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Biomedical subjects

S R Paul

Publications and source records attributed to S R Paul.

34 records · Page 2Linked to original sources

Stage IV neuroblastoma in infants. Long-term survival.

Before the advent of multiagent chemotherapy, the prognosis for patients with Stage IV neuroblastoma of all ages was dismal. More recently, marked improvement in infants with Stage IV neuroblastoma has been reported. Twenty-four infants with Stage IV neuroblastoma have been treated at the Dana-Farber Cancer Institute/The Children's Hospital, and the Joint Center For Radiation Therapy, Boston, Massachusetts, between 1970 and 1988. Twenty-three of these patients were treated with multiagent chemotherapy and one with a single drug. In the initial report, ten of 11 patients were alive without evidence of disease after intensive therapy. In this report the authors update their initial series of patients and include 13 additional patients who subsequently presented to our institutions with Stage IV neuroblastoma younger than 1 year of age. The 5-year actuarial event-free survival for the 24 patients is 75%. No patient without bone metastases died from neuroblastoma, and 12 of 16 patients with bone metastases remained disease free. These results confirm that infants with Stage IV neuroblastoma have a very good prognosis when treated with intensive multiagent chemotherapy.

Adrenal Gland Neoplasms↗

Direct and synergistic effects of interleukin 11 on murine hemopoiesis in culture.

We have examined the effects of a stromal cell-derived cytokine designated interleukin 11 (IL-11) on the proliferation of murine hemopoietic progenitors in methylcellulose culture. COS cell-conditioned medium containing IL-11 supported formation of granulocyte/macrophage colonies and a small number of multilineage colonies including blast cell colonies in cultures of marrow cells from normal mice. When tested with marrow cells harvested 2 days after injection of 5-fluorouracil at 150 mg/kg, IL-11 enhanced interleukin 3-dependent colony formation, whereas IL-11 alone supported only scant colony formation. Serial observations (mapping studies) of cultures of post-5-fluorouracil spleen cells indicated that the mechanism of the synergistic effect of IL-11 is to shorten the dormant period of stem cells, an effect very similar to that of interleukin 6. When pooled blast cells were plated into medium containing IL-11 and erythropoietin, only macrophage colonies were observed. Thus, IL-11 can directly support the proliferation of committed macrophage progenitors and, and like interleukin 6 and granulocyte colony-stimulating factor, act synergistically with interleukin 3 to shorten the Go period of early progenitors.

Animals↗

Molecular cloning of a cDNA encoding interleukin 11, a stromal cell-derived lymphopoietic and hematopoietic cytokine.

Hematopoiesis occurs in close association with a complex network of cells loosely termed the hematopoietic microenvironment. Analysis of the mechanisms of microenvironmental regulation of hematopoiesis has been hindered by the complexity of the microenvironment as well as the heterogeneity of hematopoietic stem cells and early progenitor cells. We have established immortalized primate bone marrow-derived stromal cell lines to facilitate analysis of the interactions of hematopoietic cells with the microenvironment in a large animal species. One such line, PU-34, was found to produce a variety of growth factors, including an activity that stimulates the proliferation of an interleukin 6-dependent murine plasmacytoma cell line. A cDNA encoding the plasmacytoma stimulatory activity was isolated through functional expression cloning in mammalian cells. The nucleotide sequence contained a single long reading frame of 597 nucleotides encoding a predicted 199-amino acid polypeptide. The amino acid sequence of this cytokine, designated interleukin 11 (IL-11), did not display significant similarity with any other sequence in the GenBank data base. Preliminary biological characterization indicates that in addition to stimulating plasmacytoma proliferation, IL-11 stimulates the T-cell-dependent development of immunoglobulin-producing B cells and synergizes with IL-3 in supporting murine megakaryocyte colony formation. These properties implicate IL-11 as an additional multifunctional regulator in the hematopoietic microenvironment.

Amino Acid Sequence↗

A comparison of tests of homogeneity of odds ratios in K 2 x 2 tables.

We conducted a simulation study to determine the performance of nine procedures for testing the homogeneity of odds ratios in K 2 x 2 contingency tables. We recommend Tarone's approximate score test, based on the Mantel-Haenszel estimator of the common odds ratio, for use in practice. We also recommend a non-iterative statistic developed by Gart and based on the modified Woolf estimator of the common odds ratio for very large samples in balanced or mildly unbalanced designs. We base our recommendation of a statistic on its performance in terms of size and power in comparison with the other statistics considered.

Odds Ratio↗

Bleomycin hypersensitivity in dyskeratosis congenita fibroblasts, lymphocytes, and transformed lymphoblasts.

We studied the responses of several dyskeratosis congenita (DC) cell lines to the DNA strand-cleaving and base-damaging agent bleomycin. Fibroblasts, peripheral blood lymphocytes, and transformed lymphoblasts of six DC patients and an obligate DC heterozygote showed more chromatid breaks than did respective controls exposed to various concentrations of bleomycin during the G2 phase of the cell cycle (P less than 0.0001). Unsynchronized DC fibroblasts in culture also showed decreased survival, compared to normals, following bleomycin treatment. DC lymphocytes treated with bleomycin for the final 24 h of culture showed more chromatid- and chromosome-type damage than did normals (P less than 0.0001) or G0-treated DC lymphocytes. Spontaneous chromosome breakage was normal in all six DC cell lines. The ability to distinguish affected and heterozygous DC cells without spontaneous chromosome instability from normals on the basis of their bleomycin hypersensitivity provides a marker for future studies of the pathogenesis of this disorder.

