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Leukocyte differential analysis was performed in various species, particularly laboratory animals, by the laser multi-angle polarized light scattering separation method. Venous blood specimens were drawn from the following subjects: healthy adult men and women ("humans"); cynomolgus monkeys ("monkeys"); common marmosets ("marmosets"); beagle dogs ("dogs"); miniature potbelly pigs ("swine"); Japanese white rabbits ("rabbits"); Hartley guinea pigs ("guinea pigs"); and Sprague-Dawley rats ("rats"). 90 degrees/10 degrees scatter plot: Basophils and mononuclear-polymorphonuclear cells were separated in all subjects, but individual 10 degrees and 90 degrees scatter plots overlapped in dogs and guinea pigs, respectively. 90 degrees depolarized /90 degrees scatter plot: Neutrophils and eosinophils were clearly separated in human, monkey, guinea pig, swine and rat subjects. The eosinophil cluster was not clearly plotted in marmoset, dog, or rabbit. 0 degree/10 degrees scatter plot: Regarding this plot for monocytes and lymphocytes, cells were plotted in the following order in all subjects: lymphocytes < basophils < or = monocytes in the 0 degree (size) scatter; and lymphocytes [symbol: see text] monocytes < or = basophils in the 10 degrees (complexity) scatter. Compared to other species, the rat scatter showed a tendency to overlapping plots in both the 0 degree and 10 degrees scatters in the monocyte and lymphocyte clusters. In both dog and guinea pig, the monocyte and neutrophil plots overlapped in the 0 degree and 10 degrees scatters. Basobox: In the human and rabbit subjects, the basophil cluster was plotted within the established basobox, but no clear cell cluster was plotted in the other subjects. As a result of comparing the percentage values for leukocytes in various species obtained by using the CD3500 apparatus versus the corresponding values obtained manually, good correspondence was found in the monkey, and eosinophils in the marmoset were lower with CD3500 than manually. In the rabbit, the mean measured value for basophils matched in the manual and CD3500 findings. In the guinea pig, the CD3500 values were lower than the manual values for lymphocytes, but higher for monocytes and neutrophils. The above findings suggest that the laser multi-angle polarized light scattering separation method is indeed capable of analyzing leukocytes from various species based on cell size and cell complexity, i.e., the presence or absence of nuclei, granules and cell enclosures.

Prostaglandin (PG) D2 is the most abundant prostanoid produced in the central nervous system of mammals and has been implicated in the modulation of neural functions such as sleep induction, nociception, regulation of body temperature, and odor responses. We generated gene-knockout mice for lipocalin-type PGD2 synthase (L-PGDS) and found that the intrathecal administration of PGE2, an endogenous pain-producing substance, failed to elicit allodynia (touch-evoked pain), which is one typical phenomenon of neuropathic pain, whereas it evoked thermal hyperalgesia, in L-PGDS-/- mice. We also found that the allodynic response induced by the gamma-aminobutyric acid (GABA)A receptor antagonist bicuculline was selectively abolished in the L-PGDS-/- mice, among excitatory and inhibitory agents that induced allodynia in wild-type mice. Interestingly, simultaneous injection of a femtogram amount of PGD2 with PGE2 or bicuculline induced allodynia in L-PGDS-/- mice to the same extent as in wild-type mice. The PGE2- or bicuculline-evoked allodynia in wild-type and in PGD2-supplemented L-PGDS-/- mice was blocked by a PGD2 receptor antagonist given in a femtogram amount. These results reveal that endogenous PGD2 is essential for both PGE2- and bicuculline-induced allodynia.

The expression of cyclin E, one of the important positive cell cycle regulators, was examined immunohistochemically in gallbladder carcinomas. Cyclin E gene product was detected in 58 (49%) out of 118 cases. The degree of cyclin E expression was not associated with any clinicopathological factor including histology, the depth of tumor invasion, tumor stage and patient prognosis. Cyclin E expression was not correlated with that of p53 protein statistically, whereas it was correlated with the proliferative activity of the tumor cells by PCNA (p<0.05). These results suggested that cyclin E expression may confer progression of gallbladder carcinomas.

Plasmodium falciparum causes the most severe form of human malaria, which kills approximately 1.5-2.7 million people every year, but the molecular mechanisms underlying the clinical symptoms and the host-parasite interaction remain unclear. We show here that P. falciparum produces prostaglandins (PGs) D2, E2, and F2alpha. After incubation with 1 mM arachidonic acid (AA), cell homogenates of P. falciparum produced PGs as determined by enzyme immunoassay and gas chromatography-selected ion monitoring. PG production in the parasite homogenate was not affected by the nonsteroidal antiinflammatory drugs aspirin and indomethacin, and was partially heat resistant, whereas PG biosynthesis by mammalian cyclooxygenase was completely inhibited by these chemicals and by heat treatment. Addition of AA to the parasite cell culture markedly increased an ability of the parasite cell homogenate to produce PGs and of parasitized red blood cells to accumulate PGs in the culture medium. PGD2 and PGE2 accumulated in the culture medium at the stages of trophozoites and schizonts more actively than at the ring stage. These findings are the first evidence of the direct involvement of a malaria parasite in the generation of substances that are pyrogenic and injurious to the host defenses. We will discuss a possible contribution of the parasite-produced PGs to pathogenesis and host-parasite interaction of P. falciparum.

