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We examined the association between cognitive functioning and health-related quality of life (HR-QOL) in military veterans with a history of mild traumatic brain injury (mTBI) using two methods to assess cognition: mean performance on cognitive composite scores and across-test intraindividual variability (IIV). The sample included 73 veterans (84.9% male; age, mean = 32.47 years) who completed neuropsychological testing and self-report questionnaires ∼7 years post-injury. Three cognitive composite scores representing mean performance were computed, including memory, attention/processing speed (A/PS), and executive functioning (EF). Three IIV indices were also calculated reflecting degree of dispersion across the same cognitive domains: memory-IIV, A/PS-IIV, and EF-IIV. The Posttraumatic Stress Disorder (PTSD) Checklist-Military Version (PCL-M) was used to assess current PTSD symptoms, and the World Health Organization Quality of Life Short Version Physical Health domain was used to assess HR-QOL. Hierarchical linear regressions adjusting for PTSD symptoms demonstrated that IIV indices, but not mean cognitive composite scores, significantly predicted HR-QOL. Specifically, memory-IIV, A/PS-IIV, and EF-IIV, when taken together, made an independent and significant contribution to the prediction of HR-QOL. Examination of the standardized coefficients showed that the A/PS-IIV index was uniquely associated with HR-QOL, such that higher A/PS-IIV scores significantly predicted poorer HR-QOL. Our results are the first to show that, in veterans with remote mTBI histories, greater fluctuations in cognitive performance significantly contribute to poorer HR-QOL, even after accounting for PTSD symptom severity. Moreover, findings suggest that, compared to traditional mean cognitive performance scores, measures of IIV may represent more sensitive indicators of clinical outcome and better align with subjective experiences of distress.

Mitochondrial respiratory chain disorder (MRCD) can cause liver failure requiring liver transplantation (LT), although it is often difficult to diagnose before LT. From 2005 to 2016, 9 MRCD patients with the median age at LT of 6 months underwent LT in our institute. Their clinical courses were retrospectively reviewed and the laboratory parameters were compared between the MRCD patients and 10 patients with acute liver failure unrelated to MRCD (non-MRCD). Five patients had extrahepatic manifestations, including developmental disorders in 3 and failure to thrive in 3, before LT. Only 3 patients (33.3%) were diagnosed before LT. Between MRCD and non-MRCD, lactate was significantly high and lactate-to-pyruvate ratio (L/P ratio) tended to be higher in MRCD. From the receiver operating characteristic curve, the optimal cutoff value of lactate was 50.0 mg/dL and that of L/P ratio was 23.2. Patient survival rate of MRCD was 77.8%, although 2 patients with mitochondrial depletion syndrome suffered from de novo pulmonary hypertension after LT. Our experiences showed the difficulty of preoperative diagnosis, and preoperative extrahepatic manifestations did not always mean poor outcome. Our study showed that lactate value and L/P ratio can be excellent predictors of MRCD.

We have demonstrated that carbohydrates in Cry j 1, the major allergen of Cryptomeria japonica pollen, play a major role in promoting Cry j 1-specific Th2 response. However, little is known as to whether the carbohydrates directly participate in allergic responses.We sought to determine whether Cry j 1-related oligosaccharides function as IgE and/or T cell epitopes. In addition, the regulatory effect of Cry j 1-related oligosaccharide on Cry j 1-specific T cell responses was investigated.Two monovalent oligosaccharides largely found on Cry j 1, Manalpha1-6(Manalpha1-3)(Xylbeta1-2)Manbeta1-4GlcNAcbeta1-4(Fucalpha1-3)GlcNAc (M3FX), and GlcNAcbeta1-2Manalpha1-6(GlcNAcbeta1-2Manalpha1-3)(Xylbeta1-2)Manbeta1-4GlcNAcbeta1-4(Fucalpha1-3)GlcNAc (GN2M3FX) were prepared. Manalpha1-2Manalpha1-6(Manalpha1-2Manalpha1-3)Manalpha1-6(Manalpha1-2Manalpha1-2Manalpha1-3)Manbeta1-4GlcNAcbeta1-4GlcNAc (M9A) was used as control. Competitive inhibition ELISA for Cry j 1-specific IgE was performed using these oligosaccharides as inhibitors. In addition, T cell lines specific for Cry j 1 or purified protein derivative of Mycobacterium tubecurosis (PPD) were established, and cellular responses against these oligosaccharides were investigated in the presence or absence of the respective antigens.Overall, neither M3FX nor GN2M3FX displayed inhibitory effect on the binding between IgE and Cry j 1. In addition, M3FX did not by itself stimulate Cry j 1 or PPD-specific T cells. However, M3FX significantly inhibited Cry j 1-induced proliferation and IL-4 production in Cry j 1-specific T cells. Such an inhibitory effect was not seen in PPD-specific T cell responses.These results suggest that Cry j 1-related oligosaccharides are not major epitopes for IgE or T cells. However, these oligosaccharides have a novel potential to inhibit Cry j 1-specific T cell responses selectively.

In the last 30 years, maternal and perinatal mortality rates have markedly improved in Japan. These results are supported by the advanced technologies and newly developed treatments in obstetric and neonatal medicine, the evidence of which will be described through the authors' experiences. Ultrasound-guided treatments for fetuses and pediatric surgery for extremely tiny infants have been performed with cooperation among cardiac surgeons, anesthesiologists and perinatologists. The remarkable achievements in neonatal medicine are surfactant replacement therapy, application of high frequency oscillation (HFO) respirator, nitric oxide and extracorporeal membrane oxygenation (ECMO) systems and transcutaneous blood gas monitoring. The possibility to have a safe pregnancy and delivery arose for women with severe medical complications such as diabetes mellitus (DM), heart diseases, and hemo-dialysis, factors formerly regarded as contraindications to pregnancy. The accumulative data of these high-risk pregnancies treated in our center are introduced. It is noted that molecular mechanisms in fetal growth have been elucidated to some extent. The insulin-like growth factor I (IGF-I) and IGF-binding protein 1 (IGFBP1) system, and cytokines, are involved in the fetal growth. Newly developed treatments such as urinary trypsin inhibitor (Urinastatin) for prevention of preterm delivery and amnioinfusion to cases of preterm premature rupture of the membrane are summarized. Finally, the reference to advanced medicine and its side effects lead to broad discussions regarding the future development of perinatal medicine.