Bleomycin↗

On testing departure from the binomial and multinomial assumptions.

This paper is concerned with testing the multinomial (binomial) assumption against the Dirichlet-multinomial (beta-binomial) alternatives. In particular, we discuss the distribution of the asymptotic likelihood ratio (LR) test and obtain the C(alpha) goodness-of-fit test statistic. The inadequacy of the regular chi-square approximation to the LR test is supported by some Monte Carlo experiments. The C(alpha) test is recommended based on empirical significance level and power and also computational simplicity. Two examples are given.

Computer Simulation↗

Enteritis necroticans among Khmer children at an evacuation site in Thailand.

A severe illness characterised by bloody diarrhoea and intestinal dysfunction was recognised at an evacuation site on the Thai-Kampuchean border. From June, 1985, to July, 1986, the illness occurred in 62 Khmer children aged 10 months to 10 years (mean 4 years); it was characterised by bloody diarrhoea (94%), fever (90%), and abdominal pain (78%). The overall mortality rate was 58%. Among 16 children who died and underwent necropsy, small-intestinal necrosis of varying severity was found; in 5 of these children small-intestinal lesions with areas of full-thickness necrosis were seen that histologically resembled those in cases of enteritis necroticans (pigbel) in Papua New Guinea. Beta-toxin-producing Clostridium perfringens type C was isolated from 2 of 23 children from whom specimens for anaerobic cultures were collected, and antibodies to beta toxin were detected in 5 of 9 survivors but not in 10 healthy, age-matched control children. These cases show that enteritis necroticans can cause substantial morbidity and mortality outside Papua New Guinea.

Adult↗

Analysis of proportions of affected foetuses in teratological experiments.

This paper is concerned with the analysis of proportions affected when an increasing dose of a compound is applied to a group of laboratory animals. Several sets of data, including a set from a teratological experiment at the Shell Toxicology Laboratory, Sittingbourne, are analysed and some simulations are performed. Among the distributional models, the beta-binomial model is, in general, found to be the most sensitive to departures from the binomial. For testing the equality of two proportions, a comparison is made between the pseudo-t test, based on the jackknife method, and the likelihood ratio test, based on the beta-binomial model. From the limited comparison, no definite advantage of one approach over the other has been found; at the 5% level of significance both approaches lead to similar conclusions.

Animals↗

Physiologic and hematologic values in Nelson desert bighorn sheep.

Physiologic and hematologic values were established for two groups of free ranging Nelson desert bighorn sheep (Ovis canadensis nelsoni). Eleven sheep (Group I) were captured with a drop net, 16 sheep (Group II) were immobilized with Etorphine introduced in projectile syringes. The mean glucose level, respiration rate and leucocyte count values for Group I sheep were more than twice those observed in Group II sheep. There were no differences between the groups in the other values. Data obtained were compared to values previously established for free ranging and captive Rocky Mountain bighorn sheep (O. c. canadensis), California bighorn sheep (O. c. californiana) and domestic sheep (O. aries).

Animals↗

Treatment of bovine and equine ocular squamous cell carcinoma by radiofrequency hyperthermia.

Forty-five ocular squamous cell carcinomas (SCC) in 17 cattle and 8 horses were treated by radiofrequency hyperthermia, resulting in 80% complete regression and 16% partial regression. Tumors were histologically diagnosed as SCC; 50% of the tumors were recurrent, having been treated previously by surgery, cryosurgery, radiation, or immunotherapy. After hyperthermic treatment, most animals were available for tumor measurement at 4 to 6 weeks and at 8 to 16 weeks, with a final observation period of 2 to 10 months for all. Complete regression occurred in 8 of 12 tumors given a second hyperthermic treatment. It was concluded that hyperthermia is an effective and easily applied treatment modality for ocular SCC in cattle and horses; however, it cannot be recommended for large tumors (larger than equal to 5 cm diameter) that have deep eyelid or conjunctival penetration.

Animals↗

A 14/28 dicentric Robertsonian translocation in a Holstein cow.

A new dicentric Robertsonian translocation is described in a Holstein cow. The translocation appears to have arisen spontaneously from the centric fusion of autosomal acro centrics 14 and 28 which resulted in a diploid chromosome number of 59. Behavioral and phenotypic anomalies of the affected cow are discussed.

Journal Article↗

Chronic frontal sinusitis and osteolysis in desert bighorn sheep.

Chronic frontal sinusitis and osteolysis in a herd of desert bighorn sheep (Ovis canadensis nelsoni) in Zion National Park, Utah, was attributed to bacterial infection secondary to aberrant nasal bot migration. Analysis of skulls and live adult sheep (equal to 1 year old) showed that 9 to 22 animals were affected. One ram and 1 ewe were treated by trephination and irrigation. Treatment was successful for the ewe, but not for the ram. Radiography, thermography, and blood profiles were used in an attempt to find a way to diagnose sinusitis in its early stages; at this point, only thermography shows promise.

Animals↗