Biomedical subjects
M Ross
Publications and source records attributed to M Ross.
Patterns of failure in anorectal melanoma. A guide to surgical therapy.
Anorectal melanoma is an aggressive tumor with a reported 5-year survival rate of 6%. Recommendations for local surgical therapy vary from local excision to abdominoperineal resection. Therapy, patterns of failure, and survival were retrospectively examined in 32 patients with anorectal melanoma. Twenty-six patients were treated surgically, 14 with abdominoperineal resection and 12 with local excision. Local recurrence occurred less frequently in patients undergoing abdominoperineal resection (4 [29%] of 14) compared with patients undergoing local excision (7 [58%] of 12) but developed concomitantly with distant or regional metastasis in all but 2 of the 11 patients whose operations failed locally. Inguinal nodal disease developed in 15 patients (47%). Pelvic nodal disease became apparent in only 2 patients (7%). There was no difference in overall survival between the two surgically treated groups (median survival, 19.5 months for patients treated with abdominoperineal resection vs 18.9 months for patients treated with local excision). Therefore, local excision is recommended when technically feasible since these patients eventually succumb to metastasis regardless of surgical therapy.
Transgenic tobacco plants and their progeny derived by microprojectile bombardment of tobacco leaves.
Transgenic tobacco plants and progeny carrying coding sequences for neomycin phosphotransferase II (NPTII) and beta-glucuronidase (GUS) were recovered following microprojectile bombardment of tobacco leaves. Transgenic plants were regenerated from bombarded leaf pieces of tobacco cvs. 'Xanthi' and 'Ky 17' which were cultured in the presence of 100 or 200 micrograms/ml kanamycin for six to eight weeks. Among 160 putative transgenic plants from at least 16 independent transformation events 76% expressed NPTII, and 50% expressed GUS. Southern analysis of plants expressing either one or both of the enzymes indicated DNA in high molecular weight DNA in 8 of 9 independent transformants analyzed. Two independent transformants and their progeny were analyzed in detail. Analysis of progeny for quantitative enzyme levels of NPTII and GUS, and Southern analysis of parents and progeny clearly demonstrated that the genes were transmitted to progeny. One transformant demonstrated Mendelian ratios for seed germination on kanamycin-containing medium while the other transformant had non-Mendelian ratios. DNA analysis of progeny indicate complex integration of the plasmid DNA, and suggest that rearrangements of this DNA has occurred. These results are consistent with other methods of direct DNA uptake into cells, and verify that the microprojectile bombardment method is capable of DNA delivery into intact plant cells which can give rise to transgenic plants and progeny.
The use of a sociobiological questionnaire (SQ) for the assessment of sexual dimorphism.
A sociobiology questionnaire (SQ) (Thiessen and Kittrell, 1980) was administered to 527 undergraduate males and females. Twenty-seven predictions were tested. Sixteen of the predictions were statistically confirmed, and eight were in the expected direction. Overall, females appeared to be more interested in their mate's success than their own and were more selective in the choice of mates. Males gave more evidence of competitiveness and tended to mate polygamously. The results are compatible with theoretical expectations about mating strategies (Buss, 1987; Rushton et al., 1984; Thiessen and Gregg, 1980). A number of problems with regard to the application of sociobiological and sociocultural theories to human behavior are discussed.
High-dose carboplatin, cyclophosphamide, and BCNU with autologous bone marrow support: excessive hepatic toxicity.
Intensive doses of carboplatin, cyclophosphamide, and BCNU with autologous bone marrow support were given to four patients with advanced melanoma. Three developed clinically diagnosed, severe veno-occlusive liver disease, which was fatal in two cases. The dose of carboplatin (450 mg/m2) was comparable with that used in ambulatory regimens. At the doses and schedule employed, this three-drug combination produced excessive hepatic toxicity. Caution is suggested when giving carboplatin in combination with intensive doses of other chemotherapeutic agents with known hepatotoxic potential.
A quantitative assay for neomycin phosphotransferase activity in plants.
A sensitive, simple, and quantitative assay for determining neomycin phosphotransferase (NPT) activity in plant cell extracts is described. The procedure retains the simplicity of previously published methods, yet offers up to a 140-fold increase in sensitivity. This increase is due to (1) the addition of bovine serum albumin (BSA) to the assay mixture, (2) desalting of crude maize extracts to remove a low-molecular-weight inhibitor of the enzyme, and (3) use of a different extraction buffer and an improved extraction procedure to liberate more enzyme from the cells. This method has been used successfully to detect and quantitate both stable and transient expression of NPT in transgenic tobacco and maize tissue.
