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Biomedical subjects

A Takeda

Publications and source records attributed to A Takeda.

At least 235 records · Page 13Linked to original sources

Change of zinc distribution in rat brain with increasing age.

Zinc (Zn) accumulation in the brain of rats of various ages was studied to look into the significance of Zn for the development and function of the brain. The Zn concentration of the cerebral hemisphere was relatively low in 1- to 11-day-old rats. The Zn concentration of the cerebellum gradually increased after birth and reached nearly a plateau at 11 days old. At 48 weeks old, the Zn concentrations of the cerebral cortex and hippocampus formation were approximately twice that of the cerebral hemisphere at the early stage after birth and significantly higher than that of the cerebellum. When 65ZnCl2 was injected into two groups of rats at 5 days and 48 weeks old for comparison, 65Zn distribution in the brain of the former group was higher than that of the latter. In the neonatal rats, the highest concentration of 65Zn was found in the cerebellum, followed by the hippocampus formation, a Zn-containing neuron-rich region. In the adult rats, the highest concentration of 65Zn was found in the CA3 and dentate gyrus of the hippocampus formation. At 48 weeks, 65Zn distribution in the cerebellum was relatively low and at about the same level as in the cerebral cortex. These results suggest that Zn is highly demanded by the cerebellum, which develops rapidly after birth. The increase in Zn concentration with increasing age may reflect the Zn requirement for functioning as an neuromodulator as well as for brain development.

Aging↗

Zinc distribution in the brain of Nagase analbuminemic rat and enlargement of the ventricular system.

65ZnCl2 was intravenously injected into Nagase analbuminemic rats (NAR), which have a genetical mutation affecting albumin mRNA processing and lack serum albumin, to test the hypothesis that albumin is necessary for zinc (Zn) transport into the brain. One hour after injection, 65Zn was largely concentrated in the choroid plexus of NAR as well as normal parental Sprague-Dawley rats (SDR). Six days after injection, in both groups, the 65Zn concentration in the choroid plexus decreased, with increases in other brain regions. The finding that there was no significant difference in brain distribution of 65Zn between NAR and SDR suggests that Zn transport into the brain and its distribution through the blood-cerebrospinal fluid barrier as well as the blood-brain barrier are not dependent on serum albumin. A most interesting observation was that the cerebral ventricles were considerably enlarged in NAR.

Animals↗

Immunohistochemical localization of advanced glycation end products, pentosidine, and carboxymethyllysine in lipofuscin pigments of Alzheimer's disease and aged neurons.

Lipofuscins are intracellular fluorescent pigments accumulating in the central nervous system (CNS) with aging and degenerative processes such as Alzheimer's disease (AD). Although they are thought to be lipid peroxidation products derived from malondialdehyde, their biogenesis remains controversial. We further characterize the chemical nature of lipofuscins in brain tissues from AD patients and normal aged subjects. Advanced glycation end products (AGEs), pentosidine and carboxymethyllysine (CML), were identified by appropriate specific antibodies. They have physicochemical properties similar to those of lipofuscin and also increase with aging. Pentosidine and CML were identified in the neuronal perikarya and the extraneuroperikaryal deposits of both the AD and aged brain. Pentosidine, but not CML, was present in the fiber-like structure within the neuropil and the core of classical senile plaque. In the brain of young subjects without CNS disease, pentosidine and CML staining was faint. Pentosidine and CML co-localized with lipofuscin pigments in the neuronal perikarya of both the AD and aged brain. We demonstrate for the first time that lipofuscin is constituted not only of lipid peroxidation products but also from glycation products which may be the origin of fluorescent pigments. Lipofuscins should thus be considered as fluorescent pigments generated by lipid- and sugar-derived Schiff base-protein polymers.

Adolescent↗

Tumor cell growth is inhibited by suppressing metallothionein-I synthesis.

