Reconsideration of discrepancies between clinical and histopathological features in acute eosinophilic pneumonia.

BACKGROUND AND OBJECTIVES: Acute eosinophilic pneumonia (AEP) is a very rare condition, with only one paper published so far discussing histopathological findings at surgical biopsy. In that paper, AEP is considered to be an acute and proliferative stage of DAD accompanied by eosinophilia. However, acute respiratory distress syndrome, acute interstitial pneumonia, and acute exacerbation of idiopathic pulmonary fibrosis, which, unlike AEP are mostly life-threatening diseases, also exhibit DAD. AEP also presents with severe hypoxia but rapidly improves on treatment with corticosteroids alone, without subsequent fibrosis. In contrast, the other above-mentioned diseases with the same histopathology show greatly different clinical courses. The reasons for these differences remain unclear. METHODS: Here we investigated the histopathology of AEP in 2 surgical lung biopsy and 14 transbronchial lung biopsy cases. Additionally, we determined the presence or absence of different phases of DAD by histopathology in these AEP cases. RESULTS AND CONCLUSION: Characteristic histopathological findings of AEP consist of alveolar edema with infiltration of eosinophils and lymphocytes and edema of perivascular area and interlobular septa. The alveolar spaces showed fibrinous exudates. There were no hyaline membranes or massive intraluminal fibrosis. These histopathological findings of interstitial edema and fluid exudates are consistent with radiological findings of lung edema and can explain the rapid and complete improvement.Because AEP does not exhibit lung fibrosis histopathologically, it should not to be included in DAD which is associated with lung fibrosis.

Altered cerebellum development and dopamine distribution in a rat genetic model with congenital hypothyroidism.

Thyroid hormones play crucial roles in the development and functional maintenance of the central nervous system. Despite extensive studies of the neural function of thyroid hormones, little is known about the effects of hypothyroidism on behavioural traits and the mechanisms underlying such effects. In the present study, we report an investigation of congenitally hypothyroid mutant rdw rats, revealing a novel function of thyroid hormones in the central nervous system. The rdw rats were subjected to behavioural analyses such as the rotarod test, open field test and circadian activity measurement. To determine the cause of behavioural disorders, cerebellar morphogenesis was examined by immunohistochemical analysis, and the axonal transport of dopamine in the nigrostriatal pathway was analysed by high-performance liquid chromatography and western blotting. The effects of thyroxine administration to the rdw rats were examined by behavioural analysis. The rdw rats showed severe impairment of motor coordination and balance. This could be explained by the fact that the rats showed severe retardation of cerebellar morphogenesis, which correlates with the small somata and poor dendritic arborisation of Purkinje cells and retarded migration of granule cells particularly during the first two postnatal weeks. Moreover, the rdw rats showed hypoactivity, characterised by decreased circadian locomotor activity. After weaning, thyroxine administration improved the dwarfism in rdw rats but had no effect on cerebellar function. In addition, the rdw rats showed anxiety and depression intrinsically to novel surroundings. Interestingly, the rdw rats showed high levels of dopamine in the substantia nigra and low levels in the striatum, an important centre for the coordination of behaviour. Furthermore, low levels of tubulin in the striatum were detected, indicating the aberrant axonal transport of dopamine in the nigrostriatal pathway as a result of the reduced delivery of microtubules. These findings indicate an important function of thyroid hormones in cerebellar formation and in the regulation of axonal transport of dopamine. Moreover, rdw rats will be useful for studies of brain function and behavioural disorders in congenital hypothyroidism.

Familial interstitial pneumonia in an adolescent boy with surfactant protein C gene (Y104H) mutation.

Recent studies have suggested that some cases of familial interstitial pneumonia are associated with mutations in the gene encoding surfactant protein C (SFTPC). We report here a case of familial interstitial pneumonia in an adolescent boy whose paternal grandfather and father suffered from idiopathic interstitial pneumonia (IIP). The patient was asymptomatic but showed an abnormal shadow in the chest at his medical check-up. The surgical biopsy of the patient revealed non-specific interstitial pneumonia and showed pathological findings similar to those in his father's autopsy. Genomic DNA from blood leucocytes of the patient was sequenced for the Thy104His (Y104H) SFTPC mutation. Based on these results, he was diagnosed with SFTPC mutation-associated familial interstitial pneumonia. There has been no clinical, physiologic and radiologic progression for 4 years since the diagnosis. The relation between clinical manifestation and the mutation site of the patient may broaden the spectrum of SFTPC mutation-associated interstitial pneumonia.

