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Biomedical subjects

T Sadamoto

Publications and source records attributed to T Sadamoto.

At least 37 records · Page 2Linked to original sources

[Clinico-pathological studies of alcoholic liver disease, especially on the diagnostic significance of endogenous bile acid tolerance test].

Endogenous bile acid tolerance test was performed in 88 patients with alcoholic liver disease and results obtained were compared with histological features in their liver biopsy specimens. An increase of serum fasting total bile acid (FTBA) and maximum total bile acid (MTBA) was closely reflected the degrees of hepatic fibrosis and they were seemed to be useful for differential diagnosis and clinical observation of the alcoholic liver disease. We have been reported the criteria of the grading for bile acid tolerance test at Inuyama Symposium in 1977. With the use of this criteria, we applied it to alcoholic liver disease. The results of bile acid tolerance test were normal in patients with ALF mild, fatty liver and no remarkable change, these were slightly abnormal in patients with ALF moderate and severe, these were severe abnormal in patients with ALC. Bile acid tolerance test is a sensitive liver function test. However, this method is too complex for clinical use. Therefore, we recommend to use the serum bile acid level at 60 minutes after the yolk loading (60min-TBA), because we found 60min-TBA was almost the same as MTBA and accurately reflect the liver morphology. So, we concluded measurement of FTBA and 60min-TBA were adequate, especially in outpatients, to evaluate the progress of alcoholic liver disease.

Adult↗

[Clinical study on alcoholic pancreatitis in alcoholics (especially in ERP findings)].

The pancreatic functions (PFD test and 75g GTT), pancreatic enzymes (serum-amylase, urine-amylase, serum-elastase I and serum-lipase), alcohol consumption histories, clinical symptoms, histological findings in the liver and ERP findings have been examined in 66 alcoholic patients. Fourty two out of 66 cases (64%) showed abnormal ERP findings which were compatible with chronic pancreatitis. But among these 42 cases, only 9 cases (21%) showed clinical symptoms such as epigastralgia, back pain, diarrhea and emaciation which suggest the existence of chronic pancreatitis. The degree of liver damage, alcohol consumption have no significant correlation with ERP findings. Furthermore, the severe alcoholic pancreatitis occurred in patients having mild liver injury more than those having severe liver injury such as cirrhosis. And the data of pancreatic functions and enzymes could not confirm ERP findings especially in patients with mild and moderate pancreatic injury when compared to normal ERP findings. We concluded that asymptomatic alcoholic pancreatitis occurred more frequently in painless alcoholic. It may be not suitable for only using the normal pancreatic functions test to diagnose the alcohol induced chronic pancreatitis.

Adult↗

Cardiovascular reflexes during isometric exercise--role of muscle mass and gravitational stress.

Six healthy males performed sustained static contractions of five arm- and leg muscle groups for 2 min at 40% maximum voluntary contraction (MVC) sitting and supine. Delta heart rate, blood pressure, forearm vascular resistance, and cardiac output increased during contraction incrementing increasingly in the following order: dorsi flexion of ankle, plantar flexion, third finger flexion, handgrip, and knee extension. Muscle ischemia during recovery did not change this order. The cardiovascular responses to static contraction did not relate to muscle mass involved in a simple rectilinear manner. The increments in cardiovascular responses were not reduced in the supine position, although the values were at a lower level, probably due to the combination of a decreased sympathetic nervous activity in the supine position and an increased aortic baroreceptor stimulation induced by the increased stroke volume.

Adult↗

Severe jaundice in malignant lymphoma. Report of two autopsy cases.

Two autopsy cases of malignant lymphoma with marked hyperbilirubinemia (18.6 and 36.5 mg/dl at maximum) are presented. Histology revealed the portal area to be enlarged due to lymphoma cell infiltration and cholestasis in the hepatic lobules in both. Of 30 cases of malignant lymphoma treated in our department, hyperbilirubinemia was seen in 7 cases (23%) including these two cases (6.7%) which were severely jaundiced. The occurrence rate of jaundice in malignant lymphoma to all jaundiced diseases showing serum total bilirubin levels of more than 5 mg/dl was 0.7%.

Adult↗

Inhibition of delta-aminolevulinate dehydratase in trichloroethylene-exposed rats, and the effects on heme regulation.

