Detection of proliferating hepatocytes by immunohistochemical staining for proliferating cell nuclear antigen (PCNA) in patients with acute hepatic failure

ABSTRACT— This study evaluated whether liver regeneration could take place after massive or submassive necrosis of liver cells in 25 patients with several kinds of hepatic failure by immunohistochemical staining for proliferating cell nuclear antigen (PCNA). PCNA positivity was significantly higher (P<0.01) in the patients who survived than in the patients who died. Furthermore, PCNA-positive hepatocytes were recognized diffusely in the lobule of the liver in survivors. There was positive correlation between PCNA positivity and plasma concentration of AFP (α-fetoprotein), (r = 0.77, P<0.01). These results show that liver regeneration could take place after massive necrosis of liver cells in survivors from acute hepatic failure and that immunohistochemical staining for PCNA is useful for prognostic evaluation.     

Effect of dobutamine on the arterial ketone body ratio and portal blood flow velocity in cirrhosis

ABSTRACT— We studied the relationship between the portal blood flow velocity and the arterial ketone body ratio in patients with chronic liver disease receiving a dobutamine infusion. We used an ultrasonic Doppler duplex system to evaluate the portal blood flow velocity. Dobutamine was given intravenously at 5 μg/kg/min for 20 min. Dobutamine infusion induced smaller changes in the portal blood flow velocity and ketone body ratio in liver cirrhosis than in chronic hepatitis. The existence of shunts and the poor increase of the cardiac index in response to dobutamine explained the limited improvement of portal blood flow velocity in cirrhosis patients. The ketone body ratio was improved by dobutamine in cirrhosis patients whose portal blood flow velocity was increased by more than 10%, while this ratio decreased when the increase of it was less than 10%. There was no change in portal oxygen extraction in the cirrhosis group, and portal oxygen uptake only increased when the portal blood flow velocity rose by more than 10%. Dobutamine should only be used to treat liver failure if the portal blood flow velocity is increased by more than 10% or the arterial ketone body ratio is improved by a test infusion.     

Left ventricular retraining and anatomic correction in teenage patient with congenitally corrected transposition of the great arteries.

Left ventricular (LV) retraining followed by anatomical repair would be a superior alternative in patients with congenitally corrected transposition (ccTGA) having a deconditioned morphologically left ventricle (MLV); however, LV retraining in older children is a challenging task. A retraining process of the MLV in a teenage patient with ccTGA is reported here. Cardiac catheterization at 7 years of age revealed low pressure of the MLV (33/4 mm Hg) and a LV to right ventricular pressure ratio (LVp/RVp ratio) of 0.32. The first pulmonary artery banding (PAB) was performed at 10 years of age. Although the LVp/RVp ratio reached 0.68, there was no evidence of adequate LV hypertrophy. The second PAB was performed 2 years after the initial PAB, resulting in an increase in the LVp/RVp ratio to 0.93 and an adequate LV hypertrophy. The double switch procedure was successfully performed at 13 years of age. Although the ejection fraction of the MLV mildly decreased, the patient has been doing well during a follow-up period of 4 years. The MLV in the teenage patient with ccTGA was successfully trained using a retraining strategy and has sustained systemic circulation after anatomical repair.     

Clinicopathologic Characteristics and Prognosis of Advanced Gastric Cancer Simulating Early Gastric Cancer

Background

Although the clinicopathologic features and prognosis of Borrmann type advanced gastric cancer has been well characterized, those of advanced gastric cancer simulating early gastric cancer (AGC simulating EGC) still remains unclear.

Methods

We reviewed 1985 gastric cancer patients who had undergone gastrectomy at our hospital to determine the clinicopathologic characteristics, susceptible sites for lymph node metastasis, and prognosis of AGC simulating EGC in comparison with Borrmann type advanced gastric cancer.

