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Biomedical subjects

M Feldman

Publications and source records attributed to M Feldman.

At least 397 records · Page 22Linked to original sources

Tiotidine and cimetidine--kinetics and dynamics.

Tiotidine and cimetidine kinetics and dynamics were compared to assess mechanisms of the longer duration of effect of tiotidine in man. Both drugs has similar lag times for absorption. Tiotidine with a meal was more slowly absorbed than when fasting and was also more slowly absorbed than cimetidine with a meal. The elimination rates for both drugs did not differ; they were both approximately 2 to 3 hr. Oral doses of cimetidine achieved areas under the plasma concentration curve approximately three times that of tiotidine but these concentrations were only 1/10 as potent. The cimetidine concentration inducing 50% inhibition of food-stimulated gastric acid secretion was 0.41 +/- 0.04 whereas it was 0.04 +/- 0.003 microgram/ml for tiotidine. The effect of tiotidine lasted longer than that of cimetidine because the doses recommended for use in man resulted in higher concentrations in plasma relative to effective concentration than clinical doses of cimetidine.

Adult↗

H-2K region-controlled products of the murine major histocompatibility complex differ in their immunogenic capacity when expressed on different tissues.

Reciprocal skin grafts between the C57BL/6 (H-2b) mice and the mutant strain B6.C-H(Z1) (H-2ba), which differ only in a point mutation in the K region of the major histocompatibility complex, elicit rejection reactions similar to those elicited by skin allografts incompatible at multiple loci. Thyroid grafts in the same combinations are not rejected. Analyzing the immunogenicity of H(Z1) skin and thyroid tissues, we found that secondary H(Z1) thyroid grafts were rejected by C57BL/6 mice which had rejected H(Z1) skin tissue. On the other hand, pregrafting of C57BL/6 mice with H(Z1) thyroid did not induce a rejection reaction against a second-set H(Z1) thyroid transplant. These results indicate that gene products of the K region are expressed on thyroid cells and are recognized by memory lymphocytes induced by the H(Z1) skin. Yet, unlike the skin cells, the thyroid expressed H-2k-associated determinants in a nonimmunogenic form which can induce neither an actual rejection nor a state of memory.

Animals↗

Sex-associated differences in the immune response against fetal major histocompatibility antigens.

Alloantibodies against H-2b and H-2k haplotypes were produced in C57BL/6J and C3H female and male mice in response to transplantation of F1 fetal tissue (bone) or adult F1 cells (spleen). Testing IgG1 and IgG2 antibodies by means of the fluorescence-activated cell sorter (FACS II), we found no differences between males and females in the isotype content of antisera produced against spleen cells from adult donors. In contrast, striking sex-associated differences were found in the isotypes produced against fetal allografts: females produced much more IgG1 than males, although they produced comparable amounts of IgG2. Hence, it appears that females differ from males in their humoral alloreactivity against major histocompatibility complex (MHC) gene products expressed on fetal cells. Such MHC antigens expressed on fetal tissues seem to generate different immune signals than the MHC antigens expressed on adult cells. These observations might be of relevance to the biological role played by the IgG1 alloantibodies produced during pregnancy against the MHC alloantigens of the fetus.

Animals↗

Anesthetic drugs accelerate the progression of postoperative metastases of mouse tumors.

Experiments were made to investigate the effect of four anesthetic drugs that are commonly used in surgical practice on the postoperative growth of mouse tumors in syngeneic recipients. These experiments revealed that some of the anesthetics when applied for surgical excision of the local tumor, strongly accelerated postoperative progression of spontaneous lung metastases produced by the 3LL Lewis lung carcinoma and by the B16 melanoma. Some of the drugs caused the appearance of metastases in organs, such as the liver, in which spontaneous metastases are not usually produced by these tumors. A T10 sarcoma clone that does not produce detectable metastases in immune intact mice even following intravenous injection, did produce metastases when injected into animals treated with pentothal sodium.