Effects of plasmapheresis and autotransfusion on complement recovery in dogs.
To study selectively the dilutional aspects of severe blood loss on the serum complement system, we developed an animal model consisting of isovolumic phlebotomy and reinfusion of washed autologous erythrocytes. This model avoided hypoperfusion, ischemia, and transfusion of foreign antigen. We measured total serum protein, C3 antigen, total complement hemolytic activity, and alternative pathway hemolytic activity. Each of the first three parameters dropped to 55% of initial value (P less than 0.005) by the end of the phlebotomy/reinfusion procedure and returned to normal levels by Day 1 or 2. C3 antigen and total complement hemolytic activity then rose to 150% of normal by Day 4 and gradually returned to normal within 2 weeks. Alternative pathway activity, by contrast, fell by more than 80% (P less than 0.005) within the first 6 hr, recovered by Day 4, and gradually rose to about 140% of normal by Day 21. Trauma patients treated for heavy blood loss who suffer depletion of hemolytic complement during the first few hours may be at greater risk of infection due to immune deficiencies. The implication of the results presented here is that the alternative pathway may be particularly weakened during blood loss and transfusion by simple dilution in addition to the effects of processes omitted in this model. Knowledge of the kinetics of complement recovery, independent of other effects usually accompanying trauma, may be helpful in determining whether these patients might benefit from exogenous manipulation of the complement system.
High-dose alkylating agent chemotherapy with autologous bone marrow support in patients with stage III/IV epithelial ovarian cancer.
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In vitro evaluation of the pollen extract, cernitin T-60, in the regulation of prostate cell growth.
Nine human-derived cancer and non-cancer continuous cell lines were employed to evaluate the relative in vitro activity of the pollen extract, Cernitin T-60. Responses of the cell lines to the drug were assessed by measuring growth and cell survival as determined by cell count. The results demonstrated that of the 9 continuous cell lines tested, only those derived from the human prostate were growth inhibited by the pollen extract, whereas the non-prostate derived cells exhibited variable degrees of resistance to the T-60. The selectivity of the drug for the prostate cell lines was even more pronounced in the hormone-independent models, suggesting that there might be a place for the pollen extract in the control of abnormal growth in hormone-insensitive cells.
Tap-induced blink reflex and central nervous system dysfunction in diabetics with hyperosmolality.
We studied the effect of hyperosmolality on the tap-induced blink reflex (TBR) in patients with diabetes. The TBR, consisting of R1 and R2 components, was either absent or delayed in patients compared to controls. The abnormalities correlated better with the degree of hyperosmolality than with the level of blood glucose. TBR was usually absent in unconscious patients with greatly elevated serum osmolality. In some patients with similar elevations in serum osmolality the R2' component was absent at a time when consciousness was preserved. Hence, TBR may be useful in monitoring CNS dysfunction in diabetics with hyperosmolality.
Double staining to increase the sensitivity of protein detection in polyacrylamide gels.
As more and more researchers are examining proteins that are available only in extremely limited quantities, i.e., cellular extracts or genetic engineering products, it is critical to utilize staining methods that maximize sensitivity. The protocol we describe here--double staining of polyacrylamide electrophoresis gels with Pro-Blue (colloidal blue stain) followed by silver staining--yields an extremely sensitive, nonspecific protein stain. On average, this double-staining technique resulted in a 40-fold increase in sensitivity and intensity vs. silver stain alone. This is a tremendous return for a small investment in additional time and materials.
Effect of spinal cord ischemia on compound muscle action potentials and spinal evoked potentials following spinal cord stimulation in the dog.
We recorded the compound muscle action potentials (CMAP) from the soleus muscle and spinal evoked potentials (SpEP) from the caudal spinal cord after stimulation of the rostral spinal cord via epidural electrodes in 18 dogs. We examined the changes of CMAP and SpEP after the cord was made ischemic by clamping the aorta at different levels. Clamping the abdominal aorta below the artery of Adamkiewicz (five dogs) did not change either CMAP or SpEP significantly. When the thoracic aorta was clamped above the radicular and Adamkiewicz arteries (10 dogs), CMAP disappeared entirely within 5-10 min of occlusion, but SpEP showed only minimal latency prolongation limited to the late peaks in seven of 10 dogs. In the remaining three dogs, both CMAP and SpEP disappeared within 30 min of occlusion but with the more rapid deterioration of CMAP than of SpEP. Progressive ligation of lumbar arteries (three dogs) from caudal to rostral levels did not change CMAP until ligation of Adamkiewicz artery. Then CMAP disappeared, but SpEP remained unchanged. These findings suggest that CMAP and SpEP are mediated through different pathways and that CMAP reflect anterior cord function. The described electrophysiologic technique would be useful to monitor spinal cord motor function during surgery of the spine, spinal cord, or thoracoabdominal aorta.
