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Biomedical subjects

M Nakamoto

Publications and source records attributed to M Nakamoto.

At least 19 recordsLinked to original sources

Identification of tumor markers and differentiation markers for molecular diagnosis of lung adenocarcinoma.

To identify tumor markers and differentiation markers for lung adenocarcinoma (AdC), we analysed expression profiles of 14,500 genes against three cases of type II alveolar epithelial cells, bronchiolar epithelial cells, and bronchial epithelial cells, respectively, and 10 cases of AdC cells isolated by laser capture microdissection. Hierarchical clustering analysis indicated that AdC cells and noncancerous lung epithelial cells are significantly different in their expression profiles, and that different sets of differentiation markers are expressed among alveolar, bronchiolar and bronchial epithelial cells. Nine genes were identified as being highly expressed in AdC cells, but not expressed in noncancerous lung epithelial cells. Sixteen genes were identified as differentiation markers for lung epithelial cells. Real-time RT-PCR analysis of 45 lung AdC cases further revealed that expression of four tumor markers in AdC cells was significantly higher than that in noncancerous lung cells and that expression of ten differentiation markers was retained in a considerable fraction of lung AdC cases. Five tumor markers and seven differentiation markers were not expressed in peripheral blood cells. Similarities and differences in expression profiles between normal epithelial cells from different lung respiratory compartments and AdC cells demonstrated in this study will be informative for the molecular diagnosis of lung AdC.

Adenocarcinoma↗

Highly selective one-pot synthesis of spirophosphoranes exhibiting reversed apicophilicity by oxidation of dianions generated from P-H spirophosphorane.

[see reaction]. Mild and highly selective one-pot procedures for obtaining phosphoranes that exhibit reversed (O-cis) apicophilicity are described. On the basis of the procedures, O-cis phosphorane bearing an aryl group (R = 2,4,6-tri-i-propylphenyl) could be isolated for the first time; the procedure is also applicable for alkyl derivatives. Particularly effective was the use of I2 as an oxidizing reagent.

Journal Article↗

Presence of antibodies against retinoblastoma tumor suppressor protein in patients with lung cancer.

Retinoblastoma (RB) protein and antibody against RB protein in sera from 45 lung cancer patients and 30 healthy volunteers were examined using bacterially synthesized glutathione S-transferase (GST) RB fusion protein and immunoblot analysis. RB protein was not detected in sera from any individuals with lung cancer or in any healthy volunteers. Sera from 6 patients, including 4 with non-small cell carcinoma and 2 with small cell carcinoma, reacted to a GST-RB fusion protein but not with a GST protein. Sera from 30 normal volunteers reacted to neither GST-RB fusion protein nor GST protein. The backgrounds such as age, gender, performance status, histology, stage, smoking history, and prior treatment were not significantly different between the patients with and without anti-RB antibodies. This is the first report describing the presence of anti-RB antibody in patients with malignant tumors. Further studies are needed to establish clinical significance for anti-RB antibody.

Adult↗

K-ras and rho A mutations in malignant pleural effusion.

Mutations of the Kristen ras (K-ras) gene have been implicated in the pathogenesis of human lung cancer, especially adenocarcinoma, and have been proposed to be a prognostic factor. The K-ras mutation in codon 12 is detectable even in cell-free fluids by using the enriched polymerase chain reaction (PCR) technique. On the other hand, based on experimental results, the rho A mutation in codon 14 is also proposed to be oncogenic as observed in the K-ras mutation. Malignant pleural effusion is a common complication of lung cancer. We studied the point mutation of K-ras codon 12 and rho A codon 14 using enriched PCR in specimens of pleural effusion. Forty patients with pleural effusion were enrolled in this study. The causes of pleural effusion were non-small cell lung cancer (18 cases), small cell lung cancer (6 cases), malignant mesothelioma (2 cases), metastatic lung tumor (5 cases), thymoma (1 case), malignant lymphoma (1 case), and pleuritis tuberculosa (7 cases). The K-ras mutation was detected in 4 of 14 cases with adenocarcinoma, 1 of 3 cases with squamous cell carcinoma, 1 of 1 case with large cell carcinoma, and 1 of 5 cases with metastatic lung tumor, respectively. The rho A mutation was not detected in any pleural effusion examined in this study. Our study demonstrates the usefullness of pleural effusion as a clinical specimen for a search of point mutation of oncogenes. The K-ras codon 12 mutation is readily detected in pleural effusion, and the demonstration of this mutation has potentially important implications for the diagnosis of malignant pleural effusion.

