Mitotic neurons: a dogma succumbs.
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Mitosis↗
Biomedical subjects
A Takeda
Publications and source records attributed to A Takeda.
Immunohistochemical localization of the neutral cysteine protease bleomycin hydrolase in human skin.
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Animals↗
Granulocyte-colony-stimulating-factor-producing hepatocellular carcinoma.
Patients with hepatocellular carcinoma (HCC) rarely show marked granulocytosis. We report an interesting case of rapidly growing poorly differentiated HCC associated with marked granulocytosis. The blood leukocyte count decreased following several treatments for HCC, including transcatheter arterial embolization, and increased again along with tumor regrowth. The serum levels of granulocyte colony-stimulating factor (G-CSF) were markedly elevated, and immunohistochemical study showed G-CSF staining in the cytoplasm of certain HCC cells. These findings confirm that HCC in this case was a G-CSF-producing tumor.
Aged↗
109Cd transport in rat brain.
The brain distribution of 109CdCl2 following administration into either the tail vein, the lateral ventricle or the olfactory bulb was studied to clarify permeability of the brain barrier system to cadmium (Cd) and Cd movement in the cerebrospinal fluid (CSF) and the brain extracellular fluid. One hour after intravenous (i.v.) injection, 109Cd was largely concentrated in the choroid plexus, and 109Cd concentration in the major part of the brain parenchyma, except for the circumventricular organs such as the pineal gland and the regions around them, was low. Six days after i.v. injection, 109Cd concentration in the choroid plexus was still high, and 109Cd was also detected highly in the pineal gland and small part around the median eminence. 109Cd concentration in the major part of the brain parenchyma was decreased in parallel with that in the blood. In the case of injection of 109CdCl2 into the lateral ventricle, a large portion of 109Cd was detected in the ventricular system 6 days after injection, and 109Cd concentration in the major part of the brain parenchyma was less than the detection limit. These results suggest that Cd cannot easily get into the brain and is blocked not only by the blood- brain and the blood-CSF barriers, but also by the ependymal and pial surfaces. In the case of injection of 109CdCl2 into the olfactory bulb, a large portion of 109Cd was detected in the injected area 24 h after injection, and, the next 24 h later, 109Cd distribution in the brain was not changed appreciably. These results suggest that Cd cannot easily move in the brain extracelular space, and is taken up into the brain parenchyma.
Animals↗
Congenital malformations due to antiepileptic drugs.
To identify the major risk factors for the increased incidence of congenital malformations in offspring of mothers being treated for epilepsy with antiepileptic drugs (AEDs) during pregnancy and, to determine the relative teratogenic risk of AEDs, we prospectively analyzed 983 offspring born in Japan, Italy, and Canada. The incidence of congenital malformations in offspring without drug exposure was 3.1%, versus an incidence with drug exposure of 9.0%. The highest incidence in offspring exposed to a single AED occurred with primidone (PRM; 14.3%), which was followed by valproate (VPA; 11.1%), phenytoin (PHT; 9.1%), carbamazepine (CBZ; 5.7%), and phenobarbital (PB; 5.1%). The VPA dose and level positively correlated with the incidence of malformations. This study first determined a cut-off value of VPA dose and level at 1000 mg/day and 70 microg/ml, respectively, to avoid the occurrence of malformations. The incidence of malformations increases as the number of drugs increases, and as the total daily dose increases. Specific combinations of AEDs such as VPA + CBZ and PHT + PRM + PB produced a higher incidence of congenital malformations. The incidence of malformations was not associated with any background factors studied except for the presence of malformations in siblings. These results indicate that the increased incidence of congenital malformations was caused primarily by AEDs, suggesting that malformations can be prevented by improvements in drug regimen, and by avoiding polypharmacy and high levels of VPA (more than 70 microg/ml) in the treatment of epileptic women of childbearimg age.
Abnormalities, Drug-Induced↗
Intrauterine growth in the offspring of epileptic women: a prospective multicenter study.
