Teruo Iwamasa

An ultrastructural study of chronic cadmium chloride-induced neuropathy.

SummaryAfter the long-term exposure to cadmium chloride in drinking water, the Wistar rats developed peripheral polyneuropathy. The main lesion was of myelin degeneration. Ultrastructural examination of the roots and sciatic nerves revealed segmental demyelination beginning from the node of Ranvier. There was the active autophagocytosis of Schwann cells which contained a number of myelin remmants and dense bodies. There was, on the other hand, the evidence of remyclination with toxic damage, in which the thinner myelin sheaths and abnormal myelinations were observed with increase of Schwann cells containing rich ribosomes. Axoplasmic changes were minimal, but consisted of accumulation of glycogen particles which very often produced glycogenosomes in characteristic appearance with axoplasmal dysfunction.

Two cases of necrotizing myelopathy associated with malignancy caused by herpes simplex virus type 2

SummaryTwo cases of necrotizing myelopathy were autopsied; one was complicated with lung carcinoma and the other with chronic type adult T cell leukemia (ATL leukemia). To our knowledge, they were the first cases of their type in Japan. In both cases, necrosis of the spinal cord was observed in the gray and white matter along most of its extent. Marked changes were found in the lumbar segment. The patients were not treated with intravenous cancer chemotherapy or irradiation. Immunohistochemical and electron microscopic examination revealed an extremely strong infection of herpes simplex virus (HSV) type 2. However, HSV type 1 and cytomegalovirus antigens were not detected.

Demonstration of acid α-glucosidase in different types of Pompe disease by use of an immunochemical method

The nature of mutant acid alpha-glucosidase (AAG) in muscle was studied in 6 patients with Pompe disease, consisting of 2 each of the infantile, childhood and adult types. Anti-human liver AAG rabbit antibody prepared in the present study was confirmed to be monospecific by immunodiffusion, immunotitration and immunohistochemical methods. It was found by the immunodiffusion and enzyme immunoassay methods using this antibody that the mutation produced a normal amount of enzyme protein but the latter was an inactive form, suggesting structural gene mutation in 5 of the 6 cases. In the remaining childhood type case there was no detectable amount of enzyme protein, suggesting that the mutation causes a reduction in the amount of the enzyme protein or synthesis of unstable enzyme protein. Similarly, the enzyme activity of AAG was markedly reduced in all patients, but that of neutral alpha-glucosidase was the least reduced in the adult type, medium in the childhood type, and the most reduced in the infantile type.

Physicochemical and Ultrastructural Studies on Glycogenosomes in Newborn Rat Hepatocytes

In the newborn rat liver, glycogenosomes appeared at about 6 hours after birth and gradually increased in number, despite high activity of lysosomal acid alpha-glucosidase. The glycogenosomes then disappeared completely with 2 days after birth. Glycogen extracted from fetal rat liver differed in molecular structure from that of adult rat liver. In measurements of optical rotatory dispersion (ORD) and circular dichroism (CD) absorption spectra, fetal-type glycogen showed the Cotton effect whereas the adult rat liver glycogen did not. The degree of branching and S-values of the two glycogens were also different. With the disappearance of glycogenosomes, fetal-type glycogen disappeared completely, and adult-type glycogen then appeared strongly. This was demonstrated in the intracytoplasmic matrix by electron microscopy. The present experiments indicate that glycogenosomes may be formed even under conditions of high acid alpha-glucosidase, and that autophagy of glycogen macromolecules in the lysosomal system is closely related to different structural features of fetal-type glycogen in the neonatal period.

Glycogen Storage Disease: Studies Related to the Mechanism of Glycogenosome Formation

Glycogen storage diseases of type I, II, III, IV, V and the other muscle types, were examined electron microscopically, biochemically and physicochemically. Glycogenosomes (glycogen containing vacuoles) were found in the affected tissues of type II, type III variant of muscle glycogen storage disease, type IV and muscle type phosphorylase b kinase deficiency (disorder of the phosphorylase b kinase activation mechanism). The acid alpha-glucosidase activity was decreased only in the case of type II glycogen storage disease (Pompes disease). The other types of glycogen storage disease showed no decrease in acid alpha-glucosidase activity. Moreover, one patient with type II disease also revealed a decrease in neutral alpha-glucosidase activity. In all cases where glycogenosomes were found, the extracted glycogen macromolecules showed some molecular abnormality or deviation when compared with normal native glycogen macromolecules.