The effect of metallothionein (MT)-I antisense oligodeoxynucleotide (ODN) on the growth of three kinds of tumor cells was studied, since MTs may be involved in cell growth. When MT-I antisense ODN was added to leukemia P388 cells, cell growth was inhibited in a manner dependent on the dose and incubation time. MT-I antisense ODN was also inhibitory for other tumor cell lines, i.e. Ehrlich carcinoma and sarcoma 180. A significant decrease in the level of MT, but not of Zn, was observed in MT-I antisense ODN-treated cells. On the other hand, control ODN did not inhibit the cell growth appreciably. These results indicate that MT-I expression may be necessary for the growth and survival of these tumor cells.

Animals↗

Neuronal inclusions in the dentate fascia in patients with multiple system atrophy.

Ubiquitin-immunoreactive neuronal inclusions in the granular cells in the dentate fascia (UNIDs) of patients with multiple system atrophy (MSA) were examined for immunohistochemical and ultrastructural characterization especially in comparison with those which were recently reported for amyotrophic lateral sclerosis with dementia (ALS-D). Eight of 23 MSA patients had UNIDs which were also identified by Gallyas-Braak impregnation but immunonegative for other antibodies including against tau, neurofilaments, and alphaB crystallin. Ultrastructurally, loosely aggregated fibrils without limiting membrane located around the nucleus, which was confirmed by the results of ubiquitin-immunoelectron microscopy. The formation of UNIDs in MSA and ALS-D was suggested to be caused by different types of degeneration because UNIDs in MSA differ from these in ALS-D in terms of their stainability by Gallyas-Braak impregnation and ultrastructurally. In this study hippocampal involvement in MSA differing from ALS-D was clarified.

Aged↗

Zinc transport in the rat olfactory system.

To study zinc (Zn) mobility in the rat olfactory tract, brain distribution of 65Zn after injection into the olfactory bulb or amygdaloid nuclei was analyzed by autoradiography. Twenty-four hours after 65Zn injection into the olfactory bulb, 65Zn was distributed in the ipsilateral piriform cortex, amygdaloid nuclei and the anterior commissure. Moreover, in the case of injection of a higher level of 65Zn into the olfactory bulb, 65Zn was distributed in the ipsilateral entorhinal cortex in addition to the above regions. Twenty-four hours after 65Zn injection into the amygdaloid nuclei, 65Zn was distributed in the ipsilateral piriform and entorhinal cortex. These results suggest that Zn is intraneuronally transported along the olfactory tract. Zn may be taken up by the piriform neurons after release from the secondary olfactory neuron terminals and transported to the entorhinal area.

Amygdala↗

CD45-associated protein is a lymphocyte-specific membrane protein expressed in two distinct forms.

CD45-AP is a recently identified CD45-associated protein. The two proteins interact specifically through their respective transmembrane segments. Northern hybridization analysis of CD45+ T lymphocytes and their CD45- variants demonstrated that the production of CD45-AP and CD45 mRNA is regulated independently. On the other hand, Western blotting analysis indicated that the CD45-AP protein has a shorter half-life in the absence of CD45 in three out of four variants. Similar analysis of various types of leukocytes demonstrated that CD45-AP is expressed in T, B, and pre-B cells, but not in plasma cells or cells of the monocyte/macrophage lineage. Two forms of CD45-AP mRNA exist in all types of CD45-AP-expressing lymphocytes analyzed. One form corresponds to the previously reported CD45-AP cDNA and the other form encodes an additional 12 amino acids at the N terminus. The two CD45-AP proteins are identical in their capacity for specific binding to CD45, but employ different mechanisms for endoplasmic reticulum membrane translocation.

Amino Acid Sequence↗

Preferential binding with Escherichia coli hsp60 of antibodies prevalent in sera from patients with rheumatoid arthritis.

