Search PubMed⌕ Search

Biomedical subjects

A Takeda

Publications and source records attributed to A Takeda.

At least 109 records · Page 6Linked to original sources

C-terminal alpha-synuclein immunoreactivity in structures other than Lewy bodies in neurodegenerative disorders.

alpha-Synuclein is a presynaptic terminal protein that accumulates abnormally in plaques in Alzheimer's disease (AD), in Lewy bodies in Lewy body disease (LBD) and in filamentous inclusions in multiple system atrophy. Since it has been previously shown that proteinase K or formic acid pretreatment enhances alpha-synuclein immunoreactivity in Lewy bodies and plaques, we hypothesized that the immunoreactivity in tangles, glial cells and Pick bodies might be revealed by such pretreatment. Brain sections from patients with AD, LBD, progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) and Pick's disease were pretreated with proteinase K or formic acid and immunostained with antibodies against the N-terminal, C-terminal or non-amyloid beta component of AD amyloid (NAC) regions of alpha-synuclein. This study showed that after proteinase K (but not formic acid) pretreatment the anti-C terminus antibody immunostained neurofibrillary tangles of AD, PSP and CBD, and glial inclusions of PSP and CBD, as well as Pick bodies. Western blot analysis confirmed that in cases other than LBD, the anti-C terminus antibodies also recognized the native alpha-synuclein band and no cross-reactive bands were observed. In contrast, in LBD, after formic acid pretreatment with the anti-NAC antibody astroglial cells and granular neurons were immunostained. The N-terminal region antibody only recognized the lesions in LBD cases and not those of other neurodegenerative disorders. These results support the view that different fragments of alpha-synuclein might play an important role in the pathogenesis of several neurodegenerative disorders.

Aged↗

A patient with rectal ulcer with severe stenosis presenting with perforated peritonitis.

We report a patient with rectal ulcer with severe stenosis, who underwent urgent surgical treatment for perforated peritonitis. The 54-year-old man suddenly developed cramping abdominal pain and fever while hospitalized, with signs of peritoneal irritation. An emergency laparotomy was performed, and severe stenosis of the rectum and a perforated lesion on the oral side approximately 10 cm distant from the stenosis were found, with massive abdominal purulent fluid. He was treated by rectosigmoid colon resection with transverse colon loop colostomy. Histopathologically, the stenosis was caused by ulceration extending to all muscular layers of the rectum, with inflammatory changes. Benign rectal stenosis is so rare that differential diagnosis from malignancy may be difficult when there are inflammatory changes in the surrounding tissues. However, it is necessary to keep in mind the likelihood of this disease in differentiation from rectal cancer.

Constriction, Pathologic↗

DNA single-strand breaks are increased in muscle diseases with rimmed vacuoles.

Some pathological similarities between Alzheimer's disease and muscle diseases with rimmed vacuoles (RV) have been pointed out. For example, several pathological hallmark proteins have been reported to be immunopositive in the lesions of both diseases. Since apoptotic processes or primary DNA damage are suggested to play a role in the pathomechanism of Alzheimer's disease, we examined DNA double-strand breaks (DSB) and single-strand breaks (SSB) in the muscle biopsy specimens of several diseases, including muscle diseases with RV. Although no DSB-positive myonuclei were detected in any muscles examined, the number of SSB-positive myonuclei markedly increased in the muscles from cases with polymyositis and muscle diseases with RV. In polymyositis, SSB-positive myonuclei were observed in regenerating fibers and muscle fibers in the vicinity of inflammatory infiltrates, suggesting that the increase of SSB is due to muscle fiber regeneration following necrosis and inflammation. In muscle diseases with RV, however, SSB-positive myonuclei were observed in small angulated fibers and in morphologically normal fibers, regardless of necrosis, regeneration or inflammation. These findings suggest that muscle diseases with RV may share a common pathological process involving DNA damage.

Adolescent↗

Extraskeletal myxoid chondrosarcoma with multiple skeletal metastases.

Pulmonary metastases are not unusual in extraskeletal myxoid chondrosarcoma; however, only two patients have been reported with multiple bony metastases. We report here one patient with extraskeletal myxoid chondrosarcoma associated with lung and multiple bony metastases. After chemotherapy, the primary lesion was resected, but lung and multiple bony metastases were found 20 months later. The bony metastases were in the right femur, right humerus, and at multiple vertebral levels. Because of a pathologic fracture of the right femur, the metastases in the right femur and right humerus were surgically stabilized. After chemotherapy, the lung metastases were resected, and those in the vertebral bodies were treated with radiotherapy.

