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Biomedical subjects

H Ohta

Publications and source records attributed to H Ohta.

At least 433 records · Page 24Linked to original sources
PubMed1993

Cellular and cytokine responses of the human central nervous system to intracranial administration of tumor necrosis factor alpha for the treatment of malignant gliomas.

To elucidate the role of tumor necrosis factor alpha (TNF alpha) as a biological response modifier, we studied cellular and cytokine responses of the central nervous system to TNF alpha administered intracranially in a phase I clinical trial for patients with malignant gliomas. Six patients received injections of TNF alpha (1.25 x 10(3)-10 x 10(3) U/injection) into the tumor cavities, and regional fluids (RF) and lumbar cerebrospinal fluids (CF) were serially sampled before and after the injections. Recruitment of neutrophils occurred, mostly peaking 8 h after TNF alpha injection, and fewer numbers of CD4+ T cells and monocytes/macrophages migrated, subsequently peaking at 24 h. The CF leukocytosis persisted for 48 h and was associated with an increased level of neutrophil chemotactic activity in the CF. This neutrophil chemotactic activity was attributed to interleukin-8 (IL-8) by HPLC. The level of IL-6 activity in the CF and RF consistently increased; beginning 2 h after TNF alpha injection and reaching the maximum between 8 h and 12 h. It returned to the basal level within 48 h. IL-1 beta was detected in the CF of three patients, its level peaking at 8 h. Prostaglandin E2 also increased after injection of TNF alpha, peaking between 4 h and 12 h and then gradually decreasing. Transforming growth factor beta was found in all cases tested and one patient showed a significant change after TNF alpha injection. IL-2 activity, interferon alpha (INF alpha) activity, IFN beta, and granulocyte/macrophage-colony-stimulating factor were not detected in the CF or RF. In conclusion, TNF alpha is biologically effective in inducing migration of immune cells and generating multiple cytokine responses in the human central nervous system.

Adult↗
PubMed1993

The immunohistochemical evaluation of PSP/reg-protein in normal and diseased human pancreatic tissues.

In order to elucidate the characteristics of reg-protein, which is identical to pancreatic stone protein (PSP/reg-protein), and the relationship between the generation and evolution of chronic pancreatitis and the expression of PSP/reg-protein in the pancreas, we investigated the expression of PSP/reg-protein in normal and diseased human pancreatic tissues by immunohistochemistry. The PSP/reg-protein was expressed in all cases with normal pancreas or chronic pancreatitis, and in 70.6% of cases with pancreatic cancer. This protein was present in the cytoplasm of acinar cells and, in some cases, in the intraluminal contents of ductules in nonmalignant tissues. From the view of distribution and cellular localization, PSP/reg-protein was expressed more broadly and densely in chronic pancreatitis with mild to moderate injury than in the normal pancreas. However, the protein was less expressed in severely damaged chronic pancreatitis tissue, such as calcifying pancreatitis, than in the normal pancreas. These findings suggest that mild to moderate injury to pancreatic tissue may stimulate the synthesis of PSP/reg-protein, whereas more severe injury tends to depress it.

Calcium-Binding Proteins↗
PubMed1993

Liver scintigraphy in a patient with Gaucher disease.

Liver scintigraphy including SPECT was performed in a patient with Gaucher disease and compared with other methods. Multiple photon-deficient areas in the liver and spleen were recognized, and in evaluating the reticuloendothelial system of the liver, liver SPECT image was superior to US, CT and MR images.

Adult↗
PubMed1993

99mTc-HMDP accumulation in a phyllodes tumor of the breast, a case report.

In a patient with breast tumor, 99mTc-HMDP accumulation in the tumor was recognized in evaluating bone metastasis. Surgery and histopathology revealed that the tumor was a phyllodes tumor. This scintigraphic finding was thought to be rare and phyllodes tumor should be included in differential diagnosis when 99mTc-HMDP accumulation in the breast was recognized.

Breast Neoplasms↗
PubMed1993

67Ga citrate and 99mTc(v)-DMSA scintigraphy in a case of maxillary sinus liposarcoma.

