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Biomedical subjects

S Green

Publications and source records attributed to S Green.

At least 235 records · Page 13Linked to original sources
PubMed1994

Immunoassays for serum and urine myoglobin: myoglobin clearance assessed as a risk factor for acute renal failure.

We compared four immunoassays for serum and urine myoglobin. Within-run CVs were 5-13%, with biases seen between assays. Myoglobin was stable for 1 month in serum and 12 days in urine when the pH was adjusted to between 8.0 and 9.5. Hemoglobin caused no interference. We assayed 91 pairs of serum and timed urine specimens from 41 patients admitted for acute trauma or rhabdomyolysis. Most were treated with mannitol and alkalinization. Upon initial presentations, 21 patients with either low serum myoglobin concentrations (< 400 micrograms/L) or high myoglobin clearances (> or = 4 mL/min) had normal creatinine clearances and no clinical evidence of renal disease. The remaining 20 had low myoglobin clearances. Seven were in rhabdomyolysis-induced acute renal failure, or subsequently developed this complication. We suggest that low myoglobin clearance may indicate a high risk for developing renal failure or may be an early marker for kidney dysfunction. Low myoglobin clearance may prove useful in indicating failure of prophylactic treatment to clear myoglobin.

Acute Kidney Injury↗
PubMed1993

Immunoaugmentative therapy. An unproven cancer treatment.

While it is statistically true that clinical cancer occasionally occurs following development of immune incompetency, the fact remains that the most common forms of cancer (ie, breast, lung, and colon) are not experienced by immunosuppressed individuals. Since there is strong scientific evidence that the unprovoked, normal immune system does not recognize and destroy cancer cells that arise spontaneously, the concept of an immune surveillance system that continuously protects clinically normal humans from cancer remains an appealing but unproven hypothesis. Burton's theory of immune surveillance against cancer appears to be nothing more than a rehash of the hypotheses of many other investigators, embellished with his postulate that four specific anticancer protein factors exist and function in the normal human immune system. The IAT he invented as a treatment for cancer is based on his presumption that he has proven the existence of these factors. But neither his declarations nor those of his proponents offer any objective evidence to support such a conclusion. They have not proven that the IAT components exist or can be extracted from blood without the loss of biologic activity. The tests that are described cannot quantitatively measure the specific IAT proteins and there is no evidence that the IAT fractions possess any immunologic activity. Thus, Burton's tumor antibody has never been shown to be a tumor specific immunoglobulin that can interact with tumor antigens and activate complement. His tumor complement fraction has no complement activity (written communication, G.J. Gray, PhD, June 21, 1984), his blocking protein has not been shown to block anything, his deblocking protein has not been shown to deblock anything, and his human tumor cells have never been shown to lyse following the interaction of tumor antibody and tumor complement. Finally, since there is no information on the quality control procedures being used in the manufacture of the IAT materials, there is the possibility that they may be unsterile and, therefore, hazardous for use in humans. Patients who are considering IAT as treatment for cancer should be made aware of these facts when attempting to reach an informed decision regarding its safety and potential efficacy. While this paper was being reviewed for publication, an IAT proponent newsletter called The Cancer Chronicles published the news that Lawrence Burton died of a heart attack in March 1993. The editor of this newsletter, Ralph Moss, PhD, stated that Burton's clinic would remain open under the direction of its medical director, R. John Clement, MD, and would continue to offer IAT to cancer patients.(ABSTRACT TRUNCATED AT 400 WORDS)

Complementary Therapies↗
PubMed1993

PPAR-RXR heterodimer activates a peroxisome proliferator response element upstream of the bifunctional enzyme gene.

A DNA sequence that confers a response to a class of rodent hepatocarcinogens termed peroxisome proliferators has been identified 2947bp upstream of the rat peroxisomal bifunctional enzyme gene. Two members of the steroid hormone receptor family, termed the peroxisome proliferator activated receptor (PPAR alpha) and the retinoid X receptor (RXR alpha), co-operate to bind specifically to this sequence. Importantly, this response element (PPRE) is similar to that identified upstream of other peroxisome proliferator responsive genes such as those encoding acyl CoA oxidase and cytochrome P450 IVA6. These data therefore provide further evidence that PPAR alpha plays an important role in mediating the action of peroxisome proliferators.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed1993

Lucky charms.

Explore the source record for details and available documents.

Contract Services↗
PubMed1993

Properties of a purified estradiol-dependent calf uterus tyrosine kinase.

