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Biomedical subjects

K Mukai

Publications and source records attributed to K Mukai.

At least 109 records · Page 6Linked to original sources

Nonfunctioning islet cell tumors of the pancreas: clinical, imaging and pathological aspects in 16 patients.

BACKGROUND: Nonfunctioning islet cell tumors (NFICTs) usually reach a large size prior to detection, at which stage patients have some symptoms or signs. Recently, NFICTs have been discovered in asymptomatic patients with increasing frequency owing to advances in diagnostic imaging techniques. This study investigated clinical, imaging and pathological features in recent cases of NFICT. METHODS: The medical records, radiographs and pathological specimens of 16 patients with NFICT who were evaluated between April 1991 and March 1996 were reviewed. RESULTS: Tumor sizes ranged from 0.8 to 17 cm (average, 5.2 cm). Five patients (31%) had some symptoms or signs at the time of diagnosis; however, the other 11 (69%) had no symptoms. Of 10 patients with a tumor of size 5 cm or less, nine were asymptomatic and all tumors were histologically benign. In contrast, in six patients with a tumor larger than 5 cm, four had some symptoms and five tumors were malignant. The detection rates of pancreatic tumor mass on ultrasonography and computed tomography were 94% (15/16) each. All 14 patients in whom the tumor was completely resected survived without recurrence; however, the remaining two patients with liver metastases died following recurrence. CONCLUSIONS: US and CT are useful in detecting NFICTs even if the tumor is small and the patient is asymptomatic. The detection of NFICTs of small size and their complete removal are essential for a successful cure.

Adenoma, Islet Cell↗

Hereditary nonpolyposis colorectal cancer associated with duodenal carcinoma: a case report.

Hereditary nonpolyposis colorectal cancer is an autosomal, dominantly inherited disease, characterized by an early age of onset, right colon predominance and an association with various extracolorectal malignancies. We present a case of a 47-year-old woman who met the clinical criteria for the diagnosis of hereditary nonpolyposis colorectal cancer from her past and family histories. She had undergone operations for uterine cancer (histology not confirmed) at age 35 and for advanced cancer of the ascending colon at age 45. Gastroendoscopy revealed a flat elevated lesion, 20 mm in size, with a protrusion (type IIa + Is) in the second portion of the duodenum in March 1996. Additionally, colonoscopy showed a flat elevated lesion, 30 mm in size, with an irregular and nodular surface (type IIa, laterally spreading tumor) in the descending colon. After the operation, the resected specimen of the duodenum histologically showed a well-differentiated adenocarcinoma associated with a tubulo-villous adenoma which had invaded the submucosal layer. The tumor of the colon was histologically confirmed to be a moderately-differentiated adenocarcinoma with submucosal invasion. A high frequency of replication error positivity (4/5 loci) was detected in both of the tumors. Reports of early cancer of the duodenum, associated with extracolorectal malignancies in hereditary nonpolyposis colorectal cancer, are very rare in the literature. Although it is difficult to determine which extracolorectal tumor sites should be taken into consideration by screening programs, we believe that careful observation by upper gastrointestinal endoscopy, which includes the duodenum, is necessary for patients with hereditary nonpolyposis colorectal cancer.

Colonoscopy↗

Survival and function of hepatocytes on a novel three-dimensional synthetic biodegradable polymer scaffold with an intrinsic network of channels.

