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Biomedical subjects

A Katz

Publications and source records attributed to A Katz.

At least 73 records · Page 4Linked to original sources

Norditerpenoid alkaloids from the roots of Delphinium stapeliosum.

From the roots of Delphinium stapeliosum three new norditerpenoid alkaloids, 14-demethyltuguaconitine (1), 14-deacetyl-14-isobutyrylnudicauline (2), and 14-deacetyl-14-isobutyrylajadine (3), and nine known norditerpenoid alkaloids, delbonine (4), methyllycaconitine (5), 14-deacetylnudicauline (6), ajacine (7), deltatsine (8), delcosine (9), 14-deacetylajadine (10), nudicauline (11), and ajadine (12), were isolated. Structure elucidation and identification were based on NMR and mass spectra.

Alkaloids↗

Therapeutic potential of curcumin in human prostate cancer-I. curcumin induces apoptosis in both androgen-dependent and androgen-independent prostate cancer cells.

In an effort to find an alternative nontoxic means of inducing the apoptosis potential in both androgen-dependent and hormone refractory prostate cancer cells, attention was focused on curcumin (turmeric), traditionally used in medicine and cuisine in India and other south-east Asian countries. The results indicate that curcumin is a novel and potent inducer of apoptosis in both androgen-dependent and androgen-independent prostate cancer cells. This was accomplished by down-regulating apoptosis suppressor proteins and other crucial proteins such as the androgen receptor. It is concluded that curcumin may provide an alternative, nontoxic modality by which the clinician may prevent the progression of prostate cancer to its hormone refractory state or to treat advanced prostate cancer by forcing them to undergo apoptosis. Prostate Cancer and Prostatic Diseases (2000) 3, 84-93

Journal Article↗

Brain perfusion monitoring with frequency-domain and continuous-wave near-infrared spectroscopy: a cross-correlation study in newborn piglets.

The newborn piglet brain model was used to correlate continuous-wave (CW) and frequency-domain (FD) near-infrared spectroscopy. Six ventilated and instrumented newborn piglets were subjected to a series of manipulations in blood oxygenation with the effects on brain perfusion known to be associated with brain hypoxia-ischaemia. An excellent agreement between the CW and FD was demonstrated. This agreement improved when the scattering properties (determined by the FD device) were employed to calculate the differential pathlength factor, an important step in CW data processing.

Animals↗

Is creatine kinase responsible for fatigue? Studies of isolated skeletal muscle deficient in creatine kinase.

Creatine kinase (CK) is a key enzyme for maintaining a constant ATP/ADP ratio during rapid energy turnover. To investigate the role of CK in skeletal muscle fatigue, we used isolated whole muscles and intact single fibers from CK-deficient mice (CK(-/-)). With high-intensity electrical stimulation, single fibers from CK(-/-) mice displayed a transient decrease in both tetanic free myoplasmic [Ca(2+)] ([Ca(2+)](i), measured with the fluorescent dye indo-1) and force that was not observed in wild-type fibers. With less intense, repeated tetanic stimulation single fibers and EDL muscles, both of which are fast-twitch, fatigued more slowly in CK(-/-) than in wild-type mice; on the other hand, the slow-twitch soleus muscle fatigued more rapidly in CK(-/-) mice. In single wild-type fibers, tetanic force decreased and [Ca(2+)](i) increased during the first 10 fatiguing tetani, but this was not observed in CK(-/-) fibers. Fatigue was not accompanied by phosphocreatine breakdown and accumulation of inorganic phosphate in CK(-/-) muscles. In conclusion, CK is important for avoiding fatigue at the onset of high-intensity stimulation. However, during more prolonged stimulation, CK may contribute to the fatigue process by increasing the myoplasmic concentration of inorganic phosphate.

Animals↗

Oral etoposide for Merkel cell carcinoma in patients previously treated with intravenous etoposide.

