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Biomedical subjects

Y Haruna

Publications and source records attributed to Y Haruna.

At least 37 records · Page 2Linked to original sources

Beta-blockade does not improve orthostatic intolerance induced by 20 days bed rest.

To assess if propranolol influences orthostatic intolerance induced by prolonged bed rest (BR), a lower body negative pressure test (LBNP) and left ventricular (LV) echocardiography before and during -40mmHg of LBNP were performed with and without intravenous propranolol administration (0.04mg/kg) in 9 healthy volunteers (mean age: 21 years) before and after 20 days BR. LBNP tolerance time (LBNP-T), endpoint heart rate(HR), and percentage changes from 0 to -40mmHg LBNP in HR, LV diastolic dimension(LVDd), stroke volume (SV), cardiac output (CO), and systemic vascular resistance(SVR) were measured. After BR, percentage changes in CO during LBNP was not altered by propranolol (-12+/-21% vs. -24+/-24%; with and without propranolol; p>0.05) because the effect on percentage changes in HR (18+/-11% vs. 26+/-12%; p<0.05) cancelled out the effects of percentage changes in LVDd (-9+/-6% vs. -15+/-10%; p<0.05) and percentage changes in SV (-26+/-16% vs. -39+/-22%; p<0.05). In addition, propranolol decreased end-point HR (85+/-15bpm vs. 119+/-l4bpm; p<0.05) and percentage changes in SVR (25+/-32% vs. 53+/-57%; p<0.05). As a result, LBNP-T after BR was unchanged by propranolol (8.8+/-3.3min vs. 10.8+/-5.0min; p>0.05). In conclusion, propranolol failed to change orthostatic intolerance induced by BR.

Adrenergic beta-Antagonists↗

Prolonged bed rest impairs response of the small arteries to cold pressor test.

Cold pressor test (CPT) has been known to increase vascular resistance through adrenergic stimulation. To assess the effect of prolonged bed rest (BR) on sympathetic neural control, blood flow velocity of the proper palmar digital artery (resistance vessel) was measured in 10 healthy volunteers during a 90 seconds CPT by pulsed Doppler ultrasound using a 7.5 MHz linear transducer before and after 20 days BR. Blood flow velocity in the proper palmar digital artery decreased during the first half of the CPT both before and after BR, but decreases in peak flow velocity became less prominent (p<0.05) after BR (-48+/-20%) than before bed rest (-61+/-25%). The only subject whose lower body negative pressure tolerance time was prolonged after BR showed prominent decreases in peak flow velocity during the first half of the CPT after BR. Peak flow velocity returned to the pre-test value during the latter half of the CPT in 7 subjects before BR, but in only 2 subjects after BR (p<0.05). Thus, 20 days BR impairs the response of the small digital arteries to CPT, suggesting that a decrease in a adrenergic stimulation occurs after prolonged BR.

Adolescent↗

Detection of hepatitis C virus RNA sequences in hepatocellular carcinoma and its precursors by microdissection polymerase chain reaction.

OBJECTIVE: Chronic hepatitis C virus (HCV) infection is frequently associated with the development of hepatocellular carcinoma (HCC), but the mechanism of malignant transformation is unknown. To analyze the association of HCV with HCC, we developed a microdissection technique for the detection by polymerase chain reaction of positive (genomic)- and negative (replicative)-strand HCV RNA in histologically confirmed HCC and the surrounding cirrhotic and macroregenerative nodules. MATERIALS AND METHOD: Five HCCs and one macroregenerative nodule and the surrounding cirrhotic liver tissues of all cases were selected for this study. The method entails extraction of RNA from selected areas of formalin-fixed, hematoxylin-stained histologic sections, followed by strand-specific reverse-transcription double polymerase chain reaction and Southern blotting. RESULTS: Positive- and negative-strand HCV RNA sequences were detected in five of six tumors and the surrounding cirrhotic livers. CONCLUSIONS: These results verify the method of polymerase chain reaction detection of HCV RNA from histologically defined, selected lesions. In addition, the findings suggest that HCV RNA persists and replicates in hepatocytes during malignant transformation.

Aged↗

Identification of bipotential progenitor cells in human liver development.