A pronounced and irreversible depression of the erythroid and liver delta-aminolevulinate dehydratase (porphobilinogen synthase; 5-aminolevulinate hydro-lyase, EC 4.2.1.24) activity was observed in rats exposed to trichloroethylene, a widely used solvent. The depression could not be restored after the treatment with dithiothreitol and zinc; however, radioimmunoassay of delta-aminolevulinate dehydratase indicated that trichloroethylene exposure did not essentially decrease the amount of enzyme. The depression of the enzyme activity thus proved to be due not to a reduction in the enzyme amount but to enzyme inhibition. The purified holoenzyme (fully activated delta-aminolevulinate dehydratase with 1 atom zinc per subunit) and apoenzyme (fully activated enzyme with the remaining zinc less than 0.1 atom per subunit) were prepared to investigate the in vitro inhibition of the enzyme by trichloroethylene. Incubation with trichloroethylene did not inhibit the holoenzyme, but inhibited the apoenzyme dose-dependently. Trichloroethylene inhibited the holoenzyme when incubated with the mixed function oxidase system. The in vitro experiments reported here indicate two mechanisms of the enzyme inhibition by trichloroethylene. In the liver of rats exposed to trichloroethylene, cytochrome P-450 concentration and heme saturation of tryptophan pyrrolase (EC 1.13.11.11) are reduced; in addition, the activity of delta-aminolevulinate synthase (EC 2.3.1.37) increased. After exposure to trichloroethylene at 2.14 g/m3, urinary delta-aminolevulinic acid increased to 142% of the control, while the excretion of coproporphyrin was reduced to 19.6% of the control.

Animals↗

Mechanisms for modification of bromobenzene hepatotoxicity by coadministered toluene and chlorobenzene.

Hepatotoxicity of bromobenzene (2 mmole/kg) in combination with toluene or chlorobenzene (4 mmole/kg each) were studied in vivo on the basis of GPT elevation and histological examinations. Both toluene and chlorobenzene suppressed bromobenzene hepatotoxicity 24 hr after the treatment, and chlorobenzene dramatically potentiated the toxicity at 48 hr. The glutathione level became lower at 12 hr and recovered at 24 hr when bromobenzene was given alone. The recovery delayed until 48 hr when chlorobenzene was coadministered. In experiments in vitro with microsomes from phenobarbital-pretreated rats, both toluene and chlorobenzene at 0.6 mM inhibited p-bromophenol formation noncompetitively but had no effect on o-isomer formation. Multiple factors may determine overall hepatotoxicity in combined exposure; bromobenzene hepatotoxicity will be suppressed in the early phase owing to metabolic inhibition of 3,4-epoxidation, but potentiated later because of delayed recovery in the glutathione level. A time-saving yet reliable assay system with an ECD-gas chromatograph was developed for bromobenzene metabolism study.

Animals↗

Effects on cochlear microphonics in guinea pigs induced by prolonged exposure to low-frequency sound.

The effects on CM induced by 46.5 h exposure to low-frequency sound of 0.125 kHz at 115 dB (SPL) and 100 dB (SPL), which frequency is considered to be in the vicinity of the lowest limit of audiofrequency for guinea pigs, were investigated by the sound pressure levels at which CM output voltages produced 50 microV (50 microV isopotential responses) at test frequencies of 0.06, 0.08, 0.12, 0.18, 0.25, 0.5, 1, 2, and 4 kHz, and by the intensity function measured from 65 to 120 dB (SPL) at test frequencies of 0.06, 0.08, 0.12, 0.18, 0.25, 0.5, 1, and 2 kHz. The results obtained were as follows. In 50 microV isopotential responses measured at about 30 min after the termination of sound exposure, the mean dB in the 115 dB-exposed group tended to elevate at all test frequencies of 0.06 kHz to 4 kHz as compared with those in the control group. Significant dB elevations were especially observed at 0.06, 0.12, 1, 2, and 4 kHz. In the 100 dB-exposed group, however, no significant dB elevations were observed at any test frequencies as compared with those in the control group. In the intensity function measured at about 40-60 min after the termination of sound exposure, the mean output voltages in the 115 dB-exposed group induced by test stimuli of 0.18 kHz-2 kHz at higher intensities showed significant depression in comparison with those in the control group (by over 110 dB at 0.18 and 0.25 kHz, and by over 90 dB at 1 and 2 kHz).(ABSTRACT TRUNCATED AT 250 WORDS)

Acoustic Stimulation↗

Cytochrome P-450 system dependent depression of delta-aminolevulinic acid dehydratase activity by bromobenzene in rats.

