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[Combined pars plana vitrectomy, lens removal and intraocular lens implantation for complications of diabetic retinopathy. Surgical results in 120 cases].

We performed combined vitrectomy, lens removal and posterior chamber intraocular lens implantation for proliferative diabetic retinopathy in 120 eyes of 101 patients. Follow-up periods ranged from 3 to 63 months, with a mean of 17 months. Three lens removal methods were used: extracapsular cataract extraction (14 eyes), phacoemulsification and aspiration (49 eyes), and pars plana phacoemulsification (57 eyes). Preoperative rubeosis iridis or neovascular glaucoma was found in 21 eyes. Gas or temporary silicone oil tamponade was employed in 32 eyes. Surgical results were good, and the postoperative vision was finger counts or below only in 13 eyes. Thus the combined surgery proved to have no serious problems. Our results indicate two important points. (1) It is best to chose either of the following two methods for the lens surgery: phacoemulsification with continuous circular capsulorhexis, self sealing sclerocorneal incision, and in-the-bag fixation of the posterior chamber lens, or pars plana phacoemulsification leaving the anterior capsule, rub off and aspirating the lens epithelial cells, continuous circular capsulorhexis, and posterior chamber lens implantation in front of the anterior capsule from a self-sealing sclerocorneal wound. (2) It is mandatory to do complete vitrectomy and cut out the vitreous gels incarcerated in the sclerotomy site.

Adult↗

Direct measurement of phagolysosomal esterase activity.

A new method of directly measuring esterase activity within phagolysosomes has been developed. Decanoyl fluorescein- binding microspheres were prepared and phagocytosed by human peripheral neutrophils. Within phagolysosomes lysosomal esterase hydrolyzed decanoyl fluorescein on the microspheres, causing the conversion of decanoyl fluorescein- binding microspheres (non-fluorescent) into fluorescein- binding microspheres (fluorescent). The activity of phagolysosomal esterase in intact neutrophils was assayed by the measurement of the fluorescence intensity without rupturing cells. By use of a flow cytometer, esterase activity within phagolysosomes in single cells was measured.

Esterases↗

The CDKN2 gene alterations in various types of adult T-cell leukaemia.

The CDKN2 gene, encoding the cyclin-dependent kinase-4 inhibitor p16, is a putative tumour-suppressor gene because it is frequently altered in many malignant tumours. We analysed the CDKN2 gene in 44 cases of adult T-cell leukaemia (ATL) by Southern blot analysis, polymerase chain reaction-mediated single-strand conformation polymorphism (PCR-SSCP) analysis, and direct sequencing. Southern blot analysis detected a homozygous deletion of the CDKN2 gene in 5/44 patients (11.4%). Mutational analysis by the PCR-SSCP method and direct sequencing showed one nonsense mutation at codon 72 (nucleotide 232), and two missense mutations at codon 43 (nucleotide 146) and codon 97 (nucleotide 309, 3/44, 6.8%). Therefore we found changes in the CDKN2 gene, including point mutations, in 18.2% of the patients with ATL. Interestingly, most of these patients had acute type ATL. Our results suggest that the CDKN2 gene is inactivated not only by homozygous deletion but also by point mutation, and these alterations contribute to the aggressiveness of ATL.

Adult↗

Successful treatment of partial nephrogenic diabetes insipidus with thiazide and desmopressin.

OBJECTIVE: To clarify whether combination treatment with desmopressin (DDAVP) and thiazide was clinically effective in a patient with congenital nephrogenic diabetes insipidus (CNDI), we evaluated the treatment in a 7-year-old boy with CNDI who had demonstrated a partial response to DDAVP. METHOD: Both volume of urine and the presence of nocturia were determined during treatment. RESULT: Neither the usual therapy of a low-salt diet and a thiazide nor intranasal therapy with a large dose of DDAVP was effective. However, combination treatment resulted in a decrease in urinary volume and the disappearance of nocturia. CONCLUSION: DDAVP coupled with thiazide may be useful for CNDI in patients who have shown a partial response to DDAVP.

Deamino Arginine Vasopressin↗

[FDG-PET on the day after first chemotherapy in malignant lymphoma].

Positron emission tomography using 18F-fluorodeoxyglucose (FDG-PE) was performed in four patients with non-Hodgkin's lymphoma on the day after initial chemotherapy, in an attempt to predict the effects of chemotherapy earlier than standard methods. Twelve regions displaying intense uptake on baseline FDG-PET were selected, and decreases in the rate for each region were calculated from standardized uptake values on the day following chemotherapy. Seven of the 12 regions demonstrated decrease rates of 60% or more, and two decreased by 100%. This study indicates that FDG-PET on the day after first chemotherapy seems to reflect the effect of chemotherapy on malignant lymphoma.

