Hematogenous apoptotic mechanism in salivary glands in chronic periodontitis.

OBJECTIVE: The aim of the study is to investigate the apoptotic mechanism in salivary glands in the rat experimental periodontitis model. DESIGN: A rat periodontitis model was prepared by using a ligature around the second upper molar. In the salivary (parotid and submandibular) glands and blood samples, putative apoptotic factors and pathway molecules were investigated in vivo and in vitro. RESULTS: Four weeks of ligation (chronic periodontitis) demonstrated significant apoptotic atrophy of the salivary gland, but one week of ligation (initial periodontitis) did not. In the blood plasma, tumor necrosis factor-α (TNF-α) was increased in the periodontitis model, but interleukin-1ß and -6 were not. TNF-α receptor type 1, which has an intracellular apoptotic pathway, was expressed in the salivary glands of rats. Western blot analysis of cultured rat primary salivary gland cells demonstrated that TNF-α induced cleavage of poly (ADP-ribose) polymerase (PARP) and caspase-3 in a dose-dependent manner, indicating apoptosis induction. Additionally, we found increment of circulating lymphocytes in the model. Expression of mRNA and immunoreactive cells for the B lymphocyte marker CD19 were increased in the salivary gland in the model. Western blotting showed that coculture with extracted B cells from the periodontitis model increased cleaved PARP in salivary gland cells. CONCLUSIONS: Chronic periodontitis status leads to an increase in circulating TNF-α and B lymphocyte infiltration, resulting in apoptotic atrophy of the salivary gland as a periodontitis-induced systemic response.

Cross-cultural comparison of the sleep-disordered breathing prevalence among Americans and Japanese.

The aim of the present study was to compare the prevalence of sleep-disordered breathing among Hispanic and white Americans and Japanese. A 1-night sleep study using a single-channel airflow monitor was performed on 211 Hispanics and 246 Whites from the Minnesota field centre (St Paul, MN, USA) of the Multi-Ethnic Study of Atherosclerosis (MESA), and 978 Japanese from three community-based cohorts of the Circulatory Risk in Communities Study (CIRCS) in Japan. The respiratory disturbance index and sleep-disordered breathing, defined as a respiratory disturbance index of > or =15 events x h(-1), were estimated. The prevalence of sleep-disordered breathing was higher in males (34.2%) than females (14.7%), and among Hispanics (36.5%) and Whites (33.3%) than among Japanese (18.4%), corresponding to differences in body mass index. Within body mass index strata, the race difference in sleep-disordered breathing was attenuated. This was also true when body mass index was adjusted for instead of stratification. The strong association between body mass index and sleep-disordered breathing was similar in Japanese and Americans. The prevalence of sleep-disordered breathing was lower among Japanese than among Americans. However, the association of body mass index with sleep-disordered breathing was strong, and similar among the race/ethnic groups studied. The majority of the race/ethnic difference in sleep-disordered breathing prevalence was explained by a difference in body mass index distribution.

Nocturnal intermittent hypoxia and the development of type 2 diabetes: the Circulatory Risk in Communities Study (CIRCS).

AIMS/HYPOTHESIS: Although the associations between obstructive sleep apnoea and type 2 diabetes mellitus have been reported in cross-sectional design studies, findings on the prospective association between the two conditions are limited. We examined prospectively the association between nocturnal intermittent hypoxia as a surrogate marker of obstructive sleep apnoea and risk of type 2 diabetes. METHODS: A total of 4,398 community residents aged 40 to 69 years who had participated in sleep investigation studies between 2001 and 2005 were enrolled. Nocturnal intermittent hypoxia was assessed by pulse-oximetry and defined by the number of oxygen desaturation measurements < or =3% per h, with five to <15 per h corresponding to mild and 15 events or more per h corresponding to moderate-to-severe nocturnal intermittent hypoxia, respectively. The development of type 2 diabetes was defined by: (1) fasting serum glucose > or =7.00 mmol/l (126 mg/dl); (2) non-fasting serum glucose > or =11.1 mmol/l (200 mg/dl); and/or (3) initiation of glucose-lowering medication or insulin therapy. Multivariable model accounted for age, sex, BMI, smoking status, current alcohol intake, community, borderline type 2 diabetes, habitual snoring, excessive daytime sleepiness, sleep duration and (for women) menopausal status. RESULTS: By the end of 2007, 92.2% of participants had been followed up (median follow-up duration [interquartile range] 3.0 [2.9-4.0] years) and 210 persons identified as having developed diabetes. The multivariable-adjusted hazard ratio (95% CI) for developing type 2 diabetes was 1.26 (0.91-1.76) among those with mild nocturnal intermittent hypoxia and 1.69 (1.04-2.76) among those with moderate-to-severe nocturnal intermittent hypoxia (p = 0.03 for trend). CONCLUSIONS/INTERPRETATION: Nocturnal intermittent hypoxia was associated with increased risk of developing type 2 diabetes among middle-aged Japanese.

