Takashi Wakabayashi

Plasma cell granuloma of the stomach. A report of a case associated with gastric cancer

Plasma cell granuloma arose multifocally in the stomach combined with gastric cancer (adenocarcinoma). The immunohistochemical study demonstrated the polyclonal nature of the plasma cells in the former lesion, and confirmed the diagnosis of plasma cell granuloma.

MECHANISM OF THE FORMATION OF MEGAMITOCHONDRIA INDUCED BY COPPER-CHELATING AGENTS

Processes of the formation of cuprizone‐induced megamitochondria in mouse liver have been studied in detail by electron microscopy. The earliest change observed was the presence of large intramitochondrial granules. The next stage was the formation of myelin flgures by which mitochondria were apparently connected. The third stage was characterized by megamitochondria connected with each other by their outer membranes. Continuity of mitochondria were further examined by serial sections, and megamitochondria were proved to be connected to each other far more frequently than expected on one plane of section. A model for the mechanism of megamitochondrial formation is proposed based on electron microscopic evidences, involving the fusion of mitochondrial membranes. Possibillty is also discussed that cuprizone‐induced megamitochondria may fuse to one single branching mitochondrion.

Induction of megamitochondria in the mouse liver by isonicotinic acid derivatives.

Abstract Megamitochondria were induced in mouse hepatocytes simply by feeding the animal for 7 to 10 days with a diet containing isonicotinic acid derivatives, namely, nialamide, isoniazid, and iproniazid. Monoamine oxidase activities of megamitochondria were invariably decreased significantly. Isonicotinic acid, however, did not induce megamitochondria and had no effect on monoamine oxidase activity of mitochondria. Coupling efficiencies of megamitochondria induced by the reagents, specified above, were not affected. Cytochrome c oxidase and ATPase activities of megamitochondria were also unchanged compared to the control. Isoniazid, iproniazid, and nialamide affected monoamine oxidase activity of mitochondria not only in vivo, as described above, but also in vitro: the activity was inhibited by 50% at concentrations of 5.8 mM, 215 and 140 μM for isoniazid, iproniazid, and nialamide, respectively. Rotenone-insensitive NADH-cytochrome c reductase of megamitochondria, another marker enzyme for mitochondrial outer membrane besides monoamine oxidase, was not affected so much: the lowest activity was 88.6% of the control in the case of nialamide-induced megamitochondria. These reagents had no effect on the enzyme activity in vitro. These data seem to indicate that the reagents examined in the present study affected monoamine oxidase specifically. Mechanism of the formation of megamitochondria is discussed with respect to membrane fusion phenomenon.

High incidence of peliosis hepatis in autopsy cases of aplastic anemia with special reference to anabolic steroid therapy.

The livers were collected from 47 autopsy cases of aplastic anemia aiming to study the correlation between the use of androgenic anabolic steroid and the formation of peliosis hepatis. Association of peliosis hepatis was found in 7 cases out of 19 cases with anabolic steroid therapy, while peliotic cavities were found only in one case out of the remaining 28 cases without anabolic steroid therapy. Out of 7 cases specified above, peliotic cavities in 5 cases were phlebectatic; phlebectatic and parenchymal types of peliotic cavities coexisted in one case, and one case was parenchymatous. Besides these cavity formations, remarkable dilatation of sinusoids often distinct at the periphery of the hepatic lobule was found in the 7 cases.

Induction of megamitochondria in the mouse and rat livers by hydrazine

The correlation between structures of chemicals and their inducibility for megamitochondrial formation was investigated. Since the chemical structure universal to the inducers of megamitochondria previously reported (cuprizone and isonicotinic acid derivatives) is the carbazoyl group (-CONHNH2), semicarbazide (NH2NHCONH2) was tested first. Then, hydrazine (NH2NH2) was tested, replacing the carbazoyl group of semicarbazide by an amino group (-NH2). The present study demonstrates that (1) megamitochondria were induced in mouse and rat hepatocytes by feeding the animals with a diet containing semicarbazide or hydrazine, suggesting that the carbazoyl group was not essential for megamitochondrial formation; (2) hydrazine-induced megamitochondrial formation was a reversible process. Coupling efficiencies and activities of ATPase and cytochrome oxidase of megamitochondria induced by hydrazine were slightly decreased, while the activity of monoamine oxidase was moderately decreased. Freeze-fracture electron microscopy revealed particle-free regions in the outer membranes of megamitochondria fixed with glutaraldehyde at 22 degrees C; the regions disappeared at 25 degrees C, indicating that the temperature of the liquid crystalline to gel state lipid phase transition in the megamitochondrial outer membrane was elevated. It is speculated that chemical structure of inducer of megamitochondria could be simplified to NH2-G (G, substituting group).

