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Biomedical subjects

K Wada

Publications and source records attributed to K Wada.

At least 631 records · Page 35Linked to original sources

Plasma protein S in disseminated intravascular coagulation, liver disease, collagen disease, diabetes mellitus, and under oral anticoagulant therapy.

Plasma levels of protein S (PS) antigen, both total and free fractions, were measured together with C4b-binding protein (C4bp) and protein C (PC) antigen in 39 patients with disseminated intravascular coagulation (DIC), 34 with liver disease, 17 with collagen disease, 17 with diabetes mellitus, and 51 under stabilized warfarin treatment. In patients with DIC, mean concentrations of total PS and free PS were normal, while PC was reduced and C4bp were elevated. Total PS, free PS, C4bp and PC were all decreased in liver disease, elevated in diabetes mellitus, and normal in collagen disease. In warfarin-treated patients, total PS, free PS and PC were moderately decreased, but the decrease in C4bp was minimal. The concentration of PS correlated positively with PC in liver disease, diabetes mellitus, and during oral anticoagulation, but did not in DIC. These results indicate that PS and PC behave similarly when liver synthetic function is principally affected, but in contrast to PC, PS is hardly consumed during intravascular coagulation.

Administration, Oral↗

Distribution of alpha 2, alpha 3, alpha 4, and beta 2 neuronal nicotinic receptor subunit mRNAs in the central nervous system: a hybridization histochemical study in the rat.

Previous studies have revealed the existence of a gene family that encodes a group of neuronal nicotinic acetylcholine receptor (nAChR) subunits. Four members of this family have been characterized thus far; three of these subunits (alpha 2, alpha 3, and alpha 4) are structurally related to the ligand binding subunit expressed in muscle and form functional nAChRs when combined with the beta 2 gene product in Xenopus oocytes. In addition, the alpha 4 gene appears to encode two different products (alpha 4-1 and alpha 4-2) that have been proposed to arise by alternative mRNA splicing. Nine different [35S]-complementary ribonucleic acid (cRNA) probes were used in the present study to map the distribution of these nAChR subunit mRNAs throughout the central nervous system (CNS) of the rat. It was found that the beta 2 gene is expressed in most regions of the CNS, as are the alpha subunit genes as a group. However, each alpha gene is expressed in a unique, although partly overlapping, set of neuronal structures. Alpha 4 is the most widely expressed alpha gene, and the evidence suggests that mRNAs for the alpha 4-1 and alpha 4-2 products are virtually always found in the same regions, in approximately the same ratios (alpha 4-2 greater than alpha 4-1). In addition, there are several examples of cell groups that express beta 2 but none of the alpha subunit mRNAs examined here (particularly in the hypothalamus), as well as all groups that express the converse, thus suggesting that additional neuronal nAChR subunits remain to be characterized. Finally, the extensive expression of multiple alpha subunits in certain regions, particularly for alpha 3 and alpha 4 in the thalamus, suggests that there is microheterogeneity in a small population of cells or that some neurons may express more than one alpha subunit. This problem needs to be examined directly with double labeling methods but raises the possibility that some neuronal nAChRs may be composed of more than one kind of alpha subunit. The wide expression of these receptor genes suggests that nAChRs constitute major excitatory systems in the CNS.

Animals↗

Autoradiographic visualization of a calcium channel antagonist, [125I]omega-conotoxin GVIA, binding site in the brains of normal and cerebellar mutant mice (pcd and weaver).

An in vitro autoradiographic technique has been used to localize [125I]omega-conotoxin GVIA binding sites in the brains of normal and cerebellar mutant mice. In the brains of normal mice, the highest densities of binding sites were observed at glomeruli of the olfactory bulb, cerebral cortex, caudate nucleus-putamen, hippocampus, and the nucleus of the solitary tract. Moderate densities of the silver grains occurred on the granular layer of the olfactory bulb, the molecular layer of the dentate gyrus, the molecular layer of the cerebellum, and the cochlear nucleus. No specific binding appeared in the white matter or the deep nucleus of the cerebellum, the corpus callosum, the internal capsule and the external plexiform layer of the olfactory bulb. Autoradiographic studies of the cerebella of Purkinje cell degeneration (pcd) mice showed that the distribution of binding sites on the molecular layer of the cerebellum are not affected by the degeneration of Purkinje cells. However, only background levels of the silver grains occurred on the cerebella of agranular weaver mutant mice, suggesting that the receptors for omega-conotoxin GVIA in the cerebellum are predominantly distributed on the parallel fibers of granule cells.

