The correlation of alcoholic liver disease in relation to alcohol dehydrogenase (ADH) isozyme activity, serum enzyme activity and drinking patterns was studied statistically and the following conclusions were obtained:
1) Total liver ADH (T-ADH) activity was related with a condition of liver disease; the more progressive the lesion, the lower the T-ADH activity. The T-ADH activity was significantly reduced in the cirrhotic liver. The reduction in the T-ADH activity was due to the reduced activity of pyrazole sensitive-ADH (PS-ADH).
2) An increase of several serum-enzyme activities was shown in only the cases with decreased liver PS-ADH activity. Therefore, a correlation between the decrease of the PS-ADH activity and the liver damage was recognized by the serum-enzyme activities. The patient with the cirrhotic liver showed the low activities of both the serum-enzymes and PS-ADH of the liver, suggesting that a reduction in activities of both the serum-enzymes and the liver PS-ADH gives a probable indication of the alcoholic liver cirrhosis.
3) Liver PS-ADH activity was shown to decrease with the increase of daily alcohol intake. On the other hand, the increase of total alcohol intake, daily alcohol intake and the drinking period was shown to be related with the increase of liver pyrazole insensitive-ADH (PI-ADH). This suggests that PI-ADH plays a main role in the metabolism of alcohol of the patient suffering from alcoholic liver disease.
4) Liver cirrhosis was significantly seen in the group where the T-ADH activity was low and the ratio of PI-ADH activity to T-ADH activity was high. This suggested that the increase in the ratio of the PI-ADH activity to T-ADH activity was related with cirrhogenesis.

View full abstract

Na+, K+-ATPases were isolated from human kidney medulla and electric organ of Torpedo californica and their enzymatic properties were examined with reference to the sensitivity of the enzyme to ouabain. The specific activity of the purified Na+, K+ -ATPase from human kidney was 93 μmol Pi/mg/h. SDS-polyacrylamide gel electrophoresis revealed that the human enzyme consisted of a and β subunits having molecular weights of approximately 92, 000 and 44, 000, respectively, as the enzymes from other sources. Kd for ouabain of the human enzyme was estimated to be 1.9 nM, while k1 and k-1 of the Torpedo enzyme in the reaction with ouabain were 7.5×10-3s-1m-1 and 0.21×103s-1, respectively. Thus it is apparent that the human enzyme is similar to, but the Torpedo enzyme is different from, the lamb enzyme with respect to their sensitivity to ouabain.

View full abstract

An in vitro incubation procedure for the estimation of some cholesterol dynamics in serum was devised, taking advantage of a purified specific goat antiserum against human serum β-lipoprotein to achieve the fractionation of a- and β-lipoprotein fractions. The new method was based on the two principles that the decrease of free cholesterol (FC) in the β-lipoprotein fraction during incubation should represent the amount of FC transferred from β- to α-lipoproteins and that the increase in the amount of esterified cholesterol (EC) in the β-lipoprotein fraction during incubation should be equal to the amount of EC transferred from α- to β-lipoproteins since the esterification of cholesterol occurs only in α-lipoprotein particles. The amount of esterified cholesterol which was transferred from α- to β-lipoproteins was calculated. The values of free cholesterol and esterified cholesterol in α- and β-lipoprotein fractions before and after the incubation were estimated with various serum samples taken from young and old women. The results obtained in this study indicated that the cholesterol dynamics are influenced considerably by several factors, such as LCAT activity, and the levels of cholesterol, triglyceride and phospholipid in the serum. Differences in the cholesterol dynamics between the young and old women indicated the possibility that the new method is useful for investigating the pathogenesis of atherosclerosis.

