Development of advanced photon calibrator for Kamioka gravitational wave detector (KAGRA).

The Kamioka Gravitational wave detector (KAGRA) cryogenic gravitational-wave observatory has commenced joint observations with the worldwide gravitational wave detector network. Precise calibration of the detector response is essential for accurately estimating parameters of gravitational wave sources. A photon calibrator is a crucial calibration tool used in laser interferometer gravitational-wave observatory, Virgo, and KAGRA, and it was utilized in joint observation 3 with GEO600 in Germany in April 2020. In this paper, KAGRA implemented three key enhancements: a high-power laser, a power stabilization system, and remote beam position control. KAGRA employs a 20 W laser divided into two beams that are injected onto the mirror surface. By utilizing a high-power laser, the response of the detector at kHz frequencies can be calibrated. To independently control the power of each laser beam, an optical follower servo was installed for power stabilization. The optical path of the photon calibrator's beam positions was controlled using pico-motors, allowing for the characterization of the detector's rotation response. Additionally, a telephoto camera and quadrant photodetectors were installed to monitor beam positions, and beam position control was implemented to optimize the mirror response. In this paper, we discuss the statistical errors associated with the measurement of relative power noise. We also address systematic errors related to the power calibration model of the photon calibrator and the simulation of elastic deformation effects using finite element analysis. Ultimately, we have successfully reduced the total systematic error from the photon calibrator to 2.0%.

Serum CRP in patients with gout and effects of benzbromarone.

OBJECTIVE: C-reactive protein (CRP) is associated with increased risk for myocardial infarction, atherosclerosis, and peripheral artery diseases, while increased serum uric acid level is suggested to be independently associated with an increased risk of cardiovascular mortality. Accordingly, to investigate whether hyperuricemia is associated with serum CRP, we compared serum CRP levels between healthy subjects and patients with gout. In addition, we also examined whether benzbromarone has effects on serum CRP levels in patients with gout and the expression of CRP messenger RNA of CRP in the hepatoma cell line HuH7. METHODS: In the first experiment, 40 healthy males and 43 male patients with gout were enrolled, then blood samples were drawn from each after an overnight fast. In the second experiment, 42 male patients with gout were given uric acid-lowering therapy with benzbromarone. Blood samples were drawn after an overnight fast before and 1 year after beginning benzbromarone treatment. In the third experiment, the effects of benzbromarone on IL1beta-induced CRP expression were determined in HuH7 cells. RESULTS: Log serum CRP levels were not significantly different between the patients with gout and healthy subjects, while log serum CRP levels were decreased by 11% after benzbromarone treatment, as compared to the values before treatment (p < 0.01). In addition, log serum adiponectin levels were elevated by 2% after treatment (p < 0.01). Furthermore, our in vitro findings demonstrated that benzbromarone down-regulated IL1beta-stimulated CRP gene expression. CONCLUSIONS: These results suggest that hyperuricemia may not contribute to an increase in serum CRP level, while benzbromarone may have a favorable effect on CRP.

Effects of bovine milk ingestion on urinary excretion of oxypurinol and uric acid.

OBJECTIVE: Although allopurinol is a xanthine oxidase inhibitor, its overall effect may be due to the action of oxypurinol, a metabolite of allopurinol and another xanthine oxidase inhibitor, since the biological half-life of oxypurinol is longer than that of allopurinol. Oxypurinol shares a renal transport pathway with uric acid and ingestion of bovine milk increases the urinary excretion of uric acid. Therefore, we investigated whether its ingestion promotes the urinary excretion of oxypurinol. SUBJECTS/METHODS: Bovine milk (15 ml/kg body weight) was administered to 6 healthy subjects who took allopurinol (300 mg) 12 h prior to ingestion. In addition, a control experiment was performed with the same subjects using the same protocol, except for the ingestion of water instead of bovine milk. Blood and urine samples were collected before and after bovine and water ingestion. RESULTS: In the bovine milk ingestion experiment, the urinary excretion values of oxypurinol and uric acid were increased by 18% and 38%, respectively, and the fractional excretion values of oxypurinol and uric acid were increased by 20% and 40%, respectively, whereas those did not change in the control experiment. In addition, the concentration of alanine and sum of concentrations of amino acids were increased by 16% and 20%, respectively, in the bovine milk ingestion experiment. CONCLUSION: These results suggest that bovine milk ingestion promotes the urinary excretion of oxypurinol as well as uric acid by increasing amino acid concentration.

