Biomedical subjects

T Nakashima

Publications and source records attributed to T Nakashima.

At least 163 records · Page 9Linked to original sources

PubMed1999

Magnetic sensory cortical responses evoked by tactile stimulations of the human face, oral cavity and flap reconstructions of the tongue.

Magnetoencephalography (MEG) is a procedure that analyzes the magnetic responses of neurons. An MEG system with a 37-channel superconductivity quantum interference device (SQUID) was used to record magnetic signals from the human brain in response to tactile stimulations of the face and oral cavity. Six normal individuals were studied as well as three patients who had undergone hemiglossectomies as treatment for carcinoma of the tongue and reconstruction with a pectoralis major myocutaneous flap. When the locations of the magnetic responses having latencies of 40 ms from onset of tactile stimulation were identified, these corresponded to the primary somatosensory cortex. In patients whose tongues had been reconstructed with a pectoralis major myocutaneous flap, the magnetic response upon stimulation of the flap was recorded in a sensory cortical area identical to that corresponding to the tongue. MEG systems such as the one described permit functional mapping of the cerebral cortex on stimulating the face and oral cavity.

Adult↗

PubMed1999

Overexpression of p53 nuclear protein in premalignant and malignant laryngeal lesions.

To investigate the role of p53 nuclear protein mutations in the initiation and progression of laryngeal carcinoma, 111 premalignant and malignant laryngeal lesions (19 specimens with hyperkeratosis and 92 with carcinoma) were studied immunohistochemically. Over-expression of p53 was observed in 8 cases (42%) of laryngeal hyperkeratosis and 44 cases (47%) of laryngeal carcinoma. However, the expression of p53 showed no relationship to patients' clinical courses. Our study confirms that p53 overexpression can be found in laryngeal carcinogenesis and is an early event but not a useful prognostic marker.

Carcinoma, Squamous Cell↗

PubMed1999

Induction of apoptosis in maxillary sinus cancer cells by 5-fluorouracil, vitamin A and radiation (FAR) therapy.

The triple combination of 5-fluorouracil (5-FU), vitamin A and radiation (FAR therapy) has been used since 1972 to treat malignant tumors of the head and neck at Kyushu University. Using nick end labeling of tumor specimens, cells of human maxillary sinus carcinomas were observed previously to undergo apoptosis in response to FAR therapy. The present study evaluated the in vitro effects of FAR therapy on a human maxillary sinus cancer (IMC-4) cell line. We further compared the effects of FAR therapy on this cell line with those effects seen on tissue samples taken from patients with maxillary sinus cancers. DNA electrophoresis and electron microscopic examination of the IMC-4 cells after treatment with FAR therapy revealed typical apoptotic features. The effects of 50-100 micrograms/ml 5-FU, 10(-4) M all-trans-retinoic acid and radiation to 6 Gy on IMC-4 cells were evaluated by trypan blue dye exclusion and a cell colony formation assay. 5-FU and radiation caused direct cell death, while vitamin A mainly inhibited cell growth. The combination of these treatment as FAR therapy synergistically enhanced cell death and inhibited cell growth. Flow cytometry demonstrated that FAR-treated cells were arrested in the G1 phase of the cell cycle before undergoing apoptosis. To further investigate possible biological parameters influencing a tumor's apoptotic sensitivity, we also examined the expression of p53 in human maxillary sinus cancer cells and analyzed the relationship between p53 expression and apoptosis. However, no relationship was found between these two markers at the time point studied.

Antineoplastic Agents↗

PubMed1999

Contribution of endothelin-1 to disruption of blood-brain barrier permeability in dogs.

We examined the effect of intracisternal application of endothelin-1 (ET-1) on the permeability of fluorescein into the cerebrospinal fluid (CSF) in beagle dogs in order to evaluate its role in disruption of blood-brain barrier (BBB) permeability seen in the subarachnoid hemorrhage animal model. Intracisternal application of their autologous blood for producing a canine two-hemorrhage model revealed an enhanced fluorescein permeability into the CSF together with the development of cerebral vasospasm. A single dose of ET-1 (40 pmol/animal) significantly increased penetration of fluorescein compared with that in normal dogs. Although its magnitude was much less than that in the two-hemorrhage model after the first administration of ET-1, the second challenge of the same dose of ET-1 with a 48-h interval produced marked disruption of BBB permeability similar to those in the animal model. Moreover, the ET-1-induced enhancement of fluorescein permeability into the CSF was completely prevented by intracisternal pretreatment with an endothelin ET(A)-receptor selective antagonist, S-0139 (0.03 mg/kg), as were the ET-1-induced cerebral vasoconstriction and behavioral changes as previously reported. Thus, we conclude that ET-1 acting on the adventitial site of brain in dogs contributes to the disruption of BBB permeability via endothelin ET(A)-receptor mediation.