Prostaglandin (PG) D2 is one of the major prostanoids in the mammalian brain and eye tissues. Its function is mediated by the prostanoid DP receptor, which is specific for PGD2 among the various prostanoids. In this study, we cloned the full-length cDNA for the rat DP receptor and used it for detection of DP receptor mRNA in various rat tissues. Northern blotting and RT-PCR analyses revealed that this DP receptor was expressed most intensely in the eye tissues, moderately in the leptomeninges and oviduct, and weakly in the epididymis. The tissue distribution profile of the mRNA for the rat DP receptor is overlapped with those of hematopoietic and lipocalin-type PGD synthases. Among rat eye tissues, the expression was the highest in the iris. In situ hybridization and in situ RT-PCR revealed DP receptor mRNA to be localized in the epithelium of the iris and ciliary body and in photoreceptor cells of the retina, suggesting the involvement of the receptor in the physiological regulation of intraocular pressure and the vision process. In the brain, DP receptor mRNA was dominantly expressed in the leptomeninges and was not detected in the brain parenchyma including the ventral rostral forebrain, the surface area of which is reportedly involved in sleep induction by PGD2.

Background: Although a specific syndrome of the uterus didelphys, obstructive hemivagina, and ipsilateral renal agenesis had been reported in gynecologic literatures, it is not familiar to radiologists. We introduce this syndrome with radiological, especially MR findings., Methods: Imaging findings and medical records of seven patients with this syndrome were retrospectively reviewed., Results: MR clearly demonstrated uterus didelphys with obstructed hemivagina in six of the seven patients. A remaining one showed uterus didelphys with left-sided hematometra and hematosalpinx who had undergone vaginal septum incision prior to the MR. We could also recognize ipsilateral renal agenesis in all five patients, in whom renal areas were examined on MR. After vaginal septum resection, symptoms disappeared in six patients. We could observe the disappearance of the obstructive complications with MR in three patients., Conclusions: MR can do much for the early diagnosis and the prevention against further complications of this condition because it can demonstrate the müllerian duct anomaly complicated with obstructed hemivagina in detail and even ipsilateral renal agenesis.

Purpose: Our purpose was to present imaging findings of six cases proven or supposed to be von Meyenburg complexes (VMCs) with a basis of reviewing the pathologic literature and to describe imaging points for the diagnosis of typical VMC along with its differential diagnosis., Method: Six cases were diagnosed as VMC of the liver with imaging modalities (one had histopathologic proof). Both ultrasound (US) and CT were available for all cases, and MRI was used for three cases. Follow-up with US, CT and/or MRI was performed in five cases., Results: US detected varying abnormalities of the livers in four cases. CT and MRI revealed multiple or numerous intrahepatic tiny (usually < 5 mm) cystoid lesions in all of the cases. The lesions were scattered throughout the livers, and some of them were located more frequently adjacent to the medium-sized portal veins than to the hepatic veins of similar size on CT. Moreover, some lesions were apparently located in the subcapsular areas (up to the hepatic capsules). They were usually irregular in shape and showed no enhancement but increased in number by approximately 80-150% after administration of intravenous contrast medium. The T2-weighted MR images and MR cholangiopancreatography showed the lesions to be much more apparent and to be more numerous than T1-weighted images did. Follow-up of five cases with imaging modalities did not show remarkable change of the lesions., Conclusion: Despite our limited experience, VMC lesions seem to show some CT and MR features different from those of other multiple small hepatic lesions. They presented as multiple or numerous intrahepatic tiny cystoid lesions usually with irregular contour, scattered throughout the liver up to the subcapsular areas, and were detected in far greater number by enhanced CT or T2-weighted MR images than by unenhanced CT or T1-weighted images. They showed no remarkable change on long term follow-up imaging. We propose that a diagnosis of typical VMC could be made after analyzing CT or MR images carefully with good understanding of its pathologic basis, but imaging follow-up is necessary in oncology patients.

Molecular mass (M(r)) microheterogeneity of beta-trace protein (beta TP) in cerebrospinal fluid (CSF) from patients with various neurological disorders was analyzed by sodium dodecyl sulfate capillary gel electrophoresis. Under the conditions employed, beta TP with a M(r) distribution of 23,000-30,000 was roughly separated into two subfractions containing the major peaks with M(r) of 26,000 and 28,500, respectively. The peak area ratios of the two subfractions of the electropherograms varied among the samples examined, and elevation in the total beta TP level in the CSF from patients with organic diseases in the central nervous system (CNS) was often accompanied by changes in the ratios of the subfractions. The quantitative changes in the subfraction level in CSF beta TP are considered to reflect the pathological alterations in the CNS.

