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Biomedical subjects

M Tamai

Publications and source records attributed to M Tamai.

At least 109 records · Page 6Linked to original sources

Expression of cytokine genes in a patient with conjunctival melanoma compared with other pigment cells.

Conjunctival melanomas, which have a relatively good prognosis as compared to other mucosal melanomas, have been investigated morphologically and pathologically. We examined the gene expression of several cytokines in a patient with conjunctival melanoma and compared them to those of other pigment cells of the eye, because no reports have discussed cytokine expression in melanoma of the eye. Samples were collected from a 64-year-old woman with conjunctival melanoma and mRNAs were extracted and reverse-transcriptase polymerase chain reaction was performed. We found that potent inhibitors of tumor cell growth such as interleukin 2, 4, 6 and gamma-interferon were expressed in the tumor. These inhibitors were not expressed in other pigment cells of the eye, in blood, in conjunctival melanosis or in choroidal melanomas. The basic fibroblast growth factor gene, which has also been known to stimulate melanoma cell growth, was not expressed in the conjunctival melanoma, and it showed +/- or weak expression in choroidal melanomas, but it was expressed in the pigment cells in the eye and in conjunctival melanosis. Although only limited cytokine expression was examined here, these results may suggest an influence of these cytokines to the growth of conjunctival melanoma.

Adult↗

Increased expression of low-affinity NGF receptor in rat retinal Müller cells after ischemia and reperfusion.

Low affinity nerve growth factor receptor (p75LNGFR) it is thought to play an important role in recovering damaged nerve. To investigate the possible role of p75LNGFR in transient retinal ischemia, we investigated p75LNGFR gene expression and localization. Using rats under anesthetized conditions, we incised the bulbar conjunctive around the limbus, and then clamped the eyes. A sham operation was performed on the contralateral eyes. Ocular ischemia was maintained for 90 minutes. The p75LNGFR gene expression in ischemic rat retinas was examined by semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) at 0, 3, 6, and 72 hours after reperfusion, and the localization of p75LNGFR protein in rat retinas was examined by light and electron microscopic immunohistochemistry. The expression of p75LNGFR gene in ischemic rat retinas increased, as compared with that of the contralateral eyes after 6 hours and 3 days of reperfusion. The p75LNGFR protein increased in the outer plexiform layer and in the outer limiting membrane by immunohistochemical technique. Electron microscopic immunohistochemistry demonstrated that the staining is present in the Müller glial cells. The fact that p75LNGFR gene expression increased in Müller cells after reperfusion suggested that p75LNGFR expression may play a curative role in ischemic injury.

Animals↗

Preparation of liposome-encapsulating adenosine triphosphate.

Liposomes encapsulating adenosine triphosphate (ATP) were prepared by sonication, and the liposomes were evaluated for use in a drug delivery system. The liposomes, which were composed of phosphatidylcholine and cholesterol, were about 1.1 microm in size, as observed under a microscope. From their size, the vesicles were thought to be multilamellar. The maximum concentration of ATP in the liposomes was 1.0 mM, when the initial concentrations of lipid and ATP were 20 mM and 300 mM, respectively. The maximum entrapment ratio of ATP in the liposomes was 88%, when the initial concentrations of lipid and ATP were 20 mM and 500 mM, respectively. About 4% of ATP was encapsulated in these experiments. When liposomes contained 4-7% of cholesterol, about 35% of encapsulated ATP was released from the liposomes for 90 hours at 37 degrees C in vitro. These findings indicated that liposomes encapsulating ATP could be used for the treatment of ischemic retina.

Adenosine Diphosphate↗

Thyrotropin secreting pituitary adenoma effectively treated with octreotide.

