Mutations in the cardiac troponin I gene associated with hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM), the most common cause of sudden death in the young, is an autosomal dominant disease characterized by ventricular hypertrophy accompanied by myofibrillar disarrays. Linkage studies and candidate-gene approaches have demonstrated that about half of the patients have mutations in one of six disease genes: cardiac beta-myosin heavy chain (c beta MHC), cardiac troponin T (cTnT), alpha-tropomyosin (alpha TM), cardiac myosin binding protein C (cMBPC), ventricular myosin essential light chain (vMLC1) and ventricular myosin regulatory light chain (vMLC2) genes. Other disease genes remain unknown. Because all the known disease genes encode major contractile elements in cardiac muscle, we have systematically characterized the cardiac sarcomere genes, including cardiac troponin I (cTnI), cardiac actin (cACT) and cardiac troponin C (cTnC) in 184 unrelated patients with HCM and found mutations in the cTnI gene in several patients. Family studies showed that an Arg145Gly mutation was linked to HCM and a Lys206Gln mutation had occurred de novo, thus strongly suggesting that cTnI is the seventh HCM gene.

GPR40-induced insulin secretion by the novel agonist TAK-875: first clinical findings in patients with type 2 diabetes.

AIM: Free fatty acids act as signalling molecules for modulating insulin secretion, and their insulinotropic effects are glucose-dependent and mediated through G protein-coupled receptor 40 (GPR40). This mechanism is a potential target for new treatments for managing diabetes. In this study, we present the first clinical data for TAK-875, a novel highly selective, orally bioavailable GPR40 agonist, in Japanese patients with type 2 diabetes insufficiently controlled by diet or exercise therapy. METHODS: This was an exploratory phase II, multicentre, randomized, double-blind, parallel group study comparing the efficacy and tolerability of TAK-875 100 and 400 mg, and placebo, all administered once daily for 2 weeks. RESULTS: After 2 weeks of treatment, TAK-875 produced marked glucose lowering effects in a 75 g oral glucose tolerance test (OGTT) as evidenced by mean ± SE intergroup differences in plasma glucose AUC(0-3 h) of -12.98 ± 1.48 (p < 0.0001) and -8.12 ± 1.49 mmol·h/l (p < 0.0001), for TAK-875 400 mg vs. placebo and TAK-875 100 mg vs. placebo, respectively, and 2 h plasma glucose [-4.95 ± 0.71 (p < 0.0001) and -3.21 ± 0.71 mmol/l (p < 0.0001), respectively]. This was accompanied by a significant increase in insulin AUC(0-3 h) [34.68 ± 12.16 (p < 0.01) and 31.49 ± 12.20 (p < 0 · 05) µIU·h/ml, respectively]. Improvement in glycaemic profile was mirrored by a significant change in fasting plasma glucose [-2.37 ± 0·27 (p < 0.0001) and -1.88 ± 0.27 mmol/l (p < 0.0001), respectively]. No cases of hypoglycaemia were observed despite the significant reduction in plasma glucose. CONCLUSIONS: These exploratory findings provide evidence of the glucose-dependent insulinotropic potential of the GPR40 agonist TAK-875, and the promising clinical changes support future longer term clinical investigation.

Efficacy and safety of alogliptin added to metformin in Japanese patients with type 2 diabetes: a randomized, double-blind, placebo-controlled trial with an open-label, long-term extension study.

AIMS: To evaluate the efficacy and safety of alogliptin added to metformin versus metformin monotherapy in Japanese patients with type 2 diabetes who achieved inadequate glycaemic control on metformin (500 or 750 mg/day) + diet/exercise. METHODS: In a randomized, double-blind trial, 288 patients with type 2 diabetes mellitus T2DM received either 12.5 or 25 mg alogliptin once daily + metformin or placebo + metformin for 12 weeks. Thereafter, 276 patients continued on one of the two alogliptin dosages + metformin in an open-label extension for 40 weeks. The primary efficacy endpoint in the randomized, double-blind phase was the change in HbA1c from baseline (week 0) to the end of treatment (week 12). The primary endpoint during the long-term extension phase was adverse events. RESULTS: After 12 weeks both dosages of alogliptin + metformin produced significantly greater changes from baseline in HbA1c than placebo (metformin monotherapy: with changes in LS means - 0.55 and - 0.64% vs. 0.22%, respectively; p < 0.0001). Incidences of adverse effects were comparable between groups, with no increases in hypoglycaemia. Over 52 weeks, there were no safety or tolerability concerns with alogliptin when added to metformin. CONCLUSIONS: Alogliptin 12.5 and 25 mg once daily was safe and effective when added to metformin (500 or 750 mg/day) in Japanese patients with inadequately controlled type 2 diabetes on metformin alone.