Male Wistar rats (200-230 g) were treated with bromobenzene in soybean oil intraperitoneally (i.p.) (4 mmol/kg) once a day for 1 or 2 days while control rats received soybean oil alone. delta-Aminolevulinic acid dehydratase (ALA-D) activity was depressed to 80% and 43% in bone marrow after 24 h and 48 h, respectively. ALA-D activity was also depressed significantly in the liver after the administration of bromobenzene while the activity in peripheral erythrocytes was not altered. After the administration of bromobenzene, the concentration of reduced non-protein sulfhydryls in liver was the lowest at 24 h and increased thereafter. No significant change was observed in the activity of delta-aminolevulinate synthase in liver. The decrease of ALA-D activity was also reproducible in vitro. The 105 000 g supernatant fractions of rat bone marrow lyzates as ALA-D source were incubated with liver microsomes prepared from rats treated with phenobarbital. ALA-D activity was decreased by bromobenzene but no decrease was observed when the microsomes were preincubated with CO to inhibit cytochrome P-450. The effect of bromobenzene on ALA-D purified from rat erythroid cells was studied in incubations containing a reconstituted cytochrome P-450 system prepared from rat liver. The decrease of ALA-D activity was proportional to both the incubation time and to the concentration of P-450 while no decrease was detected when P-450 was inhibited by CO before the incubation.

5-Aminolevulinate Synthetase↗

Inhibition of delta-aminolevulinic acid dehydratase by trichloroethylene.

Male Wistar rats (8 animals/group; 180-200 g) were exposed continuously to trichloroethylene (TRI) for 48 or 240 h or methylchloroform (1,1, 1-trichloroethane: MC for 48 h at 50, 400 and 800 ppm. The inhibition of delta-aminolevulinic acid dehydratase (ALA-D) was examined in liver, blood and bone marrow of naive and phenobarbital pretreated animals exposed to TRI. A clear cut dose-effect relationship between the exposure concentration or duration of exposure and the inhibition of ALA-D activity was seen for rats exposed to TRI. In addition to this finding, significant interaction between TRI exposure and phenobarbital treatment was observed in the inhibition of ALA-D in liver and blood. MC did not produce inhibition. Trichloroacetic acid and trichloroethanol failed to inhibit the ALA-D activity in vitro. It seems that a metabolite(s) of TRI other than the above 2 substances may play a role in the inhibition of ALA-D. The inhibition of ALA-D (38% or 48% of the control in liver or in blood, respectively) observed after the 240 h exposure at 400 ppm to TRI was accompanied by the significant elevation of delta-aminolevulinic acid synthase (186% of the control) in liver and the increase in excretion of delta-aminolevulinic acid in urine (142% of the control). This occurred without an apparent weight loss, liver injury or hematological changes.

5-Aminolevulinate Synthetase↗

An experimental study of the effects of lead acetate on hearing. Cochlear microphonics and action potential of the guinea pig.

Guinea pigs were poisoned with repeated i.p. injections of 1% lead acetate. After 5 weeks, the animals were examined electrophysiologically by using cochlear microphonics (CM) and action potential (AP). The thresholds of maximum voltage of N1 in the AP of the animals injected with a total of 100 mg lead acetate were elevated about 15 dB and increased N1 latency was also observed. However, no significant changes in those of CM were found. The results suggest that lead acetate not only induces damage to the peripheral nerves, but also to the cranial nerves.

Action Potentials↗

Effects of trichloroethylene exposure on hearing. An investigation of cochlear microphonics and action potential of the guinea pig.

Four groups of guinea pigs with normal Preyer's reflex were exposed to trichloroethylene (TCE). Each group consisted of nine to 10 naive male albino Hartley guinea pigs of 9 weeks of age with a body weight of approximately 400 g. To test the suggestion that TCE causes damage to the cochlear system, a study was conducted involving four experiments. The results were as follows: No significant difference was observed between the intensity functions of the CM (4 kHz) and AP (7 kHz) potentials of the control groups and those of the TCE-exposed groups by analysis of variance. It was considered that there was no difference in the cochlear reaction to high frequency sound between guinea pig and man. It therefore might be suggested that acute exposure to TCE of a high concentration does not always induce dysfunction of the organ of Corti and the 8th nerve in man.

Action Potentials↗

Skeletal muscle tension, flow, pressure, and EMG during sustained isometric contractions in humans.