Scintigraphic images with 67Ga citrate and 99mTc(v)-dimercaptosuccinic acid and MR image of a 16-year-old male with maxillary sinus liposarcoma (predominantly myxoid type) are reported. The MR image clearly indicated the exact location, size and anatomical relationship of the tumor. Scintigraphic evaluation was useful in suggesting the malignant nature of the tumor and showed no distant metastasis. Both examinations were effective in treating this case.

Adolescent↗
PubMed1993

Biliary papillomatosis with the point mutation of K-ras gene arising in congenital choledochal cyst.

Biliary papillomatosis is a rare entity. A case of biliary papillomatosis associated with congenital choledochal cyst and intrahepatic gallstones is reported here. Percutaneous transhepatic cholangioscopy revealed multiple papillary lesions of the right intrahepatic duct and the common bile duct. Microscopically, the papillary mucosal lesion showed papillary proliferations of bile duct epithelial cells with mild atypia. Furthermore, a point mutation at codon 12 of the K-ras oncogene was found in the papillary lesion. To the best of our knowledge, this is the first case of biliary papillomatosis arising in congenital choledochal cyst. Although the pathogenesis of biliary papillomatosis in our case was unclear, biliary irritation associated with choledochal cyst may be related to biliary papillomatosis with point mutation at codon 12 of K-ras gene.

Aged↗
PubMed1993

Impairment of acquisition but not retention of a simple operant discrimination performance in aged Fischer 344 rats.

Although deterioration of learning and memory in aged rodents has been reported using a variety of tasks, little information is available on the effects of aging on acquisition and retention of reference memory in food-motivated tasks. In the present study, to examine reference memory, a simple operant discrimination task was used. Aged (24 month) and young (5 month) Fischer 344 rats were trained to discriminate brightness for food reward in an operant chamber. Aged rats showed significantly impaired learning compared to young rats, and the level of discrimination of aged rats was significantly lower than that of young rats. The aged rats also exhibited impaired learning in discriminating an auditory cue. Aged rats as well as young rats had good retention of brightness discrimination performance 30 days after the last training session. Scopolamine (0.3 mg/kg) did not impair discrimination learning nor affect well-trained discrimination performance in young rats. These data suggest that acquisition but not retention of reference memory is impaired in aged rats, and that the impaired acquisition observed in aged rats may not be due to dysfunction of the central cholinergic systems.

Aging↗
PubMed1993

Biphasic effects of typical antidepressants and mianserin, an atypical antidepressant, on aggressive behavior in socially isolated mice.

Effects of several typical antidepressants and of an atypical antidepressant, mianserin, on the aggressive behavior (AGB) in long-term isolated mice were examined. IP administration of maprotiline (2.5 and 5 mg/kg), amitriptyline (5 and 10 mg/kg), clomipramine (2.5 and 5 mg/kg), and mianserin (5 mg/kg) significantly increased the duration of AGB. However, at higher doses (maprotiline, 10 mg/kg; amitriptyline, 20 mg/kg; clomipramine, 10 and 20 mg/kg; mianserin, 10 and 20 mg/kg) these antidepressants either did not affect AGB or inhibited it. Amitriptyline (20 mg/kg) and mianserin (10 mg/kg) but not maprotiline (10 mg/kg) or clomipramine (20 mg/kg) decreased spontaneous motor activity in isolated mice. Yohimbine (0.5 mg/kg, IP), an alpha 2-antagonist, changed the antidepressant-induced enhancement of AGB into inhibition without affecting the basal aggressive responses. Prazosin (0.3 mg/kg, IP), an alpha 1-antagonist, did not affect either maprotiline- or clomipramine-induced enhancement of AGB, but it changed the mianserin-induced enhancement of AGB into inhibition. These results indicate that antidepressants that inhibit noradrenaline uptake and/or stimulate noradrenaline output from nerve terminals have biphasic effects on AGB in isolated mice and that the antidepressant-induced enhancement of AGB is mediated by noradrenergic stimulation of alpha 2-adrenoceptors, whereas the antidepressant-induced inhibition of AGB may be mediated by non-alpha 2-adrenoceptors or by nonadrenergic system(s).

