Phospholipid metabolism of dog liver under hypoxic conditions induced by ligation of the hepatic artery.

Ischemic hypoxic liver was induced in dogs by ligation of the hepatic artery. About 67% of the dogs died of liver necrosis within 1 or 2 days (severe cases), and the rest survived (mild cases). In the severe cases, the decreases in the contents of total lipids, phospholipids and proteins of the liver after 24 h were 24, 46 and 12%, respectively, of the original values. The marked decrease in phospholipids was due to decreases in the microsomal and mitochondrial fractions. In the mild cases, similar but smaller decreases occurred and decrease of phospholipids occurred only in the microsomal fraction. The main phospholipids were choline and ethanolamine glycerophospholipids, and their molecular species were analyzed. In the severe cases, ligation resulted in relative increases in mono- and diene species and a decrease in polyene species. No increase in phospholipase activity was found at various times after ligation of the hepatic artery. Penicillin-treated dogs all survived and showed little decrease in liver phospholipids.

Changes in mitochondrial phosphorylative activity and adenylate energy charge of regenerating rabbit liver.

The changes in the cellular concentrations of ATP, ADP, and AMP and in oxidative phosphorylation of mitochondria were investigated in the remaining liver of partially hepatectomized rabbits. The energy charge (defined as half of the average number of anhydride-bonded phosphate groups per adenosine moiety) of the liver remnant decreased from 0.866 to 0.767 (p less than 0.01) within 24 hr after hepatectomy, and then increased to a substantially higher level than normal within 7 days. On the other hand, the mitochondrial phosphyorylative activity increased rapidly to 170 per cent of the control within 12 hr and then retruned to normal within 7 days. The mitochondrial phosphorylative activity was inversely correlated with energy charge of the liver remnant (r = -0.75, p less less than 0.01). The maximal enhancement of mitochondrial phosphorylative activity was found in mitochondria obtained from the liver remnant with the lowest level of energy charge, suggesting a response of mitochondria in vivo involving enhanced biosynthetic ATP-utilizing reactions at an early stage of the regenerating process. The enhancement of phosphorylative activity was accompanied by a rise in the respiratory control ratio, P/O ratio and state 3 respiration. The adenylate kinase [EC 2.7.4.3] activity in the liver remnant increased to more than 160% of the control within 2 days after partial hepatectomy, while the pyruvate kinase [EC 2.7.1.40] activity decreased remarkably. However, the changes in the two enzyme activities did not correlate with those of mitochondrial phosphorylative activity or the energy charge of the liver remnant.

Cortical activation with sound stimulation in cochlear implant users demonstrated by positron emission tomography.

Six postlingually deaf patients using multi-channel cochlear implants were examined by positron emission tomography (PET) using 15O-labeled water. Changes in regional cerebral blood flow (rCBF) were measured during different sound stimuli. The stimulation paradigms employed consisted of two sets of three different conditions; (1) no sound stimulation with the speech processor of the cochlear implant system switched off, (2) hearing white noise and (3) hearing sequential Japanese sentences. In the primary auditory area, the mean rCBF increase during noise stimulation was significantly greater on the side contralateral to the implant than on the ipsilateral side. Speech stimulation caused significantly greater rCBF increase compared with noise stimulation in the left immediate auditory association area (P < 0.01), the bilateral auditory association areas (P < 0.01), the posterior part of the bilateral inferior frontal gyri; the Broca's area (P < 0.01) and its right hemisphere homologue (P < 0.05). Activation of cortices related to verbal and non-verbal sound recognition was clearly demonstrated in the current subjects probably because complete silence was attained in the control condition.

Changes of upper gastrointestinal blood flow after hemorrhage in rabbits.

