検索

A high performance lipuid chromatographic method for the determination of urinary trichloroacetic acid, a metabolite of trichloroethylene, is described. A stainless steel column packed with Hitachi gel 2618 (H form) was used and the mobile phase was one per cent aqueous phosphoric acid. Urine can be analyzed directly without any solvent extraction or pretreatment. The minimal detection limit was 0.5 micrograms per analysis. The present method is simple and specific, and can be performed within 10 min.

Differences in urinary excretion of trichloroethylene were studied in rabbits, rats and mice. Trichloretylene (1 m mole/kg) was injected intra-peritoneally, then urinary trichloroacetic acid and trichloroethanol glucuronide were measured. The results were: 1. The ratio of total excretion of trichloroethylene metabolites to the administered trichloroethylene decreased in the order of mice, rats and rabbits. 2. The ratio of total trichloroethanol to trichloroacetic acid in urine decreased in the order of rabbits (69.2), mice (12.8) and rats (2.3). The high ratio in rabbits was due to the extremely small amount of trichloroacetic acid in the urine. 3. Differences in these two urinary metabolites in the three kinds of animals and in human subjects were discussed.

A reproducible animal model of fulminant hepatic failure was developed by intraperitoneal administration of D-galactosamine hydrochloride to Sprague-Dawley rats. Biochemical and morphological hepatic injury and brain edema resembled human fulminant hepatic failure. This model would facilitate further studies of the pathogenesis of brain dysfunction and evaluation of treatment in fulminant hepatic failure.

Peripheral blood lymphocytes and the various lymphocyte fractions from patients with cancer of the colon were cultivated with target cells (P-4788) derived from the colon cancer. Changes in the surface ultrastructure during tumor cell destruction were studied by scanning electron microscopy (SEM). P-4788 cells adhering to the coverslip showed various surface activity. The surfaces of some cells were relatively flat; others were smooth or had fine granules. Still other cells were villous, round or had marked blebs. When host lymphocytes were added to the target cells, adhesion of the two cell groups began by many fine projections. After incubation for 6 h, some lymphocytes had adhered to the target cells. Many lymphocytes had adhered to the target tumor cells by 24--48 h incubation. Ultimately the tumor cells became swollen and disrupted. Most lymphocytes adherent to the target cells had few microvilli. Lymphocytes after elimination of phagocytes by carbonyl iron treatment also adhered readily. Some target cells showed adhesion with lymphocytes passed through nylon-wool columns, although the number of lymphocytes adhering was fewer than in the case of lymphocytes not passed through nylon-wool columns. T cells were collected from lymphocytes that form rosettes with SRBC by isolation with NH4Cl. They had markedly elongated microvilli which in places were sparsely scattered and tended to be localized on the side, a finding which suggests loss of cell activity by the time of SEM. Only a few T cells adhered to target cells and they seemed to be T cells without activity. It was thought that there are cytotoxic cells among T cells and that the co-existence of T cells, non-T cells and monocytes caused target cell destruction.

In order to locate the target cells for malignant transformation by BK virus (a human papova virus) in hamster brain, electron microscopic observation of tumor originally induced in hamster brain by BK virus was performed. With light microscopy, the BK virus-induced tumor (Vn 17) bore a close resemblance to human malignant ependymoma. Under the electron microscope, numerous microvilli and few cilia were visible on the surface of the tumor cells. These tumor cells were joined to each other by desmosomes. Gap junctions were not observed. Multilayered cuboidal cells were observed around the lumen and blood vessels in the tumor. With regard to fine structure, three types of Vn 17 cells were recognized; ependymal like cells, tanycytes with prominent cell processes, and undifferentiated cells with few cytoplasmic organelles. There was no basal lamina between the ependymal cells and the connective tissue stroma. The Vn 17 cells showed some similarity to the ultrastructural features of the epemdymal cells of newborn rabbits, suggesting that the target cells for Vn 17 may be cells related to ependyma. Malignant transformation of the cells would be initiated in the early stages after BK virus inoculation into the brain of newborn hamsters.

