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D Schultz

Publications and source records attributed to D Schultz.

At least 73 records · Page 4Linked to original sources
PubMed1995

Ultrastructure and motility of spermatozoa in macropodid and potoroidid marsupials.

In order to gain some understanding of the significance of the morphological features of spermatozoa within the Macropodoidea, the motility of spermatozoa from two macropodids (Petrogale xanthopus and Dendrolagus matschiei) and the motility, number and distribution of spermatozoa from three potoroidids (Aepyprymnus rufescens, Bettongia penicillata and Potorous tridactylus) were examined. Sperm were collected by electro-ejaculation or from the cauda epididymides. Epididymides from the potoroidids were divided into 12 regions. One epididymidis per animal was fixed for light and transmission electron microscopy and, on the contralateral side, the number of sperm, their distribution and motility were determined. In general, spermatozoa of all five species differed markedly from one another in head and flagella dimensions. Spermatozoa from B. penicillata and P. tridactylus were significantly longer and broader and had a smaller acrosome relative to head length, and there was a radial displacement of dense fibres. They also progressed more rapidly in standard culture media. Spermatozoa from at least three species were able to alter their motility pattern in vitro as media viscosity increased. Sperm movement in all species appeared to be restricted to one plane and showed no evidence of rotation, whereas lateral head displacement was often pronounced; there was no evidence of a sinusoidal mode of progressive motility. Testicular and epididymal sperm numbers in A. rufescens and P. tridactylus were relatively high (approximately 17.5-50 x 10(6)). In A. rufescens, approximately 69% of all epididymal sperm were located in the cauda epididymidis compared with approximately 40% in P. tridactylus. This study demonstrated that marked radial displacement of the dense fibres is probably closely associated with the ability to develop a sinusoidal mode of progressive movement, and that this feature of the sperm tail structure is not just linked with sperm size. Sperm size, however, is associated with sperm velocity.

Animals↗
PubMed1995

The inhibition of foam cell formation by sodium diethyldithiocarbamate.

A prominent feature of human atherosclerosis is the lipid-laden foamy macrophage, which often also contains the insoluble pigment, ceroid. The culture of macrophage-like cells, P388D1s, with artificial lipoproteins composed of cholesteryl linoleate (CL) and bovine serum albumin (BSA) results in foam cell formation with lipoprotein uptake and the intracellular accumulation of ceroid. Ceroid accumulation is accompanied by the oxidation of the cholesterol ester as monitored by gas chromatography. The sodium salt of diethyldithiocarbamic acid (DDC) at 1-5 microM effectively inhibited lipoprotein uptake, cholesteryl linoleate oxidation and ceroid accumulation in cultures of P388D1. Further studies showed that intracellular ceroid accumulation appeared to require the presence of cystine in the medium. Lipoprotein oxidation by this macrophage-like cell therefore appears to involve a mechanism dependent on cystine metabolism which is consistent with previous reports of macrophage-mediated lipoprotein oxidation. Studies on CL/BSA-induced ceroid accumulation in human monocytes also showed that DDC behaved in much the same manner. This inhibitory effect of DDC on foam cell formation, often considered a primary event of atherosclerosis, at concentrations as low as 1 microM, suggests the need for further, more comprehensive, studies on this compound's activities.

Albumins↗
PubMed1995

A multivariate analysis of clinical and pathological factors that predict for prostate specific antigen failure after radical prostatectomy for prostate cancer.

A Cox regression multivariate analysis was done to determine the clinical and pathological indicators that predict for prostate specific antigen (PSA) failure in 347 patients who underwent radical prostatectomy for clinically localized prostate cancer between 1989 and 1993. In the patient subgroups (PSA less than 20 ng./ml. and biopsy Gleason sum 5 to 7 or PSA more than 10 to 20 ng./ml. and biopsy Gleason sum 2 to 4) not classifiable into those at high and low risk for postoperative PSA failure using PSA and biopsy Gleason sum, the status of the seminal vesicles and prostatic capsule on endo-rectal coil magnetic resonance imaging (MRI) allowed for this categorization. Specifically, 2-year actuarial PSA failure rates were 84% versus 23% in patients with and without seminal vesicle invasion, respectively, on MRI (p < 0.0001) and 58% versus 21% in those with and without extracapsular extension, respectively (p = 0.0001). In patients with extracapsular extension but without pathological involvement of the seminal vesicle(s) or poorly differentiated tumors (pathological Gleason sum 8 to 10), the 2-year actuarial PSA failure rates were 50% (margin positive), 28% (margin negative with established extracapsular disease) and 9% (margin negative with focal microscopic extracapsular disease). Therefore, endo-rectal coil MRI showing seminal vesicle invasion or extracapsular extension when the PSA level is less than 20 ng./ml. and the biopsy Gleason sum is 5 to 7 or the PSA level is more than 10 but less than 20 ng./ml. and the biopsy Gleason sum is 2 to 4 predicted for PSA failure. In patients with extracapsular extension who had pathological Gleason sum less than 8 disease with uninvolved seminal vesicles, the margin status and extent of extracapsular disease predicted for PSA failure.