The connected health of cardiovascular medicine: current status and future directions.

The technologies of cardiovascular connected health stand to dramatically alter the management and prevention of cardiovascular disease, a worldwide leading cause of death. The American Heart Association has outlined seven key health metrics including physical activity, adequate blood pressure control, weight and a healthy diet, which lie at the core of cardiovascular disease management. Controlling these metrics has been demonstrated to result in substantial reductions in cardiovascular mortality. These metrics are ideally suited to a connected health management strategy involving enhanced patient empowerment and augmented physician engagement. As more patients and healthcare providers adopt technologies that allow for self-monitoring and point-of-care diagnostics, the physician has access to a greater depth of data concerning their patient's health and how best to influence it.

Historical changes in epidemiology of diffuse panbronchiolitis.

BACKGROUND AND OBJECTIVE: Japanese pulmonologists, experienced in treating patients with diffuse panbronchiolitis (DPB) prior to the 1980s, have uniformly observed that new incidences of DPB are now a rare event in Japan. However, there is no epidemiological data to support this observation. We examined epidemiological trends of the number of patients with DPB in a large company. DESIGN: The computerized health records of JR East Company employees were used to identify patients with DPB and then these were followed up using the assessments of these patients in JR Tokyo General Hospital and two other JR hospitals. The whole study period was 27 years (1976-2003), although detailed analyses were carried out for three specific periods; the first was 1976-1980, the second was 1989-1993, and the third was 1999-2003. RESULTS: In the first period, 11 DPB cases (four incidence, and seven prevalence) were detected among a total of 355,572 workers. In the second period, three DPB cases (one incidence, and two prevalence) were identified from a total of 180,359 workers. In the third period, no case was found in a total of 144,485 workers. CONCLUSION: This epidemiological trend suggests that both the incidence and prevalence of DPB may have decreased.

Induction of EMT-like phenotypes by an active metabolite of leflunomide and its contribution to pulmonary fibrosis.

Drug-induced interstitial lung disease (ILD), particularly pulmonary fibrosis, is a serious clinical concern and myofibroblasts have been suggested to have a major role, with it recently being revealed that some of these myofibroblasts are derived from lung epithelial cells through epithelial-mesenchymal transition (EMT). In this study, we examined the EMT-inducing abilities of drugs known to induce ILD clinically. EMT-like phenotypes were induced by A771726, an active metabolite of leflunomide having an inhibitory effect on dihydroorotate dehydrogenase (DHODH). Smad-interacting protein 1 (a transcription factor regulating EMT) and the Notch-signaling pathway but not transforming growth factor-ß was shown to be involved in A771726-induced EMT-like phenotypes. When the cultures were supplemented with exogenous uridine, the A771726-induced EMT-like phenotypes and activation of the Notch-signaling pathway disappeared. Similarly, an A771726 analog without inhibitory activity on DHODH produced no induction, suggesting that this process is mediated through the inhibition of DHODH. In vivo, administration of leflunomide stimulated bleomycin-induced EMT-like phenomenon in pulmonary tissue, and exacerbated bleomycin-induced pulmonary fibrosis, both of which were suppressed by coadministration of uridine. Taken together, these findings suggest that leflunomide-dependent exacerbation of bleomycin-induced pulmonary fibrosis is mediated by stimulation of EMT of lung epithelial cells, providing the first evidence that drug-induced pulmonary fibrosis involves EMT of these cells.

Pirfenidone in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease without proven effective therapy. A multicentre, double-blind, placebo-controlled, randomised phase III clinical trial was conducted in Japanese patients with well-defined IPF to determine the efficacy and safety of pirfenidone, a novel antifibrotic oral agent, over 52 weeks. Of 275 patients randomised (high-dose, 1,800 mg x day(-1); low-dose, 1,200 mg x day(-1); or placebo groups in the ratio 2:1:2), 267 patients were evaluated for the efficacy of pirfenidone. Prior to unblinding, the primary end-point was revised; the change in vital capacity (VC) was assessed at week 52. Secondary end-points included the progression-free survival (PFS) time. Significant differences were observed in VC decline (primary end-point) between the placebo group (-0.16 L) and the high-dose group (-0.09 L) (p = 0.0416); differences between the two groups (p = 0.0280) were also observed in the PFS (the secondary end-point). Although photosensitivity, a well-established side-effect of pirfenidone, was the major adverse event in this study, it was mild in severity in most of the patients. Pirfenidone was relatively well tolerated in patients with IPF. Treatment with pirfenidone may decrease the rate of decline in VC and may increase the PFS time over 52 weeks. Additional studies are needed to confirm these findings.

