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Biomedical subjects

M Tamai

Publications and source records attributed to M Tamai.

At least 235 records · Page 13Linked to original sources

Decrease of opsin content in the developing rat photoreceptor cells by systemic administration of L-glutamate.

L-Glutamate, a putative photoreceptor cell neurotransmitter, causes thinning of the inner layers of the retina and has been used for preparing biologically fractionated photoreceptor cells. However, it is possible that absence of the inner retinal layers may affect the remaining retina, and/or glutamate may directly affect photoreceptor cells. We evaluated quantitatively the effects of L-glutamate on the developing photoreceptor cells by measuring the rod photoreceptor cell-specific protein, opsin. We purified rat rhodopsin and used it as the standard for measuring opsin content of rat retinas with competitive enzyme-linked immunosorbent assay. Various concentrations of glutamate were injected into 7-day-old rats, and the effects of the amino acid concentration on opsin expression were determined on postnatal day 14. Inner layers of the retina degenerated when 10 microliters or 15 microliters of 2.4 M glutamate/gram body weight was administered subcutaneously. Opsin content of these glutamate-treated retinas decreased significantly compared with control retinas. We administered glutamate to rats at various stages of development and determined the effects by light microscopy on postnatal day 14. The administration of glutamate resulted in no degeneration of the inner retina if injected on postnatal day 1 or 2, degeneration of the inner retina between day 3 to 7, and again, no degeneration after postnatal day 13. Opsin content decreased significantly when glutamate was administered between postnatal day 1 to 7, but not after day 13, the day the blood-retinal barrier seems to reach maturity. Our findings indicate that systemic administration of L-glutamate affects the expression of opsin in the developing rod photoreceptor cells.

Animals↗

Analysis of rhodopsin gene in patients with retinitis pigmentosa using allele-specific polymerase chain reaction.

Point mutations within the rhodopsin gene have been found recently in some patients with autosomal dominant retinitis pigmentosa (ADRP). Currently, four types of point mutations at codons 23, 58 and 347 have been identified. The purposes of this study were to establish simple methods for screening patients with retinitis pigmentosa (RP) to detect these point mutations, and to apply these methods to determine if these mutations are found in Japanese patients with RP. Utilizing the polymerase chain reaction (PCR), a one-step method was developed to detect point mutations at codon 23. This method was then applied to screen genomic DNAs from 30 patients with various types of RP, including ADRP, autosomal recessive RP, simplex RP, Leber's congenital amaurosis or Usher's syndrome. Subsequently, point mutations at codons 58 and 347 were detected by restriction enzyme digestion (Dde I or Msp I) of exons 1 and 5 amplified by PCR. To date, no mutations have been found in codons 23 and 58 in Japanese patients. By using the allele-specific PCR, however, two patients from one pedigree of ADRP were confirmed to have a C-to-T transition at the second nucleotide of codon 347, which results in the substitution of leucine for proline. Our findings indicated the availability of this simple method for detecting these point mutations.

Alleles↗

Cisplatin treatment renders tumor cells more susceptible to attack by lymphokine-activated killer cells.

We investigated whether tumor cell lysis by lymphokine-activated killer (LAK) cells was enhanced by treatment of the tumor cells with cisplatin (CDDP) in vitro. Tumor cells were treated with CDDP in vitro, and the cytotoxic activity for LAK cells was measured by 4-h 51Cr-release assay. The alterations of succinate dehydrogenase (SD) activity, and DNA,RNA synthesis of tumor cells were analysed. The susceptibility of CDDP-treated (2 micrograms/ml, 2h) Daudi and KATO-III cells to lysis by short term-cultured LAK cells was enhanced, as was the susceptibility of CDDP-treated (2 micrograms/ml, 12h) autologous tumor and Daudi cells to lysis by long term-cultured LAK cells. SD activity and DNA synthesis in tumor cells were impaired by 12-h treatment with 2 micrograms/ml of CDDP, whereas those were not altered by 2-h treatment with 2 micrograms/ml of CDDP. The enhancement of the susceptibility of CDDP-treated tumor cells to long term-cultured LAK cells was thus elucidated; it was shown to be due to alterations of the tumor cells with regard to their SD activity and DNA synthesis. It is suggested that the combined therapy with CDDP and LAK cells offers hope for increasing the response rate and the long-term survival of cancer patients.

