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Biomedical subjects

J Shani

Publications and source records attributed to J Shani.

At least 109 records · Page 6Linked to original sources

Evidence that intracellular synthesis of 5-fluorouridine-5'-phosphate from 5-fluorouracil and 5-fluorouridine is compartmentalized.

L1210 cells were exposed to equitoxic concentrations of [14C]5-fluorouracil and [3H]5-fluorouridine for 4 hours. The RNA from these cells was separated into cytosolic and nuclear fractions, and then further fractionated by chromatography on poly-U Sepharose, Sephadex G-200 and DEAE-cellulose. The ratio of tritium to carbon-14 incorporated into various species of RNA differed by as much as 6-fold, indicating that the respective 5-fluorouridine-5'-monophosphates synthesized from the two precursors are localized in separate pools that do not mix rapidly.

Animals↗

Distal coronary power injection during percutaneous transluminal coronary angioplasty.

A modification of the standard percutaneous transluminal coronary angioplasty (PTCA) procedure is described using a power injector instead of a hand-held syringe for distal coronary contrast injections. This system was used in 215 dilatations without complications related to the power injector. We found this system to simplify the PTCA procedure and allowed for improved distal visualization even with the steerable PTCA catheters containing an intraluminal guide wire.

Angioplasty, Balloon↗

High mortality early reinfarction with first nontransmural myocardial infarction.

Thirty-eight patients with first nontransmural myocardial infarction were studied to determine prognosis and clinical markers of a high-risk subgroup. We found a high incidence of reinfarction (18%) at a median time of 16 days post nontransmural infarction (seven patients). Reinfarction was uniformly associated with death within 24 hours. A total of 14 patients (37%) either died (eight patients) or required urgent revascularization (six patients). Predominant ST segment depression with presenting nontransmural infarction and a history of prior angina were associated with increased mortality (p less than 0.05 and p = 0.05, respectively). We conclude that patients with nontransmural infarction are at high risk for early recurrent infarction. Patients with history of prior angina and predominant ST segment depression may be at particularly high risk. Reinfarction in these patients is frequently extensive. We recommend that these patients be considered for early coronary angiography.

Aged↗

Radioiodinated prolactin as a potential mammary tumor localizing agent.

The feasibility of using radioiodinated prolactin for early detection of solid mammary tumors was studied in the rat. Radioiodinated prolactin was first injected into tumored and control rats in order to define the localization of the labeled hormone in their target organs, then it was injected into extracorporeal blood-loop of tumored and healthy rats, in order to study its clearance in those animals. At 15 min post injection, 75-82% of the labeled hormone was recovered, of which 4-5% were counted in the tumor. Deiodination was apparent only 30 min after injection. As much as high deposition of the labeled hormone was not achieved in the hormone-dependent tumor lines investigated, some of the pitfalls that may be encountered are documented. The clearance of the labeled prolactin as determined by the blood-loop technique is 3.3 min in the R3230 tumor, and 6.4 min in the 13762 mammary tumor. The healthy rats had a blood clearance of 4.6 min.

Animals↗

Controlled release of radioprotective agents from matrix tablets--effect of preparative conditions on release rates.

Release rates of radioprotective agents from insoluble matrix tablets were measured as a function of ethylcellulose/stearic acid ratio and active ingredient concentration in the matrix. The influence of the compacting pressure applied during tablet formation on the release of these aminothiol compounds was also examined. The kinetic data conformed with the Higuchi square root equation and first order release. As both plots were linearly acceptable, a statistical method for release mechanism identification using the kinetic experimental results obtained without any further transformation was used. This non-linear regression search procedure accompanied by the chi 2-square test has shown that that aminothiol release from the matrix tablets definitely follows the Higuchi square root equation. Increasing the ethylcellulose amount in the matrix consequently improves the degree of wettability and leads to a faster rate of solvent penetration. This tends to release the aminothiols more rapidly from the matrix tablets. Solvent penetration, which also follows a square root of time relationship, is probably the rate-limiting factor in the release process. The linear increase in release rates of the aminothiols observed with ethylcellulose concentration is explained by a parallel increase in the porosity of the matrix tablets. Increase in the drug concentration in the tablet increases the cysteine hydrochloride release rate and decreases the cysteamine hydrochloride release rate. A similar effect was also observed by applying increasing compacting pressure during matrix tablet formation. It was suggested that these two experimental factors differently affect the internal structure of the matrix during the preparation process.(ABSTRACT TRUNCATED AT 250 WORDS)

Cellulose↗

Dilated cardiomyopathy in identical twins.

Identical twins had dilated cardiomyopathy and evidence of an autoimmune process involving both the heart and thyroid gland. An inherited abnormality of immune regulation is suggested as a possible basis for these unusual findings.

Adult↗

Clinical significance of slow paroxysmal atrial tachycardia.

