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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.

From the histochemical study on the vascular distribution of limb muscles of cats and rats, the following results were obtained. 1. The red, white and intermediate fibers of the soleus and gastrocnemius individually present dissimilar patterns of the vascular distribution. In the transverse section of the muscle, most of the capillaries are found preferentially assembled around the small red fiber. Usually the red fibers are supplied with 4-6 capillaries, while the intermediate fibers 3-4 capillaries and the white 1-2 capillaries. 2. In the longitudinal section, the capillaries run parallel with the muscle fiber. Occasionally, these capillaries branching out for anastomoses cross the fiber almost at right angle. These anastomoses are more frequently observed on the red fibers. 3. The soleus muscle is better supplied with capillaries than is the gastrocnemius, because this muscle is composed only of two types of capillary rich fibers, namely, the red and intermediate fibers. 4. The mean capillary-fiber ratio of the cat gastrocnemius proves to be 0.6 and that of the soleus 1.4. 5. From these observations, it is considered that there is an intimate relationship between the capillary distribution pattern and the type of individual muscle fibers. 6. The red fibers being with a high oxidative enzyme activity and rich in mitochondria may require an abundant supply of oxygen and have a greater number of capillaries. In contrast to this, the white fibers with a lower enzyme activity and a fewer mitochondria need not to consume so much oxygen and are supplied with a fewer capillaries, because they participate only in phasic contraction. The intermediate fibers, with a moderate enzyme activity, may be considered to have a moderate number of capillaries.

Mononuclear cells from rabbit joint fluid were studied after synovitis was induced by various means, including the intra-articular injection of bacterial endotoxin or of aggregated human gamma globulin in normal rabbits, or of HGG in rabbits previously sensitized to this material. The large majority of mononuclear cells in all groups were monocytoid rather lymphocytoid, and these cells were most readily labeled with tritiated thymidine on the first day after injection. On day 2 and 3, the numbers of labeled cells decreased, except for the animals previously sensitized with HGG, in which there was an upswing of labeling on day 3. This upswing was associated with a considerable increase in numbers of cells resembing synovial cells, and may possibly be a reflection of synovial proliferation. Macrophages loaded with engulfed polymorphonuclear cells were observed in all experimental groups, a finding which emphasizes the lack of specificity of this reaction.

A high incidence of subnormal serum folic acid levels was observed in 48 patients receiving anticonvulsants (75 %). In peripheral blood, macrocytosis was detected in 46 % and an increase of hypersegmented neutrophils was also seen in 24 % of the patients. Correlation existed between these signs and low serum folate levels. The growth response of Lactobacillus casei and L. leichmannii was not suppressed by the addition of various anticonvulsants to the medium of the bioassay systems. Administration of 5 mg of folic acid for a month corrected macrocytosis and an increase of hypersegmented neutrophils significantly. Folic acid supply also decreased mean diameters of the nuclei of oral epithelial cells significantly. It is concluded that subclinical folic acid deficiency is common among the patients receiving anticonvulsants. Absorption of 3H.folic acid from the small intestine of rats was inhibited by large dose of diphenylhydantoin (20 mg) not by 5 mg. This fact suggests that in patients on diphenylhydantoin, the quantity balance of folic acid and diphenylhydantoin in the intestine regulates the absorption of folic acid.

I) On an identified giant neurone of the right parietal ganglion in a snail's subesophageal ganglion-complex, the synaptic contribution to the production of the plateau formation of biopotential or grouped spike discharges of the soma has been studied in the presence of a convulsant. 2) The orthodromic stimulation of a peripheral nerve (the intestinal nerve) can elicit the plateau formation of biopotential, instead of normal spike discharges, in the identified neurone treated with a convulsant. 3) With the application of a convulsant, for example bemegride which was in a concentration less than that necessary to produce the plateau formation, an EPSP accompanied a spike with a constant delay. This EPSP is a product of a proprioceptive reflex arc consisting of two excitatory synapses with a certain subordinate neurone. 4) Later, in the presence of a convulsant, spontaneously conveyed multiple EPSP's were observed on the biopotential of the identified neurone. These multiple EPSP's produced grouped spike discharges or the plateau formation of biopotential of the neurone. 5) The multiple EPSP's may be produced by the grouped spike discharges of the subordinate neurone, the membrane property of which would be changed by a convulsant. It is presumed that the grouped spike discharges or the plateau formation of biopotential often occurs synchron. ously in many neighboring neurones by means of synaptic triggering in the presence of a convulsant.