Clinical trials of immuno-chemotherapy were conducted on malignant lymphoma patients. Patients during the period from 1972 through 1977 were allocated to two groups retrospectively according to the mode of treatment, i.e., chemotherapy alone (historical control group, 35 patients) and chemotherapy with OK-432 (treated group, 15 patients). Comparisons were made of the two groups, which were homogeneous with regard to induction chemotherapy, maintenance chemotherapy, stage and histologic type of disease. The treated group had a higher remission rate, and a longer remission duration and survival than the control groups, especially in patients with Hodgkin's disease but the difference was not statistically significant owing to the limited number of cases.

The autopsy case of an 80-year-old female with pseudomyxoma peritonei arising in the left ovary is reported. The patient was admitted with complaints of anorexia, sense of fullness and abdominal distension of two months' duration, and died of intestinal obstruction four months later. The autopsy revealed extensive tumor dissemination over the entire peritoneal cavity without any visceral invasion or distant metastasis. A part of the sigmoid colon showed marked stenosis and perforation with abscess formation. Histologically, the tumor was composed of various sized multiple cysts which were completely or incompletely lined by a layer of mucin-producing columnar epithelial cells with moderate nuclear hyperchromatism, and of a papillary pattern in some parts, indicating low grade malignancy.

The alterations of lipid composition in sera of patients with liver diseases, particularly intrahepatic cholestasis and biliary obstruction, were studied by ultracentrifugation and polyacrylamide-gel disc-electrophoresis of lipoproteins and apoproteins. The elevation of serum cholesterol in intrahepatic cholestasis was greater than in biliary obstruction. The appearance of lipoprotein X in obstructive disease accounted for most of the increased cholesterol. The level of non-lipoprotein X cholesterol in intrahepatic cholestasis was significantly elevated, this being in part ascribed to the appearance of a new class of cholestatic lipoprotein, Slow-migrating HDL. The electrophoretic pattern of lipoprotein in cholestasis was generally characterized by a decrease in alpha band intensity and, in some types of cholestasis, by the appearance of Slow-migrating HDL. In addition, other abnormal lipoproteins exhibiting the characteristics of triglyceride-rich LDL (LP-Y), LP-X-like HDL and LDL-like HDL were found in some cases of intrahepatic cholestasis and biliary obstruction.

An unusual case of orbital tumor with high renin content and severe hypertension is described. The patient was a 15-year-old girl with juvenile hypertension (200-140 mmHg) associated with right exophthalmos and hypokalemia. The patient showed extremely high levels of plasma renin activity and plasma aldosterone concentration. No difference was present in plasma renin activity from either side of the renal veins. Preoperatively, hypertension responded to treatment with spironolactone. The tumor could not be completely removed because of intracranial metastasis and infiltration, and the hyperreninemia and secondary hyperaldosteronism persisted. The renin content in the orbital tissue was 1,403-2,225 ng/angiotensin I generated/h/g wet weight of tissue. The postmortem histopathologic diagnosis was orbital hemangiopericytoma. This is the first case of extrarenal (ectopic) renin-secreting (or -producing) hemangiopericytoma of the orbital origin. Furthermore this case is worthy of note in the point of view of the presence of the extrarenal renin-angiotensin system, particularly in the brain.

A heat stable cell growth inhibiting factor was isolated from rat liver microsomes by hot salt extraction, ethanol fractionation and the hot phenol method. The factor was contained in the RNA fraction (designated as mhRNA). mhRNA inhibited the growth of mouse fibroblast (L-929) cells at a relatively low concentration (55 microgram/ml of culture medium). The molecular weight of mhRNA was about 27,000 and the base composition was guanine and cytosine rich.