Analysis of Variance↗

PubMed1999

Solitary fibrous tumor of the paranasal sinuses.

Although solitary fibrous tumors are well-recognized in the pleura, their occurrence in the paranasal sinuses is decidedly uncommon. We have encountered two cases of solitary fibrous tumors in the paranasal sinuses and report the clinicopathological findings including CD34 immunoreactivity. One tumor arose in a 55-year-old Japanese businessman and the other in a 53-year-old man who had been in the hospital for schizophrenia for 20 years. The tumors showed characteristic findings. Immunoperoxidase stains on paraffin sections showed staining of the cells for anti-vimentin, but there was no staining for anti-keratin, anti-S-100 protein, anti-desmin, anti-glial fibrillary acidic protein (GFAP), or anti-actin. Anti-CD34 monoclonal antibodies also reacted with these tumors, as those of the pleura generally do, and were found to be useful in diagnosing these tumors. CD34 immunoreactivity [8]. Fukunaga et al. [6] reported that CD34 immunoreactivity presented in a solitary fibrous tumor of the nasal cavity, but separate tumors of the paranasal sinuses have not been analyzed. We have recently encountered two cases of solitary fibrous tumors of the paranasal sinuses. In this report, the clinicopathological features of these tumors of and their CD34 immunoreactivity were analyzed.

Antibodies↗

PubMed1999

Inhibitory effect of a new anti-rheumatic drug T-614 on costimulatory molecule expression, cytokine production, and antigen presentation by synovial cells.

The present study was undertaken to investigate the immunoregulatory effects of T-614 (3-formylamino-7-methylsulfonylamino-6-phenoxy-4H-1-benzopyran-4-o ne) on synovial cells in vitro. Synovial cells were cultured with T-614 in the presence or absence of various cytokines. After incubation, the costimulatory molecule expression on synovial cells and cytokine production in culture supernatants were analyzed by an indirect immunofluorescence method and enzyme-linked immunosorbent assay, respectively. We also examined the effect of T-614 on the function of synovial cells as antigen-presenting cells (APCs). The costimulatory molecules including CD54, CD58, and CD106 were constitutionally expressed on the surface of synovial cells. However, neither CD80 nor CD86 nor CD102 was found on the surface, and these costimulatory molecules could not be induced by any cytokines. T-614 itself did not affect the costimulatory molecule expression and cytokine production of unstimulated synovial cells. The stimulation of synovial cells with interferon-gamma (IFN-gamma), interleukin-1beta, or 12-O-tetradecanoyl phorbol 13-acetate enhanced the expression of costimulatory molecules and the proinflammatory cytokine production of these cells. Both the up-regulated expression of these costimulatory molecules and the enhanced production of proinflammatory cytokines were significantly inhibited by T-614. Autologous T cell proliferation in response to purified protein derivative by IFN-gamma-treated synovial cells was significantly suppressed by T-614. T-614 has considerable immunosuppressive effects on synovial cells by inhibiting the costimulatory molecule expression and cytokine production of these cells and the antigen-specific T cell proliferation mediated by the synovial cells. These results suggest that T-614 plays an important immunoregulatory role in rheumatoid synovial tissues.

Adjuvants, Immunologic↗

PubMed1999

Tumor necrosis factor-alpha and interleukin-1beta increase the Fas-mediated apoptosis of human osteoblasts.

