The effect of intraperitoneal injection of adenosine 200 mg/kg on the tissue levels of PRPP was investigated in male mice. The liver PRPP level was increased, peaked at 30 min, after adenosine administration. In contrast, the spleen, heart and erythrocyte PRPP levels were decreased. However, the erythrocyte PRPP level began to increase two hours later adenosine administration. A similar increase was observed in the spleen PRPP, but the magnitude was less than that in erythrocytes. Concomitantly, marked decrease of plasma Pi concentration was observed.
The effects of adenosine, inosine a n d guanosine on free and available PRPP concentrations were also investigated in rat and chicken erythrocytes, and mouse splenic lymphocytes in vitro. Under physiological Pi concentrations, these purine nucleosides diminished free and available PRPP concentrations in rat erythrocytes and free PRPP concentration in chicken erythrocytes, but stimulated available PRPP synthesis in chicken erythrocytes. As concerns lymphocytes, the purine nucleosides, especially adenosine, decreased the free PRPP concentration in the presence of physiological Pi concentrations. Available PRPP synthesis was inhibited by adenosine, but not by inosine and guanosine.
Dibutyryl cyclic GMP (Bt₂cGMP) stimulated available PRPP synthesis in the lymphocytes. On the other hand, dibutyryl cyclic AMP (Bt₂cAMP) showed no change in the available PRPP formation. However, Bt2cAMP antagonized the Bt2cGMP response. Adenosine also blocked the Bt₂cGMP effect. ACh as well as Bt₂cGMP enhanced the available PRPP formation in the presence of 1 mM Ca⁺⁺, which was antagonized by Bt₂cAMP.
These findings suggest that immunosuppressive effects of adenosine and severe combined immunodeficiency disease with adenosine deaminase deficiency may be explained at least partly from decrease of PRPP synthesis.

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A pronounced hyperuricemic state was induced, peaked at 30 min, after intraperitoneal administration of xylitol or fructose at a dose of 0.5 g/kg in male mice. The level of uric acid increased more after xylitol than after an equivalent dose of fructose.
Xylitol and fructose markedly elevated the liver PRPP levels, peaked at 15 min, after the intraperitoneal administrations in mice. Increase in the PRPP level after xylitol injection was dose-dependent and much higher than that after fructose. However, the PRPP levels in the erythrocytes were not changed or rather decreased by xylitol or fructose injection.
On the other hand, no substantial increase of both the liver PRPP and serum urate level was found by glucose administration.
Xylitol-induced elevation of the liver PRPP was not due to stimulation of insulin release by this compound, because this response was also observed in the alloxan-treated mice.
These observations suggest that not only stimulate d degradation of ATP but also enhanced PRPP level followed by stimulation of purine de novo synthesis in the liver may play an important role in the mechanism of hyperuricemia induced by xylitol and fructose.

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Purine nucleotide biosynthesis in human leukocytes completely depends on the salvage pathway since no capacity of purine biosynthesis de novo has been recognized in them. Since the report by Giblett et al. of the primary immunodeficiency associated with purine nucleoside phosphorylase ( PNP ) deficiency, the physiological importance of PNP was further confirmed. When PNP activity is low in leukocytes, the rate of purine nucleotide biosynthesis seems to decrease, In addition, it was recognized that the growth of human T-lymphocytes in vitro was inhibited by the presence of guanosine which is one of the substrates of PNP and that the granulocyte colony formation from mouse bone marrow cells in vitro was also inhibited. The inhibition seems to occur as a result of the decrease in pyrimidine biosynthesis de novo. The PNP activity of leukemic cells was examined, which was low in AGL, AMoL and CGL. The reason of these low values of PNP is speculated.

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We reported a case with gouty attack auring tne course of psoriasis vulgaris.
A male patient, aged 74 years old, was transferred to our clinic for fever and painful swelling of the left great toe. He has been treated for psoriasis vulgaris and hypertension over 20 years. Seven years before the admission, his blood pressure was 180-100 mmHg and proteinuria was not detected. Serum uric acid concentration was 9.2 mg/100 ml, although the blood urea N and creatinine levels were within normal limits. He was readmitted to the Department Of Dermatology for psoriasis two months before. Laboratory examinations showed mild azotemia(blood urea N 37, creatinine 2.8 mg/100 ml ) and hyperuricemia. PSP excretion was 6 per cent for 15 minutes and GFR 33 ml/min. After the administration of allopurinol 600 mg a day he was struck by recurrent fever and the left great toe pain with local swelling and redness. The intravenous pyelogram showed a right renal stone. Uric acid clearance was 2.67 ml/min and the ratio of urate clearance to creatinine clearance was 10.27 per cent, which was within normal limits. In pyrazinamide suppression test the urate secretion rate and the fractional urate excretion were also within normal range, in spite of the sustained hyperuricemia and the decreased GFR. These data were quite different from those of patients with chronic renal diseases, who showed a significantly decreased value of the fractional urate excretion after pyrazinamide administration. On the other hand, the fractional urate excretion in gouty patients with a decreased GFR was almost normal, in accord with this patient's data.
It is generally believed to be difficult to diff e rentiate a secondary hyperuricemia due to chronic renal failure from a primary hyperuricemia of gouty nephropathy with a decreased renal function.
Some patients with psoriasis vulgaris show hyperuricemia, which is caused by an increased nucleic acid turnover resulting from the marked acceleration of epidermal proliferation.
It is a question in this patient which is a primary cause of hyperuircemia and gouty attacks, a decreased urate excretion from renal dysfunction or an increased urate synthesis in psoriasis vulgaris.
This patient was proven to have a renal stone and had shown asymptomatic hyperuricemia even when his blood urea N and creatinine levels had been within normal limits. From these facts the hyperuricemia of this patient is considered to result from an increased urate synthesis in longstanding psoriasis vulgaris and not from a decreased urate excretion in chronic renal failure. The results of the pyrazinamide suppression test support this possibility.
We concluded that this patient was struck by gouty attacks bacause of the sustained hyperuricemia resulting from an increased urate synthesis in longstanding psoriasis vulgaris.

