Multiplication of orally taken organisms in the intestines has been widely discusseed in order to study the onset of intestinal infectious diseases.
As to the most fundamental aspects of this problem the following experiments were carried out.
(1) Separate cultures of contents of the stomach, the jejunum, the ileum and the transverse colon acquired by laparotomy at one and a half hours and 4 hours after oral administration of Escherichia freundii, Ballerup strain, resistent to 2500 r/ml of streptomycin, to different dogs revealed the following results. With no exceptions, in three cases of the one-and-a-half-hour group, the given organisms were all proved to remain in the stomach and the jejunum, while in the 4-hour group they were discovered to move down to the ileum and the large intestines and none were found in the upper tracts.
(2) Cultures done specimens taken at frequent intervals for 24 hours after direct injection of the same strain to the stomach by laparotomy under intravenous anesthesia with Ravonal revealed that the given organisms remained in the stomach and the jejunum all through 24 hours.
(3) When the organisms were injected to the ileum in the experiments similar to Part 2, they were proved to stay there at least for 6 hours.
(4) In several cases of experiments (1) and (2), organisms labelled with Isotop P₃₂ were administered, confirming the parallel relationship between the number of the living organisms and the degree of the radioactivity in the acquired specimens. However, since the number handled here was limitted, further investigations will be necessary to reach a definite conclusion in this matter.
In conclusion through these experiments it was felt that when normal peristalsis was maintained, orally taken organisms were transfered at considerable speed and that if peristalsis was diminished they either remained in the same place for a long period or was transferned extremely slowly.
Therefore, paralizing intestines is one of the useful means of transplantation of certain organisms in a proposed portion of the intestinal tracts.

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Causative agents of food Poisoning, diarrhea and enteritis experienced from 1955 to 1959 in Tochigi district were investigated. Out of 6 cases of food poisoning S. potpdam was incriminated in 2 cases (3 strains), S. Narashino in 1 case (1 strain), S. enteritidis in 1 case (17 strains) and S. sengtenberg in 2 cases (4 strains), respectively.
From 68 cases of diarrhea and enteritis 4 strains of S. enteritidis (5.9%), 6 strains of Shigella (8.8%)(Sh. flex. 2a 2 strsins, 2b 2 strains, 3a 1 strain, Sh. son. 1 strain), 36 strains of Bethesda group (52.9%) and 3 strains of Ballerup group (4.4%) were isolated.
From 52 patients with dysenteric signs and symptos from whom, however, no strain of Shigella was recovered, 1 strain of S. enteitidis (1.9%), 23 strains of Bethesda group (44.2%), 1 strain of Ballerup group (1.9%), 5 strains of Alkalescens-Dispar group (9.6%) and 1 strain of E. coli 0-124 (1.9%) were isolated.
From 324 healthy persons, 7 strains of Shigella (2.2%)(Sh. flex. 2a 2 strains, 2b 1 strain, 3a 3 strains, Sh. son. 1 strain), 91 strains of Bethesda group (28.1%) and 7 strains of Ballerup group (2.2%) were isolated. The isolation rate of Citrobacter (Bethesda-Ballerup group) was rather high even in the group of healthy persons. In the group of diarrhea and enteritis patients, however, it was still higher, which made the pathogenicity of the agent quite probable.
The sensitivity of Salmonella, Shigella, Citrobacter, Alkalescens-Dispar and E. coil 0-124 isolated against CP, SM and TC ranged from 3.13 to 25.0 riml, the sensitivty 12.5 r/ml being most frequent. The resistance over 100 r/ml, was observed in 1 (3-antibiotics-resistant) of 13 strains of Shigella and in 4 (2 3-antibiotics-resistant strains and 2 TC-single-resistant strains) of 150 strains of Bethesda.

