Biomedical subjects

C Kim

Publications and source records attributed to C Kim.

At least 37 records · Page 2Linked to original sources

PubMed1997

Structure/function relationship of the cAMP response element in tyrosine hydroxylase gene transcription.

Expression of tyrosine hydroxylase (TH) is limited to catecholamine-producing neurons and neuroendocrine cells in a cell type-specific manner and is inducible by the cAMP-regulated signaling pathway. Previous results indicated that the cAMP response element (CRE) residing at -45 to -38 base pairs upstream of the transcription initiation site is essential for both basal and cAMP-inducible promoter activity of the 2.4-kilobase or shorter upstream sequence of the TH gene (Kim, K. S., Lee, M. K., Carroll, J. , and Joh, T. H. (1993) J. Biol. Chem. 268, 15689-15695; Lazaroff, M. , Patankar, S., Yoon, S. O., and Chikaraishi, D. M. (1995) J. Biol. Chem. 270, 21579-21589). Here, we further report that the CRE is critical for the promoter activity of the 5.6- or 9.0-kilobase upstream sequences of the rat TH gene, which had been shown to direct the cell-specific TH expression in vivo. To define the structure/function relationship of the CRE in transcriptional activation of the TH gene, we performed saturated mutational analyses of 12 nucleotides encompassing the CRE. Mutation of any nucleotide within the octamer motif results in a significant decrease of both basal and cAMP-inducible transcriptional activity of the TH reporter gene construct. Among the four nucleotides adjacent to the CRE (two 5' and two 3'), only the G residue at the immediate 3' position is important for full transcriptional activity. DNase I footprint analysis indicates a positive correlation between in vivo promoter activity and in vitro interaction between the CRE motif and its cognate protein factor(s). Reconstruction experiments using a TH promoter in which the native CRE was rendered inactive show that the CRE can transactivate transcription in either orientation through a window of approximately 200 base pairs upstream of the transcription initiation site, suggesting that CRE supports transcriptional activation of the TH gene in a distance-dependent manner. Finally, when the distance between the CRE and TATA box was changed by inserting an additional 5 or 10 bases, it was observed that both insertional mutations increased activity by approximately 3-fold. The cAMP inducibility was as intact as the wild type construct. Together, these results are consistent with a model in which transcriptional activation of the TH gene by the CRE requires that it be located within a certain proximity of the CAP site but does not depend on a stringent stereospecific alignment in relationship to the TATA element.

Animals↗

PubMed1997

Zinc as a cofactor for heparin neutralization by histidine-rich glycoprotein.

We have studied the ability of histidine-rich glycoprotein (HRG) to neutralize the anticoagulant activity of heparin in plasma and in a purified component clotting assay. Addition of HRG to plasma or to the purified component assay did not neutralize the anticoagulant activity of heparin unless micromolar concentrations of zinc were present. Higher zinc concentrations were required for citrated than for heparinized plasmas due to competition of citrate with HRG for zinc binding. Zinc concentrations as low as 1.25 microM revealed HRG to be a powerful competitor of antithrombin for heparin in the purified component assays. HRG binding of heparin also was shown by affinity chromatography of HRG from immobilized heparin in the presence and absence of zinc. In the absence of zinc, HRG was eluted by 0.1 M NaCl, but, in the presence of zinc, elution of HRG required 1.0 M NaCl. Investigation of other divalent cations (copper and magnesium) indicated that augmentation of heparin binding by HRG in the presence of antithrombin was restricted to zinc. The HRG.Zn complex effectively competes with antithrombin for heparin, which restricts the availability of heparin to bind antithrombin and allows thrombin-mediated fibrinogenesis to proceed unimpeded. This could be initiated by zinc released from activated platelets.

Antithrombin III↗

PubMed1997

Impermeant antitumor sulfonylurea conjugates that inhibit plasma membrane NADH oxidase and growth of HeLa cells in culture. Identification of binding proteins from sera of cancer patients.

