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To investigate cellular interactions between human T and B lymphocytes in various diseases, we established a technique to prove terminal differentiation of B lymphocytes into immunoglobulin synthesizing and secreting cells. We also established a double antibody radioimmunoassay to measure the amount of IgG, IgA and IgM synthesized and secreted in culture supernatants. Purified immunoglobulins were obtained from sera of patients with myeloma or macroglobulinemia. The peripheral blood lymphocytes from 25 normal individuals had the geometric mean synthetic rates of 1886 ng for IgG, 1607 ng for IgA and 1173 ng for IgM per 1 X 10(6) cells when cultured for nine days in the presence of pokeweed mitogen. The method is simple and sensitive, and is thought to be useful for examining human lymphocyte function in vitro.

Thirty-seven consecutive cases of mitral valve replacement have been retrospectively reviewed. The prognostic significance of preoperative clinical, hemodynamic and quantitative angiographic factors for survival has been evaluated. In the Mitral stenosis (MS) group, all of the patients who showed small Stroke volume index (SVI) (less than 45 ml/m2) with pulmonary hypertension died from the low output syndrome. The prognosis was poor in patients who had large cardiothoracic ratio (CTR) in the MS group. Aortic valve replacement must be considered when moderate aortic regurgitation is associated with mitral valve disease. In the MR factors for predicting the survival. The eccentricity ratio is also a sensitive parameter for recognizing a patient who will have a poor prognosis after mitral valve replacement. The main mode of death was found to be heart failure due to myocardial impairment.

Serum specimens from 12 patients with type A hepatitis were analyzed for immunoglobulin M-type antibody to hepatitis A virus (IgM anti-HA). A recently developed solid-phase radioimmunoassay kit for IgM anti-HA (HAVAB-M, Abbott Laboratories) and a competitive binding radioimmunoassay kit (HAVAB, Abbott Laboratories) with or without 2-mercaptoethanol treatment, as modified by Yano et al. (Acta Hepatol. Jpn. 21, 704-712, 1980) were used to obtain an M-index. All specimens obtained within 60 days of the onset of illness and specimens from 2 of 4 patients later than 60 days after the onset were positive with the HAVAB-M test. This test gave negative results to sera which were positive for anti-HA by a standard HAVAB test in the following: 3 patients with type B hepatitis; 5 with non-A, non-B hepatitis; 11 healthy adults; and 10 sera strongly positive for rheumatoid factor. The M-index for type A hepatitis in sera within 30 days of the onset (mean value of the M-index, m, = 1.52; standard deviation, SD, = 0.25) was significantly higher than that for non-A hepatitis (m = 1.05; SD = 0.15) and for healthy adults (m = 1.02; SD = 0.10). The simplicity and usefulness of the HAVAB-M test in diagnosis of acute type A hepatitis over those measuring the M-index by HAVAB tests were shown by direct comparison of the results.

<p>A female patient who died of apparent postradiation sarcoma in the inguinal region after irradiating a metastatic squamous cell carcinoma of the same site was reported. For approximately 20 months, the patient had received a total of 6,600 and 9,600 Roentgen to the right para-aortic and inguinal areas, respectively. About 10 years later, she developed a sarcoma, namely a malignant fibrous histiocytoma. Sputum cytology demonstrated numerous giant cells with bizarre nuclei; subsequent chest films also presented apparent metastatic tumor shadows. The cellular characteristics and also rather low incidence of detection of nonepithelial malignant tumor by sputum cytology were briefly discussed, and ways of enhancing cytodiagnostic accuracy were proposed.</p>

Papular acrodermatitis of childhood (PAC) has recently been reported to be associated with hepatitis B surface antigen (HBsAg) subtype ayw. Between September, 1978, and June, 1979, we saw 14 patients with PAC in a small epidemic occurring in Iwakuni City, Japan. HBsAg was detected in sera from all patients. Subtyping of HBsAg in 11 patients showed that 8 had a determinant adr and 3 had no detectable determinant because of low antigen titers. The result suggests that factors other than the specific HBsAg subtype contribute to the development of PAC.

Insulin binding to erythrocytes was studied in diabetic patients. Insulin binding was lower in untreated diabetics and diabetic patients treated with diet or insulin than in normal subjects. Binding variation was mainly due to decreased binding site concentration in untreated and insulin-treated patients, and to lowered insulin binding site affinity in diet-treated patients. Several patients treated with hypoglycemic agents showed higher insulin binding due to increased binding site concentration. Insulin binding to erythrocytes may not always reflect the insulin binding status of insulin sensitive tissues.