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The Progress in experimental dysentery has not been remarkable, recently however, there have been several investigations using cortison, opium, antibiotics, liver-toxin and starvation which may increase susceptibility of the host or decrease resistance to the dysentery infection.
Starvation is applied in this experiment as pretreatment to produce experimental shigellosis. Through the study of persistence of shigella in intestinal tract of mice, efforts were made to understand the mechanism of onset of dssentery.
1) As for host factors, resistance of mice, lesions of liver and changes in the intestinal flora during the starvation were studied. The starvation period is limited within two days, because most of the mice do not tolerate longer fasting period.
Fatty degeration was found in the liver of the starved mice, and this suggested that some change in the intestinal physiology might be occurring.
From these findings, it was concluded that the intestinal flora might be deranged and distribution of gram positive cocci and gram negative bacilli in intestines was, changed as the starvation went on,
Mice which were starved for two days were administered a streptomycine resistant strain of shigella flexneri 2b for three days by stomach-tube.
In this experimental group and in the streptomycine-pretreated group, the excretion period of shigella was prolonged. However, the percentage of positive stool culture in. the starved group (% of positive stool culture =number of positive stool culture/number of stool cultur was distinctly higher than that of the streptomycine-pretreated group.
2) In order to understand Parasite-factors resistant strain and sensitive strain ofshigella flexneri 2b were administered to the streptomycine-pretreated group, to the starved group, and to the untreated group.
Excretion period of shigella flexneri 2b was prolonged in the former two groups. Furthermore in the control group the resistant strain was longer excreted than the sensitive strain.
On the contrary, in the pretreated group excretion period of sensitive strain was longer than of resistant strain. Also, the percentage of positve culture in treated mice which were administered the sensitive strain was high.
Whether the strain which persisted for a long time in mouse intestine has any ability to multiply in mouse or not, was not proved.
3) Persistence and proliferation of the pathogenic bacilli in the intestine of mice are more frequently observed in the animal with few intestinal flora and this phenomenon is enhanced by the streptomycine treament and especially by the starvation.

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The purpose of this paper was to determine the influences of steroid and/or Antibiotics upon infection.
istological investigation was performed after cortisone and/or penicillin were admimistered to the rabbits, infected with Pneumococci.
Results were as Follows.
1) Among the group treated by cortisone alone, inflammation was not limitted locally but tended to show phlegmonous spread although cellular infiltration, loosening of collagenous Fibers by serous exsudation were not marked in comparison with the control group.
This tendency was more marked in the group treated with cortisone before the challenge than the one treated after the challenge.
Bacteria was seen spread in all layers of the skin until 96 hours in the group treated with cortison alone.
2) Among the group treated with cortisone and penicillin, minimal cellular infiltration, hyperemia and hemorrhage, almost no loosening of collagenous fibers and no necrosis were noted in comparison with the group treated with penicillin alone.
In short, not noly the inflammatory response was minimal but also bacteri disappeared at an early stage just like the group treated with penicillin alone.
3) The combined use of cortisone and penicillin is a) As to the dosage of cortsone and penicillin, 25mgm of cortisone were more effective than 0.5mgm of cortisone and better results were obtained with 50.000 u. of penicillin than with 1.000 unit.
b) As to the mode of administration, the group in which cortisone was combined with penicillni after the challenge showed better results than the one in which cortisone was admimistered before the challenge.
c) As to the schedule of administration, better results were obtained histologically by the administration at an early (acute) stage of the infection in which the inflammatory responses in tissue would appear.

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Sigmoidoscopic examinations, and suction and quantitative culture of rectal mucus were carried out for 402 patients and 268 carriers of bacillary dysentery.
The results were summarized as follows:
I. Sigmoidoscopic findings on symptomatically treated patients showed that the lesions reached peak on the 4th day and that in the majority of the cases the lesions remained until the 3rd to 4th week. It was observed that in delayed cases of Shigella excretion the lesions were severer than in those discharging no Shigella.
2. From the standpoint of healing of lesions, Chloramphenicol and Tetracycline were more effective than Streptomycin, Kanamycin and Colistin, especially differnce of healing was demonstrated clearly at the end of the 3rd week.
3. To quicken healing of the lesions it was necessary to use antibiotics as soon. as possible and to continue antibiotic treatment at least for 5 days.
4. Lesion-rate of rectal membrane of the carriers was 49.1% in 171 cases of healthy carriers and 60.8% in 97 cases of convalescent carriers.
5. In the carrier cases a close correlation was recognized between healing and Shigella excretion. Ninty-five-point-six percent of the healed cases no longer excreted Shigella and 29.4% of the non-healed cases continued to excrete.
6. The suction culture method of rectal mucus is more reliable for Shigella isolation technique than the rectal swab or fecal culture method.
7. It was also demonstrated that the quantitative culture method of rectal mucus is a satisfactory method for the measuremest of Shigella excretion.

