Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Antibodies to human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2) and to human T-cell leukemia virus (HTLV-1) were investigated by ELISA, Western blot and radioimmunoprecipitation (RIPA) assay in 318 sera (191 males and 127 females) obtained from syphilitic patients. The sera from 10% of the males and 3.1% of the females were positive for HIV-1. None of the sera contained antibodies to HIV-2. Antibodies to HTLV-1-2 were present in the sera of 7.1% of the males and 4.8% of the females who were seronegative for HIV. Five out of 24 (20.8%) HIV-1 positive subjects had antibodies to HTLV-1-2 as well. Sera from another group of 58 syphilitic patients (38 males and 20 females in the Anti-Venereal Disease Department), seronegative for HIV-1 and HIV-2, who denied both i.v. drug abuse and blood transfusion, were investigated in the same manner. None of the males had antibodies to HTLV-1-2, while 2 females (10%) were positive.
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PMID:Antibodies to HTLV-1-2, HIV-1 and HIV-2 in syphilitic patients. 197 26

Of nine studies in vitro, six have indicated some degree of induced chromosomal breakage after exposure to LSD; three failed to confirm these results. The damage, when found, was generally of the chromatid type, arising during or after DNA synthesis. This damage, with one exception, was the result of concentrations of drug and durations of exposure which could not be achieved in humans with reasonable dosages. There did not appear to be a dose-response relation. The magnitude of damage, when found, was in the range encompassing the effects of many commonly used substances. The absence in vitro of excretory and detoxifying systems present in vivo, as well as several negative reports, cast doubt on the relevance of in vitro results. In 21 chromosomal studies in vivo, 310 subjects were examined. Of these, 126 were treated with pure LSD; the other 184 were exposed to illicit, "alleged" LSD. A maximum of only 18 of 126 (14.29 percent) of the subjects in the group exposed to pure LSD showed higher frequency of chromosome aberration than the controls. In contrast, a maximum of 90 of 184 (48.91 percent) of the subjects taking illicit LSD showed an increase in frequency of aberrations. Of all the subjects reported to have chromosome damage, only 18 of the 108 (16.67 percent) were exposed to pure LSD. The frequency of individuals with chromosomal damage reported among illicit drug users was more than triple that associated with the use of pharmacologically pure LSD. We conclude that chromosome damage, when found, was related to the effects of drug abuse in general and not, as initially reported, to LSD alone. We believe that pure LSD ingested in moderate dosages does not produce chromosome damage detectable by available methods. No significant work on carcinogenic potential of LSD has been reported so far. No cause-and-effect relation and no increase in the incidence of neoplasia among LSD users have been demonstrated. Case reports (three in 4.0 years) of leukemia and other neoplasia in this population are rare. The results of early chromosome studies suggested that true genetic damage might be a consequence of LSD exposure. The comprehensive evidence from studies on drosophila indicates no mutagenic effect from 0.28 to 500 microg of LSD per milliliter and a definite mutagenic effect from 2,000 to 10,000 microg/ml; this is consistent with a threshold response or a sigmoid dose-effect relation. We believe that LSD is, in fact, a weak mutagen, effective only in extremely high doses; it is unlikely to be mutagenic in any concentration used by human subjects. Circular dichroism experiments suggested that the specific mechanism of action of LSD on DNA may be a direct interaction resulting in conformational changes in the DNA helix. These changes are unlikely to result in a decrease of internal stability sufficient to cause breakage of chromosomes, but they may be the physical basis of the weak mutagenicity. Early chromosomal studies implicated LSD as a potential cause of congenital malformations, fetal wastage, and germinal chromosome damage. First reports of a teratogenic effect in hamsters and rats have not been confirmed. A review of 15 rodent studies indicated a wide range of individual, strain, and species susceptibility to the effects of LSD. The applicability of such investigations to man is doubtful. In a study of human pregnancies, those exposed to illicit LSD had an elevated rate of spontaneous abortions. There is no reported instance of a malformed child born to a woman who ingested pure LSD; there are six cases of malformation associated with exposure to illicit LSD, four of which have similar limb defects. Given, however, the high frequency of unexplained "spontaneous" birth defects, the rare occurrence of malformed infants born to women who used illicit LSD may be coincidental. While there is no evidence that pure LSD is teratogenic in man, the use of any drug during pregnancy requires that its potential benefits significantly outweigh its potential hazards. From our own work and from a review of the literature, we believe that pure LSD ingested in moderate doses does not damage chromosomes in vivo, does not cause detectable genetic damage, and is not a teratogen or a carcinogen in man. Within these bounds, therefore, we suggest that, other than during pregnancy, there is no present contraindication to the continued controlled experimental use of pure LSD. Note added in proof: A brief review has been brought to our attention. Although based on a sample of only 15 studies the author reached conclusions similar to our own (92).
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PMID:LSD and genetic damage. 499 65

