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Biomedical subjects

A Takeda

Publications and source records attributed to A Takeda.

At least 73 records · Page 4Linked to original sources
PubMed2001

Does infiltration of neutrophils in peritubular capillaries indicate humoral rejection? A case displaying a characteristic lesion of a significantly high amount of neutrophils in peritubular capillaries at 1-h graft biopsy during transplant operation.

We present a case report of a 50-yr-old Japanese woman with a significant accumulation of neutrophils in the peritubular capillaries (PTC) and severe acute tubular necrosis (ATN) at 1-h allograft biopsy during transplant operation from cadaver donor after a cardiac death. Significant accumulation of neutrophils in the PTC is usually valuable diagnostically for acute humoral rejection. However, the patient showed no clinical signs of acute rejection. A second graft biopsy performed on the fifth postoperative day (POD) revealed that both infiltration of neutrophils in PTC and ATN lesions were more aggravated. Neither clinical course nor other morphological findings were compatible with humoral rejection. After the third biopsy of POD 27 revealing acute vascular rejection of moderate degree, acute rejection therapy using methylprednisolone pulse therapy and OKT-3 therapy was performed. Consequently, after a period of delayed graft function requiring haemodialysis for approximately 4 wk, graft function was restored and serum creatinine decreased to 2 mg/dL. Later, we were able obtain information from a paired graft from the same donor. Significant accumulation of neutrophils in the PTC similar to our recipient was also noted in a 1-h biopsy specimen of the paired kidney. This confirmed that the accumulation of neutrophils in the PTC noted in two recipients was transmitted from the donor kidney. The pathogenesis and clinical significance of neutrophils in the PTC has been shrouded in mystery.

Biopsy↗
PubMed2001

Activation of MKK6, an upstream activator of p38, in Alzheimer's disease.

Mitogen-activated protein kinase (MAPK) p38 has been implicated in the pathogenesis of Alzheimer's disease, but the upstream cascade leading to p38 activation has not been elucidated in the disease. In the present study, we focused on mitogen-activated protein kinase kinase 6 (MKK6), one of the upstream activators of p38 MAPK. We found that MKK6 was not only increased but also specifically associated with granular structures in the susceptible neurons in the hippocampus and cortex of Alzheimer's disease patients, but was only weakly diffuse in the cytoplasm in neurons in control cases. Immunoblot analysis demonstrated a significant increase of MKK6 level in Alzheimer's disease compared with age-matched controls. In this regard, in hippocampal and cortical regions of individuals with Alzheimer's disease, the activated phospho-MKK6 was localized exclusively in association with pathological alterations including neurofibrillary tangles, senile plaques, neuropil threads and granular structures, overlapping with activated p38 MAPK suggesting both a functional and mechanic link. By immunoblot analysis, phospho-MKK6 is also significantly increased in AD compared with control cases. Together, these findings lend further credence to the notion that the p38 MAPK pathway is dysregulated in Alzheimer's disease and also indicates an active role for this pathway in disease pathogenesis.

Adolescent↗
PubMed2001

MR imaging for evaluation of early rheumatoid arthritis.

In rheumatoid arthritis (RA), due to its superior contrast resolution and tomographic nature, magnetic resonance (MR) imaging can depict soft tissue and joint involvement better than plain radiography. Active synovitis and pannus are shown by a wide variety of contrast on T1- and T2-weighted images. They are markedly enhanced by intravenous gadolinium-chelate injection. Fat-suppressed T1-weighted imaging with gadolinium enhancement is the most sensitive technique to demonstrate these tissues. Compared with plain radiography, MR imaging is more sensitive and equally specific in the diagnosis of early RA compared with plain radiography. MR imaging is useful in the diagnosis and treatment of patients who are suspected of having early RA.

Adult↗
PubMed2001

Monitoring of p53 autoantibodies after resection of colorectal cancer: relationship to operative curability.