View full abstract

To evaluate altered GH regulation in MSG rats, plasma GH profiles were observed in unrestrained adult male MSG rats that had received a continuous infusion of human GRF [1-44] NH2. Male Wistar rats were treated with MSG (4 mg/g BW, sc) as neonates and were used for the study on 150-170 days of life. All rats were provided with two indwelling cannulae 5-7 days previously; one in the right atrium for undisturbed blood collection and the other in the inferior vena cava for 0.9% NaCI or GRF infusion. 0.9% NaCI or GRF was administered by an infusion pump (10 μl/min) for 6 h at a dose of 50 or 200 ng/kg BW/min. Serial blood samples were obtained every 20 min.
During a 6-h continuous infusion of 0.9% NaCI, plasma GH levels in MSG rats were low and revealed occasional small elevations, while in the control animals characteristic pulsatile GH secretion was observed every 173 min. During a low dose GRF (50 ng/kg BW/min) infusion in MSG rats, pulsatile GH secretion appeared at irregular intervals, while in control rats the amplitude of naturally occurring pulsatile GH secretion was significantly augmented. In MSG rats, plasma GH levels rose without pulsatile manner during a high dose GRF (200 ng/kg BW/min) infusion. When the control rats received a high dose GRF infusion, the amplitudes of pulsatile GH secretion and trough GH levels were markedly augmented but the interval of pulsatile GH secretion remained unaltered. The amount of GH released during a 6-h continuous GRF infusion -increased significantly in a dose dependent manner in both groups of rats, but it was significantly less in MSG rats than in control rats. When the rats had received goat anti-somatostatin serum previously, plasma GH levels during GRF infusion rose without pulsatile secretion.
Results show that in adult male MSG rats, pulsatile GH secretion can be resumed by a continuous infusion of GRF, but the release of somatostatin which exerts the intermittent tonic inhibition on GH secretion during a continuous presence of GRF is compromised.

View full abstract

We investigated the effect of aging on the level of glycosylated hemoglobin (HbA1) in healthy subjects and diabetic patients. On the basis of our findings in this study, and using the HbA1c level as an index to long-term plasma glucose control, we compared it with the levels of fasting plasma glucose (FPG) and post-prandial plasma glucose (PPG) in different age groups subjected to different therapies so as to explore clinical problems in measuring plasma glucose levels in elderly diabetic patients.
There were significantly positive correlations between HbA1 and HbA1c. In the healthy group examined, the HbA1 and HbA1c levels rose significantly with age. No specific relationship was found between HbA1a+b level and age. Looking for a correlation between the HbA1c level and the antecedent plasma glucose level in different age groups of the diabetic patients subjected to different therapies, we found that, in the subgroups of the "young to middle-aged" (under 60 years old) and the "elderly" (60 and above) patients, and in both the diet-treated group and those treated with the oral hypoglycemic agent (OHA), the HbA1c, level was best correlated with the FPG and PPG levels in the antecedent 3 to 8 weeks.
The coefficient of correlation between HbAI level and FPG and PPG levels in the antecedent 3 to 8 weeks did not vary from one therapy subgroup to another in the young to middle-aged patients. In contrast to this, the correlation coefficient for PPG was significantly lower than that of FPG in each therapy subgroup of the elderly patients. By examination of the mean levels and variances of plasma glucose in the antecedent 3 to 8 weeks in one-percent HbA1C strata of each therapy subgroup of each age group, the elderly group was significantly higher than the young to middle-aged group in PPG average in the over-5% and over-6% HbA1c, strata of the diet-treated subgroup and in the over-5%, over-6% and over-7% strata of the OHA-treated group.
We investigated the variation coefficient of three PPG measurements in the antecedent 3 to 8 weeks in cases under extremely stable plasma glucose control, and found no significant difference in mean coefficient between the elderly group and the young to middle-aged group.
These results strongly suggest that the PPG level varies considerably from one individual to another in elderly diabetic patients.

View full abstract

A method for determining the high risk group of hepatocellular carcinoma (HCC) and the factor related to long-term prognosis in patient with liver cirrhosis (LC) was developed, using a kind of multivariated analysis.
Eighty-six histologically proven cirrhotic patients were retrospectively classified into three groups: Group 1, 18 cases with a complication of HCC during the more than one year follow-up after the diagnosis of LC was confirmed, Group 2, 27 cases died of other causes than HCC during the less than 3-year follow-up and Group 3, 41 cases alive more than 3 years in the absence of HCC. Twenty-two parameters were selected from the routine liver function tests, physical examination and the history, obtained at the time of diagnosis.
A discriminant function for differentiating the above mentioned groups was derived using the theory of quantification. An investigation was also undertaken so as to determine which one of the 22 parameters was effective for differentiation.
Employing this function, correct differentiation was made in 84 out of 86 cases (97.7%), and only 2 cases were erroneously differentiated.
Among the parameters, age, sex, albumin, GOT, GPT, total protein, ascites and edema contributed greatly to differentiating Group 1 from Group 2 and 3. Likewise, LDH, albumin, ZTT, TTT, RBC, ascites and the family history of liver disease influenced largely on differentiation of Group 2 from Group 3.