Twenty-five men with testicular germ cell tumors were compared by developmental history and past and present psychologic adjustment to 25 men with acute leukemia. The mean age was 30 years for the cancer group and 25 years for the leukemia group. Current and Past Psychopathology Scales (18 scales of prior and 8 of present adjustment) were rated during a semistructured interview. The following differences were found in developmental history: Onset of puberty was 12.4 years for leukemics and 15.1 years for the cancer group (P less than 0.001); cryptorchidism was found in 20% of cancer patients and 4% of leukemia; incidence of opiate drug abuse was 36% in cancer patients and 24% in leukemia patients; psychiatric disturbance prior to illness characterized 32% of the cancer group and 12% of the leukemia group. Major psychiatric illness was diagnosed in 20% of the testicular cancer group and 4% of the leukemia group. Findings of delayed puberty and psychiatric disturbance in men with germ cell testicular tumors as compared to leukemics suggest a possible impairment of the hypothalamic-pituitary-gonadal axis. The etiology of this impairment is discussed (genetic factors, prenatal endocrine milieu, abnormal luteinizing hormone (LH) receptors, and abnormal interaction between dopaminergic system, LH, and endorphins).
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PMID:A comparative study of psychosexual adjustment in men with testicular cancer and acute leukemia. 734 74

To establish the in vivo cellular tropism of human T-cell leukemia virus type II (HTLV-II) in peripheral blood, subpopulations of mononuclear cells isolated from patients with a history of drug abuse and with high proviral load were analyzed by polymerase chain reaction for the presence of the proviral sequences. After purification of cellular subsets by immunomagnetic fractionation of blood cells of an infected patient, HTLV-II DNA was detected in CD4+ and CD8+ T-cells as well as in CD19+ B-cells. A positive PCR signal was obtained for purified B-cells also at limiting dilutions. This observation was confirmed by purifying the B-cell fraction by a two-step immunomagnetic procedure from the peripheral blood of another patient with very high HTLV-II copy number and quantifying the B-cell proviral load by means of competitive PCR. A proviral copy number of 90/100 B-cells was found, demonstrating that the great majority of these cells were infected by HTLV-II in this subject. The results indicate that HTLV-II has a broad host range in some infected individuals, showing an enlargement of cellular tropism to B lymphocytes and suggesting that this expression is associated with an increase in proviral load.
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PMID:Cellular tropism of human T-cell leukemia virus type II is enlarged to B lymphocytes in patients with high proviral load. 753 16

The hexapeptide Thr-Gly-Glu-Asn-His-Arg (HLDF-6), which was first identified as an active fragment of the human leukemia differentiation factor (HLDF) molecule, displays differentiation-inducing, neuroprotective and anti-drug abuse activities. Most of its in vivo effects were revealed only on male animals. We have studied HLDF-6 effects on a variety of organism functions and behavioral reactions, which are known to be dependent on androgen steroid hormones, both on castrated and normal (sham-operated) animals. Male NMRI mice were castrated or sham-operated at the age of 55 days (after puberty). After that, HLDF-6 peptide was injected daily during 3 weeks, followed by behavioral, morphological and biochemical testing. HLDF-6 increased testosterone level (1.5- to 2-fold) both in sham-operated and castrated animals. Sexual activity and pain sensitivity, which are strongly reduced in castrates, were completely or partially recovered by HLDF-6. At the same time, the peptide caused some effects similar to castration in sham-operated animals: aggression and locomotor activity were decreased; oral grooming was prolonged. Morphological studies of accessory sex glands showed that HLDF-6 partially normalizes the morphology and functional activity of seminal vesicles in castrates, but it does not prevent castration-induced apoptosis of prostate epithelial cells. Based on these observations, we can assume that HLDF-6 peptide displays at least two effects on androgen hormones metabolism in males: it stimulates testosterone biosynthesis by both testes and adrenals and simultaneously inhibits its conversion to dihydrotestosterone (DHT), most probably by diminution of 5alpha-reductase isoform 1 mRNA expression.
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PMID:HLDF-6 peptide affects behavioral reactions and organism functions dependent on androgen hormones in normal and castrated male mice. 1568 Apr 77

