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<P>Peripheral T-cell lymphoma (PTL) is a distinctive clinical entity, albeit it comprises several diseases with histologically heterogeneous diagnoses. We studied prognostic factors on 30 patients diagnosed and treated at Shikoku Cancer Center Hospital. Clinical findings and laboratory data were evaluated by statistical analysis to investigate the important factors influencing survival duration. Variables influencing survival were stage, leukemic change, bone marrow infiltration (BMI), anti-human T-lymphocyte virus-type I antibody, white blood cell count, and lactate dehydrogenase (LDH). Multivariate analysis revealed high level of LDH and positive BMI as the important factors for short survival. Histological classifications of the Working Formulation and the T-lymphoma classification by Suchi et al. were also evaluated whether these were related with prognosis. Our data revealed that there was no significant relationship between histological subtype and survival duration. The study of prognostic factors provides valuable aids for us to understand the clinical characteristics of PTL patients with various backgrounds.

In order to clarify difference of the mucosal immunity in various sites of normal large and small intestines, we studied the population of lymphocyte subsets and immunoglobulin (Ig)-containing cells in situ in biopsy specimens taken from various sites (ascending colon, sigmoid colon and rectum) of the large intestine and from the duodenum using an immunohistochemical method. Monoclonal antibodies against pan-T (Leu 1), cytotoxic/suppressor T (Leu2a), helper/inducer T (Leu3a), suppressor T (Leu15) and natural killer/K (Leu7) cells, and polyclonal antibodies to human IgG, IgA and IgM were used. In the duodenum, intraepithelial lymphocytes (IELs) were more prominent than in the large intestine. Immunoelectron microscopic observation revealed that some Leu2a+ IELs possessed pseudopods extending into intestinal epithelial cells, indicating that some IELs belong to the cytotoxic T cell subset. Leu7+ IELs were scarcely observed and Leu7+/Leu1+ ratio was higher in the large intestine than in the duodenum. Furthermore, the number of Leu7+ cells were more in the distal than the proximal colon. In the lamina propria Ig-containing cells tended to be fewer in the rectum than in the duodenum and the proximal colon. Our findings may suggest the variation of local immune responses and the difference of assigned immunological functions among the various sites of the intestines.

Some mechanisms to reduce methemoglobin (metHb) formation for the maintenance of normal oxygen transport have been proposed. To study the role of catalase (EC 1.11.1.6), metHb formation in the hemolysate of normal and Japanese acatalasemic human subjects were examined spectrophotometrically. Significantly increased level of metHb was induced by potassium ferrocyanide in the hemolysate of acatalasemic subject. The addition of catalase reduced the metHb formation, while 3-amino-1,2,4-triazole (AT), a specific inhibitor of catalase-H2O2 compound I, increased it. These results obtained from human subjects were well consistent with those from mice and suggested that catalase plays a role in protecting erythrocytes against metHb formation.

We investigated the antitumor activities of 5-fluorouracil (5-FU), 5'-deoxy-5-fluorouridine (5'-DFUR), 1-hexylcarbamoyl-5-fluorouracil (HCFU) and 1-(tetrahydro-2-furanyl)-5-fluorouracil (FT-207) in combination with hyperthermia in vitro. The antitumor effect of 5-FU (10(-4) M) was slightly enhanced by combination with hyperthermia (42 degrees C) for 2h, and the effect was determined to be additive. Synergistic enhancement of antitumor activity was obtained by the concurrent use of hyperthermia (42 degrees C, 2h) and 5'-DFUR (10(-4) M) or HCFU (10(-5) M). However, the antitumor effect of FT-207 (10(-4) M) in combination with hyperthermia was comparable that of hyperthermia alone. The synergistic enhancement of antitumor activity was not obtained for all drugs when the cells were preheated at 42 degrees C for 2h. On the other hand, when cells were pretreated with drugs before heat exposure, weak interactions were obtained after 5-FU and 5'-DFUR treatment, and a synergistic interaction was obtained after HCFU treatment. It is speculated that the metabolites of 5'-DFUR and HCFU enhance the cytotoxicity of 5-FU, or might change the threshold concentration for a cytotoxic effect of 5-FU in cancer cells.