There are few reports about the quality of life (QOL) and morbidities of pediatric living donor liver transplantation (LDLT) donors. We evaluated the potential morbidities and identified the predictive factors regarding the QOL of living donors after pediatric LDLT. This cross-sectional study was a single-center analysis of 100 donors for pediatric LDLT. The severity of morbidities was assessed with the Clavien classification, the QOL was investigated with the short form-36 (SF-36), and the decision-making process regarding donation was analyzed with questionnaires. The median follow-up period was 3.8 years (range, 2.2-6.0 years). A total of 13% of the donors developed postoperative complications of Clavien grades I (7%), II (3%), and IIIA (3%). There was no grade IV morbidity or mortality. Eighty-one donors responded to the questionnaire and SF-36. The analysis of the questionnaires revealed that the donors had difficulty in the decision-making process, and suggested that it may be necessary to administer multistep informed consent. We identified unique predictive risk factors for lower SF-36 scores in the donors, which were the time to donation (more than 4 weeks) and the predonation self-oriented perception. The donors who have risk factors require enhanced pre- and post-donation psychological care.

A recently developed wearable device has gained attention in the area of self-discipline for the prevention of lifestyle-related diseases. The present study aimed to clarify the relationship between circadian rhythm and body shape change using actigraphy. Using a body shape vector, we classified 24 women in their 40s and 50s into 3 groups with different body shape changes. A circadian rhythm experiment was conducted on weekdays for 1 week with 24 healthy women. Amounts of activity of the non-dominant wrist and trunk, subjective evaluation of sleep quality, and subjective state of activity were surveyed. In order to maintain a constant body shape throughout life, a less sedentary lifestyle with more trunk movement during the day, getting adequate sleep at night, and having a varied sleep-wake cycle may be important factors.

To facilitate making the physical fitness programs for obesity control, we investigated the effects of obesity on the ventilatory response during exercise and exercise tolerance. One hundred eighteen adults were divided into a normal group and fatty group by percentage of body fat. Each subject performed a submaximal exercise test under the gas-exchange measurement. The fatty group was inferior to the normal group in exercise tolerance. The respiratory mode, during exercise, in the fatty group was characterized by higher respiratory rate and less tidal volume compared with the normal group. This mode may result in increased dead space and therefore unavailable ventilation capacity. These data suggest that the characteristic respiratory mode in the fatty group was a factor in the lower exercise tolerance.

Patients surviving more than 10 years on hemodialysis (HD) are at risk of developing serious morbidity from unrelated conditions and from the many complications of long-term dialysis, such as cardiovascular disease, cerebrovascular disease, malignant tumors ectopic vascular calcification, diabetes mellitus, and disuse atrophy of the bladder. Long-term dialysis affects transplant patient outcomes and long-term graft survival. We analyzed 436 patients who underwent kidney transplantations between January 1987 and December 2007 to determine the impact of long-term dialysis on kidney transplant outcomes. The 39 patients who had been treated pretransplantation with dialysis for more than 10 years had an average length of dialysis treatment of 15.8 years (range, 10.0-32.5 years); they were denoted as the long-term hemodialysis group. The remaining 397 recipients showed an average of 3.7 years period of end-stage renal disease (ESRD) (range, 0-9.8, years; short-term hemodialysis group). There were significant differences in patient survival rates between the 2 groups: 93.2% vs 98.6%, at 1 year; 79.3% vs 95.4% at 5 years; and 58.4% vs 93.1% at 10 years (P = .0034). Also, graft survival was significantly different between the 2 groups: 89.2% vs 95.8% at 1 year; 60.4% vs 88.5% at 5 years; and 33.4% vs 80.4% at 10 years (P = .0026). Our results suggest that dialysis treatment for more than 10 years produces negative effects on post-transplantation patient and graft survival.

The aim of this study was to evaluate the operative techniques of total arch replacement, the clinical results and the survival curves of patients following this procedure.Since December 2001, 92 patients have undergone surgical treatment for aortic dissection and aneurysm. The total aortic arch replacement was performed in 24 of these patients. There were 16 men and 8 women, and the age range was 42 to 81 years with a mean age of 59.4 years. As the operative technique for total arch replacement, we used the 4-branched prosthetic graft, selective cerebral perfusion (SCP), continuous cold blood cardioplegia (CCBC), and open distal anastomosis under circulatory arrest. The combined operations were coronary bypass grafting in 4 patients, aortic valve suspension in 1 patient and a Bentairs procedure in 1 patient. Eleven (73.3%) patients with acute dissection required emergency operation.The hospital mortality rate was 25% (6 of the 24 patients). The causes of death were multiple organ failure (MOF) due to renal and mesenteric ischemia in 3 patients, cerebral infarction in 2 patients, myonephropathic metabolic syndrome (MNMS) in 1 patient, respectively. The data concerning extracorporeal circulation was 204+/-53 min in total pump time, 136+/-43 min in aortic cross clamp time, 83+/-14 min in SCP time and 48+/-10 min in circulatory arrest time, respectively. The long-term result in actuarial survival rate was 76% for 5 years.We consider the technique of total arch replacement using 4-branched prosthetic graft, SCP, CCBC, and open distal anastomosis is a useful operative method in patients with aortic aneurysm.

We present a rare case of a dissecting aneurysm of the left anterior cerebral artery (ACA) with persistent pearlstring sign on cerebral angiograms over a period of 8 years. A 43-year-old woman with disturbance of consciousness and right sided hemiparesis was conservatively treated. Computed tomographic (CT) scan revealed a low-density area in the left frontal lobe. Initial angiography, which was performed at 6 months after the onset, showed a pearlstring sign at the A2 portion of the left ACA. After 8 years, repeat angiography again showed persistent pearlstring sign at the same portion of the left ACA. We discussed the changes in findings usually obtained in cerebral angiography concerning dissecting aneurysms in ACA.

A 36-year-old man was admitted to our hospital because of impalement injury due to a downwards fall upon some reinforced steel rods. An emergency operation was performed using percutaneous cardiopulmonary support (PCPS). The steel rods were taken out in the operating room. The heart, great vessels, vertebrae, and spinal cord were not involved in the impalement wounds. We performed a bronchoplasty of the torn and separated right main bronchus, and repaired the impaled left lung without any pulmonary resection. He recuperated without sequelae.