Epidemiology of sarcoidosis in Japan.

The present study was designed to identify recent clinical phenotypes using the National Epidemiological Survey and to compare findings with those of previous surveys in Japan. Pathologically confirmed sarcoidosis cases newly diagnosed in 2004 were eligible for the present study. Disease parameters were recorded and compared. A total of 1,027 patients were enrolled from a cluster encompassing 79.4% of the entire Japanese population. The study participants consisted of 364 males and 663 females, providing an average incidence rate of 1.01 per 100,000 inhabitants (0.73 for males and 1.28 for females). The age-specific incidence rate displayed a biphasic pattern in the whole patient population and in the females. The male incidence rates peaked in the 20-34-yr-old group. A second peak for 50-60-yr-old females showed a higher incidence than the first younger peak. Patients with abnormalities in eyes, skin and cardiac laboratory findings accounted for 54.8, 35.4 and 23.0% of cases, respectively. The female/male incidence ratio was increased, and the frequency of eye and skin involvement and cardiac abnormality was higher than in previous surveys conducted in Japan. In conclusion, the data obtained in the present study differ from those of other countries and showed changes in sarcoidosis clinical phenotypes compared with previous studies in Japan.

Dietary fat and meat intake and idiopathic pulmonary fibrosis: a case-control study in Japan.

SETTING: There is sparse epidemiologic information regarding the role of dietary factors in the development of idiopathic pulmonary fibrosis (IPF). OBJECTIVE: To examine the relationship between specific types of fatty acids and selected foods high in fat and IPF in Japan. DESIGN: Included were 104 cases aged > or = 40 years who had been diagnosed in the last 2 years in accordance with the most recent criteria. Controls aged > or = 40 years consisted of 56 hospitalised patients diagnosed as having acute bacterial pneumonia and four out-patients with common cold. RESULTS: Intake of saturated fatty acids, mono-unsaturated fatty acids, n-6 polyunsaturated fatty acids and meat was independently associated with an increased risk of IPF. Specifically, the multivariate OR for comparison of the highest with the lowest quartile of intake of saturated fatty acids was 6.26 (95%CI 1.79-24.96, P for trend = 0.01) and for meat it was 7.19 (95%CI 2.15-27.07, P for trend = 0.02). Intake of cholesterol, n-3 polyunsaturated fatty acids, fish, eggs and dairy products was not related to the risk. CONCLUSION: These findings suggest that consumption of saturated fatty acids and meat may increase the risk of IPF.

Enhanced vagal modulation and exercise induced ischaemia of the inferoposterior myocardium.

OBJECTIVE: To determine whether the Bezold-Jarisch reflex or enhancement of vagal nerves, which are preferentially distributed in the inferoposterior myocardium, results from exercise induced ischaemia in this region. METHODS: On the basis of exercise myocardial scintigraphy and coronary angiography, 145 patients were classified as follows: group I, 34 patients with inferoposterior ischaemia; group A, 32 with anterior ischaemia; and control, 79 without ischaemia. The relation between ischaemic areas and ECG leads with ST segment changes and vagal modulation assessed by heart rate variability (HRV) (high frequency (HF) component (0.15-0.40 Hz) and coefficient of HF component variance (CCVHF), which is the square root of HF divided by mean RR interval) were assessed. RESULTS: The rate of ST segment depression in any lead did not differ between group I and group A. HF and CCV(HF) were similar before exercise but higher in group I than in group A and the control group after exercise (mean (SEM) HF: 94 (17) ms2, 41 (7) ms2, and 45 (6) ms2, respectively, p = 0.021; CCV(HF): 1.18 (0.09)%, 0.81 (0.07)%, and 0.89 (0.05)%, p = 0.0053). Furthermore, the percentage change in CCV(HF) before and after exercise was higher in group I than in group A or controls (mean (SEM) 22 (10)%, -24 (4)%, and -21 (3)%, p < 0.0001). The optimal cut off for diagnosis of inferoposterior ischaemia was -5% with a sensitivity of 74%, specificity 75%, and accuracy 75%. CONCLUSIONS: Vagal modulation as assessed by HRV analysis was enhanced in association with exercise induced inferoposterior ischaemia. Exercise ECG testing combined with HRV analysis would increase accuracy in the diagnosis of ischaemic areas in selected patients with angina pectoris.