The effect of hemorrhage and blood transfusion on the regional blood flow of the upper gastrointestinal tract was measured with radioactive microspheres in a rabbit shock model. Fifteen minutes after hemorrhage, mucosal blood flow in the esophagus, corpus, and antrum and total blood flow in the duodenum decreased drastically. The persistent reduction of mucosal blood flow continued until 60 minutes after hemorrhage. In spite of these distribution patterns of mucosal blood flow during hemorrhage, no macroscopic change was seen in any part of the gastrointestinal mucosa. One hour after blood reinfusion, the mucosal blood flow in the corpus was increased markedly, and innumerable hemorrhagic erosions appeared in this region. It may be that the striking increase of mucosal blood flow due to blood transfusion caused bleeding from the disrupted mucosa of the corpus. At this time the impaired flow in the esophagus, antrum, and duodenum tended to be improved already. Six hours after blood reinfusion, the bleeding from the mucosal foci in the corpus ceased and the mucosal blood flow returned to almost normal. Thus the higher susceptibility of the corpus to hemorrhagic shock may be due to the greater degree of rapid increase of mucosal blood flow occurring in this portion alone after blood transfusion as well as to its higher vulnerability to ischemia in the hemorrhagic period. The flow patterns in the muscular layer almost paralleled those in the mucosal layer during hemorrhage and blood transfusion.

Influence of unilateral deafness on auditory evoked magnetic field.

To investigate the effect of unilateral deafness on central auditory mechanisms, we examined patients with unilateral deafness of various durations. Auditory evoked magnetic fields (AEF) were recorded using a whole-head neuromagnetometer. In patients who had unilateral deafness for more than 3 weeks, the average N100m latency in the ipsilateral hemisphere did not differ from that in the contralateral hemisphere. In addition, in some patients with congenital or early onset deafness, the equivalent current dipole (ECD) moment was larger in the ipsilateral hemisphere than in the contralateral hemisphere. These findings suggest that unilateral deafness may cause reorganization of the central auditory pathway. They also suggest that central auditory pathway in adults has some plasticity, though not as much as in childhood.

Cortical speech processing mechanisms while vocalizing visually presented languages.

To elucidate cortical processing during vocalization, we used positron emission tomography to measure regional cerebral blood flow during vocalization in six Japanese subjects. During reading Japanese sentences used daily or short syllables aloud, the visual cortices, the left Heschl's gyrus, Broca's area, the primary motor area of the articulatory organs, the supplementary motor area and the cerebellum were significantly activated, compared with resting conditions. The superior temporal gyri were rarely activated. Significant activation of the cerebellum was observed by comparing cortical activity during reading sentences used daily with that during reading meaningless short syllables. These results suggest that vocalization of familiar materials is taken over by the cerebellum, rather than cortical speech areas, and without engagement of the superior temporal gyri.

Cortical processing mechanism for vocalization with auditory verbal feedback.

To investigate the relationship between motor and sensory speech center, cortical activity was examined using PET while normal subjects perceived their own voice which sounded different to the articulated one. The results showed significant activation in the superior temporal gyri with absence of activity in the supplementary motor area (SMA). In a previous study we found significant activation in SMA with no activity in the superior temporal gyrus when normal subjects simply vocalized. Thus, two different cortical pathways for vocalization were delineated: programmed pathway in SMA, and pathway with auditory verbal feedback. The former is thought to be the mature system in the adult, and the latter may be related to speech acquisition.

The role of the temporal coding system in the auditory cortex on speech recognition.

To elucidate the temporal coding system for speech recognition, we synthesized stimulation sounds which do not contain formant information but do contain temporal information by transforming original sound wave to click sequences. Using this stimulation sound, we performed a recognition test and used PET to examine the cortical activities in normal subjects listening to this sound. The results of the recognition test showed a good perception of the sounds made from sequential speech. The PET study demonstrated significant activation of the superior temporal gyri while listening to the stimulation speech sounds. Our results imply that these stimulation sounds were processed semantically in the auditory cortices. The temporal processing system is thought to make an important contribution to speech recognition.

Topographic study of the feline trigeminal ganglion via the horseradish peroxidase tracer method.