To investigate the genetic predisposition toward the accumulation of oral microorganisms, the association between the alleles of HLA-DQA1, -DQB1 and -DRB1 and the salivary numbers of mutans streptococci and lactobacilli were examined in 102 young adults in Japan. HLA-DQA1*0102, DQB1*0604, DRB1*0802, and DRB1*1302 were weakly associated with the numbers of lactobacilli in saliva samples (P0.05). HLA-DQB1*0601 was associated with the salivary numbers of mutans streptococci (P0.01). Two HLA class II haplotypes, HLA-[DRB1*0802-DQA1*0301-DQB1*0302] and HLA-[DRB1*1302-DQA1*0102-DQB1*0604], were also weakly associated with the salivary numbers of lactobacilli (P0.05). These observations suggest that HLA class II alleles may be related to the salivary populations of oral microorganisms, such as mutans streptococci and lactobacilli.

A continuing shortage of cadaveric liver even for adult patients has motivated not a few centers to proceed to living-donor liver transplantation using right lobe grafts. One of controversies is potential congestion in the graft anterior segment by the deprivation of the middle hepatic vein.Hepatic tissue oxygenation and hemoglobin concentration were investigated with a near-infrared spectroscopy in the course of harvesting and implantation in living-donor liver transplantation. Twenty adult recipients of right lobe graft were involved in the study. The aim of the analysis was to detect tissue congestion or ischemia.No significant change in mean hepatic tissue oxygenation and hemoglobin was noted in the right lobe during donor operation even after hepatic parenchymal transection, although some trend for relative congestion, i.e., increased tissue hemoglobin, compared with the left lobe was observed. After graft reperfusion in the recipient, both mean hepatic tissue oxygen saturation and hemoglobin decreased significantly in the anterior segment, which was accompanied by increased heterogeneity of tissue hemoglobin and oxygenation. Increased heterogeneity of oxygenation and decreased tissue hemoglobin were observed also in the posterior segment.The anterior segment in right lobe living-donor liver transplantation is sensitive to ischemia, rather than congestion, at least in the immediate phase after graft reperfusion. The anterior segment seems to be also more prone to circulatory disturbance than the other part of the graft.

Recently life expectancy has become longer and longer. The purpose of this study was to analyse whether arterial surgery for patients over 80 years of age is advisable.During the last 14 years, 527 patients, 50 of whom were over 80 and 477 of whom were under 80 years of age, received graft replacement or bypass surgery. They suffered from ruptured abdominal aortic aneurysm (R-AAA, n=21), non-ruptured abdominal aortic aneurysm (N-R AAA, n=133) or arteriosclerosis obliterans (ASO, n=373). Complications such as cerebrovascular disease, ischemic heart disease, respiratory and kidney dysfunction, and risk factors for ASO were also checked.All of the patients over 80 with R-AAA (n=3/3) and 50% of the patients under 80 with R-AAA (n=9/18) died during their stay in the hospital. However, none of the N-R AAA patients over 80 (n=0/7) and only one of the 126 N-R AAA patients (0.8%) under 80 died. For the patients over 80 with ASO, the graft patency rate was better than the patients survival rate. There were no age-specific factors that should condemn arterial surgery for patients over 80 years of age.Arterial surgery should not be ruled out on the basis of age alone.

Modality of living donor liver transplantation (LDLT) has been expanded to adult cases. However, the safety of right lobectomy from living donors has not yet been proven.A total of 62 cases of LDLT, using the right lobe, were reviewed. Study 1: Discrepancy between estimated graft volume and actual graft weight was evaluated. Study 2: Postoperative liver functions were analyzed in relation to residual liver volume (RLV) or age. Residual liver volume of donors was defined using two indices, (RLV = estimated whole liver volume - estimated graft volume and %RLV = RLV/estimated whole liver volumex100). Donors were divided into two groups on the basis of either %RLV (40%; 40%or =) or age (50 years old; 50 years oldor =). Study 3: Right lobe donors were compared with left lobe donors (35 cases) in terms of their postoperative liver functions.Study 1: The relationship between estimated graft volume and actual graft weight was linear (y=159.136+0.735x, R2=0.571, P0.001). Study 2: %RLV ranged from 23.5% to 55.8% (mean +/- SD: 43.2+/-6.0). Fifteen cases showed %RLV less than 40%. Postoperative bilirubin clearance was delayed in that group (%RLV40%). Serum total bilirubin values on postoperative day 7 in the older group (ageor =50) were significantly higher than those in the younger group (age50). Study 3: Postoperative liver functions of right lobe donors were significantly higher than those of left-lobe donors. Eleven donors (17.7%) had surgical complications, all of which were cured with proper treatment.Right lobectomy from living donors is a safe procedure with acceptable morbidity, but some care should be taken early after the operation for donors with small residual liver and aged donors.

Technetium-99m-diethylenetriaminepentaacetic acid-galactosyl-human serum albumin (99mTc-GSA) is a liver scintigraphy agent which binds to asialoglycoprotein receptor in hepatocyte. Twenty-six patients with liver dysfunction were examined with 99mTc-GSA liver scintigraphy using two-compartment and two-parameter model (2C2P model). The 99mTc-GSA was assumed to move within two compartments (whole blood and liver). k1 and k2 were parameters which represented transfer rate constant from blood to liver, and from liver to blood, respectively. Two differential equations based on 2C2P model were integrated, so that k1, k2, k1/k2 and VLmg were estimated from the time-activity curves of the heart and liver. VLmg was computed as maximum amount of 99mTc-GSA binding to liver. The results were compared with the liver function tests and the conventional 99mTc-GSA indices: HH15, LHL15, and LU15. k1/k2 and VLmg values had positive correlation with the result of the serum liver function tests, Plt., T.Bil., ChE, GOT, LDH, ALP and gamma GTP. It is concluded that this new method using 2C2P model is not invasive and simplest in the 99mTc-GSA liver scintigraphies, and may be useful in evaluating liver function.