Intermediate filament proteins have been reported to be expressed in a cell lineage-specific manner during morphogenesis. We studied the expression of cytokeratin (CK)14, CK19, and vimentin and of the hepatocyte-specific HepPar1 antigen during the development of human liver. Nineteen fetal livers (gestational ages 4 to 40 weeks), 3 normal infant livers, and 3 normal adult livers were studied by immunoperoxidase staining of paraffin sections with monoclonal anti-CK19, anti-vimentin, and HepPar1 antibodies and polyclonal anti-CK14 antibodies. Double-immunostaining for CK14 and CK19 as well as bile duct cytokeratin and HepPar1 antigen was also done. CK19 and HepPar1 antigen were the first markers detected in immature progenitor cells of the liver primordium at 4 weeks' gestation. During subsequent liver development, the progenitor cells expressed HepPar1 antigen, CK14, and CK19, from 8 to 14 weeks' gestation. As hepatocyte differentiation progressed, expression of HepPar1 antigen increased, and CK14 and CK19 were abrogated from hepatoblasts at 14 to 16 weeks' gestation. In contrast, as progenitor cells transformed into ductal plate cells, CK19 expression increased and persisted in differentiated bile ducts, whereas CK14 and HepPar1 antigen were lost. Vimentin was detected in ductal plate and biliary epithelial cells from 9 to 36 weeks' gestation, but not in hepatoblasts or hepatocytes. Double-immunostaining confirmed coexpression of CK14 and CK19 in the progenitor cells for a short time (8 to 14 weeks' gestation) during early development. Double immunostaining for bile duct CK and HepPar1 antigen clearly demonstrated the divergence of the hepatocyte and bile duct epithelial cell lineages. Our findings suggest that hepatic progenitor cells differentiate in steps marked by the acquisition or loss of specific phenotypic characteristics. Commitment of the HepPar1+CK19+ progenitor cells to either hepatocyte or bile duct epithelial cell lineages results in increased expression of one marker and loss of the other marker. These characteristics clearly identify bipotential hepatic progenitor cells in the developing human liver.

Adult↗

Blood pressure and heart rate responses to sudden changes of gravity during exercise.

Heart rate (HR) and blood pressure responses to sudden changes of gravity during 80- to 100-W leg exercise were studied. One group was exposed to sudden changes between 1.0 and 0 g in the head-to-foot direction (Gz+), starting upright and with repeated 30-s tilts to the supine position. Another group was exposed to sudden Gz+ changes between 1.8 and 0 g in an aircraft performing parabolic flight. Arterial blood pressure at the level of the carotid (carotid distending pressure, CDP) showed a large transient increase by 27-47 mmHg when Gz+ was suddenly decreased and a similar drop when Gz+ was suddenly increased. HR displayed a reverse pattern with larger transients (-22 to -26 min-1) in response to Gz+ decreases and more sluggish changes of lower amplitude in the other direction. Central blood volume, as estimated from the inverse of transthoracic impedance (1/TTI), varied in concert with Gz+. A model is proposed in which HR responses are described as a function of CDP and 1/TTI after a time delay of 2.3-3.0 s and including a low-pass filter function with time constants of 0.34-0.35 s for decreasing HR and time constants of 2.9-4.6 s for increasing HR. The sensitivity of the carotid component was around -0.8 to -1.0 min-1 . mmHg-1 (4-7 ms/mmHg). The cardiopulmonary baroreceptor component was an additive input but was of modest relative importance during the initial HR responses. For steady-state HR responses, however, our model suggests that inputs from carotid and cardiopulmonary receptors are of equal importance.

Adult↗

Identification of bipotential progenitor cells in human liver regeneration.