Adult↗

Low serum albumin in elderly continuous ambulatory peritoneal dialysis patients is attributable to high permeability of peritoneum.

Our study was carried out to investigate changes in nutrition and individual peritoneal membrane transport characteristics in elderly patients on continuous ambulatory peritoneal dialysis (CAPD), expressed as the personal dialysis capacity (PDC). We performed 376 PDC tests in 229 non diabetic patients who were undergoing CAPD from May 1995 to May 1999 in a multicenter study in Japan. We divided the patients into three groups: elderly (age > or = 65 years, n = 56), middle-aged (age 50-65 years, n = 150), and young (age < 50, n = 170). No significant differences were seen in duration of CAPD and incidence of peritonitis between the groups. We then compared the peritoneal function calculated by PDC test in the groups. Serum levels of albumin in elderly patients were significantly lower than those in middle-aged and young patients (elderly: 3.2 +/- 0.1; middle-aged: 3.4 +/- 0.1, p = 0.0447 vs elderly; young: 3.4 +/- 0.1, p = 0.0272 vs elderly). Plasma protein loss from the peritoneum in elderly patients was significantly higher than in middle-aged and young patients (elderly: 0.11 +/- 0.01; middle-aged: 0.09 +/- 0.01, p = 0.0136 vs elderly; young: 0.09 +/- 0.01, p = 0.0161 vs elderly). No significant differences in ultrafiltration volume and water permeability were seen between the groups. Peritoneal area in the elderly group was significantly higher than in the middle-aged and young groups. Peritoneal creatinine clearance (CCr) and Kt/V in elderly patients were significantly higher than in middle-aged and young patients. However, no significant difference in protein nitrogen appearance (PNA) or protein catabolic rate (PCR) was seen between the groups. Urea and creatinine generation rates in elderly patients were significantly lower than in the middle-aged and young patients. These data show that elderly patients receiving CAPD are well maintained from the perspective of urea and water metabolism, indicating that CAPD therapy for the elderly is more acceptable than expected. However, caution should be exercised, owing to the lower serum albumin seen in elderly patients.

Adult↗

Sodium sulfite and N-acetylcysteine: new additives to dialysate for inhibiting formation of glucose degradation products and advanced glycation end-products.

The present study evaluated the inhibiting effect of various chemicals on the advanced glycation end-product (AGEs) cross-linking caused in protein by glucose degradation products (GDPs). We evaluated a few dozen organic and inorganic chemicals--in addition to previously reported AGE inhibitors, such as thiazolium derivatives and aminoguanidine--for their inhibiting effect. Collagen IV (from human placenta) or human serum albumin (HSA) was incubated with an AGE accelerator and one of the selected chemicals in phosphate buffer solution at 37 degrees C for as long as 14 days. Fluorescence intensity (440 nm) was determined after a given incubation time. Among 36 chemicals tested, 8 new chemicals and 5 previously known AGE inhibitors significantly suppressed the increase in fluorescence intensity seen after incubation of HSA with methylglyoxal. We believe that 6 chemicals may effectively quench GDPs and inhibit AGE cross-link formation, in a manner different from that of aminoguanidine and thiazolium.

Acetylcysteine↗

cDNA-derived amino acid sequence of acetoacetyl-CoA synthetase from rat liver.

In order to examine the primary structure of acetoacetyl-CoA synthetase (acetoacetate-CoA ligase, EC 6.2.1.16; AA-CoA synthetase), the cDNA clone encoding this enzyme has been isolated from the cDNA library which was prepared from the liver of rat fed a diet supplemented with 4% cholestyramine and 0.4% pravastatin for 4 days. Nucleotide sequence analysis of cloned cDNA revealed that AA-CoA synthetase of rat liver contains an open reading frame of 2019 nucleotides, and the deduced amino acid sequence (672 amino acid residues) bears 25.0 and 38.9% homologies with acetyl-CoA synthetases of Saccharomyces cerevisiae and Archaeoglobus fulgidus, respectively.

Amino Acid Sequence↗

Zonisamide - induced urinary lithiasis in patients with intractable epilepsy.

