Light extraction efficiency enhancement of GaN-based light emitting diodes on n-GaN layer using a SiO2 photonic quasi-crystal overgrowth.

In this paper, GaN-based LEDs with a SiO2 photonic quasi-crystal (PQC) pattern on an n-GaN layer by nano-imprint lithography (NIL) are fabricated and investigated. At a driving current of 20 mA on Transistor Outline (TO)-can package, the better light output power of LED III (d = 1.2 microm) was enhanced by a factor of 1.20. After 1000 h life test (55 degrees C/50 mA) condition, Normalized output power of LED with a SiO2 PQC pattern (LED III (d = 1.2 microm)) on an n-GaN layer only decreased by 5%. This results offer promising potential to enhance the light output power of commercial light-emitting devices using the technique of nano-imprint lithography.

Visually induced self-motion sensation adapts rapidly to left-right visual reversal.

After 1 to 3 hours of active movement while wearing vision-reversing goggles, 9 of 12 (stationary) human subjects viewing a moving stripe display experienced a self-rotation illusion in the same direction as seen stripe motion, rather than in the opposite (normal) direction. This result indicates that the neural pathways which process visual self-rotation cues can undergo rapid adaptive modification.

[A follow-up study on the clinical characteristics among patients with diabetes mellitus combined with acute myocardial infarction].

Objective: To investigate the clinical characteristics of diabetic patients combined with acute myocardial infarction (AMI) and to compare the prognosis between diabetic and non- diabetic patients in 4-5 years after the onset of AMI. Methods: Followed the certain inclusive and exclusive criteria, a total of 420 patients with acute myocardial infarction were included and divided into diabetes group (group D) and non-diabetes group (group N) with numbers as 161 people and 259 respectively. Baseline data, clinical information, short-term outcome and long-term prognosis of the two groups were compared and analyzed. Results: Among the patients with diabetes, the average age was older (65.65±11.33 vs. 63.30±15.34), with fewer males (64.59% vs. 79.92%); and more likely to have other complications as hypertension (64.60% vs. 53.28%) or hyperlipidemia (42.24% vs. 26.25%). 59.29% of the patients in group D showed pathological changes in 3 major coronary arteries, which were significantly more than its counterpart (40.83%). The proportion of patients that had undergone the coronary artery bypass, grafting (11.11% vs. 5.31%) appeared also higher. There was no significant difference seen in the short-term outcomes between the two groups, but results from the long-term follow-up program showed that both the incidence of Major Adverse Cardiovascular Events (MACE) (50.67% vs. 27.72%) and the all-cause mortality (20.00% vs. 9.90%) in group D were higher than those appeared in group N (27.72%). Conclusions: Patients suffered from the combination of both diabetes and acute myocardial infarction appeared older in age, more in females, with more complications and the coronary artery lesions were more severe and wider. During hospitalization, no significant difference was seen regarding the short-term outcomes between the two groups but the results from long-term follow-up process showing that the risk of MACE events was significantly higher in patients with type2 diabetes.

Organizing principles of the axoglial apparatus.

On axonal surfaces that flank the node of Ranvier and in overlying glial paranodal loops, proteins are arranged within circumscribed microdomains that defy explanation by conventional biosynthetic mechanisms. We postulate that the constraint of proteins to these loci is accomplished in part by discriminative membrane-embedded molecular sieves and diffusion barriers, which serve to organize and redistribute proteins after delivery by vesicular transport to neural cell plasma membranes. One sieve likely comprises a moveable, macromolecular scaffold of axonal and glial cell-derived transmembrane adhesion molecules and their associated cytoplasmic binding partners, located at the ends of each elongating myelin internode; this sieve contributes to restricting the sodium channel complexes to the node. We also anticipate the existence of a passive paranodal diffusion barrier at the myelin/noncompact membrane border, which prohibits protein diffusion out of contiguous paranodal membranes.

The presynaptic particle web: ultrastructure, composition, dissolution, and reconstitution.

We report the purification of a presynaptic "particle web" consisting of approximately 50 nm pyramidally shaped particles interconnected by approximately 100 nm spaced fibrils. This is the "presynaptic grid" described in early EM studies. It is completely soluble above pH 8, but reconstitutes after dialysis against pH 6. Interestingly, reconstituted particles orient and bind PSDs asymmetrically. Mass spectrometry of purified web components reveals major proteins involved in the exocytosis of synaptic vesicles and in membrane retrieval. Our data support the idea that the CNS synaptic junction is organized by transmembrane adhesion molecules interlinked in the synaptic cleft, connected via their intracytoplasmic domains to the presynaptic web on one side and to the postsynaptic density on the other. The CNS synaptic junction may therefore be conceptualized as a complicated macromolecular scaffold that isostatically bridges two closely aligned plasma membranes.