Our recent work demonstrated functional Fas expression on human osteoblasts, and the histologic examination of the periarticular osteoporosis region in patients with rheumatoid arthritis (RA) showed apoptosis in osteoblasts. High concentrations of interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), and IL-6--which are thought to increase bone resorption--have been determined in RA synovium. We investigated the effect of these cytokines on the Fas-mediated apoptosis of human osteoblasts. The human osteoblastic cell line MG63 and human primary osteoblast-like cells from bone biopsy specimens were used as human osteoblasts. Fas expression on these cells was examined by flow cytometry, and Fas-mediated apoptosis induced by anti-Fas immunoglobulin M (IgM) was determined by a chromium 51 release assay, the presence of cells with hypodiploid DNA, staining with Hoechst 33258 dye, and the detection of DNA fragmentation on agarose gel electrophoresis. The proliferation of osteoblasts was analyzed by a tritiated thymidine incorporation assay. Spontaneous apoptosis was not found on cultured osteoblasts. The apoptosis of human osteoblasts was not induced by TNF-alpha, IL-1beta, or IL-6 alone in the absence of anti-Fas IgM. In addition, proliferation of the cells was not affected by these cytokines. Fas was constitutively expressed on unstimulated osteoblasts, and treatment of these cells with IL-1beta or TNF-alpha significantly augmented Fas expression. Human osteoblasts were committed to apoptosis with anti-Fas IgM, and the treatment of both IL-1beta and TNF-alpha markedly increased Fas-mediated apoptosis. TNF-alpha augmented both Fas expression and Fas-mediated apoptosis more efficiently than did IL-1beta. In addition, an additive effect on both Fas expression and Fas-mediated apoptosis was demonstrated when TNF-alpha and IL-1beta were added to osteoblasts. IL-6 influenced neither Fas expression nor the Fas-mediated apoptosis of osteoblasts. Furthermore, no synergistic effect of IL-6 with IL-1beta or TNF-alpha was observed. IL-1beta, TNF-alpha, or IL-6 did not change Bcl-2 expression. Our results suggest that IL-1beta and TNF-alpha regulate osteoblast cell number by up-regulating the Fas-mediated apoptosis of osteoblasts, one of the putative mechanisms inducing periarticular osteoporosis in patients with RA.

Apoptosis↗

PubMed1999

Enhancement of sensitization to nicotine-induced ambulatory stimulation by psychological stress in rats.

1. The authors investigated the influence of psychological stress (PSY-stress) on sensitization to nicotine (0.5 mg/kg, s.c.)-induced ambulatory stimulation. 2. Rats were exposed to the emotional responses of animals which received foot-shock (FS), which they, themselves, did not receive. Ten daily exposures to PSY-stress for 20 min enhanced sensitization to the nicotine-induced ambulatory stimulation compared to that in non-stress rats. 3. However, the increased serum corticosterone levels following nicotine (0.5 mg/kg, s.c.) administered 24 hr after the tenth injection of nicotine in the behavioral study was almost the same in the rats exposed to PSY-stress as compared to non-stress rats. 4. These results suggest that PSY-stress may promote sensitization to nicotine-induced ambulatory stimulation and that the combined effect of PSY-stress and nicotine would facilitate the development of sensitization to nicotine.

Animals↗

PubMed1999

Microtubule-associated protein-2 in the hypothalamo-neurohypophysial system: low-molecular-weight microtubule-associated protein-2 in pituitary astrocytes.

Microtubule-associated protein-2 is the most abundant microtubule-associated protein in the brain and is responsible for morphogenesis and maintenance of the nervous system. In the present experiments, we have examined the localization of microtubule-associated protein-2 in the hypothalamo-neurohypophysial system of the rat using western blots and immunohistochemistry. Two monoclonal antibodies against microtubule-associated protein-2, antibody C and AP20, were used: antibody C recognizes both the high- and low-molecular-weight isoforms of microtubule-associated protein-2; antibody AP20 specifically detects high-molecular-weight microtubule-associated protein-2 only. Western blot analysis revealed expression of high-molecular-weight microtubule-associated protein-2 in the whole brain, hippocampus and whole hypothalamus. While the supraoptic nucleus expressed only high-molecular-weight microtubule-associated protein-2, the adult posterior pituitary predominantly expressed low-molecular-weight microtubule-associated protein-2, which was also seen in the embryonic whole brain. Light microscopic immunohistochemistry revealed that both antibody C and AP20 intensely stained dendrites of the dendritic and somatic zones in the supraoptic nucleus. Double labeling with antibodies against microtubule-associated protein-2 and oxytocin (or vasopressin) demonstrated that microtubule-associated protein-2 was localized in dendrites of magnocellular neurons in the supraoptic nucleus. In the posterior pituitary, however, antibody C stained fine processes and cell bodies of astrocytes, which were identified by an antibody against glial fibrillary acidic protein. Antibody AP20 also stained fine processes of some astrocytes in the posterior pituitary, but the intensity of immunoreactivity with antibody AP20 was weaker than that with antibody C. This result suggests that microtubule-associated protein-2 in astrocytes of the posterior pituitary is predominantly of the low-molecular-weight type. Moreover, western blots revealed low-molecular-weight microtubule-associated protein-2 of the posterior pituitary at a molecular weight slightly higher than embryonically expressed low-molecular-weight microtubule-associated protein-2, indicating that low-molecular-weight microtubule-associated protein-2 in the posterior pituitary is possibly the isoform microtubule-associated protein-2d. The present results demonstrate that astrocytes in the posterior pituitary of adult rats still retain the ability to express the immature variant of microtubule-associated protein-2, low-molecular-weight microtubule-associated protein-2, and its expression is probably linked to structural plasticity.