We report here three patients with intractable epilepsy who developed urinary lithiasis during zonisamide (ZNS) treatment. Abdominal pain due to left-sided hydronephrosis was the initial symptom in the first patient, and it was resolved after the excretion of a stone. The second patient, who had no specific symptoms, was found to have a thick sludge of calcium phosphate in the bladder when he suffered from aspiration pneumonia and dehydration. The third patient, who had a history of recurrent urinary obstruction, was also found to have a thick sludge of calcium oxalate in the bladder. The urinalysis of the three patients revealed alkaline urine and hypercalciuria. Although their urinary lithiasis was resolved by discontinuation of ZNS and supportive therapy, routine examination of urine parameters such as pH and sediments, and daily urine-output checks are thought to be necessary during treatment with ZNS, especially for patients who are bedridden for a long time and receive multiple antiepileptic drugs.

Adolescent↗

Eph receptors and ephrins.

The Eph receptors are the largest known family of receptor tyrosine kinases. The Eph receptors and their membrane-attached ligands, ephrins, show diverse expression patterns during development. Recent studies have demonstrated that Eph receptors and ephrins play important roles in many developmental processes, including neuronal network formation, the patterning of the neural tube and the paraxial mesoderm, the guidance of cell migration, and vascular formation. In the nervous system, Eph receptors and ephrins have been shown to act as positional labels to establish topographic projections. They also play a key role in pathway finding by axons and neural crest cells. The crucial roles of Eph receptors and ephrins during development suggest involvement of these genes in congenital disorders affecting the nervous system and other tissues. It has also been suggested that Eph receptors and ephrins may be involved in carcinogenesis. It is therefore of clinical importance to further analyse the function of these molecules, as manipulation of their function may have therapeutic applications.

Animals↗

Transforming growth factor-beta is involved in the pathogenesis of dialysis-related amyloidosis.

BACKGROUND: Advanced glycation end product-modified beta2-microglobulin (AGE-beta2m) is an important component of dialysis-related amyloidosis (DRA). Its presence induces monocyte chemotaxis and the release of the proinflammatory cytokines through macrophage activation. Transforming growth factor-beta (TGF-beta) is a multifunctional cytokine that also has chemotactic activity for monocytes at very low (0.1 to 10 pg/mL) concentrations and inhibits proinflammatory cytokine production of macrophages. In this study, we investigated the role of TGF-beta in the pathogenesis of DRA. METHODS: We performed an immunohistochemical study of DRA tissues (8 cases) to confirm the existence of TGF-betas and their receptors; we also performed a chemotaxis assay of human monocytes as well as enzyme-linked immunosorbent assay (ELISA) of TGF-beta1, tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and interleukin-1 receptor antagonist (IL-1Ra) in the supernatant of human monocyte-derived macrophage cell culture under varying conditions of incubation with TGF-beta1, AGE-beta2m, and TGF-beta1 antibody additions. RESULTS: There was positive staining for TGF-betas (types 1, 2, and 3) and their receptors (types I, II, and III) in infiltrated macrophages (CD68+), synovial lining cell, as well as vascular walls around amyloid deposition. AGE-beta2m also induced TGF-beta1 production by macrophages in a dose-dependent manner (410 +/- 80 pg/mL at 12.5 microg/mL, 621 +/- 62 pg/mL at 25 microg/mL, and 776 +/- 62 pg/mL at 50 microg/mL of AGE-beta2m). AGE-beta2m induced significant TNF-alpha and IL-1Ra production by macrophage. The addition of exogenous TGF-beta1 (0.1 to 10 ng/mL) decreased AGE-beta2m-induced TNF-alpha production and increased IL-1Ra production in a dose-dependent fashion. IL-1beta production was not effected by any experimental conditions. In chemotaxis assay, anti-TGF-beta1 antibody (0.1 to 10 microg/mL) attenuated AGE-beta2m-induced monocyte chemotaxis. CONCLUSIONS: These results provide the first evidence to our knowledge for the presence of TGF-beta in DRA tissue, as well as the stimulatory action of AGE-beta2m on tissue macrophages. In turn, TGF-beta suppresses the proinflammatory activation of macrophages, suggesting a dual role for TGF-beta in the inflammatory process of DRA. These observations may provide a pathophysiologic link between TGF-beta and DRA.

Aged↗

[A study of the minimum number of slices required for quantification of pulmonary emphysema by computed tomography].

