Effects of a new analog of thyrotropin-releasing hormone, N alpha-[(S)-4-oxo-2-azetidinyl) carbonyl]-L-histidyl-L-prolinamide dehydrate (YM-14673) on spinal reflex potentials and flexor reflexes in spinalized rats

Experiments were performed on spinalized rats, transected at the Cl level. The intravenous administration of TRH and its analog YM-14673 (N alpha-[(S)-4-oxo-2-azetidinyl) carbonyl]-L-histidyl-L-prolinamide dehydrate) produced marked increases in the amplitude of mono- and polysynaptic reflex potentials and those of the withdrawal flexor reflexes. The effects of YM-14673 were stronger and longer-lasting than those of TRH. The stimulant action of TRH and YM-14673 on the flexor reflexes was not antagonized by prazosin, chlorpromazine, haloperidol or cyproheptadine, suggesting no involvement of the release of catecholamines or serotonin in the stimulant effects of TRH and its analog. Therefore, YM-14673 may be beneficial for the treatment of several spinal motor neuron diseases.     

Severe hypoglycaemia in a person with insulin autoimmune syndrome accompanied by insulin receptor anomaly type B.

AIMS: A rare case of the insulin autoimmune syndrome (IAS) accompanied by insulin receptor anomaly is reported. METHODS: Antibodies to insulin and insulin receptor were determined in the patient with severe hypoglycaemia before and after the treatment with prednisolone. RESULTS: Titers of antibody to insulin and insulin receptors were 73.0% and 41.5%, respectively. Drug-induced lymphocyte stimulation tests were all negative for the suspicious drugs. Her HLA-DR was DRB1*0403/04051. Following steroid therapy, the formation of antibodies was suppressed and alleviated her symptoms. Scatchard analysis yielded findings specific to polyclonal antibodies. CONCLUSIONS: The changes in autoantibodies resulted in alleviation of the hypoglycemic symptoms as a result of steroid therapy.     

Use of Glycopeptidolipid Core Antigen for Serodiagnosis of Mycobacterium avium Complex Pulmonary Disease in Immunocompetent Patients

We report the development of a serodiagnostic method for Mycobacterium avium complex (MAC) disease with an enzyme immunoassay (EIA) with the MAC-specific glycopeptidolipid (GPL) core as the antigen. In this study, we confirmed by EIA that the GPL core antibody was in the sera of immunocompetent patients with MAC disease. The EIA for quantifying the GPL core antibody was evaluated as a clinical tool for serodiagnosis of pulmonary MAC disease. A significant increase in GPL core antibodies (immunoglobulins G, A, and M) was detected in sera of patients with MAC pulmonary diseases when they were compared to patients who were colonized with MAC, patients with Mycobacterium kansasii disease or tuberculosis, and healthy subjects. The sensitivities and specificities of the GPL core-based EIA for diagnosis of MAC pulmonary disease were 72.6% and 92.2%, respectively, for IgG, 92.5% and 95.1%, respectively, for IgA, and 78.3% and 91.0%, respectively, for IgM. The best sensitivity and specificity were obtained by measuring immunoglobulin A antibodies against GPL core antigen. The level of GPL core antibodies reflected disease activity, since it decreased in cured MAC patients who had responded to chemotherapy. Measurement of serum antibodies against GPL core is useful for both diagnosis and assessment of disease activity in MAC disease of the lung.     

Human Tumor–infiltrating Lymphocytes Transfected with Tumor Necrosis Factor Gene Could Augment Cytotoxicity to Autologous Tumor Cells

Human tumor–infiltrating lymphocytes (TILs) derived from pleural or ascitic fluid were incubated with recombinant interleukin 2 and transfected with human tumor necrosis factor (TNF) a gene by the lipofection procedure. The resulting TILs secreted significant amounts of TNF in the culture supernatant and exhibited cytotoxicity against established cell lines, such as K562 and Daudi, and autologous tumor cells. The TNF gene–transfected TILs exhibited an augmented killing of autologous tumor cells.     