The objective of this study was to characterize a 26-kDa seminal plasma protein previously shown to be prevalent in bulls of high fertility. Spots of this protein, excised and electroeluted from two-dimensional SDS-PAGE gels, were used for N-terminal amino acid sequencing and for preparation of antiserum in rabbits. The N-terminal amino acid sequence (ALQPNFEEDKFLGRWFTSGL) was 75% identical and 100% homologous to lipocalin-type prostaglandin (PG) D synthase isolated from human cerebrospinal fluid (CSF). Western blots of purified 26-kDa protein cross-reacted with polyclonal antibodies against lipocalin-type PGD synthase isolated from rat brain and human CSF. Immunoreactive bands at 26 kDa appeared in Western blots of seminal plasma and cauda epididymal fluid (CEF). A 29-kDa band appeared in blots of rete testis fluid (RTF). PGD synthase activity was detected in seminal plasma, CEF, and RTF. The cDNA for bovine lipocalin-type PGD synthase, isolated by reverse transcription-polymerase chain reaction, contained a coding region of 573 base pairs corresponding to 191 amino acids. The amino acid sequence was 63-80% identical to that of the enzyme of other mammals. These results establish that the 26-kDa fertility-associated protein in bull seminal plasma is lipocalin-type PGD synthase. Although we do not yet know the role of lipocalin-type PGD synthase in the male genital tract, we speculate that this protein may play an important role in both the development and the maturation of sperm.

Prostaglandin D synthase (PGDS) activity was detected in human seminal plasma (0.05-1.83 nmol/min per milligram protein). The enzyme was purified from human seminal plasma by immunoaffinity chromatography and found to be 27 kDa in size and N-glycosylated, similar to PGDS in the cerebrospinal fluid. The N-terminal amino acid sequence of 16 residues of the seminal enzyme, APEAQVSVQPNFQQDK, was identical to that of the cerebrospinal fluid PGDS. Although PGDS activity and the content determined by the immunoassay each highly varied in the seminal plasma, the concentration was significantly (p < 0.001) lower in the oligozoospermic group (2.47 +/- 0.51 microg/ml) than in the normozoospermic group (9.75 +/- 1.49 microg/ml). Prostaglandin (PG) D2 was detected in the seminal plasma (5.00 +/- 0.65 ng/ml) with a positive correlation to the PGDS concentration (p < 0.05). PGD2 was converted to the J series of PGs in the seminal plasma with a half-life of 6.5 h. Northern blot analysis revealed that mRNA for PGDS was expressed in the testis, prostate, and epididymis. Through immunohistochemistry, PGDS was localized in Leydig cells of the testis and in epithelial cells of the prostate and ductus epididymidis.

Purpose: Prostaglandin (PG) D synthase is present in neural tissues and cerebrospinal fluid (beta-trace). This enzyme belongs to the lipocalin family which consists of transporter proteins for lipophilic substances in the extracellular space. PGD synthase is found in retinal pigment epithelium, from where it is secreted into the interphotoreceptor matrix. The authors have undertaken the localization of this unique enzyme within the tissues and spaces of the anterior segment of the eye., Methods: Iris, ciliary body, lens, and aqueous and vitreous humors were collected from adult rats and mice. PGD synthase activity was determined, and the protein was quantified by Western blot analysis and localized immunohistochemically. Finally, in situ hybridization was performed to localize PGD synthase mRNA., Results: PGD synthase was most abundant in the aqueous and vitreous humors. It was less abundant in tissue cytosolic fractions; these fractions had almost 10-fold as much as their corresponding membrane-bound fractions. Lens tissue had the lowest amount observed. PGD synthase was localized to the epithelial cells of the iris and the ciliary body and to the adjacent extracellular chambers, but PGD synthase mRNA was found only within the epithelial cells. Several glycosylated forms of PGD synthase were also detected., Conclusions: PGD synthase was synthesized within the epithelial cells of the iris and the ciliary body and was then secreted into the aqueous and vitreous humors, where it accumulated as an active enzyme.

Lipocalin-type prostaglandin D synthase (L-PGDS) is localized in the central nervous system and male genital organs of various mammals and is secreted as beta-trace into the closed compartment of these tissues separated from the systemic circulation. In this study, we found that the mRNA for the human enzyme was expressed most intensely in the heart among various tissues examined. In human autopsy specimens, the enzyme was localized immunocytochemically in myocardial cells, atrial endocardial cells, and a synthetic phenotype of smooth muscle cells in the arteriosclerotic intima, and accumulated in the atherosclerotic plaque of coronary arteries with severe stenosis. In patients with stable angina (75-99% stenosis), the plasma level of L-PGDS was significantly (P < 0.05) higher in the great cardiac vein (0.694 +/- 0.054 microg/ml, n = 7) than in the coronary artery (0.545 +/- 0.034 microg/ml), as determined by a sandwich enzyme immunoassay. However, the veno-arterial difference in the plasma L-PGDS concentration was not observed in normal subjects without stenosis. After a percutaneous transluminal coronary angioplasty was performed to compress the stenotic atherosclerotic plaques, the L-PGDS concentration in the cardiac vein decreased significantly (P < 0.05) to 0.610 +/- 0.051 microg/ml at 20 min and reached the arterial level within 1 h. These findings suggest that L-PGDS is present in both endocardium and myocardium of normal subjects and the stenotic site of patients with stable angina and is secreted into the coronary circulation.

Hematopoietic prostaglandin (PG) D synthase is the key enzyme for production of the D and J series of prostanoids in the immune system and mast cells. We isolated a cDNA for the rat enzyme, crystallized the recombinant enzyme, and determined the three-dimensional structure of the enzyme complexed with glutathione at 2.3 A resolution. The enzyme is the first member of the sigma class glutathione S-transferase (GST) from vertebrates and possesses a prominent cleft as the active site, which is never seen among other members of the GST family. The unique 3-D architecture of the cleft leads to the putative substrate binding mode and its catalytic mechanism, responsible for the specific isomerization from PGH2 to PGD2.