Noduloulcerative or "malignant" syphilis occurring in an otherwise healthy woman: report and review of a dramatic dermatosis.
We present the case of an otherwise healthy woman with noduloulcerative ("malignant") syphilis, the first female patient reported with this dermatosis in fifty years. This rare form of secondary syphilis is characterized by noduloulcerative lesions with rupioid crusts that dramatically involve the face while usually sparing the palms and soles. The aggression and destruction of the skin lesions may mimic that of other granulomatous and infiltrative dermatoses. Since the incidence of syphilis is increasing, physicians should be aware of this variant that is so disfiguring it has historically been referred to as lues maligna.
The use of recombinant human granulocyte-macrophage colony-stimulating factor in autologous bone marrow transplantation.
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Immunopharmacologic purging of breast cancer from bone marrow for autologous bone marrow transplantation.
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Detecting maternal cell contamination in prenatal diagnosis.
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A key functional role for the insulin-like growth factor 1 N-terminal pentapeptide.
In order to elucidate the role of the N-terminus of insulin-like growth factor 1 (IGF-1) with respect to its biological properties, we chemically synthesized analogues of IGF-1 truncated by one to five amino acid residues from the N-terminus. In a bioassay that measured the stimulation of protein synthesis in rat L6 myoblasts, the concentrations required to produce a half-maximal response were: IGF-1, 13 ng/ml; des-(1)-IGF-1, 10 ng/ml; des-(1-2)-IGF-1, 13 ng/ml; des-(1-3)-IGF-1, 1.5 ng/ml; des-(1-4)-IGF-1, 5.1 ng/ml; des-(1-5)-IGF-1, 1200 ng/ml. When tested for their abilities to compete with 125I-IGF-1 binding to L6 myoblasts at 3 degrees C, the concentrations required for 50% competition were: IGF-1, des-(1)-IGF-1 and des-(1-2)-IGF-1, 20 ng/ml; des-(1-3)-IGF-1, 14 ng/ml; des-(1-4)-IGF-1, 40 ng/ml; des-(1-5)-IGF-1, greater than 1000 ng/ml. Receptor-binding experiments at 25 degrees C, however, gave results suggesting that the myoblasts were secreting a binding protein selective for the three longest peptides. This interpretation was confirmed by binding studies with medium conditioned by the L6 myoblasts as well as binding protein purified from MDBK-cell-conditioned medium. In both cases IGF-1, des-(1)-IGF-1 and des-(1-2)-IGF-1 competed for tracer IGF-1 binding at least 60-fold better than did the three shorter peptides. The results obtained account for the increased potency of des-(1-3)-IGF-1 and des-(1-4)-IGF-1, since their activities are not attenuated by the binding protein, and the relatively lower potency of des-(1-4)-IGF-1 is a consequence of this peptide binding less well to the L6-myoblast receptor.
Insulin-like growth factor (IGF)-binding proteins inhibit the biological activities of IGF-1 and IGF-2 but not des-(1-3)-IGF-1.
(1) Many cell types secrete insulin-like growth factor (IGF)-binding proteins that can be expected to sequester free IGF and modify the biological activities of the growth factors. (2) A binding protein purified from bovine kidney (MDBK) cells potently inhibited the ability of IGF-2 to stimulate DNA synthesis or protein accumulation as well as to reduce rates of protein breakdown in chick embryo fibroblasts. The binding protein did not influence the biological activities of des-(1-3)-IGF-1, while effects on IGF-1 were intermediate. Since the chick embryo fibroblasts contain only the type 1 IGF receptor, the MDBK-cell binding protein must have reduced the accessibility of IGF-2 and IGF-1 to that receptor. Binding to the type 2 receptor on L6 myoblasts was also inhibited. (3) Inhibiting effects on both protein breakdown responsiveness to IGF and IGF binding to cell receptors were also observed with human amniotic fluid binding protein, although here IGF-1 and IGF-2 were equipotent. These results contrast with stimulatory responses on different IGF-1 actions of the same binding protein reported previously [Elgin, Busby & Clemmons (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 3254-3258]. (4) The biological potencies of IGF-1, IGF-2 and des-(1-3)-IGF-1 correlate inversely with their binding to proteins released into the medium by cells, so that the enhanced potency of des-(1-3)-IGF-1 is a consequence of it not binding to purified binding proteins or those released by cultured cells.