Molecular mechanisms associated with cocaine-induced modulation of human T lymphocytes proliferation.
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Calcium↗
Biomedical subjects
K Matsui
Publications and source records attributed to K Matsui.
How to prevent pleural opening in harvesting the internal mammary arteries.
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Coronary Artery Bypass↗
Levels of somatostatin and cholecystokinin in the brain of ataxic mutant mice.
Changes in immunoreactive somatostatin (SOM) and cholecystokinin (CCK-8) levels in the cerebellum and cerebrum were investigated in three types of genetically-determined ataxic mutant mice: rolling mouse Nagoya (RMN), weaver, and Purkinje cell degeneration (PCD) mice. The cerebellar pathology in each of these types differs. The concentration of both SOM and CCK-8 (ng/mg weight) was significantly higher in the cerebellum and the cerebrum of the three types of ataxic mutant mice than in these regions in the respective controls. SOM and CCK-8 content (ng/organ) was significantly higher in PCD and RMN than in controls but this was not in the weaver mice. The possible involvement of both peptides in manifestations of ataxia is discussed.
Animals↗
Rapid degradation of cucumber cotyledon lipoxygenase.
The lipoxygenase activity from cucumber cotyledons grown with their embryonic axis was separated into two fractions having M(r)s of 90,000 and 96,000, respectively, by hydrophobic chromatography. However, from de-embryonated cucumber cotyledons, only one form of lipoxygenase having a M(r) of 90,000 was purified. The three lipoxygenases could not be distinguished from each other either immunologically or by their enzymatic properties. Furthermore, peptide maps of the 90,000 and 96,000-lipoxygenases were identical. In a crude homogenate of cucumber cotyledons, the 96,000-lipoxygenase was rapidly degraded to the 90,000-form. Thus, it was inferred that the 90,000-lipoxygenase was probably the 96,000-form which had lost a peptide fragment of 6,000. It is suggested that there is a specific proteolytic activity for the degradation of 96,000-lipoxygenase. Estimation of changes in the proteolytic activity during seedling growth suggests that the activity at least partly contributes to the rapid in vivo degradation of cucumber cotyledon lipoxygenase.
Amino Acid Sequence↗
Cocaine suppresses proliferation of phytohemagglutinin-activated human peripheral blood T-cells.
Cocaine has been reported to modulate the immune system of experimental animals. Also, we observed that the drug suppresses the phytohemagglutinin (PHA)-induced proliferation of human peripheral blood mononuclear cells (PBMCs) but at concentrations extremely high relative to those seen in the blood of drug abusers. This suggested that cocaine had a relatively weak effect when tested under conditions of optimum proliferation. We, therefore, decided to examine the effect of lower concentrations of cocaine on suboptimum PHA-induced proliferation. At 0.09-12 microM, cocaine had no effect on the proliferation of PBMC in response to 0.2 micrograms/ml PHA. However, depleting the population of B-cells and monocytes resulted in a drug-induced suppression of the residual T-cells. Maximum suppression by cocaine was observed at 3 microM with both higher and lower concentrations of the drug causing less suppression. Suppression of proliferation was not influenced by either the age or sex of the peripheral blood lymphocytes (PBL) donors. The suppression of T-cell-enriched PBLs induced by cocaine could be eliminated by increasing the dose of the mitogen but was enhanced by preincubating the cells with the drug for 24 h. Also, the drug suppressed cytosolic free calcium mobilization in Fura 2/AM loaded enriched T-cell populations. These results show that cocaine moderately but consistently suppresses PHA-induced proliferation of T-cells from random blood donors at drug concentrations observed in drug abusers. The suppression is only evident under conditions of suboptimum proliferation and is accompanied by a corresponding decrease in the mobilization of cytosolic free calcium. It is suggested that the weak suppressive effect of cocaine is reversed by either helper factors produced by accessory cells or increasing concentrations of mitogen. These factors when present possibly overcome a drug-induced reduction in calcium mobilization and lymphocyte activation.
Adult↗
Analysis of prognostic factors in patients with resected peripheral T1 adenocarcinoma of the lung.
