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Biomedical subjects

M Katayama

Publications and source records attributed to M Katayama.

At least 181 records · Page 10Linked to original sources

Significant existence of deleted mitochondrial DNA in cirrhotic liver surrounding hepatic tumor.

To understand the role of mitochondria in carcinogenesis, we compared the amount of deleted mtDNAs between human hepatic tumors and surrounding cirrhotic portion of the liver of ten patients by using polymerase chain reaction (PCR). Multiple mtDNA deletions were detected in cirrhotic portion, but no deletions were detected in the tumor portion. Direct sequencing of the fragments revealed a 7,079-bp deletion (nucleotide position 8,992-16,072) involving no direct repeated sequences and a 7,436-bp deletion (position 8,649-16,084) involving a 12-bp directly repeated sequence of 5'-CATCAACAACCG-3' exists in both the ATP6 gene and the D-loop region. These mtDNA mutations could be one of the endogenous factors that induce somatic mutations in nuclear genome and etiologically contribute to human carcinogenesis.

Adenoma, Bile Duct↗

Compact apparatus for measurement of ventilatory response to carbon dioxide in newborns and infants.

We developed a rebreathing system for measuring response to carbon dioxide (CO2) of newborns and infants for use at the bedside. The system based on Read's method is small, easy to operate, and includes a computer-controlled gas switching sequence, computerized calculation, and display functions. We measured the CO2 response in 11 infants with or without apnea, who were born at 26-33 weeks gestation and were 12 to 215 days old at the time of the study. Our results suggest that the presence of apnea in premature infants may correspond to a low CO2 response. The method was convenient for clinical use because it allowed an investigator to carry out bedside tests in only a few minutes. With our system we were able to assess respiratory center function in newborns and infants.

Apnea↗

Pharmacokinetic analysis of antibody localization in human colon cancer: comparison with immunoscintigraphy.

The biodistribution and imaging characteristics of the 111In-labeled anti CEA monoclonal antibody ZCE-025 were studied in five patients with suspicion of colorectal carcinoma. Evaluation included antibody pharmacokinetics and assessment of antibody distribution in surgical specimen, making a comparison with whole-body imaging with a gamma camera. ZCE-025 localization in tumors was demonstrated by gamma-camera imaging in 4 of the 5 patients, corresponding to surgical findings. Persistent accumulation of 111In in the lymph nodes was observed in one patient, whereas surgical exploration of these lymph nodes showed no gross or microscopic evidence of metastases of colon carcinoma. Analysis of individual plasma by size exclusion HPLC showed two radioactivity peaks, labeled antibody and free DTPA. No transchelation of 111In to circulating transferrin was observed. The blood clearance was fitted to a two-compartment equation and its half-lives were found to be 10.8 +/- 8.7 h and 69.5 +/- 21.8 h for t1/2 alpha and t1/2 beta, respectively. Total urinary excretion averaged 0.3% of the injected dose/h with a small patient to patient variation. At 24 hrs postadministration the predominant radiolabeled species in urine was free DTPA. Thereafter, radioactivity in urine was partly present as a low molecular weight catabolic product. No apparent correlation between CEA content and uptake of 111In-ZCE-025 in tumors resected by surgery could be found. How 111In-labeled antibody is accumulated into tumors as well as into some nontumor tissues needs further study.

Aged↗

Urinary laminin fragments as a tumour marker potentially reflecting basement membrane destruction.