The antitumor sulfonylurea LY237868 (N-(4-aminophenyl-sulfonyl)-N'-(4-chlorophenyl)urea) was conjugated through the A ring to alpha-cyclodextrin or agarose bead material (Affigel 10) to prepare impermeant conjugates for activity measurements and affinity isolation of binding proteins from serum. When conjugated to alpha-cyclodextrin, the resulting LY237868 conjugate inhibited both NADH oxidase activity and growth of HeLa cells in culture. The conjugate was at least one order of magnitude more potent as an inhibitor than the parent compound. These findings confirm previous results that demonstrate an antitumor sulfonylurea-binding protein with NADH oxidase activity at the external plasma membrane surface of HeLa cells that is shed into culture media conditioned by growth of HeLa cells. A comparable activity, responsive to sulfonylurea, was present in sera of cancer patients. LY237868 conjugated to agarose beads as the affinity support bound a large number of serum proteins. However, compared to serum from normal patients, the affinity support bound two proteins of M(r) approx. 33.5 and 29.5 not found in sera of normal patients. The 33.5 kDa protein from human sera reacted with antisera to a 33.5 kDa protein from culture media conditioned by growth of HeLa cells that blocked and immunoprecipitated the sulfonylurea-responsive activity from HeLa cell plasma membranes. The results point to the 33.5 kDa protein from cancer patient sera that bound to the sulfonylurea affinity support as representing the circulating equivalent of the previously identified 34 kDa sulfonylurea-binding protein, with NADH oxidase activity at the external cell surface of cultured HeLa cells and a corresponding 33.5 kDa protein shed into culture media conditioned by growth of HeLa cells.

Antineoplastic Agents↗

PubMed1997

Age-related change in the neuropeptide Y and NADPH-diaphorase-positive neurons in the cerebral cortex and striatum of aged rats.

Age-related changes of neuropeptide Y (NPY) and nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) were examined in the rat cerebral cortex and striatum by immunohistochemical and histochemical methods. Double labeling for NPY and NADPH-d showed that about 30-70% of NPY-immunoreactive (NPY-IR) neurons in the cerebral cortex of the control (4-month-old) rats contained NADPH-d and that 50-75% in the aged (24-month-old) rats. The aged rats showed a significant increase in percentage of colocalization of NPY and NADPH-d in comparison with the control rats in the temporal cortex, occipital cortex, cingulate cortex, insular cortex, retrosplenial cortex and caudatoputamen. However, colocalization percentage between control and aged rats in the frontal cortex, parietal cortex, perirhinal cortex, entorhinal cortex and nucleus accumbens were practically identical. In the aged group, the number of NPY-IR/NADPH-d-positive neurons was not significantly decreased in the cerebral cortex and striatum compared to the control group. However, the number of NPY-IR/NADPH-d-negative neurons was significantly decreased in all cerebral cortical areas and caudatoputamen in the aged group except in the nucleus accumbens. Major loss of NPY-IR/NADPH-d-negative neurons in the aged group were observed in the neurons of layer II/III and V/VI. These results demonstrate that the NADPH-d containing NPY-IR neurons are less influenced by aging than the control group in the cerebral cortex and striatum of rats.

Aging↗

PubMed1997

cAMP and protein kinase C elevate LH beta mRNA levels by activating transcription rather than stabilizing mRNA in rat pituitary cells.

The mechanisms by which GnRH modulates synthesis of LH beta subunit and release of LH from the pituitary gonadotropes are not clearly understood. However, GnRH actions in the pituitary gonadotropes have been suggested to be mediated by the PKC- and/or cAMP-dependent pathways. Thus, in the present study we have examined 1) whether the activations of either the PKC- and/or cAMP-dependent signaling cascades could elevate the levels of LH beta mRNA, and if so, 2) whether this increase of LH beta mRNA levels is the result of transcriptional activation or the result of suppressing the turnover of LH beta mRNA. In the present experiment, the activators of protein kinase C and the adenylate cyclase, PMA (5 nM) and forskolin (10 microM) respectively, have elevated the steady state levels of LH beta mRNA significantly by 18 h at the specific concentrations shown in the parenthesis. Subsequently, we have determined whether the elevation of LH beta mRNA levels by either PMA or forskolin is due to the new synthesis of LH beta mRNA or the suppression of LH beta mRNA turnover. Result showed that the ability of PMA or forskolin to elevate the LH beta mRNA levels was suppressed by the addition of actinomycin D, an inhibitor of transcription. Result further showed that the turnover of LH beta mRNA was not suppressed either by PMA or forskolin. These results indicate that the activation of PKC as well as the elevation of cAMP by GnRH leads to the increase in the levels of LH beta mRNA by stimulating the new synthesis of LH beta mRNA instead of increasing the stability of pre-existing LH beta mRNA.

Adenylyl Cyclases↗

PubMed1997

Coronary AVE micro stents: serial quantitative angiography and histology in a canine model.