The aim of the present study was to evaluate the risk of intrauterine growth delay in the offspring of epileptic mothers and to quantify the risks of intrauterine exposure to antiepileptic drugs (AEDs). Data concerning 870 newborns, prospectively collected in Canada, Japan and Italy, using the same study design, were pooled and analyzed. The overall proportion of newborns whose body weight (7.8%) or head circumference (11.1%) at birth were below the 10th percentile was not increased. However, logistic regression analysis showed that the risk of small head circumference was significantly higher in Italian than in Japanese (RR 4.2; 95% CI: 2.2-8.0) or Canadian children (RR 2.6; 95% CI: 1.1-6.5), and in children exposed to polytherapy (RR 2.7; 95% CI: 1.2-6.3), phenobarbital (PB) (RR 3.6; 95% CI: 1.4-9.4) and primidone (PRM) (RR 4.5; 95% CI: 1.5-13.8). Country was also the only factor affecting low body weight, with Italian children having a higher risk than Japanese (RR 5.2; 95% CI: 2.6-10.4) or Canadian (RR 8.8; 95% CI: 2.0-38.1) children. Due to the small categories, the influence of AED doses and plasma concentrations was studied for each individual AED, without adjustment for the other potential confounding factors. A clear dose-dependent effect was found for PB and PRM in terms of both small head circumference and low body weight, and a concentration-dependent effect for PB in terms of small head circumferences. The size of the difference between the Italian and the other two populations, which is only partially explained by differences in therapeutic regimens, suggests that genetic, environmental and ethnic factors also need to be taken into account when considering possible explanations.
Anticonvulsants↗
Metallothionein: localization in human transplant endomyocardium, relation to cytokines and allograft function.
BACKGROUND: The aim of this study was to investigate the role of metallothionein in cardiac transplants in relation to cytokines and allograft function. Recent studies have revealed an association of allograft dysfunction with elevated proinflammatory cytokines independent of cellular rejection. In animal experiments, cytokines induced overexpression of metallothionein, a low-molecular-weight protein implicated in cellular stress response. METHODS: In 105 consecutive biopsies from 15 patients during the first 3 months after heart transplantation, metallothionein expression was investigated immunohistochemically. Its relation to serum interleukin-6, tumor necrosis factor-alpha, interleukin-2 (IL-2), soluble interleukin-2 receptor rejection, and echocardiographic parameters was determined. Forty-three biopsies of 12 patients with idiopathic ventricular tachycardia served as controls. RESULTS: Metallothionein expression was demonstrated in small vessels, cardiomyocytes, fibrocytes, and interstitial round cells. A positive relation between interleukin-6 levels and the number of metallothionein-positive small vessels (p < 0.028) was observed. Patients with lower serum IL-2 levels showed significantly higher numbers of metallothionein-positive small vessels (p < 0.043). Grafts with prolonged ischemic time (>150 minutes) showed a significantly higher myocardial metallothionein score (p < 0.021). Metallothionein expression was associated with lower fractional shortening, larger left ventricular end-systolic diameter, and lower mean arterial pressure but not with acute cellular rejection. CONCLUSIONS: Metallothionein expression is associated with elevated interleukin-6 and decreased interleukin-2 serum levels and left ventricular allograft dysfunction in the absence of rejection.
Acute Disease↗
Detection of hepatitis C virus RNA in the hearts of patients with hepatogenic cardiomyopathy.
We examined the Hepatitis C virus (HCV) genome in the myocardium and liver obtained at autopsy from seven patients with HCV-positive liver cirrhosis and hepatocellular carcinoma (HCC) by in situ hybridization and histopathological studies. The HCV virus genome was detected in the myocardium of one patient as well as in the liver in three out of seven patients. However, Epstein-Barr (EB) virus genome could not be detected in liver or myocardium. In the patient who showed positive reaction to HCV in myocardium, both serum HCV and Hepatitis B virus (HBV) antibodies were positive. It is unknown whether this was related to an immunological abnormality of the host or to an interaction between RNA and DNA viruses. In conclusion, we could identify the HCV genome in the myocardium of a patient with hepatogenic myocardosis.
Aged↗
Pretreatment of human keratinocyte sheets with laminin 5 improves their grafting efficiency.
