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Biomedical subjects

F Nakayama

Publications and source records attributed to F Nakayama.

At least 19 recordsLinked to original sources

CD15 expression in mature granulocytes is determined by alpha 1,3-fucosyltransferase IX, but in promyelocytes and monocytes by alpha 1,3-fucosyltransferase IV.

The CD15 carbohydrate epitope is expressed in mature human neutrophils, monocytes, and promyelocytes. We aimed to determine the alpha1,3-fucosyltransferase responsible for the expression of CD15 in each subpopulation of leukocytes. Three alpha1,3-fucosyltransferases, FUT4, FUT7, and FUT9, are expressed in human leukocytes. We demonstrated that FUT9 exhibits 20-fold stronger activity for CD15 synthesis than FUT4, whereas FUT4 exhibits 4.5-fold stronger activity for CDw65 synthesis than FUT9. By competitive reverse transcriptase-polymerase chain reaction, FUT9 was found to be strongly expressed in mature granulocytes and peripheral blood mononuclear cell, but not in monocytes. CD34(+) and CD15(+) cells in cord blood and myeloid cell lines (HL-60 and U937) did not express FUT9 at all. FUT4 transcripts were ubiquitously expressed in all blood cells and all cultured cell lines, with HL-60 and U937 cells in particular expressing a number of FUT4 transcripts. Transfection of the FUT9 gene into Jurkat and U937 cells demonstrated that FUT9 has the potential to express CD15 in myeloid and lymphoid cells. These findings suggest that the expression of CD15 in mature granulocytes is directed by FUT9, whereas it is determined in promyelocytes and monocytes by FUT4. Measurement of CD15 synthesizing activity in cell homogenates of each cell population using the polylactosamine acceptor further supported these conclusions.

Antigens, CD↗

Expression of cutaneous lymphocyte-associated antigen regulated by a set of glycosyltransferases in human T cells: involvement of alpha1, 3-fucosyltransferase VII and beta1,4-galactosyltransferase I.

Cutaneous lymphocyte-associated antigen (CLA), which plays a key part in skin homing of human CD4+ memory T cells via CLA/E-selectin binding, is upregulated by IL-12 and downregulated by IL-4. Although alpha1,3-fucosyltransferase VII is essential for synthesis of the CLA carbohydrate epitope, little is known about how the CLA expression is regulated by a number of glycosyltransferases. A 6 wk long-term culture for the in vitro differentiation of naïve Th cells to memory Th1 cells was employed. By repeated activation in the presence of IL-12, naïve T cells differentiated into memory Th1 cells, resulting in the upregulation of CLA expression. The switching of cytokine from IL-12 to IL-4 at three cycles resulted in a marked downregulation of CLA. The transcript levels of 16 glycosyltransferases and P-selectin glycoprotein ligand-1, all considered to be potentially involved in CLA synthesis, were determined after each cycle. The level of CLA expression was well correlated with the amounts of alpha1,3-fucosyltransferase VII and beta1,4-galactosyltransferase I. Both were upregulated by IL-12 and downregulated by IL-4. In particular, alpha1,3-fucosyltransferase VII levels decreased markedly in the presence of IL-4. P-selectin glycoprotein ligand-1 and Core 2 beta1, 6-N-acetylglucosaminyltransferase were progressively up-regulated by repeated IL-12 stimulation, but they were not downregulated by IL-4. The transcript levels of some genes examined were constitutive without any correlation to CLA expression. These results suggest that the level of CLA expression is determined by alpha1, 3-fucosyltransferase VII and beta1,4-galactosyltransferase I, the other enzymes merely participating in the synthesis of CLA. In peripheral blood mononuclear cells, IL-12 and IL-4 profoundly upregulated and downregulated the alpha1,3-fucosyltransferase VII transcripts, respectively, but not the beta1,4-galactosyltransferase I ones, within only 2 h of in vitro culture. This suggested that alpha1,3-fucosyltransferase VII is transcriptionally regulated directly by IL-12 and IL-4.

Antigens, Differentiation, T-Lymphocyte↗

Lewis and secretor gene dosages affect CA19-9 and DU-PAN-2 serum levels in normal individuals and colorectal cancer patients.