Cisplatin↗

Presumed drusen of optic nerve head in siblings with Usher syndrome.

Two siblings with Usher syndrome had optic disc mulberry tumors that were photographically documented over a 5-year period. During this period, growth of these tumors was demonstrated. These lesions were reported histologically to be drusen. The existence of presumed optic disc drusen in siblings with Usher syndrome may be related to similar pathogenetic mechanisms rather than genetic implications.

Child↗

Lysosomal acid hydrolases in vitreous fluid of patients with proliferative diabetic retinopathy.

Using a new method to collect vitreous fluid safely during vitrectomy, vitreous specimens were obtained from 18 eyes of diabetic patients with proliferative diabetic retinopathy (PDR) and from 14 eyes of nondiabetic patients. The activities of four lysosomal acid hydrolases in these samples were measured and compared with those in serum. Of these enzymes, only N-acetyl-beta-glucosaminidase (NAG), a suspected retinal angiogenic factor, showed higher activity in the vitreous than in the serum in both diabetic (P less than 0.005) and nondiabetic eyes (P less than 0.05). However, no significant difference was found in any enzyme activity between diabetic and nondiabetic samples. These results suggested that this enzyme apparently does not have a significant effect, at least on the pathologic condition, during the late stage of PDR, and that NAG is usually present at higher activity in the vitreous than in the serum of diabetic as well as nondiabetic patients.

Acetylglucosaminidase↗

[Development of image processing system for fundus video-angiography with non-stroboscopic illumination].

A new recording system for fluorescein video-angiography using a highly sensitive color charge coupled device (CCD) camera was developed. An image processing unit installed in a personal computer made it possible to process video signals from the camera and/or a video tape recorder. Functions of the unit are on-line and/or off-line operations on image data such as smoothing, digital subtraction, differentiation etc. Application of the unit improved the quality of images observed on a monitor screen. This system enabled observation of the ocular fundus with illumination of low intensity, which reduced physical and psychological suffering of patients. In addition continuous and whole sequences of fundus fluorographs were recorded, without using strong stroboscopic lights. Extraction of a clear image from ambiguous records at any moment was possible through off-line processing on the stored data. Furthermore quantification of the blood flow in any blood vessels was possible by subtracting two successive images. With this system, quantitative expression of a slight difference in the color of the fundus could be made through calculation of the ratios among R-, G-, and B-components of signals at any place. Finally, comparative study of images of the fundus with natural color could be made with those of fluorography. These features may provide further information on the physiology and pathology of the fundus.

Animals↗

[A case of CA19-9 producing adenocarcinoma of the lung associated with idiopathic interstitial pneumonia].

A 63-year-old female, who had been suffering from idiopathic interstitial pneumonia (IIP) since two years and four months previously, was admitted with general fatigue, body weight loss, bloody sputum and progression of dyspnea. Chest roentgenogram on admission showed diffuse coarse ring shadows in the right middle and lower lung fields and in the left middle lung filed. Chest CT clearly showed honeycombing in bilateral dorso-basal segments of the lung. Serum CA19-9 level was elevated, and continued to increase during her clinical course. Sputum cytology was positive. Autopsy showed papillary adenocarcinoma of the lung (alveolar cell type). Immunohistochemical study of lung tissue showed positive CA19-9 staining on the surface of adenocarcinoma cells.

Adenocarcinoma↗

Corneal perforation in a patient with Cockayne's syndrome.

A 10-year-old boy with Cockayne's syndrome had an aseptic perforation centered in a corneal opacity of the right eye. Exposure keratitis, which was caused by anhidrosis, loss of blinking, and lack of Bell's phenomenon, was considered responsible for this condition. A therapeutic soft contact lens was applied to heal the corneal wound.

