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Biomedical subjects

T Abiko

Publications and source records attributed to T Abiko.

At least 19 recordsLinked to original sources

Relationship between autofluorescence and advanced glycation end products in diabetic lenses.

Autofluorescence and advanced glycation end product (AGE) levels were measured in the lenses of 9 diabetic Chinese hamsters and 6 age-matched controls. Lens autofluorescence also was measured in 37 diabetic patients and 14 age-matched controls. Lens autofluorescence values were measured noninvasively with a lens measurement system using color filters with peak transmission at 365- and 434-nm wavelengths (excitation and emission, respectively) that are characteristic of AGE fluorescence. The peak lens autofluorescence level was used as the lens autofluorescence value, and the mean lens autofluorescence values from both eyes of each subject were used for statistical analysis. The AGE levels in one lens from each hamster were measured by noncompetitive enzyme-linked immunosorbent assay with a polyclonal anti-AGE antibody. We found a 2.2 times increase of the mean lens autofluorescence value of diabetic hamsters in comparison with that of controls (P<0.01). We also found a 1.5 times increase of the mean AGE level from the lenses of diabetic hamsters in comparison with that of controls (P<0.01). Moreover, a statistically significant positive correlation between the AGE level and autofluorescence value in the same lenses was observed in all hamsters (rho=0.58, P<0.05). In human subjects, we found a 1.4 times increase of the mean lens autofluorescence value of diabetic patients in comparison with that of age-matched controls (P<0.01). Our results suggest that non invasive measurement of lens autofluorescence may be a guide to AGE levels in lenses.

Aged

Diurnal variation of corneal autofluorescence in normal and diabetic eyes.

PURPOSE: To examine the diurnal variations in corneal autofluorescence in normal and diabetic patients. METHODS: We measured corneal autofluorescence using a fluorophotometer fitted with an anterior segment adapter. Corneal autofluorescence was measured 10 times at 3 min intervals to evaluate the reproducibility of this instrument in 4 eyes of 4 normal subjects. The diurnal variation in corneal autofluorescence was determined by measuring the fluctuations in 10 eyes in 10 normal subjects and one unoperated eye each of 10 patients with proliferative diabetic retinopathy (PDR). We performed five consecutive measurements at 1000, 1130, 1400, 1630 and 1900 hours. The mean value of five measurements, the variation range and the coefficient of variation were analysed. RESULTS: The mean coefficient of variation in the measurement using this instrument was 8.6 +/- 1.0%. In the patients with PDR, the mean corneal autofluorescence value was significantly higher (p < 0.001), the variation range was significantly wider (p < 0.001) and the coefficient of variation was significantly greater (p < 0.01) than in the normal subjects. CONCLUSIONS: The results of this study suggest that corneal autofluorescence changes over the course of a day in patients with diabetes. This may be caused by the breakdown of the blood-aqueous barrier that we reported previously.

Adult

Corneal and lens autofluorescence in young insulin-dependent diabetic patients.

To study the early ocular abnormalities in young diabetic patients, corneal and lens autofluorescence was measured by fluorophotometry in 30 eyes of 30 insulin-dependent diabetic patients without retinopathy. The lens [f(l)] and the corneal [f(c)] autofluorescence values in diabetic patients were significantly higher than in controls. In diabetic patients, f(l) was significantly correlated with the duration of diabetes, the f(c) was significantly correlated with the duration of diabetes and the indices of metabolic control, i.e. HbA1c and fructosamine. Our study demonstrated that young diabetic patients clearly had corneal and lens abnormalities before the appearance of overt diabetic retinopathy. The f(c) value might be a good indicator of metabolic control in diabetic patients.

Adolescent

Functional roles of phenylalanine(7) of thymic humoral factor-gamma 2 in the impaired blastogenic response of uremic T-lymphocytes.

The peptide analogs of thymic humoral factor-gamma 2 (THF-gamma 2) in which phenylalanine residue at the 7th position are replaced by phenylglycine (Phg), homophenylalanine (Hph), and 1-naphthylalanine (1-Nal) were synthesized by a solid-phase method and the immunological significance of the aromatic amino acid of this position was comparatively investigated. The in vitro restoring effect of the synthetic peptides on the impaired phytohemagglutinin (PHA) response of T-lymphocytes from uremic patients was tested. The observed activities of these peptides were in order (1-Nal7) thymic humoral factor [THF]-gamma 2 > 4-Fluoro (Phe7) THF-gamma 2 > THF-gamma 2. However, the other two analogs, [Phg7] THF-gamma 2 and [Hph7] THF-gamma 2, had no restoring effect even at a higher concentration.

