Pathogenic effects of pathogenic E. coli are ascribed to a combined mechanism of two different pathogenic actions, namely 1 spreading capacity and 2 tissue-pathogenic activity.
Spreading capacity is represented by the capacity of bacteria to spread from an infant to another in the so-called closed circumstances. By periodical bacteriological examinations of the stool of infants in an orphanage, for example, it is sometimes noticed that some strains of E. coli spread very rapidly from an infant to another, but others do not. A pathogenic E. coli strain, carried into an orphanage, spreads rapidly among all infants, whether it causes diarrhea or not. However, some other E. coli strains, not obligatorily pathogenic, may likewise have such spreading capacity sometimes. The pathogenic effect of E. coli can not, therefore, be attributed to its spreading capacity alone, and some additional factor must be taken into consideration for a complete explanation of pathogenicity. Tissue-pathogenic action of pathogenic E. coli is assumed as such.
When those E. coli strains, possessing spreading capacity, reach the small intestine, passing the stomach, a rapid proliferation takes place. This proliferation is an important factor in the spreading capacity. E. coli strains, devoid of such proliferative activity, do not display a spreading effect at all. Pathogenic E. coli, proliferating in the small intestine, exerts tissue-pathogenic actions on the lining cells of intestinal wall, probably through a substance in the bacterial cells, either liberated in the intestinal cavity or bound to bacterial cell bodies. As a result, diarrhea is induced. At the same time, pathogenic E. coli cells flow down to the colon in an enormous amount, brought about by their proliferation, expel resident coli strains and settle there for a certain short period.

View full abstract

In order to elucidate the problems concerning the pathogenicity of “pathogenic” coli, the present work deals with the growth rate of the orally administered organisms, in comparison with that of “non-pathogenic” strains.
1) One of the pathogenic coli strains, O-111: B-4, administered orally to 20 adult volunteers, predominated the intestinal flora in their majority and caused mild diarrheain 10 cases.
2) In adults, “non-pathogenic” strains, when introduced from the outside, were suppressed by pre-existing intestinal flora. In infants, their multiplication was allowed only in a small number of cases, while in newborns their growth and persistence were confirmed invariably.
3) When a Streptomycin resistant coli strain was given orally, together with Streptomycin injection, it replaced pre-existing strains with its active proliferation and persisted in the intestine. The outcome was, however, different, when the pre-existing strains acquired Streptomycin resistance in a short time. They suppressed the exogenic strain, even when the latter belonged to “pathogenic” strains.

View full abstract

To understand the role of pathogenic coll in coll enteritis, the author and his co-workers have been engaged for several years in a comparative study of pathogenic and normal or non-pathogenic coll strains. The results are summarized as follows:
1) A strict and fundamental discrimination of the two coll groups was neither in their contagiosity nor in their persistence practicable, as indicated by the results of bacillus isolation from the feces of healthy and morbid examinees, consisting of infants, children and adults. The difference was merely a relative one.
2) Excepting 0-113, 126 standard strains out of E. coll 0-1 to 0-127, as well as isolated strains were seeded in a modified Andersen's synthetic medium, in which NH4Cl was substituted by various amino acids as the nitrogen source. The bacterial growth was determined photometrically.
i) Utilization of amino acids as the nitrogen source varied according to the kind of amino acids employed and to different o-antigen groups. Pathogenic strains tended to be associated with an intense utilization of amino acids. The results were regarded to be of importance, because some amino acids, such as glutamic acid, aspartic acids, etc., could be liberated in the small intestine as decomposition products of milk.
ii) Utilization of sugars as the carbon source exhibited likewise a remarkable variati on, according to the kind of sugars and strains. It was noteworthy, that only a small number of strains, including almost all pathogenic strains, could utilize sucrose (0-25, 0-26, 0-55, 0-111, 0-126, 0-127, etc.).
iii) These results indicated that the majority of pathogenic coll strains was endowedwith a greater advantage in the multiplication in the small intestine.
3) No definite relation was confirmed between the o-antigen groups and the hemolytic action of the bacilli on goat's erythrocytes, skin reaction in rabbits or the quantity of histamine or tyrarine as revealed by paper chromatography and indi cative of the activity of hitamine or tyrosine decarboxylase.
4) In view of fatty degeneration of the liver, reported in many autopsy cases of coll enteritis, experimental investigations were performed to induce degenerative liver changes in mice. Aqueous extracts of the standard strains of E. coll 0-1 to 0-127 as well as the isolated strains were injected intraperitoneally in an uniform quantity equivalent to 2mg. of the bacilli. The animals were sacrificed in 2 to 5 days, and the liver was examined histologically. The most remarkable fatty degeneration was induced by strains 0-11, 23, 35, 65, 66, 68, 81, 85, 99, 111, 112 and 120. Almost all liver cells were filled up with small fat droplets. The next most remarkable changes were those due to strains 0-3, 6, 8, 10, 16, 18, 20, 21, 26, 54, 55, 57, 58, 60, 62, 67, 71, 72, 80, 82, 83, 84, 86, 90, 93, 103, 105, 106, 107, 108, 117, 123 and 125. Strains 0-4, 13, 15, 17, 19, 22, 24, 27, 30, 32, 36, 41, 43, 61, 64, 60, 73, 74, 75, 78, 87, 97, 98, 100, 102, 104, 118, 119, 121, 122, 124, 126 and 127 caused remarkable, though somewhat slighter, fatty degeneration. The other remaining strains caused only slight, if any, or no fatty degeneration. It was noticed that the capacity of inducing fatty degeneration of the liver was by no means confined to pathogenic strains, though the majority of the latter caused the intensive changes.
5) Endotoxin was regarded to be the main factor responsible f or the pathogenicity of coll strains in coll enteritis.
6) o-agglutinin against normal and pathogenic coll was demonstrated in varying quantities in the sera of infants, adults and pregnant women.
7) Further investions from other points of view were required for the problems concerning the pathogenicity of coll strains.

