[Present state of countermeasure to AIDS in the world today].

UNLABELLED: 1. INTRODUCTION: Only about 10 years have passed since HIV was discovered but WHO presumes that there will be 30 to 40 million infected cases by the year 2,000. This then possesses the possibility of more frequent contact with such persons and thus means we must look for how to protect ourselves. I would like to discuss the present state of AIDS, particularly in eastern European countries such as Bulgaria, Hungary, Romania and Russia, based on recent data I have compiled. 2. AIDS-related laws at present in various countries. (1) Comparison of major laws (17 countries) including 1) patient (17 countries) and infected person (13 countries) notification, 2) protection of privacy (9 countries), 3) prohibiting infected person discrimination (3 countries) and 4) other matters including restraint on behavior to spread infection (6 countries). (2) Entry laws from foreign country (10 countries) applicable to patient and infected person for 1) entry (3 countries) and 2) long period of stay (8 countries). 3. Present countermeasures to AIDS. (1) Data for 8 countries including Japan, U.S.A. U.K., France, Germany and three eastern European countries with regard to 1) budgets, 2) examinations, 3) medical care, 4) consultation and guidance and 5) education. I shall also discuss the following 2 countermeasures in Japan. I have proposed to the Diet: 1) Examination to detect HIV-antibodies in donated blood. This measure is present in effect since Nov. 1st, 1986, as a result of my proposal made to the Diet on March 14th, 1986. 2) For person infected by transfusion of the blood products without heat treatment, I proposed that expenses should be defrayed according to the CD4 level at either CD4 < or = 200 or CD4 < or = 500. (2) Present situation in eastern European countries. Common features are as follows: 1) Infected person and patient are quarantined if they request, since they know their condition which was disclosed based on data from past mass screening test under communism. 2) At present infected persons are few in number. 3) This number will rapidly increase with greater active interchange with western countries following elimination of the Berlin Wall. 4) AIDS countermeasures such as blood and blood products examinations are inadequate due to insufficient funds. In Bulgaria, the government has conducted AIDS tests on more than half the population and in Romania, there is the tragic situation. (3) Guidelines for WHO-ILO countermeasures to AIDS at work places. 4. Present situation in research. The development of effective medicines and vaccines is the primary objective of AIDS research. Research programs may be enumerated as follows; 1) In the U.S.A., NIH and CDC are major organizations which lead research around the world. The major objective is synthetic medicine. 2) In U.K., the development of vaccines for monkey and cat is being sought. 3) In China, herb medicine is administrated to patients in Un-nan-sho where AIDS patients are quite numerous. 4) In Japan, a recombinant vaccine is being sought through use of BCG, vaccinia viruses and the like. 5. Topics related to AIDS include 1) informed consent to be treated by a AIDS-infected doctor, 2) suits against doctors who fail to make infected person known infection and 3) government control laws for AIDS in Russia.

Tissue factor in plasma of patients with disseminated intravascular coagulation.

Recently it has been shown that tissue factor (TF), an important trigger for initiating blood coagulation, is present in the circulating plasma. In order to assess the clinical implications of TF in plasma, plasma concentration of TF was quantitated in 65 patients with disseminated intravascular coagulation (DIC). The mean concentration of plasma TF was elevated in patients with DIC at presentation as compared with healthy subjects (446 +/- SD 536 pg/ml vs. 138 +/- 51 pg/ml, P < 0.001). Abnormally high levels were found only in 46.2% of the patients, predominantly in patients with non-hematological solid tumors and acute leukemia. Plasma TF did not correlate with hemostatic markers of DIC such as thrombin-antithrombin III complex, prothrombin fragment 1 + 2, plasma-alpha 2-plasmin inhibitor complex, FDP, D-dimer, or fibrinogen. Serial determinations of plasma TF demonstrated that plasma TF changes roughly in parallel with the course of DIC in most patients with elevated TF at presentation of DIC. These findings suggest that plasma TF is potentially valuable for monitoring the progress of DIC in a limited population of patients.

Evaluation of oral anticoagulant therapy by measuring plasma prothrombin fragment 1 + 2.

