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Biomedical subjects

M Jacob

Publications and source records attributed to M Jacob.

At least 199 records · Page 11Linked to original sources

A placebo-controlled double-blind comparative clinical study of the disulfiram- and calcium carbimide-acetaldehyde mediated ethanol reactions in social drinkers.

Treatment for 2 days with disulfiram (3.5 mg/kg once daily) and calcium carbimide (0.7 mg/kg twice daily) in social drinkers produced, as compared to controls, similar blood ethanol values, 2- to 3-fold increases in blood acetaldehyde, respectively, and increased heart rate, pulse pressure, skin temperature, and flushing following 0.15 g/kg of ethanol taken 12 hr after the last drug administration. Peak blood acetaldehyde concentration was greater for calcium carbimide compared to disulfiram (p less than 0.05) and subjects treated with calcium carbimide experienced greater discomfort compared to disulfiram due to palpitations and shortness of breath, and they reported less intention to drink during the reaction. However, neither drug produced sufficient aversion to curtail further drinking totally. With repeated drinks, there was an overall reduction of blood acetaldehyde concentration for calcium carbimide of 85% and for disulfiram of 35%. These data may provide a biochemical basis for the claims of certain alcoholics that they can drink to "burn off" the effects of these drugs.

Acetaldehyde↗

Effects of metabolic acidosis on zinc and calcium metabolism in rats.

To delineate the potential role of renal acidosis on zinc and calcium metabolism, 24 male Charles River rats, with a mean weight of 154 g, were assigned to four groups of 6 rats each. Three groups of rats were given ammonium chloride for 5 days by stomach tube at dosages of 4, 8, 16 mEq/kg/day, respectively. The control group received the solvent (normal saline) only. The animals were fed a semi-purified diet containing 100 ppm of zinc. The total food intake averaged 18, 16, 17 and 18 g/day, respectively, for the control and the three treated groups. On the 4th and 5th day, two 24-hour urinary collections for net acid excretion, zinc and calcium excretions were obtained. The net acid excretion progressively increased from 0.85 +/- 0.21 muEq/min/kg in the control rats to maximal values of 10.61 +/- 0.87 muEq/min/kg in the acid-loaded rats. The net acid excretion is highly correlated with the urinary calcium excretion (r = 0.95, p less than 0.01). However, the acid-loading has no effect on the carcass retention of zinc as documented by isotope studies or urinary zinc excretion.

Acidosis, Renal Tubular↗

[Pathogenesis of cysts of the external meniscus].

A classification of cysts of the menisci into three groups is proposed. The first is secondary to dystrophy of the meniscus. The second is secondary to traumatic lesions of the meniscus. Third is related to degenerative changes in the meniscus. The authors have studied 7 cases in the first group, 23 in the second group and 15 in the third group. They emphasize the role of a horizontal defect in the meniscus with subsequent formation of a cyst. They consider that, in monopodal weight-bearing, intra-articular pressure forces synovial fluid into the defect to initiate the formation of a cyst. The authors propose that the cyst and the damaged meniscus should be systematically removed to avoid recurrence.

Cysts↗

[Antibacterial therapy in surgery of the inner and middle ear. A study of co-trimoxazole penetration into the perilymph (author's transl)].

Studies of the type presented here have rarely been undertaken and should be useful in surgery and pathology of the inner and middle ear. Samples of perilymph were collected during stapedectomy in patients with otosclerosis. In view of the very small volume of perilymph obtainable from each patient's vestibule (2 to 4 microliter), the only assay method that could be used to measure drug levels was thin layer chromatography on silica gel. Despite pooling of the perilymphs of 5 patients, trimethoprim (TMP) levels could not be measured but the authors were able to demonstrate that sulfamethoxazole (SMZ) does penetrate into the perilymph. Since the TMP-SMZ combination (co-trimoxazole) is active against the pathogens usually encountered in middle ear fluids, it is concluded that the drug could be of benefit in the treatment of middle and inner ear infections or after surgical operations on this area.

Adult↗

Accessibility of U1 RNA to base pairing with a single-stranded DNA fragment mimicking the intron extremities at the splice junction.

A DNA fragment containing a 16 nucleotide sequence mimicking the intron extremities of premessenger RNA aligned as proposed previously (1,2) in a model of splicing mechanism was prepared and used as a probe for accessibility of the 5' extremity of U1 RNA. Hybridization of U1 RNA to the probe under non denaturing conditions and digestion of the hybrid with RNase H revealed that the sequence of U1 RNA which is complementary to the extremities of introns is accessible to hybridization and to enzymes. Therefore, the configuration of isolated U1 RNA satisfies the criteria required for the alignment of introns and further enzymatic reactions of splicing.

Base Composition↗

The orderly splicing of the first three leaders of the adenovirus-2 major late transcript.

