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Biomedical subjects

N Yokota

Publications and source records attributed to N Yokota.

At least 19 recordsLinked to original sources

Attenuated left prefrontal activation during a verbal fluency task in patients with depression.

Functional neuroimaging studies on patients with depression have found abnormal activity in the left prefrontal and anterior cingulate cortex compared with healthy controls. Other studies have shown that these regions become active in healthy subjects during verbal fluency tasks, while patients with depression show impaired performance on such tasks. We used functional magnetic resonance imaging to investigate changes in cerebral blood oxygenation associated with a verbal fluency task in depressed patients and healthy volunteers. In contrast to 10 age- and sex-matched healthy control subjects who activated the left prefrontal cortex and the anterior cingulate cortex during word generation, 10 depressed subjects showed attenuated activation in the left prefrontal cortex and did not show significant activation in the anterior cingulate cortex. These findings suggest that impaired performance during verbal fluency task in depressed patients is associated with abnormal neural responses within these regions.

Brain Mapping↗

Neural activity of the globus pallidus interna and its anatomical relations to the optic tract in Parkinson's disease.

BACKGROUND: To reveal landmarks for placing the globus pallidus interna (GPi) target on MR images, visual evoked potentials (VEPs) of the optic tract (OT) and neural activities of the GPi were studied retrospectively. METHODS: The dorsal and lateral border of the OT were determined by VEPs of the OT, and neural activity in the pallidal region was recorded with a semimicro-electrode in 20 patients. The Unified Parkinson's Disease Rating Scale (UPDRS) was used to assess the condition of each patient before and 6 months and 12 months after surgery. FINDINGS: The location of trajectories relative to the lateral border of the OT were 3 mm medial (-3) in 6, 2 mm medial (-2) in 7, 1 mm medial (-1) in 8, at the lateral border (0) in 6, 1 mm lateral (+1) in 5, 2 mm lateral (+2) in 6, and 3 mm lateral (+3) in 5. The mean amplitudes along trajectories -3 and -2 mm were significantly higher than the others (post-hoc, p<0.01). In dorsoventral relations, the amplitudes from 5.1 mm to 6.8 mm of the medial trajectories (-3 to 0 mm) were significantly higher than others (post-hoc, p<0.01). The lesions placed medial to the lateral border of the OT located just above the lateral border of the OT on postoperative MR images (n=12) and brought better surgical benefits of total motor score, rigidity and bradykinesia than those placed lateral to the OT (n=8). INTERPRETATION: Our data indicate that hyperactive cells of the GPi are located medial to the lateral border of the OT and at least 5.1 mm above its dorsal surface, and this corresponds to the area just above the lateral border of the OT on MR images.

Aged↗

In vitro antifungal activity of posaconazole against various pathogenic fungi.

The antifungal activity of posaconazole (SCH56592), a new triazole antifungal, against stock cultures and fresh clinical isolates of a wide range of pathogenic fungi was compared with that of itraconazole, fluconazole and amphotericin B. Posaconazole inhibited growth of all the fungal species tested except Fusarium spp. at 1 mg/l or lower concentrations, showing a broad-spectrum antifungal activity. The activities of posaconazole for all the fungal species far surpassed those of fluconazole and were even superior to those of itraconazole for Aspergillus spp. as well as for many other fungal species.

Antifungal Agents↗

Olfactory neuroblastoma with epithelial and endocrine differentiation transformed into ganglioneuroma after chemoradiotherapy.

We report a 56-year-old man in whom an olfactory neuroblastoma with epithelial and endocrine differentiation transformed into a mature ganglioneuroma after chemoradiotherapy. The tumor arising from the sphenoidal and maxillary sinuses showed rapid growth into the frontal lobe and metastasis to the cervical lymph nodes. The patient showed signs of a syndrome of inappropriate secretion of antidiuretic hormone (SIADH). A radical craniofacial resection of the primary tumor was performed after 16 Gy of local irradiation and systemic chemotherapy. Three months after the operation, the patient died of mediastinal metastasis. The biopsy before chemoradiotherapy showed a neuroblastoma with Homer-Wright rosettes, fibrillary matrix, Flexner-Wintersteiner rosettes and antidiuretic hormone production. After chemoradiotherapy, the histology changed to that of a ganglioneuroma consisting of large ganglion cells and Schwann cells without immature neuroblastoma components. Although transformation to ganglioneuroma in an adrenal neuroblastoma is common, an olfactory neuroblastoma showing ganglioneuronal maturation after chemoradiotherapy has not been reported. The pluripotent progenitor cells of the olfactory neurons may be the origin and their existence explains why various neoplasms with neuronal and epithelial differentiation arise from the olfactory mucosa.