We attempted to determine the minimum number of slices required for quantification of overall emphysema by computed tomography (CT). Forty-nine patients underwent CT scanning with a 15-mm slice interval, and 13 to 18 slices per patient were obtained. The percentage of low attenuation area (LAA%) per slice was measured with a method that we reported on previously, utilizing a CT program and NIH image. The average LAA% values for 1, 2, 3, and 6 slices evenly spaced through the lungs [LAA% (1), LAA% (2), LAA% (3), and LAA% (6)] were compared with those for all slices [LAA% (All)]. The correlation coefficients for LAA% (1), LAA% (2), LAA% (3), and LAA% (6) with LAA% (All) were 0.961, 0.981, 0.993, and 0.997, respectively. Mean differences +/- SD were -3.20 +/- 4.21%, -2.32 +/- 3.00, -0.20 +/- 1.84, and -0.16 +/- 1.26, respectively. From these results, we concluded that overall emphysema can be quantified by using at least three slices: one each of the upper, middle, and lower lung.

Adult↗

Chronic intestinal pseudo-obstruction due to dialysis-related amyloid deposition in the propria muscularis in a hemodialysis patient.

Dialysis-related amyloidosis (DRA) is one of the most serious complications interfering with rehabilitation in dialysis patients. Here, we report a case of beta2-microglobulin (beta2M)-related amyloidosis, in which the patient developed a severe intestinal pseudo-obstruction. The patient was a 42-year-old male who had been undergoing hemodialysis for 13 years, and who had no history of osteoarticular involvement of DRA. The first symptoms of the disease were severe abdominal fullness and nausea after meals. The whole intestinal wall biopsy revealed massive amyloid deposition in the propria muscularis. The patient became malnourished and died of acute subendocardial infarction 3 years after the onset. An autopsical examination revealed a massive deposition of amyloid, which was positively stained with anti-beta2M antibody but not AA amyloid, predominantly in the gastrointestinal muscular layer, including the tongue, esophagus, stomach, small intestines, colon, and rectum. These results suggest that the gastrointestinal involvement of beta2M-related amyloidosis might occur during the course of hemodialysis treatment, and that this possibility should be considered if patients suffer from intestinal pseudo-obstruction without osteoarticular symptoms.

Adult↗

Intraoperative navigation for breast cancer surgery using 3D ultrasound images.

The aim of this work was to develop an intraoperative image-guidance system for breast cancer surgery using three-dimensional (3D) ultrasound imaging. Using a 10-MHz annular array mechanical sector probe, ultrasound images were obtained from nine volunteer patients with breast cancer immediately before removal of the tumor in the operating room. A 3D tumor image was reconstructed using a workstation, then superimposed on the video image of the breast based on geometrical data. These data were obtained simultaneously by an optical 3D position sensor. The 3D images of the tumors were validated by the pathological data obtained after the surgery. In eight cases, the superimposed images were successfully obtained in approximately 15-20 min following scanning of the tumor. Scattered lesions around the main tumor were also visualized in the reconstructed tumor images, but artifacts of the ductal lesion caused by noise could not be eliminated in some cases. This system should be very effective in helping the surgeon to recognize the extent of a tumor within the breast itself and to determine the margin of surgical resection for breast conservation surgery.

Adult↗

Effects of a parathyroidectomy on the immune system and nutritional condition in chronic dialysis patients with secondary hyperparathyroidism.

BACKGROUND: Parathyroid hormone (PTH) has an adverse effect on the immune system and may cause immunologic disorders in patients with chronic renal failure. The in vivo effects of a parathyroidectomy on the immunologic parameters was examined. METHODS: Thirty-four patients under dialysis therapy received a parathyroidectomy (PTx) for secondary hyperparathyroidism (HPT). They were prospectively studied regarding serum immunoglobulins, complements, CD markers, and serum soluble IL-2 receptor (sIL-2R) until 12 months after PTx. RESULTS: The serum levels of IgG, IgA and IgM showed significant increase until 12 months after PTx (P<0.001, respectively). C3, C4, and CH50 also indicated significant increase at 12 months after PTx. In cellular immunity, only serum sIL-2R showed significant increase 2 weeks after PTx (P = 0.028). The hematocrit and serum albumin also improved significantly at 12 months. CONCLUSIONS: PTx showed beneficial effects on humoral immunological markers. The effects are probably due to the remarkable PTH reduction and partly improved nutritional state after PTx.

Adult↗