Biomedical subjects
Publications and source records attributed to J Diaz.
Amebostomes are labile sucker-like structures repeatedly observed and described in Naegleria by different authors. Studying the phagocytic action of some Acanthamoeba species on Vero cells, the formation of similar structures to the Naegleria amebostomes was observed, apparently related to the phagocytic activity on cells.
1. The acquisition of developmental milestones and maturational motor reflexes were compared in three rat strains (culled to 8 pups/litter), F344, Buff and SD. 2. Open field behavior on postnatal day 21 was scored for locomotor activity, rears and center entries. 3. F344 rats, which model ADHD, were the slowest of the three strains in acquiring a number of developmental milestones and in gaining weight; but they were intermediate in their scores for locomotor activity and rearing during open field testing at postnatal day 21. 4. Preliminary autoradiographic data using the D-1 specific ligand [3H]SCH 23390 are included which suggest that D-1 receptors, which display age-dependent changes in concentration and distribution, are relevant to day 21 open field behavior. 5. F344 rats demonstrate developmental "dysmaturation" which is consistent with that observed in children with ADHD in that somatic growth is disproportionately delayed in comparison to neurological and motor maturation.
Thirty patients undergoing resection of arteriovenous malformations with deliberate hypotension were randomized to receive 1 of 3 hypotensive agents. Anesthesia was maintained with isoflurane and nitrous oxide in all patients. Mean arterial pressure was reduced 20% to 60-65 mm Hg with use of either isoflurane (less than or equal to 4%), sodium nitroprusside (less than or equal to 8 micrograms.kg-1.min-1), or esmolol (less than or equal to 24 mg/min). Esmolol was associated with a decrease in cardiac output from 6.2 +/- 1.3 to 3.8 +/- 0.8 L/min, which, because of a 22% increase in systemic vascular resistance, far exceeded the reduction in mean arterial pressure. Systemic vascular resistance increased despite a 32% decrease in plasma renin activity. In contrast, with sodium nitroprusside or isoflurane, the decrease in mean arterial pressure was associated with decreases in systemic vascular resistance of similar magnitude, with no change in cardiac output. Plasma renin activity levels increased 48% with sodium nitroprusside and 126% with isoflurane. Heart rate increased 13% with sodium nitroprusside, remained unchanged with isoflurane, and decreased 23% with esmolol. Although esmolol may be used as a primary hypotensive agent, the potential for marked myocardial depression must be recognized. The differences in pharmacologic properties for the different hypotensive agents suggest that combinations of these agents may provide a pharmacologic profile superior to either agent alone.
The effects of age on the pharmacokinetics and pharmacodynamics of vecuronium in eight elderly patients aged 72-86 yr and eight younger adults aged 26-48 yr undergoing elective surgical procedures under nitrous oxide-fentanyl anesthesia were studied. Vecuronium (0.1 mg/kg) was given as an intravenous bolus, and the ulnar nerve was stimulated with a square-wave impulse of 0.2-ms duration. The response to stimulation at a frequency of 0.1 Hz was measured and recorded with a force displacement transducer applied to the thumb. Spontaneous recovery was significantly longer in elderly patients than in younger patients (50% recovery time, 97.1 +/- 29 vs 39.8 +/- 14 min, mean +/- SD; recovery index [25%-75%], 49.4 +/- 11 vs 15.0 +/- 8 min). In addition, in elderly patients elimination half-life of vecuronium was significantly prolonged (125 +/- 55 vs 78 +/- 21 min, P = 0.04) and plasma clearance reduced (2.6 +/- 0.6 vs 5.6 +/- 3.2 mL.kg-1.min-1, P = 0.049). The prolonged duration of action of vecuronium in the elderly surgical patients thus appears to be secondary to altered pharmacokinetics consistent with an age-related decrease in renal and hepatic functions.
