It is known that acute viral hepatitis is very common among sojourners in developing countries. In order to conduct effective health control, epidemiological studies were made on viral hepatitis which occurred among Japanese staying in developing countries, and evaluations were carried out on preventive measures.
The subjects of present study were a group of Japanese people staying in developing countries for two years. Mid year population of the group was 1732 in 1988. Period of the present study is ten years from 1979 to 1988. The study was conducted based on the reports from offices ices in each country, survey trips and serological studies on the subjects.
In 1979, frequency of hepatitis A (HA) was very high showing 79% of total hepatitides. However after starting of inoculation of human immune serum globulin (ISG), the frequency of HA declined remarkably. Statistical significance was recognized in the efficacy of ISG.
Among 35 cases of hepatitis B (HB) (34 males and 1 female), 2 derived from HBe antigen carrier while the remaining 34 were regarded as infected during their stay in developing countries. No cases of HB were recognized among those who received injections of HB vaccine. The rate of people whose HB marker turned positive during their stay is showing a tendency of increase (4.2% in 1987). The frequency of infection with HB virus is especially high in Asian and African countries where the carrier rates of native people were also high.
Ten cases of non-A non-B hepatitis were recognized. Among them 7 were infected in Asia, 1 in Africa and 1 in Central America. The route of infection of the most of the cases were regarded as oral one.
When Japanese people stay in developing countries, the danger of contracting acute viral hepatitis is high. As preventive measures, inoculation of ISG is effective against HA as well as paying attention to food and drinks. The changes of infection with HB virus is also high. As routes of infection, sexual intercourse is considered to be important as well as medical practices. The efficacy of HB vaccine to those who stay in developing countries was confirmed.

View full abstract

The IgM and IgG antibody capture methods of the enzyme-linked immunosorbent assay (ELISA) for human parvovirus B19 were performed using Horseradish peroxidase (HRPO)-labeled anti B19 monoclonal antibody.
Serially obtained serum samples from one erythema infectiosum (E.I.) patient were examined at once by this methods. The dOD values of the IgM and IgG antibodies decreased on the typical curves according to the course of recovery.
In the epidemic case of E.I. among students of one nurse school, 1) The first patients was estimated by comparing the change of dOD values of sera obtained at end of the epidemic and 1.5 months later. 2) In the pre-existing antibody positive persons, the dOD values of IgG antibody did not changed during the epidemic. 3) After the E.I. epidemic, and approximately 30% of the students were remained uninfected.

View full abstract

It is well known that erythromycin (EM) therapy is effective on chronic lower respiratory tract disease, including diffuse panbronchiolitis (DPB). In this study we investigated the relationship between clinical findings and neutrophil chemotactic activity (NCA) in bronchoalveolar lavage fluid (BALF) in patients with DPB receiving orally EM therapy.
The NCA in post-EM therapy BALF was significantly reduced (p<0.001) compared with that in BALF before EM therapy (30.17±7.84% vs 53.05±10.65%).
On the respiratory function before and after EM therapy, DPB patients (20 cases) showed significant improvement of %VC, FEV1.0, RV/TLC (p<0.001, each) and V₂₅ (p<0.05). And on the post-EM therapy blood gas, PaO₂ and AaDO₂ level were confirmed to be significantly improved (p<0.001). In addition, we examined the correlation between the improvement ratio of clinical finding and the reduction of NCA in BALF after EM therapy in 10 patients with DPB. We found the significant correlation between the improvement ratio of PaO2 and the reduction NCA in BALF of those patients (p<0.05). There were no significant relationships between the improvement ratio in other parameters as stated above and the reduction of NCA in BALF.
These findings indicate that EM restrains the NCA in BALF of patients with DPB and impairs the accumulation of neutrophils in respiratory tract, ultimately contributes to the improvement of clinical symptoms such as sputum and clinical findings such as PaO₂ in patients with DPB.

View full abstract

During a three-year period (1987 & 1990), a comprehensive attempt was made toisolate verocytotoxin-poducing Escherichia coli (VTEC) from 96 bovine, 89 porcine, 67canine and 18 feline cases suffering from gastroenteritis. VTEC were isolated from 11 cows and 1 cat. Bead-ELISA and oligonucteotide probes were used to type the verotoxins (VT) and it was foundthat the VTEC strains from cows produced not only the currently recognized VT1, VT2 and VT2vh but also produced two new VT's tentatively designated as VTx and VTy. The strain from the cat produced VTy. Serotyping of the strains revealed that some animal strains belonged to similar serotypes as those isolated from human patients with hemorrhagic colitis and hemolytic uremic syndrome. Cattle, especially cows, and domestic pets apparently are reservoirs of VTEC and probable sources of infection in our country as has been previously documented in Canada and USA.