Recent studies, including our own, suggest that intermediate filament proteins, particularly bile duct-specific cytokeratin 19 (CK19) and the hepatocyte-specific HepPar1 antigen define the developmental stages of hepatic progenitor cells during liver morphogenesis. We hypothesized that the HepPar1+ CK19+ progenitor cells are activated during human liver regeneration after massive hepatic necrosis and proliferate with the formation of so-called ductular hepatocytes or neocholangioles. We demonstrated previously that the ductular hepatocytes proliferate and share phenotypic characteristics with hepatocytes and biliary epithelial cells. In this investigation, we compared the expression pattern of intermediate filament proteins and HepPar1 antigen in ductular hepatocytes with that of bipotential hepatic progenitor cells. CK14, CK19, vimentin, and HepPar1 antigen were localized by immunoperoxidase staining in 13 human livers with regeneration after massive hepatic necrosis. Double immunostaining of three cases for CK14/CK19 and HepPar1/CK19 was also performed. CK19 reaction exhibited diffuse staining of the cytoplasm of many ductular hepatocytes and bile ducts in all cases. CK14 was expressed in the cytoplasm of ductular hepatocytes and few bile ducts in 5 of 12 specimens. HepPar1 staining was positive in many ductular hepatocytes in 11 of 13 cases. Vimentin was detected in the perinuclear cytoplasm of ductular hepatocytes and some bile duct epithelial cells in all regenerating livers. Double immunostaining for HepPar1/CK19 demonstrated that the ductular hepatocytes contained either HepPar1 or CK19 and that some ductular hepatocytes coexpressed both antigens. CK14, CK19, vimentin, and HepPar1 expression in ductular hepatocytes in human liver regeneration resembles the pattern seen in the developing human liver from 4 to 16 weeks' gestation. This suggests that the ductular hepatocytes recapitulate the developmental stages of bipotential liver progenitor cells and differentiate in steps marked by the acquisition or loss of specific phenotypic characteristics.

Adolescent↗

Improvement of liver fibrosis in chronic hepatitis C patients treated with natural interferon alpha.

To investigate the histological change (change of liver fibrosis) produced by the anti-viral effect of interferon on hepatitis C virus, 40 patients with chronic hepatitis C treated with natural interferon alpha were divided according to the existence of viremia at the end of treatment and 6 months after the end of treatment. The condition of liver fibrosis was scored numerically with a new "hepatic fibrosis score" which is sensitive to more subtle changes than Knodell's fibrosis score. Each portal zone was evaluated separately. End-of-treatment biopsy for the HCV RNA-negative group (negative for HCV RNA at the end of treatment) showed a significant improvement of the "hepatic fibrosis score" as well as the alleviation of necrosis and inflammation. At the end of treatment and 6 months after that, serum procollagen type III peptide levels and serum type IV collagen-7s levels had also decreased significantly in the HCV RNA-negative group. The present study showed that treatment with interferon alpha could alleviate fibrosis in addition to necrosis and inflammation.

Adult↗

Detection of hepatitis B and hepatitis C viral sequences in fulminant hepatic failure of unknown etiology.

In a significant number of patients, the etiology of fulminant hepatic failure (FHF) is unknown. To determine whether hepatitis B virus (HBV) and hepatitis C virus (HCV) play a role in patients without serologic markers of HBV and HCV infection, the authors examined tissue samples from 15 liver explants with massive hepatic necrosis for the presence of viral sequences by the polymerase chain reaction (PCR). The specimens were derived from nine patients with FHF of unknown etiology; two with serum hepatitis B surface antigen (HBsAg); two with antibodies to HCV; one with antibodies to hepatitis A virus (HAV) and anti-HBc of the IgM class; and one with isoniazid toxicity. Nucleic acids were extracted from frozen liver samples. RNA was used as a template for reverse transcription, followed by double PCR with nested primers for the 5'-untranslated region of HCV. DNA was tested by single PCR for S gene sequences of HBV. Hepatitis B virus sequences were detected in the specimens of the two HBsAg positive patients, the anti-HAV/anti-HBc positive patient, and three of nine patients with FHF of unknown etiology. Hepatitis C virus sequences were present in the explant of one patient with FHF of unknown etiology, but not in the two patients with antibodies to HCV. In two specimens with molecular findings of HBV infection (1 from a patient with serum HBsAg and 1 without), there was immunohistochemical evidence of coinfection or superinfection with hepatitis delta virus (HDV). In conclusion, in this patient population, HBV, alone or with HDV or HAV, causes fulminant hepatic failure more often than HCV infection. However, in the majority of patients, the etiology of fulminant hepatic failure remains unknown.

