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Despite the current diagnostic and serologic testing for SLE, the interval between the onset of symptoms and the diagnosis is still long. In this study, we aimed to show the interval between the initial symptoms and the diagnosis of SLE and to investigate the presence of any relationship between the interval and the initial symptoms. One hundred and thirty-six patients were diagnosed with SLE using the 1982 ARA criteria. The mean age of the patients at diagnosis was 29.9 +/- 10.5 years. The mean interval between the onset of symptoms and the diagnosis of SLE was 21.82 +/- 30.32 months. The subjects were evaluated twice, at intervals of < or = 3 and < or = 12 months after the onset of symptoms. Although arthritis and/or arthralgia were the most common initial symptoms (60.3%), only 26.8% of the patients with these symptoms were diagnosed earlier than 3 months after the onset. If the first initial symptoms were butterfly rash or pericarditis, pleuritis, spontaneous abortion or cognitive dysfunction, they led to early diagnosis. In conclusion, since arthritis and/or arthralgia are the most common initial symptoms of the disease, every young woman with these symptoms should be carefully evaluated for SLE.

The purpose of this study was to compare the MR characteristics of renal cell carcinomas against histologic findings and to assess the correlations among signal intensity, tumor enhancement, and pathologic findings. Fifty-four patients (56 lesions) were examined by MR imaging and then underwent partial or radical nephrectomy. The pathologic diagnosis of all lesions was renal cell carcinoma. All MR examinations were performed as dynamic studies using the same 1.5-T scanner. MR characteristics were compared against pathologic findings after resection, and the correlations among signal intensity, tumor enhancement, and pathologic findings were then assessed. A significant correlation was observed between tumor grade and tumor enhancement, with G3 lesions tending to show little enhancement. Regardless of the histologic classification, G3 tumors were found to contain highly heterotypic cancer cells and very few vessels by histopathologic examination. No significant correlations were noted between the other MR characteristics and pathologic findings. Renal cell carcinomas showing little enhancement tend to be highly malignant lesions based on the pathologic findings. Special consideration is required for these tumors with regard to the selection of surgical intervention and follow-up observation.

We studied the association of gamma-glutamyltransferase (GGT) and other serum markers of liver injury with daily alcohol consumption in a healthy population of 1,043 Japanese males. A positive correlation between daily alcohol consumption and biochemical markers, such as log GGT (r = 0.432), log AST (r = 0.244) or log LAP (r = 0.246), was seen in all drinkers. However, there was a negative correlation, such as log GGT (r = -0.434), log AST (r = -0.424) or log LAP (r = -0.430), in heavy drinkers who consumed more than 70 g ethanol a day. On the other hand, a positive correlation, such as log GGT (r = 0.426), log AST (r = 0.247) or log LAP (r = 0.216) was found in moderate drinkers who consumed less than 70 g ethanol a day. Interestingly, there was a tendency toward negative association between alcohol consumption and the Tokyo University ALDH2 Phenotype Screening Test (TAST) score in the heavy drinkers, and there was a tendency toward positive association between GGT and TAST score in this group. Our results suggest that there are 2 groups of drinkers, those with elevated GGT (good responders) and those with normal GGT (poor responders) despite heavy drinking.

We observed a bilateral and symmetrical variation of the anterior belly of the digastric muscle during the dissection of a 35-year-old female cadaver. The accessory muscle bundles were arranged in a cross. These bundles were found superficial to the mylohyoid muscle and deep in the platysma. Such a variation from perfect symmetry has not been previously reported. To avoid misinterpretation of radiological tests, it is important to be aware of bilateral and symmetrical variations of the anterior belly of the digastric muscle when examining the floor of the mouth and the submental region.

The purpose of this study was to elucidate the role of extracellular matrix components such as aggrecan, fibronectin, and laminin in the extraocular muscle of patients with strabismus. Resected tissues of the medial rectus muscle of 47 patients with intermittent exotropia obtained during recession-resection surgery were frozen under liquid nitrogen and pulverized by a Freezer/Mill to solubilize the tissue for enzyme immunoassay. The total amounts of aggrecan, fibronectin, and laminin in the resected tissue were correlated with clinical data of patients such as age, exodeviation, and refractive error. The amount of aggrecan decreased significantly with the advance of age (P < 0.0001, Spearman rank correlation test), while the amount of laminin or fibronectin had no correlation with age. Patients with basic type intermittent exotropia showed larger, although not significantly, amounts of aggrecan than those with convergence insufficiency type (P = 0.0538, Mann-Whitney U-test). The amount of aggrecan may be related to motor aspects of intermittent exotropia.