This study examines the clinical setting, characteristics, and follow-up of 173 patients who had slow paroxysmal atrial tachycardia (SPAT) (greater than 4 beats, rate less than 150 bpm) during 24-hour Holter monitoring. These episodes were classified by probable mechanism according to recognized ECG criteria and included AV nodal reentry (AVNR), sinoatrial nodal reentry (SANR), and automatic (A). There were 76 males (44%) with a mean age of 72 years and 97 females (56%) with a mean age of 73 years. The indications for Holter recording revealed that the SANR and A subgroups had a higher frequency of cerebral symptoms compared to AVNR (p less than 0.01). Chest pain was more common in the SANR group as compared to the other two groups (p less than 0.01). There was no difference in the frequency of palpitation in the three subgroups. The mean rate of SPAT for the entire group was 115.2 +/- 14 and these episodes had a mean duration of 5.58 +/- 3.07 seconds. The SANR subgroup had a significantly slower rate (107.1 +/- 9.2) as compared to the AVNR subgroup (p less than 0.01). One hundred fourteen patients were available for follow-up. The average period of follow-up was similar for all three groups. At follow-up the frequency of sick sinus syndrome as determined clinically and permanent pacemaker insertion was significantly greater in the SANR subgroup (p less than 0.01) as compared to the other subgroups which did not differ from each other.

Aged↗

Structure activity correlation for diuretic furosemide congeners.

The structure activity correlation of several groups of anthranilic acid derivatives was studied. 59 compounds, most of them possessing the anthranilic acid moiety, were synthesized and tested for diuretic and saluretic activities. Equations correlating the biological activities of these compounds with their physicochemical constants suggest positive dependence of the diuretic activity on log P (octanol:water partition coefficient). It is concluded that, within limits, the variation in biological activity is primarily governed by the lipophilicity of the molecule, and further increase in log P value will not enhance this activity.

Animals↗

Dosimetry and preliminary human studies of 18F-5-fluorouracil.

The relative distribution, metabolism and kinetics of 18F containing compounds, following administration of 18F-5-fluorouracil, has been proposed as a prognostic aid in predicting response to 5-fluorouracil chemotherapy. Because 18F has a relatively short physical half-life (t1/2 = 110 min), and the distribution and kinetics of the radiolabeled 5-fluorouracil need to be studied over periods of time that range over several half-lives of the radionuclide, significant quantities of the labeled drug must be administered in order to obtain good counting statistics. The distribution of 18F, following injection of 18F-5-fluorouracil to rats and mice, has been well documented in our previous work. It appears that the distribution of 18F in humans, following administration of 18F-5-fluorouracil is similar to that in rats. We calculated the radiation dose according to the MIRD technique for the eleven main target organs for a reference man. The critical organs, according to these calculations, are the bladder wall, the kidney and the liver, receiving a radiation dose of 729, 184 and 114 mrad per mCi injected, respectively.

Animals↗

Tissue distribution of 2- and 4-[203Hg]-estradiol in mammary-tumor-bearing rats.

The newly synthesized 2-[203Hg]-estradiol-17 beta and 4-[203Hg]-estradiol-17 beta were injected into Fischer female rats bearing transplanted mammary adenocarcinomas and into Sprague-Dawley female rats bearing spontaneous mammary tumors. Four days after injection, tumor to blood ratios (and uterine to blood ratios) in the various groups were between 5 and 14, compared to a ratio of unity observed in normal mammary glands. When injected into male rats, the accumulation of 4-[203Hg]-estradiol in the prostate and in the epididimis was very low. With minute doses of 4-[203Hg]-estradiol injected into healthy male rats, the whole-body retention of the drug was found to decrease exponentially with time, and biphasic first order kinetics were observed. With pharmacological doses of the same drug, the clearance exhibited a biphasic pattern.

Adenocarcinoma↗

Serum bromine levels in psoriasis.

Serum bromine levels in psoriatic Danes increased 2- to 3-fold during a 4-week bathing course in the Dead Sea. This increase correlated well with the improvement in their clinical and psychic condition. Serum bromine levels in psoriatic Danes were somewhat lower than those in healthy subjects residing in Denmark, but the difference was not significant. Israelis working in the open air in the Dead Sea area (air bromine 20-fold higher than in Jerusalem) had higher bromine levels than psoriatic or healthy Israelis residing in Jerusalem or healthy Israelis working in air-conditioned rooms in the Dead Sea area (p less than 0.05), but those levels were still within the normal range. As our animal experimentation indicates that the skin is a major target organ for 82Br, applied either by bathing or as an aerosol, we conclude that the higher bromine levels noticed in the psoriatic Danes after their 4-week stay at the Dead Sea may be equally due to their contact with the bromine-containing aerosol and the high bromine level of the Dead Sea waters.

Adult↗

Metabolic and distribution studies with radiolabeled 5-fluorouracil.