Risk factors for lymph node metastasis in histologically poorly differentiated type early gastric cancer.

BACKGROUND: We retrospectively evaluated the predictive factors for lymph node metastasis in poorly differentiated early gastric cancer (poorly differentiated tubular adenocarcinoma, signet-ring cell carcinoma, mucinous adenocarcinoma) in order to examine the possibility of endoscopic resection for poorly differentiated early gastric cancer. METHODS: A total of 573 patients with histologically poorly differentiated type early gastric cancer (269 mucosal and 304 submucosal), who had undergone curative gastrectomy, were enrolled in this study. Risk factors for lymph node metastasis were evaluated by univariate and logistic regression analysis. RESULTS: Lymph node metastasis was observed in 74 patients (12.9%) (6 with mucosal cancer and 68 with submucosal cancer). By univariate analysis risk factors for lymph node metastasis were lymphovascular invasion (LVI) (presence), depth of invasion (submucosa), and tumor diameter (> 20 mm), ulcer or ulcer scar (presence), and histological type (mucinous adenocarcinoma). By multivariate analysis, risk factors for lymph node metastasis were LVI, depth of invasion, and tumor diameter. In mucosal cancers, the incidence of lymph node metastasis was 0% irrespective of LVI in tumors smaller than 20 mm, and 1.7% in tumors 20 mm or larger without LVI. In submucosal cancers, the incidence of lymph node metastasis was 2.4% in tumors smaller than 20 mm without LVI. CONCLUSIONS: A histologically poorly differentiated type mucosal gastric cancer measuring less than 20 mm and without LVI may be a candidate for endoscopic resection. This result should be confirmed in a larger study with many patients.

Effects of benzbromarone and allopurinol on adiponectin in vivo and in vitro.

When treating gout patients, we have incidentally found elevated serum levels of adiponectin in some after administration of benzbromarone. In the present study, we determined whether benzbromarone increases the serum level of adiponectin in gout patients and investigated the mechanism involved. Sixty-nine patients with gout were separated into two groups, and then treated for 1 year with uric acid-lowering therapy using benzbromarone or allopurinol. After overnight fasting, blood samples were drawn before and at 1 year after beginning of treatment. In an in vitro study, 3T3L1 cells were incubated in medium containing benzbromarone, allopurinol, pioglitazone, or uric acid, after which real time PCR assays were performed for messenger RNA of adiponectin, aP2, and CD36. Furthermore, 3T3L1 cells were incubated in medium containing GW9662 (PPARgamma antagonist) together with benzbromarone or pioglitazone, after which real-time PCR assays were performed for messenger RNA of adiponectin. In the in vivo study, benzbromarone increased the serum concentration of adiponectin in the subjects, whereas allopurinol did not. In vitro, benzbromarone and pioglitazone each increased the levels of messenger RNA of adiponectin, aP2, and CD36 in 3T3 cells, whereas allopurinol and uric acid did not. Also, GW9662 suppressed the increase in adiponectin mRNA induced by benzbromarone as well as that by pioglitazone. Together, our results suggest that benzbromarone enhances the production of adiponectin via activation of PPARgamma, which is a weak agonist for PPARgamma.

Acarbose alleviates rise in plasma uric acid concentration induced by sucrose ingestion.