Prognostic factors in patients with surgically-treated peripheral T1 (< or = 3 cm in greatest diameter) adenocarcinoma of the lung were analyzed in 45 cases. Statistical difference in survival was observed between stages I + II and III + IV (p < 0.05). However, neither sex, age, location of tumor, histological subtype, histological grade, tumor ploidy, nor presence of central fibrosis was of prognostic determinance. Our results suggest that only clinical stage is of prognostic importance in surgically-treated peripheral T1 adenocarcinoma of the lung.
Adenocarcinoma↗
Phase I and pharmacologic study of irinotecan in combination with cisplatin for advanced lung cancer.
We have conducted a Phase I trial to determine the maximum tolerated dose of CPT-11 together with a fixed dose of cisplatin in patients with advanced lung cancer, and the dose-limiting toxicities of this combination. Fourteen previously untreated patients with stage IIIB or IV disease were treated with CPT-11 (90-min intravenous infusion on days 1, 8, and 15) plus cisplatin (60 mg m-2, intravenously on day 1). The starting dose of CPT-11 was 60 mg m-2, and diarrhea was the dose-limiting toxicity at the 90 mg m-2 dose level. All three patients (all four cycles) given 90 mg m-2 of CPT-11 experienced grade 3 diarrhea. Hematologic toxicity was relatively mild. Elimination of CPT-11 was biphasic with a mean (+/- s.d.) beta half-life of 11.36 +/- 7.26 h. The mean terminal half-life of the major metabolite (7-ethyl-10-hydroxycamptothecin; SN-38) was 22.13 +/- 13.28 (s.d.) h, and modest escalation of the CPT-11 dose from 80 mg m-2 to 90 mg m-2 resulted in a statistically significant apparent increase in the plasma concentrations of SN-38. There were one complete response (7%) and five partial responses (36%) among the 14 patients for an overall response rate of 43%. The recommended dose for Phase II studies is 80 mg m-2 of CPT-11 and 60 mg m-2 of cisplatin.
Adult↗
Bounds to the central electron-pair density with applications to two-electron atoms.
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Journal Article↗
Enhanced antitumor efficacy of a combination of CPT-11, a new derivative of camptothecin, and cisplatin against human lung tumor xenografts.
The objective of this study was to evaluate the antitumor efficacy of combined use of 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin (CPT-11) and cisplatin (CDDP). The antitumor activities of CPT-11, CDDP and their combination against 3 human lung tumor xenografts were estimated using congenitally athymic BALB/c (nu/nu) mice. The doses were 47 mg/kg for CPT-11 and 6 mg/kg for CDDP on days 1, 5 and 9. In combination therapy, half of the single dosage of each agent was used. The doses were administered intraperitoneally. The antitumor activity and toxicity were evaluated in terms of the tumor volume and body weight change of mice, respectively. The combination therapy resulted in a statistically significant tumor regression compared to the use of only CPT-11 or CDDP in two tumor xenografts out of three. The toxicity of the combination therapy was no higher than that of CPT-11 or CDDP alone. These results suggest that the antitumor activity of the combination of CPT-11 and CDDP is superior to that of CPT-11 or CDDP alone.
Animals↗
Lung carcinoma mimicking malignant lymphoma: report of three cases.
Three cases of lung carcinomas with unusual histologic appearances that have received little or no comment in the literature are presented. They were initially confused with malignant lymphoma because of a diffuse proliferation of relatively monotonous cells simulating large-cell immunoblastic lymphoma. In each case, the possibility of malignant lymphoma was excluded with confidence after the immunohistochemical study (leucocyte common antigen negative and cytokeratins positive), although with conventional microscopy several foci of cohesive groups of tumor cells were observed. The tumors were ranked at the clinical stage II or III when they were initially discovered, but all patients died of disease within 1 year. The present three tumors show an aggressive behavior and could be classified into a peculiar variant of 'large cell' carcinoma. It is necessary for surgical pathologists to have an idea of these variants of lung carcinoma in order to avoid erroneous diagnosis.
Adult↗
Use of a dual chamber pacemaker with a novel fallback algorithm as an effective treatment for sick sinus syndrome associated with transient supraventricular tachyarrhythmia.