The presence of soluble laminin fragments in urine of healthy subjects, patients with diabetes, and patients with tumours was studied using sandwich immunoenzymometric assay technique. The form of urinary laminin (ULN) fragments was dramatically different from that of intact laminin, so ULN could be detected only by using monoclonal antibodies. Mean levels of ULN in lung tumour were significantly higher (171 micrograms gram-1 creatinine) than those in healthy subjects, patients, with diabetes, patients with stomach tumour, and patients with colon tumour (respectively 91, 92, 77 and 53 micrograms gram-1 creatinine). Immunopurified ULN fragments showed an apparent molecular mass of 42 KD on electrophoresis. This fragment was recognised as being derived from the N-terminal region of laminin B2 chain, because the N-terminal residues of ULN were found to be completely homologous to B2 chain. These data suggested that ULN was almost all fragmented, consisted mainly of N-terminal domain of the B2 chain, and was suspected of a tumour-associated protein fragments probably derived from basement membrane degraded proteolytically by tumour cells. ULN, increased in tumour patients, could be a potential clinical marker for monitoring the turnover of basement membrane in tumours.

Amino Acid Sequence↗

Non-opioid-dependent inhibitory action of loperamide on cholinergic neurotransmission in canine isolated bronchial smooth muscle.

The effect of loperamide on cholinergic neurotransmission in canine bronchial smooth muscle was studied under isometric conditions in-vitro. Addition of loperamide decreased contractile responses to electrical field stimulation in a dose-dependent fashion, the maximal decrease from the control response and the IC50 value being 65.4 +/- 5.9% and 1.5 microM, respectively. In contrast, loperamide was without effect on the responses to exogenously administered acetylcholine. The inhibitory effect of loperamide was not altered by pre-incubation of tissues with propanol, 6-hydroxydopamine, bicuculline, or naloxone. These results suggest that loperamide attenuates the neurally mediated airway contraction probably by inhibiting acetylcholine release from cholinergic nerve terminals through a non-opioid-dependent mechanism.

Animals↗

An assessment of mucosal damage in vivo: effect of oral pretreatment with 5-fluorouracil on the intestinal first-pass metabolism of salicylamide in rabbits.

An assessment of 5-fluorouracil (5-FU)-induced mucosal damage in vivo by measuring the metabolism of salicylamide (SAM) was investigated in rabbit intestine. The mucosal damage in the intestine 48 h after oral administration of 5-FU (30 mg/kg) was examined using a scanning electron microscope. By the oral pretreatment with 5-FU, the morphological changes of jejunal and ileal mucosa were recognized compared with the control. The intestinal first-pass metabolism of SAM was studied using in situ intestinal sacs with complete mesenteric venous blood collection. The appearance of both SAM and its metabolites into the mesenteric venous blood was measured directly by cannulating the mesenteric vein of exposed intestine and collecting all venous blood draining from the absorbing region. Following oral pretreatment with 5-FU, the appearance of SAM glucuronide (SAMG) in the mesenteric venous blood was significantly increased. The increased blood concentration of SAMG following intraduodenal administration of SAM in vivo was observed in rabbits pretreated with 5-FU orally. However, the blood concentration of SAMG after intravenous administration of SAM was not increased compared with the control. These findings suggest that the change in intestinal first-pass metabolism of SAM may be due to the intestinal mucosal damage by oral pretreatment with 5-FU. The alteration of intestinal first-pass metabolism of a marker compound may be utilized for the assessment of intestinal mucosal damage in vivo.

Administration, Oral↗

An assessment of indomethacin-induced mucosal damage in vivo by measuring the metabolism of salicylamide in rabbit intestine.

Indomethacin-induced mucosal damage was assessed in vivo by measuring salicylamide (SAM) metabolism in rabbit intestine. Intestinal mucosal damage 48 h after oral indomethacin (500 mg/kg) administration was examined using a scanning electron microscope. Duodenal, jejunal and ileal mucosal toxicity was compared with that in controls. Intestinal first-pass metabolism of SAM was studied using in situ intestinal sacs with intact mesenteric venous blood collection. The appearance of both SAM and its metabolites in the mesenteric venous blood was measured following cannulation of the mesenteric vein of the exposed intestine and collecting all venous blood draining from the absorbing region. Following oral pretreatment with indomethacin, the appearance of SAM and SAM glucuronide (SAMG) in the mesenteric venous blood was significantly increased. The concentrations of SAM and SAMG in the blood increased following intraduodenal administration of SAM in vivo in rabbits orally pretreated with indomethacin compared with controls. However, after intravenous administration of SAM, the blood concentration of SAM and SAMG was not increased compared with controls. These findings suggest that the differences in intestinal first-pass metabolism of SAM may be due to the intestinal mucosal damage induced by oral indomethacin pretreatment. The results indicate that the alteration of intestinal first-pass metabolism of a marker compound may be utilized to assess intestinal mucosal damage in vivo.