Twenty-seven previously untreated patients with unresectable non-small cell lung cancer were treated with a 3-drug combination of ifosfamide, cisplatin, and vindesine as a phase II study. Patients received ifosfamide, 1.3g/m2, on days 1 to 5; cisplatin, 20mg/m2, on days 1 to 5; and vindesine, 3mg/m2, on days 1 and 8; with a sufficient parenteral hydration. Courses were repeated every 4 weeks. Twenty males and seven females with a median age of 61 years were treated and fully evaluated. Five patients had stage IIIA, seven had stage IIIB, and 15 had stage IV disease. One patient with adenocarcinoma achieved a complete response and 16 achieved a partial response, for an overall response rate of 63% (95% confidence limit: 45% to 81%). The median duration of response was 34 weeks (range: 9 to 52 weeks). The median survival time was 58 weeks for patients with IIIA/B disease, and 33 weeks for those with IV disease. The major toxicity was myelosuppression, however, it was generally well-tolerated. These results indicate that the 3-drug combination is active against non-small cell lung cancer and warrants further clinical trials.

To gain further insight into the central nervous system (CNS)-action of beta-adrenergic blocking agents (beta-blockers), we examined the effects of various kinds of beta-blockers on opioid receptors (Op-Rs) using radiolabeled receptor assay (RRA). We demonstrated that beta-blockers are competitively bound to Op-Rs in the CNS. Sodium index of beta-blockers in [3H]naloxone binding study indicated that beta-blockers had the mixed agonist-antagonist activity of opiates. The relative potency of beta-blockers in opioid RRA was negatively correlated with their membrane stabilizing activity. Neither beta-blocking activity nor intrinsic sympathomimetic activity was correlated with IC50 values of beta-blockers in opioid RRA. While it is widely accepted that beta-blockers have a tranquilizing activity, a part of the tranquilizing action of beta-blockers may be mediated through Op-Rs in the CNS. Although beta-blockers may have effects on their own receptors (beta-receptors) in the CNS, the more precise mechanisms of central action of these drugs must be further investigated.

A centrifugal pump was successfully used as a left ventricular assist device (LVAD) in a 54-year-old female who developed cardiogenic shock following open heart surgery. Cardiac index prior to the LVAD support was 1.4 l/min/m2 and increased to 3.0 l/min/m2 at removal of the device, which assisted for 88h. She resumed her daily activity 10 months after the operation and is in New York Heart Association functional class I.

A monoclonal antibody (MAb-1E7), generated against bovine retinal homogenate, labeled the outer and inner segment layers of the vertebrate retina. Immuno-electron microscopic observation clearly demonstrated that antigen(s) bound by MAb-1E7 was localized in the cell membrane of the outer segment and the distal portion of the inner segment. Western blot analysis revealed that MAb-1E7 recognized 40 kD- and 27 kD-polypeptides. Mouse retina with hereditary photoreceptor degeneration (C3H/He and CBA strains) did not involve the MAb-1E7 immunoreactive structures. The present immunocytochemical observation demonstrated that MAb-1E7 was highly specific to the outer segment of the photoreceptor cells and, therefore, can be a useful marker for the cells.

Effects of Gabexate mesilate (GM) (([ethyl-4-(6-guanidino hexanoyloxy) benzoate] methane sulfonate)), a protease inhibitor, on the activities of catalase in liver, erythrocytes and reticulocytes from acatalasemic mice were examined. Preincubation without GM at 37 degrees C for 160 min lowered the catalase activities of liver, erythrocytes and reticulocytes from acatalasemic mice, to 24%, 40% and 10% of the initial levels, respectively. But, preincubation with GM at 37 degrees C for 160 min delayed the rapid decrease in activities of residual catalases in the liver, erythrocytes and reticulocytes of acatalasemic mice to 65%, 93% and 85% of the initial values, respectively. At 20 degrees C or below, no reduction in catalase activity of reticulocytes from acatalasemic mice occurred with or even without GM. At pH 5.0, the decrease in catalase activity of acatalasemic mice was small both in the presence and the absence of GM. In the alkaline range, the reduction in the enzyme activity of the mutant mice without GM was enhanced with increase in pH values up to 8.5. But the presence of GM during preincubation at pH 7.5, retained the catalase activity of acatalasemic mice, to 64% of the activity at pH 6.5. These data suggest that some factors affected by GM, might be responsible for the low stability and activity of catalase in the acatalasemic mice.