Adjuvants, Immunologic

[Clinical analysis in patients undergoing extended resection of pT3 non-small cell lung cancer].

Among pT3 cases there contain various subgroups in terms of the organ which is involved in. We analyzed medical records of 85 consecutive patients who underwent extended surgery with diagnosis of pT3 excluding interlober invasion. As regards to the site of invasion, there are not significant differences in survival between pleural invasion, chest wall involvement, pericardial invasion, and diaphragmatic invasion. However, survival of patients who showed involvement of main bronchus seemed better than other groups. Survival of pT3 cases are in part determined by lymph node involvement, N0 group showed 36.0% 5 year survival rate whereas N1 group 20.0%, and there are no patient with N2 disease who survived 5 years. Among pleural and chest wall involvement group, N0 group showed 34.2% 5 year survival and there are no survival in N1 and N2 group. As regards to histologic subgroups, there are not significant differences between each group. Thus we conclude that in pT3 cases, N0 cases are the best candidate for surgical resection, and that adjuvant therapy is necessary for those with N1 or N2 involvement. Cases with bronchial extension should not be argued in the same field of locally invasive lung cancer because of better survival.

Adult

Changes in corneal and lens autofluorescence and blood glucose levels in diabetics: parameters of blood glucose control.

PURPOSE: We investigated corneal and lens autofluorescence in patients with proliferative diabetic retinopathy (PDR) to determine a correlation between the two parameters and blood glucose levels and HbA1c. METHODS: Corneal and lens autofluorescence levels in 17 PDR patients and 8 healthy controls were measured with a fluorophotometer fitted with an anterior segment adapter. We measured the lower blood glucose level (BS1), corneal autofluorescence (CA1), and lens autofluorescence (LA1) simultaneously and the higher blood glucose level (BS2), CA2, and LA2 simultaneously on the same day. We defined parameter changes as: delta BS = BS2 - BS1, delta CA = CA2 - CA1, and delta LA = LA2 - LA1. RESULTS: Corneal and lens autofluorescence significantly increased in the patients, compared with the controls (p < 0.001). Lens autofluorescence had a significant positive correlation with HbA1c (r = 0.656, p < 0.01) in the patients. delta CA (ngEq/ml) correlated significantly with delta BS (mg/dl) (r = 0.631, P < 0.01). CONCLUSIONS: Results suggest that lens autofluorescence might represent the long-term control of diabetes, and corneal autofluorescence levels may represent short-term changes in the blood glucose level, because hyperglycemia accelerates with increasing corneal autofluorescence in PDR patients. Corneal and lens autofluorescence may be related to the breakdown of the blood-aqueous barrier.

Adult

Effect of timolol and UF-021 (a prostaglandin-related compound) on pulsatile ocular blood flow in normal volunteers.

The effects of topically applied timolol (a nonselective beta-blocker) and UF-021 (a prostaglandin-related compound) on pulsatile ocular blood flow (POBF) were investigated in 9 healthy volunteers. One drop of either UF-021 or timolol was instilled in one randomly selected eye and the fellow eye received physiologic saline. Before and 90 min after drop instillation, we measured intraocular pressure (IOP), POBF, heart rate (HR) and blood pressure (BP). After a washout interval of at least 1 week, the other drug was instilled in the previously treated eye. IOP, POBF, HR, and PB were measured following the same protocol. After timolol administration, IOP and POBF decreased significantly in the treated eye (26%, p = 0.01, and 13%, p = 0.02, respectively) and in the fellow eye (11%, p = 0.01, and 11%, p = 0.03, respectively). HR also decreased (10%, p = 0.03), but BP did not change significantly. After UF-021 administration, no significant changes were found in IOP, POBF, HR, or BP. Our results suggest that in normal subjects timolol decreases POBF in both the treated and the untreated eyes, whereas UF-021 has no action on either IOP or POBF.

Administration, Topical

[Early ocular changes in a tree shrew model of diabetes].