OBJECTIVE: To evaluate the survival and function of hepatocytes (HCs) on a novel three-dimensional (3D) synthetic biodegradable polymer scaffold with an intrinsic network of interconnected channels under continuous flow conditions. SUMMARY BACKGROUND DATA: The authors' laboratory has investigated HC transplantation using 3D biodegradable polymers as scaffolding as an alternative approach to treatment of end-stage liver disease. Previous studies have demonstrated survival of HCs transplanted on polymer discs in peripheral tissue sites and partial correction of single enzyme liver defects. One of the major limitations has been the insufficient survival of an adequate mass of transplanted cells; this is thought to be caused by inadequate oxygen diffusion. METHODS: HCs and nonparenchymal liver cells from Lewis rats were seeded onto 3D biodegradable polymer scaffolds. Microporous 3D polymers were created using 3D printing on copolymers of polylactide-coglycolide. The cell/polymer constructs were placed in static culture or continuous flow conditions. The devices were retrieved after 2 days and examined by scanning electron microscopy and histology. Culture medium was analyzed for albumin by enzyme-linked immunosorbent assay (ELISA). Differences in culture parameters including pH, PCO2, PO2, glucose, lactate, and HCO3 were examined. RESULTS: Scanning electron microscopy revealed successful attachment of HCs on the 3D polymer in both static and flow conditions. Histology demonstrated viable HCs in both conditions. ELISA demonstrated a significantly higher mean concentration of albumin in flow conditions than in static conditions. Culture parameter analysis revealed a significantly higher PO2 and glucose level, and a more physiologic pH in flow conditions than in static conditions. CONCLUSIONS: HCs cocultured with nonparenchymal cells can attach to and survive on the 3D polymer scaffolds in both static and flow conditions in the size and configuration used in this study. Flow conditions may provide a more conducive environment for HC metabolism and albumin synthesis than static conditions. The authors hypothesize that flow through directed channels will be necessary for the transfer of large masses of cells when implantation studies are initiated.

Animals↗

Expression of cytochrome P450 3A4 in foveolar epithelium with intestinal metaplasia of the human stomach.

The expression of cytochrome P450 3A4 (CYP3A4) in the foveolar epithelium of the human stomach with intestinal metaplasia was studied using immunohistochemistry, western blotting and reverse transcription polymerase chain reaction (RT-PCR). CYP3A4 was immunohistochemically detected in the foveolar epithelium with intestinal metaplasia, but was not detected in foveolar epithelium without intestinal metaplasia, in the pyloric gland or in the fundic gland of the stomach. Western blotting and RT-PCR demonstrated that CYP3A4 protein and mRNA were expressed in the liver and pyloric gland mucosa with intestinal metaplasia, but not in the fundic gland mucosa without intestinal metaplasia. Possible roles of CYP expression in the gastric mucosa with intestinal metaplasia in human stomach carcinogenesis are briefly discussed.

Cytochrome P-450 CYP3A↗

A proposal for a new histological classification scheme for predicting short-term tumor recurrence and death in patients with invasive ductal carcinoma of the breast.

Tumor recurrence rate (TRR) and mortality rate (MR) of invasive ductal carcinoma (IDC) of the breast in short-term follow-up are relatively low. Nevertheless, it is extremely important to identify patients at risk of early recurrence or death after surgery. The aim of this study was to establish a new histological prognostic classification scheme for IDC in order accurately to predict the short-term outcome. The following histological parameters were analyzed in 201 IDCs: 1) tumor size, 2) structural atypia, 3) nuclear atypia, 4) number of mitotic figures, 5) fibrotic focus (FF), 6) vascular invasion, 7) tumor necrosis, 8) skin invasion, 9) muscle invasion, 10) nodal status and 11) extramammary fat invasion. Multivariate analysis showed that nuclear atypia, presence of FF, and the invasive length of fat invasion (ILFI) were the most important histological parameters correlated with TRR or MR of IDCs. Accordingly, a new histological classification based on nuclear atypia, FF and ILFI (Nucleus-Fibrotic focus-Fat invasion, NFF) was devised. Comparative studies were performed with the following existing prognostic classifications: 1) histological grade, 2) modified Scarff-Bloom-Richardson histological grade, 3) prognostic index and 4) pathological TNM (pTNM) stage classifications. Patient grouping defined by NFF classification significantly correlated with tumor recurrence or death of IDCs in all cases, cases at stages I and II, those without lymph node metastasis and those who were estrogen receptor (ER)-positive after adjustment for the other four classifications, using multivariate analysis. NFF classification appeared superior to existing prognostic classifications for the accurate prediction of the short-term outcome for patients with IDCs in low risk groups.

Adipose Tissue↗

Low-grade B cell lymphoma of mucosa-associated lymphoid tissue in the thymus of a patient with rheumatoid arthritis.

