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Biomedical subjects

G H Weiss

Publications and source records attributed to G H Weiss.

At least 55 records · Page 3Linked to original sources

Exact random-walk models in crystallographic statistics. V. Non-symmetrically bounded distributions of structure-factor magnitudes.

Derivations of exactly formulated Fourier-series representations of probability density functions (p.d.f.'s) of the magnitude of the structure factor are based on the fact that the structure factor and its real and imaginary parts are bounded. In some situations the bounds of the real and imaginary parts of the structure factor are different, and this gives rise to modified forms of the p.d.f.'s. Three physical examples that call for such modifications are investigated: (i) effect of dispersive scatterers on the p.d.f. of a centrosymmetric structure factor, (ii) effect of the presence of a centrosymmetric fragment in the asymmetric unit of a non-centrosymmetric space group, and (iii) effect of heavy scatterers in special positions of a non-centrosymmetric space group, where the imaginary part of the trigonometric structure factor for these special positions vanishes by symmetry. The general form of an exact Fourier p.d.f., taking account of such modifications, is derived, and expressions for Fourier coefficients are obtained for selected examples of the above three situations. It is seen that the effects of pseudocentrosymmetry may be most pronounced and those of dispersion are significant mainly in the range of small values of the structure factor.

Data Interpretation, Statistical↗

Clonal growth of bladder cancer cells in a double layer soft agar assay: needles addition of multiple culture supplements.

The necessity of multiple culture supplements, characteristic of Hamburger and Salmon (H&S) soft agar assay (1977), for the clonal growth of bladder cancer cells was systematically investigated. One murine and 6 human cell lines were cultivated in different culture supplemented conditions based on the H&S method. All cell lines successfully formed colonies in the absence of supplements. The inclusion of 2-mercaptoethanol to supplement-free medium stimulated the clonal growth of murine (MBT-2) cells, whereas it did not affect the growth of human cell lines. DEAE-dextran suppressed the clonal growth of 5 out of 7 lines. Tryptic soy broth stimulated the growth of 2 human cell lines, whereas it suppressed the other 2 cell lines. The chemosensitivity of MBT-2 cells was not affected by these supplements.

Animals↗

Suramin in adrenal cancer: modulation of steroid hormone production, cytotoxicity in vitro, and clinical antitumor effect.

Suramin, a drug known to have antiparasitic effects, has been previously shown to have adrenocorticolytic activity in primates. We now confirm preferential accumulation of this compound in the normal adrenal gland, evaluate its in vitro effect against two human adrenocortical carcinoma cell lines (SW-13 and NCI-H295), and report the clinical activity of suramin in 17 patients with metastatic adrenocortical carcinoma. Inhibition of colony formation occurred in both adrenal cell lines in vitro at concentrations that are clinically achievable in humans. In addition, suramin concentrations as low as 100 micrograms/mL were able to inhibit glucocorticoid, mineralocorticoid, and androgen production by the NCI-H295 cell line. Of 16 patients with adrenocortical carcinoma now evaluable for tumor response, 2 achieved a partial response, 2 had a minor response, and 5 remained with stable disease for periods ranging from 3-10 months; the remainder progressed. One of 7 patients with excessive steroid hormone production achieved a partial normalization of her steroid levels for the duration of suramin therapy in the setting of radiographic disease stabilization. An additional patient treated off-study for lack of radiographically measurable disease, achieved complete normalization of plasma aldosterone levels. We conclude that suramin preferentially accumulates in adrenal cells, induces cytotoxicity and significant down-regulation of steroid hormone production in vitro, and has some therapeutic efficacy as a single agent in patients with metastatic adrenocortical carcinoma.

Adrenal Cortex Neoplasms↗

Exact conditional distribution of a three-phase invariant in the space group P1. I. Derivation and simplification of the Fourier series.

An exact expression is derived for the conditional probability density function of a three-phase invariant and the general result is applied to the space group P1. The expression for the conditional density is given in terms of a sixfold Fourier series. A straightforward numerical evaluation of this series, without further analysis, is extremely time consuming. Much of the present paper is therefore devoted to an exposition of symmetries hidden in the various summations. The computational effort required for the evaluation of the above expression is thereby reduced to manageable proportions in a number of interesting cases. Results of numerical computations of the exact conditional density are given in the second paper in this series. It is also shown that the exact expression for the conditional probability reduces to that given by Cochran [Acta Cryst. (1955), 8, 473-478].

Chemistry, Physical↗

Exact conditional distribution of a three-phase invariant in the space group P1. II. Calculations and comparison with the Cochran approximation.