A strategy based on the hybridization of labeled nucleoplasmic RNA to a short cloned cDNA probe was devised to study the ligation of the three first leader sequences (Le1, Le2, Le3) of the major late adenovirus-2 transcript. The hybridized RNA was subsequently fractionated by electrophoresis and identified with the aid of restriction fragments of the DNA probe. The ligations were shown to occur stepwise and in an orderly fashion. Le1 and Le2 were first ligated without detectable lag time. The tripartite leader was formed after a lag time of 10-15 min probably due, for a large part, to the stepwise excision of the intervening sequence between Le2 and Le3. The possible processing intermediate Le2-Le3 was not detected.

Adenoviruses, Human↗

[Ultrasonographic assessment of traumatic muscle injuries in athletes (author's transl)].

In the absence of reliable objective methods to assess traumatic muscle injuries in athletes, the authors have chosen to perform routine ultrasonography. Taking the thigh as an example, they describe the appearance of normal muscles on ultrasonographic images and compare these with CT sections. The results of examination in 61 athletes with traumatic injury are reported. The different ultrasonic patterns are described and compared with surgical findings in 16 cases. All lesions could be detected by ultrasonography, and 87% were correctly identified. Ultrasonography provides direct and clear imaging of the muscles. It constitutes an excellent means of detecting severe lesions and locating them accurately before surgical repair. It is highly reliable and deserves to be adopted by all physicians and surgeons specialized in sports medicine.

Athletic Injuries↗

U2 RNA shares a structural domain with U1, U4, and U5 RNAs.

We previously reported common structural features within the 3'-terminal regions of U1, U4, and U5 RNAs. To check whether these features also exist in U2 RNA, the primary and secondary structures of the 3'-terminal regions of chicken, pheasant, and rat U2 RNAs were examined. Whereas no difference was observed between pheasant and chicken, the chicken and rat sequences were only 82.5% homologous. Such divergence allowed us to propose a unique model of secondary structure based on maximum base-pairing and secondary structure conservation. The same model was obtained from the results of limited digestion of U2 RNA with various nucleases. Comparison of this structure with those of U1, U4, and U5 RNAs shows that the four RNAs share a common structure designated as domain A, and consisting of a free single-stranded region with the sequence Pu-A-(U)n-G-Pup flanked by two hairpins. The hairpin on the 3' side is very stable and has the sequence Py-N-Py-Gp in the loop. The presence of this common domain is discussed in connection with relationships among U RNAs and common protein binding sites.

Animals↗

Primary and secondary structures of chicken, rat and man nuclear U4 RNAs. Homologies with U1 and U5 RNAs.

U4 RNA from chicken, rat and man was examined for nucleotide sequence and secondary structure. Three molecular species, U4A, U4B and U4C were detected in the three animal species. U4A is 146 nucleotide long and U4B RNA only lacks the 3' terminal G. four nucleotides are missing at the 3'-end of U4C RNA which, in addition, differs from U4A and U4B RNAs at two internal positions. Thus, U4C RNA is encoded by another gene as U4A and U4B RNAs. Only one nucleotide substitution occurred between chicken and man showing that U4A, U4B and U4C RNAs have been extremely conserved throughout evolution. The three molecular species are capped, they contain three psi, a 2'-P methyl A and a m6A. An additional post-transcriptional modification close to the cap structure is observed in man. On the basis on an experimental study, two models of secondary structure may be proposed for U4 RNA. The 3'domain is the same in both models and is homologous to that of U1 and U5 RNAs. It consists of a single-stranded region, containing the sequence Py-(A)2-(U)n-Gp flanked by two stable hairpins probably involved in tertiary interactions. The 5' domain is less stable than the 3' domain and its structure is different in the two models. However, a long single-stranded pyrimidine region containing modified nucleotides is found in both models as in U1 and U5 RNAs. Several other nucleotide sequence homologies related to specific features of secondary structure suggest that U1, U4 and U5 RNAs derive from a common ancestor and may have common function.

Animals↗

Small RNAs in HnRNP fibrils and their possible function in splicing.

Several arguments are in favor of a function of snRNA in the processing of premessenger RNA. A large fraction of snRNA is localized in hnRNP which are assumed to be the site of processing. The different snRNA species are not bound to hnRNP in a unique manner but are associated with both proteins and hnRNA which suggests the possibility of metabolic exchanges in the course of processing. There is approximately 1-2 molecules of snRNA per individual hnRNP. We reexamined the possibility that U1A RNA might serve for the alignment of the extremities of the intron sequences of premessenger RNA insuring correct condition for cutting and splicing. We found that only a UCCA (3' leads to 5') sequence at position 8-11 of U1A RNA was complementary to an AG-GU (5' leads to 3') around a putative splice point for 69 different introns sequenced so far. On the basis of secondary structure of U1A RNA, the UCCA sequence would be available for hybridization. The UCCA sequence is also present in U2 RNA and 4.5 S RNAI. It might associate with AG-GU in a manner similar to that of codon-anticodon, the stability of the complex being insured by the configuration of hnRNP. The possible formation of larger hybrids stable by themselves is unlikely upon examination of the nucleotide sequence of various introns adjacent to the splice point. As there is no direct experimental evidence for the function of snRNA in splicing, there considerations are speculative at the present time. The possibility that adenovirus encoded VA RNA would play a role in splicing was also examined. Various arguments suggest that this possibility is rather remote.

Adenoviridae↗