In five healthy males sustained isometric torques during elbow flexion, knee extension, and plantar flexion correlated positively with intramuscular tissue pressure (MTP) in the range 0-80% of the maximal voluntary contraction (MVC). During passive compression of the muscle at rest 133-Xenon muscle clearance stopped when MTP reached diastolic arterial pressure (DAP) indicating that the muscle vascular bed was occluded. However, during sustained contraction this relation between DAP, flow and MTP was not seen. In two cases 133-Xenon clearance from M. soleus did not stop in spite of an 80% maximal contraction and MTP stayed below DAP. In other cases MTP would reach as high as 240 mm Hg before clearance was zero. In the deeper parts of the muscles MTP during contraction was increased in relation to the more superficial parts. The means values for the % MVC that would stop MBF varied between 50 and 64% MVC for the investigated muscles. Mean rectified EMG (MEMG) showed a high correlation to MTP during sustained exhaustive contractions: When MEMG was kept constant MTP also remained constant while the exerted force decreased; when force was kept constant both MEMG and MTP increased in parallel. This demonstrated that muscle tissue compliance is decreasing during fatigue. Muscle ischemia occurring during sustained isometric contractions is partly due to the developed MTP, where especially the MTP around the veins in the deeper parts of the muscle can be considered of importance. However, ischemia is also affected by muscle fiber texture and anatomical distorsion of tissues.

Animals↗

Electrophysiological responses in guinea pig cochlea to low frequency sound stimuli: distortion of cochlear microphonic (CM) wave form.

The present experiment investigated whether or not auditory responses of the middle and/or inner ear in guinea pigs to low frequency sound stimuli [ 60 Hz-2 kHz at 90-120 dB(SPL) ] exhibited the harmonic distortion phenomenon resulting from cochlear microphonics (CM). Measurement of CM leading in turn I by the differential electrode recording method involved measurement of 50 microV isopotential responses, output voltages and CM wave form distortion at each constant sound pressure. The results obtained were as follows: (1) On the 50 microV isopotential response curve and the output voltage curves, the changes at 60-90 Hz were different from those at higher frequencies. (2) At stimuli of 90 or 100 dB(SPL), CM wave form distortion appeared frequently at frequencies below 120 Hz, but were less pronounced above approximately 200 Hz. (3) When raised to 110 and 120 dB(SPL), almost all CM wave forms were distorted at all test frequencies between 60 and 500 Hz. (4) The patterns of CM wave form distortion at frequencies below approximately 120 Hz showed peak clipping and triangular wave distortions, while those at frequencies above approximately 200 Hz showed little of these distortions.

Acoustic Stimulation↗

Cardiovascular effects of simulated zero-gravity in humans.

UNLABELLED: Head-down and head-up [correction of heat-up] tilted bedrest (5 degrees) and head out water immersion (HOWI) for 6 hr were compared. PARAMETERS: Cardiac output (rebreathing method), blood pressure (arm cuff), forearm blood flow (venous occlusion plethysmography), total peripheral (TPR), and forearm vascular (FVR) resistances, Hct, Hb, relative plasma volume (PV) changes, and plasma catecholamines (single-isotope assay). During HOWI there was as expected a decrement in TPR, FVR, Mean arterial pressure (MAP, from 100 to 80 mmHg), Hct, and PV, and--as a new finding--catecholamines, which were 30-50% lower compared with both +5 and -5 degrees bedrest. During head down tilt, MAP was elevated (to 100-110 mmHg) and catecholamines did not fall, while TPR and EVR slowly decreased over 6 hr. HOWI is a stronger stimulus than -5 degrees bedrest, probably because HOWI elevates central venous pressure more markedly emptying the peripheral veins, while bedrest permits a distension of veins, which induces an increase in sympathetic nervous activity.

Adaptation, Physiological↗

Gravitational effects on human cardiovascular responses to isometric muscle contractions.

Isometric exercise induces profound cardiovascular adaptations increasing mean arterial pressure and heart rate. We investigated effects of simulated +Gz and -Gz respectively on the central and peripheral cardiovascular system. Sustained handgrip exercise was performed at 40% of maximum for 2 minutes in five subjects. This maneuver increased mean arterial pressure by 40-45 mm Hg both during head out water immersion which simulates weightlessness, as well as bedrest during -25, 0, and +25 degrees tilt from the horizontal. Lower body negative pressure (-60 mm Hg for 10 min) attenuated the response to handgrip exercise to 30 mm Hg. It also increased the heart rate minimally by about 20 beats per minute while the water immersion, as well as head up, head down and horizontal bedrest showed increments of about 50 beats per min. It was concluded that the response to isometric contraction is mediated through the high pressure baroreceptors, because similar responses were seen during stresses producing a wide variation in central venous pressure. During lower body negative pressure the increased sympathetic nervous activity itself increased resting heart rate and mean arterial pressure. The responses to static exercise were, therefore, weaker.

Adaptation, Physiological↗