View full abstract

The present investigation has been undertaken to elucidate the effects of hemodialysis on the mean volume of regional cerebral blood flow (m.r.CBF) in patients suffering from chronic renal failure.
Eighteen patients who had undergone hemodialysis were studied. Ten patients had chronic glomer. ulonephritis (CGN group) and 8 patients had diabetic nephropathy (DM group). Hemodialysis was performed in the form of acetate dialysis, using a Hollow-fiber type for 4 hours. An infusion of 133Xe was made into the internal carotid artery and the m.r.CBF was measured. Measurement were made 4 times, prior to dialysis, 1 hour and 3 hours after the initiation of dialysis and at the termination of dialysis. At the same time, the arterial blood pressure, cardiac output and blood gas analysis were measured as well.
A comparative study of m.r.CBF in the CGN and DM groups prior to hemodialysis disclosed a higher value in the CGN group, which showed a diclining trend significant after 3 hours. An identical trend was also comfirmed at the termination of hemodialysis. In both groups the value of arterial pH was normalized. However, the blood pressure and cardiac output remained unchanged.
The improvement of acidosis contracted the arterial wall. The improvement of arterial pH was significantly correlated with the decrease of m.r.CBF among patients with CGN. However, in the DM groups, the m.r.CBF was unchanged in spite of the improvement of the acidosis. This could well be explained on the assumption that the persisting arterioscrelosis in this group may exist as one of the resistant factors of the m.r.CBF improvement, while the arterial pH improved markedly. Although a number of previous researchers have observed the effect of hemodialysis on CBF among various groups of patients, the results have sometimes diverged. The reason could be that arterioscrelosis is one of the cardinal influential factors on the m.r.CBF and this fact may lead to various conclusion concerning the functional correlation of m.r.CBF in the CGN and DM groups. This requires further investigative clarification or elcidation in the future.