To assess the degree of haemostatic system activation, plasma levels of prothrombin fragment 1 + 2 (F1 + 2), a direct indicator for thrombin generation in vivo, were measured in 49 patients with thrombotic disease undergoing long-term warfarin therapy (Thrombotest values < or = 40%). In these patients, vitamin K dependent coagulation factors (factors II, VII, IX and X) were decreased together with the anticoagulant proteins C and S, but the mean plasma concentration of F1 + 2 was significantly decreased compared with 48 healthy subjects. In warfarin-treated patients, F1 + 2 was positively correlated with the Thrombotest value, factors II, VII, IX and X. When analysed according to the intensity of anticoagulation, patients with Thrombotest values less than 30% showed a significant decrease in F1 + 2, but the mean F1 + 2 level was normal in patients with Thrombotests higher than 30%. These findings indicate that long-term oral anticoagulant therapy suppresses thrombin generation approximately in parallel to the decrease in coagulation factors, and levels of F1 + 2 lower than healthy subjects are observed when Thrombotest values are less than 30%.

Early Erythroblastic Leukemia Presenting as De Novo Acute Leukemia.

Early erythroblastic leukemia is a newly defined type of leukemia in which the blasts have the same characteristics as erythroid precursors at the level of CFU-E. The blasts are characterized by the presence of carbonic anhydrase I, CD 36 antigen, platelet peroxidase (PPO)-like activity, and ferritin-containing granules. Early erythroblastic leukemia appears to have characteristic clinical features; in the original report of nine cases, only one patient had typical de novo acute leukemia. We report here a case of early erythroblastic leukemia that presented! as de novo acute leukemia. The blasts from this patient had almost the same ultrastructural and phenotypical characteristics as those of the originally reported cases, even though our case was not examined for anti-carbonic anhydrase I antibodies. As a single marker, PPOl activity can no longer be considered specific for the megakaryocyte-platelet lineage, even though the significance of transient expression of PPO-like activity in immature erythroblastic cells at the level of CFU-E still remains to be clarified. When leukemic blasts show positivity for CD36 and negativity for megakaryocytic or monocytic markers, the diagnosis of early erythroblastic leukemia should be suspected and electron microscopical characteristics should be studied.

Plasma von Willebrand factor proteolysis in patients with chronic myeloproliferative disorders: no possibility of ex vivo degradation by calcium-dependent proteases.

Patients with chronic myeloproliferative disorders (CMPD) frequently have abnormalities of plasma von Willebrand factor (vWf) multimers. The pathogenesis of this phenomenon is still unknown. In order to evaluate the possibility of ex vivo degradation of vWf during blood processing, we compared vWf antigen, ristocetin cofactor and the multimeric composition of vWf in plasmas obtained in the presence of trisodium citrate with or without calcium-dependent protease inhibitors (leupeptin, N-ethylmaleimide and Na2EDTA). The subjects included 20 patients with CMPD, 11 with other diseases and 8 normal subjects. In patients with CMPD and normal subjects, the values of vWf antigen, ristocetin cofactor, ristocetin cofactor/vWf antigen ratio and the relative amount of large multimers of vWf did not significantly differ from each other in plasma samples with and without protease inhibitors. In other diseases, especially in a patient with disseminated intravascular coagulation, a somewhat higher amount of large multimers were found in plasma with protease inhibitors than without inhibitors. These findings indicate that the ex vivo proteolysis during blood processing is negligible in patients with CMPD, and that the observed abnormalities in vWf is an in vivo phenomenon.

Plasma levels of protein C and vitamin K-dependent coagulation factors in patients on long-term oral anticoagulant therapy.

Plasma levels of protein C (PC) and vitamin K-dependent coagulation factors (factors II, VII, IX and X) were measured in 100 specimens from patients on long-term warfarin therapy. Both activities and antigens of these coagulation factors were decreased, depending on the thrombotest values. Factor II activity/antigen ratio and factor X activity/antigen ratio were correlated well with thrombotest values, indicating that the concentration of inactive molecules (PIVKAs) relative to normal proteins increases with increasing intensity of anticoagulation. Although PC antigen (PC:Ag) was also decreased, the ratios between PC:Ag and vitamin K-dependent coagulation factor antigens remained constant, being independent of the intensity of warfarin therapy. These findings indicate that long-term oral anticoagulant therapy results in the suppression of the synthesis of both vitamin K-dependent coagulation factors and PC, but the production of the coagulant and anticoagulant proteins is well-balanced.