Animals↗

An assessment of salicylic acid-induced mucosal damage in vivo by measuring the metabolism of salicylamide in rabbit intestine.

An assessment of salicylic acid-induced mucosal damage in vivo by measuring the metabolism of salicylamide (SAM) was investigated in rabbit intestine. The intestinal first-pass metabolism of SAM was studied using in situ intestinal sacs with complete mesenteric venous blood collection. The appearance of both SAM and its metabolites into the mesenteric venous blood was measured directly by cannulating the mesenteric vein of exposed intestine and collecting all venous blood draining from the absorbing region. Following oral pretreatment with salicylic acid, the appearance of SAM glucuronide (SAMG) in the mesenteric venous blood was significantly increased compared with the control. The increased blood concentration of SAMG following intraduodenal administration of SAM in vivo was observed in rabbits pretreated with salicylic acid orally. The blood concentration of SAMG after the intravenous administration of SAM was not increased compared with the control. We suggest that the change in the intestinal first-pass metabolism of SAM may be due to the intestinal mucosal damage induced by oral pretreatment with salicylic acid. The measurement of SAM metabolites may be of value in the assessment of intestinal mucosal damage in vivo.

Animals↗

Heparin-binding (fibroblast) growth factors are potential autocrine regulators of esophageal epithelial cell proliferation.

A serum-free culture system supplemented with neural tissue extract for normal human esophagus was applied to the culture of mouse esophageal epithelium. Similar to mouse mesenchyme and skin epithelium, esophageal epithelial lines (MEE) emerged after serial culture. The cells had an apparent unlimited life-span, but retained morphology and other characteristics of normal epithelial cells. A screen for growth factors that stimulated growth of MEE cells in the absence of neural extract revealed that epidermal growth factor (EGF) and heparin-binding (fibroblast) growth factors (HBGF) were most effective. An HBGF-like activity was apparent in extracts of rapidly proliferating, but not quiescent MEE cells at low or confluent densities. A cloned cell line (MEE/C8) was selected from MEE cell cultures in the absence of neural extract. MEE/C8 cells proliferated independent of either EGF or HBGF at rates equal to MEE cells, cell extracts exhibited HBGF-like activity at all stages of proliferation, and the cells formed invasive tumors in syngenic hosts. The HBGF-like activity present in extracts of tumorigenic MEE/C8 cells had properties similar to HBGF-1 (acidic fibroblast growth factor).

Animals↗

[Mitral valve prolapse associated with partial absence of commissural chordal insertion: report of two cases].

We reported 2 cases of mitral valve prolapse (MVP) associated with partial absence of the chordae tendineae. Case 1 was a 25-year-old man who was admitted to our hospital for further examinations of an apical pansystolic murmur (Levine 4/6) and the abnormal shadow on his chest radiograph. He was diagnosed as having grade 3 + mitral regurgitation (MR) by the Sellers classification and pulmonary varix by cardiac catheterization. Transesophageal echocardiography revealed MVP of the rough zone of the anterior mitral leaflet and MR blowing into the pulmonary varix. Case 2 was a 60-year-old man who was admitted to our hospital because of congestive heart failure and apical pansystolic murmur (Levine 4/6). Parasternal echocardiography revealed prolapse of both the anterior and posterior mitral leaflets and moderate MR. In both cases, absence of insertion of anterolateral commissural chordae was confirmed after surgery, and the abnormalities of chordal arrangement and insertion were considered as causes of MVP in these cases.