QT dispersion and left ventricular morphology in patients with hypertrophic cardiomyopathy.

OBJECTIVE: To evaluate the relation between QT variables and disproportion of left ventricular wall hypertrophy in patients with hypertrophic cardiomyopathy. DESIGN: Retrospective analysis of the results of echocardiography and electrocardiography. SETTING: University hospital (tertiary referral centre). PATIENTS: 70 patients with hypertrophic cardiomyopathy were divided into four groups according to the distribution of left ventricular wall hypertrophy on cross sectional echocardiography: group A--hypertrophy confined to the interventricular septum; group B--hypertrophy confined to the interventricular septum and left ventricular anterior wall; group C--hypertrophy confined to the interventricular septum, left ventricular anterior wall, and lateral free wall; group D--hypertrophy involving all portions of the left ventricle. MAIN OUTCOME MEASURES: QT intervals and QT dispersion in precordial six lead ECGs. RESULTS: There were no significant differences in the maximum left ventricular wall thickness among the four groups, and maximum and minimum QTc intervals also did not differ. QTc dispersion was increased significantly in groups A and B compared with groups C and D. Dispersions of the interval from the J point to the end of the T wave (JTc dispersions) in groups A and B were also increased significantly compared with groups C and D. By linear regression analysis, QTc and JTc dispersions correlated with the ratio of the interventricular septal thickness to left ventricular posterior wall thickness (p = 0.0152 and p = 0.0075, respectively). CONCLUSIONS: QT dispersion may be affected by not only electrical inhomogeneity but also by morphological inhomogeneity of the left ventricle in patients with hypertrophic cardiomyopathy.

Radiographic observation of a case of gastrointestinal stromal tumor in stomach.

A case of gastrointestinal stromal tumor (GIST) in stomach was presented. Serial barium meal x-ray examinations revealed an enlarging elevated lesion on the fornix of the stomach. Tumor volume doubling time was found to be 299 days. Microscopic and immunohistochemical studies of the resected tumor disclosed GIST, uncommitted type, low grade malignant/potentially malignant. A radiographic feature of this rare type of gastric submucosal tumor was demonstrated in this report.

[Trends in the incidence of cardiovascular diseases and risk factors among urban and rural Japanese males].

OBJECTIVES: To examine long-term trends in the incidence of coronary heart disease, stroke, and their risk factors among Japanese populations, we explored 32 years of surveillance data for male residents in urban and rural areas in Japan. METHODS: The surveyed populations were 40-79 year-old male residents in M community (population over 40 years old in 1995 was 11,121) of Y City in Osaka (urban area; Osaka) and I town (n = 3,571) in Akita prefecture (rural area; Akita). Incidence rates of coronary heart disease (myocardial infarction, angina pectoris), sudden cardiac death, percutaneous transluminal coronary angioplasty (PTCA) and stroke per 1,000 person-years were calculated for 1964-71, 1972-79, 1980-87 and 1988-95. Risk factors were evaluated by cross-sectional surveys conducted in the median years for each period. Dietary intake was examined by the 24-hour recall method in the latter three periods. RESULTS: Age-adjusted incidence of coronary heart disease per 1,000 men increased progressively from 0.27 in 1964-71 to 0.90 in 1988-95 (P = 0.222 for trend) among 40-59 year old residents in Osaka. Among their 60-79 year old counterparts, though the incidence was 2.62-3.11 and did not change over the periods studied, the combined rates for coronary heart disease and men who had a PTCA reached 3.79 in 1988-95. In contrast, the incidence of coronary heart disease among Akita residents did not change over time and stroke declined 70 percent between 1964-71 and 1988-95 (P < 0.001) in both 40-59 and 60-79 year age group: The decrease in cerebral infarction was less marked between 1980-87 and 1988-95 among 60-79 year old individuals. Significant increases in diastolic blood pressure, total serum cholesterol, body mass index, salt intake and total fat percent of total energy in Osaka, were associated with the elevation in the incidence of coronary heart disease. In Akita, blood pressure leveled off over the study period, but decreased less during the last decade whereas the prevalence of obesity increased. CONCLUSION: Trends in cardiovascular diseases and their risk factors differ among different geographical areas. The present long-term study, in particular, demonstrated an increase in the incidence of coronary heart disease among urban Japanese male residents in Osaka between the 1960s and the 1990s.