OBJECTIVE: To investigate the clinical use of p53 autoantibodies as a marker in the postoperative monitoring of colorectal cancer. DESIGN: Retrospective study. SETTING: Teaching hospital, Japan. SUBJECTS: 40 patients with colorectal cancer who had p53 autoantibodies in their serum preoperatively. INTERVENTIONS: Serial assay of p53 autoantibodies by ELISA before and after resection. MAIN OUTCOME MEASURES: Interpretation by a qualitative analysis. RESULTS: A significant correlation was observed between curability by surgical resection and postoperative disappearance of p53 autoantibodies. Twenty-seven (96%) of 28 patients, who had p53 autoantibodies and whose cancer was completely removed, had no such antibodies after resection and no recurrence after 7 to 26 months. CONCLUSIONS: Postoperative assays of p53 autoantibodies are potentially useful for predicting recurrence of colorectal cancer in patients who have p53 autoantibodies preoperatively.

Colorectal Neoplasms↗
PubMed2001

Oxidative damage is the earliest event in Alzheimer disease.

Recently, we demonstrated a significant increase of an oxidized nucleoside derived from RNA, 8-hydroxyguanosine (8OHG), and an oxidized amino acid, nitrotyrosine in vulnerable neurons of patients with Alzheimer disease (AD). To determine whether oxidative damage is an early- or end-stage event in the process of neurodegeneration in AD, we investigated the relationship between neuronal 8OHG and nitrotyrosine and histological and clinical variables, i.e. amyloid-beta (A beta) plaques and neurofibrillary tangles (NFT), as well as duration of dementia and apolipoprotein E (ApoE) genotype. Our findings show that oxidative damage is quantitatively greatest early in the disease and reduces with disease progression. Surprisingly, we found that increases in A beta deposition are associated with decreased oxidative damage. These relationships are more significant in ApoE epsilon4 carriers. Moreover, neurons with NFT show a 40%-56% decrease in relative 8OHG levels compared with neurons free of NFT. Our observations indicate that increased oxidative damage is an early event in AD that decreases with disease progression and lesion formation. These findings suggest that AD is associated with compensatory changes that reduce damage from reactive oxygen.

Aged↗
PubMed2001

Rapid appearance of secondary immune responses and protection from acute CD4 depletion after a highly pathogenic immunodeficiency virus challenge in macaques vaccinated with a DNA prime/Sendai virus vector boost regimen.

Heterologous prime/boost regimens are AIDS vaccine candidates because of their potential for inducing cellular immune responses. Here, we have developed a prime/boost regimen leading to rapid control of highly pathogenic immunodeficiency virus infection in macaques. The strategy, priming by an env and nef deletion-containing simian-human immunodeficiency virus (SHIV) proviral DNA followed by a single booster with a Gag-expressing Sendai virus (SeV-Gag), efficiently induced virus-specific T cells, which were maintained for more than 3 months until challenge. While all naive control macaques showed acute CD4(+) T-cell depletion at week 2 after an intravenous SHIV89.6PD challenge, all the macaques vaccinated with the prime/boost regimen were protected from depletion and showed greatly reduced peak viral loads compared with controls. Vaccination with the DNA alone or SeV-Gag alone was not enough to confer the consistent protection from the depletion, although it led to efficient secondary CD8(+) T-cell responses at week 2 after challenge. At week 1, a difference in the secondary responses between the protected and the unprotected macaques was clear; rapid augmentation of virus-specific CD8(+) T cells was detected in the former but not in the latter. Thus, our results indicate the importance of rapid secondary responses for reduction in the peak viral loads and protection from acute CD4(+) T-cell depletion.

AIDS Vaccines↗
PubMed2001

Cardiac (123)I-meta-iodobenzylguanidine (MIBG) uptake in dementia with Lewy bodies: comparison with Alzheimer's disease.

