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Biomedical subjects

A Kaplan

Publications and source records attributed to A Kaplan.

At least 91 records · Page 5Linked to original sources
PubMed1996

Retinoid induction of CRABP II mRNA in human dermal fibroblasts: use as a retinoid bioassay.

Cellular retinoic acid binding protein II (CRABP II) mRNA is selectively induced by all-trans retinoic acid in human skin and dermal fibroblasts. In order to determine whether this response can be used as a reliable measure of retinoid potency and activity, we treated human skin fibroblasts for 24 h with increasing concentrations of several natural and synthetic retinoids. CRABP II mRNA levels were measured by quantitative Northern blotting and compared, when possible, with those obtained after topical application of the same retinoids to human skin. All eight active retinoids tested induced a concentration-dependent CRABP II mRNA response in the fibroblast assay. In contrast, one known inactive retinoid (meta-carboxy TTNPB), differing from the active form only in the position of the carboxyl substituent, failed to evoke a response. The fibroblast and human skin bioassays agreed with respect to relative potency and response amplitude for three of the three retinoids tested. Retinoic acid was approximately 10-fold more potent than retinal in both assays, suggesting that oxidation to retinoic acid underlies the activity of retinol in fibroblasts as well as in intact skin. In support of this hypothesis, treatment with liarozole, an inhibitor of P450-mediated retinoic acid oxidative catabolism, significantly increased fibroblast CRABP II mRNA levels and potentiated the effects of retinol by 1.5-fold at concentrations at which it had no effect on its own. Taken together, these results identify the fibroblast CRABP II response as a reproducible measure of retinoid bioactivity with promise as a predictor of human skin responses and further suggest that metabolism is an important determinant of retinoid bioactivity in vivo.

Biological Assay↗
PubMed1995

The effects of cyclosporin A and FK506 on proliferation and IL-8 production of cultured human keratinocytes.

The present study was conducted to determine whether cyclosporin A (CsA) and FK506 could be effective in inhibiting the proliferation and cytokine secretion of normal human epidermal keratinocytes (NHEK). NHEK proliferation in the presence of CsA and FK506 at the concentrations 10(-9) to 10(-5) M at 24 and 48 h time points was measured colorimetrically by the MTS assay. CsA had inhibitory effects from 10(-6) to 10(-5) M, while FK506 had no effect, except for toxicity at the very highest concentrations (5 x 10(-6) M and higher). NHEK cells spontaneously secrete IL-8 (243.4 +/- 55.5 pg/ml), and this baseline level was augmented by TNF-alpha alone, or synergistically by TNF-alpha and IFN-gamma, which are thought to be secreted by T cells. Neither CsA nor FK506 had any significant effect on either spontaneous or cytokine-stimulated keratinocyte IL-8 production. Therefore, it is most likely that the two drugs indirectly inhibit the keratinocyte inflammatory response through their actions on T cells or other immunocompetent cells.

Cell Division↗
PubMed1995

The genomic region of rbcLS in Synechococcus sp. PCC 7942 contains genes involved in the ability to grow under low CO2 concentration and in chlorophyll biosynthesis.

Several genes involved in the ability of Synechococcus sp. PCC 7942 to grow under different CO2 concentrations were mapped in the genomic region of rbcLS (the operon encoding the large and small subunits of ribulose-1,5-bisphosphate carboxylase/oxygenase). Insertion of a cartridge encoding kanamycin resistance within open reading frame (ORF) 78, designated ccmJ, located 7 kb upstream of rbcLS, resulted in a kanamycin-resistant, high-CO2-requiring mutant, M3, which does not contain normal carboxysomes. ccmJ shows significant homology to csoS1 encoding a carboxysomal shell polypeptide in Thiobacillus neopolitanus. Analysis of the polypeptide pattern of a carboxysome-enriched fraction indicated several differences between the wild type and the mutant. The amount of the ribulose-1,5-bisphosphate carboxylase/oxygenase subunits was considerably smaller in the carboxysomal fraction of the mutant when compared to the wild type. On the basis of the sequence analyses, ORF286 and ORF466, located downstream of ccmJ, were identified as chlL and chlN, respectively, which are involved in chlorophyll biosynthesis in the dark.