The majority of thymic lymphomas are either lymphoblastic lymphoma, large B cell lymphoma or Hodgkin's disease, and other types of non-Hodgkin lymphoma are rare. A case of low-grade B cell lymphoma of mucosa-associated lymphoid tissue (MALT) in the thymus is reported. A 55-year-old Japanese female with a history of rheumatoid arthritis (RA) complained of back pain. A mediastinal tumor was identified by computerized tomography and magnetic resonance imaging, and the thymus was resected through median sternotomy. The solid and nodular tumor had several small satellite extensions and was completely confined to within the thymus. Histologically, monotonous medium-sized centrocyte-like cells occupied the medulla of the thymus and infiltrated Hassall's corpuscles (lymphoepithelial lesions). Immunohistochemically, tumor cells were positive for CD20 and CD79a. IgA and kappa light chain restriction were also found in plasmacytoid cells in the tumor. Clonal rearrangement of the immunoglobulin heavy chain gene was demonstrated by polymerase chain reaction. This case was diagnosed as MALT-type low-grade B cell lymphoma in the thymus. This is the first report of low-grade B cell lymphoma in the thymus associated with RA. As autoimmune diseases are known to be associated with lymphoid neoplasms, it is suggested that the RA played an important role in the development of malignant lymphoma in this case.

Antigens, CD20↗

Ganglion cells in Ewing's sarcoma following chemotherapy: a case report.

A case of Ewing's sarcoma of the bone, arising in the right radius of a 12-year-old girl, which showed unique histologic features after pre-operative treatment, is reported. The light microscopic features of a biopsy sample were those of a small round cell tumor showing positive immunoreaction with antibodies against the product of the MIC 2 gene (O13), neuron-specific enolase, neurofilament, and synaptophysin, but no morphological differentiation. The patient received combined intensive multi-drug chemotherapy and radiation before surgery. Examination of the surgical specimen showed that the tumor was less cellular than that in the biopsy specimen, and was composed mainly of loosely textured large cells mimicking ganglion cells, occasionally forming Homer-Wright rosettes. An immunohistochemical study revealed that neural differentiation was enhanced. Immunoreactivity for Leu-7 also became positive. Although the patient underwent postoperative chemotherapy, she died of multiple lung and bone metastases 30 months after the diagnosis. Autopsy showed that metastatic foci were made up of densely packed small round cells like those seen in the biopsy samples, but associated with prominent Homer-Wright rosettes. To the authors' knowledge, this is the first report of a tumor being replaced almost entirely by ganglion cells after pre-operative chemotherapy and radiotherapy.

12E7 Antigen↗

Gene cloning and characterization of an acidic xylanase from Acidobacterium capsulatum.

The gene xynA encoding an acid endo-beta-1,4-xylanase from an acidophilic bacterium, Acidobacterium capsulatum 161, was cloned and expressed in Eschrichia coli. The nucleotide sequence of the 1.6-kb DNA fragment containing xynA was analyzed, revealing an open reading frame of 1,215 bp encoding a peptide of 405 amino acid residues. The deduced amino acid sequence of XynA was very similar to other xylanases that are from the glycosyl hydrolase family 10. XynA was purified to homogeneity by SDS-polyacrylamide gel electrophoresis from E. coli transformants. The molecular mass and isoelectric point of XynA were 41 kDa and 7.3, respectively. The xylanase activity of the cloned XynA is an endo-acting enzyme that shows optimal activity at pH 5.0 and 65 degrees C, and is stable pH between 3.0 and 8.0. The K(m) and Vmax with oat spelt xylan as a substrate at pH 5.0 and 30 degrees C are 3.5 mg/ml and 403 mumol/min/mg.

Amino Acid Sequence↗

Dentinal tubule occlusion with lanthanum fluoride and powdered apatite glass ceramics in vitro.

