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M Jacoby

Publications and source records attributed to M Jacoby.

13 recordsLinked to original sources
PubMed1992

A plan to suppress or prevent the immune rejection of allografted organs.

Progress in the resolution of allograft rejection and associated complications has been hampered by the nonselective nature of current immunosuppressive therapy. In the following protocol, we proposed instead of broadly suppressing immunoreactivity to remove selectively from the bloodstream supplying the transplanted organ only those T lymphocytes and/or antibodies capable of reacting with and destroying the allograft. This goal is to be accomplished by offering them (T cells and/or antibodies) a decoy of antigenically identical tissue. The proposed procedure has the added advantage that it may activate suppressor T cells specific for the allogenic tissue, thereby further promoting acceptance of the graft while providing the host immune system the opportunity to recognize the allograft as autochthonous.

Animals↗
PubMed1989

Localization of barriers to water flow in toad urinary bladder.

Although it is well accepted that vasopressin (ADH) increases the permeability to water of the toad bladder granular cell's luminal membrane, recent studies have suggested that regulation also takes place at an additional "postluminal" site within the epithelial granular cell. These studies are based upon the observation that a number of experimental maneuvers can alter tissue permeability to water, but do not change the number of particle aggregates observed on the protoplasmic face of the granular cell's luminal membrane with freeze-fracture electron microscopy. These aggregates are believed by many investigators to mediate the transport of water across the luminal membrane. The dissociation between permeability and aggregate frequency described above has been variously interpreted as the consequence of changes in the permeability of the aggregates themselves, or of changes in the permeability of a "postluminal" barrier that is functionally in series with the luminal membrane. We attempted to distinguish between these 2 possibilities by studying paired toad bladders during 3 protocols that alter vasopressin-stimulated water flow across the intact tissue without altering aggregate frequency. Estimates of the permeability of postluminal barriers were obtained by exposing the luminal surface to amphotericin B, an antibiotic that forms water-permeant channels in the luminal membrane. Of the 3 protocols, only diminishing bladder filling volume decreased the water flow elicited by luminal amphotericin B, suggesting that only that protocol indeed decreased the permeability of some postluminal barrier. The other 2 protocols, increasing PCO2 and repeatedly stimulating the bladder with vasopressin, did not alter amphotericin B-elicited flow, suggesting that postluminal barriers were not altered by these 2 protocols.(ABSTRACT TRUNCATED AT 250 WORDS)

Amphotericin B↗
PubMed1988

Protein synthesis inhibitors attenuate water flow in vasopressin-stimulated toad urinary bladder.

Vasopressin stimulates the introduction of aggregated particles, which may represent pathways for water flow, into the luminal membrane of toad urinary bladder. It is not known whether water transport pathways are degraded on removal from membrane or whether they are recycled. We examined the effect of the protein synthesis inhibitors cycloheximide and puromycin using repeated 30-min cycles of vasopressin followed by washout of vasopressin, all in the presence of an osmotic gradient, a protocol that maximizes aggregate turnover. "High dose" cycloheximide (200 micrograms/ml) inhibited flow immediately. "Low dose" cycloheximide (1 microgram/ml) did not affect initial flow; however, flow was inhibited by the fourth restimulation. On further rechallenge, inhibition persisted but did not increase. In the absence of vasopressin, inhibition did not develop. Despite the inhibition of flow in vasopressin-treated tissues, the cAMP-dependent protein kinase ratio (-cAMP/+cAMP), an index of in vivo cAMP effect, was elevated in cycloheximide-treated tissues, suggesting modulation at a distal site in the stimulatory cascade. Cycloheximide inhibited flow when 10 microM forskolin or 0.2 mM 8-BrcAMP was substituted for vasopressin in the fourth period; however, MIX (4 mM)-stimulated flow was enhanced by 1 microgram/ml cycloheximide but inhibited by 200 micrograms/ml cycloheximide. [14C]urea permeability was not inhibited by cycloheximide. Puromycin (0.5 mM) also inhibited water flow by the fourth challenge with vasopressin. The data suggest that protein synthesis inhibitors attenuate flow at a site that is distal to cAMP-dependent protein kinase.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-3-isobutylxanthine↗
PubMed1987

Comparison of effects of forskolin, cAMP, and vasopressin on Pf/Pd(w) of toad urinary bladder luminal membrane.

