Interferon (IFN) was administered intermittently for 6 months to the patients with non-A non-B chronic hepatitis (CHNANB), and the effectiveness of the treatment for improving the hepatic function was evaluated. Of 26 patients with CHNANB, 16 received intermittent IFN therapy (IFN group), and 10 were treated by conventinal therapies without IFN (non-IFN group). All patients were observed for 1 year. IFN was administered once a day at 3 MU in principle (1 MU in some patients and 6 MU in 1 patient) daily for 1 week immediately after the beginning of the therapy and 3 times a week for the subsequent 6 months at the outpatient clinic. The patients were followed up for at least 6 months after completion of the treatment. In the IFN group, the serum GPT level normalized in 11 (68.8%) of the 16 patients 1 year after the beginning of the treatment. In these 11 patients (normalized group), HCV-RNA was negative or became negative in 3 of the 6 patients in whom the serum HCV-RNA could be examined. Histological grades of inflammation in the liver were also markedly alleviated in the normalized group. The hepatic function did not normalize in any of the 10 patients in the non-IFN group. These findings indicate that IFN therapy is useful for CHNANB

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Priming effect of monocyte culture supernatant on polymorphonuclear neutrophils (PMN)-chemiluminescence (CL) was studied in patients with systemic lupus erythematosus (n=11) and mixed connective tissue disease (n=4). In normal controls, N-formyl-methionyl-leucyl-penylalanine (FMLP) induced PMN-CL was enhanced when PMN were previously incubated for 15 minutes with monocyte culture supernatant (MS) or T lymphocyte culture supernatant (TS) or T lymphocyte culture supernatant (TS).
The enhancing effect of MS on PMN-CL was greater than that of TS. This enhancing effect of MS was inhibited by adding of dexamethasone (1μg/ml) during the culture. Recombinant human TNF also enhanced PMN-CL as well as MS. When compared the enhancing effects of MS between patients and normal controls, that of patients under corticosteroid therapy (average predonisolone dose 39.5mg/day) was reduced significantly. Thus, we concluded that the cytokines from monocyte contributed PMN phagocytosis of invading microorganisms, and that this monocyte-mediated PMN phagocytosis was suppressed partly by corticosteroids in collagen disease.

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Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most important microorganisms in nosocomial infection. The Hospital staff working in MRSA endemic wards are known to have MRSA in their nasal cavity. The nasal carriage of MRSA was detected in staff members and patients of two hospitals. In Niigata University Hospital, 10 out of 109 nurses and 8 out of 142 doctors were found to be MRSA carriers. On the other hand, in Nagaoka Red Cross Hospital, 25 out of 448 nurses were found to be MRSA carriers, however, no carrier was found in 23 docters. These strains were also resistant to MCIPC, IPM, TFLX and OFLX, whereas they remained sensitive to VCM.
The coagulase types of MRSA isolated from the hospital staff and patients were II, IV and VII, although those of Meticillin-sensitive S. aureus (MSSA) consisted of all types. Elimination of nasal MRSA from the carriers was considered for avoiding hospital outbreaks caused by this potential pathogen. Forty hospital staff and 19 patients, in who's MRSA was found persisting in their nasal cavity, were treated by povidon iodine and chloramphenicol (CP) MRSA disappeared in 44% and 84% of the nasal carriers by povidon iodine and CP, respectively.

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This study was performed to demonstrate the early immuno-responses of lymphocytes in an experimental pneumonia with K. pneumoniae in mature mice (45 week-old) comparing with it in juvenile ones (4 week-old).
Acute mice pneumonia was made by inhalation with K. pneumoniae DT-S strains into lung. Changes in lymphocytes including their subpopulation in bronchoalveolar lavage fluid (BALF), peripheral blood, hilar lymphnodes and lung tissue were observed after the inhalation.
In addition, lung tissue and hilar lymphnode were examined immunohistologically.
The following results were obtained:
1. Total lymphocytes in BALF were more rapidly increased in the mature group than in the juvenile one. But there was no significant change in leukocyte count in peripheral blood between both groups.
2. Such a rapid increase in lymphocytes in BALF in mature group was depended on L3T4-Ly6c cells and L3T4-LFA 1 cells. These cells in juvenile group were not accumulated in BALF at initial phase of the infection. But in contrast, they were gradually increased in peripheral blood and in hilar lymphnode. There was significant time-differences in appearance of these cells in BALF between both groups. It might be, that L3T4-Ly6c cells and L3T4-LFA1 cells observed in BALF in mature animals were induced from bronchus-associated lymphoid tissue (BALT) or small lymphtissue in aveolar interstitium, but they in juvenile ones were orignated in hilar lymphnode.
3. Changes in Ly2-Ly6c cell and Ly2-LFA1 cell were shown the same tendency changes in L3T4-Ly6c cell and L3T4-LFA1 cell.
4. Accumulation of B220: Ly5-LFA1 cell in BALF was not observed in significant difference between the mature group and in the juvenile one.
5. L3T4 cells were markedly accumulation in subcortex area of hilar lymphonode in the juvenile group, but they were only seen scattered in the mature group.
6. It can be concluded that active T lymphocyte begins to response in situ in the early stage of respiratory infection in the mature host and this finding is a characteristic lymphocyte response, that is never seen in the juvnile group.