Significance of lymphocytosis in bronchoalveolar lavage in suspected ocular sarcoidosis.

Ocular sarcoidosis is frequent in Japan, but in many cases the condition remains undiagnosed in patients with suspected ocular sarcoidosis. Bronchoalveolar lavage (BAL) was performed in order to study the clinical implications of lymphocytosis of BAL fluid in such patients with characteristic ocular manifestations. The subjects included in this study were 39 patients with suspected ocular sarcoidosis. The patients were divided into four types based on high-resolution computed tomography (HRCT) findings; no lung involvement (HRCT-0), bilateral hilar lymphadenopathy (BHL) without lung involvement (HRCT-I), lung involvement and BHL (HRCT-II), and lung involvement and no BHL (HRCT-III). Transbronchial lung biopsy (TBLB) and BAL were conducted after examining serum angiotensin-converting enzyme and serum lysozyme values, skin test for purified protein derivative chest radiograph, HRCT, and gallium scintigram. Twenty patients were histologically diagnosed as having sarcoidosis, and 19 patients remained undiagnosed. Granuloma was identified by TBLB in 19 of 20 patients in type HRCT-II but in only one of 19 patients in types HRCT-0 and HRCT-I (p<0.0001). Lymphocytosis in BAL (>15%) was identified in all patients who showed lung field involvement (type HRCT-II) and in 16 of 19 patients without lung field involvement (types HRCT-0 and HRCT-I). There were 10 patients whose only relevant findings were lymphocytosis in BAL. Among these 10 patients, an increased CD4+/CD8+ ratio (>3.5) in BAL was seen in 60%. The authors conclude that high-resolution computed tomography results yield the same degree of diagnostic accuracy as transbronchial lung biopsy in ocular sarcoidosis suspects. However, bronchoalveolar lavage revealed significant lymphocytosis in patients with negative high-resolution computed tomography results. It should be kept in mind that a diagnostic group of patients with sarcoidosis who manifest ocular involvement and lymphocytosis in bronchoalveolar lavage exists.

Dynamic changes in cardiac fatty acid metabolism in the stunned human myocardium.

BACKGROUND: The chronological changes or mechanisms in cardiac fatty acid metabolism under clinical conditions of hypoxia and ischemia have not been fully elucidated. 123-15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid (BMIPP) can be used with single photon emission computed tomography (SPECT) to evaluate myocardial fatty acid metabolism. We investigated chronological changes in energy metabolism in the stunned human myocardium by means of 123I-BMIPP myocardial SPECT. METHODS AND RESULTS: We conducted 123I-BMIPP myocardial SPECT in 10 patients with stunned myocardium during the acute, subacute and chronic phases after onset. The left ventricle was divided into 9 regions on SPECT, and the degree of abnormalities in each region was scored in four grades from normal (0) to defect (4). We also examined wash-out rates on BMIPP images. The scores on early BMIPP images in the acute, subacute and chronic phases were 5.6 +/- 1.8, 13.4 +/- 3.5 and 2.5 +/- 1.1, respectively, and the score was highest in the subacute phase (p < 0.001). Similarly, scores on the late images were 2.3 +/- 1.7, 18.3 +/- 4.5 and 4.7 +/- 2.6, respectively, and highest in the subacute phase (p < 0.001). The wash-out rates (normal: 18.2 +/- 2.1%) in the acute, subacute and chronic phases were 12.1 +/- 4.8%, 44.9 +/- 10.0% and 23.1 +/- 4.6%, respectively, with the value being lowest during the acute phase (p < 0.05), and highest during the subacute phase (p < 0.001). CONCLUSION: These results suggested that fatty acid metabolism in the stunned human myocardium changes dynamically over time.

Assessment of ampulla (Takotsubo) cardiomyopathy with coronary angiography, two-dimensional echocardiography and 99mTc-tetrofosmin myocardial single photon emission computed tomography.

