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Biomedical subjects

T Klein

Publications and source records attributed to T Klein.

At least 199 records · Page 11Linked to original sources
PubMed1988

[A randomized study comparing cisplatin alone or combined in the palliative treatment of carcinoma of the head and neck. Analysis of a series of 209 patients].

Two hundred and nine patients, with locoregional or metastatic recurrences of head and neck epidermoid carcinoma, were randomized to receive a palliative chemotherapy. The chemotherapy regimens were delivered every 3 weeks, and consisted in (1) cisplatin, 80 mg/m2 given alone (CDDP regimen), or (2) in combination with vincristine, 1 mg, methotrexate 10 mg/m2 d 1, 2, 3, and bleomycin 10 mg/m2, d 1, 2 and 3 (1040 regimen). Short-term results were better for patients treated by the 1040 regimen, with a 30% response rate (including 4 complete responses) vs 15% with the CDDP regimen (P = 0.01). A superiority of combination chemotherapy was found for all tumoral sites, but was particularly significant for pulmonary and cutaneous metastases, in previously un irradiated areas (P = 0.001). Tolerance was significantly better with the CDDP regimen (P = 0.001); severe side effects, affecting mainly general status, digestive tract and bone marrow were encountered in 5% of the patients in the CDDP group, vs 21% in the 1040 group, with one death related to pancytopenia. The median duration of remissions was not statistically different in the 2 groups, as well as the 2 years overall survival. Among responders, the survival was slightly better in those treated with CDDP alone; moreover, the quality of long term results was found highly correlated with a good initial general status, and with low levels of side effects. Those results confirm recent data of the literature, and lead to the following conclusions: (1) combination chemotherapy with CDDP give a better response rate than CDDP alone, (2) response rate doesn't influence overall duration of survival, (3) tolerance to treatment is crucial to preserve quality of life, and thus, (4) palliative chemotherapy in head and neck cancer should be efficient but also as short of intensity as possible.

Actuarial Analysis↗
PubMed1988

[Randomized trial of initial chemotherapy with cisplatin alone or in combination in 241 advanced carcinomas of the upper respiratory and digestive tract].

Two hundred and forty-one patients, with advanced squamous cell carcinoma of head and neck, were randomized to receive three courses of induction chemotherapy. The chemotherapy regimens were delivered every 3 weeks, and consisted in 1) cisplatin, 80 mg/m2 given alone (CDDP regimen), or 2) in combination with vincristine, 1 mg, d 1, methotrexate 10 mg/m2 d 1, 2, 3, and bleomycin 10 mg/m2, d 1, 2, and 3 (MOB-P). Tolerance was significantly better with the CDDP regimen (p less than 0.05); severe side effects, affecting mainly digestive tract, and bone marrow, were encountered in 7% of the patients in the CDDP group, vs 15% in the MOB-P group, without death related to pancytopenia. Short-term results were better for patients treated by the MOB-P regimen, with a 42% response rate (including 9 complete responses) vs 22% with the CDDP regimen (p = 0.01). A superiority of combination chemotherapy was more significant for primary sites than regional lymph nodes. The relapse-free survival was not statistically different in the 2 groups, as well as the 2 years overall survival. Among responders, the survival was found highly correlated with a good initial general status (p less than 0.01), and with the highest total doses of cisplatin (p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis↗
PubMed1988

Drugs of abuse and virus susceptibility.

It is widely recognized that various microorganisms including viruses have immunomodulatory effects and, under appropriate circumstances, may markedly suppress the immune response mechanisms. Cannabinoids present in marijuana also have immunomodulatory effects. In the present studies THC as well as its metabolic product 11-OH THC were studied in regard to their effects in vivo and in vitro on selected parameters of the immune response system known to be important in antiviral resistance, including immunity to retroviruses. Cannabinoids markedly suppressed the ability of murine macrophages to spread on glass (an important functional marker of macrophages) as well as to phagocytize yeast particles. Splenic macrophage cultures treated with the cannabinoids also were deficient in their ability to produce interleukin 1 on appropriate stimulation with bacterial LPS. Spleen cells capable of producing antibody to sheep erythrocytes when stimulated with this antigen in vitro were markedly affected when treated with graded doses of THC or 11-OH THC. Furthermore, the blastogenic responsiveness of normal mouse splenocytes to the T-cell mitogens Con A and PHA as well as the B-cell mitogen E. coli LPS was markedly suppressed by graded concentrations of the cannabinoids in doses that did not affect the viability of the cells. Natural killer cell activity of normal mouse spleen cells was also markedly inhibited by THC and 11-OH THC. Similarly, these cannabinoids suppressed the blastogenic responsiveness and NK activity of human peripheral blood leukocytes from normal individuals. The ability of mouse spleen cells to produce interferon on in vitro stimulation was also suppressed by THC. In addition, injection of THC into mice suppressed blastogenic responsiveness of spleen cells, NK activity, and the production of interferon by lymphoid cells. Thus, it was apparent that these cannabinoids had immunomodulatory effects, both in vivo and in vitro, at noncytotoxic small doses and impaired the ability of the lymphoid cells to express immune function necessary for antiviral resistance.