Algal Proteins↗
PubMed1995

Apheresis technologies: an international perspective.

The developments in apheresis techniques and their clinical applications world-wide are technologically driven. In the past, apheresis survey statistics have high-lighted both the differences by region in clinical practice and in the types of technologies utilized. Such differences have provided a basis for the scientific and clinical assessments of these apheresis technologies and their clinical outcomes and have stimulated the marketing and business development of new technologies world-wide. A review of the regional practices and technologies utilized provides a perspective on the future role of apheresis and its developments in clinical practice. While technology is a driving force for the development of new techniques for clinical practice, it is not the only market force. For technology introduction, several other important issues need to be considered. Regulations at the local and, most importantly, the federal level impact the timing for new technology introduction. Reimbursement by healthcare payers is critically important from the initiation of the development of a technology through its clinical use. Clinical trials are critically important to show the safety and clinical- and cost-effectiveness of the technology in order for payers to provide reimbursement for its use, but these trials are sometimes long and costly. Research funding availability at the governmental and commercial levels critically impacts new technology investigation and its introduction. Apheresis technology developments offer new hopes and promises for the clinical team; however, their development, introduction, and utilization will be influenced by the prevailing market forces.

Blood Component Removal↗
PubMed1995

Predictors of cognitive change in middle-aged and older adults with memory loss.

OBJECTIVE: Previous longitudinal studies of age-related memory loss have focused on objective neuropsychological measures that predict subsequent cognitive change, yet brain metabolic function, self-perception of memory loss, and other measures may also be sensitive indicators of cognitive change. To determine such baseline predictors of change, the authors made longitudinal assessments of middle-aged and older adults with memory loss. METHOD: Forty-two persons (mean age = 60 years, range = 43-81) with memory complaints received comprehensive baseline assessments, including subjective neuropsychological measures, objective measures of visual-spatial memory (the Benton Visual Retention Test) and verbal memory (the Buschke-Fuld Selective Reminding Test), and positron emission tomography scans to determine neocortical glucose metabolism. At an average follow-up of 3 years, the objective neuropsychological measures were again used to quantify the degree of cognitive change. RESULTS: Multiple regression analyses indicated that parietal asymmetry, sex of the subject, and baseline visual-spatial memory score were significant predictors of change in visual-spatial memory; level of education and baseline verbal memory score predicted change in verbal memory. Other neocortical asymmetry scores, age, family history of Alzheimer's disease, cerebral atrophy, and self-ratings of use of mnemonics were not significant predictors of change. CONCLUSIONS: Measures of cerebral metabolism, objective memory performance, sex, and education may predict subsequent cognitive change in middle-aged and older persons with memory loss. Also, the parietal asymmetry found in persons with questionable dementia that progresses to probable Alzheimer's disease may be present very early in the course of age-related cognitive decline.

Adult↗
PubMed1995

The feasibility and reliability of using a home screening test to detect gingival inflammation.

The purpose of this study was to evaluate the feasibility and reliability of using a home screening occult blood test to detect the presence of gingival inflammation. Fifty (50) healthy male and female subjects participated in this study. Pre- and post-stimulation saliva samples were obtained and tested for occult blood. Subjects brushed for one minute to stimulate gingival bleeding associated with inflammation. Saliva samples were obtained and tested for occult blood using a commercial screening kit. Following the screening test, a bleeding index (BOP) was determined and used as an indicator of gingival inflammation. Those with a BOP > 50% were assigned to the high group. Those with a BOP of 31 to 50% were assigned to the middle group, and those with a BOP of < or = 30% were assigned to the low group. Twelve subjects in the high group, 10 subjects in the mid group, and 2 subjects in the low group tested positive for occult blood following stimulation. A chi-square analysis showed an association between the screening test for occult blood and the groups (P = 0.0001). The test sensitivity was 75.9% and the specificity was 90.5%.

Adult↗
PubMed1994

Inactivation of ccmO in Synechococcus sp. Strain PCC 7942 Results in a Mutant Requiring High Levels of CO(2).

