Fatty acid analysis of glycolipids, ceramide monohexoside (CMH) and cerebroside sulfuric ester (CSE), from brains (frontal lobe ; grey and white matter separately) of 3 cases with Alzheimer's disease was carried out, and the following findings were obtained :
1) In all cases, no gross changes were found in the fatty acid composition ;
2) In all cases, the percentage of hydroxy fatty acids (HFA) was decreased. The decrease was greater in CSE than in CMH ; and
3) Changes in the ratio of unsaturated fatty acids to the total fatty acids were different among the cases. Some remarkable increases in the ratio were found in one case, while decreases in another.
Significance of the above findings for the pathology of Alzheimer's disease was discussed. Since the decrease in the HFA percentage was found in all cases, it is considered to be essential and specific to Alzheimer's disease. Also it may well be that the fatty acid hydroxylase activity is decreased in this disease. As regards the changes in the unsaturated fatty acid ratio varying with cases, an attempt was made to relate them to the characteristics of histopathological changes in each case.

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It was observed that when normal mouse spleen cells were cultured alone in vitro (precultured) for 5 to 7 days, these precultured cells lost the ability to produce antibody during subsequent in vitro sensitization with antigen. These precultured cells, which were themselves unable to produce antibody, also actively suppressed the generation of antibody-forming cells from freshly cultured spleen cells. The supernatant from the precultured cells was not suppressive.
The suppressor cells inhibited both the primary and secondary antibody-formation responses. The suppression was nonspecific to both immunoglobulin class and antigen. The suppressor cells inhibited the mitogenic response of normal spleen cells to both phytohemagglutinin (PHA) and bacterial lipopolysaccharide (LPS), but the LPS-response was much more sensitive to the suppression than was the PHA-reponse. These results indicate that the target cells of the suppressor cells are both T and B cells, and the mechanism of action of the suppression is proliferation inhibition of target cells.

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It is known that RNA preparation extracted from lymphoid organs of immunized animals contains a factor which is called immune RNA (iRNA). The author studied the role of iRNA in immune response by assaying with plaque-forming cell (RFC) method. The iRNA was extracted with a phenol method from spleens of mice immunized with sheep red blood cells (SRBC).
The iRNA transferred antigen-specific IgM memory to non-immunized mice. The iRNA extracted 5 days after immunization seemed to have higher activity than that extracted at any other day after immunization. The activity of iRNA was lost by treatment with RNase, but was not lost with amylase, proteinase, or anti-SRBC antiserum. High activity was observed in the iRNA extracted from immunized neonatal mice, in which primary immune response was not demonstrated but immunological memory seemed to be induced. And the activity was demonstrated in the iRNA extracted from mice immunized with a low dose of SRBC, with which primary immune response was not initiated but immunological memory seemed to be initiated.
Conclusively, iRNA seemed to play some important roles in the induction of immunological memory.