View full abstract

1) Pathogenic coll bacilli were isolated in 18 (11%) out of 163 cases of sporadic diarrhea of infants. The well-known three types, o-Ill, 0-55 and 0-26 were demonstrated in 9 cases (5.5%). These three types could be recovered from the stool of the patients with monosymptomatic diarrhea or chronic dyspepsia. This indicated a close relation of pathogenic coll, especially of the three types, to acute sporadic dyspepsia.
2) Comparative examinations on the biochemical properties revealed a quantitatively higher ammonia production by pathogenic, than by normal, coll.
3) The bacterial flora in the stomach and the upper part of the intestine of infants and children was examined by means of the tube method. A close relation was confirmed between the increase of coll in the jejunum and the occurrence of diarrhea of inf ants, although none of the three types was found in the cases examined.
4) On the basis of the results of biochemical examinations, and in view of the close relationship between the coll in the jejunum and the diarrhea of infants, the f allowing conclusion would be warranted. More harmful effects are expected of pathogenic, than of normal, coll, when proliferation of the bacteria takes place in the digestive canal, so far as sporadic diarrhea cases are concerned, though the difference may be merely a relative one.

View full abstract

For the recent several years, the author has studied the pathogenic strains of E. coli, in collaboration with Dr. Hiroki of Kitasato Institute for Infectious Diseases and his co-workers. A part of the investigations is reported, especially on the epidemiology and symptomatology of coli enteritis in infants.
1) It is generally acknowledged, that 0-111: B4, 0-55: B5 and 0-26: B6 are distributed all over Japan and have hitherto been isolated mainly in the cases with diarrhea.
2) Two groups of healthy infants, consisting of 1018 and 1251 examinees, respectively, were examined for the above-mentioned three coli types in feces. The positive isolatio rate was 0% in the former, and only 0.2% in the latter, group. At that time, there occurred an epidemic of coli enteritis in our infants' home. At the time of the epidemic 88.5% of infants under a year of age and 45.7% of those over a year excreted pathogenic coli almost in a pure culture. About 30% of those, who discharged the bacilli, did not, however, exhibit any clinical disorder.
3) The clinical symptoms of gastroenteritis due to these pathogenic coli were silmilar to those of common diarrhea of infants. The severest symptoms were induced by the type O-111. The type O-26 caused in general relatively mild disorders.
4) Contrary to the above-mentioned results, which indicated a more remarkable persistence of coli in infants under a year of age, the examination of ambulatory patients demonstrated a higher rate of bacillus discharge in the older children over 1/2-1 year of age.
5) No marked seasonal fluctuation was confirmed in the frequency of enteritis due to these coli strains in our country.
6) Sporadic cases were not so rare in Japan as were assumed in the reports of other countries. They occupied 37.8% of total cases with this coli enteritis.
7) At the epidemic, which was experienced in the infants' home, the transmission of the bacilli took place mainly through bath water, diapers of children and the hands of nursing persons.
8) The incubation period in the above-mentioned epidemic ranged from 2 to 20 days approximately.
9) This coli enteritis was treated symptomatically and with adequate antibiotics. The prognosis of the cases, experienced by the author, was invariably favourable. No mortal case was observed.
10) The problems were discussed concerning the agglutination reaction with patients'sera of coli enteritis of the older children and adults, recurrence of persistence, superinf ec tion by coli strains in f ants, the coli enteritis of different types, mixed infection by several types of coli, the effect of protective inoculation and the prevention of transmission.
11) From the stool of infants with diarrhea several other types of coli were isolated, of which pathogenicity is at present suspected in Japan as well as in other countries. The isolated strains included 12 strains of O-86, O-25 and O-126, respectively, 5 strains of O-125, 8 strains of O-119 and 9 strains of O-124.