Although the pathogenesis of leukoplakia has been unclear, carcinogenic transformation is postulated to result from alterations of apoptotic signal transduction proteins in epithelial cells. The pathogenesis of oral lichen planus (OLP) has also been unclear, but apoptotic changes of the epithelial cells in OLP have been reported. In the present study, we used a histochemical approach to describe human keratinocyte-expression of several apoptotic signaling proteins in leukoplakia, in OLP, and in normal oral mucosa as a control. Mucosal biopsies from patients with leukoplakia (n=13), OLP (n=10), and normal oral mucosa (n=9) were frozen, sectioned and immunostained with monoclonal antibodies to wild-type (wt) tumor suppressive protein p53, cyclin-dependent kinase inhibitor p21WAF1/CIP1 and the oncoproteins MDM2, and Bcl-2. Apoptosis was assessed in all cases by the TUNEL method. MDM2 and Bcl-2 expression in keratinocytes were quantitatively greater in leukoplakia than in OLP. Wt-p53 and p21WAF1/CIP1 expression was quantitatively greater in keratinocytes in OLP than in leukoplakia. Keratinocyte maturation appeared histologically normal in OLP, even though wt-p53 and p21WAF1/CIP1 were expressed in these cells. Altered keratinocyte maturation was seen in leukoplakia lesions expressing MDM2 and Bcl-2. No significant difference for the number of apoptotic epithelial cells was observed between leukoplakia and OLP, in spite of the divergent outcomes of the apoptotic signaling proteins.

Little data is available recommending the adequate exercise level for physical fitness, so we hypothesized that the anaerobic threshold (AT) point is an ideal exercise level. We aimed to determine a new target heart rate formula for the adequate exercise training level in healthy subjects. This study first developed a new formula in 405 subjects (221 males, 184 females, mean age 48.9 +/- 12.3 years). The AT was determined during cycle ergometer exercise with continuous respiratory gas measurements. The correlation of heart rate at the AT to resting heart rate, age and gender was analyzed by the multiple regression method. Based on this correlation, a new formula calculating target heart rate was established as 74.8 + 0.76 x (resting heart rate) - 0.27 x (age) + 7.3 x S (male: 0 or female: 1). This formula was then compared to Blackburn's method in 210 subjects (139 males, 71 females, mean age 44.5 +/- 14.4 years). The difference between the new target heart rate and the heart rate at the AT was significantly lower than that between the target heart rate by Blackburn's method [(220 - age) x 0.7] and the heart rate at the AT (8.8 +/- 6.3 vs 12.7 +/- 8.2 beat/min, p0.001). The resting heart rate and gender are important factors in determining the target heart rate for exercise. This new formula indicates the adequate exercise training level more accurately in healthy subjects.

Hepatocellular carcinoma frequently develops during the advanced stages of chronic hepatitis C. We examined whether interferon prevents the development of hepatocellular carcinoma in chronic hepatitis C patients.Japanese patients with chronic hepatitis C (n = 1.148; 117 with portal fibrous expansion (F1), 636 with bridging fibrosis (F2), 355 with bridging fibrosis and architectural distortion (F3)) and 40 cirrhotic (F4) patients were treated with interferon. These patients were followed from 1 to 7 years after interferon therapy. Blood tests and image analysis were serially performed to assess response to interferon and to detect hepatocellular carcinoma. Fifty-five cirrhotic type C patients (control F4) not receiving interferon were enrolled in this study.Sustained (SR: 27.5%) and transient (TR: 23.0%) responders totaled 50.5%, while 49.5% did not respond to interferon. SR showed an improvement in disease stage reflected by increased platelet counts. Fifty-two patients (9 F2, 36 F3, and 7 F4) developed hepatocellular carcinoma in the follow-up period; 3 SR, 8 TR, and 41 non-responders (NR). The cumulative incidence of hepatocellular carcinoma in F2 was significantly lower (p = 0.019) in SR compared with NR, but not in SR in F3 and F4 patients. However, the cumulative incidence of hepatocellular carcinoma was significantly decreased in all SR (p = 0.0001) and TR (p = 0.0397) compared with all NR.These results indicate that interferon therapy in chronic hepatitis C patients lowered the rate of progression of hepatocellular carcinoma in sensitive cases but not in patients in an advanced stage.

Biliary complications are one of the most important problems in liver transplantation. Regardless of various improvements of surgical technique, liver transplantation is associated with significant biliary problems. In this article, we have described a biliary anastomosis method with a continuous suture (CS) technique in the posterior wall and interrupted suture (IS) technique for the anterior wall. We performed this biliary reconstruction in 28 adult patients between September 2003 and August 2007. Prior to that time our procedure was a CS anastomosis for both the anterior and posterior walls. A 5-Fr catheter is inserted into the biliary system. The current biliary complication was 3 cases (13.0%) of stenosis at the anastomosis, which is lower than that for a CS anastomosis. This anastomosis reduced biliary complications and is simple.

The effects of a long-term intranasal administration of each of the gonadotropin-releasing hormone analogs, buserelin and nafarelin on uterine leiomyomas after conservative treatment using Chinese herbal medicines, Keishi-bukuryo-gan and Shakuyaku-kanzo-to were investigated in 30 perimenopausal women with leiomyomas. Hypermenorrhea and/or dysmenorrhea as a chief complaint was moderately improved by the treatment using Chinese herbal medicines in more than 60% of the patients with less than fist-sized leiomyomas, but not the over fist-sized. Afterwards, continuous treatment using analogs produced a long-term reduction in leiomyomas (less than 60%) along with decreases in the serum levels of luteinizing hormone, follicle-stimulating hormone, estradiol, and the tumor marker CA-125, and adverse effects including slight boneloss. Long-term treatment using Chinese herbal medicines and gonadotropin-releasing hormone analogs for the management of uterine leiomyomas could be beneficial for patients a few years before menopause, though possible side effects of this treatment should be monitored.