Anesthetics↗

Efficacy of nifedipine in rest angina refractory to propranolol and nitrates in patients with obstructive coronary artery disease.

Nineteen patients with recurrent rest angina were given oral nifedipine. All patients had chest discomfort refractory to propranolol and oral or topical nitrates given to tolerance. The addition of nifedipine, 30 to 120 mg daily, abolished rest angina in 14 patients, decreased its frequency in two, and had no effect in three patients. Five of seven patients on long-term nifedipine (mean, 6.2 +/- 3.4 months) remained free of rest pain. Of seven patients who had their nifedipine dose decreased or discontinued, five had recurrent rest angina. Of the 19 patients, 16 had coronary angiography. Five had three- vessel obstructive disease (greater than 75% lesion), six had two-vessel obstructive disease, and five had one-vessel obstructive disease. The remaining three unstudied patients had pathologic Q waves in the ECG. Thus nifedipine appears to be an efficacious agent in the treatment of refractory rest angina in patients with obstructive coronary artery disease.

Adult↗

Tiotidine, a new long-acting histamine H2-receptor antagonist: comparison with cimetidine.

The effects of tiotidine, a new histamine H2-receptor antagonist, and cimetidine on food-stimulated gastric acid secretion were evaluated in duodenal ulcer patients. Homogenized steak meals were infused immediately after, 1 h after, 5 h after, and 10 h after an oral dose of medication, and food-stimulated acid secretion was measured by in vivo intragastric titration. Tiotidine and cimetidine had a similar onset of action; however, tiotidine was more potent and had a longer duration of effect. Increased potency was demonstrated by the fact that from 1 to 2 h after medication 150 mg tiotidine inhibited acid secretion to approximately the same extent as did 300 mg cimetidine, and by the fact that for a given percent inhibition of acid secretion, plasma tiotidine concentration was eight to nine times lower than plasma cimetidine concentration. Longer duration of effect was demonstrated by the fact that from 5 to 7 h after medication, acid secretion was inhibited by 80% and 97% with 150 and 300 mg tiotidine, respectively, whereas 300 mg cimetidine inhibited acid secretion by only 22%. Also, 10-12 h after medication, 150 and 300 mg tiotidine inhibited acid secretion by 22% and 53%, respectively, while 300 mg cimetidine had no inhibitory effect. The long duration of effect was due in part to increased potency and in part to a plateau in plasma concentration of tiotidine, which was maintained from 2 to 6 h after medication. Neither tiotidine nor cimetidine had a significant effect on food-stimulated gastrin release or gastric emptying of a nonabsorbable marker.

Adult↗

Neural and hormonal factors in peptic ulcer disease.

The cause of duodenal ulcer (DU) is unknown, but gastric acid and pepsin must be involved in the pathogenesis of the disorder: (1) Patients with massive acid hypersecretion due to gastrinoma almost develop peptic ulcer, usually duodenal; (2) ordinary DU patients, on the average, secrete much more acid basally and also have larger acid secretory capacities than healthy people; and (3) reduction of gastric acid secretion (e.g., with cimetidine) accelerates DU healing and prevents DU from recurring. Although factors responsible for increased basal acid secretion rates and for increased maximal secretory capacity (parietal cell mass) in many DU patients are not completely understood, it is likely that neural and hormonal factors are involved: The stomachs of some DU patients may be under increased vagal drive in the basal state. Parietal cells of DU patients are more sensitive to the hormone gastrin, which is released by food. In this review, evidence for abnormalities in vagal function and gastrin physiology in DU will be discussed, with emphasis on recent developments.

Duodenal Ulcer↗

Control of progression of local tumor and pulmonary metastasis of the 3LL Lewis lung carcinoma by different histocompatibility requirements in mice.