Results

Among 102 patients with AGC simulating EGC, 100 patients (98%) had tumors with depressed type appearance. The frequencies of serosal invasion, lymph node metastasis, lymphatic vessel invasion, blood vessel invasion, and liver metastasis were significantly lower in AGC simulating EGC than in Borrmann type tumors. The prognosis of AGC simulating EGC was significantly better than that of the Borrmann type tumors. Multivariate analysis indicated that the gross appearance was an independent prognostic factor. In patients with AGC simulating EGC which invaded to the the muscularis propria (MP), most lymph node metastasis was restricted with the perigastric lymph nodes (1st-titer lymph nodes) and lymph node metastasis to 2nd-titer lymph nodes was only observed at station 8a.

Conclusion

AGC simulating EGC is less advanced in comparison with Borrmann type advanced gastric cancer. Based on the results of susceptible sites for lymph node metastasis in the current study, limited lymph node dissection could be indicated for AGC simulating EGC whose depth of invasion is MP.     

Clustered features of the metabolic syndrome and the risk for increased aortic pulse wave velocity in middle-aged Japanese men

The association between different features of the metabolic syndrome (MS) (obesity, hypertension, hypercholesterolemia, low high-density lipoprotein cholesterol level, hypertriglyceridemia, high fasting plasma glucose level, and hyperuricemia) and the risk for increased aortic pulse wave velocity (PWV) of > or = 8.0 m/sec was examined in 2431 Japanese men aged 35 to 54 years who were not taking antihypertensive medication. After controlling for age, cigarette smoking, and alcohol intake, the odds ratios for increased aortic PWV in subjects with 1, 2, 3, and > or = 4 features of the MS, compared with those without features of the MS, were 1.35 (95% CI, 0.86 to 2.11), 1.90 (95% CI, 1.18 to 3.06), 1.57 (95% CI, 0.89 to 2.76), and 2.38 (95% CI, 1.26 to 4.49), respectively (p for trend = 0.003). A 9-year longitudinal study was also performed to prospectively examine the association between clustered features of the MS and the development of increased aortic PWV in 2073 men without aortic stiffness with a PWV < 8.0 m/sec and without antihypertensive medication during the follow-up period. The multivariate-adjusted hazard ratios for the incidence of increased aortic PWV in subjects with 1, 2, 3, and > or = 4 features of the MS, compared with those without features of the MS, were 1.39 (95% CI, 1.10 to 1.77), 1.46 (95% CI, 1.1 1 to 1.92), 1.75 (95% CI, 1.27 to 2.40), and 2.22 (95% CI, 1.52 to 3.25), respectively (p for trend < 0.001). These results suggest that clustered features of the MS are closely associated with the risk for increased aortic PWV in middle-aged Japanese men.     

High Incidence of Positive Autoantibodies against Thyroid Peroxidase and Thyroglobulin in Patients with Sarcoidosis

OBJECTIVE  Although abnormalities of the humoral immune system, such as increased immunoglobulin production, are known in sarcoidosis, the relationship between sarcoidosis and autoimmune disorders is uncertain. We studied the incidence of thyroid autoantibodies and the prevalence of Hashimoto's thyroiditis in patients with sarcoidosis.
PATIENTS AND MEASUREMENTS  Sixty-two patients with pulmonary sarcoidosis, diagnosed by a combination of clinical, radiographic and histological findings, were studied. As controls, three groups of subjects aged 40 and over without a known history of thyroid disease (60 patients with pulmonary diseases other than sarcoidosis, 88 hospital employees and 82 company workers), were also analysed. Antibodies against thyroid peroxidase (TPO-Ab) and purified thyroglobulin (Tg-Ab) were measured by radioimmunoassay and antibodies against microsomal antigen (MCHA) and thyroglobulin (TGHA), by haemagglutination.
RESULTS  Seventeen of 62 patients (27.4%) had either positive TPO-Ab or Tg-Ab or both. All the patients with positive thyroid autoantibodies were of middle or advanced age, and the incidence of positive TPO-Ab/Tg-Ab in patients with sarcoidosis aged 40 and over was 54.5% in males, 32.4% in females and 37.8% overall. The prevalence was significantly higher in males compared to age-matched control males (0–7.7% in the controls), and in female patients was twice that found in controls (11.8–16.3%). Seven patients had Hashimoto's thyroiditis, indicating that the prevalence was 11.3%, and much higher than that previously reported.
CONCLUSIONS  The data show a remarkably high incidence of thyroid autoantibodies in patients of middle or advanced age with sarcoidosis, especially in males, and a higher prevalence of Hashimoto's thyroiditis than in previous reports.     