Adult↗

[Optimal branching of hepatic artery in patients with liver cirrhosis].

Optimality in branching structure of the hepatic arterial vessel in 16 patients with liver cirrhosis was studied. The controls used in this study were 14 patients with gastric or colonic cancer not accompanied by liver dysfunction. Optimality principle was based on the concept that blood vessel size and arrangement provided for blood flow with minimum energy loss. Measurements were made of parent and branch vessel diameters from selective celiac arteriogram. After that we measured the included angles of the branch-points of portal vein using ultrasonography. The branch-points of interest were the third bifurcations of right intrahepatic portal vein and artery. The following results are presented in terms of three parameters (r2(2)/r1(2), r1/r0, and r2/r0). The theoretical equations have been shown by several authors. The curve representing these equations was shown by Zamir. We analyzed the scatter of the data points and compare the theoretical and actual results with them. The extent of the scatter is studied making a comparison between control patients and patients with cirrhosis. The data points in control patients were plotted near the theoretical curve. In patients with cirrhosis, the data points show a definite tendency to be plotted far away from the theoretical curve, when we take account of both vessel diameters and branching angles. This discrepancy between theoretical values and actual data in patients with cirrhosis is considered to be caused by the following factors which may influence the vascular structure; hemodynamic change caused by increase of intrahepatic shunt, and morphological change caused by increased fibrosis or/and parenchymal nodules of the liver.

Celiac Artery↗

[Detection of soluble forms of platelet membrane glycoproteins and its clinical significance].

Soluble forms of surface membrane glycoproteins of various cell types have been identified as makers for in vivo or in vitro cellular events, in which the receptors are involved. Using mouse monoclonal antibodies, sandwich ELISA systems to quantitate plasma concentrations of two platelet glycoproteins in soluble form were set up: one is glycocalicin (GC), a proteolytic fragment of GP Ib alpha chain and the other is GMP-140 or CD62 (GMP) known as a target for leukocyte recruitment at vascular injury sites. As in vivo markers, GC is said to reflect platelet turnover. High levels of plasma GMP were detected in patients with thrombotic thrombocytopenic purpura, being presumably indicative of microcirculation disorder. During storage of platelet concentrates, plasma levels of both markers were increased in a time-dependent fashion over 10 days. This correlated with a decrease in the surface expression of the glycoproteins on platelets, suggesting that the soluble glycoproteins entering the supernatants by proteolysis would be an useful indicator for in vitro alteration of stored platelets surface.

Biomarkers↗

Sandwich enzyme immunoassay for serum integrins using monoclonal antibodies.

We produced monoclonal antibodies (mABs) against human integrins. Competitive enzyme-linked immunosorbent assay (ELISA) revealed that each mAB bound to different antigenic determinants. We then developed sandwich-type enzyme immunoassays (EIAs) to measure the concentration of fibronectin receptor (FNR) and vitronectin receptor (VNR). Serum immunoreactive integrin levels were measured using these EIAs in various liver and malignant diseases. In almost all cases of liver cirrhosis (LC) and hepatocellular carcinoma (HCC), serum integrin levels were significantly elevated, but were in the normal range in gastric, colon, lung cancer, and acute hepatitis (AH). The correlation between serum FNR and VNR levels was statistically significant in all cases of liver disease, and no correlation was observed between these integrin levels and conventional biochemical markers such as AST, ALT, and GGT. The serum integrin levels were demonstrated to be a potential diagnostic marker for hepatic fibrogenesis and carcinogenesis, and these sandwich EIAs could be useful for determination of these integrins in clinical laboratory tests.