Purpose: The goal of our study was to investigate the appearance of the medial umbilical folds on CT., Method: We retrospectively reviewed the CT images of 30 consecutive patients with massive ascites. In addition, we inspected the inner pelvic wall in cadavers., Results: The medial umbilical folds were well recognized on CT in 21 of 30 patients, bilaterally in 20 and unilaterally in 1. In four patients the folds were undetectable after the ascites resolved. The CT findings were supported by those studied in cadavers, in which the folds were recognized as a peritoneal reflection in 13 of 20., Conclusion: We concluded that medial umbilical folds could be commonly visualized on CT when ascites was present.

We report a 71-year-old male patient with multiple hepatic peribiliary cysts. The six-year follow-up through computed tomography (CT) imaging revealed increases in the size (from less than 10 mm to more than 38 mm) and number of the cysts.

Background: In cases of mucin-producing tumor (MPT) of the pancreas, a new clinical entity of pancreatic tumor, it has been reported to be difficult to distinguish adenoma from carcinoma preoperatively. This observation caused the authors to develop a new method of p53 immunocytochemistry using cytologic samples obtained by endoscopic retrograde pancreatic duct brushing (ERPDB)., Methods: Fifteen cases of MPT (9 with carcinoma and 6 with adenoma) were examined. In all cases, histologic diagnosis was determined by surgery or autopsy. A wire with a small brush was pushed into the dilatated pancreatic duct detected by endoscopic retrograde pancreatography (ERP). Specimens obtained by brushing were prepared on slides and subsequently fixed with ethanol. Papanicolaou staining and p53 immunocytochemistry were performed simultaneously. The ability of conventional cytology to distinguish adenoma from carcinoma was compared with that of p53 immunocytochemistry., Results: Five of 9 cases (56%) with carcinoma of MPT were correctly diagnosed by Papanicolaou staining. Two of four cases, classified as benign by Papanicolaou staining, expressed p53 protein. Overall, 7 of 9 cases (78%) with carcinoma MPT were correctly diagnosed by Papanicolaou staining associated with p53 immunocytochemistry. In the cases with adenoma MPT, all cases were classified as benign by Papanicolaou staining and no case positive for p53 protein was encountered., Conclusions: These results suggest that p53 immunocytochemistry as an adjunct in cytologic diagnosis using ERPDB may contribute to differentiating adenoma from carcinoma MPT of the pancreas preoperatively.

32 stage I cases of gallbladder carcinoma (GC) were examined to evaluate TP53 mutations with special attention to growth patterns. Their growth patterns were classified into two types: polypoid (P-type) and flat (F-type). 16 cases of GC were classified as P-type and 16 as F-type. p53 immunohistochemistry was performed using a mouse monoclonal anti-p53 antibody. Mutations in exons 5-8 were examined by polymerase chain reaction single strand conformation polymorphism (PCR-SSCP) and direct sequencing. The incidence of p53 immunoreactivity was greater in the cases of F-type (11/16, 69%) than those in P-type (14/16, 25%) (P < 0.05). PCR-SSCP or direct sequencing revealed that TP53 mutations were detected in all cases positive for p53 protein. These results suggest that TP53 mutations may contribute to the carcinogenesis of the F-type GC, and than this pathway in the F-type may differ from that in the P-type GC.

Glutathione-independent prostaglandin D synthase (PGDS) is an enzyme responsible for biosynthesis of prostaglandin D2 in the CNS and is identical to a major cerebrospinal fluid protein, beta-trace. Although PGDS has been identified recently in rat leptomeninges, little information is available about human meninges or meningiomas. Here, we report PGDS to be expressed consistently in 10 human arachnoid and arachnoid villi and in 21 meningiomas by immunohistochemistry, Western blot, and reverse transcription (RT)-PCR analyses. In arachnoid, PGDS immunoreactivity was seen in arachnoid barrier cells but was negligible in arachnoid trabecula and pia mater. In contrast, in arachnoid villi, PGDS was seen in core arachnoid cells rather than in the cap cell cluster or arachnoid cell layer. Meningioma cells also showed intense immunoreactivity in the perinuclear region, and it was often concentrated within meningocytic whorls and around calcifying psammoma bodies. Immunoelectron microscopic data, when compared with the ultrastructure, showed that PGDS was localized at rough endoplasmatic reticulum of arachnoid and meningioma cells. Western blot showed a 29 kDa immunoreactive band indicating PGDS, but the extent of expression was variable from case to case, which was compatible with immunohistochemical data. RT-PCR revealed PGDS gene expression in all meningiomas studied, regardless of histological subtypes, and also in human arachnoid villi. Because human arachnoid and meningioma cells exclusively express PGDS, it can be considered their specific cell marker. These results show functional differences in various types of meningeal cells attributable to differences in PGDS expression.