Circular DNA isolated from human kidney mitochondria was studied by electron microscopy. I. Mean contour length of monomers of the mitochondrial DNA was 4.96 ± SE 0.28 /μ 2. The complex molecules (oligomers) of mitochondrial DNA were observed in frequency of 6.2 per cent. Among them circular dimers accounted for two per cent of all circular DNA molecules. 3. Circular DNA fibers with an intermediate perimeter between the　monomer and dimer, and with a contour length shorter than 3 μ were occasionally observed. 4. Some discussions were made on the emergence of the circular dimer.

A non-invasive method for measuring portal blood flow by magnetic resonance (MR) phase contrast was evaluated in a flow phantom and 20 healthy volunteers. In a flow phantom study, the flow volumes and mean flow velocities measured by MR phase contrast showed close correlations with those measured by electromagnetic flowmetry. In 20 healthy volunteers, the cross-sectional areas, flow volumes and mean flow velocities measured by MR phase contrast correlated well with those measured by the Doppler ultrasound method. Portal blood flow averaged during the imaging time could be measured under natural breathing conditions by using a large number of acquisitions without the limitations imposed on the Doppler ultrasound method. MR phase contrast is considered to be useful for the non-invasive measurement of portal blood flow.

To clarify the influence of the introduction of metal bats on the physique and batting records of the players in the National Summer High School Baseball Tournaments, a comparative analysis was conducted between height, body weight, body-weight ratio (body weight/height), batting average and home run average of the best four teams' players (n = 493) and those of the other teams' players (n = 4,590) in three periods: the period of the use of wooden bats, that of the use of both wooden and metal bats and that of the use of metal bats. In the period of metal bat use, the mean values of physique of the best four teams' players were significantly larger (P < 0.05) and their average number of home runs was significantly higher than those of the other teams' players (P < 0.01). The only significant differences between the two groups in those indices for each time period were for height in the wood and metal/wood periods. This study demonstrated that the differences between the home run average and physique, including height, body weight and body-weight ratio of the best four teams and the rest of the teams were the greatest after the use of metal bats. These findings suggest that the importance of the home run average increased and was associated with large-size of physique after the use of metal bats in the National Summer High School Baseball Tournaments.

With the parameters of a flow-volume and a volume-time curve, the discriminant analysis of bronchial asthma is described. The subjects were classified into three groups (healthy adults, mild asthmatic patients and moderates ones). The difference of the mean vectors of the parameters of the three groups was made clear by the selection methods of the discriminant analysis between any two of the groups both with 6 parameters (%FVC, FEV1.0%, peak flow rate (PF), flow rate at 50% of FVC (V50), flow rate at 25% of FVC (V25), and V50/V25) and with 8 (6 parameters mentioned above and V75, V10). Forced expiratory volume in 1 second percent (FEV1.0%) or V50 was selected at the first step with 6 parameters, and V75 was selected at the first step with 8 parameters. Probabilities of misclassification with 8 parameters were lower than those with 6 ones and the probability of misclassification at the discriminant analysis between healthy adults and mild asthmatic patients with 8 parameters was 15.75% at the final step.

In urine of diabetics, a significantly great inhibitory activity of glyceraldehyde 3-phosphate dehydrogenase (GAP-Dehyd) was observed compared with that of normal subjects. The 0.2 ml of urine from 41 patients with diabetes mellitus inhibited 0.5 units of GAP-Dehyd by 27.2 +/- 3.0% (mean +/- S.E.M.), while that from 17 normal volunteers inhibited only by 9.0 +/- 1.0% (P less than 0.05). This inhibitory substance was extracted by 90% ethanol from diabetic urine and partially purified by anion exchange chromatography using Dowex-1 (HCOO type). The molecular weight of this substance was confirmed to be 100--300 daltons by an analysis on Biogel P-4 gel filtration chromatography. And analysis by thin layer chromatography using silicagel plate showed that this inhibitor was a ninhydrin reactive substance which has not been reported previously. From the above facts, it was assumed that the inhibitory substance of GAP-Dehyd in urine of diabetics was a new acidic compound of low molecular weight containing an amino residue in the molecule.