One hundred thirty-two patients with various connective tissue disorders, including 60 with rheumatoid arthritis (RA), had antibodies against human as well as Escherichia coli hsp60 in titers significantly higher than those of normal controls. There was a correlation between titers of antibody to human hsp60 and those to E. coli hsp60. Levels of antibodies against human and E. coli hsp60 were lower in joint fluids than in sera, indicating little production of antibodies in the joint. Antibodies affinity-purified with E. coli hsp60 bound strongly with the homologous hsp60, but weakly with human hsp60. However, antibodies affinity-purified with human hsp60 bound comparably with both E. coli hsp60 and human hsp60. Antibodies affinity-purified with Mycobacterium tuberculosis hsp65 bound to human hsp60 with a reactivity similar to the reactivity of those affinity-purified with human hsp60. The reactivity to the three hsp60 species was lost when sera were absorbed with E. coli hsp60, while the reactivity to E. coli hsp60 remained after extensive absorption with M. tuberculosis hsp65 or human hsp60. These results indicate that anti-hsp60 antibodies in patients with RA and other connective tissue disorders are raised by infection with intestinal microorganisms such as E. coli. They may represent another example of autoimmune responses triggered by antigenic mimicry of host proteins to microbes and suggest that the reactivity of antibodies from RA patients with M. tuberculosis hsp65 might have been a cross-reaction with the E. coli homologue.

Antibodies↗

Different pathophysiology of cardiac hypertrophy in hypertension and hypertrophic cardiomyopathy.

In order to investigate differences in the pathophysiology of cardiac hypertrophy between patients with arterial hypertension and hypertrophic cardiomyopathy, DNA synthesis by cardiac myocytes and the effects of an angiotensin-converting enzyme inhibitor were examined in these two groups of patients. DNA synthesis and the cell cycle were investigated by flow cytometry using autopsy materials from patients with hypertension and hypertrophic cardiomyopathy. The hypertension group (n=10) included four men and six women aged 61+/-10 years (heart weight: 470+/-79 g, mean+/-s.d.); the cardiomyopathic group (n=10) included eight men and two women aged 61+/-23 years (heart weight: 615+/-211 g). The percentage of cells in G2M phase of the cell cycle was significantly decreased in the myocardium from patients with hypertrophic cardiomyopathy compared with that from hypertensive patients (cardiomyopathy v hypertension: 1.1+/-0.6 v 7.7+/-2.6%, mean+/-s.d.). Captopril, an angiotensin-converting enzyme inhibitor, was administered for 12 months to patients with hypertension (n=20) and hypertrophic cardiomyopathy (n=15). Regression of cardiac hypertrophy was assessed by echocardiography. Long-term administration of captopril achieved regression of cardiac hypertrophy in the hypertensive patients, but not in the patients with hypertrophic cardiomyopathy. In the hypertensive patients, the left ventricular mass was 234+/-9 g before treatment and 198+/-26 g after treatment (mean+/-s.d., P<0. 01). In cardiomyopathic patients, on the other hand, there was no significant difference of left ventricular mass after treatment (before v after, 305+/-85 v 285+/-90 g, mean+/-s.d.). These results suggest that the mechanism of cardiac hypertrophy differs between patients with hypertension and hypertrophic cardiomyopathy.

Aged↗

Zinc depletion suppresses tumor growth in mice.

The hypothesis that in tumor-bearing animals an increase of host hepatic zinc metallothionein (Zn-MT) causes a restriction of zinc in the tumor tissue was studied. Three types of tumors were induced in laboratory mice by cell transplant. Tumor growth appears to be inhibited under zinc-deficient conditions, even in cases where zinc deficiency was started after tumor cell transplant. The survival times of tumor-bearing mice were prolonged by administration of cadmium chloride, which induces the synthesis of a combined zinc-cadmium metallothionein derivative in the host liver, but not in the tumor tissue, leading to an increase of hepatic zinc in the treated animals. The uptake of 65Zn by the liver of Cd-treated, tumor bearing mice was significantly higher than that of controls whereas uptake of 65Zn by tumor cells was significantly higher in controls than in the treated animals. These results suggest that restriction of zinc intake suppresses tumor growth.