Animals↗

Coagulation studies in thrombotic thrombocytopenic purpura, with special reference to von Willebrand factor and protein S.

The profile of blood coagulation and fibrinolysis was studied in detail in eight patients with acute thrombotic thrombocytopenic purpura (TTP). In the majority of the patients, fibrinogen, factor XIII, antithrombin III, alpha 2-plasmin inhibitor, plasminogen, and alpha 2-macroglobulin were normal, whereas FDP, plasmin-alpha 2-plasmin inhibitor complex, and tissue-type plasminogen activator antigen were marginally or moderately elevated. Low fibronectin values were observed in four patients. Protein C and C4b-binding protein were nearly normal, whereas total protein S and free protein S were reduced in five and six patients, respectively. A positive correlation was found between total protein S and C4 and between free protein S and C3. von Willebrand factor antigen (vWf:Ag) and ristocetin cofactor (RCof) were either normal or elevated, but RCof/vWf:Ag ratio was decreased in seven patients. Crossed immunoelectrophoresis and sodium dodecyl sulfate (SDS)-agarose gel electrophoresis revealed that the large vWf multimers were either absent from or relatively decreased in all patients except one. In addition, one patient had unusually large vWf multimers, and a low-molecular-weight vWf fragment was apparently observed in three patients. These findings indicate that the intravascular generation of thrombin and plasmin was minimal in TTP and suggest that the alterations of the vWf molecule were caused not only by consumption through its participation in platelet thrombus formation but also by accelerated proteolysis. Low protein S values would be related to the immunological abnormalities underlying TTP.

Adolescent↗

Thrombin and plasmin generation in patients with liver disease.

Patients with liver disease frequently have multiple hemostatic abnormalities. Coagulation and fibrinolytic factors and inhibitors may decrease as the result of impaired synthesis and/or enhanced catabolism. In order to assess the actual degree of activation of coagulation and fibrinolytic systems in liver disease, plasma levels of thrombin-antithrombin III complex (TAT) and plasmin-alpha 2-antiplasmin complex (PAP) were measured together with cross-linked fibrin derivatives (XDP), tissue-type plasminogen activator (t-PA), and plasminogen activator inhibitor (PAI-1) in 31 patients with liver disease (five patients with acute hepatitis, seven with chronic hepatitis, nine with liver cirrhosis, and ten with hepatocellular carcinoma). Mean plasma levels of TAT (mean 4.2 +/- SD 4.0 micrograms/L), PAP (0.7 +/- 0.7 mg/L), and XDP (374 +/- 518 micrograms/L) were significantly elevated in patients with liver disease as compared with normal subjects (TAT of 1.7 +/- 0.3 micrograms/L, PAP of 0.2 +/- 0.1 mg/L, and XDP of 30 +/- 14 micrograms/L; P less than 0.005). Plasma concentrations of t-PA and PAI-1 antigens were also elevated. When plotted by the disease categories, the magnitude of elevations of these parameters was variable among subgroups. Patients with acute hepatitis had considerably higher TAT levels. The mean PAP values were relatively high in chronic hepatitis and hepatocellular carcinoma, in which an elevation of the t-PA/PAI-1 ratio was observed. Although clearance of TAT and PAP should be evaluated in the future, these findings suggest that excessive amounts of thrombin and plasmin are actually generated in patients with liver disease.

Antithrombin III↗

Thrombin generation in patients with thrombotic thrombocytopenic purpura.