Acquired Immunodeficiency Syndrome↗
PubMed1988

[Secondary cardiac localizations in different cancers. Comparison of clinical, electrocardiographic and autopsy data. Apropos of 51 cases].

The authors have investigated 910 post-mortem examinations of different primary cancers. Fifty-one cases (5.6% of the autopsies) presented cancer lesions of the heart. They have found the accuracy of clinical and paraclinical diagnostics by comparing them with autopsy findings in case of pericardial lesions, but very rarely in case of myocardial location.

Arrhythmias, Cardiac↗
PubMed1987

Differential effects of marijuana components on proliferation of spleen, lymph node and thymus cells in vitro.

The effects of delta 9 THC and 11-OH THC on the proliferative response of murine spleen cells stimulated in vitro with the T cell mitogens Con A or PHA were compared with the effects of these drugs on the mitogen-induced proliferation of murine thymus and lymph node cells. Thymus cells were found to be suppressed at lower cannabinoid concentration than either spleen or lymph node cells. However, splenic cells were more easily suppressed than were the lymph node cells. Lymphoid cell numbers were varied from 1 X 10(6) to 8 X 10(6) cells and treated with a constant dose of either THC or 11-OH THC. When suppression was noted with spleen and lymph node cells, the smallest number of cells in the assay resulted in the greatest level of suppression of cell proliferation. No significant suppression to PHA induced proliferation was found for lymph node cells at any cell number tested. Thymus cells were always more readily suppressed than spleen or lymph node cells regardless of the number of cells in culture. Furthermore, 11-OH THC suppressed the responsiveness of the thymus cells to PHA more than to Con A under the experimental conditions used. Thus, the ability of cannabinoids to induce suppression of the proliferative response of lymphoid cells to mitogens depends on the organ source of the cells, nature of the cannabinoid (THC or 11-OH THC), dose of the cannabinoid, mitogen used (PHA or Con A), and number of cells in culture.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Interferon induction by endotoxin-derived nontoxic polysaccharides.

Polysaccharide-rich preparations from Serratia marcescens-derived endotoxin and components thereof, including Lipid A, were studied in terms of their ability to induce interferon (IFN) activity in murine spleen cell cultures in vitro. Although the polysaccharide-rich derivatives, similar to intact endotoxin, were only weak stimulators for IFN induction, pretreatment of splenocyte cultures with recombinant interleukin-2 (IL-2) significantly increased IFN-inducing activity. Both an endotoxin-derived polysaccharide and a "White type" polysaccharide prepared from intact Serratia had similar ability to induce IFN in vitro, but only when spleen cells were first treated with IL-2. The polysaccharide preparations were nontoxic as compared with the high degree of toxicity of the intact endotoxin, yet induced similar IFN levels as whole endotoxin. Much of the IFN induced by these preparations was of the gamma type, since activity was either not neutralized or only incompletely neutralized by treatment with anti-alpha/beta interferon antibody.

Animals↗
PubMed1987

Enhanced suppression of blastogenic responses by weanling mouse lymphoid cells treated with tetrahydrocannabinol in vitro.

The suppressive effects of delta 9-tetrahydrocannabinol (THC) on the proliferation of lymphocytes from the spleen, lymph node, and thymus of weanling animals vs adult animals to the T-cell mitogen PHA were examined. THC had a suppressive effect on thymus cells from animals of both younger and older mice. THC suppressed spleen and lymph node cells responses to phytohemagglutinin (PHA) more readily when the cells were obtained from young mice rather than older animals. Suppression by THC in the adult mice was greater in an organ containing fewer mature T lymphocytes such as the thymus in comparison to lymphocytes in secondary organs such as the spleen and lymph nodes which contain more mature lymphocytes.

Age Factors↗
PubMed1987

Distinctive immunomodulatory effects of endotoxin and nontoxic lipopolysaccharide derivatives in lymphoid cell cultures.