UNLABELLED: Sucrose is divided by alpha-glucosidase into fructose and glucose, which are considered to raise plasma uric acid concentration through purine degradation and/or decreased uric acid excretion. AIMS: We investigated the effect of acarbose, an alpha-glucosidase inhibitor, on the increased plasma concentration of uric acid caused by sucrose. METHODS: 6 healthy males were studied. After an overnight fast, sucrose at 1.5 g/kg was ingested. Urine was collected 1 hour before sucrose ingestion and then twice at 1-hour intervals after ingestion. Blood was taken twice, at the midpoint of each 1-hour period. 2 weeks later, the same protocol was followed, with acarbose at 100 mg added at the beginning of the sucrose ingestion. RESULTS: Sucrose ingestion raised the plasma concentration of uric acid by 10%, whereas with the addition of acarbose the rise in plasma concentration of uric acid was reduced (p < 0.01) without changes in urinary uric acid excretion and fractional uric acid clearance. Urinary excretion and fractional clearance of oxypurines were unchanged in both experiments. CONCLUSIONS: Acarbose is considered to alleviate the rise in plasma concentration of uric acid induced by sucrose by inhibiting its absorption since no changes in uric acid excretion and fractional clearance were observed.

Effects of a fenofibrate/losartan combination on the plasma concentration and urinary excretion of purine bases.

OBJECTIVE: To assess the effects of a combination of fenofibrate and losartan on the plasma concentrations and urinary excretion of purine bases in healthy male subjects. METHODS: 5 healthy males participated in a fenofibrate plus losartan combination study. The plasma concentrations and urinary excretion of purine bases (hypoxanthine, xanthine, uric acid) were measured before and after administrations of losartan (100 mg o.d.) alone for 2 weeks, losartan and fenofibrate together for 2 weeks and fenofibrate (300 mg o.d.) alone for 2 weeks, which were given consecutively over a 6-week period. RESULTS: Losartan alone significantly reduced the serum uric acid concentration and increased uric acid excretion, whereas the combination of losartan and fenofibrate reduced serum uric acid concentrations further with a concomitant increased uric acid excretion. Fenofibrate alone also reduced plasma uric acid concentration with an increase in urinary excretion, although the effect was weak when compared with the combination treatment. The plasma concentrations and urinary excretion of oxypurines remained unchanged throughout the entire study. CONCLUSION: A combination of fenofibrate and losartan demonstrated an additive urate-lowering effect which may be beneficial in the treatment of patients with gout and hypertriglyceridemia.

Effect of beer ingestion on the plasma concentrations and urinary excretion of purine bases: one-month study.

To investigate the effect of long-term beer ingestion on the plasma concentrations and urinary excretion of purine bases, 5 healthy males participated in the present study, during which they ingested beer every evening for 30 days. Blood and 24-hour urine samples were collected in the morning one day before and 14 and 30 days after the initiation of the beer ingestion. During the beer ingestion period, the plasma concentration and the urinary excretion of uric acid were increased significantly, while uric acid clearance was not decreased. Further, purine ingestion was not significantly different throughout the study. These results suggest that production of uric acid by ethanol ingestion was the main contributor to the increased plasma uric acid. Therefore, patients with gout should be encouraged to avoid drinking large amounts of beer on a daily basis.

A newly discovered apolipoprotein B-containing high-density lipoprotein produced by human hepatoma cells.

Apolipoprotein B-containing high-density lipoprotein was detected in the high-density lipoprotein fraction of the concentrated conditioned medium of human hepatoma HuH-7 cells (Apo-B-containing HDLHuH-7). Electrophoretically, the Apo-B-containing HDLHuH-7 migrated more slowly and broadly than beta-lipoprotein on agarose gel. The Apo-B-containing HDLHuH-7 was not precipitated by heparin-Mn2+ treatment. High-performance gel filtration chromatography indicated that the peak of Apo-B-containing HDLHuH-7 was eluted faster than that of plasma LDL and electron microscopic analysis demonstrated that the particles of Apo-B-containing HDLHuH-7 ranged from 140 A to about 450 A, indicating the heterogeneity of Apo-B-containing HDLHuH-7. The protein/lipid ratio of HDLHuH-7 (1.35) is higher than that of plasma HDL3 (1.2). The lipids of HDLHuH-7 are composed of phospholipids (170 micrograms/mg protein), free cholesterol (410 micrograms/mg protein), cholesterol ester (20 micrograms/mg protein) and triacylglycerols (140 micrograms/mg protein). The results described above indicated that Apo-B-containing HDLHuH-7 was a novel lipoprotein discovered for the first time.