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Cryptococci react positively with various histochemical stains, including the Fontana-Masson (FM), which stains the cell wall, and mucin stains, such as alcian blue and mucicarmine, which stain the capsule. Combinations of the FM stain with both the alcian blue and mucicarmine stains were performed on paraffin-embedded tissue specimens that were obtained from 15 patients who had culture-proved cryptococcosis. Combined FM-mucicarmine and FM-alcian blue stains were compared with other individual fungal stains. The FM stain, followed by either the mucicarmine or alcian blue stain, distinctively demonstrated both the cell wall and capsule of most organisms. More organisms were recognized in the combined stains than with either stain done individually. No interference between the stains was noted. Combining the FM stain with either of these two mucin stains appears to be helpful for identifying cryptococci.
We have evidence that ristocetin and botrocetin mediate binding of von Willebrand Factor (vWF) to platelet glycoprotein Ib (GPIb) through two distinct domains on the vWF molecule. This was established by using monoclonal antibodies (MAbs) to vWF and synthetic peptides derived from the sequence of vWF. MAb 322 and MAb NMC/vW4 both recognize native vWF as well as fragments containing the GPIb-binding domain of vWF, obtained with the following enzymes: trypsin (116 kDa), V-8 protease (SpIII, 320 kDa) and V-8 protease plus subtilisin (33-28 kDa). Nevertheless, the lack of reciprocal displacement between the two MAbs in experiments of competitive inhibition for binding to vWF demonstrate that their respective epitopes are separate. Both MAbs inhibit 125I-vWF binding to platelet membrane GPIb and vWF-dependent platelet agglutination induced by ristocetin. However, only MAb NMC/vW4 inhibits these functions in the presence of botrocetin and when ristocetin-induced platelet agglutination is inhibited by MAb 322, botrocetin is still able to restore the agglutination. The involvement of two distinct domains of vWF for binding to GPIb in the presence of ristocetin or botrocetin was confirmed in experiments of binding of 125I-vWF to platelets using a competitor synthetic peptides corresponding to the GPIb binding domain of vWF (Cys 474 to Pro 488 and Ser 692 to Pro 708). At a final concentration of 2.5 mM both peptides inhibit more than 90% of the binding of vWF to ristocetin-treated platelets but are unable to modify this binding in the presence of botrocetin. In conclusion our data suggest that botrocetin and ristocetin involve distinct sites on vWF for binding to GPIb.
The contribution of diet and surgery to the brain weight deficits observed in artificially reared rats was investigated. Four day old Long Evans rat pups were assigned to an artificially reared (AR) or mother reared (MR) group. AR pups were encannulated and fed either rat milk (AR-MOM) or replacement formula (AR-MES). MR pups received a sham encannulation (MR-SHAM) or no surgery (MR-CONT) before being returned to their dam for rearing. On day 7 all the animals were killed. Brain weights and visceral organ weights were obtained. There was no significant difference between the MR groups on any measure except stomach weights. AR-MOM pups had larger visceral organ weights than pups in the other groups. AR-MOM and AR-MES pups had similar whole brain weights, smaller than those of the MR pups. However, the cerebellar weights, and to a lesser extent, brainstem weights, showed improvements in the AR-MOM group, over the AR-MES group. Neither the effect of surgery nor of diet alone can account for the organ weight differences that have been described in AR rats. The possibility that normal growth may be primarily dependent on diet at one stage of development, with other factors gaining importance at later stages is discussed.
An intrauterine device, releasing approximately 20 micrograms/day of levonorgestrel (LNg 20), used by 1124 women, was studied in a randomized trial of five years duration in comparison with the Copper T, model TCu 380Agm in 1121 women. At five years, the gross cumulative pregnancy rate of 1.1 +/- 0.5 per 100 among users of the LNg 20 devices was not significantly different from the rate of 1.4 +/- 0.4 per 100 experienced by users of the Copper T 380Ag. The steroid-releasing IUD had significantly higher termination rates for expulsion and amenorrhea, a significantly lower termination rate for other menstrual problems and pain, and a lower continuation rate. The five-year continuation rate among women using the TCu 380Ag was 40.6 per 100 as compared with that of 33.0 per 100 among women randomized to the LNg 20 device (P less than .001). Terminations attributed to amenorrhea with the LNg device primarily account for differences in continuation. These two intrauterine devices are the most effective long-term, reversible IUDs yet reported in the literature. No other contraceptive methods have exhibited such low long-term pregnancy rates in randomized comparative trials.