The somatotopic organization of the trigeminal ganglion was investigated in felines using the horseradish peroxidase (HRP) tracer method. Results were as follows. The cell bodies which send axons to the ophthalmic, maxillary and manidibular nerves were located in the anteromedial, middle and posterolateral portions of the ipsilateral trigeminal ganglion, respectively. Overlap was found, especially in the maxillary and mandibular areas.

A direct method for the estimation of ornithine carbamoyltransferase activity in serum.

Ornithine carbamoyltransferase (EC 2.1.3.3) activity was estimated by determining the amount of citrulline produced. The citrulline was colorimetrically measured by using a diacetylmonoxime-thiosemicarbazide reaction without deproteinization. The color complex which had the maximum absorbance at 515 nm was stable at room temperature in daylight for at least several hours. The proposed method was superior to other methods already reported in sensitivity, stability and simplicity.

Adaptive increase of respiratory enzymes in jaundiced patients.

A biochemical analysis of mitochondrial metabolism was made on biopsy specimens of fifteen jaundiced patients. In all but three jaundiced patients the phosphorylative activity based on mitochondrial protein was within normal limits or higher. In nine jaundiced patients the concentrations of cytochrome a(+a3), as representative of respiratory enzymes, increased to more than 1.0 x 10(-10) moles/mg protein, as compared with 0.81 of normal mitochondria, and the relative concentrations of cytochromes, flavoproteins and pyridine nucleotides in relation to cytochrome a(+a3) level remained unchanged. In such patients the phosphorylative activity per unit of cytochrome a(+a3) decreased to approximately 50 per cent of controls, whereas it was within normal limits or greater in jaundiced patients with cytochrome a(+a3) less than 1.0 x 10(-10) moles/mg protein. It is suggested that respiratory enzyme concentrations increase to compensate for the inhibited phosphorylative activity of respiratory assemblies and to maintain the energy balance in the liver in jaundiced patients.

Changes after major resection of experimental cirrhotic liver.

Liver cirrhosis was induced experimentally in dogs--hemodynamically, by constriction of the hepatic vein and pharmacologically, by administration of dimethylinitrosamine (DMNA)--after which approximately 45 per cent of the liver was resected. Results indicate that death after major resection of a cirrhotic liver was caused not only by too extensive a resection but also by the rapid progression of cirrhotic changes in the remnant liver during the postoperative course.

Glucose intolerance after massive liver resection in man and other mammals.

The relationship between changes in glucose tolerance and in mitochondrial phosphorylative activity was studied after massive liver resection. In rabbits twenty-four hours after hepatectomy, when the phosphorylative activity in the mitochondria of the remnant liver was enhanced maximally, the blood glucose level did not increase significantly after glucose administration. Forty-eight hours after hepatectomy, when the phosphorylative activity decreased to a submaximal level, the blood glucose level increased gradually but without a return toward normal. About six weeks after partial hepatectomy, mitochondrial function returned gradually to normal levels and the glucose tolerance test results returned to within normal limits. Considering the previous report that an enhancement of mitochondrial phosphorylative activity is required for a later increase in nuclear DNA synthesis, it was suggested that the plateau pattern, with hypoglycemia, and the gradual increase, with a prolonged return toward normal, in the glucose tolerance test are indicative or marked enhancement of mitochondrial phosphorylative activity preceding an increase in nuclear DNA synthesis. The changes in the glucose tolerance test results in hepatectomized rabbits also were observed in rats and in man; however, they were more rapid in rats and slower in man. From these results it was suggested that the glucose tolerance test is very useful in the evaluation of the stage of regeneration in the liver remnant after massive liver resection.

Clinicopathologic classification of congenital cystic dilatation of the common bile duct.

From 1970 to 1975, 103 patients with a localized dilatation of the biliary passages were treated at the First Department of Surgery of Kyoto University Medical Center. Of the 103, 101 had congenital cystic dilatation of the common bile duct (Alonso-Lej type I). These dilatations were classified into two sub-types, "infant type" and "adult type," based on the anatomic location and clinical features. Infant type cyst was typically large cyst of the choledochus and most common in infancy and childhood. Adult type cyst was fusiform dilatation of the biliary tract, and most common in adults. Gallstones were seen in most of the patients with this type cyst.