5-Fluorouracil (5-FU) is an effective anti-tumor drug, which has been used both as a single agent and in combination with other chemotherapeutic agents for the treatment of tumors such as breast and colorectal carcinoma. We synthesized 5-FU with trace amounts of 18F-5-FU and administered the compounds intravenously to 6 cancer patients. The patients were scanned at 2 hr intervals for 12 hrs and their urine collected whenever possible. We also injected 5-FU with the tracer 18F-5-FU, at pharmacological doses, into non-tumored rats, and sampled their bile and blood for 95 mins post-injection. For comparison, 2-14C-5-FU was injected into non-tumored rats and their bile and blood sampled at the same intervals. Minute quantities of rat bile and serum were analyzed chromatographically by high-performance TLC. 5-FU and two of its metabolites (FBAL and FUPA) were identified and quantified by this technique. Both percentage and absolute amounts of 5-FU in the bile follow comparative kinetic patterns. While the liver and the urinary bladder were clearly observable in all 16 patients, the detectability of the gall-bladder was correlated to the inverse of the alkaline phosphatase level in the blood. This work suggests that the diversity of the 5-FU metabolism in cancer patients may allow the use of 18F-5-FU as a probe for understanding those individual variabilities in clinical situations.

Adenocarcinoma↗

Comparative cardiac effects of three hepatobiliary radiopharmacologicals in the dog: concise communication.

Three hepatobiliary agents with an acetanilide-imidoacetic-acid moiety resembling that in lidocaine were investigated for their possible effects on contractility and conductivity in the heart and on arterial pressure and aortic blood flow. This was done in the light of lidocaine's numerous cardiac side effects. HIDA, BIDA, and DIPA, each with traces of decayed Tc-99m, were injected i.v. into anesthetized dogs with an A-V block, and their effects on the above parameters were followed until control levels were reestablished. Whereas lidocaine raises the diastolic threshold and prolongs the refractory period, the three agents tested do not prolong myocardial conductivity. Both HIDA and BIDA have an effect similar to that of lidocaine, but DIPA has no effect on the latter two parameters. Moreover, whereas lidocaine depressed myocardial contractility, blood pressure, and blood flow, HIDA has a less prominent effect on these parameters, and neither BIDA nor DIPA has any such effect. It is concluded that even though the effect of HIDA on the heart is milder than that of lidocaine, the effects of both BIDA and DIPA are even less pronounced, and they are less likely to cause cardiac side effects when similar doses are administered during nuclear medicine procedures.

Animals↗

Effect of prolactin and prostaglandins on the stimulation of prolactin binding sites in the male rat liver.

Induction of prolactin hepatic receptors in the male rat by exogenous prolactin and the possible involvement of prostaglandins in this process were studied. When ovine prolactin 500 microgram/kg was administered sc in saline containing 10% PVP (polyvinylpyrrolidone), twice daily for 6.5 days and the rats killed 48 h after the last injection, the specific binding of 125I-labelled ovine prolactin to prolactin hepatic receptors was raised 26-fold, while administration of prolactin in saline only caused a 7-fold increase. A well correlated log dose-response relationship was demonstrated between 12.5 and 500 microgram of prolactin in saline-PVP, with lowest dose causing an 18-fold increase in binding. A shorter 4.5 day treatment of prolactin in saline-PVP caused only a small 3-fold increase in prolactin binding. Scatchard analysis showed that these increases resulted from increases in receptor concentration. The effect of prolactin on the induction of the hepatic receptors could not be mimicked by PGE1, PGE2 or PGF2 alpha, nor could PGF2 alpha synergize with a short treatment with prolactin. Further, indomethacin caused no significant effect on this action of prolactin. It seems that prolactin does not induce its own receptors in the rat liver by stimulation of prostaglandins in this tissue.

Animals↗

Binding of iodinated rat and ovine prolactins to prolactin receptors and to its antibodies.

Most studies of prolactin receptors in rat tissues have not used the homologous 125I-labeled rat prolactin as tracers, but rather 125I-labeled ovine or human prolactin. We have compared the effect of different methods of iodination on the specific binding of rat and ovine prolactin to sites in the seminal vesicle of rats and the liver of mice post-partum. Ovine prolactin, either iodinated with lactoperoxidase or with mild chloramine-T (10 micrograms), showed 3 times the specific binding of correspondingly-iodinated rat prolactin. This greater sensitivity of rat prolactin to oxidative damage during iodination, as compared with ovine prolactin is further shown by the difference in Sephadex G-100 elution constant of unlabeled and labeled rat prolactin. . This difference was absent in the case of ovine prolactin. Parallel studies of the binding of the labeled hormone to homologous antibody revealed that immunoreactivity of labeled ovine prolactin was not affected by any of the iodination methods. Rat-prolactin immunoreactivity was depressed by lactoperoxidase iodination as compared with chloramine-T iodination. Rat prolactin was also less potent than ovine prolactin in inhibiting the binding of homologous and heterologous labeled hormone to its receptors, to a larger degree than could be expected from the bioassay potency of the various hormone preparations. These results reflect the greater sensitivity to damage of the biologically active site of rat prolactin, as compared with the ovine hormone.

Animals↗