L-Dopa and three catecholamines in the amniotic fluid before and after labor were measured to confirm the amniotic fluid catecholamine levels at the end of gestation. L-Dopa values were higher than those of three catecholamines, and dopamine which was the predominant catecholamine, rose significantly after the onset of labor. Then, to evaluate the effects of L-dopa or dopamine on prostaglandin synthesis, strips of human decidua vera obtained from fetal membranes at the time of elective cesarean sections before the onset of labor were incubated in Krebs-Ringer buffer in the presence of L-dopa or dopamine. When L-dopa was added, the net production of prostaglandin(PG)F was significantly greater than that of the control at each incubation time. On the other hand, the significant rise was observed only after 10 min of incubation for PGE2 production. Dopamine had a stimulatory effect on PGF synthesis only after 15 and 30 min of incubation, and it also stimulated the release of PGE2 at each incubation time. These results suggest that dopamine and L-dopa in amniotic fluid stimulate the production of prostaglandin by the decidua in humans.

The left ventricular studies by Doppler echocardiography were performed in 50 patients with a Bjork-Shiley (B-S) mitral valve and 50 patients after implantation of a St. Jude Medical (SJM) mitral valve; the effect of valve replacement on the hemodynamic performance at rest and during bicycle exercise was determined from serial echocardiographic data. Twenty-eight patients (56%) of the B-S group and 42 patients (84%) of the SJM group showed a good response to the exercise. There was no significant difference in the effective orifice area at rest among each sizes of the B-S valve. In the SJM valve, on the contrary, the effective valve orifice area increases in parallel to the size of the SJM valve. There was a clear relation between the valve size and pressure gradient. The pressure gradient directly depends on the valve size and the effective orifice area in the SJM valve. High pressure gradient group in both prostheses had a tendency to take negative values of percent increase in stroke volume. Further, there were no cases showing positive values of percent increase in end-diastolic volume among the patients whose pressure gradients were assumed to be more than 10 mmHg at rest. It is suggested that impairment of inflow caused by the artificial valve, prosthetic valve stenosis, is possibly a significant factor causing left ventricular dysfunction, notably a decrease in stroke volume during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Trial of Rous sarcoma virus (RSV) induction by cell fusion with chick embryo cells (CEC) and wing web test from so-called RSV-transformed human cells, KC and RSb cells, was unsuccessful. The loss of RSV inducibility was also confirmed by DNA transfection method. Southern blot and northern blot hybridization of DNA and RNA from those cells with the v-src probe revealed that the v-src genes in those cells were defective and not expressed. On the other hand, the v-src gene in RSV-transformed mouse and rat cells was complete and transforming virus was inducible from them.</P>

Ability of two neurovirulent strains (F and +GC (LPV) Miyama) of herpes simplex virus type 1 (HSV-1) to establish and maintain reactivatable latency in trigeminal ganglia (TG) was compared after intranasal inoculation of mice. The +GC (LPV) Miyama strain showed a very low rate of virus reactivation in explant cultures of TG, while the F strain showed a high rate of reactivation. These data indicate that neurovirulent strains of HSV-1 are not always competent for reactivatable latency, although most virulent strains of HSV-1 thus far reported were competent for reactivatable latency.</P>

