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Biomedical subjects

T Abiko

Publications and source records attributed to T Abiko.

At least 37 records · Page 2Linked to original sources

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↗

Solid-phase syntheses of two deacetyl-thymosin alpha 1 analogues with substitution at position 21 and their effects on low E-rosette-forming lymphocytes of uremic patients.

Two deacetyl-thymosin alpha 1 analogues containing Phe or Phe(4F) at position 21 were synthesized by the manual solid-phase method and their immunological effects on the low E-rosette-forming lymphocytes of uremic patients were studied. Fluorination of the p-position of Phe21 resulted in a marked restorative effect on the low E-rosette-forming lymphocytes of uremic patients compared with that of [Phe21]deacetyl-thymosin alpha 1. The synthetic [Phe21]deacetyl-thymosin alpha 1 was approximately equal in potency to our synthetic deacetyl-thymosin alpha 1 in uremic patients.

Amino Acid Sequence↗

Synthesis of rat parathymosin alpha fragment 1-28 and examination of its inhibitory activity towards the restoring activity of thymosin alpha 1 on the impaired T-lymphocytes of uremic patients.

A fragment corresponding to N-terminal octaeicosapeptide of rat parathymosin alpha was synthesized by assembling 5 peptide fragments, followed by deprotection with 1 M trifluoromethanesulfonic acid-thioanisole (molar ratio 1:1) in trifluoroacetic acid in the presence of dimethylselenium. Incubation of impaired T-lymphocytes isolated from uremic patients with the synthetic parathymosin alpha fragment 1-28 showed no immunological restoring effect, but when it was administered together with thymosin alpha 1, it appeared to suppress the restoring effect of the thymosin alpha 1 on the impaired T-lymphocytes of uremic patients.

Amino Acid Sequence↗

Synthesis of an immunologically active fragment analog of prothymosin alpha with enhanced enzymatic stability.

A fragment analog, [D-Arg30]prothymosin alpha fragment 1-30, containing D-arginine in place of arginine residue at position 30 was synthesized by the liquid phase procedure and studied for immunological effect on the impaired blastogenic response of T-lymphocytes isolated from uremic patients after treatment of human serum. Deacetyl-thymosin alpha 1, a synthetic octaeicosapeptide corresponding to deacetyl-prothymosin alpha fragment 1-28, has restoration ability for the impaired blastogenic response of T-lymphocytes of uremic patients but is susceptible to proteolytic digestion. On the other hand, the fragment analog, [D-Arg30]prothymosin alpha fragment 1-30 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 D-residue into the C-terminal residue of prothymosin alpha fragment 1-30 increase resistance to proteolytic degradation by exopeptidases.

Amino Acid Sequence↗

Solid-phase synthesis of biologically active fragment 29-111 of rat prothymosin alpha.

Rat prothymosin alpha fragment 29-111, an 83-residue polypeptide corresponding to desthymosin alpha 1-prothymosin alpha, has been synthesized by a solid-phase method. Hydrogen fluoride was used to deprotect and cleave the peptide from the resin. The crude product was purified by gel-filtration, ion-exchange chromatography and high-performance liquid chromatography. A 3.2-mg sample of a ca. 96% pure peptide was finally obtained. The overall yield of the synthesis was less than 1%. An increase of E-rosette-forming lymphocytes was obtained after incubation of peripheral blood from uremic patients with the synthetic prothymosin alpha fragment 29-111. The restoring effect of the synthetic prothymosin alpha fragment 29-111 was greater than that of our synthetic thymosin alpha 1.

Amino Acid Sequence↗

Arterial injury-induced smooth muscle cell proliferation in rats is accompanied by increase in polyamine synthesis and level.

Proliferation of smooth muscle cells (SMC), enhancement of polyamine biosynthesis and increase in polyamine level in response to deendothelialization in the rat aorta were studied. [3H]Thymidine incorporation into SMC in aortas denuded with a balloon catheter began 25 h after injury, and maximal incorporation occurred 33-37 h after injury. Afterwards, [3H]thymidine incorporation declined, approaching the baseline level, but was slightly higher than that of sham-operated controls until 14 days after injury. Intimal thickening started 7 days after injury, and peaked at 21 days. Prior to these proliferative changes in aortic SMC, a rapid and transient increase in ornithine decarboxylase (ODC) activity was observed within 8 h after injury. There was no significant difference in ODC activity between injured and intact aortas after 4 days. The levels of polyamines, putrescine, spermidine, and spermine increased and were maximal at 48 h after injury, 8.1, 3.4 and 1.4 times the control levels, respectively. Increased levels of polyamines, in particular spermidine, continued until 7 days after injury. These results suggest that the enhancement of polyamine synthesis and the increased polyamine content of the aorta play important roles in the proliferation of SMC and in the development of intimal thickening, particularly in the initial proliferative response of medial SMC after deendothelialization.

Animals↗