To clarify whether apoptosis is involved in doxorubicin (DXR)-induced testicular toxicity and to identify the target germ cell type, adult Sprague-Dawley rats were treated with a single intravenous dose of DXR (8 or 12 mg/kg) and euthanized at 3, 6, 12, 24, and 48 h subsequently. Histologically, germ cell degeneration was first found 6 h after dosing in meiotically dividing spermatocytes and early round spermatids of seminiferous tubules at stage 1, and subsequently observed in spermatogonia at stages I-VI showing ultrastructural characteristics of apoptosis. Coincident with the appearance of morphological changes, degenerating germ cells were shown to be undergoing apoptosis as revealed by in situ terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). The frequency of TUNEL-labeled germ cells increased in a stage- and cell type-specific manner, the peak of frequency gradually progressing from stage I of seminiferous tubules to later stages with time after dosing, suggesting that the damaged germ cells, especially spermatogonia, gradually underwent the processes leading to apoptosis. DNA laddering on gel electrophoresis was apparent 24 and 48 h after dosing. The results demonstrate that apoptosis plays an important role in the induction of testicular toxicity caused by DXR with meiotically dividing spermatocytes and type A and intermediate spermatogonia as highly vulnerable target cells.

Animals↗

PubMedDate not supplied

A new method for quantification of metamorphopsia in patients with epiretinal membrane.

PURPOSE: A new method for quantification of metamorphopsia was applied to study distorted vision in patients with epiretinal membrane. METHOD: Sixty-three patients with unilateral epiretinal membrane in the macula were examined. A modified Amsler chart (a grid of black lines on a white background measuring 12 x 12 cm with grid squares of 2 x 2 cm) was prepared. If patients saw any of the grid lines as irregular or curved, they were asked to trace these on the chart. The length of all lines drawn by the patients was measured, except those on the outer border. The length of the grid is 1200 mm, but it should be drawn longer by patients with metamorphopsia. The severity of metamorphopsia was also scored subjectively and the relationship of grid length to the subjective score and the visual acuity was analyzed. RESULTS: The grid length ranged from 1200 to 1259 mm (mean = 1223.3 mm) and was correlated significantly with the subjective score (P <.01, rho =.387). CONCLUSION: This method might be applicable for evaluating the severity of metamorphopsia and the surgical outcome in patients with epiretinal membrane.

Aged↗

PubMedDate not supplied

Comparison of scleral buckling and vitrectomy for retinal detachment resulting from flap tears in superior quadrants.

PURPOSE: To compare the surgical results of vitrectomy and scleral buckling for uncomplicated superior retinal detachment caused by flap tears. METHODS: Included in the study were 225 patients (225 phakic eyes) undergoing primary surgery by three surgeons between January 1990 and December 1996 for superior retinal detachment caused by flap tears (138 eyes by scleral buckling, 87 eyes by vitrectomy); all patients had been followed up for longer than 6 months after surgery. The choice of one of the two procedures was based on each surgeon's preference. The surgical outcome and the rate of complications were retrospectively compared between the two groups of eyes. RESULTS: Initial and final anatomical success rate were 92% and 100% after each procedure. Retinal redetachment after the initial procedure was due to new retinal breaks in 5 eyes, reopening of original breaks in 2 eyes of vitrectomy cases, and due to malpositioned buckle in 11 eyes of scleral buckling cases. Proliferative vitreoretinopathy occurred in 3 eyes of vitrectomy cases. CONCLUSION: Primary vitrectomy was as successful as scleral buckling for treating superior rhegmatogenous retinal detachment. Even though the high incidence of postoperative cataract formation was the major drawback, vitrectomy had some advantages over scleral buckling.

Adult↗

PubMedDate not supplied

Posterior synechia of the iris after combined pars plana vitrectomy, phacoemulsification, and intraocular lens implantation.