View full abstract

The sensitivity tests to sulfathiazol, chloramphenicol, Streptomycin and Terramycin were performed on 1, 444 strains of dysentery bacilli, isolated in Tochigi Prefecture from 1951 to 1953.
Resistent to sulfathiazol were 296 strains, including la, 1b, 2a and 2b, out of 368 strains isolated in 1951. No strain of Shigella sonnei exhibited a significant resistance.
The sensitivity to chloramphenicol was examined on 355 strains isolated in 1951. The growth of bacteria was observed in 7 strains (1.9%) only at a concentration of chloramphenicol below 0.5λ/cc, while 31 strains (8.6%), including 20 strains of Shigella sonnei, were not inhibited by 5.0λ/cc of chloramphenicol. The remaining 317 strains exhibited growth at a chloramphenicol concentration of 1.0λ/cc to 2.5λ/cc. In 1952, 520 strains were isolated, of which 35 strains (6.7%) grew only at a chloramphenicol concentration below 0.5λ/cc, and 96 strains (18%), including 56 strains of Shigella sonnei, were not inhibited even by 5.0λ/cc. The other 389 strains (74.8%) grew at a chloramphenicol concentration of 1.0λ/cc-2.5λ/cc. Out of 569 strains, isolated in 1953, 71 (12.4%) showed growth at a chloramphenicol concentration below 0.78λ/cc, and 78 (13.9%), including 70 strains of Shigella sonnei, were not inhibited by 6.25λ/cc. The other 419 (72, 8%) grew in the range of 1.56λ/cc-3.12λ/cc.
The sensitivity to Streptomycin was examined on 821 strains. The number of strains, of which growth was only permitted at a concentration of Streptomycin up to 12.5λ/cc, was 4 (4.4%) in 1951, 28 (10.4%) in 1952 and 34 (6.1%) in 1953. Streptomycin, even in a concentration from 50λ/cc to 100λ/cc, could not suppress the growth of 27 strains (30%) in 1951, 79 strains (29.4%) in 1952 and 116 strains (20.9%) in 1953. The remaining 623 strains grew at a concentration from 12.5λ/cc to 50λ/cc.
Resistent to Terramycin up to a concentration of 0.78λ/cc were 15 (2.7%) out of 542 strains, isolated in 1953. The growth of other 59 strains (10.8%), including 56 strains of Shigella sonnei, could not be inhibited even by 6.25λ/cc of Terramycin. The other 468 strains grew at a Terramycin concentration from 1.56λ/cc to 3.12λ/cc. Lower sensitivity to Terramycin was confirmed with 197 strains of Shigella belonging to the B-group, and with 17 strains belonging to the D-group, than with standard strains.
The above-mentioned results did not indicate a gradually elevated resistance of isolated dysentery bacilli to chloramphenicol, Streptomycin and Terramycin from 1951 to 1953.