Inactivation of ccmO in Synechococcus sp. strain PCC 7942 resulted in a mutant which possesses aberrant carboxysomes and a normal inorganic carbon uptake capability but a reduced ability to photosynthetically utilize the internal inorganic carbon pool. Consequently, it exhibits low apparent photosynthetic affinity for extracellular inorganic carbon and demands high levels of CO(2) for growth.

Journal Article↗
PubMed1994

Anti-CD11a prevents deletion of self-reactive T cells in neonatal C57BR mice.

The process of thymic maturation permits development of T cells expressing receptors which recognize self-major histocompatibility complex (MHC) determinants, but deletes T cells recognizing self-MHC determinants with high affinity. This selection process is evolutionarily conserved, and presumably serves in part to prevent the release of autoreactive cells. However, the mechanisms involved in the selection process, and the molecules required are incompletely characterized. Lymphocyte function-associated antigen-1 (LFA-1) is an accessory molecule important in T-cell activation, is involved in thymocyte-epithelial cell binding, and contributes to the maturation of CD4-CD8- thymocytes to the CD4+CD8+ stage. In this report we have investigated whether LFA-1 also contributes to the thymic deletion of potentially self-reactive cells. Neonatal C57Br mice were injected with amounts of a monoclonal antibody to LFA-1 that saturated thymic binding sites, then splenocytes were examined for T cells expressing receptors normally deleted in the thymus. The results demonstrate that V beta 17a+ T cells, normally deleted in this strain, can be detected in the spleen following administration of anti-LFA-1, thus supporting the hypothesis that LFA-1 also contributes to negative selection. The potential significance of LFA-1 involvement in multiple thymic maturation events is discussed.

Animals↗
PubMed1993

Early cystic/necrotic changes after hyperfractionated radiation therapy in children with brain stem gliomas. Data from the Childrens Cancer Group.

BACKGROUND: A higher total dose of radiation therapy administered in fractionated lower individual doses twice daily (hyperfractionated radiation therapy) has been reported to improve survival for children with brain stem gliomas. However, this higher dose of radiation therapy may cause more sequelae. METHOD: Eighty-eight children with brain stem gliomas were treated with 100 cGy twice daily to a total dose of 7200 cGy. Patients were carefully followed up for treatment-related clinical or radiographic worsening. RESULTS: Thirteen (15%) had intralesional cystic/necrotic changes within 8 weeks of completion of treatment. Children with these changes had a variable clinical course, including steady deterioration in one child; initial improvement, followed by progressive deterioration in three; and initial improvement, followed by deterioration, with subsequent improvement or prolonged stabilization of condition without additional antineoplastic treatment in nine. CONCLUSION: This latter "triphasic" course suggests that "early" worsening after hyperfractionated radiation therapy at 7200 cGy may be a sequelae of therapy, rather than a symptom of progressive tumor growth. This has substantial implications for patient care and evaluation of the efficacy of treatment.

Adult↗
PubMed1993

Cephalometric evaluation of the changes in patients wearing complete dentures: a 20-year study.

The purpose of this continuing longitudinal investigation was to study the changes on the craniofacial complex in complete denture wearers; herein are reported the 20-year findings. At the onset of the study complete dentures were made for 64 persons. Two dentures techniques were employed: a complex method of construction and a simplified method. At the start of the project the patients' ages ranged from 30 to 60 years (average age 53 years) and all had been edentulous for at least 1 year (range 1 to 30 years). Lateral cephalometric radiographs were made immediately after initial placement of the dentures and during subsequent years (1, 2, 3, 4, 5, 7, 10, 15, and 20). The same cephalostat was used throughout and all films were exposed with the teeth in centric occlusion. Thirty-four subjects presented for the 20-year follow-up. Of this number, the radiographs of 24 subjects (14 women and 10 men; average age 65.5 years [range 50-83 years]) (12 complex denture wearers; 12 simplified technique denture wearers) were used in this report (10 had denture alterations over the 20-year period that excluded them). The 20-year observations corroborate earlier findings. There is a loss of the vertical dimension of occlusion as viewed from the right profile, and the mandible rotates in a counterclockwise fashion resulting in an increase in relative prognathism. The maxillary alveolus was stable, the mandibular alveolus resorbed, and the dentures rotated counterclockwise and shifted slightly forward. The observed changes were not significantly affected by the sex of the patient or by the denture technique employed.

