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Biomedical subjects

J Jimenez

Publications and source records attributed to J Jimenez.

At least 55 records · Page 3Linked to original sources
PubMed1994

The chromaffin granule and synaptic vesicle amine transporters differ in substrate recognition and sensitivity to inhibitors.

Classical studies using bovine chromaffin granules have defined the physiologic and pharmacologic properties of the vesicular amine transporter that packages monoamine transmitters into intracellular vesicles for subsequent regulated release. The recent isolation of two distinct but closely related cDNA clones encoding vesicular amine transport suggests that the activity expressed in the brain (synaptic vesicle amine transporter or SVAT) may differ significantly from the previously described adrenal gland activity (chromaffin granule amine transporter or CGAT). A direct comparison of the two transporters now shows that SVAT has a higher affinity than CGAT for monoamine substrates, in particular for histamine. In addition, SVAT shows approximately 10-fold greater sensitivity to tetrabenazine than CGAT. [3H]Dihydrotetrabenazine shows no detectable binding to CGAT but does bind to SVAT, accounting for the differential sensitivity. Furthermore, methamphetamine preferentially inhibits transport by SVAT relative to CGAT, apparently by competing at the site of amine recognition rather than by disrupting the vesicular pH gradient. These previously unsuspected differences in the storage of monoamine transmitter in the central nervous system and the adrenal gland may help to account for several classic pharmacological observations.

1-Methyl-4-phenylpyridinium↗
PubMed1994

Oral administration of quercitrin modifies intestinal oxidative status in rats.

1. Oral administration of quercitrin to rats for 3 days increases the mucosal glutathione contents in ileum and colon as well as inhibits non-enzymatic lipid peroxidation induced in membrane fractions from jejunal and colonic mucosa. 2. After 7 days of treatment with quercitrin, rat intestinal oxidative status trends to normalize to control rats.

Administration, Oral↗
PubMed1993

Effect of chronic ethanol administration on the rat pineal N-acetyltransferase and thyroxine type II 5'-deiodinase activities.

Chronic ethanol intake resulted in a significant decrease in the rate of ponderal growth and an impaired nyctohemeral profile of pineal N-acetyltransferase (NAT) activity. In ethanol-treated animals, the onset of the nocturnal NAT increase is delayed by 2 hours when compared to control animals. Moreover, pineal NAT nocturnal peak was reached at 4 h (2 hours later than controls), while pineal type II thyroxine 5'-deiodinase (5'-D) nyctohemeral profile was not modified by ethanol administration. The effect of ethanol administration (12 weeks) on 5'-D activity in different tissues was also studied. Ethanol induced a 5'-D activity increase in hypothesis and brain frontal cortex, when compared to control animals. No change in 5'-D activity is observed in either pineal gland, Harderian gland, or brown adipose tissue. Since basal values of 5'-D activity in hypophysis or brain frontal cortex are particularly dependent on serum thyroxine (T4) concentration, the effect of chronic ethanol administration on thyroid hormone levels was studied. Serum T4 levels in ethanol-treated animals were significantly decreased when compared to controls at any time point studied. However, no change in serum 3',3,5-triiodothyronine (T3) levels were found.

Alcoholism↗
PubMed1993

Direct connection between myelinosomes, endoplasmic reticulum and nuclear envelope in mouse hepatocytes grown with the amphiphilic drug, quinacrine.

Mouse hepatocytes grown in 4 microM quinacrine had numerous myelinosomes which were directly connected to expanded cisternae of the rough endoplasmic reticulum (RER). The cisternae of the RER either subtended the electron transparent space of the myelinosome, expanded to form the outer membrane of the myelinosome or penetrated into it. Material of low electron density was frequently seen within the area where the cisternae penetrated into the electron transparent space of the myelinosome. Myelinosomes were also associated with the nuclear envelope in a pattern similar to that of the RER. Quinacrine appears to bind with the phospholipids of the membranes of the endoplasmic reticulum and nuclear envelope and this drug-lipid complex is then moved into myelinosomes effectively removing the drug from the cell.

Animals↗
PubMed1993

Adrenalectomy or superior cervical ganglionectomy modifies the nocturnal increase in rat pineal type II thyroxine 5'-deiodinase.

