Plant virus movement proteins.
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Biomedical subjects
Publications and source records attributed to M Lapidot.
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Neuroleptic-induced akathisia (NIA) and parkinsonism (NIP) continued for 3 months, despite two courses of anticholinergic treatments, a shift to low-potent neuroleptic (NL) and a NL-free period. The two adverse effects responded dramatically to electroconvulsive therapy (ECT) to reemerge 3 months after termination of ECT. The case supports the idea that ECT is effective for both NIA and NIP even when they are resistant.
A series of carboxy- and amino-terminal deletion mutations in the movement protein (MP) gene of tobacco mosaic virus (TMV) were ligated into a cloned TMV cDNA deleted for the endogenous MP gene. RNA transcripts were produced in vitro from clones carrying the various mutated MP genes. The effect of the deletion mutations on local and systemic movements of the infection was evaluated. Deletion of 9 or 33 amino acids from the carboxy terminus of the movement protein did not effect cell-to-cell movement as reflected by local lesion formation on Nicotiana tabacum cv. Xanthi NN plants. Deletion of 55 amino acids resulted in impaired MP that supported the formation of local lesions of 1 mm in diameter compared to lesions of 3-5 mm caused by the wild-type MP. Deletion of 74 amino acids (or more) from the carboxy terminus resulted in a protein that could not support virus movement. Modified viruses that contained repeated sequences in the 3' region of the MP gene lost the repeated sequences during replication and reverted to the wild type. This was evidenced by the size of the MP produced and by sequence analysis of reverse-transcribed PCR-amplified products, following infection by the modified virus. MP deleted for as few as 3 amino acids at the amino terminus could not support virus movement thus indicating that the amino-terminal domain is critical for MP activity.
The occurrence of neuroleptic malignant syndrome (NMS) was studied prospectively in two series of consecutive psychiatric in-patients (n = 223). The first group (n = 120) suffered from schizophrenia and was treated only with haloperidol. The second group (n = 103) was treated with diverse neuroleptics. All patients were on a single antipsychotic agent with no anticholinergic drug as prophylaxis. The incidence of full NMS per admission and first neuroleptic exposure was 5/223 (2.2%). Patients with bipolar affective disorder and those treated with injections were significantly over-represented in the NMS group.
Plasma membranes (PM) isolated from mouse splenic lymphocytes were successfully fused to rat basophilic leukemia (RBL) cells using intact Sendai virus virions (SV). A two-step procedure was used in which SV were first fused with the PM to create PM + SV vesicles; the vesicles formed were then incubated with the RBL cells. Insertion of lymphocyte PM into the RBL cell's membrane endows a high rate of serotonin secretion upon stimulation of the implanted RBL cells with antimouse Ig antibodies or with concanavalin-A. The results of the present work clearly suggest that activation signals can be delivered via implantation of foreign membrane preparation containing specific receptors, thus rendering the target cells susceptible to stimulation by specific reagents.
Four adult patients with active acromegaly underwent studies of their 24-hour secretory pattern of hGH and Prl prior to and at the end of 3 months of treatment with the octreotide (somatostatin analog SMS 201-995) 100 micrograms s.c. every 8 h. Blood was withdrawn at 30-min intervals with the aid of a constant withdrawal pump. The best fit cosinor method was used to define the following rhythm parameters: mesor, amplitude, acrophase and periodicity. Prior to treatment, hGH secretion was increased in all patients. The mean 24-hour ranged from 9-47 ng/ml with amplitude 5.2-23 and observed maximal pulse 41-95 ng/ml. Computed rhythms were circadian in 3 patients and ultradian in 1; in 2 patients the acrophases were shifted to daytime. hPrl secretion was altered in 3 of the patients. Two had elevated mean 24-hour of 17.7 and 22.2 ng/ml, while computed rhythms showed semicircadian periodicity in 1 of them and circadian periodicity with a shift of acrophase to daytime in the other. The third patient who had normal hPrl levels, showed ultradian 8-hour periodicity. At the end of treatment there was a marked reduction in hGH secretion in 1 patient and a lesser reduction in the other 3. The rhythm was influenced by the masking effect of the drug, to yield an 8-hour period with acrophases related to injection clock time having equal amplitudes.(ABSTRACT TRUNCATED AT 250 WORDS)
Influenza viruses were able to mediate fusion of DNA-loaded liposomes with living cultured cells such as monkey COS-7 cells. This was inferred from the appearance of CAT activity in recipient cells incubated with the combination of influenza viruses and liposomes loaded with the plasmid pSV2CAT. Influenza virions were found to be as efficient as intact Sendai virions in mediating microinjection of foreign DNA into living cells. Also, reconstituted envelopes bearing either influenza glycoproteins or the combination of Sendai and influenza glycoproteins were highly efficient in promoting fusion of loaded liposomes with recipient cells. Introduction of DNA into cultured cells required the presence of an active influenza fusion protein; namely, an active HA glycoprotein. Very little or no CAT activity was observed in cells incubated with loaded liposomes and unfusogenic influenza viruses. The virus-induced fusion event probably occurs within intracellular organelles such as endosomes following receptor-mediated endocytosis of virus-liposome complexes. This is due to the fact that the viral fusion glycoprotein is activated only at acidic pH values such as those which characterize the intraendosomal environment. Results of the present work demonstrate for the first time microinjection of foreign DNA via fusion with membranes of intracellular organelles. The potential of the present system to serve as a biological carrier for in vivo use is discussed.
A 49-year-old XYY man was found to have high myopia OU with unusual multiple retinal atrophic holes located in the posterior pole, unrelated to a posterior staphyloma or any other myopic degenerative changes. Most of the retinal holes showed signs of self-healing, with no evidence of vitreous traction or retinal detachment. High myopia and atrophic retinal holes have been found in other chromosomal disorders and in one sex-chromosomal abnormality.