Bone Neoplasms↗

Movement of zinc and its functional significance in the brain.

Zinc, an essential nutrient, is supplied to the brain via both the blood-brain and blood-cerebrospinal fluid barriers. Zinc is most concentrated in the limbic system, i.e. the hippocampus and amygdala, zinc-containing glutaminergic neuron-rich areas. A large portion of zinc serves the function of zinc metalloproteins in neurons and glial cells. In zinc-containing glutaminergic neurons, vesicular zinc, probably ionic zinc, may serve as an endogenous neuromodulator in synaptic neurotransmission. Vesicular zinc is dynamically coupled to the electrophysiological activity of zinc-containing glutaminergic neurons. Dietary zinc deprivation may influence zinc homeostasis in the brain, resulting in brain dysfunction such as learning impairment. Excessive excitation of zinc-containing glutaminergic neurons causes a decrease in vesicular zinc, and the decrease might be associated with the susceptibility to seizure. Alteration of zinc levels released into the synaptic cleft may influence neurotransmission in zinc-containing glutaminergic synapses. Therefore, zinc homeostasis in the presynaptic vesicle is important for the function of zinc-containing glutaminergic neurons.

Animals↗

The importance of laminin 5 in the dermal-epidermal basement membrane.

The skin consists of two main layers, epidermis and dermis, separated by the basement membrane. Epidermal-dermal communication through the basement membrane is important for skin homeostasis. The basement membrane contains specialized structures, called the anchoring complex, which ensure the stability of connection and communication between these two tissue compartments. The proteins within the anchoring complex provide links to both the intracellular cytoskeletal keratins in keratinocytes and connective tissue proteins of the dermis. One of the key components of the complex is laminin 5, which is essential to epidermal cell attachment. The biological function of laminin 5 has been investigated by using a skin equivalent model in vitro and during keratinocyte sheet grafting in vivo. As a major link between the epidermal basal cells and the papillary dermis, laminin 5 initiates hemidesmosome formation and provides stable attachment of the epidermis to the dermis. Laminin 5 also accelerates the assembly of basement membranes and may enhance the recovery of damaged skin. An intact basement membrane at the epidermal-dermal junction is essential to stability of the skin.

Animals↗

The effects of the traditional chinese medicine, "Banxia Houpo Tang (Hange-Koboku To)" on the swallowing reflex in Parkinson's disease.

Swallowing disorder is common in Parkinson's disease (PD). We studied the swallowing disorder in PD, and tested the efficacy of Banxia Houpo Tang (BHT, a Chinese traditional medicine) in improving the swallowing reflex of PD patients. The Swallowing reflex test is a simple method used to detect swallowing disorders in patients with cerebrovascular disease. Because we observed previously that BHT significantly improved the swallowing reflex in cerebrovascular patients, we studied whether BHT was also effective in improving the swallowing disorder in patients with PD. 23 PD patients (13 males, 10 females, mean age 66.0+/-9.3, Hoehn & Yahr (H-Y) mean score = 2.8) were evaluated for swallowing reflex and the concentration of substance-P in their saliva before and after 4 weeks of BHT treatment. The swallowing reflex before treatment was significantly delayed, according to the H-Y score (Spearman's p = 0.014, R2 = 0.463). The swallowing reflex before BHT treatment was 3.66+/-0.98 sec, and after BHT treatment, it improved significantly, to 2.27+/-0.54 sec (p < 0.0001). Substance-P concentration in PD patients saliva before treatment was significantly lower than in healthy controls (p = 0.007), but showed no significant change after BHT treatment. Our research shows that the swallowing reflex is an effective method to evaluate the swallowing disorder in PD. BHT can significantly improved the swallowing reflex in PD patients, and therefore can be a hopeful candidate for preventing aspiration pneumonia in PD.

Aged↗

Reversal of metallothionein expression is different throughout the human myocardium after prolonged left-ventricular mechanical support.