The effect of doses of the secretor (Se) and Lewis (Le) genes on the serum levels of CA19-9 and DU-PAN-2 was investigated in 400 normal individuals. It was clearly demonstrated that the Se gene dosage negatively affected both the CA19-9 and DU-PAN-2 values, whereas the Le gene dosage positively affected the CA19-9 value and negatively affected the DU-PAN-2 value. The 400 normal individuals were separated into nine groups by their Le and Se genotypes, as follows: group 1, Le/Le and se/se; group 2, Le/le and se/se; group 3, Le/Le and Se/se; group 4, Le/le and Se/se; group 5, Le/Le and Se/Se; group 6, Le/le and Se/Se; group 7, le/le and se/se; group 8, le/le and Se/se; and group 9, le/le and Se/Se. The group 1 individuals, having homozygous inactive Se alleles (se/se) and homozygous active Le alleles (Le/Le), exhibited the highest mean CA19-9 value. The CA19-9 value clearly ranged from a high in group 1 to a low in group 9. All of the Le-negative individuals who had the le/le genotype (groups 7, 8, and 9) had completely negative CA19-9 values, i.e., under 1.0 unit/ml, irrespective of the Se genotype. Group 7 individuals (le/le and se/se) showed a higher mean DU-PAN-2 value than did individuals in other groups. The Le-negative individuals in groups 8 and 9 also showed a higher mean DU-PAN-2 value than did the Le-positive individuals in groups 1-6. We recommend that the revised Le and Se genotype-dependent positive/negative cutoff values for CA19-9 and DU-PAN-2, determined in this study, be applied for more accurate cancer diagnoses. The Le and Se genotypes of 168 patients with colorectal cancer were also examined, and the CA19-9 and DU-PAN-2 values were measured before surgical resection. All 15 Le-negative patients (le/le) with colorectal cancer again showed undetectable CA19-9 values, i.e., under 1.0 unit/ml, but many of them exhibited highly positive DU-PAN-2 values. In contrast, many of the Le-positive patients (Le/Le or Le/le) had positive CA19-9 values, whereas very few of them exhibited positive DU-PAN-2 values. CA19-9 measurement is more useful than is DU-PAN-2 measurement for Le-positive patients, but it is not useful for Le-negative ones. DU-PAN-2 measurement should be performed in Le-negative patients for cancer diagnosis.

Alleles↗

Effect of streptococcal lyzate OK-432 on peripheral blood mononuclear cells in gastric cancer patients.

OK-432, a killed preparation of Streptococcus pyogenes, as well as Bacillus Calmette-Guerin (BCG) and Corynebacterium parvum are all known biological response modifiers. To examine the immunomodulatory effects of OK-432, natural killer cell activity and cytokine production by peripheral blood mononuclear cells (PBMCs) were assessed in 32 patients with gastric cancer. Skin tests for Streptococcus pyogenes A-3Su (Su-PS) and BCG were performed in all patients. Other nutritional and immunological parameters were also determined. OK-432-treated PBMCs showed a significant increase of cytotoxicity against K562 cells (p < 0.01). Increased levels of interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha) and interleukin-2 (IL-2) were found in the supernatants of cultures treated with OK-432 in 29 (90.6%), 20 (62.5%), and 8 (25.0%) out of 32 patients, respectively. Natural killer cell activity, IFN-gamma production, and the Su-PS skin test were positively correlated (p < 0.01). In contrast, the BCG test and other markers were not correlated with natural killer cell activity and IFN-gamma production. These results suggest that the Su-PS skin test could predict OK-432-induced natural killer cell activity and IFN-gamma production in patients with gastric cancer, and was therefore useful to determine whether patients were responders to OK-432.

Adjuvants, Immunologic↗

Panniculitis with eosinophilic infiltration due to gabexate mesilate (FOY): possibility of allergic reaction.

A 59-year-old Japanese man developed septal panniculitis with eosinophilic infiltration in both forearms and the dorsum of the left hand after a gabexate mesilate intravenous drip infusion for acute pancreatitis through catheters implanted in these sites. Gabexate mesilate at a dose of 1000 mg per day had been given continuously for 8 days, and antibiotics were added by the same infusion route twice a day. All the infusion routes, however, became occluded one after the other. Reddish swelling first occurred at the left wrist 6 hours after occlusion of the infusion route, and, on both forearms, reddish swelling occurred about one week after the occlusion of each route. Patch testing revealed a +2 reaction to gabexate mesilate (10% pet) at days 3 and 7, and skin testing revealed indurated erythema to gabexate mesilate (0.1% aq) at days 2 and 3. The specimens biopsied from the positive skin testing reaction sites showed perivascular infiltrate and slight septal panniculitis. The inflammatory infiltrate consisted predominantly of lymphocytes with small numbers of eosinophils. Staining of the specimen biopsied from the right forearm lesion with anti-eosinophil cationic protein (ECP) antibodies (EG1 and EG2) showed deposition of eosinophil-derived granule proteins at the damaged septal connective tissues of the panniculitis. The panniculitis improved with topical steroid treatment. This case suggested that the concentration of infused gabexate mesilate may have been high enough to damage blood vessels and that gabexate mesilate may have leaked into the surrounding connective tissues, inducing allergic reactions and resulting in lesions.

