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M M Jacobs

Publications and source records attributed to M M Jacobs.

At least 37 records · Page 2Linked to original sources
PubMed1984

Platelet membrane glycoprotein IIIa contains target antigens that bind anti-platelet antibodies in immune thrombocytopenias.

The precise pathogenic mechanism of platelet destruction in immune thrombocytopenias is not known, although many investigators have found that platelet-associated IgG is increased in these diseases. We report here the differentiation between specific binding of anti-platelet antibody, associated with platelet destruction, and the ubiquitous presence of nonspecific, platelet-associated IgG. Using an electrophoretic separation and antibody overlay technique, we have identified a specific membrane protein that bears target platelet antigens in immune thrombocytopenias. When posttransfusion purpura serum was studied, antibody binding to the PlA1 antigen on glycoprotein IIIa was readily distinguished from the nonspecific binding of immunoglobulin to a protein of 200,000 mol wt. After reduction of disulfide bonds, the PlA1 antigenicity was not observed, and IgG bound nonspecifically to a protein band with an apparent molecular weight of 45,000. We have also identified anti-platelet antibodies in patients with idiopathic thrombocytopenic purpura and determined their antigenic specificity. Antibodies which bind to a 100,000-mol wt protein were found in nine of thirteen patients with chronic disease. The antigens in three of these cases were studied in detail by using both reduced and nonreduced control and Glanzmann's thrombasthenic platelets. Target antigens were localized to glycoprotein IIIa, but are different from PlA1. The immune thrombocytopenic purpura antigenic system is clearly distinguished from nonspecific platelet-associated IgG. Sera from eight children with acute idiopathic thrombocytopenic purpura were also studied. In all cases, the nonspecific IgG binding to the 200,000-mol wt protein was observed. However, we were unable to demonstrate antibody binding to glycoprotein IIIa, which suggested that the acute childhood form of this disease may have a different pathogenic mechanism than that of the autoimmune chronic cases.

Adolescent↗
PubMed1984

Evaluation of the toxicity and carcinogenicity of hair dyes in Swiss mice.

The chronic toxicologic and carcinogenic potential of two oxidative and twelve non-oxidative hair dyes has been evaluated. The dyes were skin painted up to 3 times weekly on groups of 60 male and 60 female Eppley Swiss mice. Treatments were carried out for 20 months followed by terminal sacrifice. Nine months after treatments were initiated an intermediate sacrifice of ten mice per sex per group was carried out. Body weights and survival differed little between appropriate male and female treatment and control groups. Differences between treated and control groups in absolute and relative liver and kidney weights and in hematological and urinary values were not considered to be indicative of toxicologic effects. Microscopic examinations of the skin revealed occasional hyperplasia, necrosis, ulceration and other lesions not significantly increased by dye treatment. Chronic inflammation of the skin was observed in the control and treated mice and was significantly increased by one non-oxidative dye. The predominant tumors diagnosed were liver hemangioma, lung adenoma and malignant lymphoma. There was a statistically significant increase in the incidence of malignant lymphoma in female mice in 3 treated groups when compared to control group 2, but the differences were not significant when these groups were compared to control group 1. In addition the values in these 3 groups were within the range of control values for this tumor in female mice in the Eppley colony. No other tumors occurred at significantly increased frequencies in treated mice. We conclude that toxicological and carcinogenic effects were not clearly induced by the hair dye formulations.

Animals↗
PubMed1983

Selenium inhibition of 1,2-dimethylhydrazine-induced colon carcinogenesis.

The inhibitory effect of selenium (Na2SeO3) on 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis in male Sprague-Dawley rats is presented. A 4-ppm selenium supplement to the drinking water was provided concurrently with DMH treatment and continued until death or sacrifice. Rats were administered 10 weekly injections of 10 mg DMH per kg body weight. Thirtyone weeks following the tenth DMH injection, all surviving animals were sacrificed. At sacrifice, the colon tumor incidence in DMH-only controls was 8 of 28 (29%). Selenium supplementation significantly (p less than 0.01) reduced the colon tumor incidence to 1 of 37 (3%). The cumulative colon tumor incidence for all animals found dead or sacrificed was also significantly (p less than 0.05) reduced from 11 of 40 in DMH controls to 3 of 40 in DMH-selenium-supplemented rats. The total number of colon tumors was reduced from 13 to 3, and the average number of tumors per rat from 1.2 to 1.0 by supplemental selenium. The majority (greater than 65%) of all tumors were located in the distal colon. The serum glutamic oxaloacetic transaminase, alkaline phosphatase, and complete blood count were normal and equivalent for the DMH only, DMH-selenium, and untreated control groups in this study. The glutathione S-transferase activity in liver cytosol preparations was increased from 39.6 +/- 7.3 (S.D.) microM product/min/mg (DMH only) to 67.6 +/- 5.8 microM product/min/mg by selenium only and to 54.3 +/- 10.6 microM product/min/mg in selenium-DMH-treated rats. Protection by selenium may in part be attributed to enhanced detoxification of carcinogenic electrophiles.