We developed a tree shrew model of diabetes using streptozotocin (STZ), and studied early ocular changes of diabetes (after one week of diabetes) by fluorophotometry. STZ was injected intraperitoneally at doses of sixty to 400 mg/kg body weight. Animals injected with more than 300 mg/kg of STZ developed diabetes. Corneal autofluorescence was significantly increased one week after STZ injection. These changes may be related to impairment of the ocular homeostatic mechanisms due to the onset of diabetes. Using this model, we might be able to obtain diabetic ocular impairment data closer to human data than in previous models of diabetes, because tree shrews are primates.

Animals

Syntheses and immunological effects of thymic humoral factor-gamma 2 and its Phe7-substituted analogues.

Thymic humoral factor-gamma 2 and five analogues modified at position 7 with various phenylalanine derivatives were synthesized by a solid-phase method. The synthetic peptides were tested for their effects on the impaired blastogenic response of phytohemagglutinin-stimulated T lymphocytes of uremic patients with infectious diseases. The synthetic thymic humoral factor-gamma 2 enhanced the blastogenic response of T lymphocytes in the blood of the 2 patients tested. Of the synthetic peptides, [Phe(4F)7]thymic humoral factor-gamma 2 exhibited the most potent effect.

Amino Acid Sequence

Lenticular autofluorescence in normal tree shrews.

Lenticular autofluorescence was measured in vivo in 25 normal tree shrews using a fluorophotometer with a specially designed small animal adapter to assess the usefulness of this model of lens pathology. The average variability in the lenticular autofluorescence measurements was 8.7%. The average ratio between lenticular autofluorescence of the left eye and that of the right eye was 0.99 +/- 0.13 SD. There was a strong correlation between age and mean lenticular autofluorescence in both eyes (correlation coefficient, 0.988; p < 0.001). The calculated annual increase in lenticular autofluorescence was 23.7 ngEq/ml. This method of measurement is reliable, and lenticular autofluorescence in tree shrews varies little among animals other than a variation caused by aging. Moreover, the tree shrew, which is believed to be a primate, is small and easy to breed. This could be a useful animal model to study various lens pathologies in humans.

Aging

[Fluorophotometry of the animal eye].

We assessed the usefulness of the Fluorotron Master fitted with a small animal adapter. We also discuss the measurement conditions for the tupai, which is a promising experimental mammal. A good concentration for measurements with this instrument ranged from 0.5 x 10(-6) to 1.0 x 10(-6) g/ml. A suitable time for fluorophotometry of the tupai was 30 min. after injection of fluorescein-Na, and a suitable dose of the fluorescein-Na was 2 mg/kg. We could do ultrafiltration for measurement of the protein unbound fluorescein concentration from a minimal sample of the blood using a hematocrit tube, and thus could reduce the deleterious effects of blood sampling on the animal. This instrument is useful for the estimation of the blood-ocular barrier permeability of animal models.

Animals

Fluorophotometry with a small animal adapter.

The usefulness of the Fluorotron Master fluorophotometer fitted with a small animal adapter was evaluated with tree shrews. We also determined that the optimal measurement parameters for these animals, which are regarded as promising for experimental use in ophthalmic research, are: fluorescein-Na concentration, 0.5 x 10(-9) to 1.0 x 10(-6) g/mL; fluorescein-Na dosage, 2 mg/kg; measurement time, 30 minutes after injection of fluorescein-Na into the ocular compartments. Results indicated that ultrafiltration for the measurement of protein-unbound fluorescein can be done with a hematocrit tube and a minimal blood sample, thereby reducing the impact of the sampling on the animal's general condition. The Fluorotron Master with the small animal adapter can offer advantages in estimating the blood-ocular barrier permeability using disease models in tree shrews.

Animals

Synthesis of [Phe(4F)3]thymopoietin II and examination of its immunological effect on the impaired blastogenic response of T-lymphocytes of uremic patients.