Animals↗

Microsatellite polymorphism in the human heme oxygenase-1 gene promoter and its application in association studies with Alzheimer and Parkinson disease.

Oxidative stress has been suggested to be involved in the pathogenesis of neurodegenerative diseases, such as Alzheimer disease (AD) and Parkinson disease (PD). Heme oxygenase-1 (HO-1), a key enzyme in heme catabolism, also functions as an antioxidant enzyme. Here, we show that a (GT)n repeat in the human HO-1 gene promoter region is highly polymorphic, although no particular alleles are associated with AD or PD. This newly identified genetic marker should allow us to study the possible involvement of HO-1 in certain human diseases.

Adult↗

Abnormal cyanide metabolism in uraemic patients.

BACKGROUND: We previously investigated the factors involved in uraemic neuropathy in patients undergoing regular haemodialysis and found a significant relationship between the severity of vibration sensation impairment and the patients' smoking habits. The administration of methylcobalamin markedly improved the severity of uraemic neuropathy in terms of vibration perception thresholds. We presumed that abnormal cyanide metabolism is involved in the development of uraemic neuropathy. METHODS: Serum levels of thiocyanate (SCN-), the detoxication product of cyanide, were determined in 12 patients with preterminal chronic renal failure (PCRF), 30 patients undergoing regular haemodialysis (HD patients), and 13 healthy volunteers as a control group. Nine of the 30 HD patients were smokers. In addition, in 10 HD patients without smoking habits and 10 non-smoking healthy volunteers, the proportion of each vitamin B12 analogue in total vitamin B12 was estimated. RESULTS: The mean serum SCN- level of the 12 PCRF patients (5.1 +/- 1.5 micrograms/ml) was significantly higher than that of the control (2.8 +/- 0.9 micrograms/ml) (P < 0.01). The mean SCN- level before haemodialysis in the 21 non-smoking HD patients was identical to that in the PCRF group, whereas the level in the nine smoking HD patients (7.2 +/- 1.8 micrograms/ml) significantly higher than that in the non-smoking subgroup (P < 0.01). In 16 HD patients with methylcobalamin treatment, serum SCN- levels were lower than in those without methylcobalamin treatment (4.5 +/- 0.5 micrograms/ml in non-smoking subgroup, P < 0.05). And in the methylcobalamin-treated subgroup (n = 5), the proportion of each vitamin B12 analogue in total vitamin B12 was normal. In the untreated subgroup (n = 5), the proportion of cyanocobalamin fraction (10.5 +/- 2.6%) was as high as the level in Leber's disease patients, while the proportion of methylcobalamin fraction was low. And the serum cyanocobalamin level was higher in the treated subgroup. CONCLUSION: In uraemic patients, cyanide detoxication capability is impaired because of a reduced SCN- clearance, and increased cyanocobalamin synthesis indicates elevation of cyanide pool, which would be related to the development of uraemic neuropathy. Methylcobalamin was considered to be utilized in cyanide detoxication process via cyanocobalamin synthesis.

Adult↗

Central facial weakness due to medial medullary infarction: the course of facial corticobulbar fibres.

Two patients are reported with contralateral hemiparesis including a face of supranuclear type, caused by an infarct of the unilateral ventromedial part of the upper medulla. Data from these patients support the hypothesis that part of the corticobulbar fibres supplying the lower facial muscles descend ipsilaterally in the ventromedial part of the upper medulla and then, after decussation, ascend rostrally to the contralateral facial nucleus.

Adult↗

Hydrometrocolpos with ectopic vaginal opening to the bladder. A case report.