Thrombotic thrombocytopenic purpura (TTP) is thought to be caused primarily by endothelial cell injury or primary platelet agglutination. A coagulation screen usually shows normal or minimal changes, but a modest elevation of fibrinogen/fibrin degradation products (FDP) is observed in many patients with TTP. To assess the thrombin generation in vivo in TTP, plasma levels of thrombin-antithrombin III complex (TAT) were measured together with plasmin-alpha 2-antiplasmin complex (PAP) in ten patients with acute TTP. Plasma TAT [mean 6.7 +/- (SD) 3.7 micrograms/liter] as well as PAP (2.1 +/- 1.2 mg/liter) were elevated in patients with TTP as compared with healthy subjects (TAT of 1.7 +/- 0.3 microgram/liter and PAP of 0.2 +/- 0.1 mg/liter; n = 10). These findings indicate that considerable amounts of thrombin and plasmin are actually generated in TTP, although the majority of patients do not show signs of consumption coagulopathy.

Adult↗

Biopsy diagnosis of well-differentiated hepatocellular carcinoma based on new morphologic criteria.

Nodular hepatic lesions detected in 123 patients with chronic liver diseases were subjected to ultrasonically guided needle biopsy. Of these, 94 cases were diagnosed as hepatocellular carcinoma of a moderately or poorly differentiated type with classical histologic features of hepatocellular carcinoma. In 14 cases in whom hepatocytes had minimal atypical changes and were mostly of normotrabecular arrangement (one to two cells thick), a diagnosis of well-differentiated hepatocellular carcinoma was made on the basis of the following three histologic criteria: nuclear crowding, increased cytoplasmic basophilia and microacinar formation. The nodules which showed two or more of these findings were diagnosed as well-differentiated HCC. The diagnoses of these 14 cases were subsequently confirmed by clinical course, histology in the resected specimen and/or autopsy findings. The nodules that presented similar but equivocal changes were arbitrarily categorized as borderline lesions (five cases). The nodules showing the findings almost identical with those of pseudolobules were regarded as benign, large regenerative nodules (nine cases). The remaining one case had a hemangioma. Thus, these three histologic criteria proved to be useful in the biopsy diagnosis of nodular hepatic lesions, with certain limitations. Additionally, the majority of large regenerative nodules, borderline lesions and well-differentiated HCCs were found to be smaller than 2 cm.

Biopsy, Needle↗

Neurofibromatosis with spinal paralysis due to arteriovenous fistula.

A case of neurofibromatosis with spinal paralysis due to arteriovenous fistula is reported. Preoperatively, the appropriate diagnosis was missed because angiography had not been performed. Postoperative angiography disclosed that an arteriovenous fistula formed a tumor-like mass, and that a part of the mass had invaded the spinal canal, compressing the spinal cord. It is concluded that the possibility of an arteriovenous fistula should be kept in mind in neurofibromatosis patients with spinal cord symptoms.

Adult↗

Hepatocellular carcinoma without cirrhosis in Japanese patients.

Hepatocellular carcinoma is closely associated with cirrhosis, but it also develops, although much less frequently, in a noncirrhotic liver. It is suspected, without supporting evidence, that hepatocellular carcinoma has a different etiology when associated and not associated with chronic liver disease. In this study, 66 noncirrhotic cases found among 618 autopsies for hepatocellular carcinoma (10.7%) were analyzed retrospectively. The noncirrhotic liver was histologically unremarkable in 3 cases and in the histologically evaluable 56 cases it had fibrosis of varying degrees or mild cellular infiltrate, or both, in the portal tract. There was one liver that had portal venous changes compatible with those in idiopathic portal hypertension (Banti's syndrome). In these noncirrhotic livers, the parenchymal cells were generally unremarkable except for liver cell dysplasia that was seen in 26.8%. Serum hepatitis B surface antigen was positive in only 7.4% in contrast to 26.6% in cirrhotic cases. Three histologically unremarkable cases had no clinical or histologic evidence of chronic liver disease; two involved painter-plasterers and one a farmer. The liver weight in these cases ranged from 4400 to 6180 g. In contrast, the average liver weight in cirrhotic cases was 1998 g. Noncirrhotic patients when compared with cirrhotic patients had better liver function tests and much less frequent varices. It was concluded that approximately 11% of hepatocellular carcinoma cases in Japan are noncirrhotic, the majority having some histologic changes in the portal tracts suggestive of past or ongoing chronic liver disease, and that there are rare cases that have no histologic changes in the liver.