We report a 65-year-old woman with thyrotropin (TSH) secreting pituitary adenoma, who was diagnosed based on the lack of inhibition of serum TSH despite an increased serum free thyroxine (T4), a low response of serum TSH to thyrotropin releasing hormone, and a pituitary tumor as revealed by magnetic resonance imaging. The pituitary adenoma was, however, inoperable due to chronic respiratory failure. The treatment with octreotide in a dose of 100 microg b.i.d. resulted in inhibition of serum TSH and free T4 to euthyroid levels and considerable shrinkage of the pituitary tumor. These effects were continued over 8 months after the start of octreotide therapy without any adverse effects. These findings add further evidence that octreotide is useful for treating inoperable TSH secreting pituitary adenoma.

Adenoma↗

Ocular changes in patients with spinocerebellar degeneration and repeated trinucleotide expansion of spinocerebellar ataxia type 1 gene.

OBJECTIVE: To examine ocular changes in patients with spinocerebellar degeneration who have repeated trinucleotide expansion in the spinocerebellar ataxia type 1 (SCA1) gene. DESIGN: Ophthalmic findings in 6 patients from 3 families whose DNA analysis revealed that they had an expanded allele of the trinucleotide repeated in the SCA1 gene were compared with those of normal control subjects and other healthy family members. The DNA was extracted from peripheral blood lymphocytes of the neurodegenerative family and normal control subjects. SETTING: University medical center. RESULTS: Visual acuity gradually decreased in successive follow-up visits. Color vision and visual fields were gradually affected. Electroretinograms showed mild attenuation of oscillatory potentials. Corneal endothelial cell density was severely decreased from 600 to 1300 cells/mm2. These findings were not observed in the normal control subjects, other healthy family members, or other patients with spinocerebellar degeneration who had repeated trinucleotide expansion of other genes. CONCLUSION: To the best of our knowledge, this is the first report describing the association between ocular changes in patients with spinocerebellar degeneration and gene mutation. These ocular changes were considered specific to patients who had the expanded allele of the repeated trinucleotide in the SCA1 gene.

Adult↗

Enhancement of tumor cell susceptibility to tumor-infiltrating lymphocytes by cisplatin.

Some means of enhancing the susceptibility of tumor cells to tumor-infiltrating lymphocytes (TIL) are required in adoptive immunotherapy. This study was designed to investigate whether or not tumor cell lysis by TIL was enhanced by treatment of the tumor cells with cisplatin, and also to clarify the mechanism of cisplatin's action on tumor cells. Autologous tumor cells and established cancer cell lines, including KATO-III and MKN-28, were used. Cytotoxic activities of TIL, the surface antigens of tumor cells, conjugation of TIL and tumor cells, and the production of TNF alpha from TIL were analyzed. Tumor cells treated with 2 micrograms/ml cisplatin for 12 h in vitro were more susceptible to bulk-cultured TIL and TIL clones. The surface antigens of tumor cells were not altered by the treatment with cisplatin. Cisplatin-treated tumor cells showed a higher binding ratio to TIL than did non-treated tumor cells. The anti-(tumor necrosis factor) (anti-TNF) or anti-TNF receptor antibody blocked the enhancement of cytotoxic activity by cisplatin. Thus, it was clarified that cisplatin enhanced the susceptibility of tumor cells to bulk-cultured TIL and TIL clones. Furthermore, the enhancement of cytotoxic activity by TIL in cisplatin-treated tumor cells was caused by a higher binding ratio to TIL and higher susceptibility to the TNF produced by TIL.

Antigens, Neoplasm↗

Correlation between vitamin D receptor genotypes and bone mineral density in Japanese patients with osteoporosis.