Melittin-induced [Ca2+]i increases and subsequent death in canine renal tubular cells.

The effect of melittin on cytosolic free Ca(2+) concentration ([Ca(2+)](i)) and viability is largely unknown. This study examined whether melittin alters Ca(2+) levels and causes Ca(2+)-dependent cell death in Madin-Darby canine kidney (MDCK) cells. [Ca(2+)](i) and cell death were measured using the fluorescent dyes fura-2 and WST-1 respectively. Melittin at concentrations above 0.5 microM increased [Ca(2+)](i) in a concentration-dependent manner. The Ca(2+) signal was reduced by 75% by removing extracellular Ca(2+). The melittin-induced Ca(2+) influx was also implicated by melittin-caused Mn(2+) influx. After pretreatment with 1 microM thapsigargin (an endoplasmic reticulum Ca(2+) pump inhibitor), melittin-induced Ca(2+) release was inhibited; and conversely, melittin pretreatment abolished thapsigargin-induced Ca(2+) release. At concentrations of 0.5-20 microM, melittin killed cells in a concentration-dependent manner. The cytotoxic effect of 0.5 microM melittin was nearly completely reversed by prechelating cytosolic Ca(2+) with BAPTA. Melittin at 0.5-2 microM caused apoptosis as assessed by flow cytometry of propidium iodide staining. Collectively, in MDCK cells, melittin induced a [Ca(2+)](i) rise by causing Ca(2+) release from endoplasmic reticulum and Ca(2+) influx from extracellular space. Furthermore, melittin can cause Ca(2+)-dependent cytotoxicity in a concentration-dependent manner.

Leiomyosarcoma in the nasopharynx: MR imaging findings.

The MR imaging findings of a leiomyosarcoma arising from the nasopharynx are presented. To our knowledge, this is the first MR imaging description of this entity.

Compression of ureter caused by a retained reservoir of penile prosthesis.

Routine removal of the reservoir in explanting a malfunctioning three-piece penile implant raises debates because that the retained reservoir has little risk of erosion and it often needs a second incision to remove the reservoir. We reported a case whose retained reservoir resulted in nonbacterial inflammation around it and caused an ipsilateral hydronephrosis.

Direct transmission of the 18q- syndrome from mother to daughter.

A 34-year-old mother presented moderate mental retardation, short stature, microcephaly, and characteristic facial dysmorphism. Her 12-year-old daughter manifested moderate mental retardation, short stature, microcephaly, dysplastic external ear canals, hearing impairment, and characteristic facial dysmorphism. Cytogenetic analysis of the family revealed a normal karyotype, 46,XY, in the father, and a 46,XX,del(18)(q22.2) karyotype in both mother and daughter. Molecular marker analysis determined direct transmission of the distal 18q deletion from mother to daughter. The present case provides evidence of fertility of the affected females and a mother-to-daughter direct transmission in the familial 18q- syndrome. Identification of affected females with the 18q- syndrome should include genetic counseling of possible direct transmission and consideration of birth control or prenatal genetic testing at reproductive age.

Spectral karyotyping and fluorescence in situ hybridization analysis of de novo partial trisomy 7p (7p21.2-->pter) and partial monosomy 12q (12q24.33-->qter).

An 8-year-old boy presenting with hypotonia, moderate mental retardation, developmental delay, and psychomotor retardation is reported. Magnetic resonance imaging of the brain at age 3 years revealed a Dandy-Walker variant. Cytogenetic analysis of the peripheral blood revealed a derivative chromosome 12 with unknown additional material attached to the distal region of the long arm of chromosome 12. The parental karyotypes were normal. Spectral karyotyping (SKY) using the 24-color SKY probes and fluorescence in situ hybridization (FISH) using the specific 7p, 7q, 12p, and 12q telomeric probes confirmed a duplication of distal 7p and a deletion of terminal 12q. The karyotype of the proband was designated as 46,XY.ish der(12)t(7;12) (p21.2;q24. 33)(SKY+, 7pTEL+, 12qTEL-). The present case provides evidence for the association of partial trisomy 7p (7p21.2-->pter) and partial monosomy 12q (12q24.33-->qter) with a cerebellar malformation and the usefulness of SKY and FISH in the identification of a de novo aberrant chromosome resulting from an unbalanced translocation.