A dual chamber pacemaker having a fallback (FB) mode was utilized in nine patients with sick sinus syndrome (SSS) associated with transient supraventricular tachyarrhythmia (atrial fibrillation [Af] in three patients, atrial flutter [AF] in two, and paroxysmal atrial tachyarrhythmia [PAT] in four). Various degrees of abnormality of atrioventricular (AV) conduction were observed at the time of pacemaker implantation in five patients. In this pacemaker, a DDD mode was active during sinus rhythm, but the mode changed, through a given cycle of high rate tracking at an upper rate limit (URL), to VDI only during intrinsic atrial rate increases that were either normally or abnormally above the URL. The VDI mode automatically returned to DDD when the atrial rate fell below the URL. At follow-up periods of 7-12 months, this pacemaker appeared to be especially effective in those SSS patients with transient Af or AF. In the SSS patients with PAT, however, the FB mode was not active because the PAT rhythm was conducted to the ventricle without block (1:1 conduction) and thus the given cycles of ventricular tracking at the URL did not occur. From the repetitive FB starting tests that were performed during an Af period in one patient with transient Af, a 2:1 point setting of a given URL plus 30-50 ppm was required to quickly start the FB algorithm. Moreover, an atrial sensitivity setting that was less than half of the P wave amplitude was desirable.(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗
Immunosuppression induced by Salmonella involves inhibition of tyrosine phosphorylation in murine T lymphocytes.
It is well known that facultative intracellular pathogens such as Salmonella suppress the host immune system. In the present study we attempted to clarify the mechanism responsible for the suppression of T-cell proliferation in mice infected with Salmonella typhimurium. The proliferation of murine spleen cells stimulated with a T-cell mitogen such as phytohemagglutinin (PHA) or concanavalin A (ConA) was significantly suppressed when the mice were infected with S. typhimurium, but not with Escherichia coli. The suppression of T-cell proliferation did not necessarily parallel the level of interleukin-2 (IL-2) secretion, and was not restored by treatment with a calcium ionophore, indomethacin or IL-2. Only phorbol 12-myristate-13 acetate (PMA), an activator of protein kinase C (PKC), caused a slight recovery of cell proliferation with an augmentation of IL-2 secretion. Furthermore, Western blotting using anti-phosphotyrosine antibodies showed that the mitogen-induced tyrosine phosphorylation of 120-, 106-, 94-, 76-, 68- and 57-kDa proteins in murine splenic T-cells was inhibited by S. typhimurium infection. Also, the inhibition of tyrosine phosphorylation was not restored by treatment with PMA. These results suggest that the suppression of T-cell proliferation induced by Salmonella infection may be regulated by inhibition of tyrosine phosphorylation in T-cells, although the inhibition is not associated with PKC activation and subsequent IL-2 secretion of T cells.
Animals↗
[Efficiency of porin as a component vaccine to Salmonella infection].
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Animals↗
Effects of lipid peroxidation on surface charge density of the porcine intestinal brush-border membranes.
The effects of lipid peroxidation on the surface charge density of the porcine intestinal brush-border membranes were studied using an oxygen-radical-generating system consisting of ascorbic acid, ferrous ion and tert-butyl hydroperoxide (tert-BuOOH). Changes in the membrane surface charge density were monitored using a fluorescent dye, 8-anilino-1-naphthalenesulfonate (ANS). The incubation of the membranes with ascorbic acid/Fe2+/tert-BuOOH resulted in a decrease of the fluorescence intensity of the ANS-membrane complex with a red-shift in the emission maximum, depending on the hydroperoxide concentration and the incubation time. The kinetic studies on ANS-binding showed that the apparent dissociation constant of ANS-membrane complex decreased by treatment with ascorbic acid/Fe2+/tert-BuOOH. Similar results were also obtained by treatment of the membranes with other oxidizing systems, hematin/tert-BuOOH and dipyridyl/Fe2+/tert-BuOOH. These results proposed the possibility that lipid peroxidation of the membranes causes an increase of the positive charge on the membrane surface. The results of the dependence of the ionic strength with increasing KCl concentrations in the medium upon the ANS-binding affinity for the membranes further supported this interpretation.
Anilino Naphthalenesulfonates↗
Naturally occurring 5-lipoxygenase inhibitor. II. Structures and syntheses of ardisianones A and B, and maesanin, alkenyl-1,4-benzoquinones from the rhizome of Ardisia japonica.