In order to better understand the pathogenesis of osteoporosis, we investigated the correlation between the vitamin D receptor (VDR) genotypes defined by BsmI restriction enzyme, as well as other related factors, and the bone mineral density (BMD) at the lumbar spine in 90 Japanese patients with osteoporosis. The same study was performed in 36 patients with osteoarthrosis of the hip joint and 92 healthy volunteers. The majority of the VDR genotypes were bb, and a few of the population showed either the BB or Bb genotype in all three groups. There was no statistical difference in the frequencies of these VDR genotypes in the three groups. The mean age-matched value of BMD (Z scores) at the lumbar spine in patients with osteoporosis was significantly lower than that in patients with osteoarthrosis or healthy volunteers. The mean Z scores of the healthy volunteers with bb genotype were significantly higher than those with BB genotype, whereas those of the osteoporosis patients with BB genotype were significantly higher than those with Bb genotype. There was no significant difference in the mean Z scores between bb and Bb genotypes in patients with osteoporosis and healthy volunteers. No significant difference was seen in the mean Z scores in patients with osteoarthrosis regardless of genotype. On the other hand, body weight significantly correlated with BMD in patients with osteoporosis by simple- and multiple-regression analysis. These results indicate that the BMD at the lumbar spine in Japanese patients with osteoporosis is affected by body weight, and might be affected partially by the VDR genotypes defined by BsmI.

Adult↗

Quantitative study on regenerated retinal pigment epithelium and the effects of growth factor.

PURPOSE: To evaluate the integrity of damaged retinal pigment epithelium (RPE) with normal neural retina in a rabbit model, and to examine the effects of basic fibroblast growth factor (bFGF) on the damaged RPE. METHODS: A 3-port vitrectomy, a retinotomy, and a retinal detachment were made in pigmented rabbit eyes. The RPE was then abraded beneath the neural retina. In one group, 1 microgram(s) of bFGF was injected into the vitreous cavity (bFGF applied group). Zero, 7, 14, 21, and 28 days after the operation, fundus examination and fluorescein angiography were performed. Thereafter, the rabbits were killed, the eyes were enucleated, and the histological features were observed with light microscopy (LM), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The number of RPE cells in the treated area were counted in all experiments, and the effect of bFGF on the number of regenerated RPE cells was analyzed. RESULTS: Regeneration of the RPE was observed in the treated area at postoperative day 14. The number of regenerated RPE cells showed a linear increase. Regenerated cells observed by TEM were smaller than those of the normal RPE. The difference in the number of regenerated RPE cells between the bFGF-applied and non-applied groups was statistically significant on postoperative days 7 and 21. CONCLUSIONS: Repair of the RPE occurred in a short period of time. Similar RPE repair may be seen in humans. Intravitreal injection of bFGF increased the number of regenerated RPE in this model.

Animals↗

A correlation between computer-predicted changes in secondary structure and the phenotype of retinal degeneration associated with mutations in peripherin/RDS.

PURPOSE: To investigate a molecular understanding of how mutations can lead to different phenotypes, we analyzed the relationship between altered secondary structures predicted by missense mutations in the peripherin/RDS and clinical severity of autosomal-dominant retinal degeneration. METHODS: We analyzed thirteen different kinds of missense mutations in the second intradiscal loop of peripherin/RDS, previously reported in peer review journals. Alteration of the secondary structure of peripherin/RDS was predicted by computer-assisted protein structure analysis. The number of amino acid residues that would be involved in the secondary structural change produced by a given missense mutation was scored as a grade of molecular change. Clinical severity was estimated by the impairment based on electroretinographic recordings of rods and cones, and was scored according to the severity of their recordings. Regression analysis was carried out between both scores of molecular change and clinical severity. Effects of patients' ages on clinical severity was also analyzed. RESULTS: Significant correlation was found between scores of molecular change and those of clinical severity (rods, r = 0.89, p < 0.001; cones, r = 0.76, p < 0.005) by regression analysis. There was no correlation between clinical severity and patients' ages. CONCLUSION: . These findings indicate that the degree of change in the secondary structure of peripherin/RDS can explain in part the correlation between genotype and phenotype in autosomal-dominant retinal degeneration associated with missense mutations in the peripherin/RDS gene.

Adult↗

Determination of ascorbic acid in human vitreous humor by high-performance liquid chromatography with UV detection.

