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Biomedical subjects

T Nagashima

Publications and source records attributed to T Nagashima.

At least 55 records · Page 3Linked to original sources

The role of nitric oxide in reoxygenation injury of brain microvascular endothelial cells.

OBJECT: The role of nitric oxide (NO) in reperfusion injury of the brain is still controversial. The authors demonstrate that NO injures the brain capillary endothelial cells in a reoxygenation state by the formation of peroxynitrite. MATERIALS AND METHODS: 1) Rat brain capillary endothelial cells (BCECs) were isolated by a two-step enzymatic purification method. The BCECs were identified by the presence of factor VIII. 2) Anaerobic cell preparations were achieved by purging under nitrogen gas with 0.5% CO2 at 37 degrees C for 20 minutes and then reoxygenating in an incubator. To ascertain the degree of BCEC injury after anoxia and reoxygenation, lactate dehydrogenase (LDH) release was measured. The production of NO was measured by the Griess method. 3) The cell-protective effects of superoxide dismutase (SOD), NG-nitro-L-arginine (L-NAME), and S-Methyl-ITU (i-NOS blocker) were studied. RESULTS: 1) Both L-NAME and SOD protected the cells from reoxygenation injury. The protective effect of L-NAME was dose-dependent. S-Methyl-ITU did not protect the cells. 2) The NO production after anoxia/reoxygenation was blocked by L-NAME. CONCLUSION: NO from the BCEC can injure the cells themselves through the formation of peroxynitrite under anoxia/reoxygenation conditions. Increased NO production after anoxia can be attributed to the induction of e-NOS.

Animals↗

Cytomorphometric differentiation of intraductal proliferative breast lesions.

BACKGROUND: Although cytologic examination has been an indispensable procedure for the diagnosis of various breast diseases, it is often difficult to make a precise diagnosis of intraductal proliferative breast lesions preoperatively. The present study attempts to clarify the differentiation of the lesions by the cytologic morphometric approach. METHODS: Cytologic specimens from 21 intraductal lesions, including nine ductal carcinomas in situ (DCIS), seven ductal hyperplasias (DH), and five papillomas were evaluated. Using a microscope connected to a computerized video system, the mean nuclear area, the perimeter, the form factor, the largest to smallest diameter ratio of the nuclei (LS ratio), and the coefficient of variation of the nuclear area (NACV) were measured and analyzed. RESULTS: The mean nuclear area and perimeter were significantly higher in the cases of DCIS than in DH (p < 0.01) and papilloma (p < 0.005). Similarly, DCIS had higher NACV values than the other groups (p < 0.05 and p < 0.005, respectively). There were no significant differences in form factor or LS ratio. CONCLUSIONS: The quantitative estimation of cytologic nuclear features is useful for preoperative differential diagnosis of intraductal proliferative lesions of the breast.

Adult↗

Quantitative ultrasound as a predictor of node metastases and prognosis in patients with breast cancer.

BACKGROUND: A retrospective study was performed to determine whether preoperative quantitative ultrasound assessment could predict axillary lymph node metastases and prognosis in patients with breast cancer. We focused on the presence of a halo, which is one of the features of breast cancer on ultrasound and represents reflections from the invading margin around infiltrating malignancies. METHODS: We evaluated ultrasonography from 187 infiltrating breast carcinoma patients with tumors 5 cm or less in greatest dimension (T1, T2). Using computer image analysis, the halo area (H) and the sum of the area of halo and internal echo (total tumor area (T)) were measured, and the ratio of halo to entire tumor (H/T, halo ratio) was calculated and compared with lymph node status and prognosis. RESULTS: The mean of the halo ratio was 0.38+/-0.13. Using the value of 0.42 as a cut-off, the high halo ratio group had significantly worse prognoses for both overall and disease-free survival at 49 months in median follow-up (p <0.001 and p <0.0005, respectively). The specificity of a high halo ratio in the T1 classification for predicting axillary node metastasis was 83.1%, with a negative predictive value of 86.8%. In patients with tumors 1.0 cm or smaller, the negative predictive value was 100%. In a multivariate analysis, halo ratio was an independent predictor of disease-free survival of breast carcinoma patients (p =0.0232). CONCLUSIONS: Preoperative quantitative ultrasound may be a useful non-invasive method for predicting the presence of axillary lymph node metastases and prognosis in patients with primary breast cancer.

