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Biomedical subjects

J Quintana

Publications and source records attributed to J Quintana.

At least 55 records · Page 3Linked to original sources
PubMed1992

Alternative structures for alternating poly(dA-dT) tracts: the structure of the B-DNA decamer C-G-A-T-A-T-A-T-C-G.

The X-ray crystal structure of the decamer C-G-A-T-A-T-A-T-C-G has been solved with two contrasting cations, Ca2+ and Mg2+. Crystals with calcium are space group P2(1)2(1)2(1), cell dimensions a = 38.76 A, b = 40.06 A, and c = 33.73 A, and diffract to 1.7-A resolution. Crystals with magnesium have the same space group, cell dimensions a = 38.69 A, b = 39.56 A, and c = 33.64 A, and diffract to 2.0 A. Their structures were solved independently by molecular replacement, beginning with idealized Arnott B-DNA geometry. The calcium structure refined to R = 17.8% for the 3683 reflections greater than 2 sigma, with 404 DNA atoms, 95 solvent peaks, and 1 Ca(H2O)7(2+) ion. The magnesium structure refined to R = 16.5% for the 1852 reflections greater than 2 sigma, with 404 DNA atoms, 62 solvent peaks, and 1 Mg(H2O)6(2+) ion. The two structures are virtually identical and are isostructural with C-G-A-T-C-G-A-T-C-G [Grzeskowiak et al. (1991) J. Biol. Chem. 266, 8861-8883] and C-G-A-T-T-A-A-T-C-G [Quintana et al. (1992) J. Mol. Biol. 225, 375-395]. Comparison of C-G-A-T-A-T-A-T-C-G with C-G-C-A-T-A-T-A-T-G-C-G [Yoon et al. (1988) Proc. Natl. Acad. Sci. U.S.A. 85, 6332-6336] shows that the expected alternation of twist angles is found in the central A-T-A-T-A-T region of the decamer (A-T small, T-A large), but the minor groove remains wide at the center, rather than narrow. Minor groove narrowing is produced, in these two structures, not by overwinding of the helix, but by an increase in base pair propeller. This analysis confirms the concept that poly(dA-dT).poly(dA-dT) is polymorphous, with different local conformations possible in different local environments.

Base Sequence↗
PubMed1992

[Hemodynamic differences do not exist in patients with adult respiratory syndrome with or without infection].

BACKGROUND: To verify whether patients with adult respiratory distress syndrome (ARDS), associated to sepsis or not, may be differentiated according to the values of the hemodynamic variables. METHODS: Thirty-two consecutive patients with ARDS admitted to an intensive care unit over a period of 32 months were prospectively studied. In 18 patients ARDS was associated to sepsis. The value of the hemodynamic variables were compared between both groups of patients (18 with sepsis and 14 without) within the first 24 hours of diagnosis of the syndrome. RESULTS: Mortality of patients with ARDS associated with sepsis was greater than in those without sepsis (78% vs 57%). In general both groups of patients with ARDS presented similar values of pulmonary hypertension (28 +/- 6 and 25 +/- 4 mmHg) with elevated pulmonary vascular resistance, and with an above normal cardiac index and ventricular function parameters. No significant differences were found in hemodynamic values, ventricular function and oxygen transport among patients with ARDS, with or without sepsis, or among survival or death in each group, or those considered in general. CONCLUSIONS: This study demonstrated that patients with the septic adult respiratory distress syndrome (ARDS) have the same hemodynamic changes as those observed in patients with ARDS without sepsis. This absence of differences may be explained by the presence of mechanisms common in sepsis and ARDS.

Adult↗
PubMed1992

Platelet serotonin and plasma tryptophan decreases in endogenous depression. Clinical, therapeutic, and biological correlations.