Efficacy and safety of alogliptin added to pioglitazone in Japanese patients with type 2 diabetes: a randomized, double-blind, placebo-controlled trial with an open-label long-term extension study.

AIM: To assess the efficacy and safety of alogliptin added to pioglitazone versus pioglitazone monotherapy, in Japanese patients with type 2 diabetes who achieved inadequate glycaemic control on pioglitazone plus diet/exercise. METHODS: Patients were stabilized on pioglitazone 15 or 30 mg/day plus diet/exercise during a 16-week screening period. Patients with HbA1c of 6.9-10.4% were randomized to 12 weeks' double-blind treatment with alogliptin 12.5 or 25 mg once daily or placebo, added to their stable pioglitazone regimen. The primary endpoint was the change in HbA1c from baseline to week 12. Patients had an option to continue in a 40-week, open-label extension study, with those originally randomized to alogliptin remaining on the same dosage regimen while patients treated with placebo were randomly allocated to alogliptin 12.5 or 25 mg (added to their stable pioglitazone). RESULTS: The change from baseline in HbA1c after 12 weeks was significantly greater with alogliptin 12.5 mg added to pioglitazone and alogliptin 25 mg added to pioglitazone than with placebo added to pioglitazone (-0.91 and -0.97% vs. -0.19%; p < 0.0001). Responder rates (HbA1c <6.9% and HbA1c <6.2%) and changes in fasting and postprandial blood glucose levels showed a similar positive trend in terms of glycaemic control. The benefits seen with alogliptin were sustained during the 40-week extension period. Alogliptin added to pioglitazone was generally well tolerated; hypoglycaemia was infrequent and increases in body weight were minor. CONCLUSIONS: Once-daily alogliptin was effective and generally well tolerated when given as add-on therapy to pioglitazone in Japanese patients with type 2 diabetes who achieved inadequate glycaemic control on pioglitazone plus lifestyle measures. Clinical benefits were maintained for 52 weeks.

Quantitation of human herpesvirus-6 (HHV-6) DNA in a cord blood transplant recipient with chromosomal integration of HHV-6.

Chromosomal integration of the human herpesvirus-6 (HHV-6) genome (CIHHV-6) is an important consideration if HHV-6 DNA is detected during the course of transplantation. A 4-year-old girl with refractory anemia with excess blasts type-2 was diagnosed with CIHHV-6 before a cord blood transplantation. HHV-6 DNA was serially quantitated by polymerase chain reaction assay in the transplant period. The possibility of HHV-6 reactivation in a transplant recipient with CIHHV-6 was suspected in our case.

FOXO3 is essential for CD44 expression in pancreatic cancer cells.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal types of cancer and the 5-year survival rate is only 5%. Several studies have suggested that cancer stem cells (CSCs) are thought to be involved in recurrence and metastasis and so it is essential to establish an approach targeting CSCs. Here we have demonstrated that cyclic guanosine monophosphate (cGMP) suppressed CD44 expression and the properties of CSCs in PDAC. Microarray analysis suggested that cGMP inhibited Forkhead box O3 (FOXO3), which is known as a tumor suppressor. Surprisingly, our data demonstrated that FOXO3 is essential for CD44 expression and the properties of CSCs. Our data also indicated that patients with high FOXO3 activation signatures had poor prognoses. This evidence suggested that cGMP induction and FOXO3 inhibition could be ideal candidates for pancreatic CSC.

Argyrophilic nucleolar-organizer region counts and DNA status in bronchioloalveolar epithelial hyperplasia and adenocarcinoma of the lung.