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Cl. chauvoe appears in tissues and cultures as a straight, roundended rod measuring-about 0.6 X 3-8μ. It usually appears singly, and this fact is useful in distinguishing it from Cl. septicum and other anaerobic bacilli which frequently occur in materials suspected of blackleg which is similar to gasgangrene in human beings. Cl. septicum usually occur in long chains or in long filament. Spores are oval and appear excentrically, swelling the rods into lemon-shaped structures. Very young cultures are motile by means of pertrichic flagella. It is strictly anaerobic and will not grow on ordinary glucose agar. The addition of blood or tissue makes ordinary broth and agar favorable for it. It grows well on all media made with a liver extract but not luxuriantly.
Deep colonies in tube agar are delicate and compact, being lensshaped. In liver-liver broth the fluid becomes moderatly clouded. Gelatin containing a little serum is slowly liquefied, and a few gas bubbles are formed. Acid and gas are formed from glucose, levulose, galactose, maltose, lactose, and sucrose. Inulin, mannitol, glycerol, rhamnose, and dulcit are not fermented. All strains produce antign for agglutination, which. is kowever not shared with Cl. septicum.
This organism exists in the soil, and when pastures or grazing grounds once contaminated with it, it will infect ruminants, susceptible to the diseasease especially cattle year after year. The disease seems to be a wound infection and to be similar to gasgangrene in human beings.
In rare cases, some strains form R type colonies in tube agar, which are very simiar to those of Cl. septicum, and it is very difficult to distinguish them from Cl. septicum from the point of the shape of colonies, and the characters of R type is not. clarified yet. Therefore, the author made a variant of Cl. chauvoei, R type, by means of serial passage through liver-liver broth added with acriflavin and compared the characters and pathogenecity between S type and R type straits.
1) Artificial variation of chauvoei.
Virulent strain Hokkaido (II) or Okinawa (0) was cultivated in liver-liver broth added with acriflavin at 0.01% for 72 hours at 37°C, thereafter a drop of cultivated. broth was poured in tube agar. A deep colony in the tube agar was fished and inoculated. in acriflavin-added liver-liver. broth. Thus, the cultivation was carried out alternately and S type colonies variated to R type. In case of the strains O.R type, colonies of 30-80 generations of serial passage and in case of the strains H.R type, colonies of 50-110 generations were used for experiments. The former was named as O.R and the latter H.R.
2) Bio-chemical charactrs of R type organisms.
a) R type colnies of both strains are very similar to those of Cl. septicum, and the organisms occur in long filament like Cl. septicum.
Spores were not readily formed. The organism dcmonstrated a lesser degree of resistance to the heating and survived for a shorter in refrigerator than S type. Even young cultures became much less motile suggesting the loss of flagella
b) There is no difference in fermentation of sugars between S type and R type, but only strain H.R lost its coagulability of milk.
3) Sero-reaction in case of R type.
Original strains 0 and H, and variant strains O.R and H.R were used for making: antiserum by means of hyperimmunization against rabbits. In addition to these strains, . Cl. septicum was used to prepare hyperimmunized serum to compare the antigenicity of both bacilli.
a) Stype organisms (O and H) could not absorb the and-R serum completely leaving a part of antibody unabsorbed R. type organisms showed simiar results. Namely, it might be said that R type organisms lost a part of S type and was shared with other antigen.
b) R type organisms showed a decrease of the ability in producing antibody in rabbit and of agglutinability in contrast to the S type organisms.