Adult↗

Spontaneous peritumoral haemorrhage associated with sinus confluence meningioma: case report.

BACKGROUND: Torcular or sinus confluence meningioma is rare and surgically formidable. This reported sinus confluence meningioma was associated with peritumoral intracerebral hemorrhage. The surgical strategy and the mechanism of peritumoral hemorrhage are discussed. CASE DESCRIPTION: A 42-year-old woman presented with a history of headache, vomiting, and cerebellar dysfunction for 2 months. Plain computed tomography (CT) scan and magnetic resonance imaging (MRI) demonstrated a high-density mass in the torcular region involving both lateral sinuses. MR angiography demonstrated complete occlusion of the left lateral sinus and straight sinus and stenosis of the right lateral sinus. Two years after her first operation she experienced sudden headache and left upper quadrant hemianopsia. Plain CT scan and MRI showed a hyperintense tumor in the torcular region with an intracerebral hematoma in the right occipital lobe. An angiogram demonstrated occlusion of the caudal part of the superior sagittal sinus, bilateral transverse sinuses, and straight sinus. Gross total removal of the tumor was done along with the left lateral sinus through a suboccipital and a supratentorial occipital craniotomy in the first operation. The patient underwent total resection of the tumor at second operation through a bilateral occipital and suboccipital craniotomy along with resection of the dura including the confluence, the caudal part of the superior sagittal sinus, the right lateral sinus, and the straight sinus. The postoperative course was uneventful and postoperative MRI showed total removal of the tumor. CONCLUSION: Sinus confluence meningioma may present with peritumoral hemorrhage. Radical removal may be possible when the sinus confluence is completely occluded and there is good collateral drainage.

Adult↗

Oculopharyngeal muscular dystrophy in a Japanese family with a short GCG expansion (GCG)(11) in PABP2 gene.

Clinicopathological and molecular genetic findings on a new Japanese family with oculopharyngeal muscular dystrophy are reported. The family has 54 members, ten of whom are affected (seven male and three female), in 3 generations. Three affected males, one affected female and one unaffected female of seven living siblings in the third generation were examined. Bilateral ptosis developed in the 4th and 5th decades in the three male cases, and in the 7th decade in the female, and this was followed by diplopia, nasal voice, dysphagia and muscle weakness. In addition, severe external ophthalmoplegia, dysphonia, and proximal amyotrophy were prominent in this family. Electromyographs revealed myogenic/neurogenic changes, and computed tomography disclosed selective muscle wasting with fatty replacement, predominantly in the lower extremities. Muscle biopsy in the four affected patients showed variation in fiber size, and the presence of small angulated fibers and occasional rimmed vacuoles. Electron microscopic examination revealed an accumulation of filamentous inclusions in muscle fiber nuclei. DNA analysis identified that (GCG)(6) in the PABP2 gene was expanded to (GCG)(11) in the four affected cases examined. All studies were negative in the one unaffected. These results confirm that OPMD is caused by GCG short expansion and provides insights into the genetic mechanisms which may contribute to adult onset myopathy, confined to oculopharyngeal muscles.

Aged↗

Preliminary individual adjuvant therapy for gliomas based on the results of molecular biological analyses for drug-resistance genes.

New adjuvant therapy individualized by the results of reverse transcription-polymerase chain reaction (RT-PCR) for drug-resistance genes has been used to treat malignant gliomas. Protocol studies for malignant gliomas were not so encouraging in their therapeutic results because of heterogeneity and the various drug-sensitivities of the tumors. Individualization of glioma therapy is recommended. Drug-resistance genes messenger ribonucleic acid (mRNA) expressions were investigated in drug-resistant human glioma cell lines derived from U87MG and 46 frozen samples of retrospectively examined neuroepithelial tumors (12 low grade neuroepithelial tumors, 16 Grade III gliomas, 11 glioblastomas, and 7 other malignant neuroepithelial tumors such as medulloblastomas and primitive neuroectodermal tumors) by RT-PCR with the specific primers for O6-methylguanine DNA methyltransferase (MGMT), multidrug-resistance gene 1 (MDR1), multidrug-resistance-associated protein (MRP), and glutathione-S-transferase-pi (GST-pi). Thirty-seven preliminary individual adjuvant therapies (IAT) based on RT-PCR results, mainly in MGMT expression, were performed on 30 consecutive patients with neuroepithelial tumors. In the retrospectively examined series, the initial response to 1-(4-amino-2-methyl-5-pyrimidynyl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU) was correlated most significantly to the MGMT mRNA expression among 11 independent prognostic factors (p = 0.0037) in multivariate logistic regression analysis. In the preliminary IAT, 17 of 32 evaluable therapies had a partial or complete response (53.1% response rate). Our IAT based on RT-PCR seemed to be more effective than conventional therapies for malignant gliomas.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