Endotoxin derived from Serratia marcescens, as well as a hydrolyzed polysaccharide-rich derivative from the bacteria similar to the White-type polysaccharide (WPS), and hydrolyzed split products of endotoxin, including Lipid A and the nontoxic polysaccharide (PS), were studied in terms of their ability to induce mitogenic proliferation of murine spleen cells in vitro and enhancement of antibody formation to sheep erythrocytes. The intact endotoxin and the Lipid A component induced marked proliferative activity of normal lymphoid cells, but the PS components obtained after a 30 min or longer mild hydrolysis of the endotoxin had much less mitogenic activity. The WPS preparation retained mitogenic activity after 30 min but lost it during continued hydrolysis. Nevertheless, all of the components were marked adjuvants for murine spleen cells in vitro in terms of enhancing the antibody response to sheep red cells. Both the intact endotoxin as well as the Lipid A component induced interleukin-1 and interferons, including alpha/beta and gamma, following stimulation of spleen cell cultures for 24 h in vitro. Although only the endotoxin and Lipid A, but not the PS components, were mitogenic for murine splenocytes, all of these preparations had immune adjuvant effects and induced spleen cells to produce or release interferons. However, the PS-rich derivative did not induce tumor necrosis factor. These distinct properties of components of endotoxin indicate that the nontoxic PS-rich derivative, as compared to the toxic endotoxin or Lipid A, has some immunostimulatory activities but lacks others.

Adjuvants, Immunologic↗
PubMed1987

[Trophoblastic tumor of placental location or trophoblastic pseudotumor. Apropos of 2 cases. Review of the literature].

Two cases of trophoblastic tumor of placental site are reported, less than 30 such lesions being listed in the published literature. Identification of this tumor from among other trophoblastic lesions is facilitated by immunohistochemical and electron microscopy technics, and demonstration of histoprognostic and biologic criteria improves assessment of evolutory potential of this type of tumor and allows adaptation of therapy. Treatment at the localized stage requires early diagnosis and wide surgical excision, results of chemotherapy in metastatic forms being, inversely than with choriocarcinoma, very deceiving.

Adult↗
PubMed1986

Value of steroid hormone receptor analysis in predicting time to treatment failure in operable breast cancer.

An analysis of prognostic factors for predicting time to treatment failure (TTF) was performed on 246 patients who were referred for adjuvant chemotherapy after mastectomy. Oestrogen receptor (ER) and progesterone receptor (PgR) analyses were carried out on 172 and 102 patients respectively. Prognostic factors predicting for TTF were, in decreasing order of significance: nodal status, tumour size, ER status and age of the patient. Comparison of TTF for ER+ and ER- (without categories of other prognostic factors) showed that ER status is prognostic irrespective of nodal status. ER is prognostically significant within both categories of PgR. PgR predicted significantly for TTF only in patients without nodal involvement.

Adult↗
PubMed1986

Tetrahydrocannabinol-induced suppression of macrophage spreading and phagocytic activity in vitro.

The effects of tetrahydrocannabinol (THC) on several parameters of macrophage function in vitro were assessed. Delta 9 THC added to cultures of normal mouse peritoneal cells in vitro affected the ability of the cells to spread on glass surfaces and also had some effect on their ability to phagocytize yeast. These effects were dose related. A concentration of 20 micrograms of THC almost completely inhibited macrophage spreading, but it also decreased viability and the total number of these cells. Doses of 10 or 5 micrograms of THC also inhibited spreading but had little effect on cell viability or number. A dose of 1.0 microgram of THC had some inhibitory effect on spreading and the lowest dose affecting spreading appeared to be about 0.05 micrograms per culture. Higher doses of THC were necessary to inhibit phagocytosis of yeast particles as determined by direct microscopic examination or use of radiolabeled yeast as the test particles. These results indicate that several readily measured functions of macrophages may be suppressed by THC.

Animals↗
PubMed1986

Molybdate and the molecular properties of the vervet monkey estrogen receptor.

The Vervet monkey (Cercopithecus aethiops pygerythrus) uterine estrogen receptor was partially characterised. The effect of the molybdate oxyanion on various molecular properties of the receptor was investigated. Molybdate appeared to affect the subunit structure and apparent heterogeneity of the receptor. Anion exchange chromatography of uterine cytosols yielded two ligand binding subunits in a 1:1 ratio in the absence of sodium molybdate, while only a single labelled complex could be demonstrated in cytosols prepared in molybdate containing buffers. Chromatofocussing of the nonstabilized cytosols revealed substantial receptor heterogeneity (7 peaks) while a much simpler pattern (2 peaks) could be observed in the presence of the molybdate. Likewise, iso-electric focussing of labelled cytosols on agarose gels yielded at least 3 high affinity binding components (pI:6.8, 6.2, 5.9) in the absence and only one major band in the presence of sodium molybdate (pI 5.9).

