The 448-PI-Vero, African green monkey kidney cell line (Vero) persistently infected (PI) with a temperature sensitive (ts) mutant, P-448 of measles virus has been studied in culture for 6 years.
The Edmonstone strain of measles virus induced interferon (IFN) in BSC-1 cells derived from African green monkey kedney, but the P-448 virus with which the persistent infection was established, did not produce IFN in BSC-1 cells. Both of the Edmonstone and P-448 viruses did not induce IFN in Vero cell culture.
Vero cell culture which was maintained during the 6 years, but not infected with measles virus, produced IFN by the infection of Newcastle disease virus, but another Vero cell line(Vero-F) obtained commercially did not.
The virus derived from the persistently infected 448-PI-Vero at 500 days (19 passages) after the initial infection showed decreased temperature sensitivity but did not produce IFN.
The virus derived at 558 days (20 passages) showed reversion to ts' phenotype and produced IFN.
Viruses from 448-PI-Vero maintained longer than 715 days (29 passages) steadily had the IFN-inducing capacity and showed unstable temperature sensivity. The culture showed definitely decreased cytopathic change, when excreted the is virus.
In Veto-F cells, persistent infection was easily established with viruses from 448-PI-Vero which had been maintained for 558 to 1, 500 days, only when the virus was inoculated at multiplicity of infection (MOI) of 0.08 or more.
From the results described above, it is concluded that firstly IFN-production is not necessary to establish the PI culture, and secondly the maintenance of the PI culture could be related to the IFN-production in cells and a selection of mutants with decreasing cytopathogenicity as well as presumably a development of defective interfering particles. 448-PI-Vero produced highly heterogeneous mutant viruses after a long incubation periods.

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A histological study of the cerebral arteries was made on 30 patients (15 male, 15 female, average age 56) who died from subarachnoideal hemorrhages as a result of the rupture of berry aneurysms in the Willis' circle. Particular attention was paid to the small-sized arteries less than 300μm in diameter which are located in the cerebral cortex, medulla, putamen, pallidum, cerebellum, mid brain and pons.
For comparison, vascular alteration were observed in 12 patients (10 male, 2 female, average age 60) with cerebral hemorrhages of hypertensive nature, and 10 patients (6 male, 4 female, average age 67) with cerebral infarction. Most arteries examined in the above mentioned three groups showed considerable changes in the intima, media and adventitia in variable extent. In the patients with subarchnoideal hemorrhages and with cerebral hemorrhages, commonly seen were plasma imbibition, focal aneurysmal dilatation due to partial defect in the media, marked dilatation with attenuated wall and fibrous sclerosis with distension-all of which showed irregular asymmetrical contours. In comparison with cerebral hemorrhages, the arteries of the patients with subarachnoideal hemorrhages were consistently characterized with plasma imbibition into the media and partial medial defect, especially in the subarachnoideal branches.
Thus it can be postulated that small-sized arteries of the patients with subarachnoideal hemorrhages were exposed to repeated circulatory dysfunction which caused recurrent and aggravated hemodynamic abnormalities, resulting in plasma imbibition into the media and damage of smooth muscle cells of the media. It is possible to assume that irregular asymmetrical shaped arteries were due to repeated abnormal arterial movement. Berry aneurysms may occur in such sites of locus minoris by abnormal pressure as in the arteries of the Willis' circle.
The author believes that the rupture of the berry aneurysms as a cause of a subarachnoideal hemorrhage is one of the final events on the continuation of repeated burdens to subarachnoideal arteries, while various mural alterations of these arteries take place as a result of dysfunction of arterial wall movement over a long period.

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Arteries distributed to the head of the pancreas are morphologically clarified as dominated by the arterial arcade originating in two systems, namely the celiac trunk and the superior mesenteric artery respectively. In addition, they have complicated communication with the gastroduodenal artery in the upper part and the jejunal artery in the lower part.
Recently, many clinico-anatomical studies on the distribution of arteries distributing to the head of the pancreas have been conducted, using precised angiographic techniques. However, many controversial points should be clarified by fundamental anatomical studies. Thus, the author examined the pattern of distribution of arteries to the head of the pancreas by the corrosion-casting method in 30 Japanese fetuses and the following results were obtained.
1) Although most cases had 2 arterial arcades in the head of pancreas, one being the anterior arcade and the other the posterior, some had three arcades. The numbers of duodenal branches originating in the anterior and posterior arcades averaged 8 and 7, respectively.
2) The dorsal pancreatic artery was found in 80.2% of cases and it originated most frequently (44%) in the superior mesenteric artery. One case was peculiar in having its origin in the gastroduodenal artery.
3) The branches arising from the dorsal pancreatic artery and reaching the uncinated process anastomosed to the following arteries : (1) the upper jejunal artery in 3 cases, (2) the superior anterior pancreaticoduodenal artery in 2, and (3) the inferior mesenteric artery in one.
4) The arteries distributed to the uncinated process of the pancreas were supplied with blood from (1) the superior posterior pancreaticoduodenal artery or (2) the right hepatic artery originating in the superior mesenteric artery in 2 cases lacking the dorsal pancreatic artery.