Intrafootpad inoculation of syngeneic mice with Lewis lung carcinoma (3LL) cells led to the growth of a solid tumor at the site of transplantation, followed by development of metastases in the lungs. Surgical excision of the primary tumor resulted in an accelerated growth and increased incidence of pulmonary metastases. Inasmuch as 3LL tumor cells isolated from the local tumor differed antigenically from the cells isolated from the metastases, the genetic control of the local 3LL tumor growth and that of its lung metastases were tested. The local tumor grew in allogeneic mice, yet its growth rate was higher in syngeneic and semiallogeneic F1 hybrids than in allogeneic recipients. However, lung metastases did not appear in allogeneic animals. By analysis of the rate of growth of the local tumor in congenic mouse strains, the tumor progression appeared to be linked to the host's genetic background rather than to the H-2 region. The generation of lung metastases required compatibility at both background and H-2 haplotype. Tests of the development of metastases in mice of congenic resistant recombinant strains revealed that metastases developed only in animals that shared with the tumor the gene products of the D-end of the major histocompatibility complex. Thus metastasis formation was controlled by both a non-H-2 gene(s) and a gene(s) linked to the H-2D region or another nearby region to the right of H-2D.

Animals↗

Metastatic properties conferred on nonmetastatic tumors by hybridization of spleen B-lymphocytes with plasmacytoma cells.

The P3-NSI/1-Ag4-1 (NSI) plasmacytoma, when transplanted sc in syngeneic BALB/c mice, grows locally without forming spontaneous metastases. We tested whether somatic hybridization of the NSI cells with spleen B-lymphocytes would render them metastatic in (C57BL/6 X BALB/c) F1 mice. We found that the hybridomas thus produced generated spontaneous metastases with distinct organ specificities. Some hybridomas produced metastases in both liver and spleen, whereas others produced metastases in only the liver. Cells derived from spleen-and liver-seeking hybridomas, when transplanted sc, produced tumors that metastasized to both the liver and spleen. Tumor cells derived from spleen metastasis produced, on transplantation, a tumor that generated spleen metastasis of a larger mass than did tumors derived from liver metastases. Cells derived from liver-seeking hybridomas metastasized to only the liver. Similar patterns of organ specificity were observed after iv injection of the hybridoma cells. The spleen seemed to play determining role in controlling the production of liver metastases by hybridomas that produced both liver and spleen metastases. Such hybridomas did not produce liver metastases when injected into splenectomized recipients. Hybridomas that were only liver-seeking did produce metastases in splenectomized recipients.

Animals↗

Noninvasive cardiopulmonary monitoring.

Contrast dilution curves have been utilized for evaluation of hemodynamic function. Noninvasive techniques for this purpose usually have been qualitative, expensive, and cumbersome with minimal applicability to the newborn infant. The technique of roentgen densitometry has been utilized to screen children with heart murmurs. Characteristic curve patterns were identified for normal subjects and for patients with shunts with correlation to catheterization data. This technique is now being applied in a quantitative fashion to estimate cardiac output and left-to-right ductal shunts. Cardiac output volumes were inversely proportional to the difference of the second moments of the dilution curves obtained--the second moment being a measurement of the peak dispersion. The estimation of the percent of left-to-right shunt is related to the exponential decay of the left-sided curve.

Absorptiometry, Photon↗

Antibodies to inhalant fungal antigens in patients with asthma in Israel.

Thirty-eight of 97 asthmatic patients, seven of 26 normal subjects and two of 39 patients with chronic obstructive pulmonary disease (COPD) were found to have antibodies to one or more of the inhalant fungi and candida antigens assayed by both immunodiffusion and counterimmune electrophoresis. Atopy was demonstrated in 33 of the 38 asthmatic patients with antibodies. Eleven asthmatics had anti-alternaria antibodies while only two reacted to aspergillus.

Alternaria↗

'Partial' sham feeding releases gastrin in normal human subjects.

