Sensitivity to bleomycin-induced pulmonary fibrosis was tested in various strains of mice. Among the strains examined, ICR, C57BL/10(H-2b), and C3H/He(H-2k) mice were highly sensitive to the induced pulmonary fibrosis; C57BL/6(H-2b), DBA/2(H-2d), A/J(H-2a), B6C3F1 and BDF1 mice were moderately sensitive, and CBA/JN(H-2k), BALB/c(H-2d), CDF1 and CBF1 mice were less sensitive. In congenic mice, which differ from each other only in the H-2 locus, C57BL/10(H-2b) was highly sensitive; B10·D2(H-2d) was moderately sensitive; and B10·BR(H-2k) and B10·A(H-2a) were less sensitive. Thus, the sensitivity differed depending on the haplotype of the H-2 genes. Furthermore, non-H-2 genes also seemed to be involved in the sensitivity to the pulmonary fibrosis. There was no correlation between the sensitivity to pulmonary fibrosis and enzyme activities such as superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase in the lung tissues, but the levels of reducing agents such as ascorbic acid and tocopherol in the lungs were inversely correlated with the sensitivity to the pulmonary fibrosis, except in the case of BALB/c and its F1 mice.
Mazindol decreased food intake and the body weight of rats with monosodium glutamate (MSG)-induced obesity as well as of control rats. The drug suppressed acyl-CoA synthetase and triglyceride synthesizing activities in epididymal adipose tissue of the obese rats but not of the control ones.
The effect of a geometrical difference in dietary fat on mammary tumorigenesis was studied. Female Sprague-Dawley rats were fed a purified diet containing olive oil (cis-monoene fat), partially hydrogenated corn oil (trans-monoene fat), or a blend of these two oils at the 10% level and received a single oral dose of 7, 12-dimethylbenz(a)anthracene (DMBA). The difference in the fatty acid composition of dietary fats was confined to the geometry of octadecenoate with an appropriate supply of linoleic acid (2% of total energy). The latency period, the rate of the tumor incidence, and the tumor yield 20 weeks after DMBA treatment were all comparable among the three groups. The growth of transplantable mammary tumors in female Wistar rats fed 5% fat diets was also the same between trans- and cis-fat. In DMBA-treated rats, plasma eicosanoid (PGE1, PGE2, and TXB2) levels of the trans-fat groups tended to be higher, while the concentration of 6-keto-PGF1α was comparable. The trans-fat reduced the ratio of arachidonate to linoleate in plasma and liver, but apparently not tumor phosphatidylcholine. The results indicate that the trans-fat is at least equally effective as cis-fat in terms of mammary tumorigenesis.
A primary prevention study based on the double blind method was conducted to clarify both the improvement of serum lipid levels and the prevention of the arteriosclerotic diseases through the long-term administration (3 to 5 years) of MDS (1, 800mg per day) to male subjects with asymptomatic hyperlipidemia (136 in MDS group, 136 in control group), whose ages ranged from 30 to 60 years old. During the study, four ischemic heart diseases occurred in the control group, while no such diseases occurred in the MDS group. Thus, the incidence of ischemic heart diseases was significantly lowered in the MDS group, in which serum lipid levels in type IIa and type IIb hyperlipidemia were significantly lowered. The first primary prevention study for the arteriosclerotic diseases through the double blind method in Japan proved that the long-term administration of MDS at 1, 800mg per day was useful for improving serum lipid levels, and effective for the primary prevention of ischemic heart diseases such as myocardial infarction and angina pectoris.
We performed longitudinal studies on patients with two different types of rheumatic diseases, systemic erythematodes (SLE)-like and rheumatoid arthritis (RA)-like, to elucidate the relationship between hydrolytic enzymes and immunological disturbances. The plasma levels of 9 hydrolytic enzymes and subpopulations of T-cells, OKT4 and OKT8 cells, in peripheral blood were checked periodically for 6 months. Analysis of the obtained data by a method of spectral analysis utilizing Akaike's autoregressive approach clearly demonstrated the existence of a dynamic network between the hydrolytic enzymes and the immune system. In testing the behavior of this network, we obtained data suggesting that the response of OKT4 cells when an impulse is given to OKT8, is abnormal in the SLE-like syndrome, and that this abnormality may be related to the malfunction of suppresser T-cells in this pathological condition. Principal component analysis suggested that the behaviors of kallikrein and carboxypeptidase B are quite different between the two types of immunological disturbances. The network relationships between the hydrolytic enzymes and the immune system seem to play important roles in the pathophysiology of rheumatic diseases.
To clarify relationships between the pattern of diet intake and the circadian adrenocortical rhythm, we measured plasma cortisol levels at circadian intervals in two groups of patients who had been receiving total enteral nutrition (TEN) for about 11 days: one group was given a liquid diet intraduodenally and continuously (continuous TEN), whereas the other received their nutrition discontinuously from 0700-2300h every day (cyclic TEN). In patients with cyclic TEN there was a clear cortisol rhythm with a peak at 0700h, which pattern is quite similar to the well-established cortisol rhythm seen in normal subjects. However, patients with continuous TEN did not show any consistent circadian cortisol rhythm, although the 24-h mean cortisol level was nearly the same as that in the case of cyclic TEN. Plasma glucose levels showed circadian fluctuations in the cyclic TEN group, but remained fairly constant in the continuous TEN group. These results indicate that the periodicity of nutrient intake is essential for the maintenance of the circadian cortisol rhythm and suggest the importance of the timing of diet intake as a synchronizer (zeitgeber) of the rhythm in man, as proposed in laboratory animals.
A protein-sparing modified fasting diet containing 240kcal per day with supplemental nutrients was used for weight reduction of 15 Japanese patients with obesity. The effects of this treatment on glucose and lipid metabolism, uric acid and hormone levels, and body weight loss were investigated. The rate of body weight reduction was about 500g per day in the first week, and 300g per day thereafter. The average weight loss after 4 weeks was 12% of the initial relative weight obtained from standard body weight. Glucose tolerance was improved, and no significant alterations in the measured variables were observed except positive ketonaria, a slight increase in plasma uric acid during the first 2 weeks, and a decrease in the T3 level.
A solid-phase radioimmunoassay was developed for estimating antibody to myelin basic protein. Conditions of the various procedures were established for optimal specific antibody binding. Myelin basic protein was bound to microtiter plates, followed by incubation with diluted test serum. 125I-protein A was used to measure the IgG bound to the antigen-coated well. Sera from 47 patients with multiple sclerosis, cerebrovascular disease, neuro-Behçet's disease, and other neurological diseases were tested for antibody to myelin basic protein. Positive serum antibody was predominantly found in patients with significant basic protein antigen in their cerebrospinal fluids.