Shin'ichi Shoji

Serum Prealbumin and Retinol-Binding Protein Concentrations in Japanese-Type Familial Amyloid Polyneuropathy

Serum concentrations of prealbumin and retinol-binding protein were measured in 28 patients with Japanese-type familial amyloid polyneuropathy, 46 relatives and normal controls. Both the serum prealbumin and retinol-binding protein concentrations were significantly decreased in the patients when compared with normal controls. The mean serum levels of these proteins in the asymptomatic relatives were intermediate between controls and patients.

Calcium flux of erythrocytes in Duchenne muscular dystrophy

The calcium flux of erythrocytes from patients with Duchenne muscular dystrophy (DMD) was measured. Passive influx was determined using erythrocytes incubated with lanthanum chloride as a specific inhibitor to calcium transport. There was no significant difference in calcium influx into cytosol and into membrane fractions between DMD and control age-matched boys. Influx of calcium was also determined using ATP-depleted erythrocytes incubated without the inhibitor. Again there was no significant difference between DMD and control values. Efflux of calcium was measured using erythrocytes loaded with calcium ionophore A23187. Calcium efflux speed was related to intracellular calcium concentration and the efflux reached a plateau at about 1 mM. There was no significant difference in calcium efflux rate as a function of intracellular calcium concentration between DMD and control.

Myofibrillar protein catabolism in rat steroid myopathy measured by 3-methylhistidine excretion in the urine

The fractional rate of breakdown of myofibrillar protein in rat skeletal muscle was measured during subcutaneous cortisone acetate treatment (10 mg/100 g body weight per day). The daily urinary excretion of 3-methylhistidine divided by the 3-methylhistidine pool of the skeletal muscle was used to determine the fractional breakdown rate of myofibrillar protein. The mean fractional breakdown rate remained within the normal range throughout the first 5 days, but decreased significantly from the 16th day of treatment. When the daily 3-methylhistidine excretion was divided by the creatinine excretion, the rate showed the same trend of change. These results strongly suggest that the loss of myofibrillar protein induced by cortisone administration is not caused by increased breakdown but by decreased synthesis.

Studies of protease inhibitors in the sera of patients with amyotrophic lateral sclerosis

Serum levels of 4 protease inhibitors, alpha-1-antitrypsin, C1-inactivator, alpha-2-macroglobulin and antithrombin-III were measured in 11 patients with amyotrophic lateral sclerosis (6 males and 5 females) and a control group without neurologic disease. Our results indicated no significant differences in the level of serum alpha-2-macroglobulin between the 2 groups. We found slight but significantly lower levels of serum antithrombin-III in ALS. The possibility of the participation of proteases or protease inhibitors in the pathogenesis of ALS is discussed.

Bleeding Manifestations in 24 Patients with Familial Amyloidotic Polyneuropathy

Focal or generalized hemorrhage is a commonly encountered complication in patients with many kinds of amyloidosis. We studied 24 patients (18 males, 6 females) with familial amyloidotic polyneuropathy and found that five had experienced one or more bleeding episodes. In four of these five patients, bleeding occurred in the terminal stage. The incidence of hemorrhage in familial amyloidotic polyneuropathy is lower than that of other types of amyloidosis or that which has been reported in this disease. In our experience clotting abnormalities were rare; clotting factor deficiency appeared not to exist in familial amyloidotic polyneuropathy.

Studies of protease and protease inhibitors in familial amyloidotic polyneuropathy

Serum levels of 6 protease inhibitors, alpha 1-antitrypsin, Cl inactivator, alpha 2-macroglobulin, antithrombin-3, alpha 1-antichymotrypsin and inter-alpha-trypsin inhibitor were measured in patients with familial amyloidotic polyneuropathy (FAP) and a control group without neurologic disease. No significant differences were observed between the 2 groups. The proteolytic effect of brinase, an enzyme from Aspergillus oryzae, on amyloid tissue sections from patients with FAP was also evaluated. Amyloid fibrils were degraded by brinase, while the tissue structure remained fairly intact.

Effect of thyroxine on basal and insulin-stimulated glucose uptake by fast and slow skeletal muscles of rats

1. The sc injection of 1-thyroxine (2 mg/kg bw/day) for 8 days produced a significant decrease of body weight gain in young male Wistar rats. 2. In these hyperthyroid rats there was a significant decrease in the wet weight of the extensor digitorum longus (EDL) and soleus (Sol) muscles as compared with those of control rats. 3. The basal glucose uptake by the EDL and Sol muscles was unchanged in hyperthyroid rats using the wet weight of muscle as a reference. 4. In hyperthyroid rats, the insulin-stimulated uptake of glucose by both the EDL and Sol muscles was significantly decreased. This inhibition was stronger in Sol and there was no insulin stimulation of glucose uptake by Sol.

Regulation of glucose uptake in rat slow and fast skeletal muscles

1. Regulation of glucose uptake was compared between extensor digitorum longus (EDL) and soleus (Sol) muscles in rats. 2. Insulin stimulated glucose uptake more in EDL than in Sol. 3. Under high concentrations of insulin, the glucose uptake was higher in EDL than Sol. 4. Inhibition of oxidative phosphorylation by anoxia or an uncoupler stimulated glucose uptake more in EDL than in Sol. 5. Anoxia abolished the effect of insulin on glucose uptake in both EDL and Sol. 6. The blocker to glucose transport system reduced glucose uptake more in Sol than in EDL.

In vitro degradation of amyloid material by four proteases in tissue of a patient with familial amyloidotic polyneuropathy

The effects of 4 proteolytic enzymes, alpha-chymotrypsin, bromeline, collagenase, and lysozyme on amyloid tissue sections from a patient with familial amyloidotic polyneuropathy (FAP) were evaluated. Degradation of amyloid fibrils was significant with alpha-chymotrypsin, moderate with bromeline and collagenase, and slight with lysozyme. All of these proteases except collagenase are used as oral mucolytics in humans. The possibility of their clinical usefulness in the treatment or prevention of the development of FAP is discussed.

Prealbumin and Immunoglobulin in Serum and Cerebrospinal Fluid in Familial Amyloid Polyneuropathy

Prealbumin, immunoglobulin G, A, and M concentrations in serum and cerebrospinal fluid from patients with familial amyloid polyneuropathy (Japanese type) were determined and compared with those of asymptomatic relatives or controls. Prealbumin concentrations were not significantly different between them. Using polyacrylamide disc-gel electrophoresis, no qualitative difference in the serum prealbumin was found between them. Among the serum immunoglobulins, only the immunoglobulin A concentration was significantly elevated in the patients as compared with asymptomatic relatives.