Congenital cystic dilatation of the common bile duct as a cause of primary bile duct stone.

Of the 101 patients with congenital cystic dilatation of the common bile duct, eighty-eight with adult-type cysts are reported on. The association of primary bile duct stone and adult-type cyst of this anomaly is discussed and found to be higher than previously recognized. In the cases without calculi, abnormal arrangement of the pancreaticobiliary ductal system is indicated to play an important role in the manifestation of the symptom. The anatomic and clinical features and the results of treatment for this type of cyst are reviewed.

Significance of glucose tolerance as prognostic sign in hepatectomized patients.

Glucose tolerance was determined in fourteen patients with cancer of the liver. The patients with parabolic GTT patterns fared relatively better than did those with linear GTT patterns. In the patients with successful extended right hepatectomy, gradually increasing and long-standing hyperglycemia (linear GTT pattern) in response to an oral glucose load was not observed after hepatectomy and the insulin response was significantly greater than that in controls. However, in the patient with unsuccessful extended right hepatectomy, the linear GTT pattern continued for a more prolonged period after hepatectomy.

Changes in carbohydrate metabolism and endocrine function of remnant pancreas after major pancreatic resection.

Changes of glucose tolerance after partial pancreatectomy were divided into three types depending on the extent of resection. When 88 per cent or more of the pancreas was resected, hyperglycemia developed immediately, and when 70 to 88 per cent of the pancreas was resected, diabetes occurred after six weeks or more, but diabetes did not develop at all when less than 70 per cent of the pancreas was removed. The secretion of glucagon was maintained well, but that of insulin was easily impaired after resection of 70 per cent or more of the entire pancreas.

Ligation of a branch of the portal vein for carcinoma of the liver.

Portal branch ligation, a new surgical treatment for unresectable carcinoma of the liver, was performed in twenty patients. All the patients tolerated the procedure, and morbidity and mortality were minimal, even in patients in poor general condition. The responses to ligation differed considerably, but significant palliation was attained in some patients and one survived six years. The effect of portal branch ligation on the tumor appears to be closely related to the degree of tumor vascularity, tumor malignancy, and portal circulatory disturbances such as cirrhosis, portal hypertension, or portal thrombosis. We believe that the present procedure can be recommended for clinical application in some patients with unresectable carcinoma of the liver.

Evaluation of hepatoma chemotherapy by alpha-fetoprotein determination.

Effects of chemotherapy on twenty-nine histologically proved and alpha-fetoprotein (AFP) -positive hepatomas were evaluated by changes in serum AFP levels according to the criteria of our previous report. By transfemoral local infusion of mitomycin C, six of eight patients showed more than 50 per cent decrease of AFP levels and regression of the tumor, and the others showed fair effects. By single shot infusion, 50 per cent decrease of serum AFP levels and tumor regression were noted only in three of thirteen patients, and chemotherapy by systemic infusion in eight patients was much less effective. As evaluated by AFP levels, histologically well or moderately differentiated hepatocellular carcinomas responded better to chemotherapy than poorly differentiated ones.

Effect of vestibular nerve section on cytochrome oxidase activity in the vestibular ganglion cells of the squirrel monkey.

Cytochrome oxidase (CO) activity of the vestibular ganglion cells of the squirrel monkey was demonstrated histochemically under normal and experimental conditions. Under general anesthesia, right vestibular nerve section was performed on adult squirrel monkeys between the vestibular ganglion and brain stem. The left side was left intact and was used as a within-animal normal control. One squirrel monkey that did not undergo vestibular nerve section was also included in the normal group. Following a survival period of seven months, neurons in the vestibular ganglion of both sides were examined. In the normal control sides, a significant negative correlation between the size of the neuron and its optical density for CO stain was observed. Many neurons in the vestibular ganglion survived after vestibular nerve section, but their cell sizes and optical densities of CO stain decreased compared with those of the control side.