A case of hydrometrocolpos with vaginal opening to the bladder is presented. A newborn female presented abdominal distention and postaxial polydactyly at birth. Clinical investigation revealed hydrometrocolpos, precocious puberty, urogenital sinus and other multiple malformations. The vagina was open to the bladder with a small orifice. Vaginal pull-through surgery and closure of the communication was performed. Over a hundred cases of hydrometrocolpos have been reported previously. However, we could not find a case of hydrometrocolpos with vaginal opening to the bladder among them.

Female↗

Association of interleukin 6 release from endothelial cells and pulmonary hypertension in SLE.

OBJECTIVE: To investigate how sera from 37 patients with systemic lupus erythematosus (SLE) stimulate interleukin (IL) 6 release from IL-1beta pretreated endothelial cells and compare these effects to those of sera from 16 normal controls. METHODS: Endothelial cells pretreated 18 h with IL-1beta (5 U/ml) were incubated 2 h with sera diluted 10-fold with phosphate buffered saline (PBS). IL-6 concentrations in endothelial culture supernatants collected after incubation were measured by ELISA. RESULTS: Compared with PBS, sera from controls and 24 patients with SLE suppressed IL-6 release from IL-1beta pretreated cells. However, sera from 13 patients with SLE augmented IL-6 release. Of note, sera from 5 patients with pulmonary hypertension induced the highest level of IL-6 release. IgG from control sera suppressed IL-6 release, whereas F(ab')2 did not. Both IgG and F(ab')2 from the sera of patients with SLE with pulmonary hypertension augmented IL-6 release from IL-1beta pretreated cells. CONCLUSION: IgG antiendothelial cell antibodies from patients with SLE may be associated with the pathogenesis of SLE and pulmonary hypertension.

Adolescent↗

Followup study of renal function in children with reflux nephropathy after resolution of vesicoureteral reflux.

PURPOSE: We evaluated data collected for 10 years on children with reflux nephropathy to identify a means of predicting the prognosis. MATERIALS AND METHODS: A total of 15 boys and 13 girls were enrolled in this study at least 2 years after surgical and spontaneous resolution of vesicoureteral reflux in 25 and 3 patients, respectively. They were followed for more than 10 years and renal function was periodically evaluated. Urinary beta 2-microglobulin, alpha 1-microglobulin, N-acetyl-beta-D-glucosaminidase, microalbumin and 99mtechnetium dimercapto-succinic acid uptake were measured. RESULTS: Of the 28 patients 12 had high levels of urinary alpha 1-microglobulin during followup, including all 7 in whom renal function deteriorated. In 3 children with elevated alpha 1-microglobulin urinary microalbumin gradually increased after puberty. Although elevated levels of urinary beta 2-microglobulin, N-acetyl-beta-D-glucosaminidase and microalbumin were also observed, they were less predictive of renal function than alpha 1-microglobulin. CONCLUSIONS: These results suggest that elevated urinary levels of alpha 1-microglobulin may predict the risk of abnormal renal function in children with reflux nephropathy even before the appearance of significant proteinuria.

Acetylglucosaminidase↗

[The relation between pyrimidine nucleoside phosphorylase (PyNPase) activity in colorectal cancer tissues and pathological effects].

Pyrimidine nucleoside phosphorylase (PyNPase) and IL-1 alpha concentration were measured in colorectal cancer tissues from 15 patients who preoperatively administered 5'-DFUR orally. The relation between changes of the PyNPase activity and pathological effects of resected specimens was studied. PyNPase activity changes showed that the increase cases were 9 patients and the decrease cases were 6 patients in pre- and post-administration of 5'-DFUR. The IL-1 alpha concentration in cancer tissues was 2933.65 +/- 2038.65 in the decrease cases and 1207.51 +/- 1378.83 in the increase cases. The level was significantly higher in the decrease case (p < 0.05). And there tended to be more pathologically effective in the decrease cases than in increase cases. The effects of preoperative oral chemotherapy in colorectal cancer was strongly influenced by changes of PyNPase activity and IL-1 alpha concentration in tumor tissues.

Administration, Oral↗