Effect of riluzole on Ca2+ movement and cytotoxicity in Madin-Darby canine kidney cells.

Riluzole is a drug used in the treatment of amyotrophic lateral sclerosis; however, its in vitro action is unclear. In this study, the effect of riluzole on intracellular Ca2+ concentration ([Ca2+]i) in Madin-Darby canine kidney (MDCK) cells was investigated using the Ca2+ -sensitive fluorescent dye, fura-2. Riluzole (100-500 microM) caused a rapid and sustained increase of [Ca2+]i in a concentration-dependent manner (EC50 = 150 microM). Some 40 and 50% of this [Ca2+]i increase was prevented by the removal of extracellular Ca2+ and the addition of La3+, respectively, but was unchanged by dihydropyridines, verapamil and diltiazem. In Ca2+ -free medium, thapsigargin - an inhibitor of the endoplasmic reticulum (ER) Caz+ -ATPase--caused a monophasic [Ca2+]i increase, after which the increasing effect of riluzole on [Ca2+]i was attenuated by 70%; in addition, pre-treatment with riluzole abolished thapsigargin-induced [Ca2+]i increases. U73122, an inhibitor of phospholipase C (PLC), abolished ATP (but not riluzole)-induced [Ca2+]i increases. At concentrations of 250 and 500 microM, riluzole killed 40 and 95% cells, respectively. The cytotoxic effect of riluzole (250 microM) was unaltered by pre-chelating cytosolic Ca2+ with BAPTA. Collectively, in MDCK cells, riluzole rapidly increased [Ca2+]i by stimulating extracellular Ca2+ influx via an La3+ -sensitive pathway and intracellular Ca2+ release from the ER via, as yet, unidentified mechanisms. Furthermore, riluzole caused Ca2+ -unrelated cytotoxicity in a concentration-dependent manner.

Novel effects of gossypol, a chemical contraceptive in man: mobilization of internal Ca(2+) and activation of external Ca(2+) entry in intact cells.

The effect of gossypol on Ca(2+) signaling in Madin Darby canine kidney (MDCK) cells was investigated by using fura-2 as a Ca(2+) probe. Gossypol evoked a rise in cytosolic free Ca(2+) levels ([Ca(2+)](i)) concentration-dependently between 2 and 20 microM. The response was decreased by external Ca(2+) removal. In Ca(2+)-free medium pretreatment with gossypol nearly abolished the [Ca(2+)](i) increase induced by carbonylcyanide m-chlorophenylhydrazone (CCCP), a mitochondrial uncoupler, and thapsigargin, an inhibitor of the endoplasmic reticulum Ca(2+) pump; but pretreatment with CCCP and thapsigargin only partly inhibited gossypol-induced Ca(2+) release. Addition of 3 mM Ca(2+) induced a [Ca(2+)](i) increase after pretreatment with 5 microM gossypol in Ca(2+)-free medium. This Ca(2+) entry was decreased by 25 microM econazole, 50 microM SKF96365 and 40 microM aristolochic acid (a phospholipase A(2) inhibitor). Pretreatment with aristolochic acid inhibited 5 microM gossypol-induced internal Ca(2+) release by 55%, but suppression of phospholipase C with 2 microM 1-(6-((17beta-3-methoxyestra-1,3, 5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione) had no effect. Gossypol (5 microM) also increased [Ca(2+)](i) in human bladder cancer cells and neutrophils. Collectively, we have found that gossypol increased [Ca(2+)](i) in MDCK cells by releasing Ca(2+) from multiple Ca(2+) stores in a manner independent of the production of inositol-1,4,5-trisphosphate, followed by Ca(2+) influx from external space.

Insulin action in normal and protein kinase C-deficient rat hepatoma cells. Effects on protein phosphorylation, protein kinase activities, and ornithine decarboxylase activities and messenger ribonucleic acid levels.