Acute Disease↗

Ossifying fibromyxoid tumor of soft parts of the back.

We report a first case of ossifying fibromyxoid tumor of soft parts of the back, a 10 x 9.5 x 6 cm well-circumscribed elevated subcutaneous tumor demarcated by an incomplete fibrous capsule with bone formation at its base. The tumor was composed of both myxomatous areas with spindle tumor cells and pseudoalveolar structures with oval tumor cells. The tumor cells had evenly sized, oval nuclei without atypia and slightly eosinophilic cytoplasm with intracellular vacuoles. Immunohistochemical studies revealed positivity for vimentin and focal positivity for S-100 protein. Ultrastructural examination revealed a few filopodia-like processes, discontinuous basal lamina and a few primitive cell junctions. Based on these immunohistochemical and ultrastructural results, this tumor may be related to Schwann's cells. There has been no recurrence 5 years after wide local excision.

Aged↗

Immunoglobulin gene analysis of cutaneous pseudolymphoma by polymerase chain reaction.

Polymerase chain reaction (PCR) was used to amplify the V-D-J region of the immunoglobulin heavy chain gene from DNA extracted from the formalin fixed, paraffin embedded skin of 3 cases of pseudolymphoma. The products were electrophoresed and observed under ultraviolet light after ethidium bromide staining. Specimens of two cases showed smears of polyclonal amplified DNA. The specimen of one case (Case 3), however, showed a single band with a smear. The presence of monoclonality in B lymphocyte populations may suggest the possibility of low grade malignancy of pseudolymphoma or transformation to malignant lymphoma in the future.

Adult↗

Modes of biliobiliary anastomosis in relation to the healing process and occurrence of postoperative stricture.

The inverting and everting methods of biliobiliary anastomoses were compared histopathologically and electron microscopically. Epithelialization started on the 3rd postoperative day and occurred within 8 mm of the anastomosis with an earlier and more active epithelialization being seen in the proximal area than in the distal. A rapid decrease of the mucosal defect was seen for 3-5 days which slowed down thereafter, and closure was achieved by 30 days after the anastomosis in both groups. The everted group showed a smoother and more rapid healing process, quicker epithelialization, and less mucosal defects than the inverted group. In the chronic phase, the inverted group showed more papillary hyperplasia and more pronounced fibrosis of the wall. The stricture index, being the internal circumference of the common bile duct: proximal x 2/anastomosis site + duodenal x 100, of the everted group was 123.7% compared to 146.7% for the inverted group, but there was no statistical difference. There was no difference in the total area of crypts, representing the epithelialization, between the two groups. Anastomoses with proximal dilatation therefore healed more slowly than those without dilatation. These findings show everted anastomosis to be superior to inverted anastomosis and thus support the usefulness of T-tube drainage to prevent postoperative dilatation of the bile duct.

Anastomosis, Surgical↗

Extramedullary plasmacytoma: cytological and genotypic studies.

A 62-year-old woman had multiple plasmacytomas in the skin and lymph nodes, without Bence-Jones protein or a monoclonal peak of serum immunoglobulins. Infiltrating plasmacytoid cells expressed cytoplasmic IgG (lambda) and surface CD38, without any B-cell markers. There was no visceral or bone marrow involvement suggestive of multiple myeloma. Southern blot analysis of extracted DNA from the cutaneous lesions showed two rearranged bands with an immunoglobulin, but not a T-cell receptor, gene probe. The patient showed a poor response to chemotherapy, and died of bronchopneumonia. The clinical course and cytological features differentiate multiple cutaneous extramedullary plasmacytomas from solitary cutaneous extramedullary plasmacytoma and cutaneous lesions associated with multiple myeloma.

Female↗

Adenocarcinoma of the gallbladder associated with anomalous pancreaticobiliary ductal junction.