Mitral valve hardness in the rough and clear zones was evaluated by measuring the propagation velocity (m/sec) of ultrasound through the valve, based on the hypothesis that harder tissues will have larger ultrasonic velocity values passing through the tissue. Mitral valve specimens were obtained from 16 normal subjects (age, 15-72 years) at autopsy. An acoustic microscope, operating at 450 MHz, was used to measure the ultrasonic velocity through the three layers of the valve: the atrialis; the spongiosa; and the fibrosa. Furthermore, the mean ultrasonic velocity through the three layers was measured. These measurements were conducted in the rough and clear zones of the valve. In the rough zone, the ultrasonic velocities were 1,634 +/- 71 in the atrialis, 1,574 +/- 37 in the spongiosa, and 1,726 +/- 97 m/sec in the fibrosa. In the clear zone, the ultrasonic velocities were 1,691 +/- 117 in the atrialis, 1,575 +/- 44 in the spongiosa, and 1,909 +/- 131 m/sec in the fibrosa. There were significant differences between velocities in the three layers in both the rough and clear zones. Furthermore, the mean ultrasonic velocity in the three layers in the clear zone (1,887 +/- 138 m/sec) was higher than that in the rough zone (1,642 +/- 53 m/sec; p0.001). These findings show that fibrosa, which is rich in collagen fibers, is harder than atrialis, which is rich in elastic fibers, and the spongiosa, which is poor in connective tissues, is the softest. The higher mean ultrasonic velocity in the clear zone than in the rough zone indicates that the clear zone is harder than the rough zone, although the clear zone is thinner than the rough zone.

We examined a patient with adult onset sialidosis using N-isopropyl-p-123I-iodoamphetamine single photon emission computed tomography (SPECT) and 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography (PET). A 41-year-old [correction of 47] man was admitted to our hospital because of the involuntary movement of his extremities and gait disturbance. On admission, he exhibited action myoclonus in his face and extremities with cerebellar ataxia. Ophthalmoscopy revealed cherry-red spots on his retina. Enzymological analysis of his leucocytes and skin fibroblasts revealed primary sialidase deficit. Brain MRI showed no abnormal findings. Brain SPECT showed decreased cerebral blood flow in the cortex of bilateral occipital lobes, and PET study revealed decreased glucose metabolism in the cortex of bilateral occipital lobes. This case is the thirteenth patient of adult onset sialidosis in Japan. As far as we know, there are no previous reports of SPECT or PET on sialidosis patients. Why the cerebral blood flow and glucose metabolism was decreased in the occipital lobe region remains obscure. From the literatures, we suppose that the onset time of neuronal tissue degeneration or the sensitivity to cumulative metabolites in the occipital region may be different from those in other regions. Further studies are required to confirm abnormalities of cerebral blood flow and metabolism in sialidosis.

(1 --3)-beta-D-glucan, a characteristic fungal molecule, is known to increase in blood in invasive candidiasis, aspergillosis and cryptococcosis. This report shows that the plasma glucan concentration was also elevated in four patients infected with Fusarium, Trichosporon beigelii, Saccharomyces cerevisiae and Acremonium. In three of the patients, the elevation preceded positive blood cultures by 5-17 days, and in one of them it even preceded the onset of fever by 6 days. In a fourth patient, the glucan level decreased with clinical improvement. Plasma (1 --3)-beta-D-glucan determination appears to be useful also for diagnosis and follow-up of these unusual deep mycoses.

Brain malformations are rare congenital anomalies caused by neuronal migration disorders or cerebral tissue destruction during gestation. And epileptic disorders and psychomotor retardation are sometimes induced by them. Previous understanding of these anomalies was derived from pathologic studies after autopsy. The recent advancement of neuroimaging techniques, such as magnetic resonance imaging (MRI), has allowed us to achieve a high diagnostic capability of these malformations. These abnormalities have been more widely recognized morphologically. However, cerebral function in these cases has been rarely described. To evaluate the cerebral functional state in these anomalies, 123I-N-isopropyl-p-iodoamphetamine (123I-IMP) single photon emission computed tomography (SPECT) was performed in 3 cases with brain malformations and 22 normal controls. Several regions of interest (ROI) in the cortex were determined, and the radioactivity at each ROI was counted. The regional cerebral blood flow (rCBF) distribution was evaluated semiquantitatively by calculating the cortico-cerebellar ratios at each ROI. A 23-year-old female with schizencephaly (Case-1) and a 21-year-old male (Case-2) with polymicrogyria showed increased rCBF in their abnormal cortices. And a 39-year-old male with porencephaly (Case-3) demonstrated severely decreased rCBF in his abnormal cortex with gliosis which was considered to be a result from a secondarily disturbed neuronal migration after tissue destruction during gestation. Furthermore, abnormal rCBF distribution was observed in their morphologically normal cortices in addition to their abnormal cortices compared to normal controls. Case-2 showed decreased cerebral perfusion in the morphologically normal cortex around his abnormal cortex with increased rCBF, suggesting surrounding suppression associated with epileptic foci. In contrast, the lesions with decreased rCBF in Case-1 were not around the abnormal cortices. In the cortices with decreased rCBF, despite morphologically normal imaging, of Case-3, the decrement was considered to be diaschisis, since these lesions were located in the ipsilateral hemisphere of the tissue defect. We concluded that brain malformations show various rCBF abnormalities, and these are spread over a larger area than detected by MRI. Therefore, SPECT is a valuable examination method for the determination of abnormal areas and the assessment of pathologic functional state in patients with brain malformations.

We studied the association between epidermal growth factor (EGF) binding capacity and histopathologic features or prognosis in human renal cell carcinoma (RCC) by Scatchard analysis in 67 patients. EGF binding capacity was significantly greater in metastatic than in nonmetastatic tumors, and in nuclear grade 3 than nuclear grade 1 tumors. Multivariate analysis revealed that tumor stage, nuclear grade, EGF binding capacity, and tumor size significantly correlated with overall survival. These results suggest that EGF binding may be an important determinant of prognosis in patients with RCC.

A 21-year-old man underwent aortic valvuloplasty for aortic regurgitation due to bicuspid aortic valve. After the initial procedure for valvuloplasty of the anterior cusp, transesophageal color Doppler flow imaging revealed a significant regurgitant jet directed posteriorly as observed preoperatively. After an additional valvuloplastic procedure for the anterior cusp, the size of the regurgitant signal was reduced and directed to the center of left ventricular outflow tract. The surgery was then completed. On the 5th postoperative day, an aortic regurgitant murmur reappeared and color Doppler echocardiography showed a mild but significant regurgitant jet directed toward the interventricular septum, which may have been due to contraction of the anterior cusp treated by valvuloplasty. Aggravation of the aortic regurgitation in the early stage after plastic surgery is important and requires consideration in the intraoperative assessment.