To facilitate manufacture and insertion of the Gyne T 380 IUD, design changes were instituted. Copper collars were seated flush at the ends of the horizontal crossbar of the device. A randomized study of the Gyne T 380 Slimline, the new design, was undertaken in comparison with the standard Gyne T 380. A total of 996 women were enrolled, with 698 Slimline insertions and 298 of the standard Gyne T. No statistically significant difference in ease of insertion or in performance was detected between the models. At one year, the pregnancy rate of each model was below 0.5 per 100 and the continuation rate was 79-80 per 100. Pelvic inflammatory disease or endometritis was found in one percent of subjects in the first year. This is the seventh multicenter randomized study of a collared T IUD with 380 mm2 of copper surface. In all seven, the one-year gross pregnancy rate has been 1.2 per 100 or lower.
This study explored some toxicological aspects of vanadyl sulphate (VOSO4) treatment of rats made diabetic with a single intravenous injection of streptozotocin (60 mg/kg). Administered in drinking water (0.25, 0.5, 0.75 or 1 mg of VOSO4, 5H2O ml) VOSO4 treatment partially or totally corrected some of the alterations associated with the diabetic state (hyperglycaemia, polydipsia, polyphagia, high cholesterol and triglycerides levels) and did not produce any changes in various plasma or blood cell parameters which were not previously altered by diabetes. Measurement of vanadium levels indicated that tissues accumulated vanadium in the following order of concentrations: bone greater than kidney greater than spleen greater than liver greater than lung greater than or equal to muscle greater than blood. Histopathological studies did not reveal any difference in liver, stomach, ileum, spleen, heart and lung from control, non-treated diabetic or VOSO4-treated diabetic animals. Kidney of all non-treated diabetic animals showed an epithelial cellular swelling of distal tubules while only 2 of 6 VOSO4-treated diabetic animals showed this alteration. Cellular degeneration of pancreas B-cells was less marked in VOSO4-treated that in non-treated diabetic animals. The study indicates that VOSO4 may be a potential antidiabetic agent.
Nuclear rings are cell structures found at the nuclear cortex wedged between the nuclear envelope and the chromatin fiber network. In previous publications we have dealt with their morphology, relationships with the nuclear membranes, chromatin fibers and cytoskeletal filaments; and more recently, with their measurements at high electron microscope resolution. In this article we have calculated the mass and molecular weight of 336 isolated nuclear rings from human circulating lymphocytes using a photometric procedure and polystyrene latex spheres as the standard for weight calibration. Our results show a range of mass of 0.4-35.5 x 10(-16) g (equivalent to 0.2-21.2 x 10(8) Da with a positively skewed distribution (median: 3.3 x 10(-16) g or 2.0 x 10(8) Da). Mass and volume of nuclear rings were highly correlated. In addition, it was possible to calculate the area, the whole mass and the mass per unit area of the nuclear envelope present in the center of the nuclear rings. The mass of this area also shows a lognormal distribution (median of mass/unit area: 37.3 x 10(-8) pg/nm2 or 1.9 x 10(5) Da/nm2). We discuss the significance of this results as parameters for the characterization of the nuclear rings and their possible implications for a new interpretation of nuclear cortex architecture, nucleocytoplasmic traffic and macromolecule segregation between the two main cell compartments.
1. The effects of a segment of peripheral nerve on the innervation of a skeletal muscle were investigated in the cutaneous pectoris muscle of the frog Rana esculenta. An explant of the sciatic nerve was placed in an aneural region of the muscle at a distance of 1-3 mm from the zone of neuromuscular junctions. The muscles were examined morphologically and electrophysiologically at different post-operative times. 2. After the first month nerve sprouts were seen arising from both nerve terminals and intramuscular nodes of Ranvier. Both the number of sites of sprouting and the relative distance to the explant tip increased with time (up to 5 months), suggesting spread of a nerve sprouting-promoting stimulus. 3. Most neurites resulting from sprouting were seen growing towards the nerve explant, in the vicinity of which active neurite proliferation occurred. Some of them entered the explant as observed in semi-thin and thin sections which revealed