Purification of antilymphocyte antibody (ALA) from patients with systemic lupus erythematosus (SLE) was achieved by immunoabsorption and elution. Human tonsil cells or thymocytes were used as absorbents. Complement dependent microcytotoxicity tests showed that, in comparison to the parent sera, the eluate from tonsil cells was eight times, and that from thymocytes four times, more active. Antinuclear activity was eliminated by elution. The ALA was almost entirely IgM, IgG being involved in only a few cases. IgA lacked cytotoxic activity. ALA was directed at both T- and B-cell surface determinants, which suggests that, in SLE, it has a heterogeneous biological composition.

Three patients at various stages of remission from leukemia died following the development of massive liver necrosis within only 4-6 days. All had either hepatitis B surface antigen or antibody in their sera, and two of them experienced severe epigastric pain before the onset of liver injury. Hepatitis B surface antigen appeared in two of these patients after remission from leukemia. Serum gamma-globulin levels increased with decreasing doses of prednisolone and other antileukemic drugs, and hepatic cell necrosis occurred extensively. Localization of hepatitis B surface antigen in their livers revealed a strong positive reaction in the phagocytic cells. These observations strongly suggest that hepatitis B virus may be causally related to the fulminant hepatic failure at least in two of the reported leukemic patients.

In cardiovascular diseases with potential atherosclerosis, the serum concentration of HDL cholesterol as determined by a precipitation method with dextran sulfate and Mg++ was lower while that of total cholesterol was normal or elevated. Treatment with a daily dose of 1,200 mg of Nicomol, a derivative of nicotinic acid, for 1 to 3 months increased the mean HDL cholesterol level by 3 to 5 mg/dl and reduced the total cholesterol level by 14 to 15 mg/dl and total/HDL cholesterol ratio by 0.8 (3 months) to 0.9 (1 month, p less than 0.05). Similar decreases in HDL cholesterol concentration were also found in parenchymal and obstructive liver diseases with normal total cholesterol values except in fulminant hepatitis and intrahepatic cholestasis.

Mesosomes of Staphylococcus aureus were examined morphologically under the electron microscope. Three different methods of specimen preparation (thin section, freeze-fracture, and negative staining) were used to eliminate artifacts due to sample processing. Mesosomes were rarely seen in intact cells but were quite distinct in autolysed cells incubated in 1.2M sucrose -0.33M acetate buffer (pH 5.8) at 25 degrees C. The phospholipid content increased by 20% of the control as autolysis proceeded. Since the plasma membrane did not show any other significant changes, the development of mesosomes during autolysis was shown to be a real event. Most of the well-developed mesosomes were found at the septum in negatively stained specimens. Initial wall-lysis occurred at this site, suggesting a close relationship between autolysis and the development of mesosomes in S. aureus.

A 26-year-old female with Bartter's syndrome associated with Graves' disease is reported. This patient had a history of Graves' disease from the age of 22 and anti-thyroid drug (Methimazole) had been administered for 2 years. Thyroid function returned to normal but general fatigue and polyuria continued. Hypokalemia was diagnosed at 25 years of age and she was referred to our hospital for evaluation. Blood pressure was normal and laboratory data revealed normal thyroid function, hypokalemic alkalosis, high plasma renin activity and high plasma aldosterone concentration. She showed normal pressor sensitivity to norepinephrine infusion, grossly diminished pressor sensitivity to exogenous angiotensin II infusion compared with the normal. A renal biopsy specimen showed juxtaglomerular cell hyperplasia. Electron microscopy confirmed lacis cell (agranular cell) proliferation.

Serum glutamic oxaloacetic transaminase (GOT), mitochondrial GOT (GOTm), glutamic-pyruvic transaminase (GPT) and glutamate dehydrogenase activities were determined in 43 healthy controls and in 280 cases of liver diseases. A simplified column chromatographic method coupled with UV assay was employed for separation of GOTm. The activity was measured by following decrease in abosrbance of NADH at 340 nm. The lowest activity of GOTm determined with a coefficient of variation below 10% was 6 mIU/ml. High GOTm activities were found in acute hepatitis (acute stage), subacute hepatitis and primary biliary cirrhosis and were generally associated with high total GOT (GOTt) activities. The activity ratio of GOTm/GOTt varied depending on the stage and severity of liver diseases. The GOTm/GOTt ratio was decreased in acute, fulminant and subacute hepatitides. No significant reduction in the ratio was found in bile duct obstruction, alcoholic liver injury or metastatic liver cancer. Although relatively high GOTm/GOTt ratios were found in some patients with severe hepatic injury, they had no definite association with poor prognosis. These results indicate that the marked elevation in GOTt over GPT in advanced chronic hepatitis, liver cirrhosis and primary hepatoma was mainly due to preferential leakage of cytoplasmic GOT (GOTs).