Although drug-induced gingival hyperplasia has been extensively studied, the pathogenesis of this disorder has not been clarified to date. Transforming growth factor beta (TGF beta) and basic fibroblast growth factor (bFGF) have been shown to be implicated in diverse fibrotic and hyperplastic diseases. Heparan sulphate proteoglycan (HSPG), which is composed of heparan sulphate glycosaminoglycan (HSGAG), has also been shown to play an important role in the pathogenesis of tissue overgrowth by enhancing the functions of bFGF. However, the possible implication of these growth factors in gingival hyperplasia has not been studied. Immunohistochemical localization of TGF beta, bFGF, their receptors and HSGAG was studied in 4 nifedipine-induced and 5 phenytoin-induced hyperplastic gingival tissues, and 5 non-hyperplastic control gingival tissues to elucidate the pathogenesis of this disease. Significant immunostaining against TGF beta, bFGF, the receptors of these two growth factors and HSGAG was observed in the lamina propria of hyperplastic gingival tissues while less immunostaining was observed in the controls. The mean numbers of immunostained cells against TGF beta, bFGF, their receptors in a square unit (0.1 x 0.1 mm) of the lamina propria, which were counted to 10 units of each hyperplastic gingival tissue, were significantly higher than those of the controls. The results suggest that the increased synthesis of TGF beta, bFGF, their receptors and HSGAG may be related to the pathogenesis of drug-induced gingival hyperplasia.

We studied myocardial accumulation and clearance of [123I]metaiodobenzylguanidine (MIBG) along with measurements of plasma norepinephrine concentrations.Myocardial imaging with MIBG and plasma norepinephrine concentration measurements were performed in 21 patients with chronic renal failure on dialysis and 11 control subjects. Dynamic acquisitions, begun immediately after MIBG injection, and planar images 15 and 150 min after injection were used to measure early and late myocardial uptake and clearance rates of MIBG from the heart.Early and late MIBG uptake was not significantly different from that in controls but MIBG clearance was significantly more rapid in controls. Based on echocardiographic findings, the patients were divided into three subgroups: those without left ventricular hypertrophy and dysfunction (n = 10), with hypertrophy (n = 4) and with dysfunction (n = 7). Among controls and the three patient subgroups, MIBG clearance was significantly higher in all the subgroups and also was significantly higher in patients with dysfunction than in those without hypertrophy and dysfunction. Plasma norepinephrine levels were significantly higher in patients than in controls and correlated significantly with the clearance rate.MIBG clearance from the heart was rapid in patients with chronic renal failure on dialysis, particularly those with left ventricular dysfunction or hypertrophy, suggesting cardiac sympathetic overactivity in these patients.

The object of this study was to evaluate activities of thymidylate synthetase (TS) and thymidine kinase (TK) in relation to histopathological features of human mammary carcinomas, as well as clinical classification of patients. The TS and TK are key enzymes on the de novo and salvage pathways, respectively, for pyrimidine nucleotide synthesis. High TS and TK activities have been found in rapidly proliferating tissues. Clinical stage and TNM post-surgical histopathological classification of 20 patients with mammary carcinomas, during the period of 1988-1991, and TS and TK activities in each carcinoma were determined. Elevated TS and TK activities in mammary carcinomas corresponded to progressively worse clinical stages. Papillotubular carcinomas showed lower enzyme activity than that of solid-tubular and scirrhous types. TS activities continued to rise as the malignant invasion became more severe. The clinical prognosis of patients with mammary carcinomas appears to depend on the de novo synthesis of DNA in carcinomas.

To clarify the clinical significance of serum levels of interleukin-1 alpha autoantibody in liver disease and their change during interferon therapy for chronic hepatitis.By radioimmunoassay, we studied the incidence of serum interleukin-1 alpha autoantibody in 838 healthy controls and 180 patients with liver disease and monitored the change in antibody titer during the interferon therapy for chronic hepatitis.We detected the interleukin-1 alpha autoantibody in 12.6% (106/838) of healthy controls. In patients with liver disease, we found the antibody in 15.6% (5/32) in patients with acute hepatitis, 16.3% (13/80) in patients with chronic hepatitis, 18.8% (9/48) in patients with liver cirrhosis, and 15% (3/20) in patients with autoimmune liver disease. The incidence was not related to either etiology or inflammatory activity of liver disease. Two of three chronic hepatitis patients with initially high serum levels of the antibody (2000 ng/ml) showed transient increase in antibody titers during interferon therapy.The serum level of interleukin-1 alpha autoantibody was unrelated to the etiology or activity of liver disease. Interferon therapy can cause transient elevation of serum interleukin-1 alpha autoantibody levels.

A 44-year-old woman was diagnosed as having acute promyelocytic leukemia (APL) in April 1988. On her first admission, chromosomal translocation (15; 17), +8, and +12 was detected. When she was readmitted to our hospital with the second relapse in May 1990, t(3; 13) and +8 was detected, instead of t(15;17). Complete remission was re-achieved with VP-16, MIT, and BHAC, but the third relapse occurred in September 1990. After obtaining informed consent, she was given etretinate 40 mg per day orally for 17 days, without any effect on leukemia. She was then given all-trans retinoic acid (ATRA) 60 mg per day orally for 29 days. Although a mild granulocytic recovery was observed, no sufficient hematological recovery was obtained (minor response). Besides common side effects of ATRA, such as dry skin and hypertriglycedemia, she had a myeloblastoma in the oral cavity, but it is unknown whether the symptom was a complication of ATRA therapy or not.

We investigated the side effects of interferon (IFN) on the endocrine and respiratory system in 545 cases of chronic hepatitis C. Eleven of 494 (2.2%) patients with chronic hepatitis C who were treated with natural or recombinant interferon (IFN) developed thyroid disease while on treatment. Eight patients developed hyperthyroidism and 3 patients developed hypothyroidism. All 11 patients required definitive therapy, who became euthyroid after the therapy. Two patients received nIFN alpha and one patient received rIFN alpha 2b developed diabetes mellitus. Two patients received rIFN alpha 2a and rIFN alpha 2b, respectively, developed interstitial pneumonia 12 weeks and 24 weeks later, respectively. One patient showed positive reaction for RA test and LE factor and positive LE cell, and complained of fever, arthralgia and dry cough. These phenomenon disappeared after the cessation of IFN therapy.