Antineoplastic Combined Chemotherapy Protocols↗

Recombinant erythropoietin rapidly treats anemia in ischemic acute renal failure.

BACKGROUND: The anemia associated with acute renal failure (ARF) is currently treated with blood transfusions, while the anemia of chronic renal failure is treated with recombinant erythropoietin (EPO). We hypothesized that EPO treatment during ARF could rapidly improve hemoglobin levels and be a useful therapeutic approach. In addition, as tubular epithelial cells have EPO receptors that can mediate proliferation, enhanced recovery of renal function may occur with EPO use. METHODS: An established rat model of ischemic ARF was studied, using either moderate or severe ischemia. EPO was administered in a dose of 500 or 3000 U/kg starting at time of ischemia. Hematocrit (Hct), serum creatinine, reticulocyte count, and mortality rate were measured. RESULTS: EPO treatment led to a rapid and significant increase in Hct at 48 and 72 hours after moderate ischemic renal reperfusion injury (IRI) in EPO (500 U/kg)-treated rats compared with control (saline treated) rats (mean +/- SE; 45.6 +/- 0.3% vs. 42.0 +/- 1.0%, P < 0.01) and (46.6 +/- 0.3 vs. 41.0 +/- 1.0, P < 0.01, N = 3 per group). In severe renal IRI, EPO treatment also led to significantly increased Hct at 48 (40.0 +/- 4.4% vs. 36.8 +/- 0.3%, P < 0.01, N = 3 per group) and 72 hours (43.5 +/- 1.5% vs. 34.7 +/- 2.3%, P < 0.01, N = 3 per group). Higher dose (3000 U/kg) EPO led to a more pronounced Hct increase after severe IRI at 48 hours compared with the 500 U/kg dose (43.5 +/- 0.3 vs. 40.3 +/- 0.3, P < 0.01, N = 3 per group). EPO treatment during moderate or severe renal IRI did not change the course of the renal dysfunction. EPO treatment (N = 19) had a significant protective effect on mortality during severe IRI. In addition, loss of body weight during ARF was not affected by EPO therapy. CONCLUSIONS: Recombinant EPO can rapidly increase Hct and improve mortality during ARF. Human studies are warranted to evaluate the clinical applicability of this important finding.

Acute Kidney Injury↗

Prevention of postoperative complications in skull base surgery for nasal or paranasal sinus carcinoma invading the skull base.

With recent technical advances in skull base surgery, radical resection of a nasal or paranasal sinus carcinoma invading the skull base can now be achieved. To assure a satisfactory surgical result, it is essential to prevent postoperative infection. In our series of 14 cases, serious postoperative infections occurred in the earliest 10 cases, and only 2 of these patients are still alive. The vascularised abdominal muscle flap for skull base reconstruction was fixed with fibrin glue, but was not adequate to fill the dead space, resulting in cerebrospinal fluid leakage and subsequent meningitis. Once the infection occurred, a free bone flap became the focus of infection. Based on these earlier experiences, we used a ROC fastener system to completely fill the dead space with an abdominal muscle flap, and bone flap was primarily craniectomised in the four most recent cases. With this technique, there were no postoperative infections.

Abdominal Muscles↗

Acquisition of the monocyte/macrophage phenotype in human mesangial cells.