A 63-year-old man developed generalized lymphadenopathy with skin rashes, fever, hepatomegaly and polyclonal hypergammaglobulinemia, twice, in February 1972 and in June 1979, after taking allopurinol for gout. Cervical lymph node biopsy, performed each time, showed the presence of immunoblasts and plasma cells, effaced nodal structure with involvement of the pericapsular tissue, rich vascularity and numerous mitoses, indicative of angio-immunoblastic lymphadenopathy with dysproteinemia (Frizzera, Moran and Rappaport). The existence of hypersensitivity to drugs, in particular, allopurinol in certain patients was emphasized, and induction of immunoblastic lymphadenopathy with various other therapeutic agents was briefly discussed.

From these results it is but natural to assume that the antigen-antibody reaction is involved in the phenomenon, eosinophilia. The antigen in this instance is the filtrate of hookworm emulsion, and the serum of hookworm disease as well as the bone marrow can be thought to contain the antibody. In any case, so long as the medium contains the serum or bone marrow or both of them obtained from the patient of hookworm disease, eosinophilia and the acceleration in the motility of eosinophils are brought about in the growth zone by addition of the filtrate of hookworm emulsion. Therfore, as for the mechanism inducing hookworm eosinophilia, it may by interpreted that the patient of hookworm disese is repeatedly sensitized by the antigen arising all probability from the metabolic products of hookworms or from the dead bodies of the worms; and producing the antibody in tissues and blood, thus the antigen-antibody reaction is elicited in vivo as long as hookworms live in the human body so that the increase in the mitosis and the acceration in the motility of eosinophils in the bone marrow are brought about with the resultant continuous discharge of a large quantity of eosinophils from the bone marrow parenchma into the sinusoids, there by inducing eosinophilia in the peripheral blood.

Of eosinophilias that we often encounter clinically, we selected two of the most representative ones, namely, hookworm diseae and bronchial astma, for our present sternal bone-marrow tissue culture, and studied the movement patterns and wandering capacity of eosinophils. As the results, even in those eosinophils that show no significant change other than the increase in number in ordinary stained-smear specimens of peripheral blood or bone marrow, it has been clarified that, when observed under living condition, they reveal a picture specific to individualistic behaviors according to diseases. Therefore, it can be assumed that in the pathologic condition what is known as eosinopilia not only eosinophils increase in number but also qualitative changes of eosinophlils specific to each disease are brought about, and consequently these specific changes are reflected on the movement patterns of the eosinophil.

1. With a view to grasp more simply and clearly the characteristics of this disease and in order to find a clue for prompt discovery of cases when encountered in future, the authors undertook a statistical study of the cases already reported by various authors. 2. The cases reported so far amount to 17 familial groups which consisted of 38 acatalasemic cases. These groups were distributed widely throughout Japan. The disease seemed to be prevalent in the rural communities where adherence to the custom of consanguineous marriage occurs. As yet, we have not heard of the occurrence of this disease in other countries. 3. The disease has equal distribution in both sexes. About one half of patients showed a peculiar oral gangrene (Takahara's disease). The great majority of these were noted in those less than 10 years of age. 4. The great majority of them were children whose parents were united in consanguineous marriage and have siblings with acatalasemia. 5. As for the treatment of oral lesions in this disease, extraction of tooth at the site of the lesions, removal of the diseased tissues en masse by resection, and penicillin treatment given concomitantly are effective. The course and the length of time required in healing of the wound due to the operation are about the same as in the case of normal persons. 6. The authors wish to call special attention to the phenomenon peculiar to the acatalasemic blood. The blood of acatalasemic individuals changes to brownish-black color in the absence of foaming or bubble formation upon the application of hydrogen peroxide to blood.

