Motoshige Kudo

Partial restoration of cerebral myelination of the congenitally hypothyroid mouse by parenteral or breast milk administration of thyroxine.

Abstract: We attempted to define whether thyroid hormone can ameliorate the cerebral hypomyelination present in the congenitally hypothyroid (hyt) neonatal mouse, and to define the critical time period during early postnatal life when thyroxine (T4) is essential for myelin formation. We administered T4) to the hyt mouse by breast milk during the first 20 days of postnatal life, and through the diet during the second 20 days of postnatal life. Positive results were obtained only when hormone was given during the first 20 days of postnatal life. A distinct increase in cerebral 2′,3′‐cyclic nucleotide 3′‐phosphohy drolase activity was noted, and brain sections stained for myelin basic protein correlated with the biochemical findings. The later administration of hormone through diet was ineffective.

Immunohistochemical demonstration of tissue kallikrein in the neurons of rat brain

The distribution of tissue kallikrein (EC.3.4.21.35) in the rat brain was investigated by an enzyme-linked immunosorbent assay (ELISA) and immunohistochemical technique using antiserum against rat urinary kallikrein. More than 75% of the total amount of kallikrein in the extracts of the cerebral cortex and brain stem was determined by the ELISA to be in the form of prokallikrein, suggesting that the greater part of the enzyme exists in the form of pro-enzyme in the central nervous system. Furthermore, immunohistochemical examination revealed that, although the kallikrein-positive cells were widespread and scattered in the brain, the immunoreactive substances preferentially locate in the neuronal cell bodies and their processes in both the cerebral cortex and brainstem.

Retarded growth of the suprachiasmatic nucleus and pineal body in dw and lit dwarf mice

The suprachiasmatic nucleus (SCN) and the pineal body in 3 types of inherited hormone-deficient mice, the dw, lit and hyt mice were examined by morphological, morphometric and biochemical techniques. In the dw and lit mice the SCN was underdeveloped. In the ventral part of the SCN, where most of the retinal fibers appeared to terminate, both cell number and cell size were decreased, although the size of the SCN was unaltered. In addition, the pineal bodies of both mice were morphologically underdeveloped and showed low levels of N-acetyltransferase activity. In contrast, the hyt SCN was comparable to the normal controls in every respect. The hyt pineal was well developed and showed levels of enzyme activity comparable to the controls. However, in all the deficient mice, the optic nerve appeared to be normal in morphological and biochemical studies. These results suggest that the underdevelopment of the pineal body, the reduced levels of spontaneous locomotion and the indistinct diurnal periodicity of the dw and lit mice might be related to the retarded neuronal growth of the SCN, and that growth hormone likely is indispensable for the development of the SCN.

Ganglioglial Differentiation in Medulloblastoma

A case of cerebellar medulloblastoma with clusters of mature ganglion cells and glial cells is described. The patient, a 15 ‐year ‐old girl, underwent three operations followed each time by radiation and chemotherapy during the four‐year clinical course. Histologically, the ganglion cells were clearly identifiable by their abundant eosino‐philic cytoplasm, round nuclei with prominent nucleoli, tigroid granules, and argyrophilic fibrils and axons. Im‐munohistochemically, the cells were NSE‐ and NF positive, and ultrastructurally they contained abundant tubules and filaments, neurosecretory granules and well developed rough endoplasmic reticulum. There were many cells transitional in appearance between primitive cells and mature ganglion cells. The tumor also had many mature yet atypical astrocytes and oligodendrocytes. The exact mechanism of the extensive neuronal and glial maturation of medulloblastoma cells is unclear, but the repetitive surgical interventions, radiation and chemotherapy might have had certain cytostatic effects on rapidly dividing medulloblastoma cells, giving them a chance to mature into postmitotic cells with potential for neuronal and glial differentiation. Acta Pathol Jpn 40: 50–56, 1990.

THE NATURE OF “BLUE NEVUS” IN CYSTIC TERATOMAS OF THE OVARY: An Ultrastructural Evidence for Schwann Cell Origin

The ultrastructural findings of two cases of “blue nevus” in ovarian benign cystic teratomas are described. The bipolar or dendritic pigmented cells showed features of Schwann cells with melanin synthesis, but not of ordinary melanocytes. This study supports the neural origin of blue nevus. ACTA PATHOL. JPN. 35: 693–698, 1985.