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We characterized lipopolysaccharides (LPSs) from respiratory pathogenic Branhamella catarrhalis (BC) strains, and evaluated the protective property of and-BC LPS antibody in BC respiratory infections. LPSs from four strains of BC were lipooligosaccharide having no 0-side chain and a Mr of 3 KDa, as estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). All of them produced different patterns, showing two to four bands on SDS-PAGE. We found high level of anti-BC IgG antibody in convalescent sera from a patient with BC respiratory tract infection by ELISA. This IgG antibody recognized BC LPSs on Western blots. Two respiratory pathogens of BC (strains; 87-122, 88-23) were tested in a bactericidal assay employing a convalescent sera. 87-122 strain was susceptible to antibody-dependent, complement-mediated killing, while 88-23 strain was resistant. The killing of 87-122 strain was inhibited by addition of the homologous BC LPS to the convalescent sera in a dose-dependent manner. These data support that anti-BC LPS antibody maymediate complement-lysis of some strains of BC, and play a protective role in BC respiratory infections.

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We compared two latex agglutination tests for serum candidal antigen in murine models of systemic infection and gastrointestinal colonization. In the intravascular-infection model, mannan detection test was positive at 2 hours after inoculation, but Cand-Tec was less sensitive than mannan detection test in this model.
In the gastrointestinal colonization model followed by systemic infection in neutropenic mice, the mannan antigen test became positive after 3 weeks of colonization with increased number of Candida of the stool, and Cand-Tec became positive after 5 weeks in neutropenic mice.

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Serotypes and RNA electropherotypes of group A human rotaviruses were identified in stool samples from patients with acute gastroenteritis in Kasukabe Kosei Hospital, Saitama, Japan, during three rotavirus seasons from 1988 to 1991.
Of the 665 stool samples from patients with acute gastroenteritis, 169 (25.4%) stool samples were positive for group A human rotaviruses. Of these 169 samples, 98 (58.0%) wereserotype 1, 7 (4.1%) serotype 2, 14 (8.3%) serotype 3, 3 (1.8%) serotype 4 and 47 (27.8%) were untypable. Serotype 1 was predominant over all three rotavirus seasons. Serotype 2 was most prevalent in the second rotavirus season, serotype 3 in the third season. Serotype 4 was detected only the second rotavirus season.
The ratio of subtype I to subtype II was 4.5: 95.5.
Among the 162 strains examined, 139 specimens were available to be electropherotyped. Fifteen different RNA electropherotypes were detected. Three to four different electopherotypes were more prevalent in each rotavirus season and the detection rate in each year was different within the same electropherotypes. The rotavirus strains of the same electropherotypes were observed with high prevalence for every rotavirus seasons. The same electropherotypes was found in human rotavirus strains of different serotypes that were appeared at different epidemic seasons.

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We carried out the bacteriological examination of sputum and bronchoscopy specimens from 31 cases with pneumonia due to C. psittaci.
The results obtained were as follows:
1. The positive culture of sputum and bronchoscopy specimens were 38.7%(12/31).
2. The organisms detected from them were 13 strains of gram-negative bacilli, 2 of gram-positive cocci and one gram-positive bacillus.
3. Significant differences were observed in the white blood cell count between the cases of positive culture and those of normal upper respiratory tract flora (p<0.05).
From the results we conclude that it would be better that we add the proper antimicrobial drugs to chlamydial antibiotics in the treatment of patients with leukocytosis.