Aged↗
PubMed1993

Platelet aggregometry can accurately predict failure of externally supported knitted Dacron femoropopliteal bypass grafts.

PURPOSE: Our purpose was to evaluate whether a method for quantification of platelet aggregability will predict failure of knitted Dacron femoropopliteal bypass grafts. METHODS: A numerically derived platelet aggregation (PA) score, based on the aggregation pattern and platelet count, was determined in the 40 patients available for platelet analysis who underwent 53 femoropopliteal bypass grafts with preclotted, 6 mm, externally supported knitted Dacron grafts from 1981 to 1991 (mean follow-up 50 months). The preoperative score was found to remain stable after surgery, enabling the use of postoperative values when preoperative values were not available. The PA score was available in 19 patients (23 grafts) before surgery and 23 patients (30 grafts) after surgery. The following factors were analyzed for predicting graft failure by the Cox proportional hazards regression model: PA score, age, gender, history of smoking, coronary artery disease, hypertension, hyperlipidemia, cerebrovascular disease, diabetes, claudication versus limb salvage, site of the distal anastomosis, previous ipsilateral bypass, and state of the runoff as determined by preoperative angiography. RESULTS: Of the studied risk factors, the value of the PA score was the most significant predictor of graft closure (p < 0.0001). An increase of 10 units was associated with an increased relative risk of 2.02. Throughout the follow-up period, 15 of 16 grafts remained patent in patients with a PA score of 15 or less, but only 2 grafts out of 17 remained patent in patients with a PA score of 30 or greater. CONCLUSIONS: These data suggest that the PA score is a potential risk factor for failure of femoropopliteal bypass with externally supported knitted Dacron grafts.

Adenosine Diphosphate↗
PubMed1993

High CO2 concentration alleviates the block in photosynthetic electron transport in an ndhB-inactivated mutant of Synechococcus sp. PCC 7942.

The high-concentration CO2-requiring mutant N5 of Synechococcus sp. PCC 7942 was obtained by the insertion of a kanamycin-resistant gene at the EcoRI site, 12.4 kb upstream of rbc. The mutant is unable to accumulate inorganic carbon internally and exhibits very low apparent photosynthetic affinity for inorganic carbon but a photosynthetic Vmax similar to that of the wild type. Sequence and northern analyses showed that the insertion inactivated a gene highly homologous to ndhB, encoding subunit II of NADH dehydrogenase in Synechocystis sp. PCC 6803 (T. Ogawa [1991] Proc Natl Acad Sci USA 88: 4275-4279). When the mutant and the wild-type cells were exposed to 5% CO2 in air, their photosynthetic electron transfer capabilities, as revealed by fluorescence and thermoluminescence measurements, were similar. On the other hand, a significant decrease in variable fluorescence was observed when the mutant (but not the wild-type) cells were exposed to low CO2 under continuous light. The same treatment also resulted in a shift (from 38-27 degrees C) in the temperature at which the maximal thermoluminescence emission signal was obtained in the mutant but not in the wild type. These results may indicate that subunit II of NADH dehydrogenase is essential for the functional operation of the photosynthetic electron transport in Synechococcus under low but not high levels of CO2. We suggest that the inability to accumulate inorganic carbon under air conditions stems from disrupture of electron transport in this mutant.

Amino Acid Sequence↗
PubMed1993

[Experimental use of liposomes carrying an antimetabolite (mitoxantrone) in filtering surgery].

Fibroblast proliferation plays a prominent role in closure of conjunctival filtering blebs and extensive investigations are being carried out to optimize antiproliferative pharmacotherapy in the prevention of filtering bleb failure in glaucomatous eyes with a poor prognosis undergoing surgery. Intercalating agents such as doxorubicin or daunorubicin have been shown to decrease fibroblast proliferation in tissue cultures. A liposomal delivery system was developed in an attempt to obtain a sustained release effect and to minimize ocular side effects of mitoxantrone (Novantrone, MITX), an antineoplastic agent with intercalating properties. The objectives of this study were to demonstrate the entrapment stability of MITX in multilamellar vesicles (reaching about 60% and remaining at this level for 8-weeks storage) and to investigate its activity in vitro (cell cultures) and in vivo (sclerectomy ab externo in rabbits). We showed that entrapped MITX inhibited in a dose-dependent manner subconjunctival fibroblast proliferation (ID50: 0.03 micrograms/l at D3 in cultures) and prolonged the success of filtration surgery in rabbits (decrease of intraocular pressure of 8 mm Hg in treated eyes versus 1.8 mm Hg in control eyes; p < 0.01). These results indicate the potential of MITX-entrapped liposomes in the control of conjunctival scarring in filtering bleb surgery.