PURPOSE: Combined pars plana vitrectomy, phacoemulsification, and intraocular lens implantation has become a widely accepted treatment for cataracts in patients with vitreoretinal diseases. We examined factors influencing the development of posterior synechia after this triple procedure. METHODS: One hundred and three patients (107 eyes) were evaluated. The frequency of postoperative posterior synechia, the preoperative diagnosis, whether gas tamponade was used, and the type of lens implanted were reviewed. RESULTS: Twenty-one eyes (19.6%) developed posterior synechia, and the highest rate (12/39 eyes, 30.8%) was in patients with proliferative diabetic retinopathy. Posterior synechia was more frequent after gas tamponade (28.1%) than in eyes without tamponade (10.1%). In proliferative diabetic retinopathy (PDR) patients, fibrin deposition and the amount of retinal photocoagulation were causative factors for posterior synechia. CONCLUSIONS: Factors promoting postoperative synechia after the triple procedure included (1) the existence of PDR, (2) expanding gas tamponade, (3) fibrin deposition in PDR, and (4) the amount of photocoagulation in PDR.

Adult↗

PubMedDate not supplied

Hepatic alpha(2u)-globulin mRNA levels and diethylstilbestrol-associated testicular atrophy in rats.

Biosynthesis of alpha(2u)-Globulin (alpha(2u)-g) is under multihormonal regulation. In this study, we investigated histopathologic changes in the testis and hepatic alpha(2u)-g messenger ribonucleic acid (mRNA) levels in male rats after administration of the potent estrogen diethylstilbestrol (DES) at 0. 01, 0.1, or 1 mg/kg/day by gavage for 14 days. DES treatment decreased hepatic alpha(2u)-g mRNA levels in a dose-dependent manner accompanied by atrophic histopathologic changes in the testis. In addition, alpha(2u)-g mRNA levels were lowest in animals with the most marked testicular changes. Hepatic alpha(2u)-g mRNA may be a useful biomarker for the evaluation of endocrine disruption in male rats.

Alpha-Globulins↗

PubMedDate not supplied

Combination of a teratoma and embryonal carcinoma of the testis in SD IGS rats: a report of two cases.

Testicular tumors of germ cell origin are extremely rare in rats. We encountered 2 cases of teratoma and embryonal carcinoma in the testes of 8- and 10-week-old Sprague-Dawley IGS rats. A unilateral tumor mass with bilateral testicular atrophy was observed macroscopically in both cases. Microscopic examination revealed that the tumor mass had characteristic features of a teratoma and was composed of several types of differentiated cells and tissues at various stages of maturation. Embryonal carcinoma tissue, composed of undifferentiated cells with an embryonic and anaplastic appearance, was observed within the tumor mass. In addition, foci of intratubular teratomas and embryonal carcinomas were observed in the testis on the side without any obvious mass. No obvious germ cells were observed in the seminiferous tubules in the remnant nontumorous area. Furthermore, intratubular transition of cells was observed from the embryonal carcinoma tissue to the squamous epithelium. This finding indicates that an embryonal carcinoma differentiates toward a teratoma even at a very early stage of development of the germ cell tumor.

Animals↗

PubMedDate not supplied

A new technique for separation of posterior vitreous in vitreous surgery.

To describe a new and effective technique, hydroseparation, for use in detaching the posterior cortical vitreous from the retina by the simple injection of fluid into the subhyaloid space. This technique was used in 7 eyes of 6 patients with diabetic retinopathy who had limited posterior vitreous detachment. Following core vitrectomy, a 32 gauge cannula was inserted into the subhyaloid space and a balanced salt solution (BSS) was injected. The injected fluid spread easily to the periphery, causing the vitreous cortex to be smoothly separated, except for areas with firm vitreoretinal adhesion. In those areas, we also used microscissors to separate the tissue. No iatrogenic retinal break occurred in any case. This simple technique, which exerts minimal traction force on the retina, was safe and useful for inducing posterior vitreous detachment in patients with diabetes.

Adult↗

PubMedDate not supplied

Progressive outer retinal necrosis in a patient with nephrotic syndrome.

Progressive outer retinal necrosis syndrome (PORN) is a variant of necrotizing herpetic retinopathy and the majority of the described cases were related to acquired immunodeficiency syndrome. We present a patient who is HIV negative with nephrotic syndrome and prednisolone use for 4 months who showed clinical features of PORN. Low CD4 counts and lymphocytopenia suggested immunosuppression. In the left eye, tractional retinal detachment at the posterior pole followed by incomplete posterior vitreous detachment developed. In addition to intravenous administration of acyclovir, vitreous surgeries including stripping of the posterior hyaloid and silicone-oil tamponade were successfully performed to repair the retinal detachment in the left eye and to prevent it in the right eye.

