[Round table conference. Clinical medicine and experimental medicine].
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Biomedical subjects
Publications and source records attributed to K Ando.
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We have previously reported that abdominal irradiation of mice inhibited lung metastases of a weakly immunogenic fibrosarcoma, and that transmigration after the irradiation of Enterobacter cloacae into mesenteric lymph nodes coincided with this phenomenon. In this paper, we show that Escherichia coli as well as E. cloacae reduce the number of metastatic lung colonies when these bacteria were intravenously injected into mice prior to the tumour cell challenge. The inhibition was caused not only by the administration of living bacteria but also by that of killed bacteria. Bacterial lipopolysaccharide (LPS), a component of membrane, replaced at least in part the effect of whole bacteria. Transfer of spleen cells from LPS-treated mice into intact recipients prominently inhibited metastatic development in the recipient mice. 'Cross transfer' between LPS high responders and LPS low responders suggested an indirect activity of transferred spleen cells. The antimetastatic activity of LPS depended on the tumour cell type; metastasis of fibrosarcomas was extensively inhibited by LPS irrespective of tumour immunogenicity while that of adenocarcinomas was only slightly inhibited. These results suggest that non-immunological mechanisms are involved in the antimetastatic activity of LPS.
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A differential reinforcement of low rate schedule was used with rats to test 15 psychotropic drugs. The computer analysis was based on interresponse time (IRT). Mean IRT, IRT standard deviation, median IRT, IRT midrange, modal IRT, frequency of modal IRT, and an efficiency index, in addition to numbers of responses and reinforcements and the IRT histogram were obtained for each rat in each drug test. An increase in number of responses and a peak shift to shorter IRTs in the histograms were observed with amphetamine, methamphetamine, priradrol and nicotine, as reported by many other investigators. Decrease in IRT midrange and less change in number of responses were observed with diazepam and chlordiazepoxide. Long pauses were found with LSD-25, 2,5-dimethoxy-4-methylamphetamine (DOM) and mescaline. In a factor analysis, the following main factors were obtained. High values in factor loading a1 were observed with chlorpromazine, chlordiazepoxide, pentobarbital, imipramine, nialamide, LSD-25, DOM and mescaline. With these drugs, mean IRT and IRT standard deviation were also high. Values for a2, were high with amphetamine, methamphetamine, pipradrol and nicotine. High a3 values were observed in some rats with chlorpromazine, diazepam, chlordiazepoxide, pentobarbital, pipradrol and caffeine. The changes in a3 values were correlated with changes in the IRT midrange. These results may be valuable in classifying new compounds in drug screening programs as being of the amphetamine type, nicotine type, diazepam type of LSD-25 type.
Two rare cases of strabismus resulting from contracture of the extraocular rectus muscles after retrobulbar anesthesia for cataract surgery are described. Clinical signs in both cases suggested that the development of the impaired function of the lateral and superior rectus muscles followed the same pattern: initial stimulation followed by paretic and restrictive stages. Abnormal enlargement of the muscles was identified by computed tomography (CT) and magnetic resonance imaging (MRI). The data indicate that the strabismus was the result of direct injection of anesthetics into the rectus muscle.
PURPOSE: Retrospective evaluation of epidemiological features and visual prognosis of patients with Behçet's disease (BD) who visited the University of Tokyo Hospital between 1974 and 1993. OBSERVATIONS: During the survey period, more than 100 new patients with BD visited the uveitis clinic in each 5-year period. The number of new patients decreased in the most recent 5-year period from 1989 to 1993. Although BD has always been more prevalent in men, the percentage of women has increased to 24.7% (19/77) in the most recent 5-year survey period. The percentage of patients who initially manifested ocular symptoms in their third or fourth decade was more than 70%. The proportion of the incomplete type of BD gradually had increased to 62.3% (48/77) by 1993. Among the extraocular major symptoms, oral aphtha and skin lesions have been frequent and genital ulcer has become less frequent in the last 20 years. The patients whose visual acuity was better than 0.4 at the first visit in the 1984-1993 period had a significantly better visual prognosis than the patients in the previous 10-year period. The main drug therapy consisted of colchicine and cyclophosphamide in the earlier 10-year period, and of colchicine and ciclosporin in the later 10-year period. CONCLUSIONS: Behçet's disease is still one of the most frequently encountered types of endogenous uveitis. There have been some changes in the epidemiological features of the patients with BD over the past 20 years. The introduction of ciclosporin in 1985 is probably responsible for the improvement of the visual prognosis in BD patients.
In our previous studies patients with schizophrenia and their parents had less frequent eye fixations and a more limited area of inspection than normal controls while freely viewing stationary S-shaped figures. The present study attempted to discriminate schizophrenics from non-schizophrenics using exploratory eye movements. Two groups (A and B) were formed, each comprising 30 schizophrenic and 70 non-schizophrenic subjects (10 each of patients with depression, methamphetamine psychosis, alcohol psychosis, anxiety disorder, temporal lobe epilepsy, frontal lobe lesions and healthy normal controls). Discriminant analysis was performed on group A to obtain a discriminant. The validity of applying this discriminant to group B was investigated. By focussing on exploratory eye movements, schizophrenics could be discriminated from non-schizophrenics with a sensitivity of 76.7% and a specificity of 81.4%. These results show that exploratory eye movements are a useful discriminator for schizophrenia.