Purpose: To assess the hemodynamics of the liver and of hepatocellular carcinomas (HCCs) with hepatic vein occlusion., Materials and Methods: Selected hepatic veins were temporarily occluded with a balloon catheter in 21 patients with 28 nontreated nodular HCCs. Computed tomographic (CT) arteriography was performed without and with temporary occlusion of a hepatic vein that drained the blood from segmental liver parenchyma containing tumor by using a unified spiral CT and angiography system. The degree of enhancement and change in appearance of the HCC in each condition were compared., Results: All HCCs were well-enhanced, almost round masses at CT arteriography. At CT arteriography with hepatic vein occlusion, however, HCCs were changed as follows: (a) the absolute attenuation of the HCC was decreased in 27 (96%) of 28 tumors compared with that at CT arteriography without hepatic vein occlusion, while attenuation of the surrounding liver parenchyma was increased; (b) the size of the highly enhanced area in HCC became smaller in 17 (61%) tumors (of these, two disappeared); and (c) the shape was changed in 12 (43%) tumors., Conclusion: Hepatic vein occlusion resulted in reciprocal hemodynamic changes in the liver parenchyma relative to HCCs: Enhancement of the liver increases and that of HCCs decreases.

The toxic effects of arsenic compounds on cell divisionwere studied, using Chinese hamster V79 cells. Seven arsenic compounds weretested. Inorganic arsenic compounds (arsenite and arsenate), which have beenfound in drinking water, inhibited cell growth at very low concentrations. Monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), and trimethylarsineoxide (TMAO), which are methylated metabolites of inorganic arsenics, wereless cytotoxic than the inorganic arsenics themselves. The cytotoxicity ofthe three methylated metabolites decreased as the number of methyl groupsincreased. Arsenobetaine (AsBe) and arsenocholine (AsC), which have beenfound in some marine products, did not show any cytotoxicity. Threemethylated metabolites; MMA, DMA and TMAO induced mitotic arrest. Tetraploidyproduction was observed in cells exposed to DMA or TMAO. Arsenite, arsenate,AsBe and AsC did not induce mitotic arrest or tetraploids. These resultssuggest that MMA, DMA and TMAO exert some effect on cell division inmetaphase and may thereby give some clue as to the carcinogenic mechanism ofarsenic.

We describe an efficient and highly stable injection-locked, laser-diode end-pumped cw Nd:YAG laser. With 22.3-W pump input from two fiber-coupled laser diodes, combined with 700 mW of power injected by a singlefrequency master laser, the injection-locked slave laser emits 10 W of linearly polarized, TEM(00)-mode output in a single longitudinal mode. In addition to high efficiency, the injection-locked laser also possesses excellent output stability. At 300 Hz, the measured relative intensity noise and the frequency-noise spectral density are 2 x 10(-5)/ radicalHz and 50 Hz/ radicalHz, respectively. To improve frequency stability further, we lock the frequency of the injection-locked laser to an external high-finesse reference cavity. When the frequency was stabilized, a minimum frequency-noise spectral density of 40 mHz/ radicalHz was measured at the frequency-stabilization loop error point at 1 kHz.

Glutathione-Independent prostaglandin D synthase, identical to beta-trace, (a major CSF protein), is localized in the CNS. This enzyme, lipocalin-type prostaglandin D synthase, is a member of the lipocalin family of secretory proteins that transport small lipophilic substances. This enzyme's activity in adult rat retina was enriched sixfold in retinal pigment epithelium (RPE) and even more in interphotoreceptor matrix (IPM), all higher than brain. Western blots with anti-lipocalin-type prostaglandin D synthase showed three distinct immunoreactive bands. In the retinal cytosolic fraction, only one band was observed (M(r) 25,000); in IPM, the larger component occurred (M(r), 26,000). The RPE membrane-bound fraction showed two bands (M(r) 20,000 and 23,000), indicating synthesis, and the cytosolic fraction contained two bands (M(r) 23,000 and 26,000), indicating modification for release into IPM. At least two glycosylation sites occurred on the prostaglandin D synthase moiety, explaining the three immunoreactive bands in Western blots. Immunohistochemistry with polyclonal antibodies against this lipocalin-type enzyme showed intense localization in RPE, but less in photoreceptor outer and inner segments. In situ hybridization showed mRNA specifically expressed in RPE. Thus, lipocalin-type prostaglandin D synthase is predominantly expressed in RPE and actively accumulated in IPM. This may demonstrate gene sharing because, while catalyzing prostaglandin D2 synthesis, it may perform an additional, unrelated role in IPM. This enzyme is secreted from the RPE into IPM from which it is then taken up by photoreceptors. However, the nature of its ligand(s) is not known; they may be retinoids and/or docosahexanoic acid.

Objectives: Anomalous junction of the pancreaticobiliary duct (AJPBD) is thought to be an important risk factor for gallbladder carcinoma in Japan. In this report, we examine histopathology and cellular kinetics of gallbladder mucosae of patients with AJPBD and the possible risk of gallbladder carcinoma., Methods: We examined 62 gallbladders from patients with AJPBD (group A), 16 gallbladder carcinomas from patients with AJPBD (group B), 60 gallbladder carcinomas from patients without AJPBD (group C), and six normal gallbladders from patients without AJPBD (group D). Histopathology, mucosal heights, and proliferative cell nuclear antigen-labeling index were obtained from routinely processed tissue specimens., Results: The incidence of hyperplastic changes in group A and in the noncancerous regions (NCRs) of group B was greater than in the NCRs of group C (p < 0.05). The incidence of dysplastic changes in the NCRs of group B was greater than in the NCRs of group C (p < 0.05). The mucosal heights in group A and in the NCRs of group B were higher than in the NCRs of group C (p < 0.05). A high proliferative cell nuclear antigen-labeling index was observed in group A and in the NCRs of group B, where hyperplastic changes were frequently observed., Conclusions: These results suggest that a sequence of hyperplastic changes with a corresponding increase in cellular kinetics with progression through dysplasia to carcinoma may be important in carcinogenesis in gallbladders of patients with AJPBD. AJPBD itself may be a possible risk for gallbladder carcinoma.