Adult↗

Activated renin-angiotensin-aldosterone system and its effects on cardiovascular system during 20-days horizontal bed rest.

Change in circulating blood volume by bed rest has been suggested to effect on many cardiovascular responses after bed rest including orthostatic intolerance and exercise performance. However, there is a lack of consensus on effect of renin-angiotensin-aldosterone system (RAAS) on baseline heart rate and blood pressure during bed rest, although RAAS is the most potent fluid regulating system. The purpose of this study was to clarify the effect of RAAS on changes in baseline cardiovascular system and urine excretion.

Aldosterone↗

Effects of 20 days bed rest on mechanical efficiency during upright cycling and leg muscle mass in young males.

Delta efficiency defined as increase in work over the corresponding increase in energy liberation (delta work/delta energy) may be used to express the efficiency of working muscles under standard conditions where work is performed with similar changes in muscle length, identical pedal revolution frequencies, and contraction-to-relaxation ratios. The Delta efficiency is probably the most valid measure of the efficiency of muscular work, so it may be influenced by the difference in distribution and/or density of muscle fiber types in exercising muscles. It has been reported that after bed rest of 7-14 days, not only maximum oxygen uptake (VO2 max) but also oxygen uptake (VO2) at 3-min submaximal upright exercise decreased. However, the decrease might be apparent, and the mechanical efficiency might be unchanged. On the other hand, muscle mass of bicycling legs was decreased after continuous horizontal bed rest of 10 days and 20 days. Because the decreased muscle mass is probably related to decrease in the density of the slow twitch muscle fibers (ST-fiber), the decrease in submaximal VO2 during bicycle exercises after bed rest may result from a decrease in ST-fiber mass. Therefore, it could be hypothesized that the mechanical efficiency should increase during upright exercise because of the relative increase in amount of more efficient fast twitch muscle fibers (FT-fiber) than ST fibers in exercising muscles. The purpose of the present study was to investigate whether delta efficiency in working muscle is influenced by the decrease in muscle mass after 20 days horizontal bed rest in young males.

Adult↗

Expression of hepatitis C virus in hepatocellular carcinoma.

BACKGROUND: Epidemiologic studies have suggested a strong association between chronic hepatitis C virus (HCV) infection and the development of hepatocellular carcinoma (HCC). To investigate the possible role of HCV in the pathobiology of HCC, the authors studied the expression of HCV in 10 cases of HCC with chronic HCV infection. METHODS: The core, envelope, and nonstructural (NS) 3 and 5 proteins were localized in liver and tumor tissues by the immunoperoxidase technique using mouse monoclonal antibodies to recombinant proteins or synthetic peptide of HCV. In addition, the positive and negative strands of HCV RNA were detected in the tissues by strand-specific reverse transcription/double polymerase chain reaction using primers for the 5'-nontranslated region. RESULTS: The HCV proteins were expressed in three of nine HCC specimens tested (the core protein in three HCC, the envelope, NS3 and NS5 proteins in one HCC) and in two of nine nontumorous liver specimens adjacent to the HCC (the core protein in two specimens, envelope, NS3 and NS5 proteins in one specimen). Positive-stranded HCV RNA was detected in all tumorous and nontumorous specimens except in one tumor. Negative-stranded HCV RNA was found in six of nine HCC tested and in all nontumorous livers. CONCLUSIONS: These findings suggest that HCV persists in hepatocytes during malignant transformation, although secondary infection of tumor cells by HCV cannot be excluded. Some HCC appear to support replication and expression of HCV.

Adult↗

[Baroreceptor reflex function in young normotensive men with a family history of hypertension].