In order to investigate a possible effect of insulin-like growth factor-1 (IGF-1) on ischemic brain injury, IGF-1 was applied topically on the brain surface of reperfused rat brain after 60 min of transient middle cerebral artery occlusion. In contrast to the cases treated with vehicle, the infarct volume was greatly reduced at 24 h of reperfusion by the treatment with IGF-1. Immunohistochemical analysis in the middle cerebral artery territory showed that Caspase-3 staining was markedly reduced in the cases with IGF-1 treatment, but 72-kDa heat shock protein staining remained almost unchanged. The present results suggest that treatment with IGF-1 exerts a significant effect on ameliorating brain injury after transient focal brain ischemia. Moreover, this effect is greatly associated with the reduction of Caspase-3 staining, but is only minimally associated with a decreasd stress response at the cellular level.

A 60-year-old man was admitted to our hospital with a right inguinal swelling that had been growing in size without any pain for 7 months. We diagnosed the growth as a right inguinal hernia and operated on him. The growth, however, was found to be a tumor it situated along the spermatic cord and testicular vessels. We diagnosed it as a lipoma. The tumor was resected near part of the internal inguinal ring. Histopathological diagnosis showed well-differentiated liposarcoma of the sclerosing type. Postoperative computed tomography (CT) revealed a large residual tumor in the retroperitoneum. We believed that the tumor was a retroperitoneal liposarcoma and that it developed in the inguinal region. The residue of the liposarcoma was resected onto the right inguinal tract. A periodic follow up has been performed and no evidence of recurrence or metastasis has been seen in the 4 years and 9 months since the second surgery. No adjuvant therapy was performed. Inguinal liposarcomas are relatively rare and in most cases these tumors are thought to originate in the spermatic cord. The origin of the tumor is believed to be the retroperitoneum

The metallothionein (MT) family is a class of low molecular, intracellular, and cysteine-rich proteins with a high affinity for metals. Although the first of these proteins was discovered nearly 40 years ago, their functional significance remains obscure. Four major isoforms (MT-I, MT-II, MT-III, and MT-IV) have been identified in mammals. MT-I and MT-II are ubiquitously expressed in various organs including the brain, while expression of MT-III and MT-IV is restricted in specific organs. MT-III was detected predominantly in the brain, and characterized as a central nervous system-specific isomer. The role of MTs in the central nervous system has become an intense focus of scientific research. An isomer of MTs, MT-III, of particular interest, was originally discovered as a growth inhibitory factor, and has been found to be markedly reduced in the brain of patients with Alzheimer's disease and several other neurodegenerative diseases. MT-III fulfills unique biological roles in homeostasis of the central nervous system and in the etiology of neuropathological disorders.

The implication of low affinity nerve growth factor receptor (p75NGFR), which is believed to play a pro-apoptotic role, in delayed neuronal death (DND) after ischemia in the gerbil hippocampus was investigated. Immunohistochemistry and Western blot analysis revealed that the presence of p75 NGFR immunoreactivity (IR) was negligible in the hippocampus of the sham control gerbil but appeared clearly in CA1 neurons 3 and 4 days after 5-min transient ischemia. Terminal deoxynucleotidyl transferase-mediated UTP nick end labeling (TUNEL)

positive nuclei appeared when the level of p75NGFR IR increased. Furthermore, almost all TUNEL-positive CA1 neurons also costained for p75NGFR. These results suggest that p75NGFR contributes to DND after ischemia by an apoptotic mechanism.