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Biomedical subjects

M Kotler

Publications and source records attributed to M Kotler.

At least 127 records · Page 7Linked to original sources

Photosensitization of cultured cells and viruses by pyrene lipids.

Administration of pyrene-linked fatty acids and lipids to cultured cells or an enveloped (vesicular stomatitis) virus induced photosensitization which, following irradiation with a long ultra-violet light (LUV), resulted in killing of the cells and loss of the infectivity of the virus with the following specific effects. (i) LUV illumination of the pyrene-sphingomyelin administered cultured skin fibroblasts derived from normal individuals and patients with Niemann-Pick disease permitted selective killing of the latter. (ii) Similarly LUV illumination of pyrenedodecanoic acid (P12) incubates of leukemic cell lines mixed with human bone marrow cells permitted selective killing of the former. (iii) LUV illumination of P12 incubates of vesicular stomatitis virus decreased the infectivity of the virus by up to 12 logs.

Cell Survival↗

Suicide in the Israeli army.

The present study was an attempt to analyze the problem of suicide in the Israel Defense Forces (IDF). Suicide is increasing among populations aged 18-21, which in Israel is the age when most young people are called up for a 3-year period of compulsory military service. The service may have a catalytic effect on suicide. but on the other hand may serve as a control mechanism reducing suicide. The study used data for the period 1974-1985, and examined suicide in combat and noncombat units by duration of service and by preservice psychiatric, medical, and motivational data. The suicide groups were also compared with a matched sample of nonsuicide groups along the relevant variables. The findings seem to be consistent with some established theoretical perspectives of situational stress, social support, and status incompatibility, and seem to bear practical implications for the reduction of suicide.

Achievement↗

[Competency for military arrest as a psychiatric problem].

Military law does not invest physicians with the authority to determine whether a soldier is competent when faced with military arrest, as this is a legal determination. Therefore, medical (or psychiatric) examination carried out before or during military arrest or detention, is aimed at preventing deterioration in the health of the imprisoned soldier. Hence, medical opinion serves only as a "credential" of sorts, the formal language of the military law. In reality, the examining psychiatrist has to consider many factors, including the probability that his conclusions will provide an important basis for the decision of the military legal officer as to whether to enforce military arrest. To illustrate the complicated considerations facing military psychiatrists, several case reports are presented of patients examined in the Israel Defence Forces central psychiatric clinic as to competency for military arrest.

Forensic Psychiatry↗

[Combat stress reaction].

The case of an atypical combat reaction in a 32-year-old soldier is presented. The initial phenomenon was a self-inflicted gunshot wound of the foot, while the post-traumatic symptoms appeared after a latent period 10 months. The combat stress reaction itself was identified during psychotherapy as the reactivation of trauma experienced in a previous war. Dimensions highlighted by this case include functional versus clinical measures used in diagnosis, and therapeutic considerations, such as the principles of immediacy, proximity and expectancy involved in the immediate combat stress reaction and thereafter.

Adult↗

Avian retroviral protease and cellular aspartic proteases are distinguished by activities on peptide substrates.

The avian sarcoma/leukemia virus protease (PR), purified from avian myeloblastosis virus has a native molecular mass of 26 kDa, suggesting a dimer structure. The enzymatic activity of PR has been characterized using synthetic peptide substrates. PR is most active at pH 5.5, 35 degrees C and 2-3 M NaCl. Under these conditions PR cleaves decapeptides which are resistant in low ionic strength. This high, nonphysiological, salt concentration also increases the proteolytic activity of a cellular aspartic protease, pepsin. PR and pepsin show additional similarities: they both cleave a synthetic decapeptide at the same Tyr-Pro bond in low and high salt, while the cleavage site preferences of human renin and cathepsin-D in this substrate are altered at high salt concentrations. In addition, iodination of the tyrosine residue in this decapeptide causes an increase in the rates of hydrolysis by both PR and pepsin. However, Km values are too high to be estimated accurately for PR using Tyr-Pro and Tyr(I)-Pro decapeptides as substrates. Comparison of the digestion products of two additional decapeptides, altered in a single amino acid residue, shows that PR cleaves at fewer sites than all three cellular enzymes. Furthermore pepstatin, a strong inhibitor of pepsin, renin, and cathepsin-D has little effect on PR.

Avian Leukosis Virus↗

Delayed onset PTSD among Israeli veterans of the 1982 Lebanon War.

This is an exploratory study of the nature, course and rates of delayed post-traumatic stress disorder (PTSD). We reviewed 150 medical files of Israeli soldiers who sought help between 6 months and 5 years after the 1982 Lebanon War. Results indicated that only 10% of the cases were truly examples of delayed PTSD; in a large proportion of the cases, help-seeking rather than onset was delayed.

Adult↗

Cytocidal effect caused by the envelope glycoprotein of a newly isolated avian hemangioma-inducing retrovirus.