Cardiac (123)I-meta-iodobenzylguanidine (MIBG) uptake was measured in 11 patients with dementia with Lewy bodies (DLB), 10 patients with Alzheimer's disease (AD), and 10 age matched control subjects. The severity of cognitive impairment and duration of symptoms in patients with DLB matched that in the patients with AD. The heart/mediastinum (H/M) ratio of MIBG uptake in the patients with AD was indistinguishable from that in the control subjects. However, the H/M ratio in all patients with DLB was significantly lower than that in the patients with AD and control subjects (p<0.001). These findings indicate that local myocardial sympathetic nerves are affected in DLB and that cardiac (123)I-MIBG scintigraphy may provide a means of differentiating DLB from AD.

3-Iodobenzylguanidine↗
PubMed2001

Cell killing and mutation induction by heavy ion beams.

Carbon beam radiotherapy for cancer patients was initiated in Japan in June 1994. This study attempts to clarify the radiobiological effects of heavy ion beams. In this study, human cancer cell lines (RMG-1, MDA-MB231) and V79 cells were used. The cell killing was determined by colony forming assay, and mutation induction was determined by counting the number of 6-thioguanine resistant colonies (hprt locus mutation assay). The cell lines were irradiated with carbon (20 or 80 keV/microm) or neon beams (80 keV/microm). Carbon ions with a higher LET value (80 keV/microm) had an enhanced cytotoxic effect compared to those with a lower LET value (20 keV/microm). Carbon beams produced a slightly stronger cytotoxic effect than neon beams when irradiated at the same LET level (80 keV/microm), but the difference was not remarkable. The mutant fraction was significantly higher in all cell lines when they were irradiated with heavy ion beams, compared to the results for X-ray irradiation. The mutant fraction increased when the LET of the carbon beams increased. At equivalent LET values, the mutant fraction was lower for neon beams than for carbon beams. Fractionation of carbon beam irradiation had no effect on survival, but reduced the mutant fraction. Neon beams might be more appropriate for heavy ion therapy, especially when higher doses are being used. In addition, the fractionation of heavy ion beam administration might be appropriate for reducing the mutant fraction.

Animals↗
PubMed2001

[Two cases of acute eosinophilic pneumonia--analyses of cytokines in BALF before and after treatment].

Acute eosinophilic pneumonia (AEP) has been well recognized as sudden onset respiratory failure characterized by an increased eosinophilic cell count in the bronchoalveolar lavage fluid (BALF). Although several lines of research have demonstrated that the Th2 cytokine network is likely to play a pivotal role in the development of AEP, that mechanism has not been clearly understood yet. Previous reports published in Japan demonstrated that the BALF CD4/CD8 ratio in patients with AEP ranged between 1.1 and 5.8. In this report, we describe 2 cases of AEP in which the CD4/CD8 ratios were 0.3 and 7.8 when present. We measured IL-4, IL-5, IL-10 and IFN gamma in the BALF before and after treatment in these patients. IL-5 decreased drastically after the treatment phase, while the other cytokines did not change much. We concluded that the IL-5 concentration in the BALF is probably related to the development of AEP. In addition, we also speculated that the CD4/CD8 ratio in BALF from patients with AEP may be affected whether a patient has an atopic background or not.

Acute Disease↗
PubMed2001

[A case of pulmonary Mycobacterium avium infection with a rapid-growing solitary node].

A 72-year-old man was admitted to our hospital because of an abnormal shadow on his chest radiograph. Computed tomography revealed a 3 cm solitary nodular opacity in the right S1. Bronchofiberscopy could neither give any specific histological findings nor bacteriological findings. This nodular shadow increased in size to 1.5 times that in the first chest radiograph. In addition, since there was no abnormal finding in the chest radiograph one year before, we performed partial pulmonary resection by video-assisted thoracoscopic surgery, taking into consideration the possibility that the solitary node was malignant. The pathological findings of the resected specimen were an epitheloid cell granuloma with Langhans giant cell and caseous necrosis. We could not detect any acid-fast bacilli or malignant cells. After surgery, M. avium was detected in a 6-week culture of the resected specimen. We treated the patient with RFP, EB and CAM for 6 months. Outpatient follow-up revealed no relapse.