Platelet serotonin (5-HT) and plasma tryptophan (free and total) levels were measured in 25 unmedicated depressed patients and in 25 age- and sex-matched healthy controls. The same parameters were determined in the patients after 3 weeks and 2 months of imipramine treatment. Comparisons between patients and control values showed a significant decrease in total plasma tryptophan and platelet 5-HT in unmedicated patients. During treatment, the clinical condition of the patients improved, while plasma tryptophan and platelet 5-HT values normalized after 3 weeks and 2 months, respectively. Clinical status, plasma tryptophan, platelet 5-HT, as well as other biological parameters determined concurrently in the patients, such as platelet monoamine oxidase (MAO), 5-HT uptake, and imipramine binding were compared in search of significant correlations: neither the individual values of any of them nor the magnitude of their changes at any given stage or interval of the study, respectively, were found significantly correlated. These results suggest that a series of 5-HT-related biological parameters are altered in endogenous depression and tend to normalize with imipramine treatment leading to clinical recovery. Within individuals, those parameters are not correlated, suggesting that both the effect of the drug and clinical improvement affect them separately.

Adult↗
PubMed1992

Mnemonic and predictive functions of cortical neurons in a memory task.

Single-neuron discharge was recorded from prefrontal and posterior parietal cortex in monkeys performing a visuo-motor memory task with temporal and spatial separation between cue (color) and directional manual response. During the delay interval between cue and response, neurons in both cortices engaged in two concurrent and reciprocal trends of discharge: (a) sensory-coupled, decelerating firing apparently related to color retention, or (b) motor-coupled, accelerating firing apparently related to the anticipated response direction. In both cortices, the acceleration of the direction-anticipating activity was related to the probability with which the animal could predict, and prepare for, the correct response site. Our findings suggest that neurons from prefrontal and parietal cortex are part of distributed networks, with representational and operational properties, for visuomotor cognitive processing.

Animals↗
PubMed1992

Testicular 3 beta-hydroxysteroid dehydrogenase/delta 5-4 isomerase in the hypophysectomized rat: effect of treatment with 5 alpha-dihydrotestosterone.

The in-vivo regulatory effect of androgens on steroidogenesis was investigated. Adult (2 to 3 months old) hypophysectomized rats were treated intratesticularly with increasing doses of 5 alpha-dihydrotestosterone (DHT; 10-200 micrograms/100 g body weight) or vehicle (50 microliters dimethyl sulphoxide; DMSO) in the contralateral testis. Intratesticular testosterone concentrations were extremely low in hypophysectomized rats 15-20 days after surgery. Treatment with DHT caused a dose-dependent inhibition of testicular 3 beta-hydroxysteroid dehydrogenase/delta 5-4 isomerase (3 beta-HSD) 2 h later, and this effect was apparent at the dose of 20 micrograms/100 g body weight (P less than 0.01). The inhibitory effect of 3 beta-HSD was not due to a possible interference of DHT in the enzyme assay, since various concentrations of the androgen (0.1-100 mumol/l) were ineffective as inhibitors of 3 beta-HSD. The highest dose of DHT used in this study (200 micrograms/100 g body weight) resulted in a rapid (1-2 h) and transient (4-6 h) inhibition (approximately 80%) of 3 beta-HSD activity. Pretreatment of rats with the antiandrogen cyproterone acetate (5 mg/rat) or the protein synthesis inhibitor cycloheximide (10 mg/rat) did not affect the enzyme activity of testes injected with DMSO, but counteracted the inhibitory effect of DHT on 3 beta-HSD activity in the contralateral testis. The results presented suggest that the inhibitory effect of the non-aromatizable androgen DHT is receptor-mediated and involves the synthesis of a factor(s) that modulates 3 beta-HSD activity.

Androgens↗
PubMed1992

R5020 enhances PGE2 stimulated steroidogenesis in cultured rat granulosa cells.

Progesterone biosynthesis and metabolization to 20 alpha-hydroxyprogesterone was stimulated in granulosa cells cultured in the presence of 20 ng/ml of follicle stimulating hormone (FSH) or increasing concentrations of PGE2 (10(-9)-10(-7)M). Concurrent treatment with the synthetic progestin R5020 (10(-6) M) enhanced the FSH or PGE2 stimulated progesterone and 20 alpha-hydroxyprogesterone accumulation in culture media, as well as delta 5-3 beta-hydroxysteroid dehydrogenase activity in granulosa cell homogenates. These findings may represent another example of an autocrine control mechanism in which the steroidogenic product of the granulosa cell exerts an ultra-short loop regulation of its own production.