Aggression↗
PubMed1993

Effect of alpha 2-adrenergic drugs on REM sleep deprivation-induced increase in swimming activity.

Effects of alpha 2-adrenergic agents on rapid eye movement sleep (REMs) deprivation-induced anti-immobility effect in the forced swimming test (FST) were investigated. Mice were deprived of REMs for 24-72 h by a small pedestal method. Animals that were either group housed or socially isolated during the same period as REMs deprivation were used as the control groups. REMs deprivation for 48 and 72 but not 24 h significantly increased swimming activity without increasing locomotor activity. Clonidine HCl (30-300 micrograms/kg, IP), an alpha 2-adrenoceptor agonist, dose-dependently increased swimming activity in group-housed, isolated, and REMs-deprived mice, but the effective doses of clonidine in REMs-deprived mice were lower than those in group-housed or isolated animals. Yohimbine HCl (5 mg/kg, IP), an alpha 2-adrenoceptor antagonist, blocked the clonidine (300 micrograms/kg)- but not the REMs deprivation-induced increase in swimming activity. These results suggest that REMs deprivation enhances the sensitivity of the alpha 2-adrenoceptor and that the increase in swimming activity by REMs deprivation may be mediated by other neuronal mechanisms rather than the alpha 2-adrenoceptor.

Adrenergic alpha-2 Receptor Antagonists↗
PubMed1993

Peony and its major constituent, paeoniflorin, improve radial maze performance impaired by scopolamine in rats.

A traditional Chinese medicine, Shimotsu-to has been shown to improve spatial working memory in rats. Shimotsu-to consists of four herbs, Japanese angelica root, cnidium rhizome, peony root, and rehmannia root. In the present study, the effects of aqueous extracts of each component herb on scopolamine (0.3 mg/kg)-induced spatial working memory disruption were examined using an eight-arm radical maze task in rats. Among the four component herbs, peony root extract (0.25 and 1 g dried herb/kg, PO) exhibited the most potent antagonizing effect on the scopolamine disruption of the choice accuracy. Japanese angelica root extract (1 g dried herb/kg, PO) also significantly attenuated the scopolamine disruption, whereas neither cnidium rhizome nor rehmannia root affected it. Paeoniflorin (0.01-1 mg/kg, PO), a major constituent of peony root, dose-dependently attenuated the scopolamine-induced impairment in the choice accuracy. Scopolamine (0.3 mg/kg, IP) significantly decreased the acetylcholine contents in the hippocampus, cortex, and striatum. Although paeoniflorin alone did not affect the acetylcholine contents, pretreatment with paeoniflorin significantly prevented the scopolamine-induced decrease in the acetylcholine content in the striatum, but not in the hippocampus or cortex. These data suggest that peony root mainly contributes to the cognitive enhancing effect of Shimotsu-to and that paeoniflorin may be one of the active constituents of peony root.

Acetylcholine↗
PubMed1993

The nature of heterogeneous components of extracellular-superoxide dismutase purified from human umbilical cords.

Extracellular-superoxide dismutase (EC. 1.15.1.1., EC-SOD) is a secretory, tetrameric glycoprotein. This enzyme in plasma is heterogeneous with regard to heparin affinity and can be divided into at least three fractions approximately equally large: EC-SOD A, which lacks affinity; EC-SOD B with intermediate affinity; and EC-SOD C with high affinity. In this article, EC-SOD has been purified with a high yield from human umbilical cords. Of the umbilical cord EC-SOD, 0.8% behaved as subtype A, 1.9% as subtype B, and almost all as high heparin affinity subtype C. Purified native EC-SOD (n-EC-SOD C) showed a single band with enzymatic activity on polyacrylamide gel electrophoresis. It showed two bands with apparent molecular masses of 29.3 and 32.0 kDa on SDS-PAGE, while recombinant EC-SOD C (r-EC-SOD C) showed only one band with 32.0 kDa. By western blotting analysis with anti r-EC-SOD C antibody, two bands of n-EC-SOD C were detected at the same positions as in the gel stained with Coomassie blue. The appearance of two monomeric components with different molecular masses does not reside in the carbohydrate moiety, because the difference between the two components was not abolished by glycopeptidase F treatment; however, both bands were shifted to lower molecular weight ranges by this treatment. The two components could be clearly separated from each other by C4 reverse-phase high-performance liquid chromatography (HPLC).(ABSTRACT TRUNCATED AT 250 WORDS)