View full abstract

For the differentiation of Shigella from Escherichia coli, Indole (tryptophanase), PGUA (β-glucuronidase) and ONPG (β-galactosidase) tests were used.
A total of 377 Shigella and 124 E. coli strains was examined for each sero-and biosero-type by using these tests.
The results were as follows.
1) There were no Shigella strains showing positive reactions for both Indole and ONPG tests
2) No E. coli strains with Shigella-like characteristics (negative for lysine-decarboxylase, motility and lactose-fermentation tests) showed negative results for both Indole and PGUA tests
3) The abovementioned strains were classified into twelve types according to the results of these tests.
Shigella strains, thus, were differentiated from antigenically Shigella-like E. coli strains.
Additional use of these tests together with the conventional methods may valuable for the identification of Shigella strains.

View full abstract

Four strains of Escherchia coli O114: non-motile (NM) were isolated from patients supposed to have endemic diarrhea in 1989. The plasmid DNA profiles and restriction fragment patterns of chromosomal DNA digested with Not I analysed by pulsed-field gel electrophoresis (PFGE) of E. coli O114: NM strains were compared with those of other 9 strains of E. coli 0114 isolated elsewhere (O114: H2, 1 strain; O114: H4, 2 strains; O114: H9, 2 strains; O114: H10, 1 strain; O114: H11, 1 strain; O114: H21, 1 strain; O114: H32, 1 strain).
All of E. coli O114: NM strains showed the same plasmid DNA profile and chromosomal DNA fragment patterns. The strains of E. coli O114: NM and O114: H11, and O114: H21 and O114: H32 showed the same plasmid DNA profiles, respectively. On the other hand, these strains could be differentiated by the chromosomal DNA fingerprint patterns. The chromosomal DNA fragment pattern of allE. coli O114: NM strains is completely different from thoseof the other 9 control strains.
We suggest that chromosomal DNA fingerprinting is useful for the epidemiological study of E. coli 0114 associated endemic diarrhea.

View full abstract

[in Japanese]

View full abstract

Isolation of Chlamydia pneumoniae and serologic tests were performed on 85 children and adults patients with acute bronchitis admitted to the Kitasato Institute Hospital from January 1989 to May1991. C. pneumoniae was isolated from sputa or tonsillar swabs in 11 of 57 (19%) patients examined. Of these, 10 patients were tested serologically and 9 (90%) had 16 or higher titer of IgG antibody. A total of 68 patients were tested serologically, and 17 (25%) revealed positive; 14 had a fourfold rise or more in the titer of IgG antibody, or IgM titer of 16 or more, and 3 had IgG antibody with a titer of 512 or greater. In 34 patients, sera were tested for evidence of acute infections not only with C. pneumoniae, but also with Mycoplasma pneumoniae, influenza A virus, influenza B virus, adenovirus, respiratory syncytial virus, coxackie A9 virus, parainfluenza virus type I, II, and III. Two of the 34 patients were associated with influenza A virus, 4 with influenza B virus, whereas 6 were associated with C. pneumoniae. The data available suggest that C. pneumoniae cause bronchitis much more than has been suspected, and also confirm earlier suggestions that the agent played an important role in respiratory tract infections.
Chlamydia trachomatis was recovered from sputa and tonsillar swabs in 6 adults patients with acute bronchitis. Studies are needed for a better understanding of the epidemiology and clinical relevance of this microorganism to lower respiratory tract diseases in adults.

View full abstract

We carried out cloning of RD cells and obtained cloned cell line RD-9H8, which is highly sensitive to enteroviruses.
Cytopathic effect (CPE) of RD-9H8 cells was more remarkable than that of original RD cells.
The RD-9H8 cells were used to measure the neutralizing antibodies to coxsackievirus group B in sera from 93 medical students collected in Oct. 1990 at Iwate Medical University.
The proportions of confirmed positive sera were coxsackievirus type B1 44.1%, type B2 50.5%, type B3 46.2%, type B4 64.5%, type B5 53.8% and type B6 4.4%.