Few studies have investigated more than one cell-biological parameter in bronchioloalveolar epithelial hyperplasia (BEH) and bronchioloalveolar carcinoma (BAC). The authors have examined argyrophilic nucleolar-organizer regions (AgNORs) and DNA status in surgically resected formalin-fixed paraffin-embedded specimens, 27 BEH and 62 well-differentiated adenocarcinomas, including 30 BAC. The authors measured the mean AgNOR count in 200 nuclei from sections of these regions. The authors also quantified DNA distribution in more than 200 cancer cells from sections of these regions, stained with 4',6-diamidino-2-phenylindole, using a microspectrophotometer. Fourteen lesions were interpreted as atypical BEH. The mean number of AgNORs per nucleus in BEH was 1.25 to 2.63. The mean number of AgNORs was significantly lower in both typical and atypical BEH than in either the bronchial surface epithelial type or the bronchial gland cell type of well-differentiated adenocarcinoma (P < .05). The mean number of AgNORs in atypical BEH was intermediate between that in typical BEH and that in BAC. Quantitative DNA image analysis showed DNA aneuploidy in 2 of 18 BEHs and 18 of 52 well-differentiated adenocarcinomas. The incidence of DNA aneuploidy increased in this order: typical BEH (0%, none out of 10 lesions) through atypical BEH (25.0%, 2 out of 8 lesions), to adenocarcinoma (34.6%, 18 out of 52 cases). Thus, the incidence of DNA aneuploidy in atypical BEH (25.0%) was intermediate between typical BEH (0%) and BAC (30.0%). These results suggest that atypical BEH may be closely related to BAC.

Telomerase activity and expression of human telomerase RNA component and human telomerase reverse transcriptase in lung carcinomas.

The aim of this study was to evaluate the usefulness of determination of telomerase activity and expression of human telomerase RNA component (hTERC) and human telomerase reverse transcriptase (hTERT) for the diagnosis of lung carcinomas. The tissues studied consisted of 115 carcinomas and adjacent nonneoplastic lung, which were removed surgically without previous chemotherapy or radiotherapy. Telomerase activity was determined using a semiquantitative polymerase chain reaction-based telomeric repeat amplification protocol (TRAP) assay. The results obtained were classified into high and low telomerase groups. Localization of expression was examined by using in situ hybridization and immunohistochemistry. The correlation between telomerase activity in lung carcinoma and clinicopathologic features, including prognosis, was investigated. Telomerase activity in lung carcinomas was detected in 107 of 115 (93%) lung carcinomas, but not in any adjacent noncancerous tissues, and was significantly higher in small cell carcinoma than in any other histologic type. This activity also was significantly higher in poorly differentiated than in well-differentiated squamous cell carcinomas and adenocarcinomas. The overall survival rate (P =.020) was significantly lower in the high telomerase group. Messenger RNAs for hTERC and hTERT were mainly detected in the cytoplasm of cancer cells by in situ hybridization, and TERT protein was localized in the nuclei of these cells by immunohistochemical staining. Determinations of telomerase activity by in situ hybridization, immunohistochemistry, and TRAP assay are useful for evaluating the diagnosis and prognosis of lung carcinomas.

KM195 as an immunohistochemical marker of adenocarcinoma of the lung.

In order to improve the diagnosis of lung carcinoma, in which a complicated histologic pattern is present, the immunohistochemistry of 119 adenocarcinomas, 65 squamous cell carcinomas, 12 small cell carcinomas, 18 large cell carcinomas, and 15 metastatic adenocarcinoma in the lung were evaluated using a monoclonal antibody, KM195, against lung carcinoma, and compared with the immunohistochemical results using anti-human cytokeratin (CAM 5.2) and other monoclonal antibodies. Formalin-fixed, paraffin-embedded tissues were stained using the labeled streptavidin-biotin method. Extracts from fresh tissue homogenate, after fractionation by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, were transferred by Western blotting and stained with KM195. The anti-lung adenocarcinoma, murine, monoclonal antibody KM195 (IgG), was positive in 107 of 119 adenocarcinomas (90%), in 15 of 18 large cell carcinoma (83%), in three of 65 squamous cell carcinomas (5%), 13 of 15 (87%) metastatic adenocarcinoma in the lung, and was negative in 12 small cell carcinomas (P < 0.001). KM195-bound protein of primary and metastatic adenocarcinoma in the lung cases concentrated at about 40 kDa. In contrast, CAM 5.2 was positive in 52 of 67 (78%) adenocarcinomas, 10 of 62 (16%) squamous cell carcinomas, and was negative in six small cell carcinomas. These results suggest that the immunohistochemistry for KM195 may be a more useful marker over CAM 5.2 for the diagnosis of pulmonary adenocarcinoma.

Cerebral perfusion patterns in vascular dementia of Binswanger type compared with senile dementia of Alzheimer type: a SPECT study.