Amidohydrolases↗
PubMed1993

A synthesis of (R)-recifeiolide by the aid of biochemical reaction as the key-step.

(R)-Recifeiolide, a naturally occurring macrolactone, was synthesized in optically pure form by the aid of biocatalysts. Lipase-catalyzed lactonization of the racemic precursor afforded the desired compound with a concomitant kinetic resolution. The optically active acyclic precursor could be synthesized by the reduction of corresponding ketone with Pichia farinosa IAM 4682. The yeast reduction proceeded with the anti-Prelog rule, selecting si-face attack on the carbonyl group to give (R)-alcohol with > 95% e.e.

Acremonium↗
PubMed1993

Successful treatment of a patient with idiopathic factor VIII inhibitor with double filtration plasmapheresis and steroid administration.

We report a 74-year-old Japanese woman who had bleeding due to a factor VIII inhibitor in the absence of diseases known to be associated with its development. She abruptly developed a large painful purpura extending from the right hip to the thigh followed by an intramuscular haematoma of her left anterior chest. Examinations revealed a marked depression of factor VIII activity (5%) and the presence of 31 Bethesda units/ml factor VIII inhibiting activity. The phenotypes of these inhibitors were of the IgG-kappa and IgG-lambda types. She was treated with oral prednisolone and double filtration plasmapheresis (DFPP). The inhibitors rapidly disappeared after three sessions of plasmapheresis and her plasma factor VIII activity increased to a normal level. During this treatment, no major adverse effects such as thrombosis and infection were observed and transfusion of fresh frozen plasma (FFP) was not necessary. Heterogeneity of idiopathic factor VIII inhibitors in elderly patients is common and spontaneous disappearance or elimination of such inhibitors by treatment is often difficult to achieve. However, the combination of oral prednisolone and double filtration plasmapheresis is effective and safe for idiopathic factor VIII inhibitors and is a worthwhile approach to treatment.

Aged↗
PubMed1993

Diagnostic significance of cancer-associated carbohydrate antigen (CA19-9) concentrations in pancreatic juice: analysis in pure pancreatic juice collected by endoscopic aspiration and immunohistochemical study in chronic pancreatitis.

This study evaluated the diagnostic significance of concentrations of the cancer-associated carbohydrate antigen CA19-9 in pure pancreatic juice (PPJ) collected by endoscopic cannulation. We also attempted to elucidate the features and source of the increased CA19-9 concentration found in the pancreatic juice of patients with chronic pancreatitis (CP) by means of immunohistochemical staining. The mean output as well as the mean concentration of CA19-9 in each of the four fractions collected was highest in patients with pancreatic cancer (PC) and also was elevated significantly in patients with CP compared with controls. However, CA19-9 concentrations were not elevated in patients with cholecystolithiasis. When the cutoff value was set as the mean concentration + 2SD of the controls, significantly elevated concentrations of CA19-9 were found in the third fraction (secretory phase) in 90% of the patients with PC and 66% of the patients with CP. Immunohistochemical staining revealed that CA19-9 was expressed more widely in the ductal cells of CP tissues than in those of normal pancreatic (NP) tissues, with CP tissue showing more CA19-9-positive ductal cells per area than NP tissues. In NP tissue, CA19-9 was localized to the apical surface and supranuclear regions (apical type) in all the ductal cells stained by the antigen, while approximately 50% of cases with CP exhibited a cytoplasmic pattern showing a loss of polarity of the antigen expression. Moreover, this cellular localization pattern was more pronounced in the small ducts that had proliferated and aggregated following the destruction of lobules in CP.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1993

Sequence determination of the P gene of simian virus 41: presence of irregular deletions near the RNA-editing sites of paramyxoviruses.