The AVE Micro Stent (AVE Inc., Santa Rosa, CA) is composed of helically welded 3 mm long, zigzag crowns with stent lengths from 6 to 39 mm and diameters from 2.5 to 4.5 mm. Quantitative coronary angiography and histologic analyses of acute and chronic implantation were obtained in 52 stented coronary segments of 18 dogs. Three hearts with 8 stented coronary segments were harvested after 24 hr, 3 hearts with 9 stented segments were harvested after 2 weeks, 6 hearts with 15 stented segments were harvested at 8 weeks, and 6 hearts with 20 stented segments were harvested at 24 weeks post-deployment. There were no procedural complications, deaths, or acute vessel closures. The average lumen diameter of the stented segment was largest at 2 weeks (3.3 +/- 0.3 mm). The smallest average diameters were observed at 8 weeks after the stent deployment (2.7 +/- 0.4, P < 0.05) with an increase again at 24 weeks (2.9 +/- 0.6). The pre-explant percent of stenosis was <30% in all animals. Histologically, a peak of inflammation was visible at 2 weeks; however, the extent of luminal narrowing reached its peak at 8 weeks and the lumen dimension increased somewhat at 24 weeks. The degree of intimal thickening remained relatively constant throughout the different time points (<200 microm). Overall, these data suggest that constrictive remodeling within the stented segment occurs at 8 weeks in this animal model. The later increase of the stented segment dimensions as well as higher net gain at 24 weeks compared to 8 weeks after deployment suggests that this constriction is a transitory phenomenon.

Angioplasty, Balloon, Coronary↗

PubMed1997

Enhanced epithelial proliferation due to elevated levels of interleukin-1 receptors in middle ear cholesteatomas.

Middle ear cholesteatoma epithelium is a rich source of interleukin-1-alpha (IL-1-alpha), being involved in both keratinocyte hyperproliferation and bone destruction. IL-1-alpha exerts its effects by binding to two distinct IL-1 receptors (IL-1-R). In this study, we have examined the expression of IL-1-R type II (IL-1-R-II) in cholesteatoma samples and have quantified these levels with computer-assisted image analysis. Normal aural skin was used as control. Immunostaining demonstrated the presence of IL-1-R-II in both epidermis and cholesteatoma keratinocytes. The receptors were 3 times higher than those in normal epidermis. The presence of IL-1-alpha in cholesteatoma epithelium coupled with the induced expression of IL-1-R-II indicates the existence of a highly regulated system of autocrine stimulation of cholesteatoma keratinocytes by IL-1.

Cell Division↗

PubMed1997

Combined pituitary deficiencies of growth hormone, thyroid stimulating hormone and prolactin due to Pit-1 gene mutation: a case report.

UNLABELLED: A child exhibited postnatal obstipation and icterus together with severe growth failure during the 1st year of life, a small facial skull and a prominent forehead. Endocrine work-up established the diagnosis of combined pituitary deficiencies of growth hormone, TSH and prolactin. Subsequently, the Pit-1 gene was analysed in the patient and both parents. A single point mutation was detected in exon 6 of the child: a C to G transversion on one allele, causing arginine in position 271 to be substituted by tryptophan (R271 W). This position is known as a "hot spot" for mutations. The inheritance is autosomal-dominant, as the mutated gene product interferes with DNA-binding of the wild-type protein. In contrast, other mutations in the PIT-1 gene are inherited in an autosomal-recessive mode. CONCLUSION: Diagnosing Pit-1 gene mutations as a rare cause of combined pituitary deficiency is important both for genetic counselling as well as for predicting the future course in the patient (spontaneous puberty, no glucocorticoid substitution necessary during stress periods).

Arginine↗

PubMed1997

A new antithrombotic agent, aspalatone, attenuated cardiotoxicity induced by doxorubicin in the mouse; possible involvement of antioxidant mechanism.

A new antithrombotic agent, aspalatone (APT; acetyl salicylic acid maltol ester), was synthesized by esterification of acetyl salicylic acid (ASP) and maltol (MAL). It was suggested that APT possessed an antioxidant effect in in vitro. To evaluate the putative antioxidant effect of APT in in vivo, we developed doxorubicin (DOX)-related cardiac damage, which might be implicated by oxidative stress. Vitamin E (Vit E) was included in the present study as an example of an antioxidant. Prolonged treatments with APT, MAL and Vit E significantly reduced the mortality in animals receiving multiple dose of DOX (3 mg/kg x 4). The potential role of APT, MAL and Vit E against DOX insult may be explained by the induction of glutathione peroxidase activity accompanied by the inhibition of lipid peroxidation. Prolonged treatments of APT, MAL and Vit E also ablated histopathological evidence of DOX cardiomyopathy. ASP challenge, however, did not affect the mortality, myocardial lesion and antioxidant deficit induced by DOX treatments. In conclusion, the protective effect of APT was equipotent to that of Vit E against DOX cardiotoxicity. The results also suggest that the antiperoxidative effect of APT plays a protective role in DOX-related cardiotoxic side effect.