[Relationship between the fecal mutagenicity and metal content, smoking habit and dietary intake].

OBJECTIVE: The study was carried out to collect basic data on exposure of mucous cells of the large intestine to mutagens by investigating the genotoxicity of fecal samples from the urban population. Simultaneously, relations with food intake (food groups and nutritive components), lifestyle factors and fecal metal content was investigated. METHODS: A total of 199 self-collected fecal samples from middle aged healthy volunteer living in urban areas of Osaka city were freeze-dried and ground in a mill. The mutagenicity of aqueous extracts of the ground samples was measured by the umu-test. Metal content of the feces was analysed by atomic absorption spectrophotometlly. On the day previous to the feces collection, the contents of meals were recorded and confirmed by interview with a dietitian. Quantification of nutritive components was carried out using the 4th edition of the Japan Food Standard Vomposition Table. RESULTS: Mutagenicity of feces was higher in males than in females, and in those aged 40-49 years than 50-69 years in males but not females. Large differences were found for content of 8 metals in the feces; concentrations were in the decreasing order of calcium, potassium, magnesium, sodium, zinc, iron, manganese and copper, the highest being 20.4 mg for calcium and the lowest was 53.5 micrograms for copper. Between the metal contents and mutagenicity, values for zinc and iron showed positive correlations and for sodium a negative correlation under S9(+) conditions. A weak but significant correlation was observed between the numbers of cigarettes smoked per day and S9 (+) mutagenicity. However we could not find any relation with food groups or nutritive components. CONCLUSION: It is well known that human feces contain many mutagens and carcinogens and that these can act directly on the mucous membrane of large intestine. Therefore, it is very important to estimate exposure levels. From the present data we can conclude that relations between mutation-activity of the feces and diet are complex. Their elucidation will require a large number of volunteers who have similar living conditions to obtain appropriate data.

Plasma fibrinogen and coronary heart disease in urban Japanese.

There is little information on the relation of plasma fibrinogen concentration to the risk of coronary heart disease in Asians, including Japanese, whose plasma fibrinogen concentration has been reported to be low by Western standards. The authors conducted a prospective study with 4.8 years of follow-up of 11,977 men and women aged 21-89 years (mean value of fibrinogen = 267 mg/dl) living or working in Osaka, Japan, in 1990-1996 to examine the relation of plasma fibrinogen with the incidence of coronary heart disease (myocardial infarction and angina pectoris). Mean fibrinogen concentration was 293.6 mg/dl for men who developed coronary heart disease (n = 35) compared with 261.6 mg/dl for men free of coronary heart disease (n = 8,094; difference, p < 0.01), and 355.2 mg/dl for women who developed coronary heart disease (n = 6) compared with 276.8 mg/dl for women free of coronary heart disease (n = 3,842; difference, p < 0.01). With a Cox proportional hazards model to adjust for cardiovascular risk factors, the relative risk for the highest fibrinogen quartile (> or =295 mg/dl) compared with the lowest (<228 mg/dl) was 4.8 (95% confidence interval: 1.4, 16.8, p = 0.01) for coronary heart disease, and 3.8 (95% confidence interval: 1.1, 13.4, p = 0.04) for myocardial infarction. Plasma fibrinogen is useful to predict the risk of coronary heart disease among urban Japanese, whose mean plasma fibrinogen is relatively low.

Validity and reliability of the Japanese version of the selected anger expression scale and age, sex, occupation and regional differences in anger expression among Japanese.

To examine the reliability and construct validity of the Japanese version of the Anger Expression Scale among four Japanese communities, and to examine distributions of anger expression scores according to sex, age, occupation, and community, we performed a cross-sectional study among 1,802 men and 3,229 women aged 20-70 in four geographic populations in 1995-97. We handed a self-administered questionnaire, which was selected from the Spielberger Anger Expression Scale, to the participants in the risk factor surveys and measured anger-in and anger-out as the anger expression scale. These scales had high internal consistency (Cronbach's alpha coefficient was 0.97-0.98 for anger-out and 0.77-0.86 for anger-in) and were of almost the same structure as the original. The Pearson correlation coefficients for the anger expression scale examined in 1995 and 1996 were 0.69 for anger-out and 0.57 for anger-in (both p < 0.001). The mean scores of both anger-out and anger-in were inversely associated with age. The mean anger-out score was higher for men than for women (p < 0.001), whereas the mean anger-in score did not vary significantly between the sexes. Furthermore, the mean scores of anger-out and anger-in varied among populations and occupational groups. The present study suggests that the Japanese version of the selected Anger Expression Scale is an acceptable scale for evaluating anger expression among Japanese.

Modulation of endothelin-1 coronary vasoconstriction in spontaneously hypertensive rats by the nitric oxide system.

To determine whether nitric oxide contributes to the augmented vasoconstrictive response to endothelin-1 (ET-1) in coronary vessels of hypertensive hearts, and also whether L-arginine administration can inhibit the augmented response to ET-1, we designed experiments to measure coronary perfusion resistance in isolated hearts of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) with or without L-arginine administration (0.5 g/L) for 2 weeks. The hearts were paced at a constant rate and perfused by the Langendorff technique at constant pressure (75 mm Hg). Perfusion flow and pressure were monitored, and coronary vascular resistance (CVR) was calculated. ET-1 infusion elicited dose-dependent increases in CVR in both WKY and SHR. At an ET-1 concentration of 1.5 x 10(-9) mol/L, the response was significantly greater in SHR. In L-NAME-treated WKY and SHR, responses to ET-1 were augmented, compared with those of nontreated rats, and this augmentation was greater in WKY. L-arginine administration reduced the CVR response to ET-1 in SHR, whereas it did not change responses to ET-1 in WKY. These findings suggest that the augmented vasoconstriction of the coronary artery induced by ET-1 in hypertensive hearts was due to a reduction in nitric oxide release in coronary vessels and that L-arginine can partially inhibit the vasoconstrictive response of the coronary artery.

Comprehensive analysis of p53 gene mutation characteristics in lung carcinoma with special reference to histological subtypes.

To date, the characteristics of p53 gene mutations in lung cancer have been extensively investigated. However, current estimates of p53 alterations are inaccurate, since most investigators have limited their analyses to exons 5 to 8 of the p53 gene. We examined 52 lung carcinoma cell lines and 106 primary non-small cell lung carcinomas (NSCLC) for mutations in the entire coding region of the p53 gene, from exons 2 to 11. High resolution single strand conformation polymorphism analysis was performed using a modified electrophoretic apparatus with a high concentration gel (14%) and accurate temperature control. The prevalence of mutations was high (more than 80%) in both small cell lung carcinoma (SCLC) (15 of 18) and NSCLC cell lines (28 of 34), and 9 of 45 mutations (20%) were detected outside the region of exons 5 to 8. The frequency of the mutations in primary NSCLC was 48% (51 of 106) and was significantly different (p=0.01) between adenocarcinoma (39%) and squamous cell carcinoma (67%). A-->G transitions (14%, 6 of 43 cases) as well as G-->T transversions (26%, 11 of 43 cases) were frequently detected with significant strand bias in smoking patients, suggesting that carcinogens causing these mutations are involved in smoking associated lung carcinogenesis.

[A case of nephrotic syndrome with diabetes mellitus and primary aldosteronism].

A 65-year-old man had been followed by a family doctor for the treatment of hypertension and chronic hepatitis (type C) for about 20 years. Although he was pointed out to have impaired glucose tolerance and primary aldosteronism in 1995, he refused an adrenal tumor operation. He was admitted to our hospital on December, 1997 for further evaluation of general malaise, pitting edema of the legs, and positive urinary protein. A diagnosis of nephrotic syndrome was made on admission and a renal biopsy was performed. Histological findings indicated that he was at the early phase of diabetic nephropathy and hypertensive renal sclerosis. It is commonly believed that diabetic nephropathy develops after ten years of diabetic history and under poor control conditions. The diabetic history of this patient was only several years and the disease was under good control. In contrast to blood glucose, hypertension was not well-controlled with any antihypertensive drug, because he had a primary aldosteronism. Unfortunately, he could not take a spironolactone because of side effects. After removal of his adrenal tumor, his blood pressure was normalized gradually, and concomitantly his urinary protein was reduced and plasma protein and albumin were restored. Hypokalemia also disappeared. These findings suggest that uncontrolled hypertension may have accelerated the condition of diabetic nephropathy. The data indicates that the control of hypertension is important for inhibiting the progression of diabetic nephropathy.

Correlation between the status of the p53 gene and survival in patients with stage I non-small cell lung carcinoma.

The association of p53 abnormalities with the prognosis of patients with non-small cell lung carcinoma (NSCLC) has been extensively investigated to date, however, this association is still controversial. Therefore, we investigated the prognostic significance of p53 mutations through exons 2 to 11 and p53 protein expression in 103 cases of stage I NSCLC. p53 mutations were detected in 49 of 103 (48%) tumors. Two separate mutations were detected in four tumors giving a total of 53 unique mutations in 49 tumors. Ten (19%) of mutations occurred outside exons 5-8. Positive immunohistochemical staining of p53 protein was detected in 41 of 103 (40%) tumors. The concordance rate between mutations and protein overexpression was only 69%. p53 mutations, but not expression, were significantly associated with a shortened survival of patients (P<0.001). Furthermore, we investigated the correlation between the types of p53 mutations and prognosis. p53 missense mutations rather than null mutations were associated with poor prognosis (P < 0.001 in missense mutations and P=0.243 in null mutations). These results indicated that p53 mutations, in particular missense mutations, rather than p53 expression could be a useful molecular marker for the prognosis of patients with surgically resected stage I NSCLC.

Plasma level of homocysteine is correlated to extracranial carotid-artery atherosclerosis in non-hypertensive Japanese.

BACKGROUND: Results of some epidemiologic studies in Western countries have clarified that hyperhomocysteinemia is a plausible risk factor for atherosclerotic vascular disease, but its role in Japanese communities is not known. DESIGN: A community-based cross-sectional design. METHODS: We performed a cross-sectional study of 474 elderly men aged 60-74 years in two Japanese rural communities (Noichi in southwestern Japan and Ikawa in northeastern Japan). We examined the association between plasma concentrations of homocysteine and the maximum intima-media thickness (assessed by ultrasonography). RESULTS: The prevalence of thickening was 10.7% for the lowest tertile of homocysteine level and 21.1% for the highest tertile. For the subjects without hypertension, the odds ratio for having carotid intima-media thickening was 5.8; it was significantly higher for the highest tertile of homocysteine level than it was for the lowest after adjusting for age, hypercholesterolemia, hypoalphalipoproteinemia, diabetes, and smoking by using a multiple logistic regression model. However, its correlation was not evident for those with hypertension. CONCLUSIONS: High levels of plasma homocysteine are correlated to extracranial carotid artery atherosclerosis in elderly men without hypertension in Japanese rural communities.

[Characteristics and outcome of stroke patients discharged from hospitals in an urban area of Japan].

The purpose of this study was to obtain the overall characteristics and outcome in stroke patients in an urban area of Japan, in order to develop some strategies for a community-based care system for improvement of the prognosis and activities of daily life in stroke patients. The present study, based on 4 hospitals in Yao city in Osaka, showed results as follows: 1) The number of stroke patients discharged from 4 hospitals during a recent one year period was 377 (216 men and 161 women). 2) The proportion of patients who died was 27%. Of the living patients, the proportions of patients who had motor paralysis or speech disturbance at discharge were 54% and 27%, respectively. 3) The proportion of patients who were to return to their home was 77% for all living patients. The proportion of patients who were not able to walk by themselves, or needed assistance in at least one of the activities of daily life was 31% and 28%, respectively, for all living patients who were to return to their home. This study showed that stroke registry from major hospitals in an urban area is useful for obtaining the overall characteristics of stroke patients in the area and promote community-wide programs in the prevention and home care of stroke.

[Survival and disability in stroke by stroke subtype based on computed tomographic findings in three rural Japanese communities].

PURPOSE: We conducted an epidemiological study of survival and disability in stroke in three Japanese communities to seek community strategies for improvement in survival and disability. METHODS: A total of 297 first-ever strokes were identified between 1988 and 1992 in three rural communities (total population = 47,000) located in Akita and Ibaraki. We analyzed survival rates and activity of daily living by sex, age-group and stroke subtypes. Successful review of computed tomography (CT) for 84 percent of the strokes (249 out of 297) was possible and the data were used for subtype analyses. RESULTS: For all strokes (n = 297) survival rates were 85% for 30 day, 70% for one year, 62% for three year. The rates tended to be lower in women than in men. The rates were lowest in ages less than 60 at thirty day, and in ages 80 and older at the end of the first and third year. Intracerebral hemorrhage with ventricular rupture, subarachnoid hemorrhage and cortical cerebral infarction had lower survival rates than intracerebral hemorrhage without ventricular rupture and lacunar infarction. Based on Cox's proportional hazard model, risk ratio for death was 2.07 in ages 70-79, and 3.80 in ages 80 and older compared with ages 60-69. The risk ratio was 3.46 for intracerebral hemorrhage with ventricular rupture, 3.38 for subarachnoid hemorrhage and 2.46 for cortical cerebral infarction compared with lacunar infarction. The proportion of stroke survivors who need assistance from others in the first and third years tended to be higher in women than in men. The proportion was higher in older patients than in the younger, and higher for intracerebral hemorrhage with ventricular rupture and cortical cerebral infarction than in other subtypes of stroke. From logistic regression analysis, the odds ratio for disability in the first year was 6.55 for ages 80 and older compared with ages 60-69. The odds ratio was 5.61 for intracerebral hemorrhage with ventricular rupture, 4.53 for cortical cerebral infarction compared with lacunar infarction. In the third year the odds ratio was significant for ages 70-79, and decreased for intracerebral hemorrhage with ventricular rupture (odds ratio = 2.98), and increased for cortical cerebral infarction (odds ratio = 6.06). CONCLUSIONS: Survival and disability in stroke depended on age and stroke subtypes. Even after age adjustment, stroke subtypes with large cerebral involvement had worse prognosis than stroke subtypes. Community-based hypertension control programs are important to prevent any subtypes of stroke. Stroke subtypes as well as age should be taken into account to develop effective care and medical treatments for strokes.

Augmented response of endothelin-A and endothelin-B receptor stimulation in coronary arteries of hypertensive hearts.

To determine whether the vasoconstrictor response to endothelin-1 (ET-1) is altered in coronary vessels of hypertensive hearts and the role of ETA and ETB receptors in these responses to ET-1, the vasoconstrictor response to ET-1 in coronary vessels was measured with or without ETA and ETB receptor antagonists. In isolated hearts of spontaneously hypertensive rat (SHR) and normotensive Wistar-Kyoto (WKY) rat, the coronary perfusion pressure was measured on a Langendorff apparatus with constant pressure (75 mm Hg). Coronary perfusion resistance (CPR) (mm Hg/ml/min/g) was calculated. ET-1 elicited dose-dependent increases of CPR in both normotensive and SHR rat hearts. However, the responses were significantly greater in SHR than those of WKY. Pretreatment with the ETA antagonist FR139317 and the ETB antagonist BQ788 inhibited CPR increases with ET-1 infusion. However, vasoconstrictor responses to ET-1 were still greater in SHR than in WKY after FR139317 or BQ788 infusion. These findings suggest that the augmented vasoconstrictor response of coronary artery to ET-1 is mediated by both ETA and ETB receptors. These changes may contribute to the impaired coronary circulation in hypertension.

Sequence analysis of the Porphyromonas gingivalis dipeptidyl peptidase IV gene.

We previously constructed a Porphyromonas gingivalis genomic library and isolated the 2.9 kb EcoRV fragment which specified glycylprolyl dipeptidyl aminopeptidase (GPase). Nucleotide sequencing of this fragment identified the single 2169 bp open reading frame which coded for a 723 amino acid protein. The amino acid sequencing of the NH2-terminal domain of the native and recombinant mature enzymes suggested that the protease possessed a 16 amino acid residue signal peptide. The calculated mass of the precursor and mature proteases were 82,018 and 80,235 daltons, respectively. The homology search of this enzyme in registered protein sequences revealed that this enzyme was homologous to dipeptidyl peptidase (DPP) IV from the Flavobacterium meningosepticum and that from eukaryotic cells, including the human, mouse, and rat. Three amino acid residues, Ser-593, Asp-668, and His-700, were identified as a putative catalytic triad, a common feature of eukaryotic serine proteases. In addition, this enzyme showed a broad proteolytic spectrum toward synthetic substrates capable of splitting not only Gly-Pro-derivative but also Ala-Pro, Lys-Pro, and Phe-Pro-derivatives. Therefore, we conclude that this enzyme belongs to DPP IV rather than GPase.