A hydrophobic tetraphenylporphyrinatoiron(II) derivative bearing a covalently bound axial imidazole [Fe(II)P] was efficiently and noncovalently bound into human serum albumin (HSA) up to an average of eight Fe(II)P molecules per HSA molecule. The aqueous solutions of the HSA-Fe(II)P complex provided a reversible and relatively stable oxygen adduct under physiological conditions (pH 7.4 and 37 degrees C). The half-life of the oxygen adduct (tau 1/2) was 1 h at 37 degrees C in an air atmosphere. With Fe(II)-TpivPP (the so-called "picket-fence heme") having no axial base, an oxygenated HSA-Fe(II)TpivPP complex was obtained using a 20-fold molar excess of 1,2-dimethylimidazole, but the tau 1/2 was very short (ca. 10 min at 37 degrees C). The oxygen affinity [P 1/2(O2)] and oxygen transporting efficiency (OTE) of HSA-Fe(II)P at 37 degrees C were 30 Torr and 22%, respectively. Furthermore, the oxygen-binding and dissociation rate constants (kon and koff) are extremely high in comparison with those of hemoglobin. The HSA molecule binding eight Fe(II)P molecules can transport about 3.4 mL/dL of oxygen under physiological conditions, corresponding to about 60% of the oxygen transporting amount of human blood.
BACKGROUND AND OBJECTIVES: Mexiletine is a sodium channel blocker that has been used for the treatment of a variety of neuropathic pain syndromes. A recent double-blinded placebo-controlled study concluded that it was ineffective in the treatment of allodynia associated with neuropathic pain. However, this study failed to achieve adequate plasma levels of mexiletine. This was a study in healthy volunteers that sought to push the drug to dose-limiting side effects and then evaluate the effects on human experimental pain. METHODS: Twelve healthy volunteers were studied using a randomized, double-blind, placebo-controlled crossover study. The subjects were titrated to a maximum dose of 1,350 mg/d or dose-limiting side effects, whichever occurred first. At baseline and day 10 and 17, neurosensory testing, train-of-three thermal pulses, and side-effect measurements were performed and on day 17, intradermal capsaicin was injected on the volar aspect of the forearm and the pain and secondary hyperalgesia to von Frey hair, stroking, and thermal stimuli were measured. RESULTS: Peak plasma levels occurred on day 10 and were 0.36 +/- 0.21 microg/mL. All subjects experienced dose-limiting side effects. The mean maximum tolerable daily dose achieved was 859 mg (range, 300 to 1,350 mg). The side effects reported by the subjects included nausea, lightheadedness, muscle twitching and weakness, blurred vision, headache, tremors, difficulty concentrating, dysphoria, sedation, pruritus, and rash. These side effects occurred at an average daily dose of 993 mg (range, 600 to 1,350 mg). Compared with placebo, mexiletine had no significant effects on any of the neurosensory thresholds and pain scores after intradermal capsaicin. There was a significant reduction in the area of secondary hyperalgesia to von Frey hair stimulation only. There was a significant correlation between plasma mexiletine level and flare response. CONCLUSIONS: Mexiletine has minimal effects on human experimental pain. It is severely limited by side effects and tolerable doses seem to be void of effects on normal neurosensation and facilitated pain induced by capsaicin and thermal heat pulses.
Concentrations of immunoreactive thyrotropin-releasing hormone (ir-TRH) were measured by specific radioimmunoassay in the spinal cord of six patients with amyotrophic lateral sclerosis (ALS) and seven with non-neurological diseases. Ir-TRH concentrations were the highest in the anterior horn, compared with other areas of the spinal cord, both in non-neurological diseases and ALS. Ir-TRH concentrations in the anterior horn of ALS were significantly lower than in non-neurological diseases, but were the same in both groups in other parts of the spinal cord (e.g. posterior horn, frontal part, lateral and central part, posterior part). Ir-TRH concentrations in rat spinal cords were stable for up to seven hours when spinal cord was stored after death at 4 degrees C or 22 degrees C. An elution profile of methanol-extracted human spinal cord on Sephandex G-10 column was identical to that of synthetic TRH. The cell population in the anterior horn in ALS was decreased markedly. The findings suggest that TRH is present in the human spinal cord and its decreased concentrations in the anterior horn of ALS may be due to a decrease in the cell population.
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Effect of local hyperthermia given alone or in combination with cyclophosphamide and/or hyperglycaemia on the development of lung metastasis was studied using a non-immunogenic mouse fibrosarcoma, FSa-II. Incidence of lung metastasis was dependent upon the tumour size, and was increased when tumour-bearing mice were restrained in animal holders which were used for heat-treatment of animal tumours. The frequency of the metastatic spread was decreased following local hyperthermia at 41.5 degrees and 45.5 degrees C when compared to that following sham treatment. This decrease was independent of the heat dose. Similar reduction in the incidence of metastasis was observed after hyperthermia given following glucose administration. The administration of cyclophosphamide effectively inhibited the development of lung metastasis. However, the magnitude of the inhibition was identical to that following hyperthermia alone. In conclusion, hyperthermia given alone, or in combination with hyperglycaemia or cyclophosphamide, inhibited the development of lung metastasis.
To investigate the effect of surgical stress on the endocrine pancreas, we evaluated the changes in glucose-stimulated insulin release from the isolated perfused pancreas 4 and 7 days after laparotomy. Four days after laparotomy, insulin response to a glucose load was poor, and integrated insulin release was significantly less in the first and third phase of stimulation than in the normal rats. At 7 days, however, insulin response to a glucose load was augmented, and the integrated insulin release was significantly increased in all the phases of stimulation. These results indicate that in the early phase after surgical stress there is an impaired insulin response to a glucose load and that in the recovery stage after surgery, there is an augmented insulin response to a glucose load.