To simulate hypersensitive dentin, the smear layer and dentinal plugs of bovine root dentin specimens were removed by immersion in 10% phosphoric acid, polishing with hydroxyapatite particles, and ultrasonic cleansing. The fluoride-tannic acid-lanthanum-apatite (FTLA) group was treated with acidulated phosphate fluoride (APF) containing tannic acid followed by rubbing with a paste of lanthanum chloride (LaCl3) and powdered apatite glass ceramics. The treated specimens were immersed in a remineralizing solution that mimics saliva for 6 weeks. The SEM observations revealed that the treated surfaces of the FTLA group were completely covered with fine spherical compounds and the dentinal tubules were occluded with plugs to a depth of about 3 microns. Fluoride and lanthanum were detected to a depth of over 20 microns by EPMA observation. After the remineralization, the surface of FTLA-treated specimen did not have any opened tubules and showed a remarkable increase in the number of fine spherical deposits in the dentinal tubules. These results suggest that the reaction products produced by sequential treatment with acidic fluoride and LaCl3 and powdered apatite glass ceramics are able to effectively occlude dentinal tubules.

Acidulated Phosphate Fluoride↗

A case of immunotactoid glomerulopathy with unusual microtubular deposits.

A 57-year-old man with monoclonal gamma-globulinemia was admitted because of edema and proteinuria. A renal biopsy specimen showed lobular glomerulonephritis associated with deposition of material that was positive for IgG, C3, C1q, fibrin, kappa light chain, and lambda light chain but was not stained by Congo red. Glomeruli showed massive electron-dense deposits with two kinds of unusual, highly organized crystalline structures in the mesangial matrix and peripheral capillary loops. Clinically, the patient had nephrotic syndrome, microscopic hematuria, and hypertension. No Bence-Jones protein or cryoglobulin was found in the urine or serum. Immunoelectrophoresis of blood and urine revealed increased IgG-lambda paraprotein, but no free light chains were found. This case was not associated with amyloidosis, systemic lupus erythematosus, light chain deposition disease, cryoglobulinemia, or multiple myeloma. Immunotactoid glomerulopathy was diagnosed. Treatment with oral prednisone was effective for the management of nephrotic syndrome and renal dysfunction. Glomerular deposition of two kinds of microtubular structure in immunotactoid glomerulopathy has rarely been reported.

Glomerulonephritis↗

Biological markers as a predictor for response and prognosis of unresectable gastric cancer patients treated with 5-fluorouracil and cis-platinum.

We investigated the utility of examining biological markers to predict chemoresponse and survival. The subjects consisted of 39 unresectable gastric cancer patients treated with a combination of 5-fluorouracil and cis-platinum. The expression of p53, bcl-2, thymidylate synthase (TS), glutathione S-transferase pi (GST-pi), and vascular endothelial growth factor (VEGF) in the formalin-fixed biopsy samples of primary tumors before chemotherapy was examined immunohistochemically. The positive rate for VEGF, bcl-2, TS, p53, and GST-pi was 51, 10, 46, 38, and 69%, respectively. VEGF-positive cases showed a higher response rate than did negative cases (11 of 20 versus 2 of 19 cases; P = 0.0057). The cases that were negative for p53, TS, bcl-2, and GST-pi were more likely to respond to chemotherapy than the cases that were positive for these markers. The 10 cases having 4 or 5 favorable phenotypes (VEGF positive, p53 negative, bcl-2 negative, TS negative, and GST-pi negative) survived longer than the remaining 29 cases (P = 0.0069). Multivariate analysis revealed that the number of favorable phenotypes (> or = 4 versus < or = 3) had a greater impact on survival than performance status (0 versus 1 or 2), age (> 60 years versus < or = 60 years), macroscopic type (scirrhous versus nonscirrhous), histological type (intestinal versus diffuse), or tumor extent (locally advanced versus metastatic). Immunohistochemical examination of biological markers in biopsy samples may be useful in predicting the clinical outcome of unresectable gastric cancer patients treated with 5-fluorouracil and cis-platinum.

Adult↗

The efficiency of antioxidants delivered by liposomal transfer.