20-alpha-Dihydroprogesterone↗
PubMed1992

AIDS awareness and risk behaviors among dually disordered adults.

An exploratory needs assessment was conducted among 50 clients of an abstinence-oriented outpatient clinic for adults experiencing coexisting drug abuse and chronic mental disorders. Findings revealed that, despite education and prevention efforts, sample members possessed considerable misinformation about AIDS and continued to engage in high risk heterosexual practices. Their knowledge level was not associated significantly with their admission diagnoses. Knowledge level also did not correlate significantly with safer sexual practices. These findings have implications for the development of AIDS education and prevention programs for dually disordered clients. To be effective, AIDS prevention and education efforts must be targeted at the clients' specific needs. Clear, explicit information about AIDS must be provided. In addition, behavioral-attitudinal change strategies that focus on the high-risk situations encountered by the clients and teach them alternative safer sex practices are required.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Intra-arterial cisplatin given prior to surgery in osteosarcoma: grade of necrosis and size of tumor as major prognostic factors.

From January 1983 to August 1987, 29 evaluable patients with high-grade osteosarcoma were treated in our institution with preoperative intra-atrial cisplatin, 100 mg/m2 every 14 days for three courses. Surgery was done on day 42. Surgery consisted of limb salvage in six, amputations in 15, and disarticulations in eight. Postoperative chemotherapy included Adriamycin (ADR), 45 mg/m2 for 2 days every 6 weeks, alternated with cisplatin 120 mg/m2 every 6 weeks. The nephrotoxicity (18 out 29) was reversible in all cases. Cardiotoxicity was prominent; it was observed in 31% of patients. In six, there was congestive heart failure, but there were no fatal cases. The hematological toxicity was severe. There were three patients with fatal infections who had no evidence of disease after they had finished treatment. Seventeen of 29 patients (58.6%) were good responders and showed 60-100% tumoral necrosis after intra-atrial cisplatin. The 6-year, relapse-free survival rate was 58.6%--70.5% for the good responders and 41.6% for the poor responders (p less than 0.05). The size of the tumor was the other important prognostic factor. The rate of 6-year, relapse-free survival was 73.6% for small tumors (those measuring less than 100 cm2) and 33.3% for large tumors (p less than 0.05).

Adolescent↗
PubMed1990

Platelet imipramine binding in endogenous depressed patients and controls: relationship to platelet MAO and 5HT uptake during successful imipramine treatment.

Platelet imipramine binding was measured in 25 unmedicated depressed patients and 25 age- and sex-matched healthy controls. In the patients, the measurement was repeated after 3 weeks and 2 months of imipramine treatment leading to clinical recovery. No significant differences in imipramine binding were found between controls and unmedicated patients. In the latter, imipramine administration produced a progressive change in the binding characteristics, increasing the apparent Kd and decreasing the number of binding sites (Bmax). The results suggest that platelet imipramine binding is not altered in depression and that changes in this parameter are the consequence of the presence of imipramine in the blood stream. However, such changes accompany changes in other biological parameters, such as platelet monoamine oxidase and serotonin uptake, seen in the same patients throughout imipramine treatment, suggesting that the drug acts on a wide range of normal or altered serotonin-related cellular mechanisms while it accelerates the clinical recovery from depression.

Administration, Oral↗
PubMed1990

Disordered single crystal evidence for a quadruple helix formed by guanosine 5'-monophosphate.

The disodium salt of guanosine 5'-monophosphate (5'-GMP) has been crystallized earlier in an orthorhombic array. We have obtained a new crystal form of 5'-GMP at pH 8 which reveals a clear helical nature, with guanine bases stacked perpendicular to the helix axis. Although the X-ray pictures show partial disorder, they can be indexed on a hexagonal net with a = b = 28.6 A, c = 9.8 A, V = 6942 A3 (1A = 0.1 nm). The probable space group is P6(4), and past experience with ca. 600 A3 per base in oligonucleotide crystals suggests that the cell contains 12 GMP molecules. The crystal packing parameters and the intensity distribution agree with a model of three hydrogen-bonded guanine tetrads in the unit cell, stacked so as to build a quadruple helix similar to that proposed earlier from fiber studies (Zimmerman, S.B., J. Mol. Biol. 106, 663-672 (1976)).