For the purpose to know the pathogenesis of caseous necrosis in tuberculous lesion, authors compared the presence and the number of mycobacteria in the pulmonary tubercles of various histological types. Forty pulmonary tubercles obtained from 16 patients (9 males, 7 females; mean age 51) were examined. By Ziehl-Neelsen (ZN) method, acid-fast bacilli were detected in 40% of 5 proliferative, in 12.5% of 24 productive and none of 11 sclerotic granulomas. By immunohistological staining with anti-BCG antiserum, positive staining was observed in 60%, 87.5% and 91% of each type of granuloma, respectively. Types of necrosis were classified by silver-staining as necrosis after exudative reactions (EN), necrosis after productive reactions (PN) and filled materials after softening and liquification of necrotic lesions (LN). EN was observed in 24 tubercles, and mycobacteria were stained in 8% of EN by ZN method and in 75% by immunohistological method. PN was observed in 21 tubercles, and mycobacteria were detected in none and 5% of such type of necrosis by respective method. LN was observed in 28 tubercles, and mycobacteria were detected in 11% and 71% of these lesions by respective method. So, positive ratio by immunochemical method was significantly higher in EN and LN than in PN. Further, mycobacteria were stained with anti-BCG antiserum as granules and the number of such granules were much more numerous in EN and LN than in PN (p0.01). From these results, it was suggested that necrosis might occur by different mechanisms in exudative reactions and in productive reactions.

Nine cases of symptomatic Rathke's cleft cyst are reported. Their most frequent signs and symptoms included headache, chiasmal syndrome and hypopituitarism, while one of the cases developed a sudden onset of headache and vomiting following diabetes insipidus. Endocrinological findings showed a decreased ACTH, gonadotropin and growth hormone more frequently while there were 2 cases of hyperprolactinemia and 1 case of diabetes insipidus. In a neuroradiological examination, a plain skull X-ray showed 5 cases of ballooning of the sella turcica, and a CT scan demonstrated a low to high density of the cyst and 2 cases of marginal enhancement of the cyst. MRI mostly demonstrated a well delineated mass at the sella extending mostly into the suprasellar region and a low to high intensity of the cyst in the T1-weighted image. Two cases were marginally enhanced after gadolinium DTPA administration. The pathological examination, done on 6 cases, showed either single or multiple layers of the epithelium which were mostly ciliated. The epithelium was positive in PAS and Alcian blue in all cases and a histochemical examination showed 3 cases to be positive in EMA and 2 cases positive in CEA. A resection of the cyst wall and an opening of the cyst is thus recommended in symptomatic cases. Therefore, the transsphenoidal approach should be the choice of treatment in an intra- and suprasellar extension of the cysts with sellar enlargement.(ABSTRACT TRUNCATED AT 250 WORDS)

A successful repair of total right pulmonary venous return and intact atrial septum associated with patent left superior vena cava (PLSVC) is reported. A 31-year-old women was admitted for evaluation of heart failure. A heart murmur had been detected since her childhood without any subjective symptoms. She was diagnosed as partial anomalous venous return of all right pulmonary vein and intact atrial septum (IAS) associated with PLSVC by cardiac catheterization. Operative findings revealed that all right pulmonary vein connected to right atrium (RA) and superior vena cava (SVC), PLSVC drained into coronary sinous (CS), therefore RA, right ventricle and CS were enlarged, but SVC was small due to PLSVC. Through large incision from RA to SVC, atrial septum was opened 30 mm in diameter. Internal conduit using pericardial patch was made in order to drain anomalous pulmonary venous blood into left atrium through the ASD. Finally, SVC and RA were reconstructed by pericardial patch for prevention of conduit obstruction. One month after operation, no stenosis of SVC and right pulmonary vein was evidenced by cardiac catheterization and all through the postoperative course, arrhythmias did not detected. She was discharged with uneventful postoperative course.

Gd-enhanced MR images of two patients with clinically and histopathologically diagnosed chronic progressive radiation myelitis (CPRM) were observed chronologically. One of them had had nasopharyngeal cancer and received radiotherapy at a dose of 100 Gy to the C1-2 level of the spinal cord. She developed CPRM 25 months after the termination of radiotherapy. The other had had malignant lymphoma originating from the tonsil and received chemoradiotherapy. The dose delivered to her cervical spinal cord was 40 Gy, and she developed CPRM 30 months later. Gd-enhanced MRI in the early phase revealed a small crescent-shaped nidus with or without a very small central nonenhanced area in both cases. Enhancement was not great. At that time, patients noticed only the inability to perceive pain and temperature or paresthsia in the opposite side. In a few months, MRI revealed a much more strongly enhanced and larger nidus with enlargement of a central nonenhanced area accompanied by long segmental cord enlargement. The patients' neurological symptoms had also progressed, with hemiparesis developing, for example.

MST-16, a new orally administered bis(2,6-dioxopiperazine) analogue and an inhibitor of topoisomerase II, was given to 24 patients with adult T-cell leukemia-lymphoma (ATLL) in a Phase I-II multi-institutional cooperative study.MST-16 was administered orally daily for 7 days, with courses repeated at intervals of 2-3 weeks in 24 patients.Two complete remissions (CR) and eight partial remissions (PR) were obtained in 23 evaluable patients who received 1200-2800 mg/day of MST-16. Among 13 acute-type ATLL, one CR and five PR were obtained. Among eight lymphoma-type ATLL, two PR were detected. Among two chronic-type ATLL, one CR and one PR occurred. Remissions were obtained at 7-232 days (median, 23 days) and lasted 43-374 days (median, 68 days). The major toxic effects were leukopenia (68%), anemia (52%), thrombocytopenia (35%), and gastrointestinal disorders (22%).MST-16 was shown to be effective in ATLL, which has no standard therapy. This drug deserves further clinical trials because it shows little cross resistance to currently available antitumor drugs.

Thymidylate synthetase (TS) and thymidine kinase (TK) are known to catalyse the methylation of dUMP for the de novo synthesis of dTMP and the phosphorylation of thymidine for the salvage synthesis of dTMP in the pyrimidine pathway, respectively. High activities of TS and TK have been observed in rapidly proliferating tissues. In the present study, both enzyme activities were measured in 8 specimens of normal mammary tissues, 12 fibroadenomas and 10 adenocarcinomas in the human breast. The average activities of TS in fibroadenomas and adenocarcinomas were approximately 5- and 7-fold that in normal mammary tissues, respectively. The average activities of TK in fibroadenomas and adenocarcinomas were 4- and 14-fold that in normal mammary tissues, respectively. Thus, DNA synthesis in benign and malignant mammary tumors may be relatively predominant in de novo and salvage pathways, respectively.