Oncogenesis of human adenovirus type 12 in the brain of rats was examined. Newborn rats of Sprague-Dawley and Donryu　strains were injected intracranially with human adenovirus type 12.　The incidence of intracranial tumors was 91% (30/33) in SpragueDawley　and 56% (14/25) in Donryu rats. Except for one tumor nodule　located in the parietal cortex of a Sprague.Dawley rat, all tumors　developed in the paraventricular areas or in the meninges. Tumors were quite similar histologically to those induced in hamsters and　mice resembling the undifferentiated human brain tumors such as medulloblastoma,　ependymoblastoma and embryonic gliomas. From　the histological features and primary sites of tumor development, it is　suggested that the tumors in the brain of rats induced by adenovirus type 12 originate from the embryonic cells in the　paraventricular area　and also from the undifferentiated supporting cells of the peripheral　nerves in the　leptomeninges.

A factor, cornin, inhibiting the growth of L cells cultured in monolayer was extracted from bovine liver with boiling water and was partially purified by gel filtration with Sephadex G-200. The factor was (1) precipitable with ethanol at the concentration between 70% and 90%, (2) impermeable through dializing memo brane, (3) eluted as the last peak at the gel filtration and (4) containing protein and RNA but no DNA.

To analyze the appearance of three forms of hepatitis B antigen-associated particles (HB Ag particles) and antigen-antibody (Ag-Ab) complexes in the sera of patients with various liver diseases, electron microscopic observations with the combinations of a variety of immunological assays were made at first on the HB Ag and Ab mixed in vitro in various ratios, and then on the samples from the sera of each patient. The number of patients observed were 64 in total, which consisted of various types of hepatitis, Hodgkin's disease, Down's syndrome and an asymptomatic carrier. For the detection of HB Ag-Ab complexes a modified method of ALMEIDA was used, and for the isolation of large HB Ag particles (Dane particles) DANE'S method was employed. Electron microscopy proved to be a useful method for detecting HB Ag and the Ag.Ab complexes when the ratio of HB Ag to Ab was in the equivalence. Large aggregates of Ag-Ab complexes were frequently observed in the attacks of acute hepatitis and the recrudescences-of chronic aggressive hepatitis. The aggregates were also observed in fulminant hepatitis but the ratio of HB Ag to Ab was different from each other among 3 cases examined. The large HB Ag particles were not observed in more than half of the cases in the attacks of acute hepatitis, but appeared in the major. ity of cases in chronic aggressive hepatitis, even massively during the period with transiently elevated levels of serum glutamic pyruvic transaminase. A few large particles were also found in sera of an asymptomatic carrier, Hodgkin's disease, and Down's syndrome.

The RNA extracted from Rous sarcoma virus (RSY)induced mouse ascites sarooma cells (SR·C3H, N. P.) by means of the cold SDS-phenol was examined by the electron microscopy on the specimens spread wi th or wi thout urea according to the protein mono· layer technique. The majority of RNA molecules was found in a collapsed agglomerated form, derived from matured ribosomal RNA. Using sucrose gradient, linear molecules of RNA were observed in the interspace of the agglomerated form of RNA at the region of high molecular weight of the band sedimentation. The histogram of the distribution in length of the linear molecules involved up to 6 /1 in length wi th a modal length of 2. 28 f1 and 2.0 to 2. 2 f1 in a pro. minent peak; longer molecules up to 18 f1 in length were scarcely observed. Species of the linear RNA molecules is not exactly known, although this is not mature ribosomal RNA and likely to be messenger RNA or nascent RNA molecules, some of which might associate with RSY·RNA.

Gornin was extracted from bovine liver. The effects of cornin on DNA synthesis were compared with its effects on cell growth using L cells growing in suspension. As the first step of this experiment, a simple method of suspension culture was established with a new modification of YLE medium. Both effects of cornin paralleled with dosage. And the properties of the inhibitory factor of DNA synthesis are the same as those of growth inhibitor in respect to the heat stability and impermeability against dialyzing membrane. The inhibitor of DNA synthesis could not be separated from that of growth by gel filtration with Sephadex G-75.