New alkenyl-1,4-benzoquinones, ardisianones A (1) and B (2), and the known maesanin (3) as 5-lipoxygenase inhibitors have been isolated from the rhizome of Ardisia japonica. Their structures have been elucidated as 2-methoxy-6-[(Z)-10'-pentadecenyl]-1,4-benzoquinone and 5-hydroxy-2-methoxy-6-[(Z)-8'-tridecenyl]-1,4-benzoquinone, respectively, on the basis of spectroscopic data and chemical degradation. Ardisianone A (1), maesanin (3) and belamcandol A (7) have been synthesized starting from belamcandol B (6), readily prepared by Wittig reaction between 9-(2-tetrahydropyranyloxy)nonanal and 3,5-dimethoxybenzyltriphenylphsophonium bromide followed by selective demethylation with sodium thioethoxide.
Anisoles↗
[An oxidation enzyme for hydrogen sulfide from Hyphomicrobium neptunium ATCC15444].
We described in our previous paper that the cell-free extract from Hyphomicrobium neptunium ATCC 15444 oxidized hydrogen sulfide to sulfur. We tried to purify the enzyme used for this oxidation to determine the molecular nature of this enzyme. The 40% ammonium sulfate precipitate from the supernatant of cell sonicate of H. neptunium was chromatographed on a column of Phenyl Sepharose CL-4B and its active fractions were collected. These fractions were further purified through Superose 12 and then TSK gel G3000SW column chromatographies. A protein of molecular weight about 54,000 and isoelectric point pI 6.8 was isolated. However, this final protein was found to reduce its activity to less than one-tenth of those of ammonium sulfate precipitate and of the fraction from Phenyl Sepharose CL-4B column chromatography. This might be caused either by the loss of accessory component or by its requirement of low molecular factors necessary for its activation at the stage of gel filtration. The neutral isoelectric point of this enzyme could be suitable as the function of H. neptunium because its final product was S0, and it grows at neutral pH. In contrast, the final oxidative product of hydrogen sulfide by Thiobascillus is sulfuric acid, and they grow at acidic pH.
Bacteria↗
Spontaneous pneumothorax following partial resolution of total bronchial obstruction.
Spontaneous pneumothorax following chest irradiation is thought to occur in patients with radiation fibrosis several months or more after the completion of therapy. In the four patients presented herein, spontaneous pneumothorax was seen during or immediately after therapeutic radiation of lung cancer. All patients had bronchoscopic findings of bronchial obstruction by the tumor before treatment and radiographic improvement of atelectasis was observed during therapy. The interval between the improvement of atelectasis and the development of pneumothorax varied by less than three weeks. These common findings suggest that rupture of alveoli or emphysematous bullae and subsequent pneumothorax might be due to overinflation of the affected lung caused by partial bronchial obstruction. We should be aware of the occurrence of spontaneous pneumothorax following partial resolution of total bronchial obstruction.
Aged↗
Small, polypoid-appearing carcinoid tumors of the rectum: clinicopathologic study of 16 cases and effectiveness of endoscopic treatment.
Fifteen cases of small-size rectal carcinoid tumors (RCTs) were discovered among a total of 21,522 healthy teachers who received proctosigmoidoscopy. Adding another case seen in the outpatients, a total of 16 RCTs were clinicopathologically studied. The average age of the patients was 48.8 yr, and the incidence was predominantly among males. Prior to endoscopy, digital examination of the rectum revealed a palpable firm nodule in 13 patients. On endoscopy, RCTs were generally round, yellow-discolored polyps with a size less than 13 mm in diameter, covered by a normal-appearing mucosa. An erythematous change or depression was seen in three tumors. Histologically, they showed pure insular, trabecular, or mixed structures, and tumor cells were confined to the mucosa and/or submucosa in all cases. Immunohistochemically, RCTs never failed to show focal or diffuse positivities for chromogranin A and/or neuron-specific enolase. Pancreatic polypeptide was immunostained in 14 tumors to a varying degree. The tumors having been safely treated by endoscopic polypectomy and/or surgical excision, all of the patients are alive and clinically free of disease during the average observation period of 79 months.
Carcinoid Tumor↗