suggest that D2 receptors may not be directly coupled to cyclic nucleotide metabolizing enzymes in bovine retina.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMedDate not supplied

Soluble guanylate cyclase and nitric oxide synthase in synaptosomal fractions of bovine retina.

Cyclic GMP has been shown in recent years to directly activate ion channels in bipolar and ganglion cells, and to indirectly regulate coupling between horizontal cells, and between bipolar and amacrine cells. In all of these cases, the effects of cyclic GMP are mimicked by nitric oxide. An increase in calcium concentration stimulates the production of nitric oxide by neuronal and endothelial forms of nitric oxide synthase, which in turn activates soluble guanylate cyclases, enhancing the synthesis of cyclic GMP. Though some effects of nitric oxide do not involve cyclic GMP, the nitric oxide-cyclic GMP cascade is well recognized as a signaling mechanism in brain and other tissues. The widespread occurrence of nitric oxide/cyclic GMP-regulated ion channel activity in retinal neurons raises the possibility that nitric-oxide-sensitive soluble guanylate cyclases play an important role in cell-cell communication, and possibly, synaptic transmission. Immunohistochemical studies have indicated the presence of soluble guanylate cyclase in retinal synaptic layers, but such studies are not suitable for determination of the density or quantitative subcellular distribution of the enzyme. Microanalytical methods involving microdissection of frozen retina also showed the presence of cyclase activity in retinal plexiform layers but these methods did not permit distinction between nitric oxide-sensitive and insensitive cyclases. In this study, we fractionated retinal homogenate into the cytosolic and synaptosomal fractions and investigated the specific activity and distribution of soluble guanylate cyclase and nitric oxide synthase. The results show that both enzymes are present in the synaptosomal fractions derived from inner and outer plexiform layers. The synaptosomal fraction derived from inner retina was highly enriched in cyclase activity. Nitric oxide synthase activity was also higher in the inner than outer retinal synaptosomal fraction. The results suggest that the nitric oxide-cyclic GMP system is operational in both synaptic layers of retina and that it may play a more significant role in the inner retina.

Animals↗
PubMedDate not supplied

Value of high-frequency US for preoperative assessment of skin tumors.

The purpose of this study was to evaluate the accuracy of high-frequency ultrasound (US) in the preoperative assessment of skin tumors. A US scanner with a 20-MHz probe was used to visualize and evaluate 70 skin lesions (38 clinically suspected melanomas and 32 suspected basilar cell carcinomas [BCCs]) before surgical resection. A US morphologic study and a Doppler analysis of vascularity were performed for each tumor. Of the 70 tumors, 62 were clearly visualized, including 19 melanomas, 12 nonmalignant nevi, and 31 BCCs. Most lesions were hypoechoic. In 13 of 19 proved melanomas, the difference between the histologic and US measurements was equal to or less than 0.2 mm. Vessels were visualized in melanomas with thicknesses greater than 3 mm. All BCCs were visualized, and in 29% of cases of BCC, tumor size at US was greater than that at clinical examination. High-frequency, high-resolution US is a simple, reliable, noninvasive method for accurate preoperative assessment of skin tumor dimensions. This technique allows surgical planning to be adapted and reexcision to be avoided. However, its role is limited in the differential diagnosis of malignant and benign skin lesions.

Basal Cell Carcinoma↗