Fourier Analysis↗
PubMed1989

Effects of cooling parietal cortex on prefrontal units in delay tasks.

The effects of cooling posterior parietal cortex (areas 5 and 7) on behavior and on the activity of prefrontal neurons were assessed in monkeys performing two visual discrimination tasks with delayed choice. In both tasks, the visual cue for each trial was displayed for 0.5 s by rear projection through colored filters on a central 2.5-cm translucid button. After a variable delay, the choice stimuli were presented on two lower stimulus-response buttons; to obtain a reward, the animal had to press the correct button in accord with the cue. In one task, a red or a green cue called for the choice of that color when the two colors appeared after the delay; in the other task, a yellow or blue cue called for the choice of, respectively, the right or the left of the two white-illuminated choice buttons. Prefrontal single-unit activity (sulcus principalis area) and eye movements were recorded during task performance while parietal areas were at normal or subnormal (6-20 degrees C) temperature. Two-thirds of the units investigated showed significant spontaneous firing changes, most commonly a decrease, as a result of bilateral parietal cooling. A similar proportion of units showed cooling-related changes, excitatory or inhibitory, of their firing activity during the task; such firing changes could occur in any trial-epoch. Parietal cooling also induced misreaching, slow and inaccurate ocular movements, and longer choice reaction time, but did not alter performance in terms of correct responses. Our results suggest the involvement of posterior parietal cortex in spatial aspects of task performance (reaching speed and accuracy, eye movements, reaction time). They also suggest the existence of functional influences from parietal upon prefrontal cortex. Those influences, however, seem not essential for the basic role of the prefrontal cortex in the temporal integration of behavior.

Animals↗
PubMed1989

Pulmonary hypertension in acute respiratory failure.

In order to examine the prognostic value of pulmonary arterial hypertension (PAH) in patients with moderate and severe acute respiratory failure (ARF), 225 patients with ARF who had been treated with mechanical ventilation and admitted to our ICU during a 3-yr period (January, 1983 to January, 1986) were prospectively studied. All 70 (31%) patients with moderate and severe ARF also had some form of hemodynamic or pulmonary instability, and were monitored with a pulmonary artery catheter. Of these 70 patients, 38 (54%) had PAH (mean BP 29 +/- 6 mm Hg); their mortality was 79% (30/38). The rest of the patients (n = 32) did not have PAH (mean BP was 15 +/- 3 mm Hg) and their mortality was 44% (14/32) (p less than .01). Thirty patients met all the criteria for adult respiratory distress syndrome (ARDS), and their mortality was 70% (21/30); all of them were included among the 38 PAH patients. ARDS patients who died had a significantly higher pulmonary vascular resistance and a significantly lower cardiac index than patients who survived (p less than .001). We conclude that PAH (present in all our ARDS patients) is a good predictor of mortality in ARF of diverse causes.

Acute Disease↗
PubMed1989

R1881 regulation of steroidogenesis in cultured testicular cells.

The influence of a synthetic androgen R1881 upon hCG stimulated steroidogenesis in cultured rat testicular cells was investigated. Testicular cells were cultured for 8 days in medium alone and thereafter reincubated for 48 h with appropriate treatments before the collection of media for steroid RIA. Addition of R1881 (10(-6) M) resulted in an overall decrease of hCG (0.3-10 ng/ml) stimulated pregnenolone and progesterone production by cultured cells. The conversion of exogenous steroids of the delta 4 pathway (progesterone,17 alpha-OH-P and delta 4-A) was also studied in cultures supplemented with cyanoketone (10(-5) M) and/or spironolactone (10(-5) M) to prevent endogenous testosterone production. R1881 inhibited progesterone and 17 alpha-OH-P conversion to testosterone (T) and was ineffective when delta 4-A served as precursor for T biosynthesis. The inhibitory effect of R1881 upon Testosterone production was prevented by concomitant treatment with CPA. These observations suggest that R1881 decreases the hCG stimulated testosterone production via inhibition of CSCCE,3 beta-HSD,C17-20 Lyase and likely 17 alpha-Hydroxylase, whereas no effect on 17 beta-HSD could be observed.