Laminin 5 is essential in epithelial attachment to stromal tissues, suggesting that it might improve keratinocyte attachment in a variety of clinical situations. In this study, we examined the effect of exogenous laminin 5 upon the efficiency of transplantation of keratinocyte sheets in animal models. Keratinocyte sheets were prepared according to the method of Rheinwald & Green (1975). Purified laminin 5 was added to the sheets of group 1 (1.0 microg per cm2), Dulbecco's modified Eagle's medium alone was added to group 2. The sheets were grafted to the panniculus carnosus of nude mice (BALB/C nu/nu) (n = 12) and nude rats (Fisher 344) (n = 15). The take rate was assessed by measurement of the area of surviving epithelium at 7 d postgrafting. Laminin 5 bound the keratinocyte sheets of group 1. At 7 d postgrafting, the area of epithelialization of group 1 was significantly larger than that of group 2. Immunohistochemistry staining showed that collagen IV, laminin 5, and collagen VII stained more strongly at the dermal-epidermal junction in group 1 than in group 2. Integrin chains alpha6 and beta4 were similar in both groups. Electron microscopy at day 3 after grafting, showed the lamina densa of group 1 to be more continuous than in group 2. Pretreatment of cultured human keratinocyte sheets with laminin 5 improved the extent of epithelial coverage and increased the rate of neobasement membrane formation. The results suggest that laminin 5 promotes epithelial attachment by increasing the rate of basement membrane assembly.
Animals↗
Increased expression of TGF-beta1 but not of its receptors contributes to human obstructive nephropathy.
UNLABELLED: Increased expression of TGF-beta1 but not of its receptors contributes to human obstructive nephropathy. BACKGROUND: Previous studies have revealed an increased expression of transforming growth factor-beta1 (TGF-beta1) and deposition of extracellular matrix in the kidney of animals with ureteral obstruction. However, these relationships have not been elucidated in the hydronephrotic kidney of humans. METHODS: We analyzed the tissue expression of extracellular matrix proteins, TGF-beta1, and its receptors in the human kidney with ureteral obstruction by immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR). Obstructed kidneys (OBKs) were obtained from patients with ureteral tumors. A kidney specimen from patients with a renal tumor was used as control (CNKs). RESULTS: The interstitial volume was significantly increased in OBKs in comparison with CNKs. OBKs showed increased deposition of collagen types I and IV and fibronectin in the renal interstitium. RT-PCR revealed overexpression of collagen alpha1(IV) mRNA and fibronectin mRNA in OBKs. OBKs showed a significantly increased mRNA expression of TGF-beta1 in comparison with CNKs. The immunoreactivity for TGF-beta1 increased markedly in the interstitium of OBKs. There was a significant correlation between the TGF-beta1 mRNA level and the interstitial volume. However, there was no significant difference between OBKs and CNKs in the relative mRNA level nor in immunoreactivity for TGF-beta receptors. CONCLUSIONS: These data suggest that TGF-beta1 may contribute to the interstitial fibrosis found in the human kidney with ureteral obstruction, mainly because of an increase in the expression of this cytokine without significant changes to its receptors.
Activin Receptors, Type I↗
Detection of OXA-4 beta-lactamase in Pseudomonas aeruginosa isolates by genetic methods.
In Pseudomonas aeruginosa, resistance to cefclidin is usually associated with resistance to another third-generation cephalosporin, ceftazidime. In this study we analysed 22 isolates of P. aeruginosa, collected at Showa University Fujigaoka Hospital between 1992 and 1993, which were resistant to cefclidin but susceptible to ceftazidime. All polymerase chain reaction (PCR) products amplified by a primer pair covering the full-length gene of OXA-4 (also OXA-1) precursor beta-lactamase were 0.84 kb in length. The isoelectric points of the beta-lactamases produced by these isolates were typical of the OXA-4 type of beta-lactamase (pl 7.5) rather than the OXA-1 type (pl 7.4). All PCR products at 216 bp were amplified by the primer pair covering the A928-->T point mutation, which corresponds to the Asp48-->Val amino acid substitution of OXA-1 beta-lactamase to form OXA-4 beta-lactamase. These single-strand conformation polymorphism (SSCP) patterns are typical of the OXA-4 gene, rather than the OXA-1 gene, demonstrating that these enzymes can be classified by SSCP analyses based on the PCR method. Although OXA-4 beta-lactamase is generally plasmid-mediated, the chromosomal DNA of these isolates, but not their plasmids, hybridized with the OXA-4 gene amplified by the PCR method. Based on these results, we suspected that the plasmids encoding OXA-4 beta-lactamase had been spontaneously cured, or that the gene had been deleted from the plasmid. The distribution of P. aeruginosa producing OXA-4 beta-lactamase amongst hospital wards and clinical specimens demonstrated that the OXA-4 enzyme in this collection period was representative of hospital P. aeruginosa.