A 56-year-old woman with gonadal dysgenesis and pituitary adenoma is described. The unusual feature in this patient was the coexistence of a low gonadotropin level with secondary ACTH deficiency rather than the high gonadotropin level usually found in gonadal dysgenesis. Secretion of the other pituitary hormones was normal. Several hypotheses for such an unusual combination are presented.
Co-reconstitution of influenza and Sendai virus phospholipids and glycoproteins resulted in the formation of membrane vesicles containing the envelope glycoproteins from both viruses within the same membrane. Reconstituted influenza-Sendai hybrids (RISH) were able to lyse human erythrocytes and fuse with their membranes or with living cultured cells at pH 5.0 as well as at pH 7.4, thus exhibiting the fusogenic properties of both viruses. This was also inferred from experiments showing that the fusogenic activity of RISH was inhibited by anti-influenza as well as by anti-Sendai virus antibodies. Fusion of FISH and of reconstituted influenza (RIVE) or reconstituted Sendai virus envelopes (RSVE) with recipient membranes was determined by the use of fluorescently labeled envelopes and fluorescence dequenching methods. Observations with the fluorescence microscope were used to study localization of fused reconstituted envelopes within living cells. Incubation of RISH and RSVE with living cells at pH 7.4 resulted in the appearance of fluorescence rings around the cell plasma membranes and of intracellular distinct fluorescent spots indicating fusion with cell plasma membranes and with membranes of endocytic vesicles, respectively. The fluorescence microscopy observations clearly showed that RIVE failed to fuse, at pH 7.4, with cultured cell plasma membranes, but fused with membranes of endocytic vesicles.
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We hereby present a patient with Cushing's disease who became pregnant while being treated with o,p'-DDD and underwent a therapeutic abortion in view of the known embryotoxicity and placental transfer of this drug. Biopsy of adipose tissue in this patient showed it to be the storage site of considerable quantities of o,p'-DDD. Serum levels of o,p'-DDD determined in this patient initially four months after withdrawal of treatment and in another similar case three months after withdrawal were about 20 times higher than those found in untreated patients and reached control values only about 20 months later. Repeated evaluation of plasma and urinary free cortisol failed to reveal any correlation with the serum levels of o,p'-DDD, suggesting that the drug blood values cannot be used as a reliable indicator of the therapeutic effect on the adrenal gland. The histopathological examination of the embryo, aged about 42 days, revealed a dysmorphogenic event in the cortical primordia characterized by pycnotic sympathoblasts. It is suggested that such a toxic effect of o,p'-DDD on the embryonic cortical cells may act indirectly, affecting the viability of the migrating sympathoblasts.
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A 73-year-old woman who presented with primary adrenal insufficiency and enlarged adrenal glands on computed tomographic scanning was ultimately found to have a large-cell lymphoma that had initially involved the adrenals and the stomach. A search of the English language medical literature revealed only seven other cases of lymphoma presenting with hypoadrenalism, none of which involved the stomach. As in this case, in most of those cases adrenal enlargement was documented on computed tomographic scanning. Despite its rare occurrence, lymphoma should be searched for in patients presenting with Addison's disease and enlarged adrenal glands.
The occurrence of malignant hyperthermia in 20 patients who had had neuroleptic malignant syndrome and in their 108 first-degree relatives was retrospectively studied. The patients had experienced a total of 20 courses of ECT and 12 surgical operations in which drugs that can cause malignant hyperthermia were used, but no cases of malignant hyperthermia had occurred, and no cases had occurred in the 37 relatives who had undergone surgery or ECT. The authors conclude that patients who have had malignant neuroleptic syndrome are not at considerably greater risk than others for developing malignant hyperthermia during surgery or ECT; the clinical data suggest that the two disorders are not related.
Membrane vesicles, bearing only the influenza viral hemagglutinin glycoprotein, were reconstituted following solubilization of intact virions with Triton X-100. The viral hemagglutinin glycoprotein was separated from the neuraminidase glycoprotein by agarose sulfanilic acid column. The hemagglutinin glycoprotein obtained was homogenous in gel electrophoresis and devoid of any neuraminidase activity. A quantitative determination revealed that the hemolytic activity of the hemagglutinin vesicles was comparable to that of intact virions. Incubation of fluorescently labeled hemagglutinin vesicles with human erythrocyte ghosts (HEG) or with liposomes composed of phosphatidylcholine/cholesterol or phosphatidylcholine/cholesterol/gangliosides, at pH 5.0 but not at pH 7.4, resulted in fluorescence dequenching. Very little, if any, fluorescence dequenching was observed upon incubation of fluorescently labeled HA vesicles with neuraminidase or glutaraldehyde-treated HEG or with liposomes composed only of phosphatidylcholine. Hemagglutinin vesicles were rendered non-hemolytic by treatment with NH2OH or glutaraldehyde or by incubation at 85 degrees C or low pH. No fluorescence dequenching was observed following incubation of non-hemolytic hemagglutinin vesicles with HEG or liposomes. These results clearly suggest that the fluorescence dequenching observed is due to fusion between the hemagglutinin vesicles and the recipient membranes. Incubation of hemagglutinin vesicles with living cultured cells, i.e. mouse lymphoma S-49 cells, at pH 5.0 as well as at pH 7.4, also resulted in fluorescence dequenching. The fluorescence dequenching observed at pH 7.4 was inhibited by lysosomotropic agents (methylamine and ammonium chloride) as well as by EDTA and NaN3, indicating that it is due to fusion of hemagglutinin vesicles taken into the cells by endocytosis.
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