The function of intrinsic glomerular cells in active glomerular inflammation may be similar to that of monocytes/macrophages. Mesangial cells have phagocytic properties and release numerous mediators. In this study we examined whether human mesangial cells (hMCs) express a monocyte/macrophage phenotype in active glomerular inflammation. We report that the proto-oncogene c-fms, the macrophage colony-stimulating factor (M-CSF) receptor, which is a characteristic gene of monocytes/macrophages, is expressed in hMCs. Normal unmanipulated hMCs express weak c-fms mRNA by reverse transcriptase-polymerase chain reaction (RT-PCR), and its expression increases after stimulation with platelet-derived growth factor-BB (PDGF-BB) and epidermal growth factor (EGF). The expression of c-fms was also demonstrated by flow cytometry with a specific polyclonal antibody. By immunohistochemistry, c-fms was prominently detected in acute glomerulonephritis, IgA nephritis, and lupus nephritis. These results indicate that hMCs express c-fms in active glomerular inflammation and are consistent with mesangial cells acquiring some macrophage-like characteristics in diseased states.

Acute Disease↗

Incidentally identified syringomyelia associated with Chiari I malformations: is early interventional surgery necessary?

OBJECTIVE: The purpose of this study was to analyze clinical data and magnetic resonance imaging (MRI) findings for patients with asymptomatic, incidentally identified syringomyelia associated with Chiari I malformations who were monitored for more than 10 years, and to clarify the natural history of these lesions. METHODS: The clinical records of nine patients who had not been surgically treated and were regularly subjected to neurological and MRI examinations were analyzed. In MRI studies, the axial diameter of the syrinx at the widest level, the longitudinal extent of the syrinx, and the extent of tonsillar herniation into the spinal canal were analyzed. As a control, MRI findings for 11 patients with symptomatic syringomyelia associated with Chiari I malformations who had been surgically treated were also analyzed, and these MRI parameters were statistically compared between the asymptomatic and symptomatic groups. RESULTS: One patient underwent surgery, because of neurological changes, 7 years after the first visit. None of the remaining patients demonstrated any neurological change during the follow-up period (11.2+/-0.7 yr), and all of them have been faring well without surgery. No statistically significant differences in MRI findings between the asymptomatic and symptomatic groups were observed. CONCLUSION: The long-term clinical courses of patients with asymptomatic, incidentally identified syringomyelia associated with Chiari I malformations were observed to be benign. MRI parameters did not provide predictable values to recommend interventional surgery. Unless changes in neurological or MRI findings are detected, early interventional surgery is not necessary.

Adolescent↗

Reversible nephrotic syndrome in a patient with amyloid A amyloidosis of the kidney following methicillin-resistant Staphylococcus aureus infection.

A common form of methicillin-resistant Staphylococcus aureus (MRSA) associated glomerulonephritis is either an endocapillary proliferative glomerulonephritis or a crescentic glomerulonephritis. This report describes the development of reversible nephrotic syndrome following MRSA infection in a patient with amyloid A amyloidosis. The patient had been diagnosed as having rheumatoid arthritis for 50 years. Suppurative arthritis due to MRSA became complicated 2 years prior to admission to our hospital. In the meantime, a nonnephrotic-range proteinuria developed. Two weeks before admission, nephrotic syndrome developed. The serum creatinine level remained unchanged throughout the course, but common features characteristic of MRSA-associated glomerulonephritis were observed in this patient, such as elevated serum IgG and IgA levels. A renal biopsy specimen showed glomerular amyloid A amyloidosis of a nodular type, infiltrated mononuclear cells in the mesangium, deposition of IgG, IgA, and C3, and swelling of glomerular endothelial cells. There were no crescentic glomeruli. Following surgical eradication of the MRSA focus in the right knee joint, nephrotic syndrome disappeared. Hence, it was highly possible that MRSA infection induced a reversible nephrotic syndrome by causing reversible injuries to glomerular endothelial cells. The description of this case serves to illustrate the range of MRSA infections that may cause various forms of glomerulonephritides.

Aged↗

The optimal stimulation site for chronic stimulation of the subthalamic nucleus in Parkinson's disease.