Mortality risk attributable to atrial fibrillation in middle-aged and elderly people in the Japanese general population: nineteen-year follow-up in NIPPON DATA80.

BACKGROUND: The extent to which atrial fibrillation (AF) contributes to mortality in the Japanese general population has not been clarified. METHODS AND RESULTS: A randomly sampled general population from all over Japan (4,154 men, 5,329 women; age > or =30 years) was enrolled. Single electrocardiogram recordings were taken in the baseline survey. Stroke death, cardiovascular deaths and all-cause deaths during the subsequent 19 years were analyzed by the presence of AF at baseline. Cox's regression analysis was carried out to estimate the hazard ratios (HRs) of each cause of death attributable to AF after adjusting for other risk factors. Prevalence of AF was 0.64% in the study. The observed person-years were 162,980 among persons without AF and 699 among persons with AF. There were 1,919 deaths. Multivariate adjusted HRs for stroke death, cardiovascular death and all-cause death were 2.69, 2.76 and 1.88, respectively (p<0.05). These HRs were 14.7, 9.63 and 4.00 among persons aged 64 years or younger (p<0.05). CONCLUSION: AF affects stroke mortality, cardiovascular mortality and all-cause mortality in the Japanese general population. Careful attention should be paid to persons with AF in order to prevent future cardiovascular events.     

Angiotensin-converting enzyme insertion/deletion genotype is associated with the activities of plasma coagulation factor VII and X independent of triglyceride metabolism

BACKGROUND: The D allele of angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism and coagulation activity play important roles in cardiovascular events, however, the precise association between these two risk factors remains unclear. METHODS: We identified the ACE I/D genotype and measured the plasma coagulation factor VII and X (FVII and FX) activities and serum lipids in 172 patients (110 men and 62 women, mean age 56.7+/-13.3 years) undergoing coronary angiography. RESULTS: The frequency of the D allele was significantly higher in those with a history of myocardial infarction (MI) than in those with normal coronary arteries, but there was no significant association between FVII and FX activities and the stage of coronary disease. Plasma coagulation factor VII and FX activities were significantly lower in the DD genotype (n=42) than in the II genotype (n=67, P<0.001 and P<0.001, respectively) or the ID genotype (n=63, P<0.01 and P<0.05, respectively). The association of the ACE D allele with lower activities of FVII and FX was also seen in patients with coronary artery disease (CAD). There was a significant association between serum triglyceride levels with FVII and FX, but not with the ACE I/D genotype. CONCLUSION: We concluded that the ACE I/D polymorphism may contribute more to the onset of MI than the activities of FVII and FX and that the ACE D allele might be associated with lower plasma activities of FVII and FX. The potential link between ACE I/D polymorphism and the plasma activities of FVII and FX is probably independent of triglyceride metabolism.     

Genomic imprinting of XX spermatogonia and XX oocytes recovered from XX<-->XY chimeric testes

We produced XX<-->XY chimeras by using embryos whose X chromosomes were tagged with EGFP (X*), making the fluorescent green female (XX*) germ cells easily distinguishable from their nonfluorescent male (XY) counterparts. Taking advantage of tagging with EGFP, the XX* "prospermatogonia" were isolated from the testes, and the status of their genomic imprinting was examined. It was shown that these XX cells underwent a paternal imprinting, despite their chromosomal constitution. As previously indicated in sex-reversal XXsxr testes, we also found a few green XX* germ cells developed as "eggs" within the seminiferous tubules of XX*<-->XY chimeric testes. These cells were indistinguishable from XX* prospermatogonia at birth but resumed oogenesis in a testicular environment. The biological nature of the "testicular eggs" was examined by recovering the eggs from chimeric testes. The testicular eggs not only formed an egg-specific structure, the zona pellucida, but also were able to fuse with sperm. The collected testicular eggs were indicated to undergo maternal imprinting, despite the testicular environment. The genomic imprinting did not always follow the environmental conditions of where the germ cells resided; rather, it was defined by the sex that was chosen by the germ cells at early embryonic stage.