We describe three patients with advanced Merkel cell carcinoma who were treated with etoposide given orally for recurrent regional lymph node involvement 18 to 30 months after exposure to etoposide given intravenously. Etoposide given orally (100 mg/day) was given for 10 to 14 consecutive days and repeated every 21 to 28 days for a median of three courses (range: two to four). Toxicity was minimal and mainly hematologic. Two patients showed a complete response and one a partial response, all of very rapid onset. All three patients are alive 6, 9, and 42 months from the start of oral treatment. Two remain progression free, and one had a recurrence 1 month after completion of chemotherapy. We suggest that orally administered etoposide, a topoisomerase II inhibitor, has a strong antitumor effect in advanced Merkel cell carcinoma, even in patients previously treated parenterally with the same drug. This action may be explained by the greater dependence of the drug's efficacy on the duration of administration rather than the dose intensity.

Administration, Oral↗

Furcation groove of buccal root of maxillary first premolars--a morphometric study.

Furcation grooves on the palatal aspect of the buccal roots of 35 maxillary first premolars, randomly selected, were assessed and found to exist in 97% of the sample. The buccal roots were sectioned into slices, 1 mm thick, and morphometric horizontal and vertical measurements were taken by a Toolmaker Microscope. The slice with the deepest invaginations served as the reference plane. The deepest invaginations were found to be at a mean distance of 1.18 mm from the bifurcation, with a mean depth of 0.4 mm. The canal had a kidney-shaped appearance in cross-section, and the mean distance from the invagination to the canal wall was 0.81 mm. It is thus hazardous to use rotary instruments for flaring these roots and any circular-shaped post space preparation at this level is contraindicated. The outcome of such procedures might be root thinning, perforation, or vertical root fracture, thus causing a poor prognosis.

Bicuspid↗

Mutations in the FIE and MEA genes that encode interacting polycomb proteins cause parent-of-origin effects on seed development by distinct mechanisms.

In flowering plants, two cells are fertilized in the haploid female gametophyte. Egg and sperm nuclei fuse to form the embryo. A second sperm nucleus fuses with the central cell nucleus, which replicates to generate the endosperm, a tissue that supports embryo development. The FERTILIZATION-INDEPENDENT ENDOSPERM (FIE) and MEDEA (MEA) genes encode WD and SET domain polycomb proteins, respectively. In the absence of fertilization, a female gametophyte with a loss-of-function fie or mea allele initiates endosperm development without fertilization. fie and mea mutations also cause parent-of-origin effects, in which the wild-type maternal allele is essential and the paternal allele is dispensable for seed viability. Here, we show that FIE and MEA polycomb proteins interact physically, suggesting that the molecular partnership of WD and SET domain polycomb proteins has been conserved during the evolution of flowering plants. The overlapping expression patterns of FIE and MEA are consistent with their suppression of gene transcription and endosperm development in the central cell as well as their control of seed development after fertilization. Although FIE and MEA interact, differences in maternal versus paternal patterns of expression, as well as the effect of a recessive mutation in the DECREASE IN DNA METHYLATION1 (DDM1) gene on mutant allele transmission, indicate that fie and mea mutations cause parent-of-origin effects on seed development by distinct mechanisms.

Arabidopsis↗

ECG signal compression using analysis by synthesis coding.

In this paper, an elecrocardiogram (ECG) compression algorithm, called analysis by synthesis ECG compressor (ASEC), is introduced. The ASEC algorithm is based on analysis by synthesis coding, and consists of a beat codebook, long and short-term predictors, and an adaptive residual quantizer. The compression algorithm uses a defined distortion measure in order to efficiently encode every heartbeat, with minimum bit rate, while maintaining a predetermined distortion level. The compression algorithm was implemented and tested with both the percentage rms difference (PRD) measure and the recently introduced weighted diagnostic distortion (WDD) measure. The compression algorithm has been evaluated with the MIT-BIH Arrhythmia Database. A mean compression rate of approximately 100 bits/s (compression ratio of about 30:1) has been achieved with a good reconstructed signal quality (WDD below 4% and PRD below 8%). The ASEC was compared with several well-known ECG compression algorithms and was found to be superior at all tested bit rates. A mean opinion score (MOS) test was also applied. The testers were three independent expert cardiologists. As in the quantitative test, the proposed compression algorithm was found to be superior to the other tested compression algorithms.