To determine the optimal stimulation site within the subthalamic nucleus (STN), monopolar stimulation of four electrode contacts and the resulting effects on parkinsonian symptoms were evaluated in 10 consecutive patients. The UPDRS score for rigidity and akinesia improved significantly after stimulation at each of the contacts, compared to the pre-evaluation state (Fisher's test, p < 0.05). The most significant improvement was obtained after stimulation at contact-2 (rigidity: 74.4 +/- 20.4%, akinesia: 53.7 +/- 14.3%) (Fisher's test, p < 0.001). Contact-2 was located at the dorsal border of the STN at a mean distance of 0.3 +/- 0.7 mm. DBS at the dorsal border of the STN, where the stimulation affects the neurons as well as their axonal fibers, produces the greatest clinical improvement in parkinsonian symptoms.

Brain Mapping↗

Identification of differentially expressed genes in rat hippocampus after transient global cerebral ischemia using subtractive cDNA cloning based on polymerase chain reaction.

BACKGROUND AND PURPOSE: The purpose of this study is to identify new molecules that play important roles in the phenomena that occur in the hippocampus after transient global cerebral ischemia, as clues to better understanding of the mechanisms. METHODS: A subtractive cDNA library was established by suppression subtractive hybridization of rat hippocampal tissues after transient global cerebral ischemia. With differential screening of the library, upregulated fragments were identified. The mRNA expression levels of selected genes were measured with semiquantitative reverse transcriptase polymerase chain reaction (PCR). RESULTS: Among more than 100 isolated fragments, approximately half were determined to be identical to known sequences. The rest showed high homology to known sequences, and only 2 did not exhibit homology to any known sequences. The expression of 5 genes identified in this study increased in 24 hours after ischemia to a level twice as high as that in sham-operated controls. These included furin, prosaposin, synaptotagmin IV, heat shock protein 105, and the neutral and basic amino acid transporter (NBAT). The increases in the mRNA expression levels of the genes except NBAT, as revealed by semiquantitative reverse transcription PCR, were statistically significant at both 6 and 24 hours after ischemia. CONCLUSIONS: Genes isolated are thought to be associated with production of proteins necessary for degeneration, neuroprotection, and reconstruction of neurons. How the expression of these genes relates to functional changes after ischemia remains to be determined. PCR-based subtractive cDNA cloning is demonstrated to be a useful tool for analyzing in vivo gene expression in animal ischemia models.

Amino Acid Transport Systems, Basic↗

Protein kinase cdelta and alpha are involved in the development of vasospasm after subarachnoid hemorrhage.

We have previously shown the enhanced activity of protein kinase C in the membrane fraction of the canine vasospastic artery after subarachnoid hemorrhage, which increased with progression of angiographic vasospasm. This study examined identification of protein kinase C isoforms in the canine basilar artery, and the changes in expression and/or translocation of each isoform during the development of vasospasm. Vasospasm was produced by using the "two-hemorrhage" canine model in the basilar artery, and angiographic progression of vasospasm was assessed consecutively. Two isoforms, protein kinase Calpha and delta were identified in basilar arteries by Western blotting. Densitometric analysis showed that the expression of protein kinase Cdelta in the membrane fraction was significantly increased in the earlier stage, and protein kinase Calpha was increased later as vasospasm progressed. These results indicate that protein kinase Cdelta and alpha isoforms may play a significant role in the development and maintenance of vasospasm.

Actins↗

Endothelin-1 initiates the development of vasospasm after subarachnoid haemorrhage through protein kinase C activation, but does not contribute to prolonged vasospasm.