Child↗

[Combination of adoptive immunotherapy and chemotherapy against advanced cancer with peritoneal dissemination].

In a case of advanced gastric cancer with bilateral Krukenberg's tumors and peritonitis carcinomatosa, total gastrectomy, splenectomy and bilateral oophorectomy was performed. Since progressive peritoneal dissemination was recognized, 150 mg of CDDP and 10 mg of MMC which were proved to be effective by chemosensitivity test of anticancer drugs were administered intraperitoneally. After one month, ascites increased. So LAK cells and TIL were transferred intraperitoneally 6 times. With this treatment ascitic collection remarkably decreased, the performance status improved and serum level of IAP and CA125 normalized. Thus, it is clarified that the combination of adoptive immunotherapy and chemotherapy possesses therapeutic efficacy against advanced gastric cancer with peritonitis carcinomatosa.

Adenocarcinoma, Mucinous↗

Clinical evaluation of chemotherapy under angiotensin II-induced hypertension in patients with advanced cancer.

The clinical efficacy and indications for Angiotensin II (AT II)-induced hypertension chemotherapy were evaluated as a drug delivery system in 101 patients with advanced carcinoma. The sites of primary tumor studied included stomach (44), pancreas (18), colon (16), esophagus (6), bile duct (4), liver (3), breast (7) and 3 other single organs. Seventy four cases had distant metastases (lymph node (25), liver (29), peritoneum (16), and lung (4)). Additionally, the protocol was used 12 cases as postoperative adjuvant chemotherapy and 15 cases following exploratory laparotomy. The blood pressure was elevated to a level 1.5 times base-line. The regimens used consisted of MMC + ADR (55), FAM (38) and CDDP (8). The dosages administered were MMC 7 mg/m2, ADR 14 mg/m2 and 5-FU 350 mg/m2. The cancer chemotherapy protocol with AT II was repeated for an average of 2.6 cycles with a 2-3 week interval. The drug concentration in tumor tissues was increased 1.7 fold by AT II treatment. The response rate was 15.8% (CR 7 and PR 9), and in those patients with lymph node, liver and peritoneal metastases was 48.0, 6.9 and 6.3%, respectively. The serum levels of tumor markers decreased in 9 patients. Subjective symptoms, such as hoarseness, edema and pain, were improved. The mean survival in patients with distant metastasis who responded was 343 days, and in nonresponders was only 168 days (p less than 0.05). The side effects of this therapy were slight, typically being grade 1 and 2. Thus, the chemotherapeutic agents studied in conjunction with AT II were effective in patients with lymph node metastasis. Additionally, this regimen could be performed safely with minimal side effects.

Aged↗

[Clinical application of adoptive immunotherapy by cytotoxic T lymphocytes induced from tumor-infiltrating lymphocytes].

The tumor-infiltrating lymphocytes (TIL) were cultured with interleukin 2 (IL-2) to induce the cytotoxic T lymphocytes possessing autologous tumor-killing activity from 21 cancer patients (11 with solid tumor and 10 with malignant peritoneal or pleural effusions), and transferred into 7 patients as IL-2-activated TIL adoptively. The clinical application of activated TIL by adoptive transfer could result the complete regression of malignant pleural effusions in a patient with pancreatic cancer, and the nearly complete regression of malignant ascites in a patient with gastric cancer. The autologous tumor cells were isolated at the purity of more than 90% by Ficoll-Hypaque and Percoll discontinuous gradients, and then the TIL were cultured with IL-2 until 4 weeks. The optimal concentration of IL-2 was 1,500 IU/ml to obtain maximum proliferation and autologous tumor killing activity. The cytotoxic activities of activated TIL at 3 weeks-incubation was 72 +/- 15, 42 +/- 26, 27 +/- 21 and 22 +/- 15% against K562, Daudi, KATO-III and autologous tumor, respectively. By negative selection method, it was clarified that the killer cells recognizing autologous tumor consisted of CD4 or CD8 positive T lymphocyte in 43% of patients. The CD8 positive cells and CD56 positive cells increased, the CD4 positive cells and CD16 positive cells decreased by flow cytometry. The activated TIL could lyse not only cultured tumor cell lines, also other autologous tumor cells. The CD56+ cells were isolated by the Panning method, these cells could not lyse autologous tumor cells. Thus, it was indicated that the cytotoxic T lymphocytes recognizing autologous tumor could be generated from TIL and the adoptive immunotherapy of activated TIL was effective in cancer therapy.