View full abstract

Ferrite-Adriamycin-microcapsule (Ferrite-ADR-m.c.), a new chemo-embolic material, was developed to improve the therapeutic effect with magnetic field for transcatheter arterial chemo-embolization (TACE) of malignant tumors.
Ferrite-ADR-m.c. was prepared by the spray drying method. The physical character of Ferrite-ADR-m.c. was investigated and the embolization effect of Ferrite-ADR-m.c. under the magnetic field was studied in rabbit ear vein. Fifteen adult rabbits (male, 2.8-3.3kg) with VX₂ tumor in the right thigh, which grew up to 3.0 cm in diameter, were separated into the following three groups: (1) 7 rabbits of TACE with Ferrite-ADR-m.c., (2) 3 of ADR arterial infusion and (3) 5 of no treatment as a control group. In TACE group, a 3.0 French catheter was selectively introduced into the feeding artery of the VX₂ tumor and 41.7 mg/kg (ADR: 0.5 mg/kg) Ferrite-ADR-m.c. was infused through the catheter under 5 mT magnet. Only 0.5 mg/kg ADR was infused in the arterial infusion group. Before and after TACE, digital subtraction angiography (DSA) and computed tomography (CT) were performed. After sacrifice at seven days or natural death, histological examinations with light and scanning electron microscope (SEM) were performed.
Ferrite-ADR-m.c. consisted of 8.47 × 10^-1 g/g Ferrite as the core, which is 1.2 × 10^-2 g/g active ADR and 1.41 × 10^-1 g/g ethylcellulose as the shell. It was recognized with SEM that Ferrite-ADR-m.c. presented a spherical shape measuring 9.9 ± 2.4 μm (mean ± S.D.) in diameter, having a relatively smooth surface. The mass magnetization was 53.0 emu/g when 1 mT magnetic field was given. The release rate of ADR from Ferrite-ADR-m.c. was rated as very slow. According to the theoretical consideration, it was confirmed that Ferrite-ADR-m.c. could be fixed in arterioler lumen when the relation between the intensity of the magnetic field (H) and the velocity of the blood flow (v) was satisfied with the formula H≥7.48 × 10³ × v. Soft X-ray radiograms of the rabbit ear confirmed that Ferrite-ADR-m.c. was fixed in the ear vein and complete occlusion was made under 6 mT magnet. DSA images after TACE demonstrated that the feeding arteries of VX₂ tumor were completely embolized by Ferrite-ADR-m.c. The high density area, in which CT number from 300 to 400 H.U. indicating the existence of Ferrite-ADR-m.c., was recognized as the tumor after TACE. The microembolus was observed in many arterioles of VX₂ tumor, surrounded by degenerative and necrotic tumor cells in histologic specimens. It was confirmed by Fe stain and EDAX (Energy dispersive analysis X-ray) that the microembolus was made up mainly of iron identifiable as Ferrite-ADR-m.c. The reduction rate of the tumor and the inhibition effect of metastasis in TACE group were more excellent than those of the other two groups.
Consequently, it was concluded that Ferrite-ADR-m.c. is an useful chemo-embolic material for the following three reasons.
1) The size and the shape of Ferrite-ADR-m.c. are suitable to embolize the feeding artery of malignant tumor until the peripheral portion. Ferrite is not absorbed into the vascular wall and therefore, the material makes it possible to prevent the recanalization of embolized arteries and the formation of collateral circulations after TACE.
2) It is possible to maintain a high concentration of ADR constantly in the tumor because Ferrite-ADR-m.c. has sustained release property of ADR.
3) Because of the ferromagnetic property of Ferrite, it is possible to fix Ferrite-ADR-m.c. in the vessel under a magnetic field. Furthermore, the material would be avoided to distribute under this circumstance into other organs through capillary system and A-V shunt.

View full abstract

The auditory brainstem response (ABR) has been widely used for making a prognosis of the outcome of coma since the first report by Jewett in 1970. ABR is the early component of auditory evoked potential and the seven positive waves are recorded within 10 ms after auditory stimulation. These waves are designated I, II, III, IV, V, VI and VII in order of appearance. Of these components, we observed waves I, III and V which originated in the brainstem and were stable. In our previous report, the ABR patterns were categorized into the following five groups. Group-(A) consisted of wave I only; group-(B) waves I-III; group-(C) waves I-V, but with prolonged latencies. Group-(D) was of a normal pattern, whereas group-(0) registered no activity.
From our previous findings of the effects of cerebrovascular disease on brain stem functions, we drew the following conclusions.
1) Early abnormality of ABR indicated irreversible destruction of the brain.
2) No recovery could be expected if the initial ABR pattern were group-(0), (A) or (B).
3) In cases showing group-(C)or(D), the prognosis would be good unless fatal complications occurred.
4) The interval between IV-V was more sensitive to brain stem function, and therefore, was more useful than that between III-IV for making a prognosis.
5) Disappearance of wave III indicated a very poor prognosis.
However, when patients were in the acute phase of coma, ABR changes were unpredictable. In order to further ascertain the mechanism of brain stem dysfunction, we analyzed ABR in diabetic coma and cerebral infarction. The subjects studied were 6 patients with diabetic coma and 60 patients with cerebral infarction, including 4 with brain stem infarction. All were admitted to Mejiro 2nd Hospital. ABR was obtained by evoked response recorder (Nihon Koden, MEB-5100A). The auditory signal was a 4, 000 Hz click, with a duration of 0.1 ms. Cut-off points for the band-pass filter were set at 100-3, 000 Hz and sweep time was set at 10 ms. Recordings were obtained by averaging 2, 048 stimulus presentations. The latencies, which were the intervals between the stimulation point and the peak of each wave, were determined with 90 dB HL. Since all of the cases were at a highly acute phase requiring emergency treatment, we principally used the wave-form due to binaural stimulation in order to shorten the test time.

View full abstract