OBJECTIVES: We examined the distribution of metallothionein (MT), a stress-inducible protein, and the cardiomyocyte diameter in human hearts after left-ventricular assist device (LVAD) support. BACKGROUND: Remodeling in end-stage heart failure is characterized by myocyte hypertrophy and alterations of several inducible proteins. LVADs used as a bridge to cardiac transplantation unload the left ventricle and may lead to a reversal of the remodeling, but little is known about the pathophysiology of this process. METHODS: The immunoreactivity for MT and the cardiomyocyte diameter was analyzed in left-ventricular tissue specimens of 17 patients with end-stage heart failure before and after LVAD support. RESULTS: MT positive cells were mainly located sub-endocardially in vacuolized cardiomyocytes and in small vessels throughout the myocardium. During LVAD support, MT-positive myocytes decreased in the sub-endocardial (p < 0.008) and sub-epicardial region (p < 0.003), MT-positive vessels decreased similarly (p < 0.003). Cardiomyocyte diameter decreased significantly only in the sub-endocardium (p < 0.03). Hearts of patients supported longer than 88 days (= median) showed substantially lower MT reactivity at the time of LVAD explantation as compared to patients supported less than 88 days. CONCLUSION: Our results suggest that unloading of the left ventricle during prolonged LVAD support leads to regression of cellular hypertrophy and a decrease of MT expression. The preferential reduction of MT-positive vacuolized cardiomyocytes in the sub-endocardium is comparable with the concept of greatest reduction of wall stress in this area of the myocardium and may be due to the improvement of myocardial blood flow and the energy balance.

Adult↗

Acute humoral rejection of kidney allografts in patients with a positive flow cytometry crossmatch (FCXM).

The patients with a positive flow cytometry crossmatch (FCXM) are categorized as a high-risk group causing hyperacute or accelerated acute rejection after kidney transplantation. According to the successful results of ABO-incompatible renal transplantation, we have performed the living related transplant operations in the recipients with positive FCXM for donor T cells, but having a negative complement-dependent lymphocytotoxic reaction test. We have followed the clinical course of 4 FCXM-positive patients, and 2 of them have developed acute humoral rejection. We report the strategies for FCXM-positive living kidney transplantations and the characteristics of pathological findings of acute humoral rejection in FCXM-positive renal transplants. We have had few episodes of acute humoral rejection in ABO-incompatible kidney transplantations under immunosuppressive regimens, including cyclophosphamide, but 2 patients of 4 with FCXM-positive kidney transplantations developed acute humoral rejections. The differences in immunosuppressive regimen between ABO-incompatible and FCXM-positive kidney transplantations concern anti-lymphocyte globulin (ALG) and splenectomy. We have not performed splenectomy and ALG administration in FCXM-positive kidney transplantations. Severe acute rejection episodes have been experienced on post-operative days 7 and 9 in 2 of 4 FCXM-positive recipients. The early acute rejection episodes were clinically and pathologically diagnosed as typical humoral rejections. We have examined an immunofluorescent study to prove the diagnosis of humoral rejection in FCXM-positive kidney transplantations; both immunoglobulin M and C3 were positive for the whole course of humoral rejection. The 2 patients with acute humoral rejection recovered after treatment with double filtration plasmapheresis or plasma exchange to remove their anti-donor antibodies. The gold standard of success in FCXM-positive kidney transplantations is to suppress the production and reduce the level of anti-donor antibodies after transplant operations.

ABO Blood-Group System↗

Role of leukocyte adhesion molecules in monocyte/ macrophage infiltration in weanling rats with unilateral ureteral obstruction.

BACKGROUND: Unilateral ureteral obstruction (UUO) of rats is a well-established model for studying obstructive nephropathy. Meanwhile, pathophysiology of pediatric obstructive nephropathy is not well understood. In this report, we studied monocyte/macrophage infiltration and expression of intercellular adhesion molecule 1 (ICAM-1) and macrophage antigen 1 (Mac-1) in weanling rats with UUO. METHODS: Three-week-old male Sprague-Dawley rats underwent left unilateral ureteral ligation. Both obstructed kidneys (OBK) and contralateral kidneys (CLK) were harvested at 3, 6, 12, 24, 72 and 120 h after surgery. Monocyte/macrophage infiltration and expression of ICAM-1 and Mac-1 were evaluated immunohistochemically, and results were compared with those of sham-operated control rats (SOK). RESULTS: Monocyte/macrophage infiltration was observed in the interstitium and perivascular region in the cortex of OBK within 6 h. The CLK and SOK showed slight monocyte/macrophage infiltration. Expression of ICAM-1 was markedly observed in the periarterial and peritubular interstitium and in renal cortical peritubular capillaries 12 h after obstruction. In CLK and SOK, ICAM-1 was slightly expressed in the endothelium of microvessels and parietal linings of Bowman's capsule. Expression of Mac-1 was detected mainly in cells infiltrating the perivascular interstitium in OBK. In CLK and SOK, few Mac-1-positive cells were observed. CONCLUSIONS: Adhesion molecules, ICAM-1 and Mac-1, are expected to recruit monocyte/macrophage infiltration into OBK of weanling rats with UUO.

