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Biomedical subjects

D M Jacobs

Publications and source records attributed to D M Jacobs.

At least 91 records · Page 5Linked to original sources

Diet, lipoproteins and cholesteryl ester transfer activity in hyperlipidaemic subjects.

In order to study the response of cholesteryl ester transfer activity (CETA) to alteration in diet in humans we carried out a longitudinal study in hyperlipidaemic patients. Five subjects, all hyperlipidaemic, were first given a low fat diet for 7 to 15 days and then a diet high in fat for 7 to 21 days. In four out of five patients both diets were low in energy. The plasma lipoprotein levels and CETA were measured daily. All patients responded on the low fat diet by a decrease in total cholesterol and total triglycerides. No response on the high fat diet was noticed except in the patient for whom the high fat diet was also high in energy. In all patients the changes in CETA ran parallel to changes in (VLDL + LDL) cholesterol. It is concluded that diet induced changes in (VLDL + LDL) cholesterol are accompanied by similar changes in CETA in hyperlipidaemic subjects.

Journal Article↗

Experience with the endorectal pull-through and S pouch for ulcerative colitis and familial polyposis in adults.

An experience is reported with 23 patients who underwent rectal mucosectomy, total colectomy, creation of S-type pouch, and ileoanal anastomosis for ulcerative colitis (21 patients) or familial polyposis (two patients). There were no deaths. There were 23 complications requiring 18 operations in 16 patients. Twenty-one patients have been followed an average of 17.8 months (range 2 to 34 months) Frequency of bowel movement averaged 9.8 per day initially and 6.2 per day at the time of follow-up. None of the patients consider themselves incontinent, although 15 have had some degree of perianal soiling and at least on occasion have worn a pad. One patient intubates the pouch regularly, six intubate it on occasion, and 14 do not intubate at all. The size of the outflow treat of the pouch has been shortened from 5 to 2 cm in the last seven patients; six of these patients do not intubate and four report no soiling at all. Eleven patients have made changes in their diet or eating habits to promote more predictable bowel function and 13 take a variety of antidiarrheal medications. Nineteen patients are satisfied with the procedure and prefer the pouch to a conventional ileostomy; the other two have since undergone conversion to a Brooke ileostomy. Despite frequent bowel movements, complications, and some problems with perianal soiling, patient acceptance remains high with the endorectal pull-through and S pouch in adults, and further study, particularly using a shortened outflow tract, appears warranted.

Adult↗

Differential growth rate of rat gastric mucosal cells during postnatal ontogeny.

The growth rate of surface epithelial, chief, and parietal cells of the base and neck of oxyntic glands was studied in the albino rat by comparing morphometric measures at days 15, 21, 30, and 100 postnatally. All cells increased in size. The number of cells per micrometer squared increased rapidly for chief cells and base parietal cells, while neck parietal cells remained constant and surface epithelial cells decreased. There was a net increase in the volume density of parietal and chief cells and a slight net decrease in surface epithelial cells during postnatal development. In a second experiment, the effects of early weaning on these variables was studied. Early-weaned rats gained less body weight than normally weaned counterparts. The change in surface epithelial cell size was not affected by early weaning. However, parietal and chief cells grew more quickly, initially, in early-weaned rats than in normally weaned rats. Cell numbers were unaffected except for an initial decrease in relative number of neck parietal cells. One long-term effect of early weaning was noted. The size and volume density of neck parietal cells in early-weaned rats was smaller, in the adult animal, then in normally weaned rats.

Animals↗

Surface phenotype of LPS-binding murine lymphocytes.

We have characterized LPS+ murine lymphocytes by determining their surface phenotype using double-labeling immunofluorescence. In the spleen, 40% of cells were LPS+mu+ (B cells), 5% were LPS+Thy 1.2+ (T cells), and 5% were LPS+ cells bearing neither mu nor Thy 1.2 (null cells). Peripheral lymph nodes contained 11% LPS+ B cells and 2% LPS+ T cells, and mesenteric lymph nodes contained 15% LPS+ B cells and 3% LPS+ T cells. In contrast, the 4% LPS+ cells in Peyer's patches were all B cells, and the thymus contained 4% LPS+ T cells. Only the spleen contained LPS+ null cells. Within each lymphoid organ examined, the fraction of total lymphocytes identified as LPS+mu+, LPS+Ia+, or LPS+ delta + was similar, indicating that LPS+ B cells possessed the surface phenotype mu+Ia+ delta +, characteristic of a mature B cell. This conclusion was supported by the absence of LPS+mu+Ia+ delta + cells in newborn spleens. The fraction of mu+Ia+ delta + cells which also binds LPS was highest in spleen and lowest in Peyer's patches. Assuming that cells are, on the average, more mature in the progression from spleen to lymph nodes to Peyer's patches, it would appear that LPS+ cells are a less mature fraction of the mu+Ia+ delta + pool, distinguished by the presence of an LPS binding site or receptor. These data illustrate selective binding of LPS predominantly to mature B cells, but also to small numbers of null cells and T cells. The relationship of this binding to cell activation is discussed by considering the characteristics of cells which can be activated by LPS to clonal growth or differentiation under appropriate conditions.