We have reported that Pf/Pd(w) (the ratio of osmotic and diffusional water permeabilities) for the luminal membrane of toad urinary bladder is approximately 17 for tissues stimulated with either vasopressin or 8-bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP). In a recent abstract, Kachadorian and co-workers have shown that tissues stimulated with adenosine 3',5'-cyclic monophosphate (cAMP) or forskolin have a lower Pf than would be anticipated from the frequency of aggregates visualized on the flat portion of the luminal membrane using freeze-fracture electron microscopy. We report here measurements of Pf/Pd(w) for the luminal membrane of tissues receiving these agents: Pf/Pd(w) for submaximally stimulated tissues was the same, regardless of whether the stimulant was vasopressin (12.7 +/- 0.3), forskolin (13.7 +/- 0.9), or cAMP (12.0 +/- 1.3). The calculated Pd(w)'s for the series barrier were also identical (6.8 +/- 0.5, 6.5 +/- 0.3, and 8.2 +/- 1.0 X 10(-4) cm/s respectively). Our data, taken together with those of Kachadorian et al. are consistent with a number of possibilities: because our methodology does not permit estimation of Pf for the series barrier, we cannot rule out the possibility of a "post-luminal barrier" that is rate-limiting for Pf, but not for Pd(w) in forskolin- and cAMP-stimulated tissues, Pf and Pd(w) of the luminal surface aggregates could decrease in parallel, so that luminal membrane Pf/Pd(w) remains constant, and there could be a diminished frequency of fused aggregate-rich aggrephores, but not of aggregates that are on the flat portion of the luminal membrane. Only the latter can be unequivocally quantitated using freeze-fracture electron microscopy.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Epoxygenase metabolites of arachidonic acid inhibit vasopressin response in toad bladder.

In addition to cyclooxygenase and lipoxygenase pathways, the kidney can also metabolize arachidonic acid by a NADPH-dependent cytochrome P-450 enzyme to epoxyeicosatrienoic acids (EETs); furthermore, 5,6-EET has been shown to alter electrolyte transport across isolated renal tubules. We examined the effects of three EETs (5,6-, 11, 12-, and 14,15-EET) on osmotic water flow across toad urinary bladder. All three EETs reversibly inhibited vasopressin-stimulated osmotic water flow with 5,6- and 11,12-EET being the most potent. The effects appeared to be independent of prostaglandins. EETs inhibited the water flow response to forskolin but not (with the exception of 11,12-EET) the response to adenosine 3',5'-cyclic monophosphate (cAMP) or 8-BrcAMP, consistent with an effect on cAMP generation. For 11,12-EET the question of an additional inhibition at a site beyond or independent of cAMP has to be considered. To determine whether these effects were due to the EETs or to products of their metabolism, we examined the effects of their vicinal diol hydrolysis products, the dihydroxyeicosatrienoic acids. Nonenzymatic conversion of labeled 5,6-EET to its vicinal diol occurred rapidly in the buffer, whereas 11,12-EET was hydrolyzed in a saturable manner only when incubated in the presence of bladder tissue. The dihydroxyeicosatrienoic acids formed inhibited water flow in a manner paralleling that of the EETs. Both 5,6-EET and 11,12-EET (10(-5) M) prevented the increase in intracellular cAMP content observed in control tissues after vasopressin stimulation. Finally, 11,12- and 14,15-dihydroxyeicosatrienoic acid inhibited vasopressin- and forskolin-stimulated adenylate cyclase in the same rank order as their inhibition of water flow.(ABSTRACT TRUNCATED AT 250 WORDS)

8,11,14-Eicosatrienoic Acid↗
PubMed1981

Multiple sites for interaction of prostaglandin and vasopressin in toad urinary bladder.