Phenolic antioxidants of the hydroxychroman class, alpha-tocopherol (alpha-TOC) and 2,2,5,6,7-pentamethyl-6-hydroxychroman (PMHC), and the hindered phenols 2,3-dihydro-5-hydroxy-2,2,4-trimethylnaphtho[1,2-b]furan (NFUR), 2,6-di-tert-butyl-4-methoxyphenol (DBHA), and 2,6-di-tert-butyl-4-methyl phenol (BHT), were delivered into oxidizable (ACCEPTOR) liposomes of dilinoleoylphosphatidylcholine (DLPC) or 1-palmitoyl-2-linoleoyl-phosphatidylcholine (PLPC) from saturated DONOR liposomes of dimyristoylphosphatidylcholine (DMPC) by liposomal transfer. The antioxidant activities, k(inh), by the inhibited oxygen uptake method were compared with the k(inh)s determined when the antioxidants were introduced into the liposomes by coevaporation from organic solvents. The peroxidations were initiated using either thermal initiators, water-soluble azo-bis-amidinopropane hydrochloride (ABAP), lipid-soluble azo-bis-2,4-dimethylvaleronitrile (ADVN) and di-tert-butylhyponitrite (DBHN), or the photoinitiator benzophenone. The antioxidants PMHC, NFUR, DBHA, and BHT transferred rapidly between liposomes, but several hours of incubation were needed to transfer alpha-TOC. The average k(inh)s in liposomes, in the relative order NFUR approximately DBHA > PMHC > BHT approximately alpha-TOC, were markedly lower than known values in organic solvent. k(inh) values in liposomes appear to be controlled by effects of hydrogen bonding with water and by restricted diffusion of antioxidants, especially in the case of alpha-TOC. Product studies of the hydroperoxides formed during inhibited oxygen consumption were carried out. The cis,trans/trans,trans (c,t/t,t) product ratios of the 9- and 13-hydroperoxides formed from PLPC during inhibited peroxidation by PMHC were similar for both the coevaporated and liposomal transfer procedures. The c,t/t,t ratio for the same concentration of alpha-TOC, 1.52, compares to a value of 1.69 for PMHC at the start of the inhibition period. The higher c,t/t,t ratio observed for NFUR in DLPC, which varied between values of 7.0 at the start of the inhibition to about 1.8 after the break in the induction period, is a reflection of the increased hydrogen atom donating ability of the antioxidant plus the increased concentration of oxidizable lipid provided by DLPC.

Amidines↗

Detection of K-ras gene mutations at codon 12 in the pancreatic juice of patients with intraductal papillary mucinous tumors of the pancreas.

BACKGROUND: The authors previously found specific mutations of the K-ras gene at codon 12 in the pancreatic juice of 67% of patients (6 of 9) with pancreatic ductal carcinoma, and the detection of these mutations was useful for diagnosis. This study was performed to detect and evaluate K-ras mutations in pancreatic juice from patients with intraductal papillary mucinous tumor of the pancreas, which is considered a low grade malignancy. The results were interpreted from the viewpoint of clinical significance. METHODS: K-ras mutations were examined using seminested polymerase chain reaction analysis combined with restriction enzyme digestion, followed by nonradioisotopic single strand DNA conformation polymorphism. RESULTS: Twelve of thirteen cases (92%) of intraductal papillary mucinous tumor of the pancreas, confirmed histologically (9 adenomas and 4 carcinomas), and 26 of 43 cases (60%) of ductal carcinoma showed specific K-ras gene mutations in the pancreatic juice. Furthermore, 4 of 22 patients (18%) with chronic pancreatitis, followed for more than 1 year without a sign of pancreatic tumor, showed K-ras mutations. In contrast, no mutations of the K-ras gene were detected in the pancreatic juice from 28 normal controls. CONCLUSIONS: K-ras mutations were found in the pancreatic juice of all but one patient with intraductal papillary mucinous tumor of the pancreas, but they were not useful for distinguishing carcinoma from adenoma. The authors concluded that K-ras mutations are not a specific marker for pancreatic neoplasms because similar mutations were detected in the pancreatic juice from patients with chronic pancreatitis. At the present time, the detection of K-ras mutations in pancreatic juice should be used clinically as an adjunct diagnostic modality for pancreatic diseases.

Adenocarcinoma, Mucinous↗

Expression of cytochromes P450aldo and P45011 beta in rat adrenal gland during late gestational and neonatal stages.