We studied the response of type II thyroxine 5'-deiodinase (5'-D) activity to superior cervical ganglionectomy (SCGX) or adrenalectomy (ADX) in the rat pineal gland and other tissues. The results show that no difference was found between controls and SCGX animals during the day, but at night, SCGX modified the day-night cycle of 5'-D activity in the pineal gland. In the same way, ADX did not modify the enzyme activity during the day in pineal gland, harderian gland, hypophysis, or brain frontal cortex (BFC). However, in brown adipose tissue (BAT), where thyroid hormone metabolism is extremely dependent on alpha 1-adrenergic stimulation by blood circulating catecholamines, 5'-D activity is significantly decreased. At the time point of maximal pineal 5'-D activity in controls (02:00 h), ADX animals did not exhibit the nocturnal increase of the enzyme activity that occurs with control rats. Moreover, at 04:00 h ADX did not show any effect on pineal 5'-D activity. These results seem to suggest that the presence of catecholamines in blood is necessary for the pineal 5'-D activity nocturnal increase, although it does not participate in regulating the basal enzyme activity during the day.

Adipose Tissue, Brown↗
PubMed1993

Thrice-weekly cotrimoxazole is better than weekly dapsone-pyrimethamine for the primary prevention of Pneumocystis carinii pneumonia in HIV-infected patients.

OBJECTIVE: To compare the efficacy and safety of two intermittent regimens for the simultaneous primary prevention of Pneumocystis carinii pneumonia (PCP) and toxoplasmosis in HIV-infected patients. DESIGN: Prospective randomized open trial. SETTING: HIV outpatient clinic of an Infectious Disease Service and a 1000-bed university teaching hospital. PATIENTS: A total of 166 HIV-infected patients with a CD4 cell count < 200 x 10(6)/l or a CD4 percentage < 20%, without previous PCP or toxoplasmosis. INTERVENTION: Patients were randomized to oral (1) cotrimoxazole [160 mg trimethoprim (TMP) and 800 mg sulphamethoxazole (SMX)] twice a day on Mondays, Wednesdays and Fridays (n = 81), or (2) dapsone (100 mg) plus pyrimethamine (25 mg) (DP) once a week (n = 85). MAIN OUTCOME MEASURES: Clinical and biological evaluation was performed every 30-60 days. End-points were PCP, toxoplasmosis and death. Adverse reactions were considered as defined in the protocol. RESULTS: After a mean follow-up of 380 days, intention-to-treat analysis revealed that DP patients had a higher rate of PCP [13 out of 85 (15.2%) versus three out of 81 (3.7%); P = 0.01]. The cumulative rates of PCP at 12 and 24 months were 5 and 42% for DP patients and 3 and 10% for TMP-SMX patients, respectively (Mantel-Cox, P = 0.0007). Of the 29 patients who died during follow-up, 14 were in the TMP-SMX group and 15 in the DP group (not significant). Two patients in the TMP-SMX group and three in the DP group developed toxoplasmosis (not significant). Adverse reactions were common (66.7% of TMP-SMX patients and 42.4% of DP patients; P = 0.001). However, only 12.3% of TMP-SMX patients and 2.3% of DP patients (P = 0.01) had to discontinue therapy because of toxicity. CONCLUSIONS: At the given doses, DP was inferior to TMP-SMX in preventing first episodes of PCP. Although more patients and a longer follow-up are required, the regimens appeared to prevent toxoplasmosis equally well.

AIDS-Related Opportunistic Infections↗
PubMed1992

Mechanisms of thermoinactivation of endoglucanase I from Trichoderma reesei QM 9414.

The mechanism of irreversible thermoinactivation of endoglucanase I from Trichoderma reesei has been determined at 70 degrees C at the pH of maximum enzyme activity. The time-course of thermoinactivation did not follow first-order kinetics and kinetic constants of the process were dependent on enzyme concentration, suggesting that aggregation was the main process leading to irreversible inactivation. The enzyme was extremely resistant to urea, which in fact seemed to stabilize it against temperature. Disulphide exchange, deamidation and hydrolysis of peptide bonds were also responsible for the loss of enzyme activity at 70 degrees C.