We have previously shown that an anomalous pancreaticobiliary ductal junction (APBDJ) is a risk factor for developing carcinoma of the gallbladder. However, the incidence of APBDJ in patients with primary carcinoma of the gallbladder has been little examined. Of 53 consecutive patients with gallbladder carcinoma, 37 patients had a direct cholangiography to allow satisfactory evaluation of the pancreaticobiliary ductal junction. Eleven per cent of these 37 patients had an associated APBDJ, which was significantly higher than the reported incidence of APBDJ in human (2%). Two of these four patients were associated with choledochal cyst and the other two were not. The main clinical differences in patients with gallbladder carcinoma associated with APBDJ and those without APBDJ were that the mean age of the former group was lower by about 10 years than the latter, and none had gallstones in the former while 54 per cent had gallstones in the latter group. The results show that APBDJ is a risk factor for developing carcinoma of the gallbladder earlier, and factors other than gallstone are more causative in patients with APBDJ. The frequent association with APBDJ should be kept in mind at the time of surgical treatment of the primary gallbladder carcinoma.

Abnormalities, Multiple↗

Late development of cholangiocarcinoma after the treatment of hepatolithiasis.

Although the association of cholangiocarcinoma with intrahepatic calculi (hepatolithiasis) is well recognized, the late development of cholangiocarcinoma after the treatment of hepatolithiasis has not been reported in detail. Of 109 consecutive patients with hepatolithiasis treated during 19 years, eight patients had cholangiocarcinoma, seven of whom had cholangiocarcinoma two to 14 years, with a mean of eight years, after the treatment of hepatolithiasis. Absence of cholangiocarcinoma was confirmed when stones were removed at the time of the initial treatment. The mean age was 56 years, with a female to male ratio of 2:5. At the time of detecting cholangiocarcinoma, three patients had no gallstones and four had gallstones at the corresponding site to the carcinoma. Cystic dilatation of the intrahepatic bile duct was often observed on the direct cholangiogram. The biles were all infected mainly with Escherichia coli and Klebsiella species. Thus, bile stasis and bacteria infection seems to be the important causative factor, causing cholangiocarcinoma rather than the calculi itself. Because the symptoms only mimic those of cholangitis, the possible presence of cholangiocarcinoma should be considered even after the treatment of hepatolithiasis for early detection and curative resection.

Adenoma, Bile Duct↗

Isolation of a calcium-regulatory protein from black pigment gallstones: similarity with a protein from cholesterol gallstones.

We have previously isolated from 13 cholesterol gallstones a low molecular weight acidic bili-protein that inhibited the precipitation of calcium carbonate in vitro. We now report the isolation of a similar protein from seven black pigment gallstones. Cholesterol was removed from the stones by Soxhlet apparatus with methyl t-butyl ether, and bile acids were extracted with methanol. The protein was purified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis after demineralization of the stones with ethylenediaminetetraacetate. Structural and functional properties of the protein from the black stones that were similar to the protein from the cholesterol stones included the following: (a) an apparent molecular weight of about 5 kD; (b) a high content of acidic (19.8%) and hydrophobic (50.1%) amino acids with a low content of basic residues (8.4%) and little sulfide-containing amino acids (1.9%); (c) an inhibitory effect on both the initiation and growth of calcium carbonate crystals in vitro; and (d) very tight (possibly covalent) binding of a diazo-positive yellow pigment, presumably bilirubin, with maximum spectral absorbance at 410 nm. The structural and functional similarities of these bili-proteins from black pigment and cholesterol gallstones and their striking effects on calcium carbonate precipitation in vitro suggest that they play a common role in the regulation of precipitation of calcium salts during the formation of both types of gallstones.

Calcium Carbonate↗

Effect of chenodeoxycholate and ursodeoxycholate on nucleation time in human gallbladder bile.