UNLABELLED: We studied the causative mechanism of ampulla (Takotsubo) cardiomyopathy. METHODS: We examined 7 patients with ampulla cardiomyopathy by means of coronary angiography, two-dimensional echocardiography and 99Tc-tetrofosmin myocardial SPECT at the time of emergency admission (acute phase), at 3 to 5 days after the attack (subacute phase) and at 1 month after the attack (chronic phase). The left ventricle was divided into 9 regions on two-dimensional echocardiograms and 99mTc-tetrofosmin myocardial SPECT images, then the degree of abnormalities in each region was scored in four grades from normal (0) to severely abnormal (3). We injected nicorandil into the coronary arteries and determined the elevation in the ST segment before and after administration. RESULTS: Coronary angiography did not show stenotic lesions in any patient. The acute, subacute and chronic phase myocardial perfusion scores on 99mTc-tetrofosmin myocardial SPECT were 11.2 +/- 3.4, 2.7 +/- 2.3 and 0.4 +/- 0.5, respectively, and wall motion scores on echocardiograms were 13.0 +/- 3.6, 4.4 +/- 2.2 and 0.6 +/- 0.6, respectively, indicating improvement in all scores during the subacute phase (p < 0.01). The elevation in the ST segment (mm) on the electrocardiogram was improved from 8.3 +/- 2.7 to 4.9 +/- 1.9 after the administration of nicorandil (p < 0.05). CONCLUSION: These findings indicated that coronary microvascular spasm is one causative mechanism of ampulla cardiomyopathy.

[Assessment of myocardial damage and metabolic disorder in the left ventricle in patients with mitral stenosis using 201Tl and 123I-BMIPP myocardial SPECT].

This study was designed to evaluate the myocardial damage and metabolic disorder of the left ventricle in patients with mitral stenosis. We studied 15 patients with mitral stenosis. Their grade of chronic heart failure using New York Heart Association classification were class I: 5 patients, class II: 5, class III: 3, class IV: 2, respectively. The severely stenotic group (valve area < 1.5 cm2) included 6 patients, mildly stenotic group (1.5 cm2 < or = valve area < 2.5 cm2) included 9. A 111 MBq of 123I-BMIPP was intravenously injected at rest, SPECT images were obtained at 15 min and 3 hours after injection. A 111 MBq of 201Tl was intravenously injected at rest, and SPECT images were obtained at 15 min after injection. Washout rate (WR) of 123I-BMIPP from the whole left ventricle was obtained using polar maps. The concentration of norepinephrine (NE: pg/ml) in the blood at rest was measured. The mean values of pulmonary artery pressure was measured in ten patients using Swan-Ganz catheter. 123I-BMIPP myocardial SPECT and measurement of NE were reexamined in 5 patients after mitral valvuloplasty. NE values were 476 +/- 72 and 793 +/- 286 in classes I + II and III + IV, respectively. NE values was increased in the severe heart failure group (p < 0.05). NE values were 480 +/- 69 and 743 +/- 295 in the mildly and severely stenotic groups, respectively. NE value was increased in severely stenotic group (p < 0.05). Twelve patients showed normal uptake on both 201Tl and 123I-BMIPP myocardial SPECT. Three patients showed slightly reduced uptake on both 201Tl and 123I-BMIPP myocardial SPECT. WR was 27.2 +/- 4.8% and 44.3 +/- 6.7% in class I + II and class III + IV, respectively. WR was increased in severe heart failure group (p < 0.05). WR was 27.8 +/- 6.0% and 41.3 +/- 9.4% in the mildly and severely stenotic group, respectively. WR was increased in the severely stenotic group (p < 0.05). NE was correlated with WR (p < 0.001). In patients with mitral valvuloplasty, WR was 44.3 +/- 6.7% and 31.4 +/- 4.7% before and after mitral valvuloplasty, respectively. NE values were 857 +/- 266 and 574 +/- 165, respectively. Both WR and NE were decreased after mitral valvuloplasty (p < 0.01). In patients with mitral stenosis, WR was increased in the severe heart failure group and severely stenotic group without apparent myocardial damage. Myocardial metabolism in the left ventricle might be influenced by right heart failure through, for example, NE and neurohormonal factors.

A patient with type I CD36 deficiency whose myocardium accumulated 123I-BMIPP after 4 years.