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Previous studies indicate that transiently decreased pituitary reserve follows withdrawal of suppressive thyroid therapy from intrinsically euthyroid patients, regardless of whether they are normal or goitrous. However, little is known of such TSH secretion patterns in Hashimoto's thyroiditis. Studies were conducted in 24 women patients with Hashimoto's thyroiditis. Twelve patients with thyroid adenoma served as control (Group I). Patients with Hashimoto's thyroiditis were classified as Group II (≤10μU/ml) and Group III (>10μU/ml) on the basis of serum TSH level 8 weeks after withdrawal of the exogenous thyroid hormone. They had no signs of hypothyroidism before therapy (euthyroid Hashimoto's thyroiditis) and received either L-thyroxine (L-T₄, 200μg/day) or L-triiodo thyronine (L-T₃, 50μg/day) for varying periods (1.5-60 months)
L-T₃ withdrawal : Before L-T₃ taking off, serum levels of T₄-I, T₃ and TSH in Group II and Group III were not significantly different from those of Group I. No detectable TSH response to TRH was found in all groups. At the first week after withdrawal of suppressive medication, serum T₃ decreased abruptly, while serum T₄-I tended to increase. Thereafter, serum T₄-I and T₃ rose progressively, returning into the normal ranges by the second week, although the values of Group III appeared to be lower than those of Group I and H. The maximal basal TSH level was obtained in Group II and Group ill at the first week, followed by further decreases by the 8th week. By contrast, no change was observed in the basal serum TSH in Group I. There was an exaggerated response of pituitary TSH to TRH (500μg, iv) in Group II and III through 1-8 weeks. The higher serum TSH level was observed in Group III than in Group II.
L-T₄ withdrawal :
There was no change in serum levels of T₄-I, T₃ and TSH during L-T₄ therapy. A rapid fall in serum T₄-I and T₃ occurred at the first week after withdrawal of L-T₄, followed by a further decline to nadir at the second week. The supranormal serum TSH and exaggerated TSH response to TRH were observed at 4-8 weeks in Group II and III. The higher TSH level was also obtained in Group III than in Group II.
On the other hand, no difference in the basal serum prolactin (PRL) and TRH-stimulated PRL response between Hashimoto's thyroiditis and thyroid adenoma was observed through the study.
The present investigation has shown that basal serum TSH level can differentiate thyroid adenoma from Hashimoto's thyroiditis 1 week for L-T₃ and 2 weeks for L-T₄ after withdrawal of thyroid therapy. Serum TSH response to TRH does not potentiate this differentiation. In addition, differential sensitivity of the lactotrophs and thyrotrophs in Hashimoto's thyroiditis following discontinuing thyroid medication was also demonstrated.

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Although effects of estrogen on pituitary-thyroid axis have extensively been studied for sometimes, conflicting results have been reported in man and experimental animals. Discrepancies among previous investigations might have resulted mostly from the inadequate methodology or a choice of parameters, such as thyroid weight, thyroidal uptake or release of radioiodine, protein bound iodine, bioassayable thyrotropin (TSH) and etc. The present study was undertaken to re-evaluate and elucidate mechanisms and loci of actions of estrogen in the pituitary-thyroid axis in the rat by direct measurements of plasma concentrations of TSH, thyroxine (T₄), triiodothyronine (T₃), reverse T₃ (rT₃) and free T₄ and hypothalamic content of TSH-releasing hormone (TRH), employing sensitive and specific radioimmunoassays for respective hormones. In addition, the present study also examined possible effects of estrogen on the peripheral kinetics of thyroid hormones and on the hypothalamic regulation of this axis.
Two weeks after ovariectomy (ovx) of Wistar strain rats, daily sc injections of 25μg of estradiol benzoate (EB) were initiated and serial blood samples were obtained from jugular vein under ether anesthesia. Plasma T₃ conconcentration was linearly increased after initiation of EB and nearly doubled by the 8th day. However, neither plasma T₄, free T₄ nor rT₃ were affected by EB administration. The kinetic study of the peripheral thyroid hormone metabolism, using ¹²⁵I-T, and ¹²⁵I-T₃ with high specific activities, revealed that EB administration produced a decrease in the half-life of T₄, but not of T₃, increases in metabolic clearance rate and production rate (PR) of T₄ and also an increase in PR of T₃. Furthermore, the concomitant administration of EB and l-T₄ (1.5μg/100g B.W./ day) to ovx-thyroidectomized rats resulted in a dramatic drop in plasma T₄ concentration with normal levels of plasma T₃. These observations suggest that, in addition to the direct stimulatory action of EB to thyroid gland, EB also accelerates the peripheral conversion of T₄ to T₃ to maintain the elevated plasma T₃ levels.
The daily EB administration to ovx-rats produced not only an increase in basal levels of plasma TSH but an exaggerated response of pituitary TSH secretion to exogenous synthetic TRH. But, this stimulatory effect of EB on the pituitary TSH secretory mechanism was not evident in male rats. Thus, it appeared that there was a sex difference in this regard. Interestingly enough, elevated levels of plasma TSH during the first week after the initiation of EB treatment returned to the initial values by 2 weeks. This biphasic effect of EB on plasma TSH might be brought about by cancellation of stimulated TSH secretion by elevated plasma T₃ through the negative feedback mechanism.
Hypothalamic TRH content was not affected by EB treatment. However, complete deafferentation of mediobasal hypothalamus partially inhibited an elevation of plasma TSH induced by EB administration, suggesting the hypothalamic participation to the stimulatory action of EB in TSH release.
In conclusion, the present study indicates that estrogen is capable of direct stimulatory actions to the pituitary TSH secretion and thyroid hormone synthesis and release. More importantly, the present study provides evidences EB acts on the peripheral metabolism of thyroid hormones as to accelerate the conversion of T₄ to T₃, and that a stimulatory effect of EB on pituitarythyroid axis is brought about, at least in part, by activation of hypothalamic regulation.