Aged↗
PubMed2001

[A case of potassium-sensitive periodic paralysis with cardiac dysrhythmia controlled with imipramine and acetazolamide].

We report a patient with potassium-sensitive periodic paralysis with cardiac dysrhythmia. The patient was a 16-year-old man. He presented with asymptomatic ventricular dysrhythmia and periodic paralysis when he was 6 and 12 years old, respectively. Physical examination revealed slight dysmorphic features such as hypoplastic mandible, low-set ears and clinodactyly. Through an exercise test, a potassium tolerance test and a muscle biopsy, his illness was diagnosed as potassium-sensitive periodic paralysis with cardiac dysrhythmia. For the treatment of his episodic paralysis, we started acetazolamide, which improved both the incidence and the severity of paralysis. However, the incidence of cardiac dysrhythmia was increased after the use of acetazolamide. Routine anti-arrhythmic drugs such as lidocaine failed to control his ventricular dysrhythmia. Only imipramine showed its efficacy by improving the degree and the incidence of cardiac dysrhythmia without aggravating periodic paralysis. This syndrome is relatively rare and there have been no standard protocols for the treatment. We propose the combination of acetazolamide and imipramine as the first choice for this clinical entity. We also discussed the efficacy of the exercise test. It enabled us to confirm the diagnosis of periodic paralysis safely and easily by recording the change of compound muscle action potential amplitudes.

Acetazolamide↗
PubMed2001

[A case of Tolosa-Hunt syndrome starting from abducens nerve palsy alone].

A 59-year-old man was admitted to our hospital because of right abducens nerve palsy without orbital pain. One month later right orbital pain appeared and two months later the pain changed to an aching severe pain and the right oculomotor, trochlear and trigeminal nerves were also involved. The administration of corticosteroid dramatically reduced these symptoms. The diagnosis was Tolosa-Hunt syndrome (THS) based on these findings. THS starting with abducens nerve palsy alone is rare, representing only 5.1% of 118 patients. In our patient, the newly developed dynamic MRI was able to reveal the right cavernous sinus lesion. The diagnostic usefulness of dynamic MRI for cavernous sinus lesions has been demonstrated for such cases.

Abducens Nerve Diseases↗
PubMed2001

[Successful treatment of emotional disturbances following non-herpetic limbic encephalitis by serotonergic agents. A case report].

We report a 19-year-old woman who developed refractory status epilepticus due to non-herpetic limbic encephalitis. Because ordinary anti-epileptics were ineffective, general anesthesia under mechanical ventilation was begun with pentobarbital, midazolam, and propofol. After 4 months, we could finally discontinue the intravenous anesthetics. Then, she gradually became conscious and several weeks later, could communicate verbally. Simultaneously, she began to manifest psychomotor agitation and emotional incontinence mimicking Klüver-Bucy syndrome. Brain MRI revealed cortical atrophy in the fronto-temporal lobes and dilated anterior and inferior horns of the lateral ventricles. Dopamine blockers and benzodiazepines failed to resolve these emotional symptoms. Oral tandospirone (30 mg/day dose) was initiated and a partial regression was observed. The following administration of fluvoxamine (started with 12.5 mg/day and maintained with 75 mg/day) resulted in a dramatic improvement of her symptoms within 3 days. This clinical course suggests that impaired serotonergic neurotransmission plays a key role in her emotional disturbances and that its modulation by serotonergic agents is useful to relieve such symptoms.

Adult↗
PubMed2000

Serum p53 antibody is a useful tumor marker in superficial esophageal squamous cell carcinoma.