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Twenty-six patients with HBsAg positive chronic hepatitis were treated for over 6 months with specific substance Maruyama (SSM) extracted from the cell wall of human tubercle bacilli.
HBeAg was found to disappear in 6 out of the 14 patients (42.9%) with positive HBsAg 10.0±7.4 months after the treatment began, and HBe seroconversion was found in 4 out of the 6 cases. A decrease of more than 2² in the anti-HBc titer (IAHA) was observed in 9 out of 11 patients (82%) positive for HBeAg, and in 2 out of 7 patients (29%) negative for HBeAg. None of the patients became negative for HBsAg, although a fall in titer was found in 3 out of 10 HBeAg positive patients. A transient rise in SGOT and SGPT coincident with disappearance of HBeAg was found 3 or 6 months after the start of treatment. These results suggest that SSM induces an immunomodulatory response and has a beneficial effect on HBsAg positive chronic hepatitis.

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Exocrine pancreatic tissues from 36 human autopsy cases of hemorrhagic shock and from experimental shock rats with 50% blood loss by cardiac puncture were studied by light and electron microscopic techniques. For rule out the possibility of the autolysis, experimental autolytic changes of pancreas were also investigated.
1) In the autopsy cases, the most common case of a fatal hemorrhage was from rupture of aneurysm (66%).
By light microscopy, all cases showed acinar anisocytosis and 21 cases (65.7%) showed some localized atrophic areas of acinar cells. But it was difficult to confirm any difference of interstitial changes between shock cases and controls.
By electron microscopy, marked dilatation and possible confluence of rough endoplasmic reticulums were observed associated with decrease of mitochondriae and zymogen granules in the above described atrophic areas.
2) In experimental cases, blood pressure soon fell to 30 mmHg after blood loss, then recovered gradually. The pancreatic tissues of the rats were resected in 0.5, 1, 2, 4, 16 and 24 hours after 50% blood loss.
By light microscopy, atrophy of acinar cells was observed in teleinsular areas at 0.5 to 16 hours after blood loss. But similar to the autopsy cases, there was not particular difference in interstitial changes between the shock cases and controls.
By electron microscopy, swollen mitochondriae (0.5-4 hours cases), dilatation of rough endoplasmic reticulums (2-24 h), lysosomal change containing degenerated mitochondriae, rough endoplasmic reticulums and zymogen granules (1-16 h) and the release of lysosomal degeneration products (0.5-24 h) were observed.
3) Finally above changes were confirmed to be not related with postmortem autolysis and it is concluded that these may represent the cardinal pathological changes induced by hemorrhagic shock per se.

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To clarify the pharmacologic action of a new antiarrhythmic agent, mexiletine (Mx), its electrophysiological properties were examined in guinea pig ventricular muscles at differing concentrations of extracellular potassium ([K⁺]o) and calcium ([Ca²⁺]o) using standard microelectrode techniques. The parameters measured were as follows :(1) the maximum rate of rise of phase O of the action potential (V_max), (2) the ratio of effective refractory period to action potential duration at 90% repolarization(ERP/APD₉₀) and (3) V_max recovery kinetics. The concentrations used were 2.7, 5.4 and 10.0 mM for [K⁺]o, 1.8 and 3.6 mM for [Ca²⁺]o, and 2μg/ml for Mx.
When the [Ca²⁺]o concentration was 1.8 mM, the rate of depression of V_max by Mx was 4.0±0.7% for [K⁺]o=2.7 mM, 4.2±1.6% for [K⁺]o=5.4 mM and 14.5±5.0% for [K⁺]o=10.0 mM, while the rate of increase in ERP/APD₉₀ ratios due to the action of Mx was 5.7±4.3%,
3.5±2.0% and 11.4±2.7% for the same concentrations of [K⁺]o. The changes in the V_max and ERP/APD₉₀ rate were not statistically significant for [K⁺]o concentrations between 2.7mM and 5.4 mM, but both rates were statistically significant with respect to the control [K⁺]p=5.4 mM values when [K⁺]o was 10.0 mM (p<0.01 in all cases).
On the other hand, the rate of depression of V_max by the action of Mx decreased to 2.8±0.8 when [K⁺]o=5.4 mM and to 5.7±1.6% when [K⁺]o=10.0mM and the [Ca²⁺]o concentration was increased from 1.8 to 3.6 mM. The rates of increase in the ERP/APD₉₀ ratio decreased when [K⁺]o was 5.4 or 10.0 mM (to 2.5±1.5% and 3.6±1.3%, respectively). The rate of change for V_max and ERP/APD₉₀ when [K⁺]o=10.0 mM (p<0.01) was statistically significant with respect to the control value [Ca²⁺]o=1.8 mM (p<0.001), but not significant when [K⁺]o=5.4 mM.
The recovery of V_max was markedly inhibited by Mx, but increasing the concentration of [Ca²⁺]o encouraged recovery and shortened its time constants.
In conclusion, the depression of V_max and increase of ERP/APD₉₀ induced by Mx were ascribed to its inhibitory action in the fast sodium channel. This depressant effect was regarded as the main antiarrhythmic action of this agent. Its electrophysiologic effects were pronounced at higher potassium concentrations. For this reason, Mx may be effective in the control of ventricular arrhythmias occurring in depolarized fibers of the acute myocardial ischemia. Additionally, increasing [Ca²⁺]o restored the "depressed fast sodium channel" induced by Mx.