The homovanillic acid (HVA) concentrations in the lumbar cerebrospinal fluid (CSF) were determined in 38 epileptic and 39 control patients. The mean concentration of HVA was 23.9 ng/ml +/- 2.8 SEM for the epileptic group and 30.2 ng/ml +/- 2.1 SEM for the control group, respectively. Thus, HVA was significandly reduced in the patients with epilepsy compared with the controls. The mean HVA in the female patients was higher than in the male patients in both groups but this failed to reach statistical significance. There was no apparent relationship between the degree of reduced HVA concentration and other clinical indexes of the epilepsy (age, type and frequency of seizures, and anticonvulsant medication). For the determination of concentration gradient of HVA three fractions of the spinal CSF were obtained from 11 patients. A pronounced gradient of HVA concentration was found with a ratio of 1 : 1.46 : 1.97 for the first, second and third fractions. This suggests that a standardized conditions for collecting CSF should be employed to study HVA levels in humans.

Natural killer (NK) cell activity, lymphokine activated killer (LAK) activity and Epstein-Barr virus specific cytotoxic T lymphocyte (EBV-CTL) activity were examined in 10 children with chronic active EB-virus infection and an adult with persistently positive early antigen-antibody to EB-virus. NK cell activity against erythroleukemia cell line K-562 was significantly (p less than 0.005) lower in the patients (22.3 +/- 8.5%, mean +/- SD) than in normal controls (40.4 +/- 15.9%). Spontaneous cytotoxicity against an EB-virus transformed autologous lymphoblastoid cell line was 15.0 +/- 7.6% in the patients, and was comparable to spontaneous cytotoxicity activity in normal controls (11.7 +/- 4.3%). LAK activity against Raji cells was significantly (p less than 0.02) lower in the patients (14.6 +/- 11.4%) than in normal controls (29.2 +/- 15.9%). EBV-CTL activity against an EB-virus transformed autologous lymphoblastoid cell line was significantly (p less than 0.005) lower in the patients (11.8 +/- 5.5%) than in seropositive normal controls (33.7 +/- 14.7%). No regression of the lymphoblastoid cell line was observed when EBV-CTL activity of the patients was tested by regression assay. It is conceivable that defects in both EB-virus specific and nonspecific killer cell activities play important roles in the pathogenetic abnormalities which allow EB-virus infection to progress to a chronic active state.

Serial left ventricular (LV) echocardiographic studies were performed in 21 patients before and after aortic valve replacement for chronic aortic regurgitation. The effect of valve replacement on LV dimensions, cross-sectional area of the LV muscle and LV function was determined from the echocardiographic data. The relation between degeneration of the myocardium and surgical outcome was also investigated. The average LV end-diastolic dimension decreased from 66.0 +/- 8.3 mm to 46.3 +/- 5.7 mm twelve months postoperatively. The average LV end-systolic dimension also fell from 43.4 +/- 8.1 mm to 31.1 +/- 5.0 mm. The muscle cross-sectional area decreased from 33.1 +/- 5.1 cm2 to 24.5 +/- 4.0 cm2, indicating a decrease in LV mass. The indices of contractility (fractional shortening, ejection fraction and mean velocity of circumferential fibre shortening) had a tendency to decrease one month after surgery, but they subsequently increased to the normal level 12 months after surgery. Nineteen out of 21 patients showed a favorable outcome as to the functional status. The remaining two patients had a large LV dimension and subnormal contractility, and they failed to show a significant reduction in the follow-up period. The muscle score in the two patients was greater than 8 points, which indicated irreversible impairment of the myocardium. Patients with persistent postoperative LV enlargement have a poor prognosis and should be identified so that aggressive medical treatment can be instituted.

In order to explore the pathogenic mechanism of proteinuria in glomerulonephritis, ultrastructural changes of the glomerular basement membrane were investigated in rats with chronic serum sickness induced by repeated intravenous injections of bovine serum albumin (experimental rats). Rats injected with saline served as controls. The animals were sacrificed and examined 13 weeks after treatment, when the mean urinary protein of experimental animals reached 206 mg/24h/100g body weight. Enhanced transcapillary passage of anionic ferritin was observed in experimental rats. Purified glomerular basement membranes of control and experimental rats were examined by electron microscopy after negative staining. The glomerular basement membrane of experimental rats had enlarged pores. The results suggest that an increase in the radius of glomerular pores may be responsible for proteinuria in glomerulonephritis.