Amino Acid Sequence↗
Molecular cloning, enhancement of expression efficiency and site-directed mutagenesis of rat epidermal cystatin A.
A rat cystatin A cDNA clone was isolated from a lambda ZAP library representing newborn rat skin mRNA by screening with a synthetic oligonucleotide designed from amino acid sequence 15-23 of the cysteine proteinase inhibitor. The obtained clone contained a partial coding region of the inhibitor, lacking the 5'-untranslated region and coding sequence for the NH(2)-terminal 13 residues. The amino acid sequence deduced from the base sequence, Glu14-Phe103, coincided with that determined at the amino acid level. To obtain the recombinant cystatin A protein, the DNA was fused with a synthetic linker encoding its missing N-terminal 17 residues and introduced into an expression vector, pMK2. In Escherichia coli, however, the expression level of the semi-synthetic gene was low, 0. 5 mg of the purified recombinant protein per 1 liter culture being produced. Changing of the codon usage of the N-terminal region in a pET-15b expression system led to an increase in the yield depending on the instability of the putative secondary structure around an initiation codon of the mRNA. The expressed cystatin A showed identical characteristics with the authentic form except for the absence of the N-terminal acetyl blocking group. Using the expression system, two kinds of point mutation, the conservative Val54 in the first loop QxVxG region being changed to Lys and Glu, were introduced, but there was almost no effect on the inhibitory activity toward papain. This suggests that the conserved Val in the reactive site is not restricted and that the hydrophobicity of the position is not essential for the activity of rat cystatin A.
Amino Acid Sequence↗
Promising therapy for congenital giant pigmented nevi using acellular autograft nevi-dermal matrix.
As promising new therapy for congenital giant pigmented nevi, the authors investigated the potential use of an acellular autograft nevi-dermal matrix in combination with a split-thickness skin graft. To address whether the processed acellular nevi-dermal matrix from frozen skin could be reconstituted as a viable dermal base, the authors grafted it onto full-thickness skin defects in nude rats. Fibroblast infiltration and neovascularization into the acellular nevi-dermal matrix were observed. However, because the disappearance of the residual melanotic granules of the grafted dermis took 16 weeks, the authors excised with scissors the superficial layer of the acellular nevi-dermal matrix containing a large quantity of melanin. The appearance after using this method was relatively superior even compared with the full-thickness skin graft. The success of their experimental animal model using the acellular nevi-dermal matrix covered with split-thickness skin grafts confirms the potential value for the clinical application of this treatment for congenital giant nevi.
Animals↗
Detection of serum p53 antibodies in mucosal colorectal cancer and negative conversion after endoscopic resection.
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Antibodies, Neoplasm↗
Neuronal RNA oxidation in Alzheimer's disease and Down's syndrome.
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Aged↗
Protective effects of heme oxygenase-1 against oxidant-induced injury in the cultured human tracheal epithelium.