The effects of treatment with chenodeoxycholic acid (CDCA) or ursodeoxycholic acid (UDCA) on nucleation time, biliary lipid concentration, and vesicular lipid composition were studied. Gallbladder bile was collected at the time of surgery from 33 cholesterol gallstone patients who were divided into three groups: 16 untreated, 9 pretreated with CDCA (400 mg/day), and 8 pretreated with UDCA (600 mg/day) for 1-3 weeks before surgery. Control bile samples were also collected from nine patients without cholelithiasis. Nucleation time was prolonged significantly in both CDCA- and UDCA-treated groups [12.6 +/- 8.5 (SD) and 21.0 +/- 0 days, respectively] compared with the untreated gallstone group (3.3 +/- 3.2 days). Both treatments significantly decreased the proportion and concentration of both cholesterol and phospholipids present in the vesicular phase. Treatment with UDCA decreased the cholesterol saturation index more than did CDCA at the dose used in this study. In the CDCA-treated group, patients without much change in cholesterol saturation index (greater than 1.0) showed a prolongation of the nucleation time with a significant decrease in vesicular cholesterol concentration, indicating a shift of cholesterol from vesicles to micelles. UDCA-treated patients and CDCA-treated patients with decreased cholesterol saturation index (less than 1.0) showed a greater effect. The authors conclude that UDCA prolongs the nucleation time mainly by decreasing the cholesterol saturation index, whereas CDCA does so by the dual effect of lowering the cholesterol saturation index and shifting cholesterol from vesicles to micelles.

Bile↗

Promoting effects of both dietary cholesterol and cholestyramine on pancreatic carcinogenesis initiated by N-nitrosobis(2-oxopropyl)amine in Syrian golden hamsters.

The effects of dietary cholesterol and cholestyramine on pancreatic carcinogenesis initiated with N-nitrosobis(2-oxopropyl)amine (BOP) were investigated in 120 female Syrian golden hamsters. BOP (70 mg/kg body weight) was injected s.c. once at the beginning of the experiment. Starting 2 weeks later, the animals were then maintained on basal diet or diets containing either 0.5% cholesterol or 1% cholestyramine for a further 16 weeks. All surviving hamsters were killed at week 18, and the pancreas tissues examined histologically. The incidences of pancreatic carcinomas in hamsters fed cholesterol and the cholestyramine supplement were 40.0 and 30.0% respectively; in both cases significantly higher than the 6.9% incidence in the basal diet group. Cholesterol contents of the serum, pancreas and liver were significantly increased by cholesterol feeding and significantly decreased by the cholestyramine diet. The cholesterol diet also significantly increased pancreatic protein and DNA contents, and the concentration of total bile acids and the level of lithocholic acid in gallbladder bile. The cholestyramine diet significantly increased total pancreatic DNA and protein contents, and pancreatic weight. The results thus indicated that both dietary cholesterol and cholestyramine can enhance BOP-initiated pancreatic carcinogenesis in hamsters.

Adenocarcinoma↗

Fc epsilon receptor II/CD23+ lymphocytes in atopic dermatitis. III. Aberrant control in the in vitro expression of Fc epsilon RII/CD23 on peripheral blood T cells in atopic dermatitis.

In vitro Fc epsilon RII expression was examined in patients with atopic dermatitis, those with non-atopic eczematous dermatitis and normal individuals following stimulation of peripheral blood cells with recombinant IL-4 (rIL-4), phytohaemagglutinin (PHA), or PHA plus rIL-2. At various days cells were stained with MoAbs to human lymphocyte Fc epsilon RII and to lymphoid cell-surface antigens and analysed by flow cytometry. rIL-4, but not rIL-2, specifically induced Fc epsilon RII on T cells as well as B cells in atopic dermatitis, eczematous dermatitis and normal individual groups. Both atopics and non-atopics generated comparable proportions of Fc epsilon RII+ T cells (T epsilon cells), whereas the frequency of B cells bearing Fc epsilon RII(B epsilon cells) was significantly higher in patients with extensive atopic dermatitis than in those with mild atopic dermatitis and other subjects. Comparable levels of T epsilon cells were detected in both atopic and non-atopic donors following stimulation of peripheral blood cells with PHA or pre-activation of the cells with PHA plus subsequent incubation with rIL-2. Whereas both CD8+ and CD4+ subsets were present in T epsilon cell populations induced specifically by rIL-4, PHA and PHA plus rIL-2, patients with atopic dermatitis had a greater tendency for Fc epsilon RII expression on CD8+ T cells compared with patients with eczematous dermatitis and normal individuals. Recombinant interferon-gamma (rIFN-gamma), but not rIFN-alpha or prostaglandin E2 (PGE2), suppressed the generation of T epsilon cells by rIL-4 in atopics and non-atopics to the same degree. These results suggest the aberrant control of Fc epsilon RII expression on T cells, especially those bearing CD8, in atopic dermatitis.

Adolescent↗