Ammonium Sulfate↗
PubMed1992

twine, a cdc25 homolog that functions in the male and female germline of Drosophila.

twine is the second homolog of the fission yeast gene cdc25 to be found in Drosophila. Both string and twine cDNAs can rescue a temperature-sensitive cdc25 mutation in fission yeast, but not a deletion. We detect the expression of string but not twine transcripts in the proliferating cells of newly cellularized embryos, in third instar larval brains, and in imaginal discs. Both genes are abundantly expressed in nurse cells during oogenesis, the maternal transcripts persisting throughout the syncytial stage of embryonic development. In the testis, twine transcripts are seen in the growing stage of premeiotic cysts. Analysis of a twine mutant suggests a requirement for the gene during oogenesis, during syncytial embryonic development, and for male meiosis. Meiosis does not occur in homozygous twine males, which produce cysts containing 16 rather than 64 spermatids.

Amino Acid Sequence↗
PubMed1992

Ga-67 citrate scan in vascular graft infection.

The clinical utility of the Ga-67 scan has been studied in 9 patients with clinical suspicion of vascular graft infection. Eleven grafts were analyzed: 4 aortobifemoral, 2 iliofemoral, 3 femoropopliteal, 1 axillofemoral, and 1 axillobifemoral. The Ga-67 scan was positive in 8 grafts with bacteriological proof of infection and negative in 3 grafts in which infection was ruled out by clinical follow-up. A Ga-67 scan also demonstrated the spread of infection to the thigh in two patients and to the pelvis in another two patients. In 4 patients CT was performed. The CT findings included graft thrombosis, perigraft fluid collection and thickened graft wall. No discrepancies were found between the CT scan and Ga-67 scan. In three patients a control Ga-67 scan was carried out after specific antibiotic and surgical treatment. Two of these showed increased Ga-67 uptake and spreading of infection along the graft; in the other patient, a Ga-67 scan revealed normalization after resolution of an abdominal abscess. In conclusion, the Ga-67 scan proved useful in the diagnosis of vascular graft infection, the definition of location of the extent of the disease and in the evaluation of the efficiency of treatment.

Aged↗
PubMed1992

Purification of A-subtype pancreatic cholecystokinin receptor by immunoaffinity chromatography.

So far, no efficient affinity chromatography for CCK receptor purification has been reported that prevented obtention of sequenceable amounts of purified receptor. In this work, 10% of plasma membrane receptor sites were specifically cross-linked with the photoreactive cleavable agonist 125I-ASD-[Thr28, Ahx31]-CCK-25-33, solubilized by NP-40, chromatographied on immobilized wheat germ agglutinin and further immunopurified using anti-CCK antibodies to an overall rate of 3000-3600-fold. Analysis of eluted material demonstrated a protein migrating at Mr 85,000-100,000 and the absence of 35S-labeled impurity. This single and efficient affinity chromatography should provide enough homogeneous receptor protein for microsequence determination and leads to consider immunoaffinity chromatography on immobilized anti-ligand antibodies as a potential tool for purification of membrane receptors.

Affinity Labels↗
PubMed1992

Changes in liver microsome lipids and plasma fatty acids induced by dietary orotate in the weanling rat.

1. Dietary orotate produced a decrease in total plasma fatty acids which was reflected in low values of saturated, monounsaturated and polyunsaturated fatty acids longer than 18 carbon atoms of the n-6 series. The relative content of saturated fatty acids in microsomes of animals fed orotate was also decreased. 2. Rat liver delta-9 desaturase activity was lower in the group fed orotate. However, delta-6 desaturase activity did not show significant differences between the groups. 3. Microsomal cholesterol content was lower in rats fed orotate than in controls but phospholipid phosphorus contents were similar. These results suggest a direct effect of dietary orotate on the key enzymes which regulates cholesterol liver metabolism.

Animals↗
PubMed1992

Effects of aminophylline on contractions and 45Ca uptake in isolated rat vascular smooth muscle.

1. Aminophylline inhibited the contractions induced in rat isolated aorta by high K and noradrenaline (NA) as well as the transient contraction induced by NA in Ca-free media and suppressed the spontaneous myogenic activity in portal vein segments. 2. Aminophylline had no significant effects on 45Ca influx in resting aorta but inhibited 45Ca influx stimulated by high K or NA. 3. It is concluded that aminophylline inhibited Ca entry through voltage- and receptor-operated channels and NA-induced Ca release from intracellular stores. A part of the vascular inhibitory effects of aminophylline may be mediated by a cAMP-dependent mechanism.