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Pacemaker cells of the isolated sinus node of the guinea pig were exposed to K-free, Acetylcholine, 2-4-Dinitrophenol, cyclic AMP and Ca-free Krebs solution.
Potentials were recorded by means of a conventional microelectrode technique. The sinus node tissue closed to the crista terminalis was trimmed to 1 × 0.5mm area including the dominant pacemaker cells. The tissue was transported into a bath of 1.0ml capacity filled with the standard Kreds solution saturated with a gas mixture of 95%O₂ and 5%CO₂.
1) When the pacemaker cells were perfused in the K-free Krebs solution, they showed an after-oscillatory potential.
2) When the cells were perfused in the Ach solution, they had no oscillatory potential before and after that of the pacemaker potential.
3) In the 2-4-Dinitrophenol solution, they had a pre-oscillatory potential only before the disappearance and not after the recovery of the pacemaker potential.
4) If the cells were perfused in the cAMP solution, they showed a pre-oscillatory potential just before the disappearance and immediately after the recovery of the pacemaker potential.
In conclusion these oscillations were enhanced by the K-deficiency and the increase of the membrane resistance and were depressed by the Ca-deficiency. Results suggest that the inward Ca-current plays an important role in the oscillatory potential when the function of electrogenic pump was decreased.

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Morphological changes of interlobular bile ducts in primary biliary cirrhosis and chronic hepatitis were investigated. Results were as follows :
1) Epithelial cell swelling and/or flattening, karyopyknosis, vacuolated cytoplasm and inflammatory cells in the epithelium were generally observed in primary biliary cirrhosis and chronic hepatitis. Stratification, obstructed lumen or cellular debris and destruction of the wall were more often found in primary biliary cirrhosis than in chronic hepatitis.
2) The portal tracts were markedly infiltrated by inflammatory cells in primary biliary cirrhosis and chronic hepatitis. Follicular formation and plasma cell infiltration were usually seen in primary biliary cirrhosis. Granuloma was never found in chronic hepatitis.
3) There were same epithelial changes between symptomatic primary biliary cirrhosis and asymptomatic one. Granulomas were more frequently seen in asymptomatic primary biliary cirrhosis than in symptomatic cases.
4) Numbers of interlobular bile ducts per portal tracts were 0.23 in symptomatic primary biliary cirrhosis and 1.22 in chronic hepatitis. In 3 asymptomatic primary biliary cirrhosis, those were 0.61, 0.87 and 0.71, respectively.
5) The rates of portal tracts without interlobular bile ducts were 81% in symptomatic primary biliary cirrhosis and 18% in chronic hepatitis. In 3 asymptomatic primary biliary cirrhosis, the rates were 72%, 50% and 43%, respectively.
6) Serial sections revealed that some bile ducts can be able to followed by ductules in 2 asymptomatic primary biliary cirrhosis.

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Electrical alternans was observed in 6 cases with various underlying disorders.
As for the mechanism of the development of this unusual electrocardiographic abnormality, the classical hypothesis that the heart swinged within the pericardial cavi y was assumed to be appropriate for only 2 cases with massive pericardial effusion and cardiac tamponade. An alternative explanation that the every alternate impulse met some region of the myocardium still normally refractory from previous activation because of tachycardia was thought to be more suitable for a case with otherwise normal heart. In this case, the electrical alternans developed during an episode of tachycardia caused by paroxysmal atrial flutter with 2 : 1 conduction. On the other hand, 2 cases with isolated T wave alternans, a 16-year-old female with pheochromocytoma and a 51-year-old female with subarachnoidal hemorrhage, raised a possibility of causal relationiship of increased circulating catecholamine and/or sympathetic overactivity with this rare form of electrical alternans.

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