A uterus tyrosine kinase has been purified to a single 67-kDa protein when analyzed by SDS-PAGE. Under nondenaturing conditions the molecular weight of the enzyme ranges from 114 to 136 kDa, depending on the procedure employed. The kinase binds calmodulin in a Ca(2+)-dependent manner and the ATP analog [(fluorosulfonyl)benzoyl]adenosine. The purified enzyme phosphorylates the phosphatase-treated uterus estradiol receptor on tyrosine and activates its hormone binding. The kinase phosphorylates actin, calmodulin, and histone H2B. Whatever the substrate, the enzymic activity is dependent on purified estradiol-receptor complex and is activated by Ca(2+)-calmodulin. The kinase activates and phosphorylates the human estradiol receptor (HEO) within the hormone binding domain (HBD) [Migliaccio, et al. (1989) Mol Endocrinol. 3, 1061-1069] as well as four of the five mutants of the HEO obtained by substituting each of the five tyrosine residues present in the HBD of the receptor with phenylalanine by site-directed mutagenesis. The mutant substituted at tyrosine 537 is the only one that is neither phosphorylated nor activated by the kinase. This proves a causal relationship between the phosphorylation of estradiol receptor on tyrosine 537 and its hormone binding activity. A synthetic peptide corresponding to 11 out of 13 amino acids surrounding tyrosine at position 537 of the human estrogen receptor can be phosphorylated by the kinase. This and other findings indicate that this kinase, unlike other tyrosine kinases, phosphorylates tyrosyl residues with acidic amino acids close to the carboxyl side.

Actins↗
PubMed1993

Data monitoring committees for Southwest Oncology Group clinical trials.

A monitoring committee policy was established by the Southwest Oncology Group in 1985 to address documented problems in study conduct. Committees consisting of the study coordinators, disease committee chair, study statistician, Group chair, Group statistician, an uninvolved Southwest Oncology Group clinician, an NCI representative, and a representative from each involved group for intergroup studies have been appointed for each phase III study. Business is conducted largely through the mail and through conference calls. Since then, problems identified in older studies have been largely resolved. Appropriate and timely decisions are being made at modest additional expense to the Group.

Clinical Trials as Topic↗
PubMed1993

HIV testing among injecting drug users in Glasgow.

The use of saliva rather than blood for epidemiological studies of HIV prevalence, especially among injecting drug users, has several practical advantages. In a cross-sectional, behavioural and prevalence study among drug users in Glasgow during 1990, salivary samples were therefore obtained by the use of salivettes. Such samples were requested for anonymous anti-HIV testing from 498 persons in locations varying from residential rehabilitation centres to the open streets. Of this number, 35 refused to give a sample, resulting in a compliance rate of 93%. Of the 463 salivettes received by the laboratory, eight were found to be dry. Of the remaining 455 specimens, eight were found to be positive for HIV-1 antibody by means of an IgG antibody capture ELISA, so giving a prevalence rate of 1.8%. The results of testing saliva and blood spot samples collected at the same time on filter paper from 98 persons for HIV-1 antibody were 100% concordant. The study confirms the experience of others that specimens of saliva are easy to collect under variable conditions by non-medical staff and demonstrates that the salivette can provide an HIV antibody test result the same as that obtained from a blood spot. The prevalence of HIV antibody determined in this study is similar to that of other studies taking place in the city during the same period of time.

Cross-Sectional Studies↗
PubMed1993

Criteria for in vitro alternatives for the eye irritation test.

A proposal encompassing considerations and criteria for the development of in vitro alternatives to the eye irritation test has been developed and is presented here. Two factors need to be considered initially in developing an alternative test. The first is to determine whether the alternative assay is to be used as a screen or as a replacement for the eye irritation test. Less stringent acceptance criteria are required for an assay used as a screen than for that used as a replacement test. A screen is a preliminary test for the assessment of eye irritation. It is used for making preliminary decisions or establishing the direction for further testing. Screens answer fewer and less complex questions than a replacement test would, since the results from screens are usually confirmed by more definitive testing. A replacement test, however, must provide the same answers as in vivo methods for the assessment of eye irritation and must provide data for making a definitive toxicological assessment of eye irritation. The second factor to be considered is knowledge of the in vivo assay intended to be replaced. This knowledge should include the procedural aspects of the test and the regulatory information it provides. The following may be considered as criteria for in vitro tests used as screens or as replacements for the eye irritation test in rabbits: rationale (there should be a clear statement regarding the rationale for the use of a particular test in relation to the availability of other tests); relevance (the in vitro endpoint should have biological or physiological relevance to the effect to be detected in vivo); and validational (intralaboratory as well as interlaboratory validation must be conducted).

Animal Testing Alternatives↗
PubMed1993

Screening procedures for eye irritation.

Screens aid in identifying some severe irritants or corrosives and eliminating them from consideration for in vivo eye irritation testing. Products may be evaluated for ocular irritation potential in a stepwise progression as follows: (1) products at pH extremes of 2 or below or of 11.5 or above may be considered to be ocular irritants; (2) based on chemical structure-activity considerations, some products may be judged to have ocular irritation potential; (3) validated and accepted in vitro systems may possibly be used as a screen in the future; (4) when a test material demonstrates severe acute dermal toxicity (lethality at < or = 200 mg/kg body weight), further testing for either dermal or ocular irritation may not need to be undertaken; (5) if a substance shows a primary dermal irritation index of 5 or above, it may be considered to be an ocular irritant; (6) materials that are not removed from consideration based on these proposed screens may then be considered for testing for ocular irritation in rabbits under accepted procedures. In a survey given to participants in the workshop, a high percentage believed that screens should be used. However, opinions on the use of the individual screens varied between the different interested groups attending, with the possible future use of in vitro screens for specific product lines having the highest percentage of agreement (57-100%).