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When hemorrhagic shock occurs, it is necessary to await the further clarification of its pathophysiology. This communication deals with a correlative study of the ultrastructure of the lung as well as the biochemical characterization of surfactant materials.
A particular attention should be paid to the ultrastructual changes of the micro-circulatory system in the alveo-capillary spaces. In fact aggregate and adherent of the platelets and white blood cells in the capillary wall would play a very important role in causing the "shock lung" and the careful investigation has been carried out in this context.
The results obtained are as follows :
1) The TBA reaction substance was increased, according to the interval of each shock, which appeared to correlated with the increase in number of the neutrophil in BAL.
2) The β-glucuronidase was significantly elevated in the serum, which appeared relavant to the degradation of alveolar macrophage according to the hemorrhagic shock.
3) The value of the lactate was significantly elevated, which was also associated with the deterioration of the alveolar capillary system.
4) The ultrastructual study revealed the striking alteration in the microcirculatory system in the alveo-capillary wall.
The transformed white blood cells were aggregated in the capillary and fused platelets were also aggregated in the vascular wall. The fragment of the endothelial cell lining was also discernible, suggesting the initial site of the membrane injury in the endothelial cells. The type II epithelial cells were also undergoing the degenerative changes which correlated with the decrease of the surfactant activity in virtue of the biochemical characterization.

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Intestinal iron absorption is recognized to be supported mainly by an active transport system, which requires energy consumption. Accordingly, it is reasonable to consider that Fe²⁺ or Fe³⁺ dependent ATPase activity may participate in intestinal iron absorption, as well as in the case of Ca²⁺ absorption, in which Ca²⁺ dependent ATPase plays an important role in the process. An attempt was made to identify the presence of Fe²⁺ or Fe³⁺ dependent ATPase in the rat intestinal mucosa.
Whole particulate suspension (WPS), from rat intestinal mucosa was used as the enzyme source. Eight mM ascorbic acid (Asc) or 1 mM citric acid (Cit) was added to the incubation mixture so as to prevent spontaneous oxidation of Fe²⁺ or hydroxylation of Fe³⁺ respectively. The increase of ATPase activities were apparently observed as the function of Fe²⁺ concentrations. The increase of Fe²⁺ dependent ATPase activities was higher in the presence of Asc than in no Asc condition.
Km values of Fe²⁺ ATPase activity were 0.4 mM or 5.3 mM ;in the case of Asc (+) or Asc (-) respectively, and there was statistical difference between these values (p<0.001). However, Fe³⁺ dependent ATPase activity was not observed in the presence of Cit in this system. The activities of Fe²⁺ dependent ATPase in the presence of Asc was approximately a half of Mg²⁺- or Ca²⁺-ATPase activities in WPS. But the dependency on metal ions was dominant for Fe²⁺ comparing to Ca²⁺ or Mg²⁺. Fe²⁺ dependent ATPase activity was not sensitive to Ouabain, theophylline and L-phenylalanine at the concentrations showing inhibitory effects. ³²P-phosphorylated protein was identified from WPS in the presence of [γ-³²P] ATP and Fe²⁺, and the molecular weight of the protein was estimated as 97, 000 by SDS polyacrylamide gel electrophoresis. These results suggested the presence of Fe²⁺ dependent ATPase in the intestinal mucosa.

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