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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.

Galectins are beta-galactoside binding mammalian lectins and they share homologous carbohydrate recognition domains. To date, 11 members of galectin family have been cloned and identified. They have been shown to play roles in diverse biological events, such as embryogenesis, oncogenesis, adhesion and proliferation of the cells, receptor for advanced glycation end products, mRNA splicing, bacterial colonization, apoptosis, and in the modulation of the immune response. The mechanisms by which galectins exert these diverse effects remain largely unknown. However, the elucidation of multi-functional proteins belong to galectin family are going to open new fields in clinical science including diagnosis and therapy of autoimmune disorders, cancers, and vascular complications in diabetes and hypertension.</P>

The objective of this study was to evaluate fast and ultrafast T2-weighted images (T2WI), including echo planar imaging (EPI), using an AMI-25 agar phantom. Image quality for conventional spin echo (CSE) and turbo spin echo (TSE) was almost equivalent. In high-resolution TSE, image quality was highest due to the use of a 512 x 256 matrix. Half-Fourier single-shot turbo SE (HASTE) was associated with blurring of images, and turbo-gradient SE (TGSE) showed a deterioration of image quality. EPI also suffered from poor image quality because this method is very sensitive to magnetic field inhomogeneity. CSE showed good signal-to-noise ratio (S/N) and contrast ratio (CR), but also required the longest imaging times. Among the TSE sequences, TSE with a short echo train length (ETL) was superior in terms of S/N. The CR of EPI and fast low angle shot (FLASH) images were improved in proportion to the effective echo time (TE). At present, TSE is inferior to CSE in terms of S/N and CR. However, taking into consideration scanning time, TSE with a short ETL is thought to be suitable for routine examinations. Effective TE is an important factor in gradient echo (GRE) examinations.</P>

The immune status of thirteen living and related kidney transplant recipients with stable allografts were examined. The immunological assays consisted of a mixed lymphocyte reaction (MLR), cell-mediated lympholysis (CML) assay, interleukin-2 (IL-2) production in mixed lymphocytes culture (MLC) and IL-2 receptor (IL-2 R) expression on MLC cells. The suppression rates of the monoclonal antibodies (mAbs) against IL-2 R were tested on MLRs. The stimulation indices (SI) of the MLR against both donor and third-party cells increased compared with those of pretransplantation. The MLC responder cells stimulated by donor cells produced detectable amounts of IL-2, these amounts were lower than those by third-party cells. The MLC cells against donor cells expressed IL-2 R alpha and beta chains to the same degree as those against third-party cells. Anti-IL-2 R mAbs equally inhibited the MLRs between recipient and donor or third-party cells. Cytotoxic T lymphocytes (CTL) against donor cells were not generated, even with the addition of recombinant IL-2 in any of recipients except one, while anti-donor CTL had been detected prior to transplantation and the CTL against third-party cells were induced in posttranspalnt CML

assays. These results indicate that the clonal anergy phenomenon might mediate the specific CTL unresponsiveness observed in kidney transplant recipients and the anergy phenomenon might serve in the long-term acceptance of allograft.

Hepatitis C virus (HCV), discovered in 1989, is the major causative agent of parenteral non-A, non-B hepatitis worldwide. Following the development of a method of diagnosing HCV infection, it became apparent that HCV frequently causes chronic hepatitis. Persistent infection with HCV is implicated in liver cirrhosis and hepatocellular carcinoma. Current worldwide estimations suggest that more than 170 million people have been infected with HCV, an enveloped positive single-stranded RNA (9.6-kilobases) virus belonging to the Flaviviridae. The HCV genome shows remarkable sequence variation, especially in the hypervariable region 1 of the E2 protein-encoding region, and globally, HCV appears to be distributed with more than 30 genotypes. Complicated "quasispecies" and frequent mutations of viral genomes have also emerged. The HCV genome encodes a large polyprotein precursor of about 3,000 amino acid residues, and this precursor protein is cleaved by the host and viral proteinases to generate at least 10 proteins in the following order: NH2-core-envelope (E1)-E2-p7-nonstructural protein 2 (NS2)-NS3-NS4A-NS4B-NS5A-NS5B-COOH. These viral proteins not only function in viral replication but also affect a variety of cellular functions. Although several explanations have been proposed, the mechanisms of HCV infection and replication in targeted cells, the mechanism of persistent viral infection, and the pathogenesis of hepatic diseases (hepatitis or hepatocellular carcinoma) are all poorly understood. A major reason why these mechanisms remain unclear is the lack of a good experimental HCV replication system. Although several classical trials using cultured cells have been reported, several new, more promising experimental strategies (generations of infectious cDNA clone, replicon, animal models, etc.) are currently being designed and tested, in order to resolve these problems. In addition, new therapies for chronic hepatitis have also been developed. The enormous body of information collected thus far in the field of HCV research is summarized below, and an overview of the current status of HCV molecular virology of HCV is provided.</P>

We developed a method for human identification of forensic biological materials by PCR-based detection of a human-specific sequence in exon 3 of the myoglobin gene. This human-specific DNA sequence was deduced from differences in the amino acid sequences of myoglobins between humans and other animal species. The new method enabled amplification of the target DNA fragment from 30 samples of human DNA, and the amplified sequences were identical with that already reported. Using this method, we were able to distinguish human samples from those of 21 kinds of animals: the crab-eating monkey, horse, cow, sheep, goat, pig, wild boar, dog, raccoon dog, cat, rabbit, guinea pig, hamster, rat, mouse, whale, chicken, pigeon, turtle, frog, and tuna. However, we were unable to distinguish between human and gorilla samples. This method enabled us to detect the target sequence from 25 pg of human DNA, and the target DNA fragment from blood stored at 37 degrees C for 6 months, and from bloodstains heated at 150 degrees C for 4 h or stored at room temperature for 26 years. Herein we also report a practical application of the method for human identification of a bone fragment.</P>