Adult↗

The deviation of the body's sway center with galvanic stimulation.

We investigated galvanic body sway of ten healthy adults and eight patients by using the averaging program for measuring T1 and T2, which were latencies at the onset and at the cutoff of galvanic stimulation, respectively, and the plotting program, which adopted 1.73 sec as T1 and 0.39 sec as T2, for calculating the coordinates of the body's sway center. We estimated galvanic body sway with the difference between the coordinate of the body's sway center during stimulation and that during no stimulation. The deviation in lateral direction on the healthy subjects ranged from 0.7 or 0.9 to 2.1 cm at right- or left-side stimulation. One of the patients with peripheral disorders revealed differences between right- and left-side stimulation. The other patients did not reveal any differences. In antero-posterior direction six of the healthy subjects deviated backward at right-side stimulation and nine subjects deviated backward at left-side stimulation. The patients with peripheral disorders did not reveal any differences. The other patients revealed some differences. Waves computed by the averaging program do not always show the quantity of galvanic body sway. The deviation of the body's sway center shows the quantity of body sway consistently. The body's sway center is considered to be a suitable parameter in the galvanic body sway test for statistical analysis.

Adult↗

Isolation and sequence studies of cysteinyl peptides from Spirulina glutathione reductase: comparison of active site cysteine peptides with those of other flavoprotein disulfide oxidoreductases.

The amino acid sequences of the cysteinyl peptides of Spirulina sp. glutathione reductase were determined. Spirulina glutathione reductase was covalently bound to Thiopropyl-Sepharose 6B in the presence of 8M urea through thiol-disulfide exchange. After tryptic digestion, 4 distinct cysteinyl peptides were finally isolated from NADPH-reduced glutathione reductase and 2 from oxidized glutathione reductase. The amino acid sequences of the two cysteinyl peptides which could not be isolated from the oxidized glutathione reductase were very similar to those around the active site disulfide of the other flavoprotein disulfide oxidoreductases and a unique replacement of asparagine and valine by isoleucine and arginine between the two cysteine residues was found. The other two peptides isolated from both oxidized and reduced glutathione reductase also show considerable homology to the corresponding parts of human and Escherichia coli glutathione reductases.

Amino Acid Sequence↗

Amino acid sequences of ferredoxin isoproteins from radish roots.

Three ferredoxin isoproteins (R-Fd A, R-Fd B-1, and R-Fd B-2) were purified from white roots of radish (Raphanus sativus L. var. acantiformis cultivar Miyashige) and two isoproteins (L-Fd A and L-Fd B) from leaves. The amino acid sequences of three of them (L-Fd A, R-Fd B-1, and R-Fd B-2) were determined and compared with one another and with those of other higher plant ferredoxins so far studied. L-Fd A and R-Fd B-1 had heterogeneities at four and two amino acid sites, respectively. Two isoprotein (R-Fd B-1 and R-Fd B-2) were deduced to be expressed only in root tissue on the basis of sequence studies and amino acid compositions of all isoferredoxins isolated from the radish plant. The root ferredoxins sequenced in this study were similar to each other, but quite different from other higher plant ferredoxins, all of which were isolated from leaf tissue. The coupling activities of these ferredoxin isoproteins were measured in the NADP+-photoreduction system of radish chloroplasts and glutamate synthase [EC 1.4.7.1] systems isolated from radish leaf and root tissues. No distinctive physiological characteristics were observed among these isoferredoxins.

Amino Acid Sequence↗

Neural crest cell differentiation and carcinogenesis: capability of goldfish erythrophoroma cells for multiple differentiation and clonal polymorphism in their melanogenic variants.