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Among various sugars, glucose demonstrated the strongest indol-production inhibiting activity. Galactose added with minimal amounts of glucose also demonstrated almost the same degree of activity. The inhibition of indol-production was quantitatively investigated with the sulfamine-and streptomycin-resistant strains in comparison with their original strains, in order to study the influence of these drugs on the sugar metabolism of the latter.
The degree of inhibiting activity was measured from the turbidity of both culture fluids added with sugar and not added with it in which a certain amount of each strain was cultivated for 24 hours.
Indol was spectrophotometrically estimated by adding Ehrlich's reagent to the culture fluids and heating them for 30min. at 30°C and using the some fluid previously added with formalin as the blanc. The results were as follows:
Sulfamine-resistant strains demonstrated almost the same degree of the indol-production inhibiting activity as the original strain, while majority of the streptomycin-resistant ones showed a great deviation, hindering from slightly to strongly the activity and only 2 of the 43 strains tested demonstrated the same degree of activity as the original one.
It was concluded by the author that sulfamine hardly influenced the sugar metabolism of E. coli, whereas streptomycin greatly hindered its metabolism.

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The renal plasma flow (RPF) and glomerular filtration rate (GFR) were measured according to Smith' s standard method of kidney clearance with sodium-paraamino-hyppurate and sodium-thiosulfate respectively, in order to study renal circulatory changes, in acute infectious diseases.
Renal disorders may occur, as is well known, in the acute as well as in the convalescent stage of acute infectious diseases, originating probably from differentpathogenetical moments. Accordingly, renal circulatory changes in the acute stage were first studied by the author, with 10 cases of scarlet fever without any complications, 5 cases of typhoid fever, 2 cases of bacterial dysentery, 2 cases of Ekiri, . 1 case of angina lacunalis acuta accompanied by focal nephritis, 1 case of mumps meningitis and 1 case of lobar pneumonia affirmed by postmortem studies. For the: second time, renal circulatory changes in the convalescent stage studied with 8cases, of scarlet fever with convalescent albuminuria. The following results were obtained
A) Renal circulatary changes in the acute stage.
The following common tendencies were found regardless of the kind of the diseases.
1) A fall of RBF and RPF vaules was observed.
The average degree of reduction in 10 cases of scarlet fever was 70% that of the convalescent value. In some of them, the RPF value dropped even to 50% their conva lescent value. Ekiri demonstrated the highest reduction, the drop of RBF being 14% of it's convalescent value.
2) No definite tendency of GFR value was seen, decreasing in some cases and increasing in the other.
3) An increase of FF value associated with a decrease of RPF was always observed.
FF value reached in some cases an extraordinarily high level (0.4-0.5).
4) No correlation was seen between renal circulation and Hct value, body temperature, blood pressure, urine findings and urine amount per minute. The clinical fi ndings likely to influence the renal circulation were only marked exanthema of scarlet fever, severe diarrhea of dysentery, high body temperature of typhoid fiver and disturbance of consciousness in Ekiri, in all of which a change of the systemic blood distribution was supposed to occur.
5) Consequently, no organic injury of the kidney appeared to play a major role: in these circulatory changes.
6) It was also considered that the increase of FF value did not result from organic changes of the kidney but from physiological processes of the intrarenal autonomous regulation.
The extraordinary increase of FF value led the author to the assumption of a possible existence of the juxta-medullary shunt.
7) As for the extraordinary reduction of RPF value in Ekiri, a severe constriction of renal artery system was supposed. In the view point of biological reaction, the constriction of renal artery on Ekiri was considered to be an excessive one far from an adaptation reaction, while in the other acute infectious diseases, the RPF reduction appeared to represent a passive adaptation reaction.
8) A case of angina lacunalis acuta accompanied by hemorrhagic focal nephritis did not demonstrate any characterictic deviation from the above mentioned mode of renal circulatory changes in the acute stage.
B) Cases of scarlet fever with convalescent albuminuria
1) These cases with clinical findings characteristic of acute glomerular nephritis showed a marked reduction of GFR and FF value, but no such of RPF value. This mode of renal circulatory change is the same as that of the common acute glomerular nephritis. No peculiarity as scarlet fever was observed.
2) The above tendency of renal circulatory changes was entirely different from that in the acute stage of infectious diseases.

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