PURPOSE: Ascorbic acid (AA) accumulates in vitreous at a concentration several times higher than in plasma. It has been suggested that AA may serve as an antioxidant that protects ocular tissues from free radical attack. There are many reports about the concentration of AA in ocular tissues. However, AA in adult human vitreous humor has not been determined. We measured concentrations of AA from pathologic human vitreous samples and compared the results. METHODS: AA was measured by high-performance liquid chromatography (HPLC) with UV detection. Human vitreous humor was collected from patients undergoing pars plana vitrectomy. RESULTS: AA was quantified in vitreous humor of proliferative diabetic retinopathy (PDR), proliferative vitreoretinopathy (PVR), macular hole (MH), idiopathic premacular fibrosis (PMF), and Terson syndrome (Terson). The concentrations of AA were 120.9 +/- 36.3 micrograms/ml (mean +/- SD), 129.8 +/- 36.6, 311.5 +/- 126.7, 446.9 +/- 154.2 and 406.0 +/- 22.0, respectively. There was no significant difference between the PDR and the PVR groups (unpaired t-test). Patients with PDR and PVR showed significantly lower concentrations of AA than those with MH, PMF, and Terson (p < 0.01). CONCLUSIONS: These findings suggest that increased oxidative stress may be produced in the ocular tissues of eyes with PDR and PVR, and AA appears to be consumed (oxidized) in performing its protective role.

Ascorbic Acid↗

Histidine-like immunoreactivity in the rat retina.

PURPOSE: Histidine is an indispensable amino acid with an imidazole ring and it is a precursor of histamine, carnosine, and anserine. Histidine has been proposed to act as a neurotransmitter or neuromodulator in mammalian central nervous system (CNS), including retina. In this study, we report histidine-like immunoreactivity in the rat retina with the use of antibodies raised against histidine coupled to bovine serum albumin (BSA) with glutaraldehyde. METHODS: In order to confirm the specificity of the antiserum toward histidine, immunodots were carried out. Only the histidine conjugate showed immunoreactivity. The rat retinas fixed with glutaraldehyde were used for immunocytochemistry. RESULTS: Histidine immunoreactivity was identified in the ganglion cell layer (GCL), inner nuclear layer (INL), inner plexiform layer (IPL), and Müller cells of rat retina. CONCLUSIONS: Histidine may be a precursor of histamine in the inner retina, and Müller cells may play some role in the metabolism of histidine.

Aging↗

Oguchi disease: phenotypic characteristics of patients with the frequent 1147delA mutation in the arrestin gene.

OBJECTIVE: To characterize clinical features of patients with Oguchi disease associated with a homozygous deletion of adenine at nucleotide 1147 (1147delA) in codon 309 in the arrestin gene. METHODS: Mutation screening by single-strand conformation polymorphism analysis was done, followed by sequencing. Ophthalmologic testing included evaluation of visual acuity and color vision, fundus examination, electroretinography, fluorescein angiography, evaluation of kinetic visual field, and dark adaptometry. Nine patients with Oguchi disease from seven unrelated families and family members who were unaffected by the disease were examined. RESULTS: A homozygous 1147delA mutation in the arrestin gene was identified in eight patients from six families with Oguchi disease. All patients who were examined exhibited a golden-yellow retinal reflex associated with Mizuo-Nakamura phenomenon and impairment of rod function in dark adaptation tests, although fundus examination showed slight variation in these findings. Four patients with the mutation had slightly reduced visual acuity, and the electroretinograms of three patients showed slightly reduced amplitudes during 30-Hz flicker electroretinography. CONCLUSION: Patients with Oguchi disease associated with the arrestin 1147delA mutation typically demonstrate retarded rod adaptation, whereas some patients have slightly impaired cone function.

Adolescent↗

Bilateral horizontal gaze palsy with pontine cavernous hemangioma: a case report.

A 31-year-old man demonstrating acquired bilateral gaze palsy as an isolated symptom of a paramedian pontine reticular formation (PPRF) lesion due to a ruptured cryptic cavernous hemangioma is herein reported. MRI revealed a flow void surrounded by a hemorrhagic lesion, which was located in the lower dorsal part of the pons. This lesion corresponded to the PPRF. His eye movement almost completely recovered and MRI revealed the absorption of the hematoma 2 months later, with only conservative observation. This is a rare case presenting most likely with a minimal lesion for bilateral gaze palsy. Based on the above findings it is thus concluded that surgical removal of such a cryptic cavernous hemangioma should therefore not be the only choice.