A 35-year-old male doctor experienced an anaphylactic reaction of urticaria, unconsciousness and hypotension one hour after taking a meal including crab meat and alcohol (beer 350 ml+Japanese sake 100 ml). He recovered within several hours after emergency treatment. Another attack occurred 6 months later after taking a meal including crab meat and alcohol. Serum IgE showed 3073 IU/ml. IgE-RAST and skin tests were positive for crab. A crab meat plus alcohol challenge test revealed a slight increase in plasma histamine level. This is a rare case of food (crab meat)-dependent anaphylaxis possibly induced by alcohol.

Six patients with recurrent and/or refractory acute nonlymphocytic leukemia (ANLL) were treated with recombinant human granulocyte colony-stimulating factor (G-CSF) and cytotoxic agents administered simultaneously. Neither of the two patients who received cytosine arabinoside (ara-C) in combination with G-CSF achieved complete remission. The other four patients, who received multi-drug combination therapy together with G-CSF, all achieved complete remission. No major side effects due to G-CSF were observed. These results demonstrated that the effects of G-CSF in enhancing the sensitivity of leukemic cells to cytotoxic agents and accelerating the recovery of leukocytes could lead to its possible use in the treatment of ANLL.

The anaerobic threshold (AT) is used to determine the exercise capacity in patients with heart failure and healthy subjects. To determine the factors affecting AT, we determined the AT in healthy subjects, and examined the factors that determine AT in healthy subjects. One hundred and sixteen healthy subjects (79 men and 37 women) performed on a bicycle a stepwise increasing submaximal exercise. During the work test the parameters usually used in the detection of AT (Vo2, Vco2, VE), blood pressure, heart rate and oxygen saturation were recorded by a computerized system every minute. AT was determined from changes in ventilation and gas-exchange. The fat index was calculated from height and body weight measured at the beginning of the ventilatory function test. A significant correlation was obtained between AT and age, AT and fat index, AT and %VC, AT and maximum heart rate during exercise, AT and recovery rate of heart rate after exercise, and AT and Vo2 at rest. In addition, we examined the relationship among the parameters in 4 groups according to sex and age (30-49; younger, 50-69; older), because sex and age affected most parameters. We found a significant correlation between AT and fat index (older men and women), AT and %VC (younger and older women), AT and Vo2 at rest (younger and older men). We considered that the main factors that determined AT in healthy subjects were age, sex, fat index, %VC and Vo2 at rest.

We examined whether airway cough receptor sensitivity correlates to nonspecific bronchial responsiveness. We measured cough threshold, the lowest concentration of inhaled tartaric acid eliciting five or more coughs, and the provocative concentration of methacholine producing a 20% fall in forced expiratory volume in one second (PC20FEV1) in 38 normal and 11 asthmatic subjects. All subjects were nonsmokers. The geometric mean value of PC20FEV1 was 25.7 mg.ml-1 (GSEM1.29) and 0.63 mg.ml-1 (GSEM1.29) and the geometric mean value of the cough threshold was 115 mg.ml-1 (GSEM1.20) and 95.5 mg.ml-1 (GSEM1.35) in normal and asthmatic subjects, respectively. The PC20FEV1 was significantly (p less than 0.01) lower in asthmatics than in normals but the cough threshold did not differ between them. No significant correlation was observed between the cough threshold and the PC20FEV1 in normal subjects or in asthmatics. These results indicate that cough sensitivity does not directly correlate to bronchial responsiveness in normal and asthmatic subjects.

A 37-year-old woman was admitted to our hospital because of anemia in the 33rd week of pregnancy. On admission, the hemoglobin was 7.6 g/dl, platelets 508,000/microliters and WBC 8,300/microliters with 4% blast cells. Bone marrow aspirate demonstrated 50% erythroblasts of nucleated cells, which had prominent megaloid and polynucleic changes, and 20% myeloblast cells. We diagnosed her as having erythroleukemia. Receiving packed-red-cell transfusions, she had a cesarean section, and gave birth to a female infant (BW 2,175 g) in the 34th week of pregnancy. At the same time, she had a total hysterectomy with left adnexectomy. The postoperative course was favorable. She had a combination chemotherapy of BHAC-DMP, resulting in a partial remission. After the second induction chemotherapy with subcutaneous use of G-CSF and BHAC-DMP, complete remission was obtained, which lasted for almost 17 months. The child is growing well without any hematological disorder.

Inflammatory cell reactions in bronchial asthma have been considered to contribute directly to asthmatic attacks. Therefore, attention has been focused on the role of inflammatory cells in the airway wall. In this study, we investigated inflammatory cells in the airway wall of bronchial asthma histologically and immunohistologically using 20 autopsy cases who died of the asthma attacks (Group A) and 11 autopsy cases who died of other causes (Group B). Six autopsy cases were treated as controls (Group C). A significantly larger number of eosinophils in the bronchi and bronchioles were found in Group A. The majority of eosinophils were found to be stained with EG2. Parts of the bronchial epithelium with marked infiltration of EG2 positive eosinophils were detached from the basal layer. Immunoelectron microscopically, the matrix of EG2 positive areas within the eosinophils corresponded to that of eosinophil granules. A significantly larger number of lymphocytes in the bronchi and bronchioles was observed in Groups A and B. Almost all of these lymphocytes were determined to be activated T lymphocytes. There were significantly more IgE positive cells in cases with bronchial asthma, especially in Group A. The majority of IgE positive cells were determined to be mast cells. These results suggest that eosinophils, lymphocytes and mast cells play an important role in the pathogenesis of bronchial asthma.

By using enzyme-linked immunosorbent assay (ELISA), it was demonstrated that cultured human corneal epithelial cells produced interleukin-6 (IL-6) without any stimulation. As lipopolysaccharide (LPS)-stimulation did not induce further production of IL-6 and IL-1 alpha, it was suggested that IL-6 was produced naturally as in the case of IL-1 alpha production which has been previously reported by the author. Production of IL-1 alpha and IL-6 in the human corneal epithelial cells may play a role in amplifying immune responses on the ocular surface.