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This report covers 7-year follow-up studies on 35 HBs Ag carriers whose anti-HBc titer levels were 10 (log 2) or more and who had normal liver functions at the start of the studies, when 9 of them (25.7%) were HBe Ag positive, 24 (68.6%) anti-HBe positive and 2 (5.7%) negative to both. 1. There was no significant difference in the incidence of abnormal SGPT levels as a whole between HBe Ag positives and anti-HBe positives. But abnormally high SGPT levels of 100 KU or more were observed at a higher percentage among HBe Ag positives (4/9. 44.4%) than among anti-HBe positives (1/24. 4.2%. p less than 0.02). 2. Based on the results of the 7-year studies, all cases were classified into six clinical stages. HBe Ag positives were divided into three groups by the stage with different SGPT levels: 5 cases (15.2%) whose SGPT leves never rose above 50 KU were classified as Stage 1; 3 cases with chronic active hepatitis (9.6%) whose highest SGPT levels were over 200 KU (2 new cases and 1 case with a relapse of chronic inactive hepatitis) as Stage 2 and 1 case (3.0%) seroconverted to anti-HBe positive following an acute relapse of chronic inactive hepatitis as Stage 3. Anti-HBe positives were divided into another three groups similarly according to their mean HBs Ag titer levels: 6 cases (18.2%) whose mean HBs Ag titer levels ranged from 10 to 13 (log 2) were classified as Stage 4; 13 cases (39.4%) whose mean HBs Ag titer levels ranged from 6 to 9 as Stage 5 and 5 cases (15.2%), including 2 cases turned negative to HBs Ag, whose mean HBs Ag titer levels were below 5 as Stage 6. The average age of each group increased wth its clinical stage, namely, 32.6 in Stage 1, 34.3 in Stage 2, 33.0 in Stage 3, 34.5 in Stage 4 and 37.0 in Stage 5, but the average age in Stage 6 was 29.0. 3. All HBe Ag positives showed fluctuations in HBs Ag titer levels. The fluctuations were particularly noteworthy among cases with chronic active hepatitis in Stage 2 during an acute relapse. The HBs Ag titers rose just before the acute relapses in a case of chronic active hepatitis when SGPT levels went over 200 KU. This suggested a proliferation of the virus. On the other hand, in anti-HBe positives, a decrement of the virus was suggested by the fact that an increasing proportion of cases showed their HBs Ag titer levels to fluctuate or to become lower with the progress of stages (p less than 0.05) and two cases turned negative to HBs Ag as plotted in Stage 6. And the proportion of cases with abnormal SGPT levels decreased with the progress of stages (p less than 0.05). One case whose SGPT level was 125 KU, highest among anti-HBe positives, followed the clinical course of chronic inactive hepatitis and lowered in HBs Ag titer. 4. Between HBe Ag and anti-HBe cases, there were considerable differences in the occurrence of liver disturbances and their clinical courses...

The glycogenolytic effect of catecholamine has been proposed to be mediated by calcium ions mobilized mainly from mitochondria. In this study, the contribution of mitochondria as a source of the mobilized calcium was evaluated by use of perfused rat livers. Phenylephrine-induced efflux of 45Ca from 45Ca preloaded liver was abrupt and transient, and almost ceased within 5 min. The perfusion with 5 microM phenylephrine for 5 min caused a significant decline in the content of 45Ca retained in the liver homogenate; control, 0.97 +/- 0.11 nmol of 45Ca/mg protein (mean +/- SEM) and phenylephrine, 0.41 +/- 0.08 nmol of 45Ca/mg protein (P less than 0.01), when calculated from the specific radioactivity of calcium in the perfusate used for loading perfusion. The contents of 45Ca in mitochondria isolated subsequently from the homogenate were 0.43 +/- 0.07 nmol/mg protein in controls and 0.22 +/- 0.03 nmol/mg protein (p less than 0.05) when phenylephrine was administered. Taking into consideration that mitochondrial protein is a fraction of homogenate protein, it is obvious that the decline in mitochondrial 45Ca represents only a small portion of the total reduction of radioactivity in the homogenate. In a series of experiments in which various perfusion periods were employed for 45Ca loading and for washing-out, it was found that phenylephrine induced 45Ca efflux also from a pool with a calcium turnover rate slower than that if mitochondria. These results suggest that alpha-adrenergic stimulation enhances release of calcium not only from mitochondria but also from other compartments with a slower turnover rate. The probability of plasma membrane is proposed as the other source of calcium released in response to alpha-adrenergic stimulation.