The conditional probability density function of a three-phase invariant is computed from exact expressions derived and discussed in the first paper of this series [Shmueli, Rabinovich & Weiss (1989). Acta Cryst. A45, 361-367] and comparisons are presented of these computations with the approximate conditional density due to Cochran [Acta Cryst. (1955), 8, 473-478]. Conditional variances computed from the exact and approximate expressions are also compared. The computations are carried out for the space group P1. This is the first numerical comparison of conditional phase-invariant statistics evaluated from exact and approximate expressions. The discrepancy between these two kinds of statistics appears to be negligible if the E values involved are small and the number of atoms in the cell is moderately large. Very significant discrepancies are observed when the number of the atoms in the unit cell is small, as well as in the case of the presence of an outstandingly heavy atom. For a given triplet of magnitudes of E values or a fixed atomic composition of the unit cell the exact conditional density functions tend to have sharper peaks than the approximate ones.

Chemistry, Physical↗

Explicit Fourier representations of non-ideal hypercentric P.D.F.'s of magnitude of E.

Explicit non-ideal hypercentric distributions of the magnitude of the normalized structure factor have been derived and investigated for the space group P1. One of the distribution types investigated arises when the asymmetric unit of P1 consists of several identical centrosymmetric motifs, interrelated by additional non-crystallographic centres of symmetry. The ideal version of such distributions was studied by Rogers & Wilson [Acta Cryst. (1953), 6, 439-449]. The other distribution type studied originates from atomic arrangements in which the asymmetric unit is composed of several unrelated centrosymmetric fragments that may differ in their sizes and chemical compositions. Explicit non-ideal probability density functions (p.d.f.'s) of the magnitude of the normalized structure factor were formulated for both above types of distribution as Fourier series, were evaluated numerically and were compared with appropriately simulated distributions of magnitude of E. The computations were carried out for a range of atomic compositions, and numbers of unrelated centrosymmetric fragments that comprise the asymmetric unit; both of these factors have a significant influence on the deviation of the hypercentric p.d.f.'s from the values predicted on the basis of the central-limit theorem approximation.

Crystallography↗

Exact random-walk models in crystallographic statistics. IV. P.d.f.'s of [E] allowing for atoms in special positions.

The effect of scatterers, located in variable special positions, on the probability density function of the magnitude of the normalized structure factor has been investigated. Exact characteristic functions have been obtained for all the statistically different variable special positions in triclinic, monoclinic and ortho-rhombic space groups except in Fdd2 and in the space groups based on the point group 222, and the probability density functions have been evaluated from their Fourier or Fourier-Bessel series expansions. It is seen that the effect of heavy scatterers, located in the special positions investigated, is very marked and should be accounted for in cases of space-group ambiguities.

Crystallography↗

Interleukin 2 suppression of a murine bladder cancer implanted into kidney, bladder and skin; its organ specificity.

Little is known about organ associated tumor response to systemic interleukin 2 (IL2) therapy. The effect of IL2 on bladder cancer growth in the skin and in the genitourinary tract was investigated. C3H mice were implanted with the syngeneic transitional cell carcinoma, MBT-2, intradermally (i.d.), beneath the left renal subcapsular area, and in one experiment, simultaneously in the bladder. IL2 (human recombinant form; Biogen Research Co) was given i.p. at 5000 U thrice daily for 5 consecutive days commencing on Day 3, or for 10 to 11 days commencing on Day 10 with some doses omitted at signs of toxicity. For comparison, mice bearing 3-d and 10-d tumors in the skin and subcapsular kidney were treated with chemotherapy (cisplatin, 6 mg./kg. X 3; mitomycin C, 3 mg./kg. X 3; cyclophosphamide, 75 mg./kg. X 1). IL2 therapy mediated growth suppression of 10-d tumors in the genitourinary organs and skin at a similar rate. In contrast to IL2, systemic chemotherapy mediated tumor suppression in an organ specific manner; renal subcapsular tumors responded to the chemotherapy, whereas i.d. tumors were insensitive. Three-day tumors (both i.d. and renal subcapsular tumor) responded relatively well to each treatment compared to 10-d tumors. These data suggest that in systemic immunotherapy with IL2, anatomic location of the tumor is less important for inducing an antitumor response than in chemotherapy.

Animals↗

Reduction of bladder cancer growth in mice treated with intravesical Bacillus Calmette Guerin and systemic interleukin 2.