The changes in EEG, evoked potentials and neurological recovery after global brain ischemia in dogs

Electroencephalography (EEG), evoked potentials and neurological recovery score were compared between 10 min and 15 min transient global brain ischemia in 18 dogs. The transient global brain ischemia was induced by occluding aorta, superior and inferior caval veins. The grade of EEG (1: normal approximately 5: flat) 2 hrs after ischemia was significantly lower with the 10 min ischemic group (n = 9) than with the 15 min group (n = 9) (3.7 +/- 0.5 vs 4.1 +/- 0.3, P less than 0.05). The rate of reappearance in evoked potential waves 2 hrs after ischemia was higher with the 10 min ischemic group than with the 15 min group (auditory brainstem response 5 wave: 100% vs 33%, middle latency response Pa wave: 80% vs 0%, somatosensory evoked potential N2 wave: 83% vs 78%, N3 wave: 67% vs 33%). The neurological recovery score (0: death approximately 100: normal) 7 days after ischemia was significantly higher with the 10 min group than with the 15 min group (58 +/- 34 vs 27 +/- 23, P less than 0.05). In both groups, there was a significant correlation (r = +0.85, P less than 0.01) between the total score of EEG and evoked potential waves (0: no wave appeared approximately 6: all waves appeared) 2 hours after ischemia and the neurological recovery score 7 days after ischemia. These results suggest that the neurological recovery after transient global brain ischemia would be estimated by EEG and evoked potential waves.     

Furosemide Given by Inhalation Ameliorates Acute Exacerbation of Asthma

Previous studies have suggested that inhaled furosemide may have a protective effect against a wide variety of bronchoconstrictor agents, but a therapeutic effect has not been established in acute exacerbation of asthma. The purpose of this study was to investigate whether inhaled furosemide would exhibit any therapeutic benefit in acute asthma. We conducted a double-blind, placebo-controlled, randomized study in 40 patients with acute mild or moderate exacerbation of asthma. All patients received intravenous (IV) aminophylline 250 mg for 90 min and IV hydrocortisone 100 mg at entry. After randomization, 3 patients were excluded from the final analysis. At 30 min after starting IV aminophylline, 20 patients were given inhaled furosemide 20 mg and 17 patients received normal saline as placebo-control. Both inhalations were given by a jet nebulizer. The baseline forced expiratory volume at 1 sec (FEV₁), peak expiratory flow rate (PEFR), and serum concentration of theophylline did not differ between the two groups. An increase in FEV₁ in the furosemide group by 28.2 ± 5.9% (mean ± SE) was noted at 60 min, and this was significantly higher than in the control group. PEFR at 60 min was also significantly higher in the furosemide group than in control group. We conclude that inhaled furosemide has a bronchodilator effect on mild to moderate exacerbation of asthma when it is used with IV theophylline. Inhaled furosemide may benefit certain acute asthma patients, especially those suffering complications from the adverse effects of β₂-agonists.     

Epidemiological studies of air pollution and health effects in areas near roadways with heavy traffic in Tokyo]

Recent concern regarding health effects of air pollution in Japan has concentrated mainly on traffic-induced air pollution and its health effects in large cities. In Japan, where many people in large cities have been living near major roadways, the increase of automobile exhaust due to heavy traffic congestion will predictably cause a greater impact on people living near major roadways. We surveyed the characterization of residential suspended particulate matter (SPM) and nitrogen dioxide (NO2) concentrations along the major roadways in Tokyo, along with a health survey on the respiratory conditions of residents living in the same area, to examine the relationships between indoor pollutant levels, prevalence of respiratory symptoms and distance from roadways. The environmental monitoring was conducted in five phases. Using a newly developed SPM sampler and NO2 filter badge, continuous 4 day (96 hours) measurements were conducted in two hundred residential homes for four weeks. NO2 was measured in the living room, kitchen and outside of each home, while SPM was monitored in the living room. Health information was collected in October 1987 using ATS-DLD self-administered questionnaires. Of the 1,093 homes investigated, responses from 805 homes were received. The following results were obtained. SPM and NO2 concentrations showed large variations. Indoor pollution levels mostly depended on indoor sources, i.e. cigarette smoking and unventilated space heaters, and the effects of those indoor sources were influenced by the building structure with respect to air tightness. An association between increase in pollutant levels and the distance from the roadway was observed. However its effect is small compared to indoor source effects. The prevalence rate of respiratory symptoms was higher in those areas nearest roadways with heavy traffic both in children and adults. These results suggest the presence of a relationship between automobile exhaust and health effects.