3-Hydroxysteroid Dehydrogenases↗
PubMed1989

The androgen receptor does not mediate progestin regulation of progesterone biosynthesis in cultured rat granulosa cells.

In the present investigation the influence of androgens and progestins on the FSH modulation of progesterone biosynthesis was studied in cultured rat granulosa cells. Cells obtained from the ovaries of immature estrogen treated rats were cultured for three days in serum free medium or in medium supplemented with FSH or CPA, with or without reduced androgen DHT or the synthetic progestin R5020 alone or in combination with the anti-androgen CPA. Treatment with FSH increased pregnenolone, progesterone and 20 alpha-OHP accumulation in the culture medium 20-, 14- and 7-fold, respectively. Furthermore FSH increased the activity of the enzyme 3 beta-HSD. Concurrent treatment with DHT or R5020 augmented the FSH stimulated steroidogenesis of cultured cells. The androgen enhancement of FSH stimulated steroidogenesis of cultured granulosa cells was blocked by concomitant treatment with CPA, whereas treatment of cultures with anti-androgen did not affect the stimulatory effect of the synthetic progestin R5020.

20-alpha-Dihydroprogesterone↗
PubMed1988

Prefrontal representation of stimulus attributes during delay tasks. I. Unit activity in cross-temporal integration of sensory and sensory-motor information.

The activity of 294 single units was recorded from the dorsolateral prefrontal cortex of monkeys performing two visual discrimination tasks with delayed response. One task, delayed matching-to-sample (DMS), required memory of a colored cue for later (18 s) matching and choice of color; the cue did not connote the location of the delayed response. The other task, delayed conditional position discrimination (DCPD), required memory of a colored cue for later (18 s) choice of spatial response; the cue did connote delayed-response location. All 4 cues (red and green in DMS, yellow and blue in DCPD) were isoluminous and appeared in identical location at trial start. Differential unit reactions to the two DCPD cues were more common than those to the two DMS cues (samples). During the delay period, 15% of all units showed, in one task or the other, differential discharge depending on the cue. In DCPD, a large proportion of the units showing direction-related activity at the time of motor response also reacted with a firing frequency change to one or both (spatially identical) trial-initiating cues. Some units showed coherence of cue-related and response-related changes in accord with the behavioral association between color and direction of response (i.e., yellow-right, blue-left). The reactivity of some units was correlated with the behavioral performance of the tasks in terms of correctness or incorrectness of response. The results indicate that, during visual delay tasks, neurons in the dorsolateral prefrontal cortex may process both spatial and non-spatial information. Because of their protracted differential discharge between cue and response (i.e., during the delay), some units seem involved in the transfer of sensory information across time. These findings suggest the role of prefrontal neurons in the representation of multiple attributes of sensory stimuli, including their associated motor connotations, and the overlap of the cortical representations of different attributes. They are also consistent with the role of the prefrontal cortex in the cross-temporal mediation of sensory-motor contingencies and, therefore, the temporal organization of behavior.

Animals↗
PubMed1988

Prefrontal representation of stimulus attributes during delay tasks. II. The role of behavioral significance.

Rhesus monkeys were trained to perform two visual discrimination tasks with delayed response. In both tasks, the response depended on the color of the cue, a lighted circle in the center of a panel. Red and green guided one task, yellow and blue the other. In the course of performance, a fifth color (violet), non-relevant and inconsequential, was presented at random in the same location as the cues. All 5 stimuli were of equal brightness. Many cells in the dorsolateral prefrontal cortex (sulcus principalis and superior convexity) treated the relevant cues differently than the irrelevant stimulus. In general, cellular reactions to that stimulus were of lesser magnitude than the reactions to the cues. Cell reaction differences as a function of stimulus significance outnumbered and overshadowed differences as a function of cue-color or any other task variable. The results indicate that, during visual delay tasks, units in the dorsolateral prefrontal cortex differentiate stimuli by their behavioral significance, as well as by other stimulus attributes, including color. Because the motivational evaluation of sensory stimuli is an integral part of the cognitive processes in delay tasks (together with short-term memory and motor set), these results support the notion that the prefrontal cortex integrates motivational inputs into the structure of behavioral action.

Animals↗