Seasonal changes in the in vivo levels of the prostaglandins (PGs) PGD2, PGE2, and PGF2(alpha) were measured in the brain of the male Asian chipmunk, Tamias asiaticus (n = 111), which underwent hibernation during the period between November and March. The mean level of PGD2 ranged from 36.0 to 85.2 pg/g tissue from June to October and remained essentially unchanged (80.5 pg/g tissue) in December. However, the mean PGD2 level rose significantly to 128.6 pg/g tissue in February, and returned to 75.2 pg/g tissue in the following April, suggesting a correlation between PGD2 and hibernation phenomenon. While PGE2 level did not vary significantly throughout the year, PGF2(alpha), which appeared to be the most abundant among the three prostanoids, showed a marked circannual rhythm with a trough of 51.6 pg/g tissue in July, rising to 391.6 pg/g tissue in February and reaching the peak value of 492.7 pg/g tissue in April, the reproduction period.

Mutations in the cardiac beta-myosin heavy chain (MHC) gene of 50 Japanese patients with hypertrophic cardiomyopathy (HCM) were investigated by polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) analysis. A novel deletion mutation was detected in exon 3 of the cardiac beta-MHC gene in a Japanese family with HCM. Sequencing analysis revealed a three nucleotide deletion at codon 10 leading to a deletion of a glycine residue, which has been conserved in the myosin gene from birds to humans. Because this deletion mutation was not detected in other healthy family members, it was suggested that this 10Gly deletion is the cause of HCM in this family. The same deletion mutation has been found in three other unrelated patients with HCM. This is the first report of a one codon deletion in the beta-MHC gene in patients with HCM.

Objective: Our goal was to describe attenuation differences bordered by a straight line in the right hepatic lobe on enhanced CT in patients with right adrenal tumors and to discuss the cause of this appearance., Materials and Methods: Three patients showing attenuation differences bordered by a straight line were discovered in the CT files of 26 cases of right adrenal tumor over 3 cm in diameter. All CT scans were examined by incremental dynamic study., Results: Two patients had large zone of hyperattenuation in the right lobe bordered with a straight line intersecting both anterior branches of the right portal vein and the inferior vena cava (IVC). A third patient and one of the two patients mentioned already had zones of relative hyper- and hypoattenuation in the medial portion of the posterior hepatic segment, respectively. All three patients had large right adrenal tumors, which severely compressed the right hepatic vein near its confluence with the IVC and/or the IVC in or below its intrahepatic portion. The distribution of attenuation differences was similar to the hyperattenuation at CT arteriography or perfusion defect at CT arterial portography under temporary balloon occlusion of the right hepatic vein and inferior right hepatic vein, respectively., Conclusion: Straight-bordered attenuation differences within the right hepatic lobe at dynamic CT can be caused by compression of the right hepatic vein by large right adrenal tumors.

Purpose: To evaluate the contribution of hepatic veins to the dual blood supply in the liver under temporary hepatic venous occlusion., Materials and Methods: Selected hepatic veins in 23 patients with liver tumors were temporarily occluded with a balloon catheter. Computed tomography (CT) arteriography, CT during arterial portography (CTAP), or both were performed with a spiral technique with and without temporary occlusion of a hepatic vein., Results: After hepatic vein occlusion, a well-demarcated, wedge-shaped area of hypoattenuation was seen at CTAP and/or hyperattenuation was seen at CT arteriography in the following regions: left lobe (left hepatic vein), ventral part of the anterior segment and the medial segment except for the ventromedial part (middle hepatic vein), dorsal part of the anterior segment and the ventral part of the posterior segment (right hepatic vein), and dorsocaudal part of the right lobe (inferior right hepatic veins)., Conclusion: After hepatic venous occlusion, the portal veins become draining veins and the occluded area is supplied with arterial blood alone.

In view of the recent progress in visible lasers for next-generation optical disks, we describe the influence of source wavelength, aberration, and noise on eye-diagram jitter, which determines the ultimate disk density. The analysis indicates that the sources used in a readout of a 6× areal density, (4,22) run-length-limited code with a minimum mark length of 0.4 µm must have a wavelength that satisfies the Nyquist condition of relationship between the spot size and the minimum mark length, a wave-front aberration of less than 0.035 rms λ, and relative intensity noise of less than -125 dB/Hz.