Animals↗

PubMed1999

Two cases of piriform sinus fistula which required a long time for diagnosis.

Two cases of piriform sinus fistula which had contradistinctive occurrences, were reported. In case 1, a 58-year-old man suffered from the disease without having any symptom for a long time and in case 2, a 39-year-old woman had been troubled with repeated cervical abscess from 3 years old. In both cases, indirect laryngoscopy and laryngofiberscopy showed saliva pooling in the bilateral piriform sinus and barium fluoroscopy with the Valsalva maneuver revealed the fistula originating from the apex of left piriform sinus. In case 2, computed tomography (CT) and magnetic resonance imaging (MRI) demonstrated an abscess in and around the left lobe of the thyroid. In both cases the fistulectomy was performed and their postoperative conditions have been uneventful for more than 2 years without recurrence. The etiology, cause, clinical features, diagnosis and therapy of piriform sinus fistula were reviewed.

Adult↗

PubMed1999

Purification and characterization of lipase from Rhizopus chinensis cells.

Lipase from Rhizopus chinensis cells was purified and characterized. The molecular mass of purified lipase was 28.4 kDa and the optimal temperature and pH for its activity were 37 degrees C and 5.5, respectively. Purified lipase exhibited high hydrolytic activity against fatty acid methyl esters such as methyl caprylate, methyl laurate, and methyl palmitate. Freeze-dried lipase catalyzed the transesterification between olive oil and methyl laurate in n-hexane.

Journal Article↗

PubMed1999

Characteristics of eosinophilic inclusions within Schistosoma japonicum eggs.

Although eosinophilic bar- or droplet-like inclusions are frequently detectable inside eggs deposited in the livers of Schistosoma japonicum-infected animals, little is known of their exact nature. In the livers of mice implanted with freshly laid eggs, inclusion-positive eggs were found in 28.7 and 46.2% of deposited eggs at 2 and 4 weeks, respectively, after implantation, but in 4.3% at 5 weeks when most of the eggs had already degenerated. When the extent of granuloma formation was investigated, granulomas around inclusion-positive eggs were smaller than those around negative eggs. Host factors associated with the formation of inclusion were sought using in vivo and in vitro studies. Following the administration of anti-egg antigen serum into egg-implanted mice, no increase in occurrence of inclusion-positive eggs was seen. In a co-culture of mature eggs with infected rabbit or mouse serum, inclusions were rarely found. In contrast, they were found in 17.9% of eggs in the presence of splenic cells. The present study is the first to show that there is decreased granuloma formation in the presence of eosinophilic inclusions inside eggs and our in vitro study suggests that host cell-egg interaction is responsible for the formation of inclusions.

Animals↗

PubMed1999

Hearing immaturity found by ABR and its clinical impact on otoneurological evaluation.

Auditory Brainstem Response (ABR) is the most reliable and most frequently used procedure to evaluate audiological conditions in early infancy. However, several reports have demonstrated that developmental change in the central nervous system may affect the results of ABR in audiological evaluations. We examined statistically the reliability of ABR for the diagnosis of profound deafness in early childhood according to our experience over the past 12 years of follow-up in our facility. Subjects included 371 children among 1,041 children who were admitted to Kanariya-Gakuen (institute for pre-school deaf children) from April 1985 to March 1997. These children were examined with ABR to determine their hearing levels. In five cases with an abnormal hearing threshold determined by ABR and other audiological tests, repeated examinations carried out during a 5- to 6-month follow-up period revealed that they had normal hearing. Three of these children had been diagnosed previously with mental retardation and the remaining two were infants < 5 months old. The specificity and sensitivity of ABR were calculated as 97.3% and 100%, respectively. The predictive value of a positive result was 94.7%. There remains the possibility of a false negative for such cases, although the rate seems to be very low (< 0.2%).

Audiometry↗

PubMed1999

Fibroblasts in human vocal fold mucosa.

Fibroblasts in two portions of the vocal fold mucosa, the macula flava (MF) and Reinke's space (RS), were investigated by means of transmission electron microscopy. Five adult and five newborn larynges from autopsy cases were subjected to study. Both in adults and newborns, fibroblasts in the MF tended to be stellate in shape, to have a small nucleus/cytoplasm (N/C) ratio, and to have a well developed rough endoplasmic reticulum (rER) and Golgi apparatus (GA). They were active in producing collagenous and elastic fibres. Most fibroblasts in RS were oval in newborns and spindle-shaped in adults. They had a large N/C ratio and less developed rER and GA, indicating that they were inactive in producing fibres. We postulate that many fibroblasts in the newborn and infant MF contribute to the development of the vocal ligament, many of those in the adult MF participate in the metabolism of the vocal ligament, and many of those in RS of both age groups are activated when the vocal fold tissue is injured.