BACKGROUND: Patients with superficial (mucosal or submucosal) esophageal carcinoma (SEC) have significantly better survival rates than patients with advanced carcinoma. Some patients with advanced esophageal carcinoma have been reported to test positive for serum p53 antibodies (Abs). Because very few patients with superficial carcinoma have been examined, the aim of this study was to evaluate the clinical significance of serum p53-Abs in patients with superficial esophageal squamous cell carcinoma (SESCC). METHODS: Thirty-five consecutive patients with SESCC were studied for serum p53-Abs by enzyme-linked immunoabsorbent assay before and after treatment. The clinicopathologic features of p53 seropositive and p53 negative patients were compared. The relation between the presence of serum p53-Abs and p53 immunoreactivity of the resected specimens was examined. Three tumor markers (squamous cell carcinoma antigen [SCC-Ag], CYFRA21-1, and carcinoembryonic antigen [CEA]) were assessed to compare their sensitivities with serum p53-Abs. RESULTS: Fourteen of 35 patients (40%) were p53 seropositive. Relatively few patients tested positive for the other tumor markers: CEA, 11.4%; SCC-Ag, 14.3%; CYFRA21-1, 5.7%. There were no significant correlations between clinicopathologic features and p53 seropositivity except for tumor location. A strong correlation between p53 immunostaining and the presence of serum p53-Abs was observed (P = 0.003). Of the 14 patients with seropositive results, 12 turned seronegative after resection, and the other 2 experienced disease recurrence. CONCLUSIONS: Surveillance of serum p53-Abs is superior to the three tumor markers for detecting SESCC. This serum marker is also useful for the detection of p53 protein overexpression and for the monitoring of residual tumor cells.

Aged↗
PubMed2000

Difference in effective dosage of genistein on bone and uterus in ovariectomized mice.

Phytoestrogen including soybean isoflavones has structural similarity to estrogen and exhibits beneficial effects on bone tissue to protect against bone loss under estrogen-deficient conditions. Recent studies also indicate a possible action of isoflavones as endocrine disrupters in reproductive tissues. In this study, we administered various dosages of genistein to ovariectomized (OVX) mice, and compared the effective dosages of genistein on bone and uterus. Treatment with genistein at 0.7 mg/day prevented trabecular bone loss in OVX mice without hypertrophic effects on the uterus, while administration of 5 mg/day of genistein induced uterine hypertrophy. The serum levels of genistein in OVX mice treated with 0.7 mg/day and 5 mg/day were 3-fold (1.3 nmol/ml) and 50-fold (20.4 nmol/ml) higher than that in OVX mice. These results suggest that there is a marked difference between genistein dosages that protect against bone loss and those that induce uterine hypertrophy.

Animals↗
PubMed2000

Manganese concentration in mouse brain after intravenous injection.

Abnormal deposit of manganese (Mn) in the basal ganglia is often observed in patients with chronic liver failure and patients receiving long-term parenteral nutrition. Based on the data that (54)Mn is transported into the brain efficiently via a transferrin-independent uptake system, Mn concentration in mouse brain was determined after intravenous (iv) injection (2 mg Mn/kg/day x 5 times) of either MnCl(2) or pH 8.6 buffer-treated MnCl(2), which has a higher affinity for transferrin than untreated MnCl(2). Brain Mn concentration was significantly increased in either case. Brain Mn concentration of MnCl(2) group was significantly higher than that of pH 8.6 buffer-treated MnCl(2) groups. Mn concentration in the caudate putamen of MnCl(2) group was also significantly higher than that of pH 8.6 buffer-treated MnCl(2) group. Ninety seconds after a single injection of MnCl(2) (2 mg Mn/kg), brain Mn concentration was remarkably increased with blood Mn level, but not 1 hr after injection. On the other hand, hepatic Mn concentration was remarkably high 1 hr after injection and the brain Mn concentration was increased again at 24 hr, followed by decrease of the hepatic Mn concentration. Relative Mn concentrations in the brain 90 sec after injection were different from those 24 hr after injection, suggesting that the mechanism of the increase of brain Mn concentration via blood Mn level is different from that via the redistribution from the liver. Mn ion and/or Mn bound to low molecular weight compounds may be involved in abnormal Mn uptake in the brain.

Animals↗