The effect of systemic administration of Interleukin 2 (IL2) on intravesical Bacillus Calmette-Guerin (BCG) therapy was studied in an established murine bladder tumor, MBT-2. BCG (100 micrograms.) was administered intravesically on days 7 and 14 after seeding bladders with MBT-2 cells. IL2 (5,000 U/injection) was given intraperitoneally every eight hours for 10 times (days seven through 10 and 14 through 17). BCG or IL2 therapy alone failed to reduce incidence of tumor implantation and tumor weight; whereas, combined treatment with BCG and IL2 reduced tumor weight significantly compared to saline or BCG treated mice. Cytotoxicity was assessed in a four-hour 75Semethionine-release assay. Augmentation of natural killer cell activity was only observed in mice treated with BCG plus IL2. MBT-2 target cells were not lysed by spleen cells from mice treated with BCG or saline. IL2 therapy produced lymphokine-activated killer cell activity, though combining BCG with IL2 suppressed this activity after each course of treatment. The results suggest that combined treatment with IL2 enhances the therapeutic effect of BCG therapy. However, this enhancement of antitumor activity is not clearly explained by augmentation of natural killer or in vivo-generated lymphokine-activated killer cells.

Administration, Intravesical↗

Model for photon migration in turbid biological media.

Various characteristics of photon diffusion in turbid biological media are examined. Applications include the interpretation of data acquired with laser Doppler blood-flow monitors and the design of protocols for therapeutic excitation of tissue chromophores. Incident radiation is assumed to be applied at an interface between a turbid tissue and a transparent medium, and the reemission of photons from that interface is analyzed. Making use of a discrete lattice model, we derive an expression for the joint probability gamma(n, rho)d2 rho that a photon will be emitted in the infinitesimal area d2 rho centered at surface point rho = (x, y), having made n collisions with the tissue. Mathematical expressions are obtained for the intensity distribution of diffuse surface emission, the probability of photon absorption in the interior as a function of depth, and the mean path length of detected photons as a function of the distance between the site of the incident radiation and the location of the detector. We show that the depth dependence of the distribution of photon absorption events can be inferred from measured parameters of the surface emission profile. Results of relevant computer simulations are presented, and illustrative experimental data are shown to be in accord with the theory.

Computer Simulation↗

Predicting posttraumatic epilepsy in penetrating head injury.

Using data derived from a 15-year follow-up study of 520 veterans surviving penetrating brain wounds received in the Vietnam war, we have developed a predictive formula and tables for posttraumatic epilepsy based on time elapsed postinjury and presence of specific clinical and computed tomographic scan risk factors. Such patients remain at some increased risk for epilepsy even ten to 15 years postinjury, although most can be 95% certain of avoiding epilepsy if they have been seizure free for three years posttrauma. Epilepsy onset latency was independent of any risk factors identified.

Brain Injuries↗

Sizes and mass distributions of clathrin-coated vesicles from bovine brain.

Clathrin-coated vesicles obtained from bovine brain have been studied by ultracentrifugation and dynamic light scattering techniques to provide information on their sedimentation and mass distributions and their average diffusion coefficients. "Uncoated" vesicles, obtained by removing the protein coat from coated vesicles, have been similarly characterized. For typical preparations, maximal values of approximately 210 and 95 S are observed for the sedimentation coefficients of coated and uncoated vesicles, respectively. Corresponding values for the average molecular weights, determined from values of average sedimentation and diffusion coefficients, are 49 X 10(6) and 13 X 10(6); values obtained by equilibrium sedimentation are 37.2 X 10(6) and 10.6 X 10(6). In order to obtain these results, some minor modifications of sedimentation and light-scattering techniques have been devised which may have application to other studies of size distributions of large particles.

Animals↗

Mortality following penetrating craniocerebral injuries. An analysis of the deaths in the Vietnam Head Injury Registry population.

A population of 1127 men with penetrating craniocerebral injuries who were alive 1 week after their injuries has been followed for 15 years. During this time, 90 deaths (8%) occurred. Most of the deaths occurred early in the 1st year after trauma and were secondary to the direct effects of brain injury or the sequelae of coma. Complications, particularly infections, were significant mortality factors. Coma was the best prognostic guideline. Posttraumatic epilepsy was not related to mortality except for the risks accompanying each ictus. The population now appears to be approaching the actuarial norm of their peers.

Brain Injuries↗

Life expectancy and causes of death in a group of head-injured veterans of World War I.

The life spans and causes of death were examined for a group of Bavarian veterans of World War I who had suffered head injuries and for comparable control subjects who had not. The occurrence of posttraumatic fits was a significant prognostic factor for a higher death rate after the age of 50 years. Other indicators of the severity of injury did not lead to differences in the death rates. There were significantly more deaths due to cerebrovascular causes in the head-injured group than in the control group, but no subgroup was found to have significantly more cerebrovascular deaths than any other.

Adult↗