Insulin and tumor-promoting phorbol esters such as phorbol 12-myristate 13-acetate (PMA) share some biological activities in normal hepatocytes and in some lines of cultured hepatoma cells. To investigate the possibility that some of these common effects might involve a common pathway, we examined the effects of insulin and PMA on several biological processes in normal and protein kinase C-deficient H4IIE rat hepatoma cells. Protein kinase C deficiency was achieved by preincubating the cells in high concentrations of PMA, and was documented by direct enzyme measurement in soluble and particulate cellular fractions, and by analysis of immunoreactive protein kinase C concentrations in whole cellular homogenates. In the protein kinase C-deficient cells, the following actions of insulin remained at near normal levels: stimulated phosphorylation of the ribosomal protein S6; activation of a ribosomal S6 protein kinase; and increases in ornithine decarboxylase activity and mRNA accumulation. PMA stimulated all of these responses in the normal cells, but none of them in the PMA-pretreated cells. We conclude that insulin can exert some of its actions in a normal manner in protein kinase C-deficient H4IIE hepatoma cells (ATCC CRL 1548) and that some of the actions insulin holds in common with PMA may be due to common activation of one or more distal pathways. A candidate for such a distal step is activation of the ribosomal protein S6 protein kinase.

High level, cell-specific expression of ornithine decarboxylase transcripts in rat genitourinary tissues.

We evaluated transcript levels for the rate-limiting enzyme in polyamine biosynthesis, ornithine decarboxylase (ODC), in rat tissues by Northern blotting and in situ hybridization histochemistry, using a rat cDNA probe. ODC transcripts were expressed at a high level, relative to levels in other tissues, in the kidney and testis of the adult rat; maximal levels of transcripts in these tissues occurred after sexual maturation had taken place, i.e. between 20 and 150 days of age. In situ hybridization histochemistry revealed high level expression in the kidney, testis, prostate, and seminal vesicles of the male rat; this high level expression was limited to certain cell types: kidney, S3 cells of the proximal convoluted tubule; prostate and seminal vesicles, glandular or luminal epithelial cells; and testis, early spermatogenic cells. High level expression of ODC mRNA disappeared from the prostate and seminal vesicle epithelial cells after castration and reappeared with testosterone treatment; in contrast, levels of kidney ODC mRNA were essentially unchanged by castration and were similar in male and female adult rats. We conclude that high level ODC mRNA expression occurs in specific cell types in the adult rat, where it appears to be regulated by both androgen-dependent and independent mechanisms.

Econazole induces increases in free intracellular Ca2+ concentrations in human osteosarcoma cells.

Econazole is an antifungal drug with different in vitro effects. However, econazole's effect on osteoblast-like cells is unknown. In human MG63 osteosarcoma cells, the effect of econazole on intracellular Ca2+ concentrations ([Ca2+]i) was explored by using fura-2. At a concentration of 0.1 microM, econazole started to cause a rise in [Ca2+]i in a concentration-dependent manner. Econazole-induced [Ca2+]i rise was reduced by 74% by removal of extracellular Ca2+. The econazole-induced Ca2+ influx was mediated via a nimodipine-sensitive pathway. In Ca2+ -free medium, thapsigargin, an inhibitor of the endoplasmic reticulum Ca+ -ATPase, caused a [Ca2+]i rise, after which the increasing effect of econazole on [Ca2+]i was abolished. Pretreatment of cells with econazole to deplete Ca2+ stores totally prevented thapsigargin from releasing Ca2+. U73122, an inhibitor of phospholipase C, abolished histamine (an inositol 1,4,5-trisphosphate-dependent Ca2+ mobilizer)-induced, but not econazole-induced, [Ca2+]i rise. Econazole inhibited 76% of thapsigargin-induced store-operated Ca2+ entry. These findings suggest that in MG63 osteosarcoma cells, econazole increases [Ca2+]i by stimulating Ca2+ influx and Ca2+ release from the endoplasmic reticulum via a phospholipase C-independent manner. In contrast, econazole acts as a potent blocker of store-operated Ca2+ entry.

Neither insufficiency nor overexpression of sac1 affects the accumulation of Aß42 in Drosophila expressing Ab42.