1,2-Dimethylhydrazine↗
PubMed1981

Biochemical and clinical effects of selenium on dimethylhydrazine-induced colon cancer in rats.

The biochemical and clinical effects of selenium (Na2SeO3) on 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis in male Sprague-Dawley rats are presented. A 4-ppm selenium supplement to the drinking water was provided before, during, and after 20 weekly injections of 20 mg DMH per kg body weight. Immediately after the 20th DMH injection, part of the rats were sacrificed. The incidences of colon tumors in groups provided selenium before DMH, before and during DMH, and only during DMH treatment were reduced to 39, 43, and 36%, respectively. The incidence in the DMH only control was 63%. Other rats in all treated and control groups were maintained up to 5 months post-DMH treatment. At 10-week intervals throughout the study, selected blood and tissue components were analyzed. The following hematological changes correlated with DMH treatment. (a) Serum glutamic oxalacetic transaminase increased 2-fold (normal, 66 +/- 14 g/dl). (b) Serum alkaline phosphatase increased 24% (normal, 166 +/- 56 units/liter). (c) Serum protein decreased 14% (normal, 6.77 +/- 0.48 g/dl). (d) White blood count increased 2- to 3-fold (normal, 7.7 +/- 2.7 X 10(3)/cu mm). And (e) hemoglobin decreased 67% (normal, 18.1 +/- 1.3 g/dl). The magnitude of these changes varies with each selenium treatment group and with each 10-week analysis period. Provision of 4 ppm selenium doubled both liver and blood selenium levels compared to unsupplemented controls. The effects of selenium and DMH treatments on glutathione peroxidase and beta-glucuronidase activities and on sialic acid are presented. Possible mechanisms by which selenium protects against DMH-induced neoplasia are discussed.

1,2-Dimethylhydrazine↗
PubMed1980

Influence of selenium on vascularization in the hamster cheek pouch.

The inhibitory effect of selenium (Na2SeO3) on the vascularization induced by amelanotic tumor implants (A Mel-4B32) n the Syrian hamster cheek pouch membrane is reported. Among control animals receiving A Mel-4B32 implants, 19 developed tumors out of 19 chambers with capillary proliferation being observed on day 4 after implant. Addition of 50 microgram Se to the chamber at the time of tumor implant delayed the initial observation of capillary proliferation until day 10 after implant. In the 50 microgram Se treated group, tumor-induced vascularization developed in 11 of 15 chamber implants and not in the remaining 4. Intermediate doses of 5 and 10 microgram Se added to the chamber at the time of tumor implant delayed the initial observation of capillary proliferation to days 7 and 9, respectively, with tumors developing in all chambers. Neither sodium nor sulfite altered the vascular pattern. Capillary proliferation was observed on day 4 after tumor implant when either 50 microgram NaCl or 50 microgram S as Na2SO3 were added to the chamber at the time of implant. Provision of Se as a drinking water supplement also delayed the onset of capillary proliferation.

Animals↗
PubMed1980

Evaluation of the toxicity and carcinogenicity of hair dyes.

The chronic toxicological and carcinogenic potential following skin painting in mice was evaluated for nine oxidative and three nonoxidative hair dyes. Groups of male and female Swiss mice were treated one time weekly for at least 20 mo with one dose level of each dye. The oxidative dyes were mixed 1:1 with 6% hydrogen peroxide before treatment and the three semipermanent formulations were applied without dilution. Control groups were shaved only and received no applications. Body weights and survival rates did not differ between appropriate male and female treatment and control groups. Absolute and relative liver and kidney weights were equivalent for treatment and control groups. After 7 and 9 mo of treatment, 10 males and 10 females randomly selected from each group were necropsied and tissues taken for histopathologic evaluation. Animals found dead or sacrificed in moribund condition or at termination of the study were necropsied and evaluated histopathologically. Comparison of incidence of tumors and of nontumor pathology among the various treatment and control groups revealed no biologically significant differences. Toxicological and carcinogenic effects were not induced by the hair dye formulations.

Animals↗
PubMed1980

Maternal pulmonary edema resulting from betamimetic and glucocorticoid therapy.