Aminophylline↗
PubMed1992

Chronic ethanol intake inhibits both the vasoactive intestinal peptide binding and the associated cyclic AMP production in rat enterocytes.

1. Chronic ethanol intake during 6, 8, 10 or 12 weeks resulted in a decrease of 125I-vasoactive intestinal peptide (VIP) binding to rat enterocytes. 2. Native peptide displaced 125I-VIP binding to enterocytes, exhibiting a IC50 at about 4 nM native VIP in control and ethanol-treated animals. 3. The number of binding sites in ethanol-treated animals were significantly diminished when compared to control animals. This reduction is observed in both the high-affinity and the low-affinity binding sites. 4. Increasing concentrations of native VIP produced a similar cyclic AMP rise in enterocytes from control or ethanol-treated rats during 6 weeks. However, after 8 weeks of ethanol treatment, a significant decrease in cyclic AMP production stimulated by VIP was observed.

Animals↗
PubMed1992

Hypoglycemic activity of olive leaf.

The hypoglycemic activity of olive leaf was studied. Maximum hypoglycemic activity was obtained from samples collected in the winter months, especially in February. One of the compounds responsible for this activity was oleuropeoside, which showed activity at a dose of 16 mg/kg. This compound also demonstrated antidiabetic activity in animals with alloxan-induced diabetes. The hypoglycemic activity of this compound may result from two mechanisms: (a) potentiation of glucose-induced insulin release, and (b) increased peripheral uptake of glucose.

Animals↗
PubMed1992

Adrenergic regulation of type II 5'-deiodinase circadian rhythm in rat harderian gland.

This paper reports on the regulation of the nyctohemeral profile of type II thyroxine 5'-deiodinase (T45'D) activity in the rat harderian gland. Harderian gland T45'D activity exhibits a nighttime increase with maximal values late in the dark period (0200-0400 h) and basal values during the daytime. The nocturnal rise of the deiodinating activity was prevented by either exposure of animals to light at night, injecting the animals with both alpha- and beta-adrenergic receptor blockers, or bilateral superior cervical ganglionectomy (SCGx). However, adrenalectomy did not affet the enzyme activity in the harderian gland. In brown adipose tissue (BAT), where thyroid hormone metabolism is extremely dependent on alpha 1-adrenergic stimulation by blood-circulating catecholamines, adrenalectomy significantly decreased T45'D activity. Deiodinating activities in brain frontal cortex (BFC) and pituitary gland were unaffected by adrenalectomy. Unlike in the harderian gland, SCGx did not modify the T45'D activity in either BAT, BFC, or the pituitary gland. The results suggest that elevated plasma catecholamines are not required for harderian gland T45'D activation and that the nyctohemeral profile of the enzyme activity in the harderian gland is dependent on the noradrenergic input from the superior cervical ganglia.

Adrenalectomy↗
PubMed1991

Effect of oxidants on proteases of the fibrinolytic system: possible role for methionine residues in the interaction between tissue type plasminogen activator and fibrin.

Evidence has recently been presented that activated macrophages (M phi) express both urinary (u-PA) and tissue type (t-PA) plasminogen activator. Major cell products of M phi and polymorphonuclear neutrophils (PMN) are reactive oxidants of the HOCl/chloramine type. Since PMN and M phi are involved in inflammatory and fibrinolytic processes, we were interested in the interaction of u-PA, t-PA, and plasmin with oxidants of the leukocyte type. The enzymes were treated with chloramine-T, which at pH 8.5 is a selective oxidant for methionine residues. Oxidation by chloramine-T of t-PA abolishes about 40% of both stimulation susceptibility of t-PA by fibrinogen degradation products (FDP) and affinity of t-PA to FDP. However, the plasminogenolytic and amidolytic activity of unstimulated t-PA as well as the plasminogenolytic activity of u-PA and the amidolytic activity of plasmin are not impaired. Identification of the amino acid residues in the t-PA responsible for the interaction with fibrin might be of great importance in order to understand the mechanism of the clot- selectivity of t-PA. The present study gives evidence that fibrin specificity of t-PA partly depends on chloramine oxidizable amino acids, presumably methionine residues. Hence, experimental data on the interaction between t-PA and fibrin, using oxidized and labelled t-PA should be interpreted with caution. It may be suggested that oxidants of the leukocyte type might regulate t-PA activity and selectivity for fibrin.

Chloramines↗