Animals↗
PubMed1986

Survey of the vestibulum, and behavior of Xenopus laevis larvae developed during a 7-days space flight.

Aquatic animals have almost no body weight related proprioception for spatial orientation. Xenopus larvae, like fish, maintain their attitude in water by continuous correction with their fin(s). For these reasons a special performance of the equilibrium system compared to terrestrial animals is necessary. Evidently fish therefore have more compact (dense) otoliths; Xenopus larvae have less dense otolith (membranes) similar to land vertebrates; but their sacculus-otoliths are vertically positioned, which also may lead to a higher g-sensitivity. For plausibility reasons gravity should influence the embryonic development of gravity receptors. Yet, evaluations of photographs taken from the surface of cut deep-frozen objects by incident light show no aberration of the shape of the whole vestibulum and of the shape, density, size and position of the otolith membrane in larvae developed under near-zero g (NEXPA-BW-STATEX in D-1-Mission). The further evaluation of the "weightless-larvae" revealed a probably not yet described statolith-like formation in the dorsal wall of the vestibulum. In the weightless larvae this formation outnumbers, also qualitatively, strongly the l-g controls. An extra result is the lack of striking effects of cosmic radiation on the embryonic development of the flown Xenopus eggs. The swimming behavior of the larvae which was observed about one hour after landing of the Space Shuttle showed a typical anomaly (loop swimming), which is known from larvae developed on the clinostat or from fish flown aboard Apollo capsules.

Animals↗
PubMed1986

A quantitative structure-activity relationship and molecular graphics analysis of hydrophobic effects in the interactions of inhibitors with alcohol dehydrogenase.

An analysis of the inhibition constants of pyrazoles, phenylacetamides, formylbenzylamines, and acetamides acting on liver alcohol dehydrogenase (ADH) yields quantitative structure-activity relationships (QSAR) having a linear dependency on octanol-water partition coefficients (log P). The average coefficient and standard deviation with the log P term for six different QSAR is 0.96 (+/- 0.14). This suggests complete desolvation of the substituents (directly comparable to partitioning into octanol) on binding to the enzyme. Study of a molecular graphics model of ADH constructed from the X-ray crystallographic coordinates shows that the substituents are engulfed in a long hydrophobic channel which is so narrow that water of solvation must be removed from them in the binding process.

Acetamides↗
PubMed1986

Inhibition of chicken liver dihydrofolate reductase by 5-(substituted benzyl)-2,4-diaminopyrimidines. A quantitative structure-activity relationship and graphics analysis.

The inhibition of chicken liver dihydrofolate reductase by a series of substituted benzylpyrimidines has been investigated. From the inhibition constants a quantitative structure-activity relationship has been formulated. This mathematical model is compared with molecular graphics models constructed from the X-ray crystallographic coordinates of trimethoprim and 5-(3,4-dimethoxy-4-isopropenylbenzyl)-2,4- diaminopyrimidine bound to the enzyme. There is good correspondence between the two types of models.

Animals↗
PubMed1986

Suppressive effect of delta 9-tetrahydrocannabinol in vitro on phagocytosis by murine macrophages.

Incubation of normal mouse peritoneal cells consisting of over 90% phagocytizing macrophages with delta 9-tetrahydrocannabinol (THC) resulted in a inhibition of phagocytic function. The THC in a dose-related manner suppressed the percentage of macrophages per culture which ingested yeast and the average number of yeast particles ingested by the phagocytizing macrophages. The vehicle used to suspend the THC in vitro, i.e., DMSO, had no detectable effect on macrophage function. Suppression of phagocytosis with no effects on viability or cell number occurred with doses of 10 micrograms or less THC per milliliter culture medium. Measurable suppression also occurred after 24- to 48-hr treatment of the macrophages with the THC. This compound had little if any detectable effect on phagocytosis when added directly to the cultures shortly before testing for phagocytosis. Further studies concerning the effects of THC on macrophage function appear warranted.

Animals↗
PubMed1986

[AIDS in ENT practice--case report and review].

We present a case of AIDS with Kaposisarcoma in the oropharynx. In this case chemotherapy and radiotherapy were used with good response. Because of the clinical features of the disease otolaryngologists will be involved more and more in the management of AIDS disease. The diagnosis, therapy, and prognosis of the following three stages are described: serological identification of antibodies against HTLV-III without clinical symptoms, AIDS-related complex, full-blown-AIDS. There is no inevitable transition between these stages. The mode of infection is similar to serum-hepatitis.

Acquired Immunodeficiency Syndrome↗