The development of the rat adrenal gland during late gestational and neonatal stages was studied by following the expression of aldosterone synthase cytochrome P450 (P450aldo) and glucocorticoid-synthesizing cytochrome P450 (P45011 beta). Cells expressing P450aldo, a functional marker for the mineralocorticoid-synthesizing zona glomerulosa, were not detected until day 20 of fetal age, i.e., 2 days before birth, although the zona glomerulosa cells were histologically recognizable at the 18th day of gestation. The intensity of P450aldo staining thereafter became stronger with age in the outer portion of the cortex. Cells expressing P45011 beta, a marker for the glucocorticoid-producing zona fasciculata, were present in the fetal adrenals on the 18th day. P45011 beta-positive cells were distributed over the whole adrenal gland and intermingled with the cells containing tyrosine hydroxylase, a marker enzyme for medullary cells. The P45011 beta-positive and tyrosine hydroxylase-positive cells began to separate on the 20th day, and were completely resolved from each other around the third day after birth. Expression of P450aldo and P45011 beta, together with that of tyrosine hydroxylase, thus serves as a suitable marker for studying the development of the adrenal gland.

Adrenal Glands↗

Intraductal papillary tumors and mucinous cystic tumors of the pancreas: clinicopathologic study of 38 cases.

Clinicopathological features of 28 patients with intraductal papillary tumor (IDPT) and 10 patients with mucinous cystic tumor (MCT) of the pancreas were studied. Both IDPT and MCT showed papillary projections of the epithelium with abundant mucus secretion in the ectatic ducts or cystic spaces. The patients with IDPT comprised 19 men and 9 women with a mean age of 64.9 years. Three fourths of the IDPTs were located in the pancreatic head, and the mean tumor size was 3.5 cm. Local recurrence was observed in one patient, but none died of IDPT. In contrast, all patients with MCT were women, with a mean age of 49.4 years. None of the MCTs arose in the head, and the mean tumor size was 7.1 cm. One patient died of MCT, but all of the others survived without recurrence. Eight IDPTs and three MCTs showed invasion into the surrounding pancreatic tissue. Muconodular infiltration was mainly observed in five IDPTs and one MCTs and tubular infiltration in three IDPTs and two MCTs. A characteristic histological finding associated with the muconodular infiltration in IDPT was subepithelial "mucin droplets" that appeared to represent a change in polarity of mucus secretion. The formation of such subepithelial "mucin droplets" may be the initial step of muconodular infiltration in IDPT. Muconodular infiltration in IDPT appears different morphologically and biologically from the mucinous carcinoma subtype of conventional invasive ductal carcinoma.

Adenocarcinoma, Papillary↗

Idiopathic granulomatous mastitis: case report and review of the literature.

We report a case of idiopathic granulomatous mastitis in a 35-year-old Japanese woman, who came to our hospital complaining of a tender mass in her right breast. Because the results of initial aspiration cytology were considered highly suspicious for carcinoma, modified radical mastectomy was performed. However, the final histological diagnosis was granulomatous lobular mastitis with no evidence of malignancy. Idiopathic granulomatous mastitis is a rare inflammatory breast disease of unknown etiology. Since the clinical manifestations are similar to those of mammary carcinoma, this condition has been misdiagnosed as carcinoma and treated as such. A review of the literature revealed that idiopathic granulomatous mastitis has tended to occur in young patients with a history of childbirth or oral contraceptive usage. Clinical or imaging diagnosis has often been difficult. Complete resection or corticosteroid therapy can be recommended as the optimal treatment. Since 38% of patients experience recurrence, long-term follow-up is indicated.

Adrenal Cortex Hormones↗

Coxalgia as the initial symptom in Hodgkin's disease: a case report.

Primary Hodgkin's disease in the bone is extremely rare. We report the case of a 41-year-old woman with Hodgkin's disease, who had complained of left coxalgia 17 months prior to nodal involvement becoming evident clinically. She received combination chemotherapy with doxorubicin, bleomycin, vincristine and dacarbazine as well as radiotherapy to the pelvic lesion. Although the lymphadenopathy responded well to this treatment, the bone lesion was never in remission. The large mass of the bone lesion and its pelvic origin may explain the poor response to the cytotoxic therapies this patient received. The 22 cases reviewed showed that: 1, bony pain was the most frequent initial symptom; 2, nodal disease appeared in their clinical course in most cases; 3, the bones most commonly involved were pelvis, femur or tibia, and spine.

Adult↗