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The first case was a 73-year-old woman with chief complaints of fever, cough, purulent sputum and dyspnea. EM therapy was begun in December 1983 due to a diagnosis of diffuse panbronchiolitis (DPB). Subsequently, P. aeruginosa was persistently detected, while in February 1991 at the time of an acute exacerbation of the DPB P. aeruginosa and S. pneumoniae were detected by TTA. The second case was a 65-year-old man with chief complaints of fever, cough and purulent sputum. DPB was diagnosed and EM therapy was begun in December 1985. In January 1991, peneumonia developed, at the time when S. pneumoniae was detected by TTA. In both cases, rapid disappearance of S. pneumoniae from the sputum and alleviation of symptoms were obtained with carbapenem antibiotic administration. Both strains were resistant to EM, Tetracycline (TC), Minocycline (MINO) and Clindamycin (CLDM). Particulaly, S. pneumniae of case 2 showed low sensitivity to Ampicillin (ABPC), Cefotiam (CTM) and Cefoxitin (CFX) as well. These cases showed acute exacerbations due to EM-resistant pneumococcus during long-term therapy with EM, and are of interest in that they may shed light on the relation between long-term EM therapy and the emergence of resistant pneumococcus.

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Epidemiological and bacteriological studies on Neisseria gonorrhoeae isolated in Sapporo, Japan, in 1980 and 1991 performed and the following results were obtained.
1. The range of age in the patients infected with Neisseria gonorrhoeae tended to be younger than those in the whole country.
2. Male patients in the early 20s or younger with gonococcal urethritis were often infected by bon-professional females but those in their late 20s or older were often infected from professional females, for example prostitutes and hostesses.
3. The rate of professional females who were positive to gonococci reached 17.4% and young females in their teens with cervicitis had the highest morbidity rate of gonococci than those in the older females.
4. The latent period in gonococcal infections tended to become longer gradually.
5. The isolation rate of penicillinase producing Neisseria gonorrhoeae (PPNG) showed a peak of 23.9%(61/255) in 1985, but gradually declined thereafter and it was 3.7%(1/27) in 1991.
6. An investigation on auxotype showed a decline of proto and Pro^- strains and an increase of AHU^- strains in non-PPNG. And most of the PPNG belonged to proto or Pro^- strains.
7. With the relationship between auxotype and sensitivity to AMPC, AHU^- strains were more sensitive than proto or Pro^- strains.

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An outbreak of municipal water-associated food poisoning by Salmonella Enteritidis occurred in Takatoh Town. Nagano prefecture during September 4 to 19, 1989. The major symptoms observed in the 680 patients consisted of diarrhea (70.9%), abdominal pain (51.2%), fever (44.6%), headache (27.9%), nausea (5.9%) and vomiting (5.7%). In the outbreak, S. Enteritidis was the only suspected etiological agent isolated from both patients and municipal water supply. All of the 21 isolates were lysine decarboxylase activity negative. In other respects, the isolates conformed to the general characteristics of Salmonella. All of them were further characterized by phagovar 8 type, uniform drug susceptibilities and carrying 2.7 kb plasmid.
Inspite of the evidence that the infection caused by a peculiar strain linked to the strain in municipal water supply used by the patients, it was impossible to determine the exact source of contamination in the water.
The outbreak above seems to be the most large-scale among those of Salmonella found poisoning associated with drinking water in Japan.

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Food poisoning due to “Godofu (Sasayuki tofu)” as a main causative foodstuff which broke out on July 14, 1988. There were 670 out of 918 persons who ingested this food who became ill (incidence 73.0%).
The main symptoms were diarrhea (93.4%), fever (77.5%), abdominal pain (64.5%), and vomiting (19.9%). A high degree of fever and watery diarrhea were characteristic of this poisoning.
The average latent period was 35 hours with a range of one to 156. The O164: H-strains of enteroinvasive Escherichia coli (EIEC) were detected from 22 of the 32 fecal samples collected from the patients, five of ten samples collected from workers engaged in tofu making, and one sample of leftover Godofu.
The virulence of EIEC strains isolated from the patients, workers, and leftover food was confirmed by invasion into HeLa and HEp-2 cells, Sereny test, and ELISA test to detect invasive plasmid-derived protein of the organism (conducted at Tokyo Metropolitan Research Laboratory of Public Health).
These EIEC strains were sensitive (≤ 0.19 to 6.25μg/ml) to GM, ABPC, CBPC, CER, CET, NA, PB, MINO, TC and CP as well as KM and OFLX which were used for treatmnet. However, their susceptibility to FOM varied to some extent (6.25 to 25.0μg/ml) and one strain isolated from a tofu worker was resistant to MINO, TC, FOM and CP (25 to ≥-100μg/ml).
Since investigation revealed that Godofu was left at room temperature about 29°C until ingested, we did a experiment to check the bacterial growth in Godofu under similar conditions at the time of outbreak.
One to ten CFU/ml of EIEC O164: H-strain derived from patients was inoculated into Godofu and left at 29°C. The number of cells was increased to about 102, 105, and 105, and 108 CFU/ml after 6, 12 and 24 hrs of standing, respectively.
Patients probably ingested Godofu contaminated by multified bacteria.
The route of contamination into the causative food could not be elucidated, but contamination of EIEC to the water tank used for harding tofu was suspected.