Aged↗

Preparation and evaluation of Eudragit gels. VIII. Rectal absorption of 5-fluorouracil from Eudispert hv gels in rats.

Rectal absorption of the hydrophilic 5-fluorouracil (5-FU) in rats was studied with Eudispert hv gels with or without fatty acids as the rectal bases. In the absence of fatty acids, absolute bioavailabilities of 5-FU for Eudispert hv hydrogel and xerogel preparations increased approximately 2.5 times compared with those of Witepsol H-15 and PEG 2000 suppositories. When n-capric acid or linolenic acid was used as an absorption enhancer, absolute bioavailabilities of 5-FU were, respectively, 25.5 and 30.9% for Witepsol H-15 and 64.4 and 66.1% for PEG 2000. Furthermore, the absolute bioavailabilities of 5-FU for Eudispert hv hydrogel with n-capric acid or linolenic acid were 95.6% and 81.7%. The addition of capric acid or linolenic acid to the hydrogel was a useful method for increasing 5-FU permeability through the rectal membranes. These results are consistent with the observation that the total amounts of 5-FU remaining in the lumenal contents of the rectum and that accumulated in the rectal tissue decreased in relation to the increase in the bioavailabilities. Thus, the Eudispert hv hydrogel containing 5-FU with capric acid may be a useful rectal preparation for increasing the maximum plasma level and improving the absolute bioavailability of 5-FU.

Acrylic Resins↗

A patient with primary gastric choriocarcinoma who received a correct preoperative diagnosis and achieved prolonged survival.

Primary choriocarcinoma of the stomach is an extremely rare and highly malignant tumor. A 68-year-old Japanese man was admitted to our department with symptoms of epigastric pain, abdominal fullness, and dizziness. Primary gastric choriocarcinoma with regional lymph node metastases was diagnosed preoperatively by the detection of elevated serum levels of a tumor marker, radiography, and immunohistochemical staining of biopsy specimens. The patient underwent total gastrectomy and jejunal reconstruction (Roux-en-Y method), followed by chemotherapy. Histological examination of the resected stomach revealed typical choriocarcinoma accompanied by common adenocarcinomatous elements. After postoperative chemotherapy the patient survived for 4 years and 6 months, and died with no evidence of recurrence of carcinoma. This is the first known patient with primary gastric choriocarcinoma to have survived for such a long period without recurrent elevation of the serum level of human chorionic gonadotropin (HCG), which was a useful marker when reevaluating the patient.

Adult↗

Marked increase in ascorbate oxidase protein in pumpkin callus by adding copper.

Ascorbate oxidase from pumpkin (Cucurbita sp.) was purified from a commercially available preparation. A single polypeptide band with M(r) 64,000 was detected after sodium dodecylsulfate-polyacrylamide gel electrophoresis of the purified enzyme. In double immunodiffusion tests, antiserum against the purified preparation formed a single precipitin line with the crude extract from pumpkin fruit tissue or the callus as well as with the purified preparation. Immunological blotting method showed that mol wt of ascorbate oxidase subunit in pumpkin callus was the same as that of the purified preparation. Analysis with the single radial immunodiffusion method showed that the increase in ascorbate oxidase activity during the growth of pumpkin callus correlated with an increase in the enzyme protein. Furthermore, enzyme protein in the callus grown in the presence of 10 micromolar CuSO(4) for 2 weeks was about eight times that grown in the presence of 0.1 micromolar CuSO(4). The synthesis of ascorbate oxidase in pumpkin callus may be induced by copper, a prosthetic metal of the enzyme, or copper may help stabilize the enzyme against proteolytic breakdown.

Journal Article↗

Total assignment of the (1)H- and (13)C-NMR spectra for TZT-1027 and related compounds.

The total assignment of the (1)H- and (13)C-NMR spectra for TZT-1027 was carried out using various NMR methods (1D, 2D NMR). It was found that TZT-1027 exists in two different conformations resulting from the cis-trans isomerization of the amide bond at N-11 and C-12 in DMSO-d(6). The (1)H- and (13)C-NMR spectra of compound 1 and 2 comprised of the partial structure of TZT-1027 were also assigned to be TZT-1027. These assignments showed that compound 1 is in good agreement with TZT-1027 with regard to formation of the conformers.