Animals↗

Binding of bacterial lipopolysaccharide to murine lymphocytes.

Does LPS activate lymphocytes by binding to a specific cell-surface receptor or by nonspecific hydrophobic interaction with the plasma membrane? We examined this question by detecting cell-bound LPS using immunofluorescence microscopy and radiobinding techniques. LPS binding to splenic lymphocytes from C3H/St mice has characteristics of specific binding: saturability with respect to dose and time, selectivity for a subclass of B-cells, and a correlation between binding and mitogenesis. 125I-labeled LPS bound to cells and analyzed quantitatively by SDS-PAGE separated into 3 major components: peaks 1, 2, and 3 (1 equals the fastest moving). Lymphocytes preferentially bound peak 1, murine RBC peaks 1 and 2, and macrophages peak 2. In contrast, specific antibody preferred peaks 2 and 3. Differential staining of gels suggested that peak 3 is carbohydrate-rich and peak 1 is lipid-rich. LPS was released from these cells at different rates. We conclude that selectivity of LPS binding may be reflected in preferential binding of LPS subunits of different size and/or composition, as well as differential retention of bound LPS.

Animals↗

Mitogenic responses of frog lymphocytes to crude and purified preparations of bacterial lipopolysaccharide (LPS).

We have compared in vitro mitogenic responses of frog (Xenopus laevis and Rana pipiens) lymphocytes to various preparations of lipopolysaccharide (LPS). Commercial LPS prepared from E. coli (phenol extraction) and from S. abortus-equi (phenol and TCA extraction procedures) was mitogenic for frog lymphocytes. After reextraction of these LPS preparations with phenol-water, the remaining LPS was either considerably less mitogenic or not mitogenic. Purified E. coli 055:B5 LPS, prepared by phenol water extraction, enzyme treatment and column chromatography, was not mitogenic. Frog cells proliferated poorly or not at all with all concentrations of reextracted or purified LPS tested (0.5-400 micrograms/ml) and at all culture periods examined (days 1-7). All LPS preparations used were mitogenic for CAF1 mouse lymphocytes, whereas reextracted and purified LPS preparations were not mitogenic for lymphocytes from C3H/HeJ cells. Xenopus were also not susceptible to toxicity induced by parenterally administered LPS in concentrations which killed CAF1 mice.

Animals↗

Pedunculated liposarcoma of the esophagus: a first case report.

A large pedunculated myxoid liposarcoma of the cervical esophagus is presented. Because of its long pedicle, the presenting symptoms were primarily respiratory rather than digestive. The tumor lent itself to local excision rather than esophageal resection, given the absence of involvement of its pedicle and the resultant wide margin of excision. Review of the literature did not disclose a similar case.

Deglutition Disorders↗

Circadian ultrastructural changes in rat gastric parietal cells under altered feeding regimens: a morphometric study.

The ultrastructure of rat gastric parietal cells was studied at six timepoints of the 24-hour day. The rats, maintained on a 12 hour:12 hour light-dark regimen, had been subjected to either a 40-hour fast or to a 4-hour mid-light restricted feeding period. At each time point, the volume density (Vv) of secretory canaliculi, surface density (Sv) of microvesicles and RER, and the numerical density (Nv) of multivesicular bodies were determined in cells of the neck and base of glands. Circadian variation of the four variables was suggested in both experiments. Canalicular and microvesicular measurements suggested that a rhythm in gastric acid secretion may persist during fasting; a peak and trough, respectively, occurred in the late dark phase, as in our previous report on ad libitum-fed rats. Restriction of feeding to that which is normally the rat's resting phase caused an apparent 180 degree phase-shift in the rhythm. The data suggested, however, that additional factors may have influenced the cellular activity pattern. At all timepoints in both experiments cells of the neck of glands had higher RER and canalicular values than did cells of the base of glands. This suggests that parietal cells in glandular necks may be more active than those farther removed from the stomach lumen. There was no correlation between the Nv of multivesicular bodies and glandular location of the cells.

Acid Phosphatase↗

Immunological activities of purified preparations of enterobacterial common antigen.