To examine whether increases in heme oxygenase (HO)-1 activity have protective effects on the oxidant-induced injury of airway epithelial cells, human tracheal epithelial cells were cultured on a porous filter membrane, and electrical conductance (G) and mannitol flux across epithelial membrane were measured with Ussing's chamber methods and D-[(3)H]mannitol, respectively. Hydrogen peroxide (H(2)O(2); 1 mM) increased G with time from the baseline value of 6.0 +/- 0.6 to 17.8 +/- 0.9 mS/cm(2) at 6 h after administration (P < 0.001). Likewise, H(2)O(2) significantly increased mannitol flux through the cultured epithelium (P < 0.01). Pretreatment of cultured epithelial cells with hemin (10 microM; 8 h) or interleukin (IL)-1beta (10 ng/ml; 16 h) completely inhibited increases in G and mannitol flux induced by H(2)O(2). Tin protoporphyrin IX (50 micrometer) and zinc protoporphyrin IX (10 microM), inhibitors of HO-1, reduced hemin-induced and IL-1beta-induced inhibitory effects. Hemin treatment increased HO-1 messenger RNA expression, HO-1 protein production, and HO activity and bilirubin content as well as ferritin content in the cultured epithelial cells. Pretreatment with hemin and desferoxamine, which, like ferritin, can bind iron, inhibited H(2)O(2)-induced increases in G and mannitol permeability. Although exogenous bilirubin mimicked hemin-induced inhibitory effects, exogenous apoferritin failed to inhibit H(2)O(2)-induced effects on G and mannitol permeability. These findings suggest that HO-1 induction provides protection against H(2)O(2)-induced injury of the cultured human airway epithelial cells in part via the HO-bilirubin pathway.
Adult↗
Enhanced effects of monoclonal antibody carboplatin immunoconjugates uptake and anti-tumor effects with angiotensin II and tumor necrosis factor.
The most important factor influencing the use of monoclonal antibody immunoconjugates for cancer treatment is effectiveness of enhancement for tumor targeting. We call attention to the vasoactive agents angiotensin II (ATII) for selective increase in tumor blood flow and cytokine tumor necrosis factor (TNF) to improve the vascular permeability of the tumor. Tumor localization and biodistribution were investigated by nude mice transplanted human colon adenocarcinoma (LS-180) with radiolabeled carboplatin immunoconjugates. Tumor activity 48 h after administration of ATII and TNF was significantly higher than in the control group. However, nonspecific accumulation in normal organs was not observed. In vivo anti-tumor effects in animals with ATII and TNF was significantly stronger than in those given the same dose drug alone or immunoconjugates alone. These results indicate that ATII and TNF could be useful tools for induction of stronger inhibition of tumor growth without systemic toxicity.
Adenocarcinoma↗
[Assessment of beta-methyl lodophenyl pentadecanoic acid myocardial scintigraphy in patients with chronic pulmonary diseases].
The purpose of this study was to determine whether impaired fatty acid metabolism occurs in the right ventricle of patients with chronic pulmonary diseases (TB sequelae, TB seq.; 8, and chronic pulmonary emphysema. CPE; 14). 123I-BMIPP myocardial scintigraphy was performed on 22 subjects. The RV-BMIPP index (ratio of radioactivity in the right ventricle to that in the upper mediastinum), LV-BMIPP index (ratio of radioactivity in the left ventricle to that in the upper mediastinum), and RVc/LVc (ratio of radioactivity in the right ventricle to that in the left ventricle) were calculated to compare the distribution of radioactivity in the right and left ventricles. We also examined the correlations between these parameters and parameters of blood gas analysis and pulmonary hemodynamics. The RV-BMIPP index. LV-BMIPP index, and RVc/LVc were elevated in the TB seq. and CPE patient groups compared to the control group. The RV-BMIPP and LV-BMIPP indices demonstrated significant, negative correlations with PaO2; also a significant positive correlation was observed between the RV-BMIPP index and mean pulmonary arterial pressure. On the other hand, no significant correlation was found between the LV-BMIPP index and mean pulmonary arterial pressure. In the arm-stretching test under right heart catheterization, the RV-BMIPP and LV-BMIPP indices demonstrated significant, positive correlations with the cardiac index during exercise. These results suggest that hypoxemia accelerates fatty acid metabolism in the myocardium, and that local pressure overloading accelerates fatty acid metabolism in the right ventricle. Anomalies of fatty acid metabolism in the right ventricle may appear in patients with chronic pulmonary disease, and could be an adaptation to hypoxemia and overload, not an impairment.
Aged↗