By injecting 131I-Lipiodol into lymphatics of the dorsum of dog feet, the distribution of 13JI in the lymph nodes and other principal organs as well as its histological effect were studied periodically after the injection for the period of two months. The characteristic feature of J3JI distribution was the fact that J31I was accumulated into lymph nodes markedly higher than in any other organs and it was retained there over a long period of time. Histological examinations of the lymph nodes revealed a marked lymphocytopenia, the loss of germinal center, practically complete loss of lymphoid elements already 5 days after injection, and marked fibrosis. In the lung a considerable J3JI·distribution could be seen in early stage:, but with lapse of time it decreased rapidly. The distribution in other organs such as liver, spleen, bone marrow, kidney, ureter, bladder, thyroid gland, pancreas, testicles and small and large intestines was negligible in amount, and any specific histologic effect of irradiation could not be recognized in these organs including the lung. From these results, the authors concluded that 131I-Lipiodol has a selective activity on lymph nodes by injecting it via lymphatics and it is a safe method in clinical application to treat the patients bearing malignant lymphoma or metastatic lymph nodes.

Firstly, comparisons have been made of the secretion of human growth hormone (HGH) that was induced by insulin, lysine vasopressin and pyrogen injections in order to study whether these substances can be utilized as a rapid test of HGH secretion. In insulin test, a fall of the fasting blood glucose level by 28.6% or more seemed to be sufficient to provoke adequate HGH elevation, and 9.4 ng/ml or higher HGH increment was recognized as being normal, because lysine vasopressin and pyrogen produce varying degrees of side-effects and are less specific and unpredictable in the release of HGH. Secondly, the pharmacologic effects and mechanism of action of exogenous glucagon upon the HGH secretion were studied. In normal subjects after one mg sc glucagon, there was a mean peak blood glucose level of 142. 4±3.l mg/lOO ml at 30 min, HGH levels reached a mean peak level of 22. 6±4. 8 ng/ml at 150 min, and no false negative response was noted. In patients with hypopituitarism, there was no positive response in plasma HGH levels after the sc glucagon. The present study revealed that the rise and subsequent fall of blood glucose are not the sole mechanism responsible for the effct of glucagon on HGH secretion, and that the HGH secretion in response to the sc glucagon was not triggered by cathecholamine via the stimulation of the adrenal medulla.

Ultrastructure of microfilaria Brugia malayi was investigated with electron microscope. Microfilariae are covered by a sheath membrane with dense materials on its outer surfaces. The cuticle consists of 3 layers; namely, external cortical, internal cortical and fibrous layer. Beneath these cuticular layers, thin hypodermis is present and the muscle cells are arranged of 4 groups in a crosssection except for the head and tail. A pair of cephalic channel containing several cilial rods opens at the anterior end of the worm. A hook is situated on the anterior edge of one channel orifice, and several spines grow on the opposite side to the hook. Caudal channels paired laterally opening into the both sides of the posterior region differ from cephalic channels by the presence of a single cilial rod. A central canal runs from the buccal cavity to the inner body, and opens into the inner body cell through the filamentous apparatus. The inner body appears to consist of several cells having storage substances and a flat nucleus located on the periphery of the cell. An excretory apparatus, i. e., a cell, is composed of a nucleus and a large vesicle which has many microprojections on the luminal surfaces. The GI cell which occupies the whole width in a cross-section is larger than the R cell. R2-R4 cells appear to be in a close contact with the anal apparatus having many microprojections on the luminal surfaces. These microprojections differ from those of the excretory vesicle in their thickness and length. The characteristic patterns of these organs are compared with other microfilariae.

Electron microscopic observation was made on the length distibution of messenger RNA molecules in polyribosome pre· paration isolated from mouse ascites sarcoma cells, which was de· stroyed by ethylenediamine tetraacetate treatment in hypotonic solu. tion. The ribosomes appeared first to be a hollowed structure by swelling and then were destroyed to a rod·like structure consisting of ribonucleoprotein strand, which was clearly distinguishable from the linear structure of messenger RNA released from the polyribosomes. The length of messenger RNA was poly.dispersed measuring from 0.02 up to 6 μ, the majority (92%) of which was in the length less than 3 μ with a prominent peak between 0.6 to 0.8 μ.

The appearance of sideroblasts in hypoplastic anemia (HAl and acute myelocytic leukemia (AML), together with their sideroblastograms, was studied. Hematological studies on cases with type III sideroblast dominance by sideroblastograms produced the following results. Type III sideroblast dominant HA was observed in three of 63 cases. Two of the above three cases had what we call "atypical factor", while the remaining one became AML in its clinical course and could be considered to be leukemia in a hypoplastic preleukemic stage. Type III sideroblast dominant AML was noted in five of 32 cases. Three of these five cases are compatible with low percentage leukemia, and one of the above three cases showed ringed sideroblasts exhibiting erythroleukemia in the terminal stage. In HA and AML, type III sideroblast dominant cases have to be examined in relation to atypical HA and atypical leukemia. Changes of iron meta. bolism in erythroblasts with preleukemic stage will be attributable to disturbance of erythropoiesis such as erythroid hyperplasia in bone marrow and also, in part, to disturbance of hemoglobin synthesis.