Antimicrobials are among the most important and commonly prescribed drugs in the management of critically ill patients. Selecting the appropriate antimicrobial at the commencement of therapy, both in terms of spectrum of activity and dose and frequency of administration according to concentration or time dependency, is mandatory in this setting. Despite appropriate standard dosage regimens, failure of the antimicrobial treatment may occur because of the inability of the antimicrobial to achieve adequate concentrations at the infection site through alterations in its pharmacokinetics due to underlying pathophysiological conditions. According to the intrinsic chemicophysical properties of antimicrobials, hydrophilic antimicrobials (beta-lactams, aminoglycosides, glycopeptides) have to be considered at much higher risk of inter- and intraindividual pharmacokinetic variations than lipophilic antimicrobials (macrolides, fluoroquinolones, tetracyclines, chloramphenicol, rifampicin [rifampin]) in critically ill patients, with significant frequent fluctuations of plasma concentrations that may require significant dosage adjustments. For example, underexposure may occur because of increased volume of distribution (as a result of oedema in sepsis and trauma, pleural effusion, ascites, mediastinitis, fluid therapy or indwelling post-surgical drainage) and/or enhanced renal clearance (as a result of burns, drug abuse, hyperdynamic conditions during sepsis, acute leukaemia or use of haemodynamically active drugs). On the other hand, overexposure may occur because of a drop in renal clearance caused by renal impairment. Care with all these factors whenever choosing an antimicrobial may substantially improve the outcome of antimicrobial therapy in critically ill patients. However, since these situations may often coexist in the same patient and pharmacokinetic variability may be unpredictable, the antimicrobial policy may further benefit from real-time application of therapeutic drug monitoring, since this practice, by tailoring exposure to the individual patient, may consequently be helpful both in improving the outcome of antimicrobial therapy and in containing the spread of resistance in the hospital setting.
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PMID:Antimicrobial therapy in critically ill patients: a review of pathophysiological conditions responsible for altered disposition and pharmacokinetic variability. 1617 16

Humans and chimpanzees are the natural hosts for HIV. Non-human primate models of SIV/SHIV infection in rhesus, cynomologus and pigtail macaques have been used extensively as excellent model systems for pathogenesis and vaccine studies. However, owing to the variability of disease progression in infected macaques, a phenomenon identical to humans, coupled with their prohibitive costs, there exists a critical need for the development of small-animal models in which to study the untoward effects of HIV-1 infection. Owing to the fact that rodents are not the natural permissive hosts for lentiviral infection, development of small animal models for studying virus infection has used strategies that circumvent the steps of viral entry and infection. Such strategies involve overexpression of toxic viral proteins, SCID mice engrafted with the human PBLs or macrophages, and EcoHIV chimeric virus wherein the gp120 of HIV-1 was replaced with the gp80 of the ecotropic murine leukemia virus. Additional strategy that is often used by investigators to study the toxic effect of viral proteins involves direct stereotactic injection of the viral protein(s) into specific brain regions. The present report is a compilation of the applications of direct administration of Tat into the striatum to mimic the effects of the viral neurotoxin in the CNS. Added advantage of this model is that it is also amenable to repeated intraperitoneal cocaine injections, thereby allowing the study of the additive/synergistic effects of both the viral protein and cocaine. Such a model system recapitulates aspects of HAND in the context of drug abuse.
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PMID:Rodent models of HAND and drug abuse: exogenous administration of viral protein(s) and cocaine. 2244 95