Animals↗

PubMed1997

Aspalatone, a new antiplatelet agent, attenuates the neurotoxicity induced by kainic acid in the rat.

The antioxidant efficacy of aspalatone (APT; acetyl salicylic acid maltol ester), a new antiplatelet agent, has been characterized in vivo as well as in vitro, and several observations indicated that the antioxidant could prevent the neuroexcitation caused by oxidative stress. In this report, the effect of APT was evaluated on kainic acid (KA)-induced neurotoxicity, since the neurotoxicity induced by KA is, at least in part, mediated via the formation of free radicals. The results showed that pretreatments with APT or maltol (MAL) significantly attenuated seizure activity, oxidative stress (lipid peroxidation and protein oxidation) and the loss of hippocampal neurons induced by KA. On the other hand, the pretreatments with aspirin (ASP), ASP together with MAL or vitamin E failed to protect against the toxicity produced by KA suggesting that the mechanism of action for APT on the KA-induced neurotoxicity is different from that of ASP. These finding raise the possibility that salicylmaltol, a metabolite of APT, plays a role in preventing the neurotoxicity evoked by KA. Therefore, our results suggest that an APT-related antioxidant mechanism, which is linked to the MAL moiety, is involved in the neuroprotective effect against KA.

Animals↗

PubMed1997

Chronic use of apraclonidine decreases its moderation of post-laser intraocular pressure spikes.

OBJECTIVE: The purpose of the study is to investigate the efficacy of 1.0% apraclonidine in preventing intraocular pressure (IOP) spike after argon laser trabeculoplasty (ALT) in patients on chronic apraclonidine therapy compared with patients not on chronic apraclonidine use. DESIGN: The study design was a prospective study. PARTICIPANTS: This study consisted of 231 consecutive eyes of patients with primary open-angle glaucoma undergoing ALT: 70 eyes (30%) were started on a regimen including chronic apraclonidine 0.5% use (group A) and 161 eyes (70%) were started on a regimen without chronic apraclonidine 0.5% use (group B). INTERVENTION: Both groups received one drop of apraclonidine 1.0% 15 minutes before ALT to 180 degrees of previously untreated trabecular meshwork. Intraocular pressure was measured before the procedure and at 5 minutes, 1 hour, and 24 hours after the laser treatment. MAIN OUTCOME MEASURES: Incidences of an IOP spike and mean IOPs at 5 minutes, 1 hour, and 24 hours after the laser treatment were compared between the two groups. Multivariate logistic regression analysis also was carried out to identify the significant risk factors for post-ALT IOP spikes despite prophylactic apraclonidine 1.0% treatment. RESULTS: The incidences of IOP spikes greater than 0 mmHg, greater than 2 mmHg, and greater than 5 mmHg at 1 hour after ALT were 32.9%, 22.9%, and 12.9%, respectively, in group A versus 13.7%, 11%, and 3.1%, respectively, in group B (P = 0.0007, P = 0.009, and P = 0.004). Chronic apraclonidine 0.5% use was found to be the only significant risk factor for IOP spikes at 1 hour after ALT by multivariate logistic regression analysis. CONCLUSIONS: The incidences of IOP spikes in group A were significantly greater than in group B and approached the reported incidences of IOP spikes without perilaser apraclonidine prophylaxis. This indicates that peri-ALT apraclonidine is relatively ineffective in patients with chronic apraclonidine 0.5% use (group A) compared with patients without chronic apraclonidine use (group B), presumably because of saturation of the ocular alpha-2 receptors with apraclonidine in patients with chronic apraclonidine use. Therefore, in patients receiving chronic apraclonidine therapy, it is especially important to monitor their post-ALT IOPs and to be prepared to treat postlaser IOP spikes using agents other than apraclonidine.

Adrenergic alpha-Agonists↗

PubMed1997

The effect of adjunctive mitomycin C in Molteno implant surgery.