P-ANCA-positive Wegener's granulomatosis presenting with hypertrophic pachymeningitis and multiple cranial neuropathies: case report and review of literature.

An autopsy case of hypertrophic pachymeningitis and multiple cranial neuropathies is reported. A 53-year-old woman with paraplegia and various neurological signs which developed over a 2 year period was diagnosed as having an epidural mass with thickened dura mater extending from the lower cervical to the thoracic spinal cord. In addition, bilateral episcleritis, blephaloptosis, and blindness of the right eye with various cranial nerve deficits were found to be caused by the mass lesions involving the paranasal sinuses, orbit, and the cavernous sinus. Perinuclear antineutrophil cytoplasmic antibody (p-ANCA) was positive, but cytoplasmic antineutrophil cytoplasmic antibody (c-ANCA) was negative by enzyme-linked immunosorbent assay. The partially removed epidural mass with hypertrophied dura mater and biopsy of the paranasal lesions showed chronic granulomatous inflammation with vasculitis. The remaining lesions resolved with steroid therapy with remarkable neurological improvement. The positive p-ANCA test, paranasal involvement, the report of a similar histopathological case and a review of the literature on granulomatous pachymeningitis suggest the presence of p-ANCA-positive Wegener's granulomatosis with central nervous system involvement characterized by hypertrophic pachymeningitis and/or multiple cranial neuropathies.

Antibodies, Antineutrophil Cytoplasmic↗

Cerebral vasculitis in chronic mucocutaneous candidiasis: autopsy case report.

An autopsy case of chronic mucocutaneous candidiasis (CMCC) is reported here, in which cerebral vasculitis developed in the final stage. A 32-year-old man who had suffered from superficial candidial infection since his childhood was diagnosed as having CMCC. During the past 7 years the patient had developed various associated disorders including insulin-dependent diabetes mellitus (IDDM), common variable immunodeficiency (CVID), candidial esophagitis, multiple digestive tract ulcers and pyothorax. In 1998, at the age of 32, he developed convulsions that were accompanied by impairment of consciousness, and which were temporarily treated with steroid pulsed-medication. Epileptic status associated with widespread cerebral infarctions occurred subsequently, however, and the patient died of sepsis 2 months later. At autopsy, multiple cerebral infarctions and arterial thrombosis were evident. These were histologically proven to be primary vasculitis which was confined solely to the brain, and this was verified by general pathological examination. Thus, some as yet unknown cerebrovascular factors might be involved in the onset of an autoimmune-related vasculitis in patients with a longstanding immunodeficiency state such as CMCC.

Adult↗

Growth hormone-releasing hormone expression in pituitary somatotroph adenomas, studied by immunohistochemistry and in situ hybridization using catalyzed signal amplification system.