Four cases are presented of maternal pulmonary edema occurring in patients who had no primary cardiac disease but who were receiving terbutaline and glucocorticoids or terbutaline alone for treatment of premature labor. Fluid overload was the event that triggered this decompensation. The physiologic high-output cardiac state of pregnancy is described and the manner in which betamimetic drugs and corticosteroids exacerbate this situation and cause congestive heart failure is shown. Methods of management to avoid this complication of premature labor therapy are suggested.

Adolescent↗
PubMed1979

Selenium effects on the carcinogenicity and metabolism of 2-acetylaminofluorene.

Addition of 4 ppm Se to the drinking water of male albino rats fed diets containing 0.03% 2-acetylaminofluorene (AAF) provided protection against hepatic damage and also resulted in at least 50% reduction in liver tumor incidence. An in vitro assay system utilizing microsomes from Se supplemented or non-supplemented 3-methylcholanthrene (MC) induced rats was used to determine the effect of oral Se intake on the metabolism of AAF. Oral Se administration led to an increase in ring hydroxylation and a decrease in N-hydroxylation. Addition of Se to the microsomal assay system increased 3-OH AAF formation and decreased N-OH AAF formation, thus shifting the balance of metabolism toward detoxification pathways.

2-Acetylaminofluorene↗
PubMed1978

Effect of sodium selenite and methyl methanesulfonate or N-hydroxy-2-acetylaminofluorene co-exposure on sister-chromatid exchange production in human whole blood cultures.

Sodium selenite (Na2SeO3) was tested for its sister-chromatid exchange (SCE)-inducing ability in human whole blood cultures and for the effect of its co-exposure with methyl methanesulfonate (MMS) or N-hydroxy-2-acetylaminofluorene (N-OH-AAF) on SCE frequency. Long exposure times (77 h and 96 h) to 3.95 X 10(-6) M Na2SeO3 resulted in cell death as measured by mitotic indices, but mitotic figures were present after exposure to higher concentrations for a shorter time (19 h). High Na2SeO3 concentrations (7.90 X 10(-6) and 1.19 X 10(-5) M) resulted in a three-fold increase in the SCE frequency above background level (6--7 SCEs/cell). Exposure of lymphocytes to 1 X 10(-4) M MMS for the last 19 h of culture yielded an average SCE frequency of 30.17 +/- 0.75 while a similar exposure to 2.7 X 10(-5) M N-OH-AAF resulted in 13.61 +/- 0.43 SCEs/cell. Simultaneous addition of the high Na2SeO3 concentrations and MMS or N-OH-AAF to the cultures resulted in SCE frequencies that were 25--30% and 11--17%, respectively, below the sum of the SCE frequencies produced by the individual compounds.

Cell Survival↗
PubMed1978

Studies on ovarian and uterine weight responses to follicle stimulating hormone.

A uterine weight response may potentially provide a plausible qualitative method for detection of "asialo" follicle stimulating hormone (FSH). Asialo FSH is a biologically inert species of FSH when assayed for ovarian weight response by the hCG augmentation method. Numerous experiments have been performed under a uniform set of conditions for normalization of ovarian and uterine weight responses. The influence of several hormones and 2 injection routes on the gonadal responses to FSH have been assessed. Immature female, 24--25 day old Sprague-Dawley rats were injected subcutaneously (sc) or intraperitoneally (ip) twice daily for 3 days. On the 4th day the rats were sacrificed, the ovaries and uterus were removed, cleaned and weighed. Uterine weights were obtained before and after removal of the fluid. NIH-FSH-S9 and its asialo derivative prepared by neuraminidase digestion were the species of follicle-stimulating hormone (FSH) used in all experiments. Addition of either 21 IU prolactin or 0.05 mg histone to FSH did not significantly alter the ovarian weight response augmented by hCG (P = 0.2). Addition of histone to 90 and 180 microgram FSH elicited neither a uterine weight response when injected sc nor an ovarian weight change when injected ip. Both routes of injection of the 2 dose levels of FSH had little effect on the uterine weight. In marked contrast, 90 and 180 microgram asialo FSH injected either sc or ip gave increased uterine weight responses in the presence of hCG. On further examination the uterine weight increase in response to asialo FSH injections proved to be statistically significant (sc. P = 0.02; ip, P = 0.05). Use of the uterine weight response might be exclusively proposed as a qualitative method for detecting asialo FSH. Such biologically inactive species, which elicit no increased ovarian weight response in the hCG augmentation assay, are frequently generated in the preparation of FSH. Determination of the uterine weights may provide meaningful use of auxiliary data from the hCG ovarian augmentation assay of putative FSH preparations which fail to elicit the desired ovarian weight responses.