For the purpose to reveal the changes in stimulatory effect of dibutyryl-cyclic- AMP on erythropoiesis during ontogenetic development, the author studied syntheses of DNA, RNA and protein of erythroid cells in fetal liver, neonatal and adult bone marrows of rats. In the bone marrow of neonatal animals erythropoiesis was stimulated by the intraperitoneal injection of cyclic nucleotide with enhanced DNA, RNA and protein syntheses of erythroid cells. Enhancing effect of dibutyryl-c-AMP on the erythropoiesis decreased gradually with advance of neonatal days. Autoradiographic observations revealed that in erythoid cells isolated from fetal liver and neonatal bone marrows, DNA-, RNA- and protein-snythesis was markedly stimulated by incubating with cyclic nucleotide, but not in those from adult bone marrow. Discussion was made on the changes in the regulatory mechanism of erythropoiesis according to the transition of hematopoietic organs during development.

The effect of immunization with hamster fetal cells on the tumor induction by adnovirus type 12 was studied by in vivo and in vitro. The immunization with lO-day old fetal cells showed a recognizable inhibition on the tumor induction by adenovirus type 12. The inhibition was observed only in males but not in females. For the inhibition, immnization with 107 or more cells was required. The immunization with same dose of l2-day-old fetal cells were ineffective. The inoculation of the spleen cells from hamsters immunized with un· irradiated fetal cells strongly inhibited the adenovirus·12 onocogenesis. Membrane immunofluorescent test, however, failed to demonstrate the fetal antigens in any of adnovirus-12-induced tumor cells, SV40induced tumor cells and cells from spontaneous hamster lymphoma.

A new cell line "CK cell line" capable of continuous propagation was established from a calf kidney tissue. The bovine adenovirus type 3 could propagate well in this cell line.

The control mechanism of mitosis in the regenerating rat liver was studied in relation to the cell functions. Partial hepatec· tomy induces a series of changes prior to the initiation of mitosis, i. e. decrease in serum glucose and albumin levels, loss of glycogen from liver cells, and increased lipid mobilization to liver cells. Massive supplies of glucose and fructose suppressed significantly hepatocellu. lar mitosis with suppression of lipid accumulation and preservation of glycogen in the liver cells and of blood sugar level. Homologous serum administration also suppressed the rate of liver cell mitosis after hepatectomy preventing the decrease in serum albumin level, but did not suppress the lipid accumulation in the liver. Starvation, which would relieve the liver cell from the work of detoxication of intesti. nal toxic products, did not show any suppressive effect on the mitotic rate of liver cells after partial hepatectomy in single animals. But starvation induced severe hypoglycemia, moderate hypoalbuminemia and loss of glycogen content in the liver. These changes in metabo. lism by starvation and partial hepatectomy were suppressed by con· jugating the animals with nonhepatectomized fed.partners by aortic anastomosis, and mitosis was suppressed in the residual liver of the fasting animals in this parabiosis. The results indicate that all the major functions of parenchymal live cells tested, sugar metabolism, serum albumin production, and detoxication, are closely related to the control of liver cell mitosis. Accumulation of lipids in the liver remnant after partial hepatectomy is thought to be for the compensa. tion of reduced glycogen storage and not concerned directly with the liver cell mitosis. Discussion was made briefly on the humoral factor and portal blood factor in relation to excess load of functions on resi. dual liver cells.

Folic acid contents of plasma, whole blood, liver and spleen in Rauscher leukemic mice were estimated. Plasma and liver folate in the leukemic mice was lower than that of normal mice, suggesting that folic acid was deficient in Rauscher leukemia. Folic acid contents in whole blood and spleen were even higher in the leukemic mice than those in normal mice. Clearance study by injecting folic acid intravenously into leukemic mice showed faster disappearance of folic acid from the circulating blood, suggesting that folic acid demand of Rauscher leukemia is increased. Methotrexate administered shortly after inoculation of the virus did not prevent Rauscher leukemia. But anemia, reticulocytosis and erythroblastosis, which are commonly seen 3-4 weeks later in leukemic controls, were not marked as compared with controls. It can be concluded that the requirement of folic acid is greater in Rauscher leukemia than in controls, and methotrexate is effective for preventing hematological changes commonly seen in this type of leukemias.