Antineoplastic Agents↗

Effects of somatostatin and serotonin on calcitonin secretion from cultured rat parafollicular cells.

A primary culture of mammalian parafollicular cells was established from rat thyroid glands in order to investigate the effects of serotonin and somatostatin on calcitonin secretion. Minced rat thyroid glands were dissociated with collagenase and cultured in a Ham's F-12K medium supplemented with calf serum (5%), insulin (1.3 X 10(-6) mol/l), hydrocortisone (10(-8) mol/l), transferrin (6.1 X 10(-9) mol/l), and glycyl-L-histidyl-L-lysin (2.5 X 10(-8) mol/l). Immunohistochemical peroxidase-antiperoxidase method revealed that the cultured parafollicular cells were immunopositive for human calcitonin, and electron microscopy demonstrated the existence of dense secretory granules in the cultured parafollicular cells. Addition of the Ca2+ to the culture medium stimulated calcitonin secretion from the cells dose-dependently as measured by radioimmunoassay. Pre-incubation of serotonin with the cells produced higher calcitonin levels in a dose-dependent manner. On the other hand, pre-incubation of somatostatin with the cells significantly inhibited calcitonin secretion.

Animals↗

[Increased production of nitric oxide in the immediate and late asthmatic responses in guinea pigs].

The nitric oxide (NO) levels in exhaled air and the population of nitric oxide synthase (NOS) synthesizing epithelium in airways are reported to be increased in patients with asthma. NO may be implicated in the pathophysiology of asthma. In this study, we examined the inducible NOS (iNOS) mRNA levels in the lung of a guinea pig model of experimental asthma which exhibits both the immediate and late asthmatic responses (IAR/LAR), following challenge with antigen, using the methods of Northern blot analysis. After challenge with antigen, iNOS mRNA were increased in a time-dependent manner (before challenged < IAR < LAR). Furthermore, we estimated NO productions in the trachea using bioassay by 5-HT-induced tracheal smooth muscle relaxation which are involved in NO. The 5-HT-induced relaxations were accelerated in a time-dependent manner after challenge with antigen, reflecting increased NO production (before challenged < IAR < LAR). These observations suggest that NO would be involved in the pathophysiology of asthma.

Animals↗

Identification of volatile selenium compounds produced in the hydride generation system from organoselenium compounds.

We report a novel aqueous derivatization of selenomethionine (Semet), selenoethionine (Seet) and trimethylselenonium ion (TmSe) by NaBH4 and HCI to volatile selenium species, namely, diethyldiselenide (DeDSe), dimethyldiselenide (DMDSe), dimethylselenide (DmSe) and ethylhydrogenselenide (ESeH), in the hydride generation (HG) system. The volatile selenium compounds produced in the HG system were on-line trapped and concentrated in a U-tube that was immersed in the liquid nitrogen trap. The trapped volatile Se compounds were volatilized at 80 degrees C in a water bath, and 50-500 microL of volatile gas was injected into the GC/AED and GC/MS, respectively. It has been established that DmSe, DmDSe, and DeDSe are the predominant Se compounds that are produced in the HG system from TmSe, Semet, and Seet, respectively, followed by ESeH from Seet. Analytical methods previously employed have stated that these compounds are inactive in the HG system. Prior decomposition of Semet, Seet, and TmSe to selenous acid is essential before HG. To the best of our knowledge, current findings for the production and identification of volatile selenium compounds in the HG system are new and different from existing reports; hence, direct estimation of Semet, Seet, and TmSe is possible when coupling with a HG system using a suitable Se-specific detector.

Journal Article↗

Immunohistochemical localization of atrial natriuretic peptide receptor in bovine kidney and lung.

Receptors for atrial natriuretic peptide (ANP) were localized in the alveoli and bronchiolar smooth muscle cells of bovine lung and in podocytes of the kidney by immunofluorescence and immunoperoxidase methods. Two specific antisera were raised against the ANP receptor purified from bovine lung plasma membranes: anti-Rc 140 and anti-Rc 70. Anti-Rc 140 was raised against the 140 KD native receptor having a homodimeric structure, and anti-Rc 70 was elicited by immunizing a rabbit with the 70 KD reduced subunits. Essentially identical staining patterns were obtained with both antisera. Identification of ANP receptor sites would provide useful information in understanding the pulmonary and renal actions of ANP.

Animals↗

[Anti-Candida activities of azole antifungals in the presence of lysozyme in vitro].