Objective: Hepatobiliary (intrahepatic and peribiliary) cysts have been described for patients with autosomal dominant polycystic disease. The purpose of this study was to determine the prevalence of these cysts and to describe the wide variation in their appearance on CT scans., Materials and Methods: We studied CT scans for 64 patients (31 men and 33 women) who either had known autosomal dominant polycystic kidney disease or had renal cysts and a family member with polycystic kidney disease. Contrast enhancement was used for 31 patients. CT scans were retrospectively evaluated by consensus by two experienced radiologists. The presence, number, and size of hepatobiliary cysts and the presence and appearance of the two variations, peribiliary and intrahepatic cysts, were analyzed. Peribiliary cysts were determined to be present when many small (< or = 10-mm) cysts were seen adjacent to the larger (up to the third order) portal triad. Cysts present in the hepatic parenchyma but not in contact with the larger portal triad were regarded as intrahepatic cysts., Results: CT showed hepatobiliary cysts in 56 of the 64 patients (24 men and 32 women; 88%). Intrahepatic cysts were noted in all 56 patients; peribiliary cysts were definitely seen on CT scans for 22 patients and were probably seen (fewer than five cysts and/or cysts located only on one side of the portal vein) on CT scans for 19 patients (73% of all patients with hepatobiliary cysts). Peribiliary cysts appeared as discrete cysts in 31 patients, as a string of cysts in six patients, and as a tubular structure in four patients. Intrahepatic cysts generally were round but occasionally were polygonal. They were variable in number, size, and location., Conclusion: Hepatobiliary cysts were noted in 56 of 64 patients (intrahepatic cysts in all cases and peribiliary cysts in 73% of positive cases). Intrahepatic cysts varied widely in number, size, and location, whereas peribiliary cysts were small and appeared as discrete cysts, a string of cysts, or a tubular structure adjacent to the larger portal triad. It is important to be aware of the wide variety of findings for hepatobiliary cysts so that they are not confused with other abnormalities.

To elucidate the contribution of hepatic veins to the blood flow of liver, CT arterial portography and/or arteriography was performed in eight patients having hepatocellular carcinoma with transient occlusion of the hepatic vein and eight without occlusion. In each patient with occlusion of the hepatic vein, CT showed a well-demarcated fan-shaped area of low density during arterial portography and increased density during arteriography in the corresponding area. Hepatic vein occlusion could result in the pooling of arterial blood in the liver parenchyma. Transient segmental hepatic venous occlusion might improve the results of transcatheter arterial infusion and transcatheter arterial embolization for liver tumors.

Fifteen beta-carboline derivatives, including those found in the South American hallucinogenic plant Banisteriopsis caapi, were injected IP and IVC into mice. Subsequent behavioral changes were observed and the levels of the compounds in brain tissue were determined. It was found that following IP administration, tremors and/or convulsions were induced by beta-carbolines having aliphatic alkyl groups, but not by those with carbonyl and oxo groups substituted at carbon-1 of the C ring. These effects were potentiated by the presence of a methoxy group at carbon-7 of the A ring, and their duration of actions were prolonged by 3,4-dihydro derivatives. When induced, tremors/convulsions correlated with levels of beta-carbolines in the brain. The smaller ED50 values of beta-carbolines that cause tremors/convulsions showed lower levels of beta-carbolines in brain tissue.

Basal levels of prostaglandin E2 in the rat brain were determined by radioimmunoassay to be 0.68-0.79 pmol/g brain. About one-third of the prostaglandin E2 (0.23-0.28 pmol/g) was resistant to extraction with ethanol, but could be recovered with a mixture of ethanol and 1 N HCl (9:1, v/v), indicating that a tightly bound form of prostaglandin E2 exists in the brain. The amount of the bound form of prostaglandin E2 was almost unchanged by pentylenetetrazole-induced convulsion or by transcardial perfusion with a formaldehyde solution, although these treatments resulted in 40- to 80-fold increases in prostaglandin E2 content extracted with ethanol at neutral pH. A polyclonal antibody against prostaglandin E2-albumin conjugates recognized the bound form of prostaglandin E2, giving a punctate appearance in many neuronal cell bodies in the brain. Although almost all of the neuronal perikarya were immunoreactive for prostaglandin E2, intense immunoreactivity was observed in the mitral cell layer of the olfactory bulb, layer V of the cerebral neocortex, anterodorsal and reticular nuclei of the thalamus, supraoptic, paraventricular, accessory neurosecretory and lateral mammaillary nuclei of the hypothalamus, mesencephalic trigeminal nucleus, nucleus of the trapezoid body and deep cerebellar nuclei. When the cerebral neocortical regions were observed electron microscopically, immunoreaction products were seen as fine granules which were clustered into small patches in the cytoplasm of neuronal cell bodies and proximal dendrites. No immunoreaction products were seen in glial cells or endothelial cells. These results suggest that prostaglandin E2 is involved in fundamental processes of neurons.

A 76-year-old woman developed angiosarcoma 11 years after a radical mastectomy in the chronic lymphedema of the ipsilateral arm, referred to as Stewart-Treves syndrome. The patient was treated by intravenous and intralesional injection of recombinant interleukin 2 (rIL-2; TGP-3, Takeda Chemical Industries, LTD, Osaka). Intralesional injection was more effective than systemic administration. After a month, the lesion where the local injection was done showed little tumor cells with a dense infiltrate composed of lymphoid cells. It was observed that NK activity, LAK activity and IL-2 receptor positive T-cells in the peripheral blood increased during the administration of rIL-2. As the lesion was too large to be treated with rIL-2 alone, radiotherapy was performed. But the patient had no remarkably improvement and died 16 months later from the onset. Immunotherapy with rIL-2 can be useful for angiosarcoma and more effective regimen of rIL-2 is a important problem.