Effect of interferon-gamma on purine catabolic and salvage enzyme activities in rats.

To determine whether interferon-gamma affects rat purine catabolic and salvage enzyme activities, rats were injected with interferon-gamma (600000 U/kg, i.p.) and, similarly to a vehicle-injected control group, killed before or after injection at 6, 12, and 24 h. Organ homogenates were prepared and enzymatic reactions with substrates were carried out, after which the products were measured either chromatographically or spectrophotometrically. Western and Northern blotting also were performed. In contrast to the vehicle-injected rats, interferon-gamma-injected rats showed a significant rise in xanthine oxidoreductase activity in the liver, while enzyme activity was unchanged in the spleen, kidney, and lung. Western analysis of hepatic xanthine oxidoreductase showed an increased concentration of this protein 12 and 24 h after interferon-gamma injection. Northern analysis disclosed an enhanced mRNA expression coding for this enzyme, peaking 12 h after injection. Contrastingly, the activities of adenosine deaminase, purine nucleoside phosphorylase, hypoxanthine guanine phosphoribosyltransferase, and adenine phosphoribosyltransferase were not affected by interferon-gamma in any organ tested. While interferon-gamma causes an increased hepatic biosynthesis of xanthine oxidoreductase, the physiologic role of this enzyme induction remains undetermined.

Novel apoprotein A-I-containing lipoprotein produced by a human hepatoma-derived cell line HuH-7.

The apoprotein A-I (apo A-I)-containing lipoprotein (LPHuH-7apoA-I) was isolated from the concentrated conditioned medium of human hepatoma-derived cell line HuH-7 by immunoaffinity chromatography. LpHuH-7apoA-I consists of two kinds of lipoproteins. One is a lipoprotein of large particle size (LpL) with broad electrophoretic mobility on agarose gel ranging from the origin to the position of prebeta-lipoprotein. LpL is protein-rich in composition (protein, 75.4% by weight) and is heterogeneous in size (34-17 nm in diameter) electron microscopically. However, the most intriguing properties of LpL are its partial electrophoretic mobility towards the cathode on agar gel. The other lipoprotein is of small particle size (LpS). It demonstrates prebeta-electrophoretic mobility on agarose gel. LpS is also protein-rich in composition (protein, 95.4% by weight) and is heterogeneous in size (16.5-8.4 nm in diameter) electron microscopically. LpL is obviously different from LP-X and LP-Y in property, although LP-X, LP-Y and a part of LpL migrate towards the cathode on agar gel electrophoresis. LpS is also different from human apo A-I-containing lipoprotein without apo A-II in property, although these two lipoproteins possess the same mobility on agarose gel electrophoresis. These results indicate that both LpL and LpS are novel lipoproteins which have not yet been reported. The major isoproteins of the apo A-I of LpHuH-7apoA-I are apo A-I isoprotein 2 (apo A-I2), apo A-I isoprotein 4 (apo A-I4) and apo A-I isoprotein 5 (apo A-I5), and are different from those of apo A-I in human plasma and in the conditioned medium of hepatoma-derived cell line HepG2. This result suggests the presence of a proteinase which converts proapoprotein A-I (apo A-I2) to apoprotein A-I (apo A-I4) in the conditioned medium of HuH-7.

Purification and immunohistochemical tissue localization of human xanthine oxidase.

Xanthine oxidase was purified 1600-fold from human liver cytosol. The purified enzyme was shown as a single band of 300 kDa on polyacrylamide gel electrophoresis and 150 kDa on SDS-PAGE. Using this purified enzyme, polyclonal antibody against xanthine oxidase was raised in a rabbit. On Ouchterlony's double immunodiffusion method, the raised antibody and the human liver cytosol made a precipitation line stained by activity stain and protein stain, respectively. With the raised anti-xanthine oxidase sera, the immunohistochemical localization of xanthine oxidase in human tissues was examined. Immunostaining of frozen hepatic tissue section showed that the cytoplasm of hepatocytes and endothelial lining cells were stained. In a number of other tissues, the xanthine oxidase antigen was detected only in the endothelial lining cells from heart, kidney, brain, aorta, lung and mesentery, except for the duodenal mucosa cells. A possible role for xanthine oxidase in the endothelial cells from various human tissues in the pathogenesis of reperfusion injury was suggested.