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We have tried to characterize the blastogenic responses of murine spleen lymphoid cells from BALB/c mice immunized with Legionella pneumophila serogroup (SG) 1 (Philadelphia 1 strain) and non-treated mice. Lymphoid cells from immunized mice showed stronger blastogenic responses following stimulation with concanavalin A or formalin-treated L. pneumophila SG1 whole cell antigen than those showed by lymphoid cells from non-treated mice. These cells from immunized mice also responded strongly when stimulated in vitro with other SGs of L. pneumophila, while these responded weakly when stimulated with other species of Legionella. Serum antibody titers of immunized mice against each SG of L. pneumophila were examined and the cross reactions were also recognized. However, the relatedness of serum antibody titers and the blastogenic responses against each serogroup of L. pneumophila was small. The epitopes recognized by the cellular immunity might be different in part from those recognized by serum antibodies, and investigations should be made on what th cellular immunity recognizes and how it works.

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Trivalent vaccine, containing measles TD97, rubella TCRB-19 and mumps NK-M46 strains (MMR vaccine) was administered to a total of 116 healthy children of which 50 subjects were simultaneously injected with varicella vaccine in the opposite arm. The seroconversion rates for measles, mumps, rubella, and varicella in those who received both MMR and varicella vaccines (MMR + V group) were 100%(44/44), 91%(39/43), 100%(46/46) and 95%(39/41), respectively. And these rates were comparable to those in subjects receiving only MMR vaccine, namely 100%(64/64) for measles, 95%(57/62) for mumps, and 97%(58/60) for rubella. Fifty-eight children receiving MMR vaccine were seronegative to measles, mumps and rubella before vaccination, and 51 (88%) of them were found to be seropositive against all three viruses at 6 to 8 weeks after vaccination. Among the children injected with MMR and varicella vaccines, 36 subjects had no pre-antibodies to measles, mumps, rubella and varicella. Seroconversion in post-serum to all four viruses were found in 31 cases (86%). Clinical reactions observed in some vaccines were mild fever (17%) and exanthem (5%). There were no complications of lymphadenopathy, swelling in parotis regions, or meningitis. Our results indicate that simultaneous administration of MMR vaccine and varicella vaccine is a safe and effective method for immunizing children against these four infectious diseases.

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We studied the transmission of hepatitis A virus (HAV) in 45 families, which members were diagnosed as hepatitis A in 8 hospitals in 1990. Feces and sera from 50 patients and their 126 family members were tested for HAV-specific antigen and IgM antibody by ELISA or polymerase chain reaction (PCR) technology. From the interval of the onset of hepatitis or detection of HAV antigen in feces, HAV transmission was recognized in 11 (24.4%) of 45 families. The transmission was found to be concerned with contacts of the children and that from children to parents was found in 4 families and the revers in 2. HAV antigen was detected from feces of 4 family members before onset of icterus by ELISA and furthermore, 3 by PCR. It was indicated that these methods would be used to prevent the transmission in a family, day-care centers, or institutions for the mentally retarded.

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We experienced three cases of lower resiratory tract infections worsened after Rhinovirus infection.
Case 1: A 42-year-old male with diffuse panbronchiolits was admitted to our hospital with the complaint of dyspnea on November 21, 1988. Rhinovirus was isolated from nasal washing and P. aeruginosa was cultured from transtracheal aspiration (TTA).
Case 2: A 67-year-old male, whose underlying disease was pulmonary asbstosis, was admitted to our hospital complaining of pyrexia on June 12, 1990. Rhinovirus was isolated from TTA and H. influenzae and others were cultured from TTA.
Case 3: A 64-year-old male with pulmonary emphysema was admitted to our hospital with a complaint of dyspnea on August 11, 1989. On December 17, 1989 the patient developed rhinorrhea and complained of purulent sputum, pyrexia and dyspnea after five days. Rhinovirus was isolated from nasal washing and TTA and S. nonhaemolyticus and others were cultured from TTA.
As indicated in this report, it is interesting to study the relationship between viral infection of the upper respiratory tract and bacterial infection of the lower respiratory tract.

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