PURPOSE: The purpose of the study is to assess the effect of adjunctive intraoperative mitomycin C (MMC) in Molteno drainage device implantation for patients with recalcitrant glaucomas. METHOD: Forty-nine eyes of 49 patients who underwent one-stage, single-plate Molteno device implantation with adjunctive intraoperative MMC (0.5 mg/ml) for 3 to 5 minutes (MMC group) were compared to a historic control group of 51 eyes of 51 patients (control group) who received one-stage, single-plate Molteno device implantation without MMC. Success (survival) was defined as an intraocular pressure (IOP) between 6 and 21 mmHg, inclusive, with (qualified success) or without (complete success) glaucoma medications and with no additional glaucoma surgery, phthisis, implant removal, or loss of light perception. RESULTS: Preoperative conditions were similar between the two groups. There was no significant difference in surgical survival rate between the two groups (P = 0.13, log-rank test). There also were no significant differences in the postoperative IOP levels and numbers of antiglaucoma medications between the two groups at all times (P > 0.05). Visual acuity was improved or remained within one line of preoperative visual acuity in 76.1% of the MMC group and 78.7% of the control group at 1 year after surgery (P = 0.76, chi-square test). Complications and reoperation for complications were similar in both groups (P > 0.05, chi-square test) except for the incidence of early postoperative hypotony and the total number of eyes with complications not requiring reoperation, which were more common in the MMC group (P = 0.027, 0.005, respectively, chi-square test). The most common complications included hypotony with or without a flat anterior chamber or choroidal detachment, followed by hyphema and tube plugging. CONCLUSION: Molteno device implantation with adjunctive intraoperative MMC in patients with complicated glaucoma may not offer a better chance of surgical success compared with Molteno implantation without MMC.

Adult↗

PubMed1997

Analysis of reliability indices from Humphrey visual field tests in an urban glaucoma population.

PURPOSE: Visual field assessment is extremely important in glaucoma management, but interpretation is affected by the quality of the patient's performance. The authors have investigated the reliability of visual field performance by a randomly selected sample of the chronic glaucoma population at an urban tertiary care practice. METHODS: Patient reliability in Humphrey automated visual field testing was studied in 106 randomly selected chronic open-angle glaucoma patient charts, which provided 768 tests (mean, 7.2 +/- 4.8 fields; range, 2-18 fields). Reliability criteria were established as less than 20% fixation losses, less than 33% false-negative error, and less than 33% false-positive error, as recommended by Humphrey Instruments, Inc (San Leandro, CA). RESULTS: Patients performed reliably in 61% of right eye fields, 58% of left eye fields, and 59.5% overall. Of the 106 patients, only 35 (33%) were always reliable in both eyes, whereas 8 (7.5%) were always unreliable in both eyes. The most common cause of unreliability was fixation loss (39%), whereas false-positive error (5%) and false-negative error (9%) were less frequent. A more severely depressed mean deviation correlated significantly with poorer performance on the three reliability indices, with false-negative error having the greatest correlation, followed by fixation loss and false-positive error. Corrected pattern standard deviation correlated closely only with false-negative error. Prolonged test time also correlated with all three reliability indices. Age was a significant factor for fixation loss but not for false-negative or false-positive error. CONCLUSIONS: The authors conclude that fewer than two thirds of the Humphrey visual fields were reliable with the authors' urban tertiary care population of patients with glaucoma. Relaxing the fixation loss criterion to less than 33% improved the rate of reliability to approximately 75%. The severity of glaucomatous visual field defects, test time, and age were identified as factors influencing the reliability of the Humphrey visual fields.

Aged↗

PubMed1997

Emerging auditory response interactions to harmonic complexes in field L of the zebra finch.

Auditory responses of single units to harmonic complexes were studied in field L of the adult male zebra finch (Poephila guttata) to understand the origin of song selectivity in HVc. One of the attributes in this song selectivity is a large increase in response interactions when tones are presented simultaneously. Single units in the subdivisions of field L-L1, L2 and L3, were examined to see where these response interactions to harmonic complexes begin to develop along the auditory pathway towards HVc. Results showed relatively simple stereotyped response in L2 and widely varying ones in L1 and L3. The responses of some neurons in L1 and L3 to signals composed of the simultaneous sum of two harmonic complexes significantly differed from the linear sum of their responses to individual harmonic complexes whereas the neurons of L2 showed relatively weak response interactions. These neurons in L1 and L3 exhibited strong response interactions to harmonic complexes comparable to those of song-selective neurons in HVc. Thus, L1 and L3 are suggested to have emerging selective response properties and to provide auditory inputs relevant to the song selective HVc neurons.