Adult↗

Functional and phenotypic analyses of interleukin 2-activated tumor-infiltrating lymphocytes.

The tumor-infiltrating lymphocytes (TILs) were cultured with interleukin 2 (IL-2) to induce the activated killer cells possessing autologous tumor-killing activity, and analysed their cell surface phenotypes and assessed anti-tumor killing activity. Furthermore, the activated TILs were transferred into 7 patients adoptively resulting in complete remission in a patient with pancreatic cancer and partial remission in another patient with gastric cancer. The cytotoxic activities of activated TILs at 3 weeks-incubation was 72 +/- 15, 42 +/- 26, 27 +/- 21 and 25 +/- 15% against K562, Daudi, KATO-III and autologous tumor, respectively. The negative selection method, indicated that the killer cells recognizing autologous tumor cells consisted of CD4- or CD8-positive T lymphocytes and CD16- or CD56-positive natural killer cells. The activated TILs could not only lyse cultured tumor cell lines, but also autologous tumor cells.

Adult↗

Response of Müller cells following experimental lensectomy-vitrectomy.

We used morphological, biochemical and immunohistochemical methods to assess the response of Müller cells after experimental lensectomy-vitrectomy in rabbits. We observed widened intercellular spaces between the Müller cells and nerve fibers of ganglion cells, and increased electron opacity in the Müller cells of eyes injected with silicone oil. No apparent morphological changes were detected in the Müller cells of air-injected eyes. The specific and total activities of Müller cell-marker enzymes (glucose 6-phosphatase and glutamine synthetase) showed an initial increase, followed by a decrease. Glial fibrillary acidic protein immunoreactivity was not found in the Müller cells of the normal rabbit retina but was exhibited after surgery. Our results showed that markers of Müller cells associated with glycogenolysis and/or gluconeogenesis, glutamate-glutamine cycle and cytoskeletal protein metabolism were affected by the experimental lensectomy-vitrectomy.

Air↗

Impairment of autologous mixed lymphocyte reaction in the spleen and peripheral blood lymphocytes of patients with idiopathic portal hypertension.

The etiology of idiopathic portal hypertension (IPH) is unknown, although many studies have suggested that it might be an autoimmune disease. The autologous mixed lymphocyte reaction (AMLR) involves the proliferation of T lymphocytes when co-cultured with autologous non-T cells and may reflect immune control mechanisms in vivo. The AMLRs in the spleen and peripheral blood of three patients with IPH were measured and it was shown that the AMLRs both in the spleen and peripheral blood were significantly suppressed compared to those of normal healthy subjects. By allogeneic MLR, there was a tendency that the disturbance of non-T cells was more intensive than that of T cells. The AMLR of peripheral blood did not improve by splenectomy. Thus, the depressed cause of AMLR in patients with IPH was suggested mainly to disturbance of the antigen-presenting ability of non-T cells, and it was suggested that not only the spleen cells, but systemic immune disturbance caused the impairment of AMLR in IPH.

Aged↗

A novel N6-substituted adenosine isolated from mi huan jun (Armillaria mellea) as a cerebral-protecting compound.

Successive purification of a crude extract of cultured Mi Huan Jun mycelia, followed by an assay of the effect on complete ischemia in mice, led to the isolation of a new compound with cerebral protecting activity, hereafter designated as AMG-1. The structure of AMG-1 was proposed as being 6-(5-hydroxy-2-pyridyl-methylamino)-9-beta-ribofuranosylpurine (1) on the basis of its UV, mass, 1H-NMR, and 13C-NMR spectra.

Adenosine↗