Adult↗

Correlation between vasodilatation and secretion in the lacrimal gland elicited by stimulation of the cornea and facial nerve root of the cat.

PURPOSE: To determine whether reflex vasodilatation can be elicited in the cat lacrimal gland by electrical stimulation of the cornea, whether the vasodilatation elicited by electrical stimulation of the facial nerve root found to be the efferent arm of the cornea-lacrimal gland reflex pathway correlates with the evoked secretion in the lacrimal gland, and what kind of receptors and which autonomic ganglia are involved in lacrimal vasodilator and secretory responses. METHODS: Electrical stimulation of the cornea or facial nerve root was used to evoke a blood flow increase in the lacrimal gland and tear secretion of the urethane-chloralose-anesthetized, paralyzed, and cervically sympathectomized cat. RESULTS: The lacrimal vasodilator response depended on stimulus intensity and frequency and correlated well with the tear secretion. Injection of 2% lidocaine solution into the retrobulbar area, where the pterygopalatine ganglion is located, abolished the vasodilator and the secretory responses. Pretreatment with hexamethonium (an autonomic ganglion blocker) greatly attenuated the secretory response, even at a low dose (1 mg/kg given intravenously), although at this dose, the vasodilator response was only slightly affected. Neither phentolamine (an alpha-adrenoceptor antagonist) nor propranolol (a beta-adrenoceptor antagonist), nor a vasoactive intestinal peptide antagonist had any effect on the vasodilator or secretory responses. Scopolamine (a muscarinic receptor antagonist), although having no effect on vasodilatation, had a profound inhibitory effect on the secretory response. CONCLUSIONS: These results suggest that whereas the vasodilator and secretory responses in the lacrimal gland were well correlated, they were mediated by different mechanisms.

Adrenergic alpha-Antagonists↗

[A case of stage IVb gastric cancer effectively treated by neoadjuvant chemotherapy and total gastrectomy with no residual tumor (R0)].

PA 72-year-old man visited our hospital complaining of body-weight loss and appetite loss. The upper gastrointestinal series and gastrointestinal fibroscopy disclosed a Borrmann 3 type gastric cancer. Laparoscopic examination revealed peritoneal dissemination (P2). Continuous intravenous administration of 5-FU (500 mg/day) for three weeks and drip infusion of CDDP (10mg/day) five days per week every three weeks was given as neoadjuvant chemotherapy. This course was carried out twice. Then laparoscopic reexamination revealed complete disappearance of disseminated lesions of the peritoneum, and total gastrectomy with R0 was done. Histopathological finding of the resected specimen showed significant effects of the neoadjuvant chemotherapy. The patient has been doing well with keeping good performance status (PS) 0 for one year and seven months after first diagnosis.

Adenocarcinoma↗

In vivo cisplatin resistance of rat ascites hepatoma AH66.

The rat ascites hepatoma AH66 cell line had higher resistance to cisplatin than a variant AH66F cell line in in vivo experiments, though in vitro sensitivities to cisplatin of both cell lines were similar in a medium containing 5% fetal calf serum (FCS). When AH cells were cultured in the medium containing 5% ascites fluid (ASF), the sensitivity of AH66 cells to cisplatin was significantly lower than that in the medium containing 5% FCS, but the sensitivity of AH66F cells was almost same in the case of 5% FCS. The metallothionein (MT) contents in AH66 cells, but not in AH66F cells, increased with the incubation time in the medium containing ASF. MT in AH66 cells was also induced by treatment with zinc ion, but the induction in AH66F cells was very low. These results indicate that AH66 cells have a high ability to induce MT and thereby may acquire in vivo resistance to cisplatin.

Animals↗