Adult↗

PubMedDate not supplied

D-penicillamine cooperates with copper sulfate to enhance the surface expression of functional Fas antigen in rheumatoid synovial fibroblasts via the generation of hydrogen peroxide.

OBJECTIVE: D-penicillamine (DP) has been shown to cooperate with copper ion to inhibit cell growth in a variety of cell types. To determine whether this inhibitory action is involved in Fas-mediated apoptosis, we examined the effect of DP and copper sulfate on the expression and function of Fas antigen in rheumatoid synovial fibroblasts (RSFs). METHODS: The expression of Fas antigen on the cell surface was determined by flow cytometric analysis. Western blot analysis was performed to examine the protein expressions of Fas and Fas-ligand In addition, the amounts of apoptotic cells were determined by 4', 6-diamidino-2'-phenylindol dihydrochloride (DAPI) and propidium iodide (PI) staining. RESULTS: Although DP and copper sulfate alone did not affect the surface expression of Fas antigen on RSFs, both in combination augmented the Fas expression in dose- and time-dependent manners. The enhanced expression of Fas antigen on their surface was also observed in interleukin-1alpha (IL-1alpha) and/or tumor necrosis factor a (TNFalpha) stimulated RSFs. On the other hand, the combination of DP and copper sulfate did not increase the amounts of cellular Fas protein, as determined by Western blot analysis. To determine whether the induced Fas antigen is functional, we examined the effect of DP and copper sulfate on Fas-mediated apoptosis, using an agonistic anti-Fas antibody. The treatment of this antibody induced the apoptosis in untreated RSFs, as determined by DAPI staining. The combination of DP and copper sulfate further enhanced the Fas-mediated apoptosis. The enhanced apoptosis and cell surface expression of Fas was completely prevented by catalase, indicating that hydrogen peroxide may be involved in these effects of DP and copper sulfate. The protein expression of Fas-ligand, a natural ligand for Fas antigen, in RSFs. was expressed in untreated RSFs. However, the protein levels were not modulated by DP and copper sulfate. CONCLUSIONS: Our data demonstrated that DP cooperated with copper sulfate to enhance the cells surface expression of functional Fas antigen in RSFs. In addition, Fas-ligand was expressed in the RSFs. These findings suggested that DP might regress rheumatoid synovial hyperplasia via Fas-mediated apoptosis.

Antirheumatic Agents↗

PubMedDate not supplied

Cooperative induction of 15-lipoxygenase in rheumatoid synovial cells by IL-4 and proinflammatory cytokines.

OBJECTIVE: To clarify the role of interleukin-4 (IL-4) in the expression of 15-lipoxygenase (15-LOX), whose metabolities are known to suppress the inflammatory reaction, in freshly prepared rheumatoid synovial cells. METHODS: Adherent synovial cells were prepared by enzymatic digestion of synovia obtained from patients with rheumatoid arthritis (RA). Protein expression of 15-LOX was determined by Western blot analysis. The messenger RNAs of 15-LOX were determined by reverse transcription and the polymerase chain reaction (RT-PCR). RESULTS: Freshly prepared rheumatoid synovial cells did not express 15-LOX at either the mRNA or protein levels. IL-4 induced the protein expression of 15-LOX after 24 hours of culture. Although interleukin-1 alpha (IL-1 alpha) and tumor necrosis factor alpha (TNF alpha), major inflammatory cytokines in rheumatoid synovia, did not induce the expression of 15-LOX, IL-4 and these inflammatory cytokines synergistically enhanced the protein expression of 15-LOX. The synergistic effect was also observed at the level of mRNA. CONCLUSIONS: We demonstrate that IL-4 cooperated with the inflammatory cytokines IL-1 alpha and TNF alpha to enhance the expression of 15-LOX in rheumatoid synovial cells. Since 15-LOX metabolites have potent anti-inflammatory actions, our data suggest that IL-4 might downregulate rheumatoid inflammation via the induction of 15-LOX and its metabolites.

Alprostadil↗