We isolated a field strain of avian hemangioma retrovirus (AHV) which induces a cytopathic effect (CPE) on cultured avian and mammalian cells shortly after infection. The kinetics of cell killing were dependent on the multiplicity of infection. The CPE on avian and mammalian cells was independent of virus replication, because UV-irradiated virus led to cell death as well. Biochemical and genetic experiments indicated that AHV env gene products were responsible for the CPE. Partially purified AHV envelope glycoproteins (gp85), but not those of the Rous sarcoma virus Prague C strain, induced a CPE. Rous-associated virus type 1, in which the env region was replaced by the AHV gp85 region, induced a CPE on avian and mammalian cultured cells. Therefore, we suggest that CPE is induced by AHV via interaction between viral gp85 and the cell membrane. This mode of CPE is unique among avian sarcoma-leukemia viruses.

Alpharetrovirus↗

Officers' attitudes toward combat stress reaction: responsibility, treatment, return to unit, and personal distance.

This study examines the attitudes of 176 Israel Defense Forces officers toward combat stress reaction (CSR) in four areas: (1) the degree of personal responsibility the officer accepts for the treatment of the CSR casualty; (2) the type of treatment the officer views as most effective for CSR; (3) the officer's willingness to accept the CSR casualty's return to the unit following treatment; and (4) the personal distance the officer experiences between himself and the phenomenon. The impact of the following variables on officers' attitudes was assessed: casualty's rank, casualty's level of combat skill, presence of an additional physical injury, type of symptomatology, and respondent's background variables. Each officer was presented with one of 24 vignettes describing a CSR incident and was requested to fill in an attitudes questionnaire. Findings revealed that officers were more severe and less tolerant in relation to the CSR casualty who was an officer than toward lower ranking casualties. Officers were expected to take more responsibility for their own recovery than simple soldiers, support of commanding officers was seen as less effective in their treatment, and respondents were less willing to accept them back into their units after treatment.

Attitude↗

Audiological evaluation of nonalcoholic, drug-free posttraumatic stress disorder patients.

Auditory functions of 32 Israeli soldiers with posttraumatic stress disorder (PTSD) were evaluated and compared with those of 32 matched controls without PTSD. The evaluation included peripheral auditory functions, tolerance to noise, and central auditory informational functions. Tolerance of intense auditory stimuli by PTSD patients was similar to that of controls. Significant differences were found between left and right ear central auditory functions in a subgroup of 13 PTSD subjects, but neither in other PTSD patients nor in controls. These findings are discussed in the light of previous research concerning abnormal responses to auditory stimulus in PTSD, hemispheric disconnection, alexithymia, and psychosomatic disorders.

Adult↗

Synthetic peptides as substrates and inhibitors of a retroviral protease.

Processing of the gag and pol gene precursor proteins of retroviruses is essential for infectivity and is directed by a viral protease that is itself included in one of these precursors. We demonstrate here that small synthetic peptides can be used as both model substrates and inhibitors to investigate the specificity and molecular parameters of the reaction. The results indicate that a peptide that extends five amino acids but not three amino acids in both directions from a known cleavage site is accurately hydrolyzed by the protease of avian sarcoma-leukosis virus. Substitutions of the amino acids to either side of the peptide bond to be cleaved affect the ability of the peptide (as well as a larger precursor protein) to serve as a substrate. The specificity is more stringent for the amino acid that will become the carboxyl end after cleavage. Some substitutions produced peptides that were not cleaved but could act as inhibitors of cleavage of a susceptible peptide. Thus, small model substrates may be used to explore both the binding and catalytic properties of these important proteases.

Alpharetrovirus↗

cis-acting intron mutations that affect the efficiency of avian retroviral RNA splicing: implication for mechanisms of control.

The full-length retroviral RNA transcript serves as (i) mRNA for the gag and pol gene products, (ii) genomic RNA that is assembled into progeny virions, and (iii) a pre-mRNA for spliced subgenomic mRNAs. Therefore, a balance of spliced and unspliced RNA is required to generate the appropriate levels of protein and RNA products for virion production. We have introduced an insertion mutation near the avian sarcoma virus env splice acceptor site that results in a significant increase in splicing to form functional env mRNA. The mutant virus is replication defective, but phenotypic revertant viruses that have acquired second-site mutations near the splice acceptor site can be isolated readily. Detailed analysis of one of these viruses revealed that a single nucleotide change at -20 from the splice acceptor site, within the original mutagenic insert, was sufficient to restore viral growth and significantly decrease splicing efficiency compared with the original mutant and wild-type viruses. Thus, minor sequence alterations near the env splice acceptor site can produce major changes in the balance of spliced and unspliced RNAs. Our results suggest a mechanism of control in which splicing is modulated by cis-acting sequences at the env splice acceptor site. Furthermore, this retroviral system provides a powerful genetic method for selection and analysis of mutations that affect splicing control.

Alpharetrovirus↗

Activity of avian retroviral protease expressed in Escherichia coli.