View full abstract

Japanese encephalitis was diagnosed clinically in 132 patients, including 74 males and 58 females, in Hyogo Prefecture in the 3 years from 1953 to 1955. The epidemic began in June or July, reached its peak from the end of August to September and subsided practically in October. The age distribution was characterized by the predominance of children and young patients under 20, which was followed by the older patients over 50. Those between 21 and 50 of age were the least affected. The average case mortality rate ranged from 40 to 50%. The mortality rate was slightly higher in the female than in the male, and higher in adults than in children. In mortal cases the death occurred relatively early, within 10 days after the onset of the disease.
The serum could be obtained from 82 patients, and was examined for the complement fixation reaction of Japanese encephalitis. A positive reaction was confirmed with 29 (72.5%) out of 40 patients, whose blood could be examined not only at the initial stage of the disease, but also repeatedly thereafter with an interval of 7-10 days. On the other hand, only 6 (14.2%) out of 42 patients gave a positive reaction, whose blood examination was performed only once and within a week after the onset of the disease. The complement fixation reaction with the sera of encephalitis patients was negative in the great majority of cases up to the 7th day of disease, and turned to positive as a rule after the 8th day. The highest fiter of antibody was reached generally in about two weeks after the beginning of the disease.

View full abstract

Forty-nine specimens of cerebrospinal fluid were obtained from the cases, which were reported from 1953 to 1955 with the clinical diagnosis of Japanese encephalitis. The specimens were submitted to necessary tests, the results were evaluated in reference to the day of disease and correlated to the complement fixation reaction of the respective patient's serum.
The patients were classified into 3 groups according to the results of the complement fixation test. Group A represented serologically confirmed encephalitis cases with an elevation of antibody titers in the course of the disease. In group B the complement fixation reaction was negative at the initial stage of disease, and a further blood sample was not available for some reasons, but the diagnosis was supported by ample evidences in clinical symptoms, outcome of patients or autopsy findings. Group C was characterized by a constantly negative complement fixation reaction, not only at the initial stage, but also at the repeated blood examinations with 7 to 10 days' intervals. The serological reaction was, theref ore, not contributory to the diagnosis in this group.
The findings of cerebrospinal fluid in group A on the first 5 days of disease were as follows:
1) Appearace: waterly clear4l.0% waterly clear, but with the Tyndall phenomenonss. 3% waterly clear, but with fibrin flocculation when lei t to standl6.6% waterly clear, but with the Tyndall phenomenon and fibrin flocculation8.0%
2) Cells: maximum count 407/3 minimum count4s/3 They consisted mainly of lymphocytes.
3) Total protein maximum value4o mg/dl minimum valueio mg/di
4) Globulin reaction: Pandy reaction-l-Nonne-Apelt reaction-73% 9% 18%
5) Sugar: maximum valueioo mgidl minimum valueio mg/dl
6) Komagome reaction: potassium permanganate reaction + - Nile blue reaction+ -- 83.3% 16.6% 0%
7) a-Naphtol reaction: positiveii% negative2s%
8) Acetone bodies: maximum value8 mg/di minimum value4 mg/dl
9) Tryptophan reaction: negative in all cases

View full abstract

Brucellosis has been one of those diseases, which are hardly amenable to medical treatment. Attempts have hitherto been made by many investigators for the treatment of the disease, without any satisfactory result. The author investigated the therapeutic effect of several medicaments on experimental brucellosis of mice, infected with Brucella abortus Bang. Penicillin, Streptomycin, Aureomycin, Chloromycetin, Terramycin, Ilotycin, Achromycin a-d immune serum were administered either individually or combined to the experimental animals, after the lapse of a certain period following the infection. The treatment was carried out with varying doses and combinations of medicaments and in different modes of administration. The animals were sacrificed in a certain period after the accomplishment of therapeutic plans, and their organs were examined for bacteria and histopathological findings.
The results, summarized and compared in regard to the effect of applied therapeutic measures, indicated that a combined therapy with Aureomycin and Streptomycin was most effective, when they were administered for a long time by subcutaneous injection. The next effective was the combined therapy with Terramycin and Streptomycin. The therapeutic effect with these measures was then followed by that with Aureomycin, Terramycin and Ilotycin, given individually. Penicillin and the serum were ineffective, nor revealed Streptomycin, given singly, a definite therapeutic effect.
The results of the investigation would suggest a new principle in the therapy of brucellosis.

View full abstract

This was a case of chronic ulcerative colitis of a 26 year old female with clinical symptoms, rectoscopical, bacteriological, roentgenological and autopsy findings characteristic to the disease. Antibiotics, cortisone, ACTH and other medicaments were employed in the treatment without any satisfactory result. The antibiotics were regarded to be the cause of a cross infection of the chest observed in this case. The ineffectiveness of antibiotic therapy, together with the neurotic symptoms in this patient, suggested a psychoneurological origin of the disease. Lobotomy would reasonably be taken into consideration in the therapy of this disease, as reported by Levy.

View full abstract