Algorithms↗

The weighted diagnostic distortion (WDD) measure for ECG signal compression.

In this paper, a new distortion measure for electrocardiogram (ECG) signal compression, called weighted diagnostic distortion (WDD) is introduced. The WDD measure is designed for comparing the distortion between original ECG signal and reconstructed ECG signal (after compression). The WDD is based on PQRST complex diagnostic features (such as P wave duration, QT interval, T shape, ST elevation) of the original ECG signal and the reconstructed one. Unlike other conventional distortion measures [e.g. percentage root mean square (rms) difference, or PRD], the WDD contains direct diagnostic information and thus is more meaningful and useful. Four compression algorithms were implemented (AZTEC, SAPA2, LTP, ASEC) in order to evaluate the WDD. A mean opinion score (MOS) test was applied to test the quality of the reconstructed signals and to compare the quality measure (MOSerror) with the proposed WDD measure and the popular PRD measure. The evaluators in the MOS test were three independent expert cardiologists, who studied the reconstructed ECG signals in a blind and a semiblind tests. The correlation between the proposed WDD measure and the MOS test measure (MOSerror) was found superior to the correlation between the popular PRD measure and the MOSerror.

Algorithms↗

Patterns of accelerated junctional rhythm during slow pathway catheter ablation for atrioventricular nodal reentrant tachycardia: temperature dependence, prognostic value, and insights into the nature of the slow pathway.

INTRODUCTION: Although accelerated junctional rhythm (AJR) is a known marker for successful slow pathway (SP) ablation sites, AJR may just be a regional effect of the anisotropic conduction properties of this area of the heart. We believe that detailed assessment of the AJR might provide insight into the SP specificity of this AJR and perhaps the nature of the SP itself. METHODS AND RESULTS: Our ablation protocol consisted of 30-second, 70 degrees C temperature-controlled ablation pulses with assessment after each pulse. Serial booster ablations were performed at the original successful site and at least 2 to 3 nearby sites to assess for residual AJR after the procedure in 50 consecutive SP ablations. We defined three distinct patterns of AJR: continuous AJR that persisted until the end of energy delivery (group I, 25 patients); alternating or "stuttering" AJR that persisted throughout energy delivery (group II, 9 patients); and AJR that ended abruptly during energy delivery (group III, 16 patients). Mean ablation temperatures in the three groups was 57 degrees+/-5 degrees C, 54 degrees+/-5 degrees C, and 63 degrees+/-5 degrees C, respectively (P = 0.0002 for groups I and II vs group III). Ten of 34 (29%) patients in groups I and II ("low-temperature ablation") exhibited residual SP (jump and/or single echo beats) despite tachycardia noninducibility, and 25 of 34 (73%) patients had residual AJR during the booster ablations, but neither of these was seen in any group III patients. CONCLUSION: Ablation temperature correlates with the pattern of AJR produced during SP ablation. That higher temperature lesions simultaneously abolish all SP activity as well as the focus of AJR suggests that this AJR is specific for the SP and is not a nonspecific regional effect.

Adult↗

The relationship between neural alterations and behavioral deficits after prenatal exposure to heroin.