We determined whether sham feeding which precluded oral contact with food would release gastrin. In 16 experiments in 7 subjects, either an appetizing meal was discussed or subjects were permitted to see and/or smell a meal of their choice being prepared. In response to this 'partial' sham feeding, serum gastrin concentrations increased from 48 +/- 5 to 57 +/- 7 pg/ml (P less than 0.005). Gastric acid output also increased significantly in response to 'partial' sham feeding. These studies indicate that sham feeding releases significant amounts of gastrin in healthy human subjects and that this response is not dependent upon the presence of food in the oral cavity.

Adult↗

Effect of lactic dehydrogenase virus infection on tumor induction and tumor growth.

The ubiquitous nononcogenic lactic dehydrogenase RNA virus (LDV) is one of the most common contaminants of transplantable tumors and oncogenic viral preparations. This association of LDV with a large variety of murine tumors and the known effect of LDV infection on immune competence may suggest the existence of a possible etiological relationship between the virus and murine tumors. We have found that the inoculation of transplantable carcinoma cells to acutely LDV-infected mice is followed by an enhanced rate of tumor growth. To examine the possibility that LDV is involved in the carcinogenic process and may act as a promoter or initiator, we infected mice with LDV at various time intervals prior to, simultaneously with or after their treatment with chemical carcinogens (urethan 3-methylcholanthrene, and 9,10-dimethyl-1,2-benzanthracene) and then followed the development of the malignant disease. No differences in the rate of tumor appearance and in mortality were observed between LDV-infected and uninfected mice. In addition, LDV failed to affect the development of spontaneous reticulum cell sarcoma and lymphatic leukemia in SJL/J, AKR/Cu, and AKR/J mouse strains. It is suggested that, although LDV does not affect the induction of oncogenic processes, this virus may still be capable of promoting the progression of transplantable tumors due to its immunoregulatory properties.

Animals↗

Differential expression of H-2 gene products in tumour cells in associated with their metastatogenic properties.

Many neoplasms seem to be heterogeneous in nature, producing metastases by pre-existing variant cells with inherent biochemical and biological properties. The survival and proliferation of metastatic cells depend on various biological properties, such as enzymes which degrade basement membranes, resistance to various host defence systems, association with host cellular components, adhesiveness and expression of certain membrane glycoproteins. Recent studies have indicated that metastatic cells may differ from the local tumour cells in the expression of immune recognizable membrane-associated antigens. Such antigenic differences may result from an immunoselection of cells with distinct antigenic properties due to a specific immune response evoked against the local tumour. In view of the role of the major histocompatibility complex (MHC) system in controlling and restricting the function of immune effector cells against modified self-components, one could assume that the modulation of the expression of MHC-encoded antigens on the membrane of tumour cells influenced the interclonal relationship within a local heterogeneous tumour cell population and the subsequent generation of metastasis. The modulation of the expression of H-2 antigens on several murine tumours is well documented; however, practically no attempts were made to relate H-2 modulation with invasiveness. We now describe principal differences in the expression of H-2 parental haplotypes between a local F1 methylcholanthrene-induced tumour and its descendant pulmonary metastases. These results suggest that both the expression and the immunogenicity of MHC products strongly influence the immune relationship between the tumour and the host's immune system, thus determining the generation and dissemination of metastases.

Animals↗

Effect of photooxidation on the estrogen receptor from rat mammary tumor.

Photooxidation of estradiol receptor form MTW9 rat mammary tumor cytosol leads to a time-dependent loss of DNA-binding activity; this effect is pH-dependent. Binding of receptor to DNA does not protect the DNA-binding site from photooxidation. The estrogen binding site of the receptor is also susceptible to photooxidation, although the rate of loss of estradiol binding capacity is considerably less than that of DNA-binding capacity; this process is independent of pH. Binding of receptor to estradiol substantially protects the estradiol binding site from photooxidation. Sucrose gradient analysis of photooxidized receptor preparations showed no qualitative difference compared with nonirradiated controls. Similarly, the isoelectric focusing pattern of photooxidized receptor showed two peaks of radioactivity at pH approximately 5.6 and 6.3, as did nonirradiated receptor.

Animals↗