Protein C levels in disseminated intravascular coagulation and thrombotic thrombocytopenic purpura: its correlation with other coagulation parameters.

Protein C was measured by means of enzyme-linked immunosorbent assay (ELISA) in plasmas from 58 normal subjects, 39 patients with disseminated intravascular coagulation (DIC) and 5 patients with thrombotic thrombocytopenic purpura (TTP). Protein C levels ranged from 69.7 to 163.6% (95% confidence limits) in normal subjects. In patients with DIC, protein C concentrations were significantly decreased, with a geometric mean value of 42.1%. Protein C concentration was positively correlated with plasma prothrombin, antithrombin III and serum pseudocholinesterase, and was negatively correlated with von Willebrand factor antigen (vWF:Ag) and vWF:Ag/factor VIII ratio. These findings suggest that low protein C concentrations in DIC mean a consumption of protein C probably due to its activation by thrombin and/or impaired liver synthetic function. In patients with TTP, protein C levels were normal with a geometric mean value of 116.7%, indicating that the pathophysiology of TTP is quite different from that of DIC.

[A study on application of the function of maintaining concentration (TAF) for chronic schizophrenia].

The function of maintaining concentration (TAF) is the new method of the evaluation of fatigue that has been devised by Takakuwa. Chronic schizophrenia are observed in everyday affairs, as if they have "fall of work will and lowering of work sufficiency". Reasonable approaches to the evaluation of these state of chronic schizophrenia may be provided by TAF test. The patients who are grasped by TAF test as lowering of their ability are recovered by prescription of the apt dose of an antipsychotics. The interruption or overdose of the medicine leads again to a lowering of TAF. No change of TAF after the interruption of the medicine is considered as the remission. The all 3 cases may be indicated that TAF test has clinical application.

[Studies on the change of spontaneous locomotor activities in rats due to forced exercise (author's transl)].

The authors have devised an apparatus for monitoring the spontaneous locomotor activity of rats, with which the patterns of locomotor activity under the condition of light-dark cycle (light period: twelve hours from 6 a.m., dark period: the other half of the day) were analysed. In addition, changes in locomotor activities due to forced exercise (swimming) were recorded. The results obtained were as follows: 1. The patterns of locomotor activities in rats recorded by the monitor showed the same patterns as reported already by other researchers. The authors believe that this new apparatus can be used practically as a locomotor activity monitor. 2. Due to exhaustive exercise by swimming, changes of the ultradian rhythm in rats were observed. 3. By loading of swimming, locomotor activities in rats decreased significantly, especially in the dark period. These results suggest that this newly devised apparatus is useful as a locomotor activity monitor, and that the fatigue in rats caused by physical load can be shown as the change in locomotor activities.

[Studies on the items for diagnosis of the vibration disease. Part 1. Examination of healthy workers using vibratory tools].

1,215 male workers using bush cleaners in Hokkaido were examined by the method based on the notification of the Labor Standard Bureau. The results obtained from clinically normal 548 workers among them were analysed especially on the finger skin temperature, vibratory sense threshold, maximum grip strength. 1) Data of the vibratory sense threshold, maximum grip strength and endurable grip strength showed normal distributions. Data of the finger skin temperature, however, showed a skewed distribution. 2) In parallel with aging, the vibratory sense threshold increased, in other words, lowered in function, and the maximum grip strength lowered. 3) The endurable grip strength measured by the five-time repetition method decreased along with aging. 4) Values of one-tail limit of the finger skin temperature were calculated in all 548 workers, and those of the vibratory sense threshold, maximum grip strength and endurable grip strength were done in each age group. The values were compared with the already proposed criteria and discussed.

Effect of physical exercise on the activity of GOT isozyme in human plasma.

Untrained healthy male volunteers were subjected to the study on the effects of exercise (bicycle ergometer, 920 kpm/min for 30 min) upon GOT isozyme (supernatant GOT, s-GOT and mitochondrial GOT, m-GOT) activities in plasma. Significant increases in the levels of both s-GOT and m-GOT activity were observed after the exercise (p less than 0.001). After 30 min of rest m-GOT activity almost returned to its preexercise value. However, s-GOT activity did not return to its preexercise activity. The changes in the activity of GOT isozyme after physical exercise are discussed.