Cerebral perfusion patterns in 18 cases with vascular dementia of Binswanger type (VDBT) (8 moderate and 10 severe cases) were compared with 25 cases with senile dementia of Alzheimer type (SDAT) (16 moderate and 9 severe cases) and 14 controls by single photon emission computed tomography using N-isopropyl-p-123I iodoamphetamine (IMP) as a tracer. The cerebral: cerebellar IMP uptake ratio (%) (CCR) was used as a measured of relative cerebral perfusion. The CCRs were about 85-90% in all areas in controls. Moderate VDBT patients showed a remarkable decrease of CCRs in the basal grey region (thalamus and basal ganglia) (right 79%, left 77%) and in the frontal area (right 79%, left 80%) (P less than 0.01). In severe VDBT patients a significant decrease of the CCR was noted in all regions (P less than 0.01). The decrease of mean CCRs in the hemispheres was significantly correlated with the severity of disease determined by psychometric testing. Patients with SDAT showed a significant decrease of the CCR in the parietal (right 71%, left 74%) and right temporal (78%) areas in the moderate stage (P less than 0.01), and further progression of dementia was associated with low perfusion areas extending to the the frontal areas (78%, P less than 0.01). These differences in the perfusion patterns and their changes with progression of the illnesses may be reflected in characteristic clinical features.

Hypertrophic obstructive cardiomyopathy due to a novel T-to-A transition at codon 624 in the beta-myosin heavy chain (beta-MHC) gene possibly related to the sudden death.

Many missense mutations in the beta-myosin heavy chain have been reported in patients with hypertrophic obstructive cardiomyopathy (HOCM). However, the controversy is present whether the mutation accompanying the change of electric charge is related with poorer prognosis. The proband, a 48-year-old female, of the family was diagnosed clinically as HOCM, and a structural analysis of the cardiac beta-MHC gene showed that the proband and her junior daughter had a novel mutation with T to A transition in codon 624 replacing tyrosine with asparagine, which was not present in her husband, elder daughter and son. The proband's husband, son and two daughters were healthy except that the ECG of junior daughter (15-year-old) showed complete right bundle branch block. Proband's mother died suddenly after the delivery of the proband and the proband also collapsed suddenly. The occurrence of sudden death in proband and her mother suggested that HOCM with this novel mutation might be associated with a high risk of sudden death irrespective of the absence of charge alteration.

MICA gene polymorphism in Takayasu's arteritis and Buerger's disease.

To further clarify the HLA-linked genes susceptible to arterio-vasculitis of unknown etiology, Takayasu's arteritis and Buerger's disease, polymorphism in the MICA gene, a newly identified gene near the HLA-B gene and expressed in epithelial cell lineage, was investigated. Polymerase chain reaction (PCR)-DNA conformation polymorphism (DCP) analysis and subsequent sequencing of the MICA gene have revealed that there are 5 MICA alleles which are different in the number of a GCT repeat in exon 5: MICA alleles MICA-1.1, -1.2, -1.3 and -1.4 have 9, 6, 5 and 4 GCT repeats, respectively, and MICA-1.5 has 5 GCT repeats with a 1 bp frameshift insertion in the repeat. MICA genotyping data in 81 Japanese patients with Takayasu's arteritis, 38 Japanese patients with Buerger's disease, and 160 healthy Japanese controls showed that MICA-1.2 and -1.4 were significantly associated with Takayasu's arteritis and Buerger's disease, respectively. Because MICA-1.2 and -1.4 were in strong linkage disequilibria with HLA-B52 and -B54 in the Japanese populations, respectively, we have compared the odds ratio (OR) of the risk to the diseases for individuals having both or each of the disease-associated MICA and HLA-B alleles. It was found that MICA-1.2 gave a significantly high OR of risk to Takayasu's arteritis in the absence of HLA-B52, suggesting that the HLA-linked gene susceptible to Takayasu's arteritis is mapped near the MICA gene. In contrast, MICA-1.4 gave a significantly high OR of risk to Buerger's disease only in the presence of HLA-B54, suggesting that the HLA-linked gene susceptible to Buerger's disease is linked to the HLA-B54-MICA-1.4 haplotype, and may be differently mapped from that to Takayasu's arteritis.

Os odontoideum with vertebral artery occlusion.

A 21-year-old man developed signs of brainstem damage after being injured while playing rugby. Cervical x-ray films showed os odontoideum, and angiography revealed persistent occlusion of the right vertebral artery at the level of the second cervical spine. These findings indicated that atlantoaxial dislocation caused by os odontoideum may have induced vertebral artery occlusion, leading to brainstem infarction.