Marked increase of trypsin(ogen) in serum of linitis plastica (gastric cancer, borrmann 4) patients.

Linitis plastica, or Borrmann 4 gastric cancer, shows very poor prognosis, and the reason has not been understood. In the present study, we examined serum levels of trypsin(ogen) in 44 gastric cancer patients, including 17 early gastric cancer, 18 non-Borrmann 4 advanced gastric cancer, and 9 Borrmann 4 gastric cancer, by using the RIA gnost Trypsin kit (Hoechst Japan, Tokyo, Japan), which was expected to detect trypsin-1, trypsin-2, trypsinogen-1, and trypsinogen-2 in sera. The trypsin(ogen) concentration was much higher in the patients with linitis plastica than in the other gross types of gastric cancer. Hypertrypsinemia was identified in approximately 60% of advanced gastric cancer cases. Lymph node involvement, liver metastasis, or poorly differentiated adenocarcinoma is an important factor of hypertrypsinemia. The serum trypsin(ogen) level in linitis plastica patients was 3484.4 +/- 2319.7 ng/ml (mean +/- SD), which was significantly higher not only than that of the early gastric cancer (384.1 +/- 92.1) but also the stage IV gastric cancer patients (578 +/- 440.4), excluding those with linitis plastica. The elevated serum trypsinogen level in linitis plastica patients may be related to the malignant behavior of this type of cancer cell. Serum trypsin(ogen) of linitis plastica shows significantly higher concentrations than do the other types of advanced gastric cancer. Therefore, serum concentration of trypsin(ogen) might be a good marker of gastric cancer of linitis plastica.

In vitro oxidation of pyrazinamide and allopurinol by rat liver aldehyde oxidase.

Aldehyde oxidase was purified about 120-fold from rat liver cytosol by sequential column chromatography using diethylaminoethyl (DEAE) cellulose, Benzamidine-Sepharose 6B and gel filtration. The purified enzyme was shown as a single band with M(r) of 2.7 x 10(5) on polyacrylamide gel electrophoresis (PAGE) and M(r) of 1.35 x 10(5) on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Using this purified enzyme, in vitro conversion of allopurinol, pyrazinamide and pyrazinoic acid was investigated. Allopurinol and pyrazinamide were oxidized to oxypurinol and 5-hydroxy-pyrazinamide, respectively, while pyrazinoic acid, the microsomal deamidation product of pyrazinamide, was not oxidized to 5-hydroxypyrazinoic acid. The apparent Km value of the enzyme for pyrazinamide was 160 microM and that for allopurinol was 1.1 mM. On PAGE, allopurinol- or pyrazinamide-stained band was coincident with Coomassie Brilliant Blue R 250-stained band, respectively. These results suggest that aldehyde oxidase may play a role in the oxidation of allopurinol to oxypurinol and that of pyrazinamide to 5-hydroxypyrazinamide with xanthine dehydrogenase which can oxidize both allopurinol and pyrazinamide in vivo. The aldehyde oxidase may also play a major role in the oxidation of allopurinol and pyrazinamide in the subgroup of xanthinuria patients (xanthine oxidase deficiency) who can oxidize both allopurinol and pyrazinamide.

Effect of BOF-4272 on the oxidation of allopurinol and pyrazinamide in vivo. Is xanthine dehydrogenase or aldehyde oxidase more important in oxidizing both allopurinol and pyrazinamide?