The complete nucleotide sequence of the P gene of simian virus 41 (SV41) was determined. The gene was found to be 1406 nucleotides long and to contain a relatively small open reading frame encoding a cysteine-rich V protein with a calculated M(r) of 24076. We have demonstrated that RNA-editing events occur in SV41 P gene transcripts and that the ratio of edited mRNAs to faithfully copied mRNA (P-mRNA:V-mRNA) is about 1:5 at either 24 or 40 h post-infection. The mRNA with two G insertions was capable of encoding a P protein of 395 amino acids with a predicted M(r) of 41,992. A kinetic study of P and V proteins by Western blot analysis showed that in virus-infected cells the amounts of both proteins were almost equal although the V-mRNA was considerably more abundant than the P-mRNA. Alignment of the SV41 P and V proteins with those of nine other paramyxoviruses demonstrated that irregular gaps were present around the RNA-editing sites.

Amino Acid Sequence↗
PubMed1993

Identification of K-ras oncogene mutations in the pure pancreatic juice of patients with ductal pancreatic cancers.

Pancreatic cancer is detected on the basis of morphological changes delineated by means of various image-diagnostic methods. However, differentiation between chronic pancreatitis and pancreatic cancer, especially at the early stage, is not always simple when based upon the morphological changes alone. Therefore, we attempted to elucidate K-ras mutations in the sediment of pure pancreatic juice (PPJ) containing exfoliated ductal pancreatic cancer cells. PPJ was collected endoscopically from 20 patients with pancreatic cancer (PC) and 18 patients with chronic pancreatitis (CP). Polymerase chain reaction and allele specific oligonucleotide dot blot hybridization for K-ras mutations were performed with the DNA extracted from these samples. A K-ras mutation at codon 12 was identified in the PPJ of 11/20 (55%) of the patients with PC. On the other hand, the same mutation was not identified in the PPJ of any patient with CP. Moreover, K-ras mutations at codons 13 and 61 were not recognized in the PPJ of any patient with either PC or CP. These findings suggested that the presence of a K-ras mutation at codon 12 in PPJ would be useful in confirming the diagnosis of PC.

Adult↗
PubMed1993

Saliva-binding region of Streptococcus mutans surface protein antigen.

A 190-kDa surface protein antigen (PAc) of Streptococcus mutans binds to human salivary components. For detection of specific binding of the PAc protein to human salivary components, a simple sandwich assay was used. Microtiter plates precoated with recombinant PAc (rPAc), PAc fragments, or S. mutans whole cells were allowed to react with human whole saliva and then were incubated with biotinylated rPAc. The biotinylated rPAc bound to salivary components was detected by use of alkaline phosphatase-conjugated streptavidin and p-nitrophenylphosphate. In this assay, the binding of whole cells of S. mutans and purified rPAc to salivary components was confirmed. For determination of a saliva-binding region of the PAc molecule, 14 truncated PAc fragments were constructed by use of the polymerase chain reaction and an expression vector, pAX4a+. The binding of these truncated PAc fragments to human salivary components was determined by the sandwich assay. Among the truncated PAc fragments, fragments corresponding to residues 39 to 864 and residues 39 to 1000 of PAc showed a high ability to bind to salivary components. Shorter recombinant fragments corresponding to residues 39 to 217, residues 200 to 481, residues 470 to 749, and residues 688 to 864 did not exhibit any binding ability. The fragment that corresponds to a proline-rich repeating region (residues 828 to 1000) bound directly to the PAc protein. These results suggest that residues 39 864 of the PAc molecule are important in the binding of the surface protein to human salivary components, and the proline-rich repeating region of the PAc protein may contribute to spontaneous self-aggregation of the PAc protein.

Antigens, Bacterial↗