The purpose of this study is to evaluate the baroreflex function using lower body negative pressure (LBNP) and neck suction in young normotensive men with or without a family history of hypertension. Twenty-two young normotensive men with a family history of hypertension (FH+) and eight young normotensive men who had no family history of hypertension (FH-) were studied. FH(+) consisted of men who had a family history of hypertension within second degree relatives. We studied cardiopulmonary baroreflex function using LBNP and carotid sinus baroreflex function using neck suction and evaluated the reflex function under stimulated conditions using both LBNP and neck suction at the same time. Systolic arterial pressure (SAP)(F = 5.42, p < 0.0001) and pulse pressure (PP)(F = 15.57, p < 0.0001) decreased similarly in both groups in response to LBNP. SAP and PP responses to LBNP were not significantly affected by the family history of hypertension. Diastolic arterial pressure (DAP) increased (F = 2.89, p < 0.005) in both groups. There was a relationship between the LBNP level and family history of hypertension (F = 2.53, p < 0.013), and the increment in DAP during LBNP -30, -40 mmHg was larger in the FH(+) group. Through mean arterial pressure (MAP) was not effected by LBNP, there LBNP level was related to the family history of hypertension (F = 2.23, p < 0.02). Heart rate increased progressively (F = 25.7, p < 0.0001) with increasing levels of LBNP; however, these changes did not differ significantly in either group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Regional changes in muscle mass and strength following 20 days of bed rest, and the effects on orthostatic tolerance capacity in young subjects.

To this day, many studies have suggested that prolonged bed rest (BR) affects on muscle mass and strength not only in gravity muscles but also in ungravity muscles. However, it is still unclear whether the decrease in regional muscle strength after BR is due to the alterations in the corresponding muscle mass, or not. On the other hand, if BR decreases the mass of antigravity muscles (UGM) as well as muscle strength and then increases tissue compliance of the antigravity muscles, orthostatic tolerance capacity will be decreased by the reduction in cardiac output (CO) in spite of the increase in myocardial contractility because the more decrease in venous return due to the more increase in blood pooling within the compliant tissues of the lower body. However, this is also unclear. To make these questions clear, the present study investigated the regional muscle mass and strength and orthostatic tolerance capacity before and after 20 days of bed rest in young subjects.

Adult↗

Effects of mild supine exercise during 20 days bed rest on maximal oxygen uptake rate in young humans.

Fourteen sedentary young volunteers performed a maximal exercise test on a bicycle ergometer before, after and eight or nine weeks after 20 days bed rest. They were divided into four groups. They all went through 20 days bed rest; 5 females and 6 males as controls while 3 males performed mild pedaling supine exercise for 30 minutes twice a day. Three other males from the control group started a retraining programme after bed rest performing mild pedaling exercise in the sitting position for an hour a day, 3-4 days a week for eight weeks. VO2max was reduced after bed rest in all groups. In the control group the 6 males decreased VO2max from 2.82 +/- 0.09 1.min-1 before bed rest to 2.42 +/- 0.14 1.min-1 after. The female controls decreased from 2.55 +/- 0.24 1.min-1 to 2.22 +/- 0.23 1.min-1. The exercise regime performed by the three males during bed rest did not prevent a fall in VO2max in that group from 2.76 +/- 0.06 to 2.57 +/- 0.09 1.min-1. The three males who performed bicycle exercise in the recovery period did not attain higher recovery values at 8-9 weeks than the other males. However the 5 female controls did not recover their > 13% loss in VO2max after 8-9 weeks of recovery. Calculation of peak oxygen pulse from VO2max divided by heart rate indicated that these changes in VO2max were caused exclusively by a reduction in stroke volume of the heart, a finding supported by resting echocardiography of left ventricular end-diastolic diameter and stroke volume.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Decremental reset in basal metabolism during 20-days bed rest.

Changes in basal metabolism during 20 days bed rest were measured in 9 young healthy males and 5 females. Food intake was unrestricted and supplementary meals were allowed. All food intake was monitored. A special sleeping pattern was not enforced, although an ordinary day-night diurnal rhythm was kept in the rooms. Body temperatures were measured daily every 2 hours from 7:00 to 22:00. Basal oxygen uptake decreased significantly during the first 10 days of bed rest and levelled off during the following 10 days. Body weight and composition remained substantially unchanged in spite of a decreased energy consumption during the bed rest. In conclusion, basal VO2 was reset at a decreased level during the first 10 days of bedrest with no relationship to the dietary energy intake or to the body temperature, while no more change took place during the following 10 days.

Adult↗

Effects of 10 and 20 days bed rest on leg muscle mass and strength in young subjects.