The development of useful therapy for intraabdominal carcinomatosis originating from gastrointestinal cancer is an important theme in cancer therapy. We developed recently an experimental model of intraabdominal carcinomatosis in nude mice by intraperitoneal transplantation of human colon cancer cells (RPMI 4788). Using this model, we investigated the antitumor effects of recombinant human interferon (rIFN)-beta and rIFN-gamma administered singly or in combination. Treatment was initiated 2 days after CD-1 nude mice were inoculated intraperitoneally with 5 X 10(6) RPMI 4788 cells. Intraperitoneal administration for 10 consecutive days of either rIFN-beta (2.5 X 10(5) IU/mouse/day) or rIFN-gamma (2.5 X 10(5) JRU/mouse/day) resulted in a significant prolongation of survival compared with the saline control group [survival in the control: 41.8 +/- 5.6 days (mean +/- SD)]. Combined administration of rIFN-beta and rIFN-gamma for 10 days yielded a marked synergistic effect on the prolongation of survival (114.0 +/- 8.2 days). However, combined administration of rIFN-beta and rIFN-gamma in a single dose equal to the total dose given fractionally over 10 days did not yield a synergistic effect. These results suggest that daily administration of rIFN-beta and rIFN-gamma combined may provide a highly potent antitumor effect against human peritoneal carcinomatosis.

The surface ultrastructure of larval Anisakis type I, Anisakis type II, Raphidascaris, Contracaecum type A, Thynnascaris type A and Thynnascaris type B was examined by scanning electron microscopy. These species were identified clearly by the presence of a boring tooth, a mucron, and other morphological features. The means of the distances between transverse striations (DBTS) of larval Anisakis type I (5.45 +/- 0.125 micron), larval Raphidascaris (2.92 +/- 0.051 micron), and larval Contracaecum type A (1.68 +/- 0.056 micron) are significantly different (p less than 0.05). There was a correlation between the diameter of worm trunk (DOWT) and DBTS among these three larval types. In most cases a larva could be identified from the mean value of DBTS and DOWT even if obtained as a fragment from a patient.

The effect of the heart rate and myocardial contractile force on the extravascular resistance to blood flow of the left anterior descending coronary artery (LAD) was evaluated in 15 mongrel dogs anesthetized with sodium pentobarbital. The LAD was maximally dilated by intracoronary infusion of adenosine, which precluded the influence of vasomotor tone. Increases in the heart rate and myocardial contractile force decreased coronary blood flow in the absence of a change in coronary perfusion pressure. The changes in mean coronary resistance showed a significant linear relationship to changes in developed tension. The changes in coronary resistance caused by varying the heart rate and contractile force were so small that a normal coronary vascular tree could easily compensate for the increase in resistance. However, it is supposed that with critical stenosis of the vascular tree even a small increase in resistance might cause deleterious effects on coronary blood flow.

Upper gastrointestinal bleeding is a major adverse event of non-steroidal anti-inflammatory drugs (NSAIDs), and co-administration of proton pump inhibitors and H2 receptor antagonists has been established as a means of preventing such an eff ect. However, the incidence of bleeding associated with NSAID-induced ulcers under conditions where such strong anti-acid agents are used for prevention has yet to be clarified. We aimed to determine the annual incidence of serious upper gastrointestinal ulcer bleeding among Japanese patients in whom NSAIDs were used in our hospital. Before commencing the study, we recommended to all the physicians in our hospital the best method for caring for NSAID users, focusing on the concomitant use of proton pump inhibitors or H2 receptor antagonists. We conducted a cohort study involving 17,270 patients for whom NSAIDs had been newly prescribed. Bleeding from gastric ulcers was observed in 8 of the 17,270 patients using NSAIDs (0.05%). The pooled incidence rate for bleeding was calculated as 2.65 (95% confidence interval, 2.56-2.74) and 1.29 (1.27-1.31) per 1,000 patient years for low-dose aspirin and non-aspirin NSAID users, respectively. None of the bleeding ulcer patients required blood transfusion or were in serious condition. In conclusion, gastric ulcer bleeding occurred in low-dose aspirin or non-aspirin NSAID users, but its incidence was low and outcomes were not serious when adequate preventive measures were taken.

Leptin is a hormone which is predominantly secreted by adipose tissue. Recent studies have shown that leptin increases arterial blood pressure. Although data from available animal studies clearly indicate an association between leptin and hypertension, results of human studies have been less definitive. We conducted a case-control study to examine the association between serum leptin levels and hypertension in 111 hypertensive subjects and 222 male controls, using conditional logistic regression analyses. Mean serum leptin levels were found to be marginally higher in the case subjects than in the control subjects (3.3 ng/ml versus 3.0 ng/ml), however, conditional logistic regression analysis revealed that subjects in the highest quartile had a significantly increased risk of hypertension compared with those in the lowest quartile, even after adjusting for drinking status and diabetes mellitus (adjusted OR, 2.11;95% CI, 1.01-4.39). Our findings suggest that leptin plays an important role in the development of hypertension.