Animals↗

In Alzheimer's disease, heme oxygenase is coincident with Alz50, an epitope of tau induced by 4-hydroxy-2-nonenal modification.

In this study, we compared the neuronal induction of the antioxidant heme oxygenase-1 (HO-1) in Alzheimer's disease with abnormalities in tau marked by antibodies recognizing either phosphorylation (AT8) or conformational change (Alz50). The epitope recognized by Alz50 shows a complete overlap with HO-1-containing neurons, but AT8 recognized these neurons as well as neurons not displaying HO-1. These findings suggest that tau phosphorylation precedes the HO-1 response and that HO-1 is coincident with the Alz50 epitope. This led us to consider whether oxidative damage plays a role in forming the Alz50 epitope. We found that 4-hydroxy-2-nonenal (HNE), a highly reactive product of lipid peroxidation, reacts with normal tau and induces the Alz50 epitope in tau. It is important that the ability of HNE to create the Alz50 epitope not only is dependent on lysine residues of tau but also requires tau phosphorylation because neither methylated, recombinant, nor dephosphorylated tau reacts with HNE to create the Alz50 epitope. Supporting the in vivo relevance of this observation, endogenous paired helical filament-tau isolated from subjects with Alzheimer's disease was immunoreactive with an antibody to a stable HNE-lysine adduct, as were all vulnerable neurons in subjects with Alzheimer's disease but not in control individuals. Together, these findings support the involvement of oxidative damage early in neurofibrillary tangle formation in Alzheimer's disease and also suggest that HNE modification contributes to the generation of the tau conformation defining the Alz50 epitope. These findings provide evidence that an interplay between phosphorylation of tau and neuronal oxidative stress-induced pathology is important in the formation of neurofibrillary tangles.

Aged↗

Superiority of a new UICC-TNM staging system for gastric carcinoma.

BACKGROUND: The definition of the degree of lymph node metastasis (n-classification) for gastric cancer differs greatly in the new Union Internationale Contre le Cancer--TNM classification (5th edition) and the Japanese gastric cancer classification (JGC). The feasibility of the new TNM classification is evaluated in comparison with the JGC. METHODS: At Chiba University, 940 patients who underwent a gastrectomy were retrospectively classified into appropriate stages with both the TNM and JGC systems, and the survival curves of the respective stages were also compared. RESULTS: Patients with 1 to 6 metastatic nodes (TNM-pN1) showed similar survival rates whether the metastases were limited to the perigastric area (JGC-n1) or reached distant areas (JGC-n2). The patients with node metastasis that was limited to the perigastric area (JGC-n1) had significantly different survival rates, depending on the number of metastatic nodes (TNM-pN1 or pN2, P = .022). A similar phenomenon was also observed in patients with TNM-N2 and JGC-n2. A multivariate analysis indicated the TNM N-classification, rather than the JGC n-classification, as an independent prognostic factor. CONCLUSIONS: The new TNM classification appears to be a better prognostic indicator than the JGC system for patients with gastric carcinoma.

Female↗

Clinical benefits of steroid therapy on surgical stress in patients with esophageal cancer.

BACKGROUND: Despite improvements in surgical techniques and perioperative care, severe complications lead to long hospital stays for some esophageal cancer patients. The purpose of this study was to evaluate the safety and effectiveness of perioperative steroid therapy on the postoperative clinical course. METHODS: Fifty-seven patients operated for esophageal cancer in 1997 and 1998 were treated with perioperative steroid therapy. Fifty consecutive patients operated in 1995 and 1996 served as a control group. In the steroid group, each patient was given 250 mg of methylprednisolone intravenously before operation followed by 125 mg on postoperative days 1 and 2. Serum interleukin-6, polymorphonuclear cell elastase, and C-reactive protein levels, and the postoperative clinical course were compared between the groups. RESULTS: Morbidity rates including hyperbilirubinemia, anastomotic leakage, and liver dysfunction were significantly lower in the steroid group than in the control group. Days until extubation and hospital stay were significantly shorter for the steroid group. Inflammatory mediators, body temperature, heart rate, and respiratory index after the surgical procedure were significantly lower in the steroid group. Adverse effects possibly caused by steroid therapy were not observed. CONCLUSIONS: Perioperative steroid therapy was safe and effective for the inhibition of inflammatory mediators and the improvement of the postoperative clinical course of patients with esophageal cancer.

Acute-Phase Proteins↗