The present studies employ multitudinous approaches in order to overcome the methodological obstacles in the understanding of the relationship between neurochemical alterations and behavioral deficits induced by heroin during prenatal development. Mice were exposed prenatally to heroin via daily subcutaneous injections of 10 mg/kg, on gestation days 9-18. At age 50 days, the heroin-exposed offspring displayed behavioral deficits as assessed in the eight-arm and Morris mazes, pointing to possible alteration in the septohippocampal cholinergic innervations. Biochemically there was increased presynaptic activity of these innervations as attested to by the increased [3H]hemicholinium-3 (HC-3) binding sites and by K+-stimulated inositol phosphate (IP) formation. Postsynaptically, there was global hyperactivation along the different components of the nerve conduction cascade, including an increase in M1 muscarinic receptor Bmax, a general increase in G-proteins (GP) including the most relevant, G subtype, and an increase in IP formation and in basal protein kinase C (PKC) activity. However, there was desensitization of PKC activity in response to cholinergic agonist in the heroin-exposed offspring. Transplantation of normal embryonic cholinergic cells to the impaired hippocampus reversed the behavioral deficits and both the pre- and postsynaptic hyperactivity and resensitized PKC activity. To support and further strengthen the findings of the neural grafting study, correlation of the heroin-induced behavioral deficits with the biochemical alterations, done within individuals, was applied. The results showed high r values for IP formation, basal PKC, and PKC desensitization. The r values for HC-3 binding were statistically significant but relatively low. Taken together, the findings of the neural grafting and correlation studies bring us closer to understanding the relationship between the prenatal heroin-induced biochemical and behavioral changes. However, mammalian models possess the inherent methodological hindrances, stemming from possible maternal effects. To provide a control for these confounding variables, a chick embryo model was applied in which filial imprinting, a behavior related to a specific hyperstriatal nucleus, served as an endpoint. Heroin was administered to developing chick embryos by injecting the eggs (20 mg/kg) on incubation days (ID) 0 or 5. Prehatch exposure to heroin markedly diminished the ability for filial imprinting in the hatched chicks.

Acetylcholine↗

Locoregional recurrence patterns after mastectomy and doxorubicin-based chemotherapy: implications for postoperative irradiation.

PURPOSE: The objective of this study was to determine locoregional recurrence (LRR) patterns after mastectomy and doxorubicin-based chemotherapy to define subgroups of patients who might benefit from adjuvant irradiation. PATIENTS AND METHODS: A total of 1,031 patients were treated with mastectomy and doxorubicin-based chemotherapy without irradiation on five prospective trials. Median follow-up time was 116 months. Rates of isolated and total LRR (+/- distant metastasis) were calculated by Kaplan-Meier analysis. RESULTS: The 10-year actuarial rates of isolated LRR were 4%, 10%, 21%, and 22% for patients with zero, one to three, four to nine, or >/= 10 involved nodes, respectively (P <.0001). Chest wall (68%) and supraclavicular nodes (41%) were the most common sites of LRR. T stage (P <.001), tumor size (P <.001), and >/= 2-mm extranodal extension (P <.001) were also predictive of LRR. Separate analysis was performed for patients with T1 or T2 primary disease and one to three involved nodes (n = 404). Those with fewer than 10 nodes examined were at increased risk of LRR compared with those with >/= 10 nodes examined (24% v 11%; P =.02). Patients with tumor size greater than 4.0 cm or extranodal extension >/= 2 mm experienced rates of isolated LRR in excess of 20%. Each of these factors continued to significantly predict for LRR in multivariate analysis by Cox logistic regression. CONCLUSION: Patients with tumors >/= 4 cm or at least four involved nodes experience LRR rates in excess of 20% and should be offered adjuvant irradiation. Additionally, patients with one to three involved nodes and large tumors, extranodal extension >/= 2 mm, or inadequate axillary dissections experience high rates of LRR and may benefit from postmastectomy irradiation.

Adult↗

Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans.