OBJECTIVE: We investigated the effects of genetic down- and up-regulation of sac1 expression on Aß42 accumulation and the associated neural deficits in flies with direct expression of arctic mutant Aß42 (Aßarc) in the neurons of GF pathway. MATERIALS AND METHODS: We genetically down-regulated and up-regulated the level of sac1, encoding a major phosphoinositide phosphatases in a disease model, in which arctic mutant Aß42 is directly expressed in the neurons of a neural pathway of adult fruit flies. RESULTS: We conducted a time-course analysis of Aß42 level in the model and found an age-dependent elevation of Aß42 accumulation, closely correlated to the age-dependent decline of climbing ability in the model flies. Neither sac1 insufficiency nor sac1 over-expression significantly changed the three phenotypes. CONCLUSIONS: We found that the alterations of sac1 expression did not change Aß42 accumulation and neural deficits in the model.

Disulfide bond effects on protein stability: designed variants of Cucurbita maxima trypsin inhibitor-V.

Attempts to increase protein stability by insertion of novel disulfide bonds have not always been successful. According to the two current models, cross-links enhance stability mainly through denatured state effects. We have investigated the effects of removal and addition of disulfide cross-links, protein flexibility in the vicinity of a cross-link, and disulfide loop size on the stability of Cucurbita maxima trypsin inhibitor-V (CMTI-V; 7 kD) by differential scanning calorimetry. CMTI-V offers the advantage of a large, flexible, and solvent-exposed loop not involved in extensive intra-molecular interactions. We have uncovered a negative correlation between retention time in hydrophobic column chromatography, a measure of protein hydrophobicity, and melting temperature (T(m)), an indicator of native state stabilization, for CMTI-V and its variants. In conjunction with the complete set of thermodynamic parameters of denaturation, this has led to the following deductions: (1) In the less stable, disulfide-removed C3S/C48S (Delta Delta G(d)(50 degrees C) = -4 kcal/mole; Delta T(m) = -22 degrees C), the native state is destabilized more than the denatured state; this also applies to the less-stable CMTI-V* (Delta Delta G(d)(50 degrees C) = -3 kcal/mole; Delta T(m) = -11 degrees C), in which the disulfide-containing loop is opened by specific hydrolysis of the Lys(44)-Asp(45) peptide bond; (2) In the less stable, disulfide-inserted E38C/W54C (Delta Delta G(d)(50 degrees C) = -1 kcal/mole; Delta T(m) = +2 degrees C), the denatured state is more stabilized than the native state; and (3) In the more stable, disulfide-engineered V42C/R52C (Delta Delta G(d)(50 degrees C) = +1 kcal/mole; Delta T(m) = +17 degrees C), the native state is more stabilized than the denatured state. These results show that a cross-link stabilizes both native and denatured states, and differential stabilization of the two states causes either loss or gain in protein stability. Removal of hydrogen bonds in the same flexible region of CMTI-V resulted in less destabilization despite larger changes in the enthalpy and entropy of denaturation. The effect of a cross-link on the denatured state of CMTI-V was estimated directly by means of a four-state thermodynamic cycle consisting of native and denatured states of CMTI-V and CMTI-V*. Overall, the results show that an enthalpy-entropy compensation accompanies disulfide bond effects and protein stabilization is profoundly modulated by altered hydrophobicity of both native and denatured states, altered flexibility near the cross-link, and residual structure in the denatured state.

NMR studies of internal dynamics of serine proteinase protein inhibitors: Binding region mobilities of intact and reactive-site hydrolyzed Cucurbita maxima trypsin inhibitor (CMTI)-III of the squash family and comparison with those of counterparts of CMTI-V of the potato I family.