The combined effects of lysozyme and various antifungal agents were investigated by microbroth dilution method against Candida albicans in vitro. Synergistic anti-Candida activity was observed between egg white lysozyme and itraconazole, clotrimazole, miconazole and lanoconazole. Similar, although not as clear, combination anti-Candida activities were seen in the cases of ketoconazole, bifonazole, amphotericin B and nystatin. Anti-Candida activity of fluconazole was not affected by the addition of lysozyme, however. Physiological roles of this combination effect in anti-Candida therapy by azole antifungals were discussed.

Anti-Infective Agents↗

[Studies on the in vitro antifungal activity of lanoconazole, a new topical antimycotic, against Trichophyton spp].

In vitro studies with a new imidazole antifungal agent lanoconazole (LCZ) were carried out to confirm its fungicidal property of the anti-dermatophytic activity and unlikeliness of dermatophytes to acquire secondary resistance to this drug. Minimal cidal concentration (MCC) values of LCZ against 6 strains each of Trichophyton mentagrophytes and T. rubrum determined by the cellophane membrane method were in a range of 0.063 to 0.5 micrograms/ml, and much lower than those of bifonazole (16-32 micrograms/ml). The LCZ-sensitivity of both of the two testing strains of T. mentagrophytes did not decrease to less than one-fourth of the initial level during 15 subcultures on LCZ-containing agar. These results suggest that LCZ potently inhibits dermatophytes in a fungicidal manner and that secondary resistance to LCZ is not easily developed in the dermatophytes tested.

Administration, Topical↗

In vitro inhibition of recombinant ligand-gated ion channels by high concentrations of milnacipran.

RATIONALE: Tricyclic antidepressants are known to inhibit various ligand-gated ion-channel (LGIC) receptors, and some of their clinical features may be associated with this activity. The effects of milnacipran, a selective inhibitor of the reuptake of serotonin and noradrenaline, on LGIC receptors have not yet been investigated on such ion-channel receptors. OBJECTIVES: To determine the in vitro effect of milnacipran on four recombinant LGIC receptors, nicotinic acetylcholine, N-methyl-D-aspartate, gamma-amino butyric acid (GABA) and 5-hydroxytryptamine3A receptors. METHODS: Receptors were expressed in Xenopus oocytes and LGIC activity measured using a two-voltage clamp technique. RESULTS: There was no interaction at the GABA receptor. The results at the other LGIC receptors showed that they could be inhibited by high concentrations of milnacipran. CONCLUSIONS: At high concentrations, milnacipran can inhibit certain LGICs. It is, however, unlikely that these interactions have any clinical consequence under normal therapeutic conditions, since the concentrations required are considerably higher than those achieved in plasma of treated patients.

Animals↗

The effects of a point mutation of the beta2 subunit of GABA(A) receptor on direct and modulatory actions of general anesthetics.

The gamma-aminobutyric acid type A receptor (GABA(A) receptor) sites involved in the direct and modulatory actions of general anesthetics remain to be elucidated. The mutation of tyrosine at position 157 in the beta2 GABA(A) receptor subunit was reported to reduce sensitivity to activation by GABA, but not pentobarbital. We examined whether this mutation of the beta2 subunit (Tyr157-->Phe) affects the direct and modulatory actions of other general anesthetics such as propofol and etomidate. Using the two-electrode voltage clamp method, we recorded Cl- current in Xenopus oocytes expressing alpha1beta2gamma2s and alpha1-mutated beta2gamma2s subunits. The mutation of the beta2 subunit reduced the apparent affinity for propofol. However, the mutation had no effect on both the direct actions of pentobarbital and etomidate or on the modulatory actions of pentobarbital, propofol and etomidate. These results suggest that unique loci may exist for the direct action of propofol and that the GABA binding site may not mediate the modulatory actions of general anesthetics at GABA(A) receptors.

Amino Acid Substitution↗

Dual synchronization of chaos in Colpitts electronic oscillators and its applications for communications.

We demonstrate the dual synchronization of chaos in two pairs of one-way coupled Colpitts electronic oscillators by both experiment and numerical simulation. We use the cross coupling method, where the difference in voltage between the sum of two master oscillators and one slave oscillator is injected into the other slave oscillator as an electrical current, for dual synchronization of chaos. We have investigated the regions for achieving dual synchronization of chaos when one of the internal parameters is mismatched between the master and slave oscillators. We numerically obtain a similar curve for the accuracy of synchronization to that obtained from our experiments. A communication scheme using dual synchronization of chaos is also proposed and demonstrated.

Journal Article↗