Animal Communication↗

PubMed1997

Studies on dynamic behavior of the biosensor based on immobilized glucoamylase-glucose oxidase membrane.

Frequency response of the glucose/maltose biosensors based on immobilized glucoamylase and glucose oxidase membranes of different thickness were investigated with the sinusoidal signal generator of substrate concentration. The results were modeled by the serial combination of the dead time and the first order response blocks, and time constants and dead times were estimated. The estimated value of time constant ranged from 4.5 to 13.2 s and that of the dead time from 3.2 to 7.7 s with the tendency that both time constant and dead time increase as membrane thickness increases and number of enzymatic reaction steps increases.

Biosensing Techniques↗

PubMed1997

Water-soluble polycations as oral drug carriers (tablets).

New bioerodible materials that are noncross-linked and water-soluble copolymers of trimethylaminoethyl methacrylate chloride (TMAEMC) and methyl methacrylate (MMA) were synthesized and then bound to anionic drugs (diclofenac Na and Na sulfathiazote) to form water-insoluble complexes. These drug-polymer complexes release the bound drugs only in ionic media. Compressed tablets were prepared from these anion-exchange resins, and their release profiles follow zero-order kinetics (n > 0.89, where n is the release exponent). The effects of various excipients (dextrose, lactose, and microcrystalline cellulose) were studied, and the polymer composition was found to influence the duration of drug release. It was also found that the release of anionic drugs from drug-PTMAEM/MMA is linear and that it is possible to "tailor-make" their release kinetics by suitably altering the copolymer composition. When a high content of a water-insoluble excipient (i.e., microcrystalline cellulose) was used to fabricate the tablets, the release kinetics deviated from linearity (n = 0.73). In general, release kinetics were well described by a dissociation/erosion mechanism. Drug loading could be increased by increasing the exchange capacity of the polymer (i.e., by increasing the content of the quaternary amine monomer).

Cations↗

PubMed1997

Is the drug-responsive NADH oxidase of the cancer cell plasma membrane a molecular target for adriamycin?

Enhanced growth inhibition and antitumor responses to adriamycin have been observed repeatedly from several laboratories using impermeant forms of adriamycin where entry into the cell was greatly reduced or prevented. Our laboratory has described an NADH oxidase activity at the external surface of plasma membrane vesicles from tumor cells where inhibition by an antitumor sulfonylurea, N-(4-methylphenylsulfonyl)-N'-(4-chlorophenyl)urea (LY181984), and by the vanilloid, capsaicin (8-methyl-N-vanillyl-6-noneamide) correlated with inhibition of growth. Here we report that the oxidation of NADH by isolated plasma membrane vesicles was inhibited, as well, by adriamycin. An external site of inhibition was indicated from studies where impermeant adriamycin conjugates were used. The EC50 for inhibition of the oxidase of rat hepatoma plasma membranes by adriamycin was several orders of magnitude less than that for rat liver. Adriamycin cross-linked to diferric transferrin and other impermeant supports also was effective in inhibition of NADH oxidation by isolated plasma membrane vesicles and in inhibition of growth of cultured cells. The findings suggest the NADH oxidase of the plasma membrane as a growth-related adriamycin target at the surface of cancer cells responsive to adriamycin. Whereas DNA intercalation remains clearly one of the principal bases for the cytotoxic action of free adriamycin, this second site, possibly related to a more specific antitumor action, may be helpful in understanding the enhanced efficacy reported previously for immobilized adriamycin forms compared to free adriamycin.

Animals↗

PubMed1997

Distinguishing optimism from pessimism in older adults: is it more important to be optimistic or not to be pessimistic?

Confirmatory factor analysis revealed that the Life Orientation Test (LOT) consisted of separate Optimism and Pessimism factors among middle-aged and older adults. Although the two factors were significantly negatively correlated among individuals facing a profound life challenge (i.e., caregiving), they were only weakly correlated among noncaregivers. Caregivers also expressed less optimism than noncaregivers and showed a trend toward greater pessimism, suggesting that life stress may affect these dispositions. Pessimism, not optimism, uniquely predicted subsequent psychological and physical health; however, optimism and pessimism were equally predictive for stressed and nonstressed samples. By exploring optimism and pessimism separately, researchers may better determine whether the beneficial effects of optimism result from thinking optimistically, avoiding pessimistic thinking, or a combination of the two.

Adaptation, Psychological↗