Animals↗
PubMed1977

Inhibitory effects of selenium on 1,2-dimethylhydrazine and methylazoxymethanol colon carcinogenesis: correlative studies on selenium effects on the mutagenicity and sister chromatid exchange rates of selected carcinogens.

Selenium (Se) inhibition of either the activation of test compounds and/or mutagenic events elicited by activated compounds is suggested by experimental rat assays, mutagenesis assays, and assays with human lymphocytes in culture. The colon tumor incidence in 1,2-dimethylhydrazine (DMH)-treated rats was reduced from 87% to 40% by 4 ppm Se supplements in the drinking water. Supplemental Se decreased the total number of colon tumors induced by DMH more than three-fold and by methylazoxymethanol (MAM) almost two-fold. Coexposure of Salmonella typhimurium TA 1538 to an effective molar ratio of Se/2-acetylaminofluorene=10, Se/N-OH-acetylaminofluorene=10 and SE/N-OH-aminofluorene=300 reduced the mutagenicity to 65, 68, and 61% of their respective controls with mutagen alone. With a molar ratio of Se/N-OH-AAF=100, Se reduced the activity to 28% of the mutagenicity of N-OH-AAF alone. Preliminary data indicating MAM is mutagenic in S. typhimurium TA 1535 and His G 46(6837) are presented. In toxicity studies exposure of human lymphocyte cultures to 1.3 X 10(-9) to 1.6 X 10(-5) M Se yielded sister chromatid exchange (SCE) rates equivalent to background levels of 6--7 SCE per cell. The SCE frequencies of lymphocytes cultured with Se and selected carcinogens are discussed.

Animals↗
PubMed1977

Inhibitory effects of selenium on 1,2-dimethylhydrazine and methylazoxymethanol acetate induction of colon tumors.

Sprague-Dawley rats were injected weekly with either 1,2-dimethylhydrazine (DMH) or methylazoxymethanol acetate (MAM). Addition of 4 ppm selenium (sodium selenite) in the drinking water reduced the number of rats developing DMH-induced colon tumors from 13 to 6 groups of 15 each. The total number of tumors observed in these two groups was 39 in the DMH treated and 11 in the DMH plus selenium. The incidence of MAM-induced tumors was 93% (14/15) with the selenium additive and 100% (14/14) when MAM was administered without the selenium supplement. However, selenium decreased the total number of colon tumors induced by MAM to 42 tumors as compared to a total of 73 tumors in rats receiving only MAM. Both carcinogens induced tumors with a higher frequency in the transverse colon as compared to either the proximal or distal colon. Selenium at this level did not affect the weight gain of the animals.

Adenocarcinoma↗
PubMed1977

Inhibitory effects of selenium of the mutagenicity of 2-acetylaminofluorene (AAF) and AAF derivatives.

Selenium (Se) decreased the mutagenicity of 2-acetylaminofluorene (AAF), N-hydroxy-2-acetylaminofluorene (N-OH-AAF) and N-hydroxyaminofluorene (N-OH-AF) in the Salmonella typhimurium TA 1538 bacterial tester system. Metabolism of AAF and N-OH-AFF to the active mutagen, N-OH-AF, was accomplished by rat liver extracts. Graded decreases in mutagenicity with increasing Se concentrations were observed for each of the three mutagens. Se decreased the mutagenicity of AAF, N-OH-AAF and N-OH-AF to 65, 68 and 61% of their respective controls with mutagen alone. The effective molar ratios of Se to mutagen yielding these decreases were approximately 10:1 (Se:AAF), 10:1 (Se:N-OH-AAF) and 300:1 (Se:N-OH-AF). The largest Se effect observed was accomplished by a molar ratio of 100:1 (Se:N-OH-AAF) yielding 28% of the mutagenicity elicited by N-OH-AAF alone.

2-Acetylaminofluorene↗
PubMed1977

Effects of selenium on azo dye hepatocarcinogenesis.

Groups of male Sprague--Dawley rats were maintained on three regimens: I. basal diet plus 0.05% 3'-methyl-4-dimethylaminoazobenzene (3'-MeDAB), II. same as I plus 6 ppm selenium (Na2SeO3) in the drinking water, and III. same as I plus 6 ppm selenium added to the diet in the form of a high selenium yeast. The 3'-MeDAB was incorporated in the diet for 8 weeks and then removed. The selenium supplements in Groups II and III were continued for an additional 4 weeks. At sacrifice the liver tumor incidence from was ascertained as the ratio of animals with tumors/total number of surviving animals per group. Selenium reduced the incidence from 92% (11/12) in the Group I control, to 46% (7/15) in Group II and to 64% (9/14) in Group III.

Animals↗