A 73-year-old man with aortic regurgitation was examined by 123I-alpha-methyl-p-iodophenylpentadecanoic acid (BMIPP) myocardial single photon emission computed tomography (SPECT) in 1995. Myocardial accumulation was not evident on either the early or the delayed image obtained 15 minutes and 3 hours, respectively, after injecting 123I-BMIPP. Flow cytometric analysis of CD36 expression in monocytes and platelets identified a type I CD36 deficiency. The patient was hospitalized for severe heart failure in 1999. Upon admission, the cardiothoracic ratio on chest X-rays was 73%, and the left ventricular end-diastolic diameter on echocardiograms was enlarged to 77 mm. On the second day, we performed 123I-BMIPP myocardial SPECT. Myocardial accumulation was evident in the delayed, but not in the early image. We repeated 123I-BMIPP myocardial SPECT on the 10th day after admission. Myocardial accumulation was evident on both early and delayed images. 99mTc-tetrofosmin myocardial SPECT was immediately performed after 123I-BMIPP myocardial SPECT to distinguish myocardial from pooling images in the left ventricle, but, because the images from both 99Tc-tetrofosmin and 123I-BMIPP myocardial SPECT were idential, we considered that the 123I-BMIPP myocardial SPECT images reflected the actual myocardial condition. The CD36 molecule transports long-chain fatty acid (LCFA) on the myocardial membrane, but 123I-BMIPP scintigraphy does not show any myocardial accumulation in patients with type I CD36 deficiency, indicating that myocardial LCFA uptake occurs through CD36 on the human myocardial membrane. Even though our patient had type I CD36 deficiency, BMIPP was uptaken by the myocardium during heart failure, suggesting a variant pathway on the human myocardial membrane for LCFA uptake.

1-(3-C-ethynyl-beta-D-ribo-pentofuranosyl)cytosine (ECyd, TAS-106)1: antitumor effect and mechanism of action.

The antitumor activity, cellular metabolism and mechanism of action of the antitumor nucleoside analog, 1-(3-C-ethynyl-beta-D-ribo-pentofuranosyl)cytosine (ECyd) are described.

[Genetic variation of NADPH/NADH oxidase and susceptibility to diffuse panbronchiolitis (DPB) and chronic obstructive pulmonary disease (COPD)].

Diffuse panbronchiolitis (DPB) and chronic obstructive pulmonary disease (COPD) are both characterized by chronic airflow obstruction of unknown etiology. It is hypothesized that neutrophils play the major role in the pathogenesis of these diseases. Recent studies have suggested that genetic factors may be related to individual susceptibility to these diseases. We have investigated the association between the C 242 T polymorphism of p 22 phox, a critical subunit of superoxide-generating NADH/NADPH oxidase, and susceptibility to DPB and COPD. Blood samples obtained from both patients with DPB (n = 82), COPD (n = 53), and control subjects (n = 82) were used for this genotyping assay; and the polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) were performed to genotype the gene. The frequency of the C allele was 0.91, 0.92, 0.92 in the DPB, COPD, and control groups, respectively. There were no differences in the distribution of the genotype of p 22 phox among these groups, either. We concluded that there is no association between the C 242 T polymorphism of p 22 phox, and susceptibility to DPB and COPD.

Cloning and expression of uridine/cytidine kinase cDNA from human fibrosarcoma cells.

Uridine/cytidine kinase which converts uridine and cytidine to their corresponding monophosphates is a rate-limiting enzyme involved in the salvage pathway of pyrimidine synthesis. We isolated cDNA encoding the enzyme from human fibrosarcoma cells, then determined its nucleotide sequence by the 5'-RACE method followed by confirmation employing the human genome DNA library. The isolated uridine/cytidine kinase cDNA (UCK cDNA) consisted of 786 nucleotides encoding 261 amino acids and was found to have approximately 70% homology with mouse UCK cDNA. Northern blot analysis of human leukemia RNAs with labeled UCK gene showed a single band at 1.6 kb to be UCK mRNA, and southern blot analysis of the UCK cDNA after digestion with BamHI, SacI and XbaI enzymes showed four band signals, suggesting the UCK gene to have at least 4 exons. A truncated form of UCK cDNA was expressed as the His-tag conjugated protein in Escherichia coli. The expressed and purified protein specifically converted uridine and cytidine to their corresponding monophosphates and also phosphorylated antitumor nucleosides such as 5-fluorouridine, cyclopentenyl-cytosine and 3'-C-ethynylcytidine. The present results suggest that our cloned human UCK cDNA encodes the correct amino acid sequence for UCK protein, showing high intracellular phosphorylation activity forward natural and synthetic pyrimidine nucleosides.