Tomoichi Kusunoki

Fatty liver and its fibrous changes found in simple obesity of children.

Of 299 obese children who visited our obesity clinics, 36 were found to have elevated levels of serum transaminases by routine laboratory examination. Liver biopsy was carried out in 11 children. Based on the criteria of Adler and Schaffner (1979), the biopsy specimens were studied histologically. As a result, fatty liver (Group I) was observed in three patients, fatty hepatitis (Group II) in two, fatty fibrosis (Group III) in five, and fatty cirrhosis (Group IV) in one. The duration of obesity, but not its degree, was considered to be related to the extent of fibrosis. Accordingly, we concluded that the fatty liver of simple obesity in children may progress to liver cirrhosis and that childhood obesity should be treated as early as possible.

Neuroblastoma. Mass screening for early detection and its prognosis.

Since July 1973, the authors began developing a mass screening system using a VMA (vanilmandelic acid) spot test on 6‐to‐7 month‐old infants for early detection of neuroblastoma in Kyoto city, Japan. Using this method, six infants with this tumor were discovered; five of the six infants were cured, and one is under treatment. These patients showed a favorable prognosis on early diagnosis. in this article, 57 neuroblastoma patients from the Department of Pediatrics, Kyoto Prefectural University of Medicine, treated during the last 20 years, from July 1962 to June 1982, are evaluated. Since the mass screening program has run smoothly since July 1974, clinical findings are compared between 35 neuroblastoma cases before mass screening from the 12‐year period from July 1962 to June 1974 and 22 cases after mass screening, during the 8‐year period from July 1974 to June 1982. Before mass screening, only 20% (7/35) of the patients were discovered with neuroblastoma younger than 12 months of age and 68.6% were older than 2 years of age. After mass screening, 54.6% (12/22) of the patients were younger than 12 months of age and only 31.8% (7/22) were older than 2 years of age. Before mass screening, 17.1% (6/35) survived with five of the six surviving patients being younger than 12 months of age at the time of diagnosis; 72.7% (16/22) of the patients detected after mass screening are living now. Eleven of the 16 patients have already been cured, and the remaining 5 patients are presently undergoing treatment. A marked improvement of their prognoses is dependent on the early detection of this tumor by mass screening. To date, using the VMA spot test for early detection in infancy is convenient and effective for improvement of its prognosis.

Multicystic encephalomalacia in liveborn twin with a stillborn macerated co-twin

Computed tomography showed multiple cystic lesions in the brains of three infants with cerebral palsy. Each patient was the product of a twin pregnancy with a stillborn, macerated co-twin. In two patients angiography was performed and suggested that the cystic lesions were multicystic encephalomalacia due to perinatal arterial occlusion.

Hypothalamic lesion induced by injection of monosodium glutamate in suckling period and subsequent development of obesity

Abstract The relationship between the hypothalamic lesion, which was induced by injecting monosodium glutamate (MSG) in a suckling mouse, and subsequent growth of the mouse was studied. Hypothalamic lesions were localized mainly in the preoptic region and a region surrounding the median eminence. The severity and extent of these lesions varied according to the time of MSG injection. When 2 mgMSG/g body weight was given subcutaneously to mice successively from 1 to 5 days of age (group 1), the hypothalamic lesions included not only the preoptic and arcuate nuclei but also two-thirds of the ventromedial nucleus and a part of some other nuclei. Whereas in the mice in group 2, which had five successive injections of 2 mg/g MSG from 6 to 10 days of age, the hypothalamic lesion was milder than that in group 1 and the ventromedial nucleus was spared. When the difference of body weight gain of the mice was evaluated by a ratio of weight: length, 92% of the mice in group 1 developed overt obesity at 15 weeks of age, whereas only 22% of mice in group 2 and 3% of the control mice developed overt obesity. It is suggested that the development of overt obesity in mice treated with MSG is intimately related to damage in the ventromedial nucleus in addition to that in the arcuate nucleus.

Maturation of Purkinje cells in mouse cerebellum after neonatal administrations of cytosine arabinoside

SummaryICR-JCL strain mice were injected subcutaneously with 30 mg/kg body weight of cytosine arabinoside at 2, 3, and 4 days of age. This chemical prevented the production of the basket cells, stellate cells, and granule cells in the external granular layer of the cerebellum. Decrease in number of these microneurons affected the normal synaptic connections between the Purkinje cells and the microneurons, thus causing the disarrangement and abnormal arborization of the Purkinje cells. Of the three types of microneurons, the basket and a few stellate cells played a more important role in the disarrangement of the Purkinje cells and abnormal arborization of their primary dendrites than the granule cells did. Abnormal outgrowing directions of other smooth dendrites of the Purkinje cells were caused mainly by the diminution of stellate cells. Although parallel fibers were grossly decreased in number in the treated cerebellums, spines of the spiny dendrites of the Purkinje cells sprouted considerably in the 15-day-old mice, and then their morphological features remained even after 100 days of age.

Plasma levels of carcinoembryonic antigen in patients with ataxia-telangiectasia

platelet destruction can be shown in almost all patients with ITP? Plasmapheresis may remove antibodies and allow for increased survival of both transfused and autologous platelets. The marked rise in platelet count and the absence of plasma antiplatelet antibodies following plasmapheresis in this patient indicate the potential effectiveness of this procedure. The decrease in platelet count eight hours after ptasmapheresis suggests that repeated procedures might be needed to maintain adequate levels of platelets. These observations suggest that plasmapheresis could be of value in the management of complications of ITP. It is effective in temporarily improving platelet levels and is possibly an aid in avoiding emergency splenectomy during a hemorrhagic crisis. In an emergency where steroids and splenectomy have failed, repeated plasmapheresis might be used to support platelet counts for several days while waiting for immunosuppressive agents to be effective. We suggest that further use of this procedure be considered in pediatric patients with complicated ITP.