Suppression of Splenic Natural Killer Cell Activity in Rats with Brain Tumors

After inoculating 9L glioma cells into the brains or into subcutaneous regions of the back of rats, we investigated splenic natural killer (NK) cell activity for 3 weeks using a 4-hour 51Cr release assay. Only rats with brain tumors showed decreased splenic NK cell activity. The spleens of these rats were morphologically small and atrophic. Expansive brain tumors were compressing the basal ganglia, thalamus, and hypothalamus after 2 weeks, and the rats ultimately died of cerebral herniation, usually by 3 weeks after inoculation. The decreased splenic NK cell activity in rats with brain tumors might be the result of neuroimmunomodulation secondary to hypothalamic dysfunction due to increasing tumor compression.

Neuroectodermal Differentiation in “Extraskeletal Ewing's Sarcoma”

A small round cell tumor of soft tissue arising in the retroperitoneum of an 18‐year old woman is reported. The light and electron microscopic features of the tumor were mostly indistinguishable from Ewings sarcoma of the bone and in some parts from differentiating neuroblastoma with mature neurons and Schwann cells. An immunohisto‐chemical study using anti NSE antibody showed many widespread NSE‐positive cells lying singly and, more often, in clusters including the undifferentiated areas. The tumor was not anatomically related to the paravertebral sympathetic ganglia or adrenal glands. The present findings strongly suggest that certain extraskeletal Ewings sarcomas are very primitive neuroectodermal tumors. Acta Pathol Jpn 39: 795‐802, 1989.

Malignant choroid plexus papilloma of the IV ventricle

We report a case of malignant choroid plexus papilloma (MCPP) of the IV ventricle in a child with prominent extraventricular expansive growth, mostly into the cerebellopontine angle. Interestingly enough, the tumor was entirely covered by thin, smooth, membranous, fibrous tissue, probably derived from the pia mater. In addition, hydrocephalus was not observed. The reason for the lack of hydrocephalus remains speculative, but it is possible that the presence of pure, nonexpansive, fibrous covering on the tumor might have suppressed the tumor growth to some extent, resulting in progressively increased intratumoral pressure. This, in turn, caused the suppression of excessive cerebrospinal fluid production by the tumor cells. From the diagnostic standpoint, immunohistochemical studies, using antiepithelial membrane antigen (EMA) and antitissue polypeptide antigen (TPA), were demonstrated to be useful for diagnosing the tumor.

Induction of lymphokine-activated killer cells from rat thymocytes using recombinant human interleukin-2

SummaryUsing a 4-h 51Cr release assay, we observed that thymocytes from Fischer strain rats incubated with recombinant human interleukin-2 (rhIL-2) developed cytotoxicity to YAC-1 lymphoma, 9L-glioma, and B-16 melanoma cells (effector/target ratio =25/1). Induction of the lymphokine-activated killer (LAK) cells was as follows: (1) when 5×106/ml thymocytes were cultured with various concentrations of rhIL-2 (50, 125, 250, 500, or 1,000 units/ml) for 4 days, no cell proliferation was observed at any concentration. However, the LAK cells showed significant cytotoxicity toward all tumor cells at more than 50 units/ml. (2) When 5×106/ml thymocytes were cultured for 1 to 6 days with 250 units/ml of rhIL-2, the harvested cell count decreased markedly after the 2nd day. The cytotoxicity of all the tumor cells became significant after the 2nd day, with peak activity on the 4th day. In rat splenocytes, on the other hand, the LAK cells could not be identified because rat splenocytes developed nonspecific cytotoxicity in medium containing fetal calf serum without adding rhIL-2.

Confronting cisternae in pituitary gland thyrotrophs of congenitally hypothyroid mice

SummaryConfronting cisternae were found in pituitary thyrotrophs of congenitally hypothyroid mice. These confronting cisternae rapidly reverted back to ordinary rough endoplasmic reticulum following thyroxine administration. Confronting cisternae were not observed in the thyrotrophs of euthyroid control mice. Our results strongly suggest that confronting cisternae are a peculiar form of rough endoplasmic reticulum which appears under certain conditions of enhanced cellular metabolism.