Ultrastructural and Biochemical Studies of Glycogenosome Formation in Ascites Hepatoma AH 13 Cells

Appreciable numbers of glycogenosomes were found in ascites hepatoma cells. They were lined by a single or sometimes double membranous structure exhibiting weakly positive acid phosphatase activity. Some were closely related to the Golgi apparatus, and a few showed wrapping of glycogen particles. The glycogen extracted from ascites hepatoma AH 13 cells was of two major types: a normal adult liver type, and a muscle type. Only the latter type gave the Cotton effect on measurement of the ORD and CD spectra. Small particulate, muscle type glycogen was observed in the glycogenosomes. Autophagy of normal adult liver type glycogen was never found. The engulfment of muscle type glycogen was accompanied by high acid and neutral alpha-glucosidase activity levels.

Histochemical demonstration of total phosphorylase activity for diagnosis of carcinoma cells in human stomach and intestines.

Modified techniques for the histochemical demonstration of phosphorylase of value in the diagnosis of cancer cells of human gastro-intestinal origin are described. Preservation of the enzyme activity is especially considered; this is facilitated by the use of thoroughly dried cryostat sections. Routine use of these techniques in the clinical laboratory is suggested. Using these procedures, carcinoma cells of human stomach and intestines stained in 102 of 117 cases; normal control sections of human gastric epithelial cells are regularly unstained.

Massive edema of the ovary associated with hydrothorax and ascites

A 29-year-old woman with massive edema of the ovary which was grossly mistaken for neoplasia because it was associated with large volumes of both pleural effusion and ascites is described. The ovarian mass measured 10 X 10 X 8 cm and weighed 850 g. Total hysterectomy and bilateral salpingo-oophorectomy were performed. Microscopically, the ovary consisted of diffusely edematous stroma enveloping nests of hyperplastic theca cells or showing a loose myxomatous contexture. However, no endocrine activity of the ovary was demonstrated on the basis of laboratory endocrine values obtained by radioimmunoassay techniques.

Serial serum determination on α-fetoprotein as a marker of the effect of postoperative chemotherapy in ovarian endodermal sinus tumor

Serial serum determinations of alpha-fetoprotein (alpha FP) as a tumor marker were carried out in the management of six patients with endodermal sinus tumor (EST). Histological examinations in all six patients revealed a typical EST pattern, and in one of them another germ cell tumor, a malignant teratoma, was also found. All patients were treated postoperatively with combination chemotherapy. The serum alpha FP concentrations before treatment, using radioimmunoassay, were abnormally high and ranged from 2500 to 100,000 ng/ml. One patient having Stage Ia neoplasm is living at 50 months after diagnosis with a normal alpha FP concentration and without clinical evidence of recurrence. The other five patients with Stage III disease died from 4 to 9 months after surgery, respectively, although the serum alpha FP in all these cases during chemotherapy decreased markedly but temporarily to a normal level (less than 20 ng/ml) or to 3000 ng/ml and was paralleled by a certain improvement in the conditions of the disease. These results suggest that serial serum determination of alpha FP may be useful as a marker and prognostic indicator of endodermal sinus tumor.

Case report of dysgerminoma in a patient with 46,XX pure gonadal dysgenesis

A clinicopathological study of a 42-year-old female with pure gonadal dysgenesis and dysgerminoma was made. At the age of 29, the patient with primary amenorrhea had been evaluated clinically and cytogenetically. (1) The results of cytogenetic studies were X-chromatin positive and revealed a karyotype in peripheral blood leukocytes of 46,XX. (2) Laboratory studies indicated hypergonadotropic hypogonadism and no response of the gonads to the human menopausal gonadotropin stimulation test. (3) At laparotomy, the gonads were streak-like. Pathological examinations of biopsy specimens from both gonads revealed dense, fibrous connective tissue resembling ovarian stroma and no primary follicles. Eleven years after the laparotomy, the patient complained of lower abdominal distention and severe pain, and laparotomy then revealed a 15 X 17-cm right solid adnexal mass occupying the pelvic cavity. The histological diagnosis of tissues from the partially removed tumor was pure dysgerminoma. Second-look operation after Linac X-ray irradiation showed complete remission of the residual tumor. Insofar as we are aware, the present patient represents the first case of dysgerminoma which occurred in the dysgenetic gonads of a phenotypic female with normal 46,XX sex-chromosomal constitutions in peripheral blood leukocytes and the skin fibroblasts although a possibility exists that mosaicism was possibly present but undetected, particularly since the streak gonads were not analyzed chromosomally.