Multiple differentiation shown by a single cell line (GEM 81) of goldfish erythrophoroma (tumors of integumental erythrophores) cells after administration of chemical induction in vitro includes 1) melanogenesis, 2) formation of reflecting platelets, 3) synthesis of pteridines heterogeneous to this species, 4) formation of dermal skeletons such as teeth and fin rays, 5) production of neuronal characters, and 6) genesis of lentoid bodies. Melanogenic cells, highest in inducibility, also show remarkable phenotypic diversification in their cell morphology, pigmentation, and physiologic response. In this paper, the following findings are presented; a) multiple differentiation shown by erythrophoroma cells occurs on a clonal basis, making whole component cells of a given induced colony strikingly similar in their cell characters, and b) induced melanogenic clones manifest a remarkable polymorphism in their melanosome ultrastructure and receptor composition associated with motile response. The divergence covers concentric lamellar, multivesicular, fibrillar, and macroglobular types for the former, and a varying combination of receptors for epinephrine, melanin concentrating hormone (MCH), and melatonin for the latter. Because a spectrum of phenotypes expressed by differentiation-induced erythrophoroma cells is restricted to those of neural crest origin (except lentoid bodies) and polymorphism in induced melanized cells is composed mostly of a collection of a variety of known melanogenic characters, it is presumed that erythrophoroma cells are capable of multiple differentiation within the commitment as neural crest cells.

Animals↗

Delayed cutaneous metastasis of gastric carcinoma.

This paper describes a case of skin cancer resembling carcinoma en cuirasse associated with multiple bone lesions, which were both judged to be due to metastasis of poorly differentiated carcinoma of the stomach, the primary lesion excised ten years previously. Overt bone involvement had been observed for more than two years and a half. Histologic examination of a skin biopsy specimen showed that carcinoma cells had infiltrated into the middle and lower dermis, forming clusters and strands in an abundance of fibrous stromata. No primary lesion was detected in the remnant stomach at autopsy.

Adenocarcinoma↗

Iron concentration in teeth of Tetra-odontiform fishes and its phylogenetic significance.

It is known that iron is deposited in the enameloid of some teleost fishes, although its biological significance has not been clarified. In the present investigation, a quantitative analysis of iron in the enameloid of fishes of a primitive suborder, the Balistoidei, and an advanced suborder, the Tetra-odontoidei, of the Tetra-odontiformes of marine teleosts was performed by means of the electron microprobe. The results indicated that the enameloid of Balistoidei contained from 0.4-13.5% iron at its surface layer, whereas that of Tetra-odontoidei was very low in iron, which could not be discriminated from the background value of the emission intensity. The enameloid of three perciform species belonging to the Acanthuridae--from which the Tetra-odontiformes are considered to have been derived--also contained high iron (2.7-3.9%) throughout its entire layer. The iron concentration in the enameloid seemed to be related to the phylogeny of fishes rather than to their environmental water and feeding habits, and it is believed that the mechanisms of iron concentration into the developing enameloid have been lost during evolution from the Achanthuridae to the Tetra-odontoidei. Since a similar phenomenon has been previously observed with respect to the fluoride concentration in the enameloid of the same fishes (Suga et al., 1981a), it is speculated that the concentrations of iron and fluoride, which have originally no chemical correlation, have some special biological significance, although the timing and distribution pattern of their deposition are completely different.

Animals↗

Effect of food on nifedipine sustained-release preparation.

The effect of food on the bioavailability of a nifedipine sustained-release preparation was studied. Each of seven male volunteers received a single oral 20 mg dose with 100 mL of water under two conditions, fasting and after a meal, with a crossover after a seven-day wash-out period. Blood samples were drawn at time zero (just prior to dose), and 1, 2, 3, 4, 6, 8, 10, and 12 hours after dosing. Nifedipine assays were performed by gas chromatography. The area under the serum concentration-time curve (AUC) from 0 to 12 hours and maximum serum concentration (Cmax) were significantly increased by food. Blood pressure was significantly decreased by food. The mean AUC for fasting and meal conditions were 315.0 and 411.4 ng.h/mL, and the mean Cmax were 42.6 and 86.6 micrograms/mL, respectively. The results indicate that food may increase the bioavailability of nifedipine sustained-release preparation.

Adult↗