Verapamil and diltiazem, calcium channel blockers, inhibited significantly the glucagon-induced glucose output and 45Ca efflux from perfused rat liver at concentrations higher than 50 microM when the perfusate contained calcium. Although the blockers partially interfered with glucagon-induced elevation of cyclic AMP in the tissue, they also inhibited the effects of cyclic AMP. The blockers did not show the inhibitory effects in the absence of perfusate calcium. However, the inhibition of calcium influx into hepatocytes by omission of extracellular calcium or addition of EGTA did not interfere with these effects of glucagon and cyclic AMP. In the presence of extracellular calcium, the blockers did not inhibit cyanide-induced glucose output, indicating that the activity of glycogen phosphorylase and later processes leading to glucose output were not affected by the blockers. These data suggest that, in the presence of calcium, the blockers inhibit the effect of glucagon also at a step (or steps) subsequent to cyclic AMP production and before the activation of phosphorylase b, probably by inhibiting glucagon-induced mobilization of calcium from intracellular calcium pools rather than inhibiting calcium influx into hepatocytes.

In an attempt to elucidate the role of Ca2+ flux in the initial events of hepatic glycogenolysis, extracellular Ca2+ concentration was manipulated in rat liver perfused with Ca2+ antagonistic drugs. After the liver had been perfused with a buffer containing verapamil and 1 mM CaCl2, either the addition of ethyleneglycol-bis-(beta-aminoethyl ether)-N,N'-tetraacetic acid to the perfusate or the replacement of the perfusate with Ca2+-free buffer caused a rapid increase in glucose output as well as 45Ca2+ efflux. Substitution of diltiazem, but not 5-20 mM LaCl2, for verapamil also stimulated glucose output and 45Ca2+ efflux. However, when Ca+-free buffer was used throughout the experiment, any modes of verapamil or diltiazem perfusion were without significant effects on glucose output or Ca2+ efflux. The increases in glucose output and 45Ca2+ efflux were not affected by either 20 microM phentolamine or 300 microM ouabain, but they were inhibited significantly by 10-100 microM trifluoperazine. These results indicate that rapid decline in the extracellular Ca2+ concentration in verapamil- or diltiazem-perfused liver initiates the change in Ca2+ equilibrium on or across plasma membrane and activates glycogenolysis through a Ca2+-dependent mechanism.

In an attempt to verify the importance of calcium ions in mediating alpha -adrenergic stimulation, the effects of a calcium channel blocker, verapamil, on phenylephrine-induced glycogenolysis and calcium efflux in perfused livers prepared from fed rats were determined. The blocker inhibited phenylephrine-induced glycogenolysis in a noncompetitive and dose-dependent manner between 50 micro M and 500 micro M. However, it did not affect 2, 4-dinitrophenol-induced glycogenolysis. It had no significant effect on 45 Ca uptake by the perfused liver, but inhibited basal as well as phenylephrine-induced efflux of 45Ca from 45Ca-loaded liver. The inhibitory effects on basal 45Ca release and phenylephrine-induced glycogenolysis and 45Ca released correlated very well. All the the effects of verapamil were reproduced by another calcium channel blocker, diltiazem, suggesting that these effects are common to a variety of calcium channel blockers. These results indicate that the process of calcium influx and the function of phosphorylase per se are not directly involved in the inhibitory action of the blocker. Although it is possible that verapamil interferes with binding of the alpha -adrenergic agonist to the plasma membrane, the good correlation between the inhibitory effects of verapamil on basal 45Ca released and on phenylephrine-induced release of 45Ca suggests another mechanism, involving calcium ions. The blocker appears to inhibit the glycogen phosphorylase activity induced by phenylephrine via a cell-membrane mechanism in which calcium ion flux changes are intimately involved.

Most patients with birth palsy can be expected to recover spontaneously. But in some patients the recovery is unsatisfactory and the functional results are disappointing. One possible way to improve the prognosis for such patients is early surgical nerve reconstruction. In six infants, exploration of the brachial plexus was carried out at about six months after delivery, when there were no signs of recovery in shoulder and elbow joint movements. Preoperative metrizamide myelography, computerized tomography with intrathecal metrizamide (CT myelography), and axon reflex test (histamine test) were followed by intraoperative electrophysiologic examinations of root sensory evoked potential (SEP), nerve action potential (NAP), and evoked muscle response (M-response). Microsurgical nerve repair was performed on the basis of intraoperative diagnosis. Metrizamide myelography showed 13% false-positive root avulsion. Reliability of the histamine test was 80%. The intraoperative electro-diagnosis is essential for understanding the actual condition of the brachial plexus lesion and obtaining better results from microsurgical reconstruction in birth palsy. The surgical results, with an average follow-up evaluation of two years and four months, have been encouraging enough to continue this diagnostic and therapeutic program, though its superiority to natural recovery has not yet been clarified.