Actuarial Analysis↗
PubMed1994

Dysplastic nevi as a melanoma risk factor in patients with familial melanoma.

BACKGROUND: Familial melanoma has been associated with "clinically atypical moles" or "dysplastic nevi," (DN) which are markers for increased melanoma risk. In addition, melanomas in these kindreds present at a younger age, and tend to be multiple. METHODS: Melanoma incidence rates were determined for 710 members of 311 melanoma families, defined as kindreds in which melanoma had occurred in two or more blood relatives. Patients were classified either clinically or histologically as expressing DN. Melanomas that occurred before the first examination were recorded, and patients were followed prospectively for new melanomas. RESULTS: In prospective follow-up, the age-adjusted melanoma incidence rate was 1710/100,000 patient-years in family members with DN. In contrast, the rate was zero (no melanomas occurred) in family members without DN. For family members with DN, but without a history of melanoma, the age-adjusted incidence rate of melanoma was 413/100,000 patient-years, whereas the rate was 2779/100,000 patient-years in family members with DN and a history of melanoma. CONCLUSIONS: Dysplastic nevi and a history of melanoma are strong risk factors for subsequent melanoma. Prognostic factors are greatly improved for patients with melanomas diagnosed in follow-up compared with the first two melanomas in each kindred. These findings warrant surveillance of individuals with DN who are members of familial melanoma kindreds.

Adult↗
PubMed1994

A multivariable analysis of clinical factors predicting for pathological features associated with local failure after radical prostatectomy for prostate cancer.

PURPOSE: A multivariate analysis is used to determine the predictive value of pretreatment clinical indicators on pathologic features associated with local failure after radical prostatectomy in patients with prostate cancer. METHODS AND MATERIALS: A retrospective review of the pathologic findings of 235 patients with adenocarcinoma of the prostate treated between 1990 and 1993 with a radical retropubic prostatectomy was performed. The preoperative clinical data including the serum prostate specific antigen, clinical stage, Gleason sum, and endorectal magnetic resonance scan findings are used to identify patients prior to definitive treatment who would be at high risk for having pathologic features associated with local failure at radical prostatectomy. Outcome prediction curves are constructed from a logistic regression multivariate analysis displaying the probability of pathologic involvement of the seminal vesicle, extracapsular disease, or positive surgical margins as a function of the preoperative prostate specific antigen and Gleason sum for the cases when the endorectal magnetic resonance scan is positive, negative, or not included in the multivariate analysis. RESULTS: Factors identified on multivariate analysis as significant predictors of seminal vesicle invasion include endorectal magnetic resonance scan findings (p < 0.0001), and preoperative prostate specific antigen (p = 0.017). Endorectal magnetic resonance scan findings (p = 0.0016), preoperative prostate specific antigen (p = 0.0002), and Gleason sum (p < 0.0001) were significant predictors of extracapsular extension and preoperative prostate specific antigen (p < 0.0001) and Gleason sum (p = 0.03) were significant predictors of disease extending to the margins of resection. Clinical stage was not a significant predictor (p > 0.05) of pathologic features associated with local failure on multivariate analysis. As a single modality, endorectal surface coil magnetic resonance imaging was accurate 93%, 69%, and 72% of the time for predicting seminal vesicle invasion, transcapsular disease, and final pathologic stage, respectively. Failure to recognize microscopic penetration of the capsule found at the time of pathologic evaluation in a prostate gland with a grossly intact capsule accounts for the majority (70%) of the staging inaccuracies. CONCLUSIONS: The use of the endorectal surface coil magnetic resonance scan findings in conjunction with both the serum prostate specific antigen and Gleason sum improves the clinical accuracy of predicting those patients at high risk for clinically unsuspected extraprostatic disease. In particular, for the subgroup of patients with moderately elevated prostate specific antigen (> 10-20 ng/mL) and intermediate grade clinically organ confined prostate cancer [Gleason sum: 5-7] where the specificity of these tests to predict for occult extraprostatic disease is suboptimal, the additional information obtained from the endorectal coil magnetic resonance scan allows the physician to definitively subgroup these patients into low and high risk for seminal vesicle invasion or transcapsular disease.