The immunological activities of three purified preparations of enterobacterial common antigen (ECA) obtained by different procedures were studied. ECA-Ma (method of A. Marx) was from Salmonella typhimurium TV149 (Ra mutant), ECA-My (method of H. Mayer) was from S. montevideo, and ECA-Ro (method of E. Romanowska) was from Shigella sonnei phase I. These preparations, on a weight basis, neutralized similar amounts of ECA antibodies, indicating that the serological activities were comparable. Neither ECA-My nor ECA-Ro elicited specific delayed-type hypersensitivity skin reactions at 24 or 48 h in immunized guinea pigs. ECA-Ma, as well as the nonpurified preparations of the antigens used for immunization, elicited reactions at 24 h but not at 48 h. Thus, ECA-specific delayed-type hypersensitivity was not detected in immunized guinea pigs. Striking differences were noted in the immunogenicity of these antigens, ECA-Ma being highly immunogenic in the rabbit in contrast to ECA-My and ECA-Ro. ECA-Ma was a potent mitogen for guinea pig spleen cells, stimulating high levels of DNA synthesis; ECA-My was only slightly active. The three antigens were mitogenic to spleen cells from both CBA/J and C3H/HeJ mice, although not to the same degree, indicating that this effect is not due to contaminating lipopolysaccharide, since the latter strain of mice is resistant to endotoxin. Since an ECA-Ma extract made from an ECA-negative mutant proved to be mitogenic to murine spleen cells, the mitogenicity is not due to the ECA haptenic determinant. The mitogenic effect is polyclonal in nature, ECA-Ma producing a maximum response on day 3. Thus, the ECA preparations are both B-cell mitogens and polyclonal activators in murine spleen cells. From these studies it is evident that the biological and immunological activities of these purified antigens depend not only on the haptenic determinant but also on associated or bound components of the preparations.

Animals↗

A general interactive model for B cell activation. I. The theory.

A quantitative model of the B lymphocyte triggering apparatus is proposed in which mitogen receptors and surface immunoglobulins are described as allosteric proteins that interact with mitogens and antigens. An equation is derived that describes the activation of a cell as a function of the states of these receptors as defined by ligand and receptor concentrations, ligand receptor equilibrium constants, and receptor allosteric constants. We analyze the model and show that different parameter sets will actually generate a description of the one-nonspecific-signal model, the matrix model, or the two-signal model of B cell triggering. We suggest that our general interactive model provides a useful conceptual approach to studies of B cell activation because it encompasses other available models that are individually consistent with some experiments, but mutually exclusive to each other. A companion paper describes a series of experiments that verify the consistency of the general model.

B-Lymphocytes↗

A general interactive model for B cell activation II. Experimental verification.

The general interactive model described in the previous paper was subjected to experimental testing. We examined the high affinity anti-TNP plaque-forming cell response of cultures of murine lymphocytes exposed to lipopolysaccharide and trinitrophenylated lipopolysaccharide (TNP--LPS). From our model we predicted the effects of the addition of free LPS on the dose response to TNP--LPS, the effect of the addition of Polymyxin B to cultures stimulated with TNP--LPS, and the effect on the response to TNP--LPS preparations with different haptenation ratios. The results obtained were consistent with the predictions of the general interactive model.

Animals↗

Fundamentals for ethanol chronopharmacokinetics in nonstarved, serially sampled rats.

Fed versus starved rats were investigated for an appropriate model for studying the chronopharmacokinetics of ethanol. A serially independent dosage-sampling regimen was compared with a serially dependent one. Before beginning the pharmacokinetic studies, a number of experimental pharmacologic variables was systematically examined and quantified. When 24-hour starved rats (LD = 12:12 h) were injected intraperitoneally with ethanol at varying intervals during a single 24-hour period in a serially dependent manner, no significant differences in blood-ethanol clearance rates were observed. However, when the same dose was administered to ad-libitum-fed rats in a serially independent study, a prominent circadian rhythm in clearance rates was revealed. Interindividual variance was less with fed rats than with starved ones. These studies indicate that further characterization of this rhythm should employ ad-libitum-fed rats colony (serially independently) sampled.

Adrenal Cortex Hormones↗

Circadian morphometric variation in gastric parietal cell populations of the rat.

Gastric parietal cells of rats maintained under standardized conditions and fed ad libitum were examined by electron microscopy at 6 time points of the 24-hr day. Morphometric determinations were made on 4 cell characteristics. The volume density of secretory canaliculi was maximal at the mid-dark sampling point and decreased during the light phase; a secondary peak was seen 1 h before the onset of darkness. The surface density of microvesicles and RER fluctuated inversely with the pattern displayed by secretory canaliculi. The number of multivesicular bodies per cytoplasmic area exhibited a single peak, 1 h after the onset of darkness. It was further noted that parietal cells in the necks and bases of glands differed morphologically and that their organelle populations varied at individual circadian rates.

Animals↗

A solid-phase radioimmunoassay for bacterial lipopolysaccharide.

A radioimmunoassay for E. coli 055:B5 lipopolysaccharide (LPS) is described. The LPS was derivatised by two new methods and subsequently radiolabeled with 125I to a specific activity of 2-4 mCi/mg without apparent loss in its biophysical, immunological or biological activities. Using antibody-coated polystyrene tubes, a solid-phase radioimmunoassay was developed with a sensitivity of 10-500 ng/ml of LPS.

Animals↗