In our department we have been placing a special emphasis on the treatment and study of rheumatoid arthritis, and during the last four years we have handled about 1,600 cases visiting our outpatient clinic and approximately 100 hospitalized cases. Our experiences with these patients are only what might be called an introductory phase in the study and treatment of rheumatoid arthritis when compared with those in Europe and America. In estimating the incidence of rheumatoid arthritis in Japan from various available data, although it would not reach the level of England and U.S.A., it will be about 100 cases per 100,000 population, matching more or less the incidence in the northern Europe. As regards sex and the predisposing age we find no great difference from those in Europe and America. One striking difference that we find is the fact that patients in our country have very little resistance against salicylic acid drug used in treatment. Therefore, it is unreasonable to expect a good anti-inflammatory action by administering a large dosage of 5-10g of such a drug as aspirin per day. It must be limited within a comparatively small dosage of 1.0 to 2.0 g or with concomitant administration of prednisolone and aspirin in the hope of utilizing its analgesic effect. Furthermore, it is not feasible to introduce the results of studies made in Europe and America on the salicylic drug and its prescription all of them showing the concentration in blood 35 mg%, which is on the borderline of intoxicating dosage. This is only one example, and with some more experiences we shall undoubtedly encounter many dissimilar points. Therefore, it is essential that rheumatology specific to Japan needs to be established.

It is well known that human serum contains some sialic acid and its contents increase markedly in the blood serum of the patients bearing malignant tumors. Recently YAMAKAWA2, BHOM3, SAITO4 and YUI5 observed the sialic acid contents in the blood sera from the patients of various diseases and clarified that its contents increase not only in the sera from the cases bearing malignant tumors but also in those of rheumatic or tuberculous diseases. BOHM6 et al. measured the sialic acid contents in the cerebrospinal fluid of several diseases and ascertained that its contents increase in the cerebrospinal fuid from the cases of inflammatory diseases. In connection with these works we have observed the sialic acid contents in the cerebrospinal fluid of the patients suffering from the diseases of central nervous system, prior to the surgical operation, and revealed the markedly increased contents in the sialic acid in the patients bearing tumors of the nervous system. In this paper the data are reported in detail.

From the data presented in this communication, it might be concluded that a cancer specific substance, which can be demonstrated in gel diffusion, is present in human cancer tissue, common to various epithelial cancers of different individuals, although it may vary in its concentration. Needless to say, this substance is quite different from the so-called interspecies antigen or organ specific antigen, as proved by the present experiments. Furthermore, this substance can be eluted well by the Fluorocarbon treatment and it displays physically and chemically unstable characteristics. This substance is likely to be included in the microsome fraction and soluble fraction which was determined by gel diffusion technique. However, the association of this substance with other specific antigenic substances of human cancer, concerned with "delayed type skin reaction", "cytopathogenic antiserum against cancer cell", and "complement fixing antibody in serum of patients with cancer", has not been elucidated in this study.

Two cases (Case I, 24-year old male, and Case II, 41-year old male) of liver cirrhosis after viral hepatitis have been described with a special emphasis on the distortion of the hepatic lobular architecture induced by hepatic hemodYnamic changes. Careful and precise clinical and laboratory examinations as well as peritoneoscopic examination with liver biopsy, particularly with vascular stereograms of liver biopsy tissue, have been successively carried outfrom stage of normal lobular architecture to early stage of cirrhosis. As the result, it has been found that in the course of these examinations clinical and laboratory features of the patients have remained almost unchanged in spite of gradual aggravation of morphological pictures. It is especially noteworthy that on vascular stereograms of liver biopsy tissue the parenchymal cells under the scarred portal tracts have suffered atrophic changes. Thus, three individual portal tracts of Case I have been gathered in a single connective tissue located on the distributing area of a scarred portal tract, whereas a central vein of Case II has moved from center to side of the scarred portal tract. In the late stage, these two cases ultimately turned to liver cirrhosis.

There is as yet no plausible and convincing explanation for the etiology of rheumatoid arthritis. The authors investigated anti-synovial tissue antibody in the body fluid of rheumatoid arthritis by means of indirect immunofluorescent technic using non-affected synovial tissues as antigen. As the result the anti-synovial tissue antibody was detected in 7 cases of the 15 synovial fluid samples of rheumatoid arthritis and in two out of the six serum samples. The site of the localization of this antibody was demonstrated to be in the synovial membrane, especially in synovial cells and in the small blood vessel walls situated immediately adjacent to the synovial surface, but it was found in no connective tissues other than synovial membrane. It seems that this anti-synovial tissue antibody should be considered as an independent factor from rheumatoid factor, and that rather than the rheumatoid factor it is more actively associated with the localization and progression of chronic inflammation within the rheumatoid arthritis joint.