Adenocarcinoma↗
PubMed1994

Hypoxia-selective antitumor agents. 9. Structure-activity relationships for hypoxia-selective cytotoxicity among analogues of 5-[N,N-bis(2-chloroethyl)amino]-2,4-dinitrobenzamide.

A series of analogues of the novel hypoxia-selective cytotoxin 5-[N,N-bis(2-chloroethyl)amino]-2,4-dinitrobenzamide (6) have been prepared and evaluated, in a search for compounds which retain high hypoxic selectivity but have increased potency and/or aqueous solubility. Several analogues with ionizable or dipolar carboxamide side chains showed improved solubility but generally had reduced cytotoxic potency and hypoxic selectivity. Modification of the mustard leaving groups or replacement of the carboxamide moiety provided some compounds with superior potency, but only the mixed chloro/mesylate mustard 20 provided a gain in potency relative to solubility while retaining the hypoxic selectivity of 6. These nitrogen mustards did not show the remarkable activity demonstrated by the related aziridine 7 [CB 1954, 5-(N-aziridinyl)- 2,4-dinitrobenzamide] in Walker 256 adenocarcinoma cells and are not efficient substrates for the DT-diaphorase which activates the latter compound by aerobic nitroreduction in Walker cells. Variations in hypoxic selectivity within the dinitrobenzamide mustards appear not to be due to differences in sensitivity to activation by this enzyme. Walker cells showed intermediate sensitivity to the mono(2-chloroethyl) analogue 26 but not to the related half-mustard 27, suggesting that the inhibition of DT-diaphorase activity is due to steric effects in the 5-position. The preferred compound overall with respect to solubility, potency, and in vitro hypoxic cell selectivity was the (dimethylamino)-ethyl derivative 11. DNA elution studies and comparison of the sensitivity of AA8 and UV4 cells to this compound indicated reductive activation to form a DNA cross-linking agent under hypoxia. Radiobiological studies indicated 11 to be equally active against both aerobic and hypoxic cells in KHT tumors. It is not clear whether this reflects efficient killing of aerobic cells as a result of diffusion of reduced metabolites from hypoxic regions or whether cytotoxicity in tumors is independent of hypoxia.

Aniline Mustard↗
PubMed1994

Two-color multiparametric method for flow cytometric DNA analysis. Standardization of spectral compensation.

Spectral overlap of green fluorescence signals into the red detector (red-minus-green compensation) is one potential source of variation in two-color flow cytometric DNA analysis. Suboptimal compensation in a two-color propidium iodide (PI)/fluorescein isothiocyanate (FITC) system may be observed if compensation is adjusted using an inappropriate standard, or if changes to fluorescence detector high-voltage settings are made without corresponding readjustment of fluorescence compensation. To quantitate the influence of red-minus-green compensation on the quality of DNA histograms, data from 60 dual PI/cytokeratin (CK)-FITC stained carcinomas were acquired in parallel using two compensation standards: a PI/CK-FITC-stained T24 cell line calibrator overstained to achieve a high-intensity green fluorescence standard (HIGFS) with manually set compensation and automated compensation settings derived from commercial phycoerythrin/low intensity FITC beads (LIGF). Both compensation standards gave similar DNA hyperdiploidy results (DNA index, 1.1-2.8). However, LIGF standard yielded two falsely hypodiploid peaks (DNA index, .7 and .9). Eight left-skewed peaks became DNA diploid and symmetric, respectively, with the HIGFS. Use of HIGFS lowered the coefficient of variation percentage in 95% of cases, the greatest differences (maximum, 3.4%; mean, 1.81%) in tumors of highest intensity CK-FITC. The authors concluded that use of cell-based compensation standards (HIGFS) with intense green signals that mimic clinical tumor samples will avoid spurious aneuploidy and maximize resolution of near-diploid abnormalities.

Analysis of Variance↗
PubMed1994

Impact of improved irradiation technique, age, and lymph node sampling on the severe complication rate of surgically staged endometrial cancer patients: a multivariate analysis.