Effect of Maternal Malnutrition on Matrix Cell Proliferation in the Cerebrum of Mouse Embryo: an Autoradiographic Study

Summary: Thirty pregnant mice were undernourished by providing low protein diets (PM) or providing approximately one-third their normal diets (PCM) for 9 days from the 8th to the 16th day of gestation. Another 15 pregnant mice, which were fed a normal diet, served as the control. On the 16th day of gestation, all animals were injected with a single dose of [3H]thymidine and were killed one by one at 1− or 2-hr intervals.Mean litter size was statistically insignificant between the control group and two malnourished groups. There was, however, a significant difference in mean body weight between the control group and two malnourished groups (P < 0.005). The cerebral cortex at this stage of development consisted of three different layers, i.e., the cortical plate, the migratory zone, and the matrix layer. The width of the cortical plate of the malnourished embryos was significantly smaller (P < 0.001). There was, however, no significant difference in width of the migratory zone between the control and the malnourished groups. The width of the matrix layer in PM was significantly smaller (P < 0.001), but that of PCM showed no significant difference from the control (P > 0.1).Coronal section of the brains of the embryos were processed for autoradiography. Labeled cells were found almost exclusively at the matrix layer surrounding the lateral ventricels. Labeling index counted in the matrix layer after 1 or 2 hr of [3H]thymidine injection indicated that more than 30% of the cells in this layer were always synthesizing DNA in each group of embryos. The generation times of the matrix cell, precursor of the neurons, in the matrix layer were approximately 18.5 hr in the control and 21.5 hr and 21.8 hr in the malnourished embryos, thus indicating about 3 hr of prolongation in the latter. DNA synthetic time was about 6.5 hr in the control and 7.0 hr and 7.0 hr in the two malnourished groups. The postduplication time was about 2.5 hr in the control and 3.0 hr and 3.5 hr in the malnourished. The preduplication time was about 8.8 hr in the control and 10.6 hr and 10.3 hr in the malnourished.Speculation: Most neurons in the mouse cerebrum are produced at the matrix layer, where active cellular proliferation takes place from the 10th to the 16th days of gestation. Malnutrition during this period caused about 14% prolongation of the generation time of the matrix cell, the precursor of neurons, thus causing a decrease in neuron production. Malnutrition during the first and second trimester may cause similar results in the human embryo.

Cyclic AMP in neuroblastoma, ganglioneuroma and sympathetic ganglia

Tissue content of cyclic AMP was as much as 10 times greater in ganglioneuroma than in neuroblastoma. This high cyclic AMP in ganglioneuroma was not significantly different from that of sympathetic ganglia.

New model of hemorrhagic hypoxic-ischemic encephalopathy in newborn mice

An easy and inexpensive method is reported for producing hemorrhagic brain damage in newborn mice, involving only exposure to hypoxia. One-day-old mice, Jcl:ICR strain, were subjected to a humidified 5% oxygen, 95% nitrogen mixture for 8 hours. After the hypoxic episode, 34% of newborn mice survived, 59% manifested cerebral parenchymal hemorrhage. Cortical hemorrhage could be detected in live mice; intracranial hemorrhage was observed through the thin skin and skull. Cortical hemorrhage usually affected the bilateral parietal regions symmetrically and neuronal destruction was observed in the deeper structures, as well as in the cerebral cortex. This pattern of damage was comparable to parasagittal cerebral injury in humans. The onset of cortical hemorrhage and neuropathology in these mice suggested that hemorrhage occurred when cerebral blood flow recovered after the hypoxic event.

Deficiency of glucose-6-phosphate dehydrogenase found in a case of hepatic fructose-1,6-diphosphatase deficiency.

Summary: The first case of fructose-1,6-diphosphatase (FDPase) deficiency in Japan showed a decreased activity of glucose-6-phos-phate dehydrogenase (G6PD) in the liver, white, and red blood cells. In the enzymatic study of G6PD which was partially purified from red cells, the following characteristics were observed in the enzyme of the patient. 1) The G6PD activity of the patient was reduced to 17% of normal, but no evidence of a hemolytic episode was found in his past and family history. 2) In the investigation of G6PD of the patient, no abnormalities were observed in its enzymatic parameters such as electrophoretic mobility, Km for G6P and NADP, Ki for NADPH, the utilization of 2-deoxy G6P and deamino NADP, heat-stability, and pH curves. 3) The dissociation constants of red blood cell G6PD for NADP and NADPH, which were obtained from the investigations on the reactivation of cold-inactivated G6PD at 37°C, were about 3 times higher in the patient as compared to the values of the normal controls.Based on these findings, it might be concluded that the G6PD deficiency found in the red blood cells of this case of a FDPase deficiency is a unique variant, which could not be characterized by using only the method recommended by a World Health Organization (WHO) scientific group. Considering that the abnormality observed in the G6PD of this patient was a decrease hi the affinity of the enzyme for its coenzymes, the dissociation constants for the coenzymes in reactivation process might be another important kinetic parameter in characterizing the G6PD deficiency.Speculation: The red cell G6PD of a case of FDPase deficiency showed a decreased enzymatic activity and a lowered affinity for its coenzymes in reactivation process. Although it is strongly suggested that these two rare enzyme deficiencies take place in an individual coincidentally, a possible relationship of the two enzyme deficiencies should be considered. Further studies on these enzyme deficiencies now appear necessary to learn more about this association.