Sedentary voluntary students were exposed to 10 (n = 8) and 20 (n = 14) days bed rest to study effects of prolonged bed rest on isometric strength of knee extension and flexion, total leg strength, right hand grip and elbow flexion using different dynamometers. Further, muscle mass of right leg and arm was measured by dual energy X-ray absorptiometry, and cross sectional area of right thigh by X-ray computed tomography before and after bed rest and after 4 or 8 weeks of recovery. After 10 days bed rest, these variables tended to decrease except for the muscle mass of right arm which increased. After 20 days of bed rest, a similar trend was observed, but at a statistically significant level of p < 0.05. However, no correlation was observed between the decrease in knee extensor strength and cross sectional area of the thigh. Nor was a correlation observed between the sum total of isometric strength of the leg and the total muscle mass measured. The 24h urinary excretion of N2 and creatinine was not changed through the experiments. During recovery, the variables measured had reached the initial levels after 4 or 8 weeks. These changes were not affected by mild supine exercise training. The results suggest that isometric muscle strength was decreased in non-antigravity muscles as well as antigravity muscles by prolonged bed rest, but the rate of changes did not correlate to the corresponding changes in muscle mass. The decreases in maximum voluntary strength are probably not only due to the decrease in muscle mass but also due to reductions of neuromuscular function.

Absorptiometry, Photon↗

Cardiovascular effects of 20 days bed rest in healthy young subjects.

To evaluate the effects of inactivity on the cardiovascular system in normal subjects, left ventricular echocardiography and vascular ultrasound of the common carotid artery, abdominal aorta and femoral artery, and lower body negative pressure tests were performed in 14 healthy volunteers (mean age: 22 years) before and after 20 days of strict bed rest. Cardiac output was calculated from echocardiographic measurements and peripheral arterial flows by multiplying cross-sectional area of an artery by heart rate and time-velocity integral measured by pulsed Doppler ultrasound with angle correction. Systemic vascular resistance, lower body vascular resistance, leg vascular resistance and head vascular resistance were also calculated. After bed rest, heart rate increased (69 +/- 2 to 79 +/- 3 bpm), while left ventricular diastolic dimension (49 +/- 1 to 45 +/- 1 mm), systolic blood pressure (137 +/- 5 to 116 +/- 4 mmHg), cardiac output (6.2 +/- 0.3 to 5.4 +/- 0.3 1.min-1), abdominal aortic flow (4.1 +/- 0.4 to 3.1 +/- 0.3 1.min-1), femoral artery flow (0.66 +/- 0.07 to 0.33 +/- 0.04 1-min-1), and lower body negative pressure test tolerance time (750 +/- 71 to 582 +/- 48 s) decreased significantly (p < 0.05). However, common carotid artery flow (0.97 +/- 0.09 to 1.03 +/- 0.08 1.min-1) did not change. Although no significant changes in systemic vascular resistance, lower body vascular resistance or head vascular resistance were observed, leg vascular resistance increased significantly after 20 days of bed rest (6933 +/- 2905 to 13221 +/- 2606 dyn.s.cm-1) (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Orthostatic tolerance and autonomous nervous functions before and after 20-days bed rest.

To determine the critical factor that induces tachycardia during orthostasis after bed rest, we tested some autonomous nervous functions and the reaction to lower body negative pressure before and after 20 days horizontal bed rest. Subjects were 5 young healthy males and one female. Carotid vagal baroreflex sensitivity was evaluated by cardiac response to a gradual increase in carotid distending pressure of 150 mmHg within 10 s by neck suction after neck positive pressure. Combined effects of cardiopulmonary and aortic baroreflexes were assessed by the cardiovascular responses during Valsalva manoeuvre. Sympathetic reactivity was evaluated by a cold pressor test. The carotid vagal baroreflex tended to be diminished after bed rest in supine rest, but unchanged in seated position. Cardiac responses to Valsalva manoeuvre did not change after bed rest, although blood pressures decreased more during the manoeuvre after bed rest. Cold pressor response did not change after bed rest. Heart rate response during lower body negative pressure was increased after bed rest. In conclusion, combining our results from several autonomous nervous functions suggested that the exaggerated orthostatic tachycardia after bed rest could not be explained by the changes in sensitivity of carotid, aortic, and cardiopulmonary reflexes and sympathetic reactivity to cold stress.

Adult↗