beta-Carboline derivatives inhibited both indoleamine 2,3-dioxygenase and tryptophan 2,3-dioxygenase activities from various sources. Among them, norharman is most potent for both enzymes from mammalian sources. Kinetic studies revealed that norharman is uncompetitive (Ki = 0.12 mM) with L-tryptophan for rabbit intestinal indoleamine 2,3-dioxygenase, and linearly competitive (Ki = 0.29 mM) with L-tryptophan for mouse liver tryptophan 2,3-dioxygenase. In addition, some beta-carbolines selectively inhibited one enzyme or the other. Pseudomonad tryptophan 2,3-dioxygenase was inhibited by a different spectrum of beta-carbolines. Such a selective inhibition by the structure of substrate analogs is more evident by the use of indole derivatives. Indole-3-acetamide, indole-3-acetonitrile and indole-3-acrylic acid exhibited a potent inhibition for mammalian tryptophan 2,3-dioxygenase, while they moderately inhibited the pseudomonad enzyme. However, they showed no inhibition for indoleamine 2,3-dioxygenase. These results suggest the difference of the structures of the active sites among these enzymes from various sources.

In order to examine the possibility that the changes in electrolytes in tissue alter the effect of thyroid hormone on NaK-ATPase, rats were fed either synthetic K-deficient diet or synthetic K-normal diet. K-deficient diet induced a reduction in K content in serum or kidney, while that of the liver remained unchanged. When a daily dose of 2.5 micrograms T3 was administered for 7 days to k-deficient rats, both Mg- and NaK-ATPase of the homogenate of liver and kidney were elevated, while the same dose failed to influence those enzymes in K-normal rats. Furthermore, T3 dose increased the Na content of liver and kidney in K-deficient rats, resulting in a significant decrease in th K/Na ratio in those tissue. Based on the estimation from chloride space, the decrease in K/Na was deemed to have occurred mainly in the intracellular space. As the levels of serum thyroid hormone and liver T3 were not influenced by K-deficiency, the effect of K depletion is likely to be mediated not through the alteration in thyroid hormone kinetics, but through some other mechanism such as the elevation of intracellular Na. The present study demonstrates that K deficiency may sensitize NaK-ATPase to the effect of thyroid hormone.

When the amounts of primary prostaglandins formed from endogenous arachidonic acid were determined in homogenates of various tissues of adult rats, prostaglandin D2 was the major prostaglandin found in most tissues. It was formed actively in the spleen (3100 ng/g tissue/5 min at 25 degrees C), intestine (2600), bone marrow (2400), lung (1100), and stomach (630); moderately in the epididymis, skin, thymus, and brain (140-340); and weakly in other tissues (less than 100). Addition of exogenous arachidonic acid (1 mM) accelerated the formation of prostaglandin D2 in all tissues as follows: spleen (15,000); bone marrow, intestine, thymus, liver, and lung (1600-5200); stomach, adrenal gland, epididymis, brain, salivary gland, skin, spinal cord, and seminal vesicle (380-1000); and other tissues (80-310). The activity of prostaglandin D synthetase (prostaglandin-H2 D-isomerase) was detected in 100,000g supernatants of almost all tissues. As judged by glutathione requirement for the reaction, inhibition of the activity by 1-chloro-2,4-dinitrobenzene, and immunotitration or immunoabsorption analyses with specific antibodies, the enzyme in the epididymis, brain, and spinal cord (1.8-9.2 nmol/min/mg protein) was glutathione-independent prostaglandin D synthetase (Y. Urade, N. Fujimoto, and O. Hayaishi (1985) J. Biol. Chem. 260, 12410-12415). The enzyme in the spleen, thymus, bone marrow, intestine, skin, and stomach (2.0-57.1) was glutathione-requiring prostaglandin D synthetase (Y. Urade, N. Fujimoto, M. Ujihara, and O. Hayaishi (1987) J. Biol. Chem. 262, 3820-3825). The activity in the kidney and testis (3.7-4.5) was catalyzed by glutathione S-transferase. The activity in the liver, lung, adrenal gland, salivary gland, heart, pancreas, and muscle (0.6-5.1) was due to both the glutathione-requiring synthetase and the transferase.

To obtain an in vitro method of LATS assay which is equally sensitive to a McKenzie bioassay, we compared the quality of cAMP generation-stimulation, thyroidal adenyl cyclase stimulation, and the stimulation of T3-release from mouse thyroid slices. Among those indicators of thyroid stimulation, stimulation by IgG of the release of T3 from incubated thyroid slices is the most sensitive, reproducible and reliable indicator, reflecting faithfully the results of a McKenzie bioassay. Stimulation of cAMP generation in slice manifested less sensitivity, but reasonable reproducibility. However, adenyl cyclase stimulation by IgG of patients with Graves' disease was erratic in two successive experiments, probably due to a non-specific effect of IgG. When adenyl cyclase stimulation was adopted as a sole indicator of thyroid stimulation, the results must be interpreted cautiously.

Small pancreatic tumor is difficult to be diagnosed. Two cases of pancreatic islet cell tumors were examined by ultrasonography. One case was islet cell carcinoma, the other insulinoma. In both cases, ultrasonography was useful in detecting the tumor, judging the location of tumor during surgical operation and deciding the surgical procedure.