PURPOSE: Limited information is available regarding factors that predispose to complications following postoperative pelvic radiotherapy (RT) for endometrial cancer. To address this issue, patients with clinically staged I/II endometrial cancer who received postoperative RT following total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH/BSO) with or without lymph node sampling (LNS) were studied. PATIENTS AND METHODS: From 1960 through 1990, 235 patients with adenocarcinoma of the endometrium received postoperative RT after surgical staging. Multiple factors were evaluated to determine associations with severe complications. Pretreatment factors included age, stage, comorbidities. Treatment-related factors consisted of LNS, total RT dose, volume of RT fields, dose per fraction, total number of RT fields, number of RT fields treated per day, machine energy, and addition of vaginal implant. RESULTS: The 5-year actuarial risk of a severe complication was 5.5%. Factors associated with an increased risk of complications in univariate analysis included age more than 65 years (11% v 2%), use of only one portal per day (40% v 3%), use of anteroposterior/posteroanterior fields (23% v 4%), total dose > or = 50 Gy (8% v 2%), and LNS (11% v 3%). In a multivariate analysis, only older age, LNS, and the use of one field per day were significant. Increased risks associated with a total dose > or 50 Gy and the anteroposterior/posteroanterior technique were entirely attributable to the use of one field per day. A subanalysis among patients who had adequate RT techniques (eg, multiple fields treated per day) showed a significant increase in complications (7% v 1%) for those with and without LNS, respectively. CONCLUSIONS: Severe complications associated with adjuvant RT for endometrial cancer were increased among patients who were older or underwent LNS or received suboptimal RT technique. Pelvic RT using proper methods can be delivered with acceptable risks.

Adenocarcinoma↗
PubMed1993

Determinants of subsequent home health care nursing service use by hospitalized patients with cancer.

BACKGROUND: The authors examined the extent to which specific patient characteristics and length of hospital stay were capable of independently explaining the use of home health care nursing services by hospitalized patients with cancer after discharge. METHODS: The current study represents a secondary analysis of a data set originally gathered to identify the home health care needs of patients with cancer. The sample involved 87 patients with cancer who received home health care after hospitalization and 43 patients who did not receive such services. RESULTS: A logistic regression analysis indicated that home health care use was related to patient age, length of hospital stay, and level of symptom distress. Specifically, the likelihood of home health care use was found to increase among subjects older than 50 years of age, subjects with hospital stays of more than 7 days (apparently related to surgery), and those who experienced moderate to high levels of symptom distress. CONCLUSIONS: The results indicate a need for home health care nurses to be skilled in the management of cancer symptoms and in the complex problems commonly experienced by the postsurgical patient with cancer.

Activities of Daily Living↗
PubMed1993

Cloning, chromosomal localization, and functional expression of the alpha 1 subunit of the L-type voltage-dependent calcium channel from normal human heart.

A unique structural variant of the cardiac L-type voltage-dependent calcium channel alpha 1 subunit cDNA was isolated from libraries derived from normal human heart mRNA. The deduced amino acid sequence shows significant homology to other calcium channel alpha 1 subunits. However, differences from the rabbit heart alpha 1 include a shortened N-terminus, a unique C-terminal insertion, and both forms of an alternatively spliced motif IV S3 region. The shortened N-terminus provides optimal access to consensus sequences thought to facilitate translation. Northern blot analysis revealed a single hybridizing mRNA species of 9.4 kb. The gene for the human heart alpha 1 subunit was localized specifically to the distal region of chromosome 12p13. The cloned alpha 1 subunit was expressed in Xenopus oocytes and single-channel analyses revealed native-like pharmacology and channel properties.

Amino Acid Sequence↗
PubMed1993

Lessons from tumor progression: the invasive radial growth phase of melanoma is common, incapable of metastasis, and indolent.