View full abstract

Chlamydia trachomatis (C. trachomatis) is 0.4-0.5μm in diameter in the EB stage, with the nucleoid located eccentrically within it. We studied the relationship between the eccentric nucleoid and the host cell surface under electron microscope, when C. trachomatis was in adhesion to the host cell and during and after invasion into the host cell.
When C. trachomatis adheres to and invades a host cell, the eccentric nucleoid is located on the side distant from the host cell surface (44 of 66, 66%). The 1×3 chi-square test indicates that the difference is significant at p<0.001.
After C. trachomatis invades a host cell, the eccentric nucloid is located on the side close to the host cell surface (61 of 138, 44%). The 1×3 chi-square test shows the difference to be significant at p<0.001.
However, since the latter (44%) is less than the former (66%). C. trachomatis revolves between adhesion and the completion of the invasion. The 2×3 chi-square test shows a significant difference at p<0.001.

View full abstract

An attempt was made to measure the antibody to rubella virus in human sera by ELISA by calculating the relative potency by the method of the parallel line assay. As a standard serum, adult serum 8 months after rubella infection was used. Sample sera were collected from 42 infants before MMR vaccination and 8-10 weeks after the vaccination and 48 adults three years or more after rubella vaccination. In addition, three infant sera with rubella 6-19 days after onset of rash and three gamma immunoglobulin products were used. The dose response curve of the standard serum and that of the sample serum showed the lineality and the regression line of the sample serum was parallel to that of the standard serum. And the relative potency of sample sera was successfully calculated.
The good correlation was observed between the rubella antibody titer by hemagglutination inhibition test and that measured by ELISA. The coefficients of variance of relative potency obtained from four repeated measurements for two weeks showed from 15% to 25% in four sera of HI high titer. The reproducibility of parallel line assay was also satisfactory.

View full abstract

Five Shigella strains isolated from stool cultures of two domestic dysentery cases and three imported cases in Tokyo in 1986-1989 had an atypial serotype that agglutinated with only antiserum to S. flexneri group 6 factor antigen. These strains showed typical biochemical reactions of S. flexneri and were biochemically identical. Four of the strains were positive for Sereny test with guinea pig eye and the cell-invasion test with HeLa cells. The strains also had the virulence-plasmid encoding outer membrane proteins, indicating that these were pathogenic.
These strains were serologically identical and gave significant cross-reactions with S. flexneri lb and 4b that had group 6 factor antigen. However, results of reciprocal absorption tests showed that the 0 antigen of these strains were not identical to S. flexneri lb and 4b, and were confirmed to have a new type antigen which can not be included among the known S. flexneri type antigen I-VI.
Strain 88-893 is designated as the test strain for this new type antigen of S. flexneri.

View full abstract

We experienced a case of a 68-year-old female with β-lactam antibiotics including penicillin G (PCG) resistant pneumococcal pneumonia, leading to death during the treatment with ceftizoxime (CZX). We reported the clinical course and the mechanism of resistance of isolated bacteria. The present case is the first in Japan.
Minimum inhibitory concentration (MIC) against Streptococcus pneumoniae 88031 isolated from the present case was 1.56μg/ml in PCG and 6.25μg/ml in CZX, showing PCG resistance. The isolate was no β-lactamase production and serotype 23.
The drug susceptibility in 34 strains of S. pneumoniae which were isolated as causative organism of respiratory infection in our department in 1988 was studied. PCG high resistant strain (PCGMIC>1.56μg/ml) was only observed in the isolated strain in the present case and PCG low sensitive strains (PCG MIC=0.1-1.0μg/ml) were observed in 3 strains (8.8%). The CZX resistance was observed only in the present case.
The detection of penicillin-binding protein (PBP) and binding affinity of μ-lactam antibiotics were studied using PCG sensitive strain, S. pneumoniae type I (preserved strain PCG MIC=0.05μg/ml, CZX MIC=0.1μg/ml, CMX MIC=0.025μg/ml) and PCG resistant strain, S. pneumoniae 88031. The result obtained showed that PBP1a, detected in sensitive strain type I, was not detected in resistant strain 88031 and PBP1b was increased. The binding of ¹⁴C-PCG of PCG resistant strain to PBP1b showed lower affinity for CZX and CMX than PCG sensitive strain.
From the above observation, it was suggested that the decrease in drug sensitivity of β-lactam antibiotics resistant S. pneumonia 88031 was caused by the variation of PBP1b.