Allopurinol or pyrazinamide was administered to rats treated with BOF-4272 (a potent xanthine oxidase inhibitor) to investigate to what degree xanthine dehydrogenase participates in the oxidation of these agents. BOF-4272 markedly decreased the plasma concentration and the urinary excretion of both oxypurinol and 5-hydroxypyrazinamide. It also decreased the sum of the urinary excretion of allopurinol and oxypurinol and that of pyrazinamide and its metabolites, although it did not affect the sum of the plasma concentrations of allopurinol and oxypurinol at 105 min after administration of allopurinol or the plasma concentration of pyrazinamide during the period after the administration of pyrazinamide. These results suggested that BOF-4272 almost completely inhibited the oxidation of allopurinol and pyrazinamide and had some effect on the excretion and/or the tissue incorporation of these two compounds. Since the in vitro study demonstrated that BOF-4272 did not inhibit the activity of aldehyde oxidase, which oxidized both allopurinol to oxypurinol and pyrazinamide to 5-hydroxypyrazinamide, the results suggested that xanthine dehydrogenase was the more important enzyme in converting allopurinol to oxypurinol and pyrazinamide to 5-hydroxypyrazinamide.

Elevated levels of soluble interleukin-2 receptors in tuberculous pleural effusions.

The levels of soluble IL-2R were measured in pleural fluid from patients with tuberculosis pleurisy. There were significantly elevated soluble IL-2R values in tuberculous pleural fluid as compared with pleural fluid of nontuberculous etiology including malignant, bacterial and transudative pleural effusions. In patients with tuberculous pleurisy, the level of soluble IL-2R in pleural fluid was markedly greater than that in serum. Furthermore, a significant positive correlation was observed between soluble IL-2R levels and adenosine deaminase levels in tuberculous pleural fluid. These findings suggest that elevated levels of pleural fluid soluble IL-2R in tuberculous pleurisy could reflect the local proliferation of activated T-cells and may be clinically useful in the diagnostic procedures for patients with pleural tuberculosis.

Development of a new calcium phosphate cement that contains sodium calcium phosphate.

A cement powder consisting of sodium calcium phosphate, Na3Ca6(PO4)5, in addition to tetracalcium phosphate and beta-tricalcium phosphate was prepared by pulverizing blocks of 4 wt% sodium-, 11 wt% carbonate-containing apatite samples that were heated at 1700 degrees C for 5 h. When mixed with 30 wt% malic acid or citric acid at a powder liquid ratio of 3:1, the cement set in 3 or 7 min at room temperature with compressive strength being around 52 or 27 MPa. In HeLa-cell cultures, the cement mixed with malic acid was less cytotoxic than the cement mixed with citric acid, which was far less cytotoxic than a commercial carboxylate cement used as a negative control, suggesting malic acid to be superior to citric acid as a liquid in this regard. Similar findings were also obtained with osteoclasts, of which culture experiments clearly suggested that the number of osteoclasts on the cement mixed with malic acid was significantly greater than that on the cement mixed with citric acid. Since osteoclastic response to substrates could be used as a maker in evaluating their bioresorbability associated with osteoclasts, the above finding may suggest that the cement that is to be mixed with malic acid would be more useful as bone substitutes.

Enzymes involved in purine metabolism--a review of histochemical localization and functional implications.