[Phe(4F)3]thymopoietin II was synthesized using a conventional solution method. The deprotection of the protected [Phe(4F)3]thymopoetin II was achieved by treatment with 1 M trifluoromethanesulfonic acid:thioanisole (molar ratio 1:1) in trifluoroacetic acid in the presence of dimethylselenide and m-cresol. The synthetic f1p4(4F)3]thymopoietin II and thymopoietin II were tested for effect on impaired T-lymphocyte transformation by phytohemagglutinin in uremic patients suffering from recurrent infectious diseases. The restoring activity on the impaired phytohemagglutinin stimulation of T-lymphocytes was obtained after incubation of peripheral lymphocytes isolated from uremic patients with the synthetic [Phe(4F)3]thymopoietin II. This peptide exhibited far stronger restoring effect than that of our synthetic thymopoietin II.

Amino Acid Sequence

Synthesis of an immunologically active analog of thymic humoral factor-gamma 2 with enhanced enzymatic stability.

Acetyl-thymic humoral factor-gamma 2 chloromethyl ketone [Ac-Leu-Glu-Asp-Gly-Pro-Lys-Phe-Leu-CH2Cl], an analog of thymic humoral factor-gamma 2, was synthesized and studied for its immunological effects on the impaired blastogenic response of T-lymphocytes isolated from uremic patients. Synthetic thymic humoral factor-gamma 2 and the synthetic acetyl-thymic humoral factor-gamma 2 chloromethyl ketone both restored the impaired blastogenic response of T-lymphocytes of uremic patients. However, the synthetic thymic humoral factor-gamma 2 is susceptible to proteolytic digestion. On the other hand, the synthetic acetylthymic humoral factor-gamma 2 chloromethyl ketone retained activity and was shown to exhibit a high degree of stability when incubated in human serum, These results indicate that N-terminal acetylation and the introduction of a chloromethyl ketone residue into the C-terminal residue of thymic humoral factor-gamma 2 increase resistance to proteolytic degradation by exopeptidases without loss of immunological activity.

Acetylation

Syntheses and immunological effects of thymic humoral factor-gamma 2 and its Phe7-substituted analogues.

Thymic humoral factor-gamma 2 and five analogues modified at position 7 with various phenylalanine derivatives were synthesized by a solid-phase method. The synthetic peptides were tested for their effects on the impaired blastogenic response of phytohaemagglutin-stimulated T-lymphocytes of uraemic patients with infectious diseases. The synthetic thymic humoral factor-gamma 2 enhanced the blastogenic response of T-lymphocytes in the blood of the two patients tested. Of the synthetic peptides, [4-fluoro-Phe7]thymic humoral factor-gamma 2 exhibited the most potent effect.

Amino Acid Sequence

Synthesis of prothymosin alpha deduced from nucleotide sequence of the murine cDNA and its effect on the impaired T lymphocytes of uremic patients.

The complete murine prothymosin alpha molecule (110 residues) except for the N-terminal methionine deduced from the cloned cDNA has been synthesized by a solid-phase method. Peptide synthesis was performed manually by the stepwise solid-phase method using the base-labile Fmoc group for protecting the alpha-amino group. The peptide was assembled on a p-alkoxybenzyl alcohol resin. After the last coupling step, the Fmoc group was removed with 50% piperidine in DMF. The peptide resin was treated with thioanisole-o-cresol in TFA, and then purified by gel filtration, ion-exchange column chromatography and high-performance liquid chromatography. A 2.9-mg sample of a highly purified peptide was finally obtained. The overall yield of the synthesis was less than 1%, based on the amino acid content of the starting Fmoc-Asp (OtBu)-resin. The synthetic peptide was found to have a restoring activity on low-E-rosette-forming lymphocytes after incubation of peripheral blood from uremic patients with the synthetic peptide. This peptide exhibited far stronger restoring effect than that of our synthetic thymosin alpha 1.

Amino Acid Sequence

Synthesis of deacetyl-thymosin beta 12 and examination of its immunological effects on the impaired T and B lymphocytes in uremic patients.

Deacetyl-thymosin beta 12 was synthesized in a conventional manner by assembling six peptide fragments followed by deprotection with 1 M trifluoromethanesulfonic acid-thioanisole (molar ratio, 1:1) in trifluoroacetic acid in the presence of m-cresol and dimethyl-selenium. Incubation of peripheral lymphocytes isolated from uremic patients with the synthetic deacetyl-thymosin beta 12 showed an enhancing effect on the reduced beta lymphocytes but had no restoring effect on the impaired blastogenic response of T lymphocytes.

Amino Acid Sequence