The interaction of vasopressin with prostaglandins were examined in the toad bladder by determining water flows, cAMP levels, and cAMP-dependent protein kinase activity. Both water flow and activation of cAMP-kinase in response to vasopressin were enhanced after prostaglandin inhibition, consistent with inhibition of vasopressin-induced cAMP generation by endogenous prostaglandins. On the other hand exogeneous PGE stimulated cAMP generation. PGE1 (10(-7) M) alone did not increase water flow but activated kinase more than vasopressin only. Addition of PGE1 (10(-7) M) and vasopressin inhibited water flow as compared with vasopressin along but increased the kinase ratio above that with vasopressin only. PGE2 (10(-5) M) increased the cAMP content and kinase ratio even more than vasopressin but again resulted in no water flow. Addition of vasopressin and PGE2 (10(-5) M) increased water flow but did not alter cAMP content or the kinase ratio compared with PGE2 alone. Similar results were obtained with PGE1. Accordingly, prostaglandin dissociates cAMP levels and kinase ratio from the hydroosmotic response, suggesting that PGE2 inhibits steps distal to cAMP. Consistent with this, in bladders pretreated with naproxen or meclofenamate, PGE2 (10(-8) to 10(-6) M) inhibited the response to submaximal doses of cAMP (5 mM) or 8-bromo-cAMP (0.03 mM). Furthermore, pretreatment with naproxen significantly enhanced the response to cAMP (5 mM). These studies provide evidence for vasopressin-PGE interaction at the site of cAMP generation and also at a step(s) unrelated to cAMP generation.

Animals↗
PubMed1981

The effects of amrinone on transport and cyclic AMP metabolism in toad urinary bladder.

Amrinone is a new noncatechol, nonglycoside agent with cardiotonic and vasodilator properties. This paper examines the effects of amrinone in the toad urinary bladder, a tissue whose function may be altered by many factors which also change cardiovascular activity. Amrinone enhanced the effect of vasopressin and cyclic AMP on water and urea permeabilities, as well as the effect of vasopressin on sodium transport. Consistent with these actions, amrinone inhibited cyclic AMP phosphodiesterase activity in epithelial homogenates and increased both cyclic AMP content and the protein kinase activity ratio measured in intact epithelial cells. The inhibitory effect of amrinone on phosphodiesterase may be relevant to its cardiostimulatory and vasodilator activities.

Aminopyridines↗
PubMed1975

Partial losses of sex chromosomes induced by X-rays in spermatozoa of Drosophila melanogaster.

The frequency of induced partial and complete losses of sex chromosomes from spermatozoa of Drosophila melanogaster was determined by mating irradiated males to females heterozygous for an attached-X Y chromosome and for a bb-deficient chromosome. The relative involvement of the X- and Y-chromosomes in partial losses was determined by (a) irradiating males with an X-chromosome centromere marked by a y+ translocated to the short right arm, and a Y-chromosome marked by w+, and (b) comparing the frequencies of fragments recovered from irradiated males with a normal, marked Y-chromosome and from irradiated males and a deleted bb Y-chromsome. 50-80% of the induced losses of sex-chromosomes in rod-X/Y males were partial losses, whereas only 25% of those induced in ring-X/Y males were partial losses. More than 70% of the recovered fragments were of Y-chromosome origin. Fragments recovered from attached-X-Y sons of irradiated males wer checked for the presence of the most proximal euchromatic X-chromosome genes. Most fragments of the rod-X were broken more proximally than bb. In the ring-X there was an excess of fragments broken in the proximal euchromatin. It was concluded that many fragments of the Y-chromosome was due to breaks induced by one-hit events, in both arms of the chromosome that were folded upon themselves. A similar mechanism had been postulated earlier for fragments of the ring-X chromosome.

Animals↗
PubMed1974

Jolande Jacobi.

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History, 19th Century↗