Primary melanoma generally evolves through three clinically and morphologically discernable tumor progression steps. Transformed melanocytes first proliferate above the epidermal basement membrane, then invade the papillary dermis (the in situ and invasive radial growth phases of melanoma), and subsequently develop the capacity to grow as a tumor (the vertical growth phase). Here, we address three aspects of the invasive radial growth phase that provide the rationale for viewing it as the critical lesion for melanoma detection and therapy. We determined the fraction of melanomas having this growth phase, tested its hypothesized incapacity to metastasize, and estimated its longevity. The high prevalence of this step in tumor progression was demonstrated in a data base of 624 patients, where at least 87% of melanomas exhibited a radial growth phase. The benignity of this lesion was evinced by the perfect metastasis-free survival of 161 patients treated for pure radial growth-phase melanomas and followed for a median of 13.7 years. Its indolence was evident in an analysis of the ages of 234 patients with superficial spreading melanomas without or with vertical growth phase: The cases with lesions having only radial growth phase were 4.3 years younger than those additionally having vertical growth phase (p < 0.05). These features of the invasive radial growth phase of primary melanoma, first described by Wallace H. Clark, make it a pivotal lesion in the evolutionary biology of melanocytic neoplasia and confirm its central place in public health programs to control melanoma mortality.

Adolescent↗
PubMed1992

Loco-regional nodal relapse in melanoma.

Two-hundred and seven patients without evidence of disease following lymph node dissection (LND) were stratified into three groups: Group A, lymph node relapse within the site of prior LND; Group B, lymph node relapse in a different, but regional, lymph node group; Group C, no lymph node relapse. Decreased survival was noted in both Groups A and B versus Group C. Prognostic factors were identified as: (i) axial or subungal/volar (subvolar) location and the number of positive lymph nodes at initial LND for nodal relapse within the same lymph node group; (ii) male gender, axial/subvolar location, and the number of histologically positive lymph nodes at initial LND for nodal relapse in a different, but regional lymph node group; (iii) relapse within the initial LND site for a decreased survival. Six of 10 patients with both axial/subvolar primaries and four or more positive lymph nodes developed a relapse within the dissection site post-LND. These prognostic factors describe a subset of patients who would be candidates for postoperative adjuvant local/regional and systemic therapy trials.

Adolescent↗
PubMed1992

Case report: distinctive immune abnormalities in a patient with procainamide-induced lupus and serositis.

To gain insight into the immunopathogenesis of drug-induced autoimmune disorders, lymphocyte and immunoglobulin distributions and cytokine levels were monitored in the peripheral blood and pleural fluid of a patient with procainamide-induced lupus and pleural effusion. Approximately 80% of the B cells in both compartments were CD5+ compared to 10% to 25% in normal adults. CD4/CD8 ratio and percentage CD4 were normal in peripheral blood. Serum levels of IgG (particularly IgG2), IL-6, and soluble IL-2R were slightly elevated, and those of IgA were significantly elevated compared to normal controls. Analysis of the pleural effusion revealed an increased CD4/CD8 ratio because of an increased percentage of CD4+CD29+ helper memory T cells, lack of expression of the resting B-cell marker CD21, immune complex deposition and complement consumption, increased relative levels of ANA, abnormally high levels of IL-6 and soluble IL-2R, and detectable levels of IL-1b, IFN-g and TNF-a. These observations provide evidence for the involvement of CD5+ B cells and differential helper T-cell activity in procainamide-induced lupus and for an association between local lymphocyte activation and organ pathology.

Aged↗
PubMed1992

Molecular biology of the calcium antagonist receptor.

The calcium channel plays a key role in controlling many physiological processes in the body. Drugs that block the calcium channel have proven clinically effective for the treatment of a multitude of cardiovascular disorders. The elucidation of the precise mechanism of action of these drugs involves cloning the calcium channels on which they act. Genetic manipulation of these cloned channels is beginning to reveal the binding sites for the calcium channel blocking drugs and may lead to the development of more specific agents.

Animals↗
PubMed1991

Acceleration of activation and inactivation by the beta subunit of the skeletal muscle calcium channel.

The L-type voltage-dependent calcium channel is an important link in excitation-contraction coupling of muscle cells (reviewed in refs 2 and 3). The channel has two functional characteristics: calcium permeation and receptor sites for calcium antagonists. In skeletal muscle the channel is a complex of five subunits, alpha 1, alpha 2, beta, gamma and delta. Complementary DNAs to these subunits have been cloned and their amino-acid sequences deduced. The skeletal muscle alpha 1 subunit cDNA expressed in L cells manifests as specific calcium-ion permeation, as well as sensitivity to the three classes of organic calcium-channel blockers. We report here that coexpression of the alpha 1 subunit with other subunits results in significant changes in dihydropyridine binding and gating properties. The available number of drug receptor sites increases 10-fold with an alpha 1 beta combination, whereas the affinity of the dihydropyridine binding site remains unchanged. Also, the presence of the beta subunit accelerates activation and inactivation kinetics of the calcium-channel current.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