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Hyperuricemia is sometimes associated with various blood dyscrasias including leukemia and lymphoma, while it is rarely found in patients with nonlymphomatous solid tumors.
We reported two cases of hyperuricemic renal failure caused by solid malignant tumors. Case 1 was 51-year-old male of esophagus cancer. Laboratory data on admission were as follows: BUN,69.4 mg/dl; serum creatinine,3.8 mg/dl; uric acid,26.5 mg/dl; and LDH,1960 IU. He was treated with peritoneal dialysis. Case 2 was 60-year-old female of gastric cancer, who showed the following laboratory data: BUN,78.1 mg/dl; serum creatinine,3.1 mg/dl; uric acid,26.2 mg/dl; and LDH,624 IU.
Statistical analysis was performed on 100 patients with nonlymphomatous solid tumor. Hyperuricemia was found in 6 % of them. Hyperuricemic patients were demonstrated to have elevated blood urea nitrogen and creatinine. Furthermore, they had raised levels of GOT, LDH, total bilirubin and alkaline phosphatase, being signicantly higher (p<0.001)than normouricemics. All of six hyperuricemic patients had massive liver metastasis.
Hyperuricemia associated with solid tumor could be related to the presence of widespread massive metastasis, especially the involevement of liver.

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It has been noticed that serum uric acid levels are low in patients with cancer of the prostate. For the purpose of evaluation of this fact, comparative studies of serum uric acid levels were carried out between cancer of the prostate and prostatic hypertrophy. In addition to it, the changes of uric acid, creatinine, various proteins such as α₁-Acid Glycoprotein (α₁-AG), α₁-Antitrypsin (α₁-AT), Ceruloplasmin (Cp), Antithrombin III (AT-III), and α₂-Macroglobulin (α₂-M) in the serum following the administration of synthetic female hormone in the cases of cancer of the prostate were studied.
The results were summarized in the following. (1) Significant decreases of serum uric acid and creatinine levels were confirmed in cancer of the prostate in comparison with those in prostatic hypertrophy. (2) Following the administration of “Diethylstilbestrol diphosphate (Honvan)”, serum uric acid levels showed a tendency to decrease in cancer of the prostate. (3) Among the cancers of the urogenital tract, decreases of α₁-AG and AT-III and an increase of Cp were significantly documented in cancer of the prostate.
These findings suggest that there is the presence of the state of relative increase of “female hormone” in the cases of cancer of the prostate, and that this might be play in some role in the development of cancer in the prostate. It is also assumed that serum uric acid levels could be used as an useful parameter for the evaluation of the state of fgmale hormone in the serum.

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Intensive muscle exercise occasionally lead to hyperuricemia and/or uricosuria in man. However, these mechanism is not quite uncle ar. Recently we had a oppotunity to study the prevalance of gout and hyperuricmia on two preofessional baseball teams in Tokyo. Unusual high incidence of gout hyperuricemia, increasing of serum CPK was revealed throughout this study. The results are following.
1) The prevalance of gout 3,3 % and it of hyperuricemia was 34.0 %. The prevalance was up to 54.2 % among major Teague players. This incidence of gout was about 10 times higher than it of the s ame age normal population in Tokyo. In addition, serum creatini n e and BUNw as also more increased among these major league players than retired staff and or farm team players. (Table-2)
2) 97.1 % of the subjects showed increasing of the serum CPK level and mean value of active playsers was four to eig ht times higher than normal adults.
3) Serum uric acid highly increased during 5 mounths intensive muscle exercise among 20 farm-team players. (Table- 3)

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Recently the American Rheumatism Association Comittee on classification criteria for gout reported the "preliminary criteria for the classification of the acute arthritis of primary gout.
We assesed this diagnostic criteria from clinical, epidemiological situation, to classify the acute gouty arhtritis from other arthritis. The data were obtained from 30 gouty patients and 30 patients with rheumatoid arhtritis (RA) whose diagnosis was established under classical diagnostic criteria.
On the other hand, we added 10 cases with gout whose informations were obtained in our previous population study. The results were following.
Five or more criteria of 11 criteria were found in 96.5 % of the patients with primary gout and in 5.9 % of the patients with early stage of RA.6 or more of the eleven criteria were found 86.6 %of the patients with primary gout and none of in other arthritis.
From our these data we would like agree with the opinion which was mentioned by original outhers of this criteria.
So, if the six or more of eleven criteria were found in a patients, it may be acceptable that the patient is diagnosed as a primary gout both clinical and epidemiological study.

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