View full abstract

The antifungal effects of amphotericin B (AMPH) and flucytosine (5-FC) on three strains of Candida albicans were studied by flow cytometry (FCM).
When the IFM4954 and IFM4949 were treated with AMPH or 5-FC alone, cytograms of cell distribution changed at the concentration of 1/2 MIC, respectively.
Next, the effect of combination of AMPH and 5-FC were examined. Cytogram of cell distribution of IFM4954 and IFM4949 changed under the combination of 1/4 MIC of AMPH and 1/4 MIC of 5-FC, namely a synergic effect was observed.
In conclusion, FCM is a useful apparatus for analysis of the effect of antifungal agants.

View full abstract

In order to clarify the in vivo effect of the new quinolones in the urinary tract, we investigated the antimicrobial activities against Escherichia coli in the human urine. Human urine was prepared from a normal volunteer. After cations were removed by chelating resin, human urine was supplemented with 50, 100, or 500 pg of Mg2+ per ml using MgCl₂ or 10, 50, or 150μg of Ca²⁺ per ml using CaCl2. The pH of human urine was adjusted to 5.5, 7.0, or 8.0 with HC1 or NaOH. Four clinical isolates of E. coli and E. coli NIHJ JC-2 were used. And antimicrobial activities of the new quinolones (norfloxacin, enoxacin, ofloxacin and ciprofloxacin) against these strains were measured using various urines as mediums. Antimicrobial activities of the new quinolones were reduced in the presence of high concentration of magnesium or low pH of urine. However, there was no influence of calcium concentration of urine on antimicrobial activities of the new quinolones. From these results, the component of the urine should be checked in the treatment of the patients with urinary tract infection.

View full abstract

The effectiveness of a single 300-mg dose of tosufuloxacin and of 3-day treatment with tosufloxacin (300mg daily) were compared in a prospective trial in order to clarify the costeffectiveness of tosufloxacin for acute uncomplicated cystitis.
Fifty female patients (25 patients of each group) with acute uncomplicated cystitis received one of these treatment regimens, and the clinical data and follow-up culture results were analyzed.
The effectivenes rates of single-dose treatment and 3-day treatment after 3 days were 100% and 96%, respectively. The recurrence rates of single-dose treatment and 3-day treatment after 14 or 28 days were 0%(0/13 patients) and 15%(2/13 patients), respectively. There was no significant difference in the effectiveness rate and the recurrence rate between these two groups, statistically. All isolated strains were eliminated in both regimens.
From these results, it is suggested that single-dose treatment of tosufloxacin is effective enough for acute uncomplicated cystitis.

View full abstract

A 53-year-old male was admitted to the hospital because of Candida albicans endocarditis. He had had a thoracoplasty due to pulmonary tuberculosis and showed severe restructive lung function. In 1987 and '89, trachiostomy was made because of respiratory failure. The patient was well until nine months earlier, when he consulted a physician because of fever. The investigations failed in finding the cause of the fever. He was administered antituberculosis agents and antiinflammatory drugs but had a fever every day. Two months before admission, a cardiac ultrasonographic study showed evident vegetations with mitral regurgitation. From the above course and examinations, a diagnosis of Candida albicans endocarditis was made. Infusions of CEZ, TOB, PIPC and miconazole for more than one month was ineffective. In November, 1990, he was referred to our medical center for the purpose of operation. A blood culture proved Candida albicans infection. An intravenous administration of fluconazole 400mg/day was begun. However, there was pulmonary bleeding probably due to heparin used for prevention of atrial thrombosis and he developed fever, hypoexemia, ventricular tachycardia, and hyponatremia. He underwent mitral-valve replacement with a SJM valve. Culture of the vegetated mitral valve again proved Candida albicans. After operation, hypoexemia, ventricular tachycardia, hyponatremia were improved gradually. However he had an eosinophilia, eruption, and dyspnea. We suspected a drug eruption of fluconazole. Lymphocyte stimulating test of fluconazole proved positive. After the episode, he had no symptoms and was discharged.

View full abstract

Disseminated aspergillosis is most likely to develop in neutropenic patients with cancer, particularly in those with acute leukemia receiving intensive chemotherapy. Aspergillus has a special affinity for blood vessels. However, hematogenous miliary spread, such as seen in disseminated tuberculosis, only rarely occurs, as compared with the thrombosis and infarction noticeable in most cases. Indeed an unusual case of miliary aspergillosis has been reported in a patient with chronic alcoholism, free from other debilitating diseases. We describe here a similar case of disseminated aspergillosis characterized by miliary microabscesses which occurred during the treatment of a patient with acute leukemia.

View full abstract