Animals↗
PubMed1992

A sequence in beta-hexosaminidase from Dictyostelium discoideum required for sorting of proteins to a compartment involved in developmentally induced secretion.

To study the sorting of proteins in Dictyostelium discoideum, we used vector constructs that contain cDNA coding for the entire beta-hexosaminidase protein to prepare transformants of a mutant that lacks this enzyme activity. These transformants overexpressed active, normally processed beta-hexosaminidase. The overexpressed enzyme colocalized with other acid hydrolases in the soluble fraction of vesicles in the lysosomal region of Percoll gradients. The sorting of other hydrolases was unaltered. We also prepared transformants with constructs that contain 22 (Hex 22-Inv), 70 (Hex 70-Inv), and 532 (Hex 532-Inv) amino-terminal amino acids from beta-hexosaminidase fused in frame with the coding sequence for the yeast SUC2 gene product, invertase. Fusion molecular masses were those expected for fully N-glycosylated proteins. Hex 22-Inv was rapidly (t1/2 less than 30 min) and quantitatively secreted. The others were slowly (t1/2 greater than 5 h) and partially secreted. Each expressed invertase activity. During growth, the invertase activity of Hex 70-Inv and Hex 532-Inv was retained to the same extent as that of endogenous lysosomal enzymes. Most of the Hex 70-Inv migrated in Percoll gradients with vesicles of intermediate density (d = 1.055), but a portion co-migrated with lysosomal enzymes at d = 1.08. Hex 70-Inv was sulfated, and its N-glycosides were resistant to endoglycosidase H, indicating Golgi processing. Hex 70-Inv and Hex 532-Inv, like endogenous lysosomal enzymes, were subject to developmentally induced secretion.

Animals↗
PubMed1992

Comparative evaluation of the elasticity and flexibility of bioimpregnated knitted grafts.

Longitudinal elasticities of whole human blood clot, whole canine blood clot, Factor XIII cross-linked fibrin, glutaraldehyde-fixed human albumin, and formaldehyde-fixed collagen, gelatin and collagen/gelatin were determined and normalized to human whole blood clot. Matrices of a knitted Dacron graft were then impregnated with albumin, collagen, and collagen/gelatin and their longitudinal elasticities were determined and normalized to a preclotted graft. Comparisons were also made for the longitudinal elasticities of a virgin graft, a manipulated control for a preclotted graft, and a manipulated control for the matrix-impregnated grafts. Flexibilities were then calculated based on the weights and elasticities of these grafts and normalized to the flexibility of the preclotted graft. Fibrin had twice and 39 times more longitudinal elasticity than human blood clot and collagen, respectively. The preclotted graft has longitudinal elastic properties similar to a virgin graft, and is 2.8, 2, and 1.4 times more elastic than the albumin, collagen and collagen/gelatin grafts, respectively. The preclotted graft was 2.5, 2, and 1.4 times more flexible than the albumin, collagen and collagen/gelatin grafts, respectively.

Albumins↗
PubMed1992

A Cyanobacterial Gene Encoding Peptidyl-Prolyl cis-trans Isomerase.

The rotA gene encoding peptidyl-prolyl cis-trans isomerase has been identified, sequenced, and shown to be transcribed in the cyanobacterium Synechococcus sp. PCC7942. Inactivation of the gene by replacement of a region containing the open reading frame with a gene conferring kanamycin resistance resulted in merodiploids containing both the wild type and the modified genomic region. We were not able to isolate a kanamycin-resistant mutant in which all the genomic wild-type copies were substituted, which suggests that such replacement could have been lethal.

Journal Article↗