Adult↗

PubMed1999

Transfer of nitric oxide from the liver to erythrocytes--an ESR study using nitroglycerin-treated mice.

Nitric oxide (NO) formation in the liver and blood of the mouse following intraperitoneal treatment with nitroglycerin (glycerol trinitrate, GTN) was determined using electron spin resonance (ESR) spectroscopy. ESR signals of heme-NO complexes were detected at maximum levels within 5 min in the liver, but increased to a maximum level about 15-30 min later in the blood. GTN is not metabolized to release NO in vitro in the blood of the mouse. The hepatic microsomes which showed the heme-NO complexes ESR signals were incubated with mouse erythrocytes, with the result that a hemoglobin-NO signal was obtained from the erythrocytes. The activities of microsomal cytochrome P-450, the hepatic level of glutathione, and the reduction rate of nitroxide radicals in the in vivo liver, measured using L-band ESR spectroscopy, were temporarily decreased following GTN administration. In conclusion, NO in the liver could be scavenged by circulating erythrocytes, which might minimize NO-induced liver damage.

Animals↗

PubMed1999

Functional reconstruction of swallowing and articulation after total glossectomy without laryngectomy: money pouch-like reconstruction method using rectus abdominis myocutaneous flap.

When a total glossectomy is performed without a laryngectomy, the functional recovery of swallowing and articulation is extremely important in maintaining the patient's quality of life. The authors established a money pouch-like reconstruction method in which a round and raised tongue is rebuilt using a rectus abdominis myocutaneous flap. In this method, the skin island of the rectus abdominis myocutaneous flap is created about 20 percent larger than the defect in both width and length. The skin island is sutured to the defect such that the excess skin folds into the shape of a money pouch. This allows the tongue to be reconstructed with its tip and dorsum touching the hard palate and its base bulging in the dorsal and posterior directions. Misswallowing was not detected in the three patients who had this surgery, and each of them had improved articulation sufficient to carry out daily conversations.

Adult↗

PubMed1999

A case of generalized morphea with a high titer of anti-Borrelia burgdorferi antibodies.

A 69-year-old male had noticed pruritus on the back for the previous 3-4 years and cutaneous sclerosis with swelling of the dorsum of the neck had developed in the last one and a half years. However, he had never complained of Raynaud's phenomenon of the fingers, dry mouth, or dry eyes. At this first visit to our hospital, he complained of erythematous cutaneous sclerosis with swelling of the dorsum of the neck. Histopathological findings biopsied from the neck showed epidermal hyperplasia with elongation of rete ridges and homogeneous and fibromatous changes of the dermis with dense perivascular cell infiltration consisting of mononuclear cells or lymphocytes with several nests of incontinentia pigmenti. However, there were no sclerotic changes in blood vessels in the upper dermis biopsied from the forearm skin, although slightly homogeneous and fibromatous changes of the dermis were seen. In the clinical course, the cutaneous sclerotic change enlarged to extend to the bottom of the cheek, forearm, and lower legs. These clinical features and histopathological findings led to the diagnosis of generalized morphea. Hematologic examination showed positive anti-Borrelia burgdorferi IgM antibodies, although there were no positive anti-Borrelia burgdorferi IgG antibodies. These results revealed that there can be a close association of localized scleroderma with Borrelia burgdorferi and that generalized morphea may also represent a Borrelia infection.

Aged↗

PubMed1999

Hydroxyl radical formation following methamphetamine administration to rats.

Administration of neurotoxic doses of methamphetamine (8 mg/kg, intraperitoneally x 4 times, at 2 hr intervals) caused a significant decrease in dopamine and 3,4-dihydroxyphenylacetic acid and an increase in 3-methoxytyramine levels in the striatum along with a decrease in serotonin and 5-hydroxyindoleacetic acid levels in the striatum and hippocampus. In addition, the methamphetamine treatment caused an increase in rat rectal temperature. Intraventricular injection of salicylate 105 min. after the last injection of methamphetamine produced an increase in 2,3- and 2,5-dihydroxybenzoic acid in the striatum and hippocampus. Moreover, the ratio of 2,3-dihydroxybenzoic acid to salicylate was significantly increased in the striatum, but not in the hippocampus. These results indicate that the hydroxyl radical may play an important role in methamphetamine-induced neurotoxicity in rat striatum and that its formation may be the result of methamphetamine-induced release of dopamine.

Animals↗