Expression and adhesive ability of gicerin, a cell adhesion molecule, in the pock lesions of chorioallantoic membranes infected with an avian poxvirus.

The expression and adhesive activities of gicerin, a cell adhesion protein, in the pock lesions on chicken chorioallantoic membranes (CAM) infected with an avian poxvirus were studied. In normal CAMs, gicerin was found on the flattened epithelial cells, and neurite outgrowth factor (NOF) was in the basement membrane. However, in the pock lesions on infected CAMs, gicerin was overexpressed on the cell membranes of hyperplastic epithelial cells forming thick epithelial layers. Neurite outgrowth factor was also found mainly in the basement membrane, but occasionally showed aberrant expression among hyperplastic cells. In vitro analyses, using the dissociated cells from pock lesions, demonstrated that an anti-gicerin polyclonal antibody inhibit cell aggregation activity and cell adhesion to NOF. These results suggest that gicerin might promote the cell-cell and cell-extracellular matrix protein bindings of the hyperplastic epithelial cells by its homophilic and heterophilic adhesive activities, and contribute to pock formation on the infected CAMs.

Protein kinase C mRNA and protein expressions in hypobaric hypoxia-induced cardiac hypertrophy in rats.

AIM: Protein kinase C (PKC), cloned as a serine/threonine kinase, plays key roles in diverse intracellular signalling processes and in cardiovascular remodelling during pressure overload or volume overload. We looked for correlations between changes in PKC isoforms (levels and/or subcellular distributions) and cardiac remodelling during experimental hypobaric hypoxic environment (HHE)-induced pulmonary hypertension. METHODS: To study the PKC system in the heart during HHE, 148 male Wistar rats were housed for up to 21 days in a chamber at the equivalent of 5500 m altitude level (10% O(2)). RESULTS: At 14 or more days of exposure to HHE, pulmonary arterial pressure (PAP) was significantly increased. In the right ventricle (RV): (1) the expression of PKC-alpha protein in the cytosolic and membrane fractions was increased at 3-14 days and at 5-7 days of exposure respectively; (ii) the cytosolic expression of PKC-delta protein was increased at 1-5, 14 and 21 days of exposure; (3) the membrane expressions of the proteins were decreased at 14-21 (PKC-betaII), 14-21 (PKC-gamma), and 0.5-5 and 21 (PKC-epsilon) days of exposure; (4) the expression of the active form of PKC-alpha protein on the plasma membrane was increased at 3 days of exposure (based on semiquantitative analysis of the immunohistochemistry). In the left ventricle, the expressions of the PKC mRNAs, and of their cytosolic and membrane proteins, were almost unchanged. The above changes in PKC-alpha, which were strongly evident in the RV, occurred alongside the increase in PAP. CONCLUSION: PKC-alpha may help to modulate the right ventricular hypertrophy caused by pulmonary hypertension in HHE.

Osteopontin expression in normal and hypobaric hypoxia-exposed rats.

AIM: Experimental pulmonary hypertension induced in a hypobaric hypoxic environment (HHE) is characterized by structural remodelling of the heart and pulmonary arteries. Osteopontin (OPN) has emerged as a key factor in cardiovascular remodelling in response to pressure or volume overload. We studied the possible effects of HHE on the OPN synthesis system. METHODS: One hundred and forty-eight male Wistar rats were housed in a chamber with conditions equivalent of an altitude of 5500 m for up to 21 days. RESULTS: Plasma OPN protein level was found to be significantly decreased on day 0.5 of exposure to HHE, as was the level in the adrenal gland (which secreted highest levels of OPN protein). In the right ventricle of the heart (mRNA) and the lung (protein), OPN expression was found to be significantly increased only on day 1 and day 5, respectively, of exposure to HHE. By immunohistochemistry, the distribution and intensity of OPN protein in several organs were found to alter during exposure to HHE. However, these changes in OPN synthesis did not coincide with the moderate increase in pulmonary arterial pressure (PAP) (maximal mean PAP, 24.5 mmHg) during HHE. CONCLUSION: Pulmonary hypertension in HHE with conditions equivalent of an altitude of 5500 m may induce little or no OPN in heart and lung. Sustained induction may require a more severe PAP overload.

Expression in lung carcinomas of platelet-derived growth factor and its receptors.