The 3' end of the avian sarcoma leukosis virus (ASLV) gag gene encodes a 124-amino-acid protease (PR) responsible for processing the gag and pol polyprotein precursors into the mature virion structural proteins and the reverse transcriptase. Here we report the synthesis of the mature ASLV PR and a nucleocapsid (NC)-PR gag precursor fragment in Escherichia coli. E. coli extracts containing mature PR correctly cleaved a synthetic decapeptide homologous to a known ASLV cleavage site. Also, the NC-PR precursor fragment appeared to be correctly processed to produce NC and PR in the bacterial cells. This cleavage was blocked by a mutation in the putative active site of PR. These results strongly support the hypothesis that PR is involved in cleaving itself from the gag precursor.

Aspartic Acid↗

The radiology of cardiac valve prostheses.

The radiographic findings associated with the complications of valve implantation are presented. Complementary roles of echocardiography and cine fluoroscopy in the recognition of complications associated with this procedure are emphasized. Identification of prosthetic valves and the knowledge of the modes of action of the various types of valves are stressed.

Bioprosthesis↗

Combat-related posttraumatic stress disorder among second-generation Holocaust survivors: preliminary findings.

The authors assessed the impact of the Nazi Holocaust on the course and symptoms of posttraumatic stress disorder (PTSD) among Israeli combat stress reaction casualties. They examined a sample of 96 such casualties of the 1982 Lebanon War whose parents had gone through the Nazi Holocaust and compared them to casualties who did not have such family history for 3 consecutive years beginning 1 year after their participation in the war. Results showed that 2 and 3 years after their participation in the 1982 Lebanon War, the children of Holocaust survivors, i.e., "second-generation" casualties, had higher rates of PTSD than did the control subjects, as well as a somewhat different clinical picture. Clinical and methodological implications of the findings are discussed.

Adolescent↗

Clonal analysis of radiation leukemia virus-induced leukemic and preleukemic murine cells.

Clonality of radiation leukemia virus (RadLV)-induced thymic lymphomas was determined by detection of rearrangements in the genetic locus coding for the beta chain of the T-cell receptor (T beta). Unique T beta rearrangements were detected in four of six lymphomas. Two of the T beta-rearranged thymic lymphomas and two in which such a rearrangement was not detected had a biallelic deletion of C beta 1. With an anti-RadLV monoclonal antibody it was found that 1-2 days after virus inoculation more than one-third of the cells in the thymus were infected by the virus. The frequency of virus-positive cells gradually declined and persisted at 1-2% until the appearance of a clonal lymphoma at which time virtually all the cells in the thymus were virus positive. Transfer of thymocytes from a single, preleukemic mouse 21 days post-virus inoculation into several adoptive recipients resulted in donor-type thymic lymphomas in the majority of the mice. T beta rearrangement analysis revealed that these lymphomas were clonal and derived from different potentially leukemic (preleukemic) cells in the thymus of the donor mouse. Eleven of 15 lymphomas had a biallelic deletion of C beta 1. These results suggest that clonal, RadLV-induced thymomas are selected from an oligoclonal, RadLV-infected preleukemic T-cell population.

Alleles↗

The methylation state of the proviruses in avian sarcoma virus transformed chick and rat cells.

The endogenous viruses in the avian cells are not completely methylated, nor are the Schmidt-Ruppin RSV-D (SRD) proviruses in the infected cells completely unmethylated. Avian sarcoma proviruses integrated in rat transformed cloned cells are heavily methylated. In these cells, a region in the 3' end of the env gene is unmethylated in all the src-containing proviruses but not in the transformed defective (td) proviruses. A possible role for the hypomethylation of the 3' end of the env region is proposed.

Animals↗

A highly leukemogenic radiation leukemia virus isolate is a thymotropic, immunosuppressive retrovirus with a unique RNA structure.

Clones of N-, B- and NB-fibrotropic viruses were isolated from weakly (D-RadLV) and strongly (A-RadLV) leukomogenic RadLV preparations. A highly leukemogenic, thymotropic virus (TV) was isolated by ex-vivo infection of thymocytes with A-RadLV. This virus could not be isolated from D-RadLV. Two-dimensional fingerprint analysis suggested that TV recombines unique RNA sequences with RNA genomic material derived from a B-tropic endogenous virus. C57BL/6 (B6) mice injected with B- or NB-fibrotropic clones, but not with TV or N-tropic viral clones, developed reactive T lymphocytes (Tr), capable of differentiating into anti-tumor cytotoxic cells. The N-tropic virus isolates were non-immunogenic in B6 mice whereas the TV isolate induced suppressor T lymphocytes (Ts) that abrogated a potential Tr response. These results suggest that emergence of highly leukemogenic RadLV involves activation of endogenous fibrotropic virus which is immunogenic in its natural host strain (B6). This virus can further recombine with other retroviral genetic sequences, resulting in a suppressogenic and thymotropic, highly leukemogenic virus.

Animals↗