Insulin resistance plays an important role in the pathophysiology of diabetes and is associated with obesity and other cardiovascular risk factors. The "gold standard" glucose clamp and minimal model analysis are two established methods for determining insulin sensitivity in vivo, but neither is easily implemented in large studies. Thus, it is of interest to develop a simple, accurate method for assessing insulin sensitivity that is useful for clinical investigations. We performed both hyperinsulinemic isoglycemic glucose clamp and insulin-modified frequently sampled iv glucose tolerance tests on 28 nonobese, 13 obese, and 15 type 2 diabetic subjects. We obtained correlations between indexes of insulin sensitivity from glucose clamp studies (SI(Clamp)) and minimal model analysis (SI(MM)) that were comparable to previous reports (r = 0.57). We performed a sensitivity analysis on our data and discovered that physiological steady state values [i.e. fasting insulin (I(0)) and glucose (G(0))] contain critical information about insulin sensitivity. We defined a quantitative insulin sensitivity check index (QUICKI = 1/[log(I(0)) + log(G(0))]) that has substantially better correlation with SI(Clamp) (r = 0.78) than the correlation we observed between SI(MM) and SI(Clamp). Moreover, we observed a comparable overall correlation between QUICKI and SI(Clamp) in a totally independent group of 21 obese and 14 nonobese subjects from another institution. We conclude that QUICKI is an index of insulin sensitivity obtained from a fasting blood sample that may be useful for clinical research.

Adult↗

Dexamethasone does not significantly contribute to the response rate of docetaxel and estramustine in androgen independent prostate cancer.

PURPOSE: We evaluated the independent response rate of dexamethasone before docetaxel and estramustine administration as measured by changes in serum prostate specific antigen (PSA) in patients with androgen independent prostate cancer. MATERIALS AND METHODS: A total of 12 patients received 20 mg. dexamethasone orally every 6 hours for 3 doses repeated every 3 weeks before starting cytotoxic therapy with estramustine and docetaxel. After progression on dexamethasone 280 mg. estramustine orally 3 times daily on days 1 to 5 and 70 mg./m.2 docetaxel intravenously for 1 hour on day 2 were given. RESULTS: None of the patients initially treated with dexamethasone monotherapy (median 1 cycle, range 1 to 5) had a PSA decline of 50% or greater. Median PSA increase on monotherapy was 47% (range 0% to 22%). On estramustine and docetaxel therapy PSA decreased 50% or greater in 11 patients (92%, 95% confidence intervals [CI] 60 to 99) and 80% or greater in 7 (58%, 95% CI 29 to 84), and normalized in 5 (42%, 95% CI 16 to 71), with a median duration of response of 153 (range 42 to 371), 132 (range 84 to 287) and 84 (range 21 to 174) days, respectively. Median times to reach 50% and 80% decreases in baseline PSA were 21 (range 21 to 209) and 63 (range 21 to 138) days, respectively. In 9 patients (75%, 95% CI 43 to 93) PSA decreased at least 50% by week 9. Of 4 patients with bidimensionally measurable disease 3 had a partial response. Median time to progression was 263 days (range 91 to 378). CONCLUSIONS: Administration of 20. mg. dexamethasone orally every 6 hours for 3 doses every 3 weeks does not significantly contribute to the PSA response rate of estramustine and docetaxel.

Adenocarcinoma↗

Therapeutic potential of curcumin in human prostate cancer. II. Curcumin inhibits tyrosine kinase activity of epidermal growth factor receptor and depletes the protein.

PURPOSE: In a search for alternative and preventive therapies for prostate cancer, attention was focused on the ways in which curcumin (Turmeric), used in food and medicine in India for centuries, could interfere with the growth factor signaling pathways in both androgen-dependent and androgen-independent prostate cancer cells, as exemplified by the epidermal growth factor receptor (EGF-R) signaling. MATERIALS AND METHODS: The androgen-sensitive LNCaP and androgen-insensitive PC-3 cell lines were grown in 5 to 50 microM curcumin and analyzed for EGF-R protein by Western blotting and for EGF-R tyrosine kinase activity. RESULTS: Curcumin was a potent inhibitor of EGF-R signaling, and it accomplished this effect by three different means (1) down regulating the EGF-R protein; (2) inhibiting the intrinsic EGF-R tyrosine kinase activity; and (3) inhibiting the ligand-induced activation of the EGF-R. CONCLUSIONS: These results, taken together with our previous results that curcumin can induce apoptosis in both androgen-dependent and androgen-independent prostate cancer cells, support our view that curcumin may be a novel modality by which one can interfere with the signal transduction pathways of the prostate cancer cell and prevent it from progressing to its hormone-refractory state.

Androgens↗