Animals↗

A novel prenyltransferase for a small GTP-binding protein having a C-terminal Cys-Ala-Cys structure.

smg p25A/rab3A p25 is a member of the small GTP-binding protein superfamily which is implicated in intracellular vesicle transport. smg p25A has a cDNA-predicted C-terminal structure of Cys-Ala-Cys. The protein purified from bovine brain membranes is geranylgeranylated at both the two cysteine residues and carboxyl-methylated at the C-terminal cysteine residue. Two types of prenyltransferase for small GTP-binding proteins have thus far been reported: ras p21 farnesyltransferase (ras p21 FT) and rhoA p21 geranylgeranyltransferase (rhoA p21 GGT). Neither of them geranylgeranylated smg p25A having a C-terminal Cys-Ala-Cys structure. In this paper, a smg p25A GGT was partially purified from bovine brain cytosol and separated from the ras p21 FT and rhoA p21 GGT by column chromatographies. smg p25A GGT transferred the geranylgeranyl moiety from geranylgeranyl pyrophosphate to both the two cysteine residues in the C-terminal Cys-Ala-Cys structure of smg p25A. smg p25A GGT did not use farnesyl pyrophosphate as a substrate and was also inactive on c-Ha-ras p21 and rhoA p21 with either farnesyl pyrophosphate or geranylgeranyl pyrophosphate as a substrate. These results indicate that there are at least three types of prenyltransferase for small GTP-binding proteins in mammalian tissues.

Amino Acid Sequence↗

The posttranslationally modified C-terminal structure of bovine aortic smooth muscle rhoA p21.

rhoA p21, a ras p21-like small GTP-binding protein, has the same C-terminal consensus motif of Cys-A-A-X (A is an aliphatic amino acid and X is any amino acid) as ras p21s, which is posttranslationally processed. We here determine the posttranslationally processed C-terminal structure of the rhoA p21 purified from bovine aortic smooth muscle. Incubation of rhoA p21-expressing insect cells with exogenous [3H]mevalonolactone caused the labeling of rhoA p21, suggesting that rhoA p21 is prenylated. Consistently, Raney nickel treatment of rhoA p21 released a geranylgeranyl moiety as estimated by gas chromatography/mass spectrometry. No lipid moiety was released by KOH or NH2OH treatment. Extensive digestion of rhoA p21 with Achromobacter protease I yielded a C-terminal peptide, Ser-Gly-Cys190, that lacked the three C-terminal amino acids predicted from the cDNA but was geranylgeranylated and carboxyl methylated at the cysteine residue. Bovine brain cytosol geranylgeranylated the bacterial rhoA p21 having the three C-terminal amino acids predicted from the cDNA but not the protein lacking the three C-terminal amino acids. Bovine brain membranes methylated the synthetic C-terminal peptide with 10 amino acids of rhoA p21 which was geranylgeranylated at its C-terminal cysteine residue but not the peptide which was not geranylgeranylated. These results suggest that rhoA p21 is first geranylgeranylated followed by removal of the three C-terminal amino acids and the subsequent carboxyl methylation of the exposed cysteine residue.

Alcaligenes↗

A one step sandwich enzyme immunoassay for gamma-carboxylated osteocalcin using monoclonal antibodies.

A highly sensitive, simple and reliable one-step sandwich enzyme immunoassay (EIA) for the gamma-carboxylated form of osteocalcin (Gla-OC) has been developed using a monoclonal antibody. The minimum amount of Gla-OC detected by this EIA was approximately 0.2 ng/ml when a 10 microliter aliquot of the sample was used. The serum Gla-OC level in 30 healthy subjects was 3.6 +/- 2.19 ng/ml (mean +/- SD). A significant increase was seen in patients with chronic renal failure (20.3 +/- 4.60 ng/ml), atherosclerosis (8.3 +/- 4.94 ng/ml) and osteoporosis (10.1 +/- 4.60 ng/ml). The correlation between the values obtained by the sandwich EIA and competitive RIA methods was given by the linear regression equation, y = 2.896 + 0.759 chi, for which the correlation coefficient (r) was 0.815 (n = 58). This newly developed Gla-OC specific EIA may be useful for the diagnosis of metabolic bone disease and ectopic calcification.

Animals↗