Serine proteinase protein inhibitors follow the standard mechanism of inhibition (Laskowski M Jr, Kato I, 1980, Annu Rev Biochem 49:593-626), whereby an enzyme-catalyzed equilibrium between intact (I) and reactive-site hydrolyzed inhibitor (I*) is reached. The hydrolysis constant, Khyd, is defined as [I*]/[I]. Here, we explore the role of internal dynamics in the resynthesis of the scissile bond by comparing the internal mobility data of intact and cleaved inhibitors belonging to two different families. The inhibitors studied are recombinant Cucurbita maxima trypsin inhibitor III (rCMTI-III; Mr 3 kDa) of the squash family and rCMTI-V (Mr approximately 7 kDa) of the potato I family. These two inhibitors have different binding loop-scaffold interactions and different Khyd values--2.4 (CMTI-III) and 9 (CMTI-V)--at 25 degrees C. The reactive-site peptide bond (P1-P1') is that between Arg5 and Ile6 in CMTI-III, and that between Lys44 and Asp45 in CMTI-V. The order parameters (S2) of backbone NHs of uniformly 15N-labeled rCMTI-III and rCMTI-III* were determined from measurements of 15N spin-lattice and spin-spin relaxation rates, and [1H]-15N steady-state heteronuclear Overhauser effects, using the model-free formalism, and compared with the data reported previously for rCMTI-V and rCMTI-V*. The backbones of rCMTI-III [(S2) = 0.71] and rCMTI-III* [(S2) = 0.63] are more flexible than those of rCMTI-V [(S2) = 0.83] and rCMTI-V* [(S2) = 0.85]. The binding loop residues, P4-P1, in the two proteins show the following average order parameters: 0.57 (rCMTI-III) and 0.44 (rCMTI-III*); 0.70 (rCMTI-V) and 0.40 (rCMTI-V*). The P1'-P4' residues, on the other hand, are associated with (S2) values of 0.56 (rCMTI-III) and 0.47 (rCMTI-III*); and 0.73 (rCMTI-V) and 0.83 (rCMTI-V*). The newly formed C-terminal (Pn residues) gains a smaller magnitude of flexibility in rCMTI-III* due to the Cys3-Cys20 crosslink. In contrast, the newly formed N-terminal (Pn' residues) becomes more flexible only in rCMTI-III*, most likely due to lack of an interaction between the P1' residue and the scaffold in rCMTI-III. Thus, diminished flexibility gain of the Pn residues and, surprisingly, increased flexibility of the Pn' residues seem to facilitate the resynthesis of the P1-P1' bond, leading to a lower Khyd value.

Clinical experience of Kock pouch continent urinary diversion.

Kock continent ileal reservoir for urinary diversion was performed in 53 patients with invasive bladder cancer (52) or neurogenic bladder (1). The postoperative follow-up period was from six to thirty-nine months. The clinical results showed no metabolic disturbance of blood electrolytes or acidity. Prolapse of efferent nipple valve developed in 4 patients (7.6%); and 2 underwent revisional surgery with a good result. Another 4 patients (7.6%) suffered from poor continence and relatively frequent catheterization to empty the pouch was necessary to prevent urine leakage through the stoma. Urodynamic study of the Kock pouch in these 4 patients showed a short functional nipple valve length and small pouch capacity. The other 45 patients (84.8%) had good continence. Urodynamic study of the pouch in 20 patients showed low pressure (mean of 13.3 cm H2O) in the pouch and high pressure (mean of 72.1 cm H2O) at the efferent nipple valve. Three patients had unilateral hydronephrosis in the follow-up intravenous urography. Corrective surgery for stenosis at the right ureteroileal anastomosis was done in 1 patient with normalization of the upper urinary tract afterward. The other 2 patients were managed by close observation for the mild hydronephrosis. Symptomatic bacteriuria developed in only 3 patients (5.7%) and responded well to antibiotic management. Reservoirography demonstrated no reflux into the upper urinary tract in all the follow-up patients. There was no significant change of the renal function at twenty-four months after operation detected by radionuclide (131I-Hippuran) renal functional study. All patients were satisfied with Kock urinary diversion.

Fendiline, an anti-anginal drug, increases intracellular Ca2+ in PC3 human prostate cancer cells.

BACKGROUND: The effects of the anti-anginal drug fendiline on intracellular Ca2+ concentrations ([Ca2+]i) in human PC3 prostate cancer cells were examined. METHODS: [Ca2+]i was measured using the fluorescent dye fura-2. RESULTS: Fendiline (0.5-100 microM) increased [Ca2+]i in a concentration-dependent manner. Ca2+ removal partly inhibited the Ca2+ signals. In Ca2+-free medium, pretreatment with 100 microM fendiline inhibited most of the [Ca2+]i increase induced by 1 microM thapsigargin (an endoplasmic reticulum Ca2+ pump inhibitor), and pretreatment with thapsigargin abolished the fendiline-induced [Ca2+]i increases. Adding 3 mM Ca2+ increased [Ca2+]i in cells pretreated with 0.5-200 microM fendiline in Ca2+-free medium. Pretreatment with 1 microM U73122 to block the formation of inositol-1.4.5-trisphosphate (IP3) did not alter fendiline-induced internal Ca2+ release. CONCLUSIONS: The anti-anginal drug fendiline induced internal Ca2+ release and external Ca2+ entry. Because prolonged increases in [Ca2+]i may lead to cell injury and death, the long-term effect of fendiline on the function of prostate cancer cells should be investigated.