Two cases of megaloblastic anemia associated with anticonvulsant drugs were studied. Both cases were inpatients of psychiatric hospitals and had quite inadequate intakes of food. The former had lung tuber. culosis and the second had febril illness before the manifestation of anemia. Multiple examinations including bone marrow smears, serum iron levels, vitamin B12 levels, estimation of urinary formiminoglutamic acid after histidine loading and folic acid tolerance test revealed that this anemia was due to folic acid deficiency. Complete hematological responses were ob3erved with injection of folic acid. Retrospective nutritional study on the second case was carried out. The study revealed that folic acid content of the diet of this hospital was 152 fl.g of free folate and 522 fl.g of total folate. The folic acid mtake of the patient was about 80 /1.g of free folate and 280 l1.g of total folate daily during a month before the manifestation of megaloblatic anemia. Importance of additional factors for the development of megaloblastic anemia in patients receiving anticonvulsants was discussed and it was concluded that most important factor was nutritional deficiency of folic acid.

A subcutaneous tumor of a patient with epidermodysplasia verruciformis was studied by the light microscopy, the electronmicroscopy and the immunofluorescent test. The tumor cells were histologically pleomorphic and electronmicroscopically contained varying amounts of cytoplasmic filaments without Z-band formation. The antimyosin serum stained the tumor cells, showing their myogenic origin. No virus or virus-like particles were observed in the tumor. Tumor antigens stainable by the patient's serum were not detected. Hamsters inoculated with the tumor extract at birth developed no noticeable diseases.

We administered a branched-chain amino acid (BCAA) infusion to 16 patients with hepatic failure and two healthy subjects, and then evaluated its effects on ammonia metabolism and amino acid metabolic pool. Immediately after the BCAA infusion, the venous blood ammonia concentration increased in 12 of 15 patients with hepatic failure and in both two healthy subjects. Glutamine (Gln) also rose in all cases following the BCAA infusion, and this rise was particularly marked in the hepatic failure group. The increase in Gln due to the BCAA infusion and the arteriovenous difference in the pre-administration ammonia concentration showed a good correlation. These results suggest an increase in glutamine cycle capacity in patients with hepatic failure.

The records of 159 patients who underwent surgical resection of colorectal cancer were reviewed to assess the incidence of ovarian metastasis and to define the role of oophorectomy. Four of these patients presented with metachronous metastases, and one patient had synchronous ovarian involvement. The incidence of ovarian involvement was higher in younger patients. While most patients with ovarian involvement had the primary tumor located at the rectosigmoid region, a similar distribution of the primary tumor was observed in patients without ovarian metastasis. The histological type and degree of differentiation was similar regardless of whether or not ovarian metastasis was present. Of the patient without ovarian metastasis, 57% presented with nodal metastases and 3.2% with peritoneal dissemination, while all patients with ovarian metastasis had nodal and peritoneal involvement. Our results suggest that histological type and degree of differentiation of the primary tumor do not influence likelihood of ovarian metastasis. However, the exposure of the tumor to the serosal surface and the subsequent peritoneal dissemination may be an important route by which malignant tumor cells reach the ovaries. However, due to the wide lymphatic involvement in patients with ovarian metastasis, the lymphatic route may be important as well. Thus, we consider that oophorectomy should be performed in all postmenopausal women, when the ovaries are macroscopically affected, and in premenopausal patients with Astler-Coller B2 tumors or over.

Excised extensor retinacula of the first compartment and tenosynovium from 35 patients (6 men and 29 women) with de Quervain's disease were examined by light and electron microscopy to investigate the pathogenic mechanism. The patients, aged from 22-78 years, averaging 50 years, comprised the study group. Two hundred and thirty-two specimens from cadavers of 95 men and 75 women were macroscopically examined as the control. In the study group, the extensor retinaculum and tenosynovium were macroscopically thickened, and were histologically classified into 4 groups based on presence or absence of septum, and the location of retinacular thickening. Morphologically, the thickening of the tenosynovium and retinaculum was due to fibrosis in every layer, although fibroses were seen mainly in the middle layer. The ratios of proliferation of fibroblasts, myxoid changes and/or hyaline degeneration, and vascular proliferation were varied between layers. Minimal round cell infiltration was found in the retinaculum as well as in the tenosynovium. The results also indicate that the Iwahara-Nozue test can be used to accurately predict relatively greater thickening of the retinaculum on the extensor pollicis brevis side. Based on clinicopathological analyses, it appears that de Quervain's disease is induced not only by extrinsic factors such as superficial friction but also by intrinsic factors.