HUMAN DUCTUS ARTERIOSUS

The present study deals mainly with the ductus arteriosus of preterm infants of gestational age less than 29 weeks, birth weight less than 1200 g, and postnatal age less than 72 hours. Excised ductus were histologically examined postmortem and compared to those of infants of more advanced gestational age. Intimal cushion and duplication and/or interruption of the internal elastic lamina of the ductus arteriosus were employed as the indicators of the maturation of the ductus arteriosus. The ductus arteriosus of infants with gestational age more than 29 weeks showed histologically more mature features than those of 28 weeks or less. It is considered that there is a relation between gestational age and histologic maturation of the ductus arteriosus.

Induction Of Megamitochondria In The Rat Liver By N‐Propyl Alcohol And N‐Butyl Alcohol

Propyl alcohol and butyl alcohol had similar effects to ethyl alcohol on ultrastructure of liver mitochondria. Rats were given 32% ethyl alcohol, 32% n‐propyl alcohol, and 6.9% n‐butyl alcohol in drinking water for up to three months. After one month, mitochondria in hepatocytes obtained from the experimental animals became elongated, constricted or cup‐shaped with scanty cristae. After two months, mitochondria in some hepatocytes became gigantic. In extreme cases, the megamitochondria exceeded 10 μm in diameter.

MECHANISM OF THE FORMATION OF MEGAMITOCHONDRIA BY COPPER‐CHELATING AGENTS V. FURTHER STUDIES ON ISOLATED MEGAMITOCHONDRIA

Effect of cuprizone has been studied on some biochemical properties of megamitochondria obtained from the mouse liver. (1) Contents of Ca2+, Mg2+ and Cu2+ in the blood or the liver homogenates were not altered by cuprizone‐intoxication, whereas those in liver mitochondria were significantly altered: after 3‐4 days’intoxication, content of Ca2+ was decreased and was remarkably increased after 14‐15 days’intoxication. Content of Mg2+ behaved contrarily. (2) Both cytochrome oxidase and ATPase activities were unchanged in the liver megamitochondria, but monoamine oxidase (MAO) activity was significantly decreased. Value of I50 (50% inhibition) for MAO was determined to be 0.33 mM using the control liver mitochondria. Cuprizone had almost no effect on MAO activity of kidney or heart mitochondria both in vivo and in vitro. (3) The amount of lysolecithin was increased in the liver megamitochondria.

LUNG CANCER AND CHRONIC INTERSTITIAL PNEUMONIA ASSOCIATED WITH SYSTEMIC SARCOIDOSIS

Lung cancer and chronic interstitial pneumonia associated with systemic sarcoidosis was detected in a 66‐year‐old woman at autopsy. Histologically, hyalinized sarcoid lesions were scattered in cervical lymph nodes, thoracic lymph nodes, abdominal lymph nodes, and spleen. Scattered non‐caseating epithelioid cell granulomas with giant cells were observed in both lungs remoting cancer and chronic interstitial pneumonia. A tumor mass occupying right hilar portion was well‐differentiated squamous cell carcimona involving right upper lobe and right hilar lymph nodes. In the lower lobe of the left lung, a small nodule of poorly differentiated squamous cell carcinoma was detected. Alveolar septa, especially in both lower lobes of the lungs were thickened diffusely with fibrosis, edema, and inflammatory cell infiltration. Alveolar cavities contained hyaline membrane and large mononuclear cells. Atypical bronchiolar epithelial proliferation and squamous metaplasia associated with squamous cell carcinoma were detected. The clinical and pathological characteristics among eight reported cases of lung cancer associated with sarcoidosis and three reported cases of interstitial pneumonia associated with sarcoidosis were reviewed separately. There is no report describing both lung cancer and chronic interstitial pneumonia associated with sarcoidosis.

MECHANISM OF THE FORMATION OF MEGAMITOCHONDRIA BY COPPER‐CHELATING AGENTS IV. ROLE OF FUSION PHENOMENON IN THE CUPRIZONE‐INDUCED MEGAMITOCHONDRIAL FORMATION

Megamitochondria were induced within 36‐40 hours in mouse hepatocytes by injecting cuprizone into the peritoneal cavity. Induction of megamitochondria was dependent upon the amount and the time intervals of the injection of cuprizone: 200 mg of cuprizone/kg of body weight ‐ injected every 12 hours or 400 mg of cuprizone/kg of body weight ‐ injected every 24 hours. When the latter amount of the noxious reagent was administered to the animal every 12 hours, fatty changes of the liver was observed. Involvement of the fusion phenomenon in the mechanism of megamitochondrial formation is discussed in the light of turnover rates for various components of the mitochondrion.