Growth hormone-releasing hormone (GHRH) is a well-known hypothalamic hormone that stimulates the synthesis and release of growth hormone (GH) as well as the proliferation of GH-producing cells in the anterior pituitary gland. Recent reports have shown GHRH synthesis in pituitary somatotroph adenomas, but GHRH immunoreactivity has not been shown in previous studies. To confirm the role of locally generated GHRH for the progression of somatotroph adenomas, we investigated the expression of GHRH in 25 pituitary somatotroph adenomas immunohistochemically, through the use of both conventional avidin-biotin-complex (ABC) method and novel catalyzed signal amplified (CSA) system. In addition, we investigated the expression of GHRH mRNA and GHRH receptor mRNA with in situ hybridization (ISH) using the CSA system. The weak immunopositivity of GHRH was observed in only 2 adenomas (8.0%) of 25 somatotroph adenomas using the ABC method. In contrast, 15 adenomas (60.0%) of 25 somatotroph adenomas were immunopositive for GHRH, as shown by CSA system. Very few of nonsomatotroph adenomas were immunopositive for GHRH using the CSA system. The expression of GHRH mRNA was confirmed, using the CSA-ISH system in 13 adenomas (72.2%) of 18 somatotroph adenomas. In 11 adenomas (61.1%) of 18 somatotrophic adenomas, the expression of GHRH receptor mRNA was demonstrated using the CSA-ISH system. This is a first report that clarified histopathologically GHRH production in pituitary somatotrophic adenomas. The demonstration of GHRH and its receptor expression is meaningful in clarifying the autocrine or paracrine regulation of GHRH in GH production and progression of pituitary somatotroph adenomas.

Adenoma↗

Electron microscopic observation of intracellular expression of mRNA and its protein product: technical review on ultrastructural in situ hybridization and its combination with immunohistochemistry.

In situ hybridization (ISH) at the electron microscopic (EM) level is essential for elucidating the intracellular distribution and role of mRNA in protein synthesis. Three different approaches have been applied by the investigators in this EM-ISH study: preembedding method; non-embedding method using ultrathin frozen sections; and postembedding method. In order to obtain satisfactory morphological preservation and retain the messages, we routinely utilized 6 microns-thick frozen sections fixed in 4% paraformaldehyde for the preembedding method and tissues embedded in LR White resin for the postembedding method. The hybridization signal intensity by the postembedding method was lower, and non-specific signals were relatively frequent, in comparison with the preembedding method. The preembedding method thus appears to be easier and better than the postembedding method from the viewpoint of applicability and preservation of mRNA, although quantitative analysis of the expression of mRNA is rather difficult in the preembedding method. EM-ISH is considered to be an important tool for clarifying the intracellular localization of mRNA and the exact site of specific hormone synthesis on the rough endoplasmic reticulum. The simultaneous visualization of mRNA and encoded protein in the same cells using preembedding EM-ISH and subsequent postembedding immunoreaction with protein A colloidal gold complex is also described. This ultrastructural double-staining method for mRNA and encoded protein can be expected to provide an important clue for elucidating the intracellular correlation of mRNA translation and secretion of translated protein.

Animals↗

Spontaneous intracranial hypotension associated with bilateral chronic subdural hematomas--case report.

A 34-year-old female presented with spontaneous intracranial hypotension (SIH) manifesting as severe postural headache and meningism. Magnetic resonance (MR) imaging with gadolinium showed diffuse pachymeningeal enhancement. She developed bilateral chronic subdural hematomas 4 weeks after the onset of the symptoms. MR imaging showed descent of the midline structures of the brain. The bilateral chronic subdural hematomas were surgically drained, with no remarkable pressure. Postoperative MR imaging showed complete resolution of the pachymeningeal enhancement and relevation of the midline structures of the brain. SIH is an uncommon and probably unrecognized condition because of the usually benign course. However, this case emphasizes that SIH is not entirely benign. SIH should be considered if there is no identifiable risk for intracranial hemorrhage, particularly in young patients. Neurosurgical intervention for the treatment of the underlying cerebrospinal fluid leak may be required if SIH persists.

Adult↗

[A case of ureterocalicostomy for refractory renal calculi].

UNLABELLED: We have sometimes encountered intractable cases of nephrolithiasis, even though ESWL and endourology have dramatically developed at the present time. We could obtain satisfactory result in the treatment of intractable right nephrolithiasis with ureterocalicostomy. CASE: The patient was a 39-year-old man having undergone PNL, ESWL, pyelolithotomy for right nephrolithiasis. Ten-odd stones, measuring 5-20 mm in diameter, were detected, and his IVP revealed mild hydronephrosis with the ureteropelvic junction stenosis. Pyeloplasty was thought to be difficult to perform. Thus the stones were removed through an incision made on the lowermost portion of the kidney followed by ureterocalicostomy on September 9, 1993. After clamping of the renal artery, the lowermost portion of the renal parenchyma was resected, and the lower calyx was sufficiently exposed. Adequate hemostasis of the cut surface was made, and the renal artery was then declamped. Many stones, measuring 20 mm or less, were removed through the lower calyx, and the lower calyx and the ureter were anastomosed. After operation, ESWL was additionally performed for residue stones. The IVP in July 1997 demonstrated the sufficiently patent anastomosed site without hydronephrosis or recurrence of nephrolithiasis. DISCUSSION: Anastomosis between the lower calyx and the ureter is an effective therapeutic method because it dose not interfere urine stream or small stone passage. However, it is not easy to make anastomosis in this site because the calyceal wall is very fragile. Several cases have been reported to have stenosis in the anastomosed site. We supposed that it is an excellent method for the treatment of refractory nephrolithiasis if the procedure is selected only for appropriate candidates.