Endothelium plays a role in the regulation of vascular tone. Endothelin is a family of potent vasoconstrictive peptides, and endothelin-1 (ET-1) produced in the endothelium induces a tonic contraction via specific receptor ET(A). ET-1 has been postulated as an important factor in the development of vasospasm after subarachnoid haemorrhage (SAH). We have previously shown that protein kinase C (PKC) of the cerebral artery plays a pivotal role in the pathogenesis of vasospasm. The purpose of this study is to clarify the relationship between ET-1 and PKC in the development and maintenance of vasospasm. Using a "two-haemorrhage" canine model, chronological changes of angiographic progression of vasospasm, PKC activation, and ET-1 level of the basilar artery were assessed. In an isometric tension study with a control artery, the effects of ET(A)- and ET(A)/ET(B)-antagonists on the tonic contraction induced by ET-1 were examined. The effects of ET-1, ET-1 and an ET(A)-antagonist, and ET-1 and an ET(A)/ET(B)-antagonist on PKC activation were also evaluated. ET-1 level temporarily increased, then decreased to the control level in a later stage of vasospasm. ET-1 induced a tonic contraction and enhancement of PKC activation, but both were inhibited either by an ET(A)- or an ET(A)/ET(B)-antagonist. These results indicate that ET-1 initiates the development of vasospasm through PKC activation, but does not contribute to prolonged vasospasm.

Animals↗

Brainstem function in rapid eye movement sleep behavior disorder: the evaluation of brainstem function by proton MR spectroscopy (1H-MRS).

Brainstem function was evaluated by proton magnetic resonance (MR) spectroscopy (1H-MRS) in a 69-year-old man with idiopathic rapid eye movement (REM) sleep behavior disorder. An analysis of spectral peak area ratios revealed an increase in the choline/creatine ratio. This change suggests that brainstem neurons have functional impairment at the cell membrane level. Further, our results suggest that 1H-MRS may provide for non-invasive, metabolic evaluation of brainstem neuronal function in REM sleep behavior disorder and find application in the differentiation of secondary REM sleep behavior disorders with neurodegenerative disorders from idiopathic disorders.

Aged↗

Scalp marking for a craniotomy using a laser pointer during preoperative computed tomographic imaging: technical note.

OBJECTIVE: The preoperative localization of superficial intracranial lesions is often necessary for accurate burr hole placement or craniotomy siting. It is not always easy, however, to localize the lesions over the scalp working only from computed tomographic images. We developed a simple method for such localization using a laser pointer during the preoperative computed tomographic examination. METHODS: The angle of incidence, extending from a point on the scalp to the center of the computed tomographic image, is measured by the software included with the scanner. In the gantry, at the same angle as on the image, a laser is beamed from a handmade projector onto the patient's scalp toward the center of the gantry. The point illuminated on the patient's head corresponds to that on the image. The device and the method are described in detail herein. RESULTS: We applied this technique to mark the area for the craniotomy before surgery in five patients with superficial brain tumors. At the time of surgery, it was confirmed that the tumors were circumscribed precisely. CONCLUSION: The technique is easy to perform and useful in the preoperative planning for a craniotomy. In addition, the device is easily constructed and inexpensive.

Brain Neoplasms↗

Preoperative hyponatremia as a clinical characteristic in elderly patients with large pituitary tumor.

This study investigated the pathophysiology of preoperative hyponatremia in elderly patients with a large pituitary tumor. The tumor size, initial symptoms, and preoperative pituitary hormonal function were analyzed in 96 patients, consisting of 82 younger than 70 years old (mean age 49.7 years) and 14 older than 70 years old (mean age 72.0 years). There was no difference in tumor size between the two age groups. The initial symptom of all younger patients was visual disturbance. Preoperative hormonal evaluations revealed subclinical panhypopituitarism in four patients (4.9%). Five of the 14 older patients had severe hyponatremia (107-117 mEq/l) based on panhypopituitarism, and four of these five patients showed consciousness disturbance as the initial symptom, initiated by physical and/or psychological stress, or occurrence of intratumoral hemorrhage. Preoperative subclinical panhypopituitarism was found in another patient. The overall occurrence rate of preoperative panhypopituitarism in the older patients was 42.9%. The difference in the frequency of preoperative panhypopituitarism was statistically significant between the two groups. Preoperative severe hyponatremia associated with a large pituitary tumor is characteristic of elderly patients. The number of receptors for adrenocorticotropic hormone in the adrenal cortex decreases during the aging process. Additional physical and/or psychological stress prompts pituitary dysfunction in such patients, causing the manifestation of acute symptoms of adrenal insufficiency based on panhypopituitarism. Primary care using high dose hydrocortisone and electrolyte fluid is critical.

Adrenal Insufficiency↗