Effects of the mesenteric nerve stimulation (MNS) on the twitch contraction induced by field stimulation were investigated regarding the relationship between myenteric neurons and extrinsic cholinergic nerves in the guinea-pig mesenteric nerve-ileal preparation. The twitch contraction was inhibited after MNS. The inhibition of the twitch contraction after MNS was induced twice, just after MNS (1st inhibition) and 2-3 min later (2nd inhibition) (type I), or once, just after MNS (1st inhibition) (type II), in recovery course of twitch contraction for 6-8 min. The 1st inhibition was slightly decreased by guanethidine and hexamethonium. The inhibitory response (1st inhibition) in both types I and II was recovered to the control level by pretreatment with naloxone (recovered twitch contraction), but the late inhibitory response (2nd inhibition) was markedly observed after 2-3 min in types I and II. Either the 1st or the 2nd inhibition was not altered by capsaicin, desensitization to calcitonin gene-related polypeptide (CGRP), vasoactive intestinal polypeptide (VIP), somatostatin, or galanin. The recovered twitch contraction in types I and II was decreased by CGRP-desensitization, or capsaicin. These results suggest that the first inhibitory response was induced by enteric opioid neurons connected with extrinsic cholinergic nerves, but the 2nd inhibition was induced by unknown substances other than CGRP, VIP, somatostatin, and galanin. The twitch contraction may partly be induced by endogenous neurokinin-like substances. And, some CGRP containing neurons, which connect with extrinsic cholinergic nerves, probably activate the intrinsic excitatory neurons.

DNA repair synthesis induced in permeable mouse ascites sarcoma cells by peplomycin, an antitumor antibiotic, was studied. Mouse ascites sarcoma (SR-C3H/He) cells were permeabilized with a low concentration of Triton X-100 in an isotonic condition. Permeable cells were treated with an appropriate concentration of peplomycin to introduce single-strand breaks in permeable cell DNA. DNA repair synthesis in peplomycin-treated permeable cells was measured by incubating the cells with four deoxynucleoside triphosphates in an appropriate buffer system. The DNA repair synthesis was enhanced by ATP and NaCl at near physiological concentrations. More than 90% of DNA synthesis in the present system depended on the peplomycin-treatment. The repair nature of the DNA synthesis was confirmed by a BrdUMP density shift technique. The repair patches were largely completed and ligated in the presence of ATP. Analyses using selective inhibitors for DNA polymerases showed that both DNA polymerase Beta and aphidicolin-sensitive DNA polymerases (DNA polymerase alpha and/or delta) were involved in the repair DNA synthesis.</P>

An automated direct assay system using high performance liquid chromatography was developed for the measurement of RU38486 and its three metabolites (RU42698, RU42848, RU42633) in human serum. Serum concentrations of these compounds were measured up to 144 h following single oral administration of 200 (200 mg group, n = 3) or 400 mg (400 mg group, n = 3) of RU38486 to healthy female volunteers. The serum half-lives (200 mg group-400 mg group) of RU38486, RU42698, RU42848 and RU42633 were 31.8-33.1 h, 41.2-39.3 h, 33.9-36.6 h and 29.2-36.6 h, respectively. Our system could quantify them easily and simultaneously, and was considered to be valuable in studies on the relationship between the pharmacokinetics and the clinical effects of RU38486.</P>

We studied the use of high-performance liquid chromatography (HPLC), using a solid phase extraction column (Bond Elut cartridge column), for the simple, rapid and sensitive determination of serum clonazepam levels in epileptic patients. Extracted aliquots were analyzed by HPLC, using a reverse phase ODS column (mu-Bondapak C18). The analytical mean recovery of clonazepam added to the blank serum averaged 99.9%. The detection limit was as high as approximately 2 ng/ml in the serum. The reproducibilities were 2.3-8.6 CV % in the within-day assay and 6.5 CV % in the between-day assay, indicating that the analysis method was effective in the determination of clonazepam serum levels. Accordingly, we suggest that the present method, using a solid phase extraction column, may be useful for the routine monitoring of clonazepam serum levels in epileptic patients.</P>

Polyester-crystic cast was observed to reach the peritubular capillary plexus following injection in sheep kidneys. Microvascular structures in this region are also reported in this study. Glomeruli were found to vary in size and shape. Diameters of afferent arterioles were larger than those of efferent arterioles. The glomerulus is supplied by more than one afferent arteriole, and in some regions, the blood in afferent arterioles joins collateral circulation via the intercapillary plexus. Morphological properties at the end of the peritubular capillary plexus were found to be remarkably significant.</P>