Adult↗

[Two cases of acute myelogenous leukemia complicated with fatal gastrointestinal tract bleeding after treatment with idarubicin and cytarabine].

We describe herein two newly diagnosed patients with acute myelogenous leukemia (AML), who were treated twice with an idarubicin hydrochloride (IDR)-containing regimen as a response-orientated induction therapy. Both patients had severe gastrointestinal tract hemorrhage complications at their nadir. The two patients were as follows: a 35-year-old male, FAB-M4, and a 47-year-old female, FAB-M0. They received the same induction chemotherapy (IDR 12 mg/m2 for four days and cytarabine 100 mg/m2 for ten days). No response (NR) was obtained in either, so they underwent the same regimen again. During the period of myelosuppression, they developed severe gastrointestinal hemorrhage. One died of sepsis, and the other of acute respiratory distress syndrome without a recovery in bone marrow. The fetal gastrointestinal tract complications may have been due to severe myelosuppression and mucosal damage in these patients. Careful observation will be needed to prevent such severe complications after the treatment with IDR.

Adult↗

Age-related increases in plasma phosphatidylcholine hydroperoxide concentrations in control subjects and patients with hyperlipidemia.

BACKGROUND: The basal lipid peroxide concentration in the plasma of patients with hyperlipidemia may be related to atherosclerosis. Quantitative determination of lipid peroxides in the plasma is an important step in the overall evaluation of the biochemical processes leading to oxidative injury. Unfortunately, the currently available methods for lipid peroxidation lack specificity and sensitivity. METHODS: Hyperlipidemic patients (44 males and 50 females), ages 12-82 years (mean +/- SE, 53 +/- 2.3 years for males, 58 +/- 2.0 years for females, and 56 +/- 14 years for total cases), and normolipidemic volunteers (controls, 32 males and 15 females), ages 13-90 years (49 +/- 4 years for males, 65 +/- 4 years for females, and 55 +/- 24 years for total cases), were recruited in the present study. Plasma phosphatidylcholine hydroperoxide (PCOOH) was determined by chemiluminescence-HPLC (CL-HPLC). RESULTS: Plasma PCOOH concentrations increased with age in both controls and hyperlipidemic patients. However, the mean plasma PCOOH concentration in patients with hyperlipidemia (331 +/- 19 nmol/L; n = 94) was significantly (P <0.001) higher than in the controls (160 +/- 65 nmol/L; n = 47). Plasma PCOOH concentrations were similar in three hyperlipidemic phenotypes: hypercholesterolemia (IIa), hypertriglyceridemia (IV), and combined hyperlipidemia (IIb). The mean plasma PCOOH in patients with treatment-induced normalized plasma lipids was 202 +/- 17 nmol/L. There was no significant correlation between plasma PCOOH concentration and total cholesterol, triglycerides, or phospholipids in hyperlipidemic patients. For all subjects, there was a significantly positive correlation between plasma PCOOH and each lipid (total cholesterol, P = 0.0002; triglycerides, P = 0.0137; and phospholipids, P <0.0001). Analysis of fatty acids composition of plasma phosphatidylcholine showed significantly low concentrations of n-6 fatty acids moieties (linoleic acid and arachidonic acid) in patients compared with controls. CONCLUSIONS: Our results suggest that an increase in plasma PCOOH in patients with hyperlipidemia may be related to the development and progression of atherosclerosis, particularly in the elderly. Measurement of plasma PCOOH is useful for in vivo evaluation of oxidative stress.

Adolescent↗