Animal Testing Alternatives↗
PubMed1993

Use of ophthalmic topical anaesthetics.

Pretreatment of the eyes of rabbits with a topical anaesthetic can be viewed as a refinement of the test for eye irritation. It reduces pain at the time of test-material administration, decreases animal distress and permits easier application of the test agent to the eye. In some cases, however, use of an anaesthetic either alone or in combination with the test substance may alter ocular responses or provide little benefit. Although anaesthetic pretreatment may result in decreased pain at the time of test-compound administration, it does not affect possible pain after the effects of the anaesthetic have dissipated. Some anaesthetics are themselves irritating to eyes. In addition, anaesthetics reduce blinking and tearing, thereby maintaining the test-material concentration at the surface of the eye longer. Corneal permeability may also be increased with pretreatment use of an anaesthetic, and may bring the test agent into contact with more structures of the eye. Some anaesthetics delay healing after ocular injury. All of these varied effects may result in increased irritation to the eye. Overall, pretreatment with anaesthetics has usually resulted in a tendency for slightly higher irritation scores; eye irritancy classification is usually unaffected.

Anesthetics, Local↗
PubMed1993

The use of low-volume dosing in the eye irritation test.

The Draize rabbit eye test was developed to provide a method for assessing the irritation potential of materials that might come in contact with human eyes. The method involves the instillation of 0.1 ml of a test liquid (100 mg solid) into the conjunctival sac of an animal's eye. A refinement of the Draize test is the low-volume eye test in which 0.01 ml of a substance is placed directly on the cornea of the eye. Studies indicate that the low-volume method provides a better correlation to human eye irritation experience for some substances. The Interagency Regulatory Alternatives Group (IRAG) proposes that the low-volume eye test can be used to substantiate the irritancy of suspect severe ocular irritants that have not been eliminated by various pre-eye test 'screens'. A substance testing positive by the low-volume method can be classified as an irritant; one that tests negative will require further testing by the use of the 0.1-ml volume procedure. For all other definitive testing, the Draize test (0.1 ml) should be used. Results from a questionnaire distributed at the IRAG workshop showed that many workshop participants thought that the low-volume test should be used as an eye irritation screening procedure.

Animal Testing Alternatives↗
PubMed1993

Number of animals for sequential testing.

US regulatory agencies have used six animals in eye irritation tests. Analyses of eye irritation tests on pesticides (n = 48), consumer products and cosmetics (n = 53), Marzulli and Ruggles database (n = 139), and cleaning products and ingredients (n = 30) have greatly extended previous investigations of the merit of reducing animal sample size in the eye test. Given the existing scoring system for positive animal responses (corneal opacity > or = 1, iritis > or = 1, conjunctival redness > or = 2 and conjunctival chemosis > or = 2), the accuracy of the classification systems currently used by these agencies was determined. The US Consumer Product Safety Commission, US Food and Drug Administration, and US Occupational Safety and Health Administration use a classification system by which a substance is designated as an irritant when at least four of six animals give a positive response. This decision rule leads to a very high accuracy of at least 99% with essentially no false positive and false negative judgments. In contrast, the system used by the US Environmental Protection Agency pesticide program, in which only one or more of six treated animals result in an irritant decision, has an accuracy of only 50-80% with very high false positive rates. Analyses indicated that test sample size could be reduced to three and still preserve very good accuracy, whereas two-animal and one-animal tests did not give satisfactory responses. A two-stage test, in which two animals are tested and evaluated in the first stage before the need for testing one more animal in the second stage is determined, also demonstrated good operating characteristics. Both the one-stage/three-animal test and the two-stage test deserve consideration.

Animals↗
PubMed1993

Scoring for eye irritation tests.

Scoring of the rabbit eye test and the resulting evaluation and classification should provide useful information about the likelihood that a test material may cause injury on contact with the human eye. When an animal test is necessary, a rabbit eye test based on the following characteristics is proposed for deriving the maximum information from the fewest animals. The ocular effects of interest should include corneal opacity, iritis and conjunctival redness. Animals should be scored for each ocular effect at 24, 48 and 72 hr after the test substance is administered. If an animal is negative at all three scoring times, it can be removed from the test at 72 hr. If it shows a positive effect at a scoring time but the lesion clears at 72 hr, it can be removed at 72 hr. If it shows a positive effect that does not clear at 72 hr, it should be scored again on day 7 when the test ends. However, if an animal shows severe effects at one or more scoring times, it can be removed from the test at 72 hr. An animal is positive if any one of the following criteria is observed at 24, 48 or 72 hr: corneal opacity of 1 or above, iritis of 1 or above, or conjunctival redness of 2 or above. Severe ocular effects (noted at 24, 48 or 72 hr) that may endanger sight deserve special recognition for the classification of chemicals and include corneal opacity of 3 or above, or iritis of 2. This proposal is consistent with the opinions of the majority of respondents who attended the Workshop on Updating Eye Irritation Test Methods, Proposals for Regulatory Consensus. The most notable exception was the suggestion by respondents to add conjunctival chemosis as one of the scoring parameters.

Animals↗