Many enzymes are involved in the biosynthesis, interconversion, and degradation of purine compounds. The exact function of these enzymes is still unknown, but they seem to play important roles other than in purine metabolism. To elucidate their functional roles, it is imperative to clarify their tissue distribution at the cellular or subcellular level. The present review summarizes the currently available information about their histochemical localization and proposed functions. In general, 5'-nucleotidase has been considered as a marker enzyme for the plasma membrane, and is considered to be a key enzyme in the generation of adenosine, a potential vasodilator. However, from its wide range of localization in tissues it is also considered to be related to the membrane movement of cells in the transitional epithelium, cellular motile response, transport process, cellular growth, synthesis of fibrous protein and calcification, lymphocyte activation, neurotransmission, and oxygen sensing mechanism. Adenosine deaminase (ADA) is present in all tissues in mammals. Although the main function of ADA is the development of the immune system in humans, it seems to be associated with the differentiation of epithelial cells and monocytes, neurotransmission, and maintenance of gestation. Purine nucleoside phosphorylase (PNP) is generally considered as a cytosolic enzyme, but recently, mitochondrial PNP, a different protein from cytosolic PNP, was reported. PNP is also widely expressed in human tissues. It is found in most tissues of the body, but the highest activity is in peripheral blood granulocyte and lymphoid tissues. It is also related to the development of T-cell immunity in humans as is ADA. Moreover, its contribution to centriole replication and/or regulation of microtubule assembly has been suggested. Immunohistochemical localization of xanthine oxidase has been reported in various tissues from various animal species. Xanthine oxidase has been suggested to be involved in the pathogenesis of post-ischemic reperfusion tissue injury through the generation of reactive oxygen species, while the extensive tissue localization of xanthine dehydrogenase/oxidase suggests several other roles for this enzyme, including a protective barrier against bacterial infection by producing either superoxide radicals or uric acid. Furthermore, an involvement in cellular proliferation and differentiation has been suggested. Urate oxidase is generally considered a liver-specific enzyme, except for bovines which possess this enzyme in the kidney. Urate oxidase is exclusively located in the peroxisomes of fish, frogs, and rats, but was lost in birds, some reptiles, and primates during evolution. A histochemical demonstration of allantoin-degrading enzymes has not been performed, but these enzymes have been located in peroxisomes by sucrose density gradient centrifugation. AMP deaminase activity is higher in skeletal muscle than in any other tissues. AMP deaminase may be involved in a number of physiological processes, such as the conversion of adenine nucleotide to inosine or guanine nucleotide, stabilizing the adenylate energy charge, and the reaction of the purine nucleotide cycle. There are three distinct isozymes (A, B, C) with different kinetic, physical, and immunological properties. Isozymes A, B, C have been isolated from muscle, liver (kidney), and heart tissue, respectively. In the muscle, AMP deaminase isozymes exist in a different part, suggesting a multiple functional role of this enzyme. High hypoxanthine-guanine phosphoribosyltransferase (HGPRT) activity is found in some regions of a normal adult human brain. However, very little is known regarding the histochemical tissue localization of HGPRT. Immunohistochemical localization of its developmental expression suggests that HGPRT may not be essential for purine nucleotide supplement in the segmentation of brain cells, but may play a significant role in the developing hippocampus.

Distribution and pathophysiologic role of molybdenum-containing enzymes.

The importance of molybdenum-containing enzymes in the pathophysiology of a number of clinical disorders necessitates a comprehensive understanding of their histological localization and expression. The objectives of this review are to cover such enzymes so far reported and their enzyme- and immunohistochemical localization in various tissues and species, and to discuss their possible pathophysiological effects. The molybdenum cofactor is essential for the activity of the three molybdenum-containing enzymes, sulfite oxidase, xanthine oxidase and aldehyde oxidase. Sulfite oxidase serves as the terminal enzyme in the pathway of the oxidative degradation of sulfur amino acids, and is also involved in preventing the toxic effects of sulfur dioxide. Biochemical study has revealed a high activity of sulfite oxidase mainly in the liver, heart and kidney with lesser activity observed in other tissues. Subcellular observations have shown that this enzyme is present in the mitochondrial intermembraneous spaces. Xanthine oxidase is the final enzyme in the conversion of hypoxanthine to xanthine, and subsequently, to uric acid. Unlike sulfite and aldehyde oxidases, xanthine oxidase can be converted to xanthine dehydrogenase, and vice versa. Xanthine oxidase has been widely investigated for its role in post-ischemic reperfusion tissue injury. Enzyme- and immunohistochemical studies of its localization in various animal species and tissues have shown its ubiquitous distribution in the liver, small and large intestine, lung and kidney, and other tissues. Aldehyde oxidase shares a similar substrate specificity with xanthine oxidase. Although the tissue localization of this enzyme has not been studied as thoroughly as that of xanthine oxidase, aldehyde oxidase is reportedly found in the digestive gland of terrestrial gastropods, the antennae of certain moths as well as the mammalian liver. Recently, the ubiquitous distribution of aldehyde oxidase has been demonstrated in rat tissues. The aldehyde oxidase activity of herbivores exceeds that of carnivores, suggesting a possible role of this enzyme as a protection against the effects of toxic plants. The relationship between the tissue localization of these enzymes and their pathophysiological roles is reviewed.