Platelet-derived growth factor (PDGF) is synthesized and secreted by mesenchymal cells. We used immunohistochemistry and in situ hybridization to determine whether immunoreactivity for PDGF and PDGF receptor (PDGF-R) might be a prognostic indicator in lung carcinoma. We compared these results with those of immunohistochemistry for anti-proliferating cell nuclear antigen (anti-PCNA). Indirect immunohistochemistry and in situ hybridization were performed for PDGF B-chain, PDGF-R beta and PCNA antibodies, and PDGF B mRNA on frozen, paraffin-embedded sections of 92 surgically resected lung carcinomas (39 squamous cell carcinomas, 47 adenocarcinomas, 2 large-cell carcinomas, 2 adenosquamous carcinomas, and 2 double carcinomas). Clinicopathologic data (sex, age, stage, survival period, histologic type, and degree of cell differentiation) were evaluated using a statistical analysis system. PDGF reactivity was positive in tumor cell cytoplasm in some cases of squamous cell carcinoma (64%) and adenocarcinoma (55%) and in all cases of large-cell carcinoma, adenosquamous carcinoma, and double carcinoma. PDGF-R reactivity was detected only in tumor stroma. Positive PDGF staining was associated with a poor prognosis in patients with lung carcinoma, independent of age, sex, stage, and degree of cell differentiation (risk ratio = 2.53, p = 0.03). PDGF B mRNA was detected in 100% of PDGF-positive squamous cell carcinomas and in 85% of adenocarcinomas. There was no correlation between PDGF expression and PCNA index in lung carcinomas. Together, these results suggest that immunohistochemistry for PDGF B-chain may predict the outcome for lung carcinoma patients.

Expression of platelet-derived growth-factor B-chain mRNA and tumor angiogenesis in invasive transitional cell carcinoma of the upper urinary tract.

In several types of carcinoma, angiogenesis is associated with metastasis and might be a prognostic indicator. Platelet-derived growth factor (PDGF) is one of several growth factors known; it is involved in the regulation of cell migration and proliferation. There have been few reports, however, dealing with the expression of PDGF B-chain mRNA and angiogenesis in transitional cell carcinoma. We evaluated both the expression of PDGF B-chain mRNA and angiogenesis in transitional cell carcinoma of the upper urinary tract and examined their interrelation with metastasis, patient prognosis, and other established clinicopathologic parameters. For this purpose, formalin-fixed, paraffin-embedded tumor tissues from 91 patients with invasive tumors were analyzed with in situ hybridization for PDGF B-chain mRNA and immunohistochemical staining of Factor VIII-related antigen to assess angiogenesis. The expression of PDGF B-chain mRNA was positive in 59 (66%) of the 91 patients. Microvessel density was significantly increased in positive PDGF B-chain mRNA cases (P < .0001). There was no significance, however, in any relationship between the expression of PDGF B-chain mRNA or between the microvessel density and the clinicopathologic findings, metastasis, or prognosis. Assessment of the expression of PDGF B-chain mRNA and microvessel density seems to be of no real value in predicting either the risk of metastasis or the prognosis in transitional cell carcinoma of the upper urinary tract.

Electroencephalographic correlates of blood flow and oxygen metabolism provided by positron emission tomography in patients with cerebral infarction.

Quantitative EEG data were analyzed statistically with respect to cortical cerebral blood flow (CBF) and oxygen metabolism (CMRO2) measured by positron emission tomography in 47 patients with unilateral cerebral infarction. Relative value of the square root of average power was used as a percentage power fraction (PPF) for each frequency category. Power ratio index (PRI) was calculated by dividing the combined delta-PPF and theta-PPF by the combined alpha-PPF and beta-PPF. Delta-PPF, theta-PPF and PRI correlated negatively with regional CBF (rCBF) and CMRO2 (rCMRO2) whereas alpha-PPF and beta-PPF correlated positively. In the acute stage, delta-PPF, alpha-PPF and PRI correlated with rCBF at all but the frontopolar region whereas the correlation with rCMRO2 was poor. Alpha-PPF and PRI correlated also with rCMRO2 in the frontal, central, parietal and occipital regions while delta-PPF correlated with rCBF only in the parietal and occipital regions in the subacute stage. In the chronic stage, all EEG quotients correlated significantly with both rCBF and CMRO2 in the central and parietal regions. In the frontopolar region, only the theta-PPF correlated with rCBF throughout. In the comparison of hemispheric mean values, the correlations were always closer for the affected hemisphere than for the contralateral hemisphere. Although hemispheric mean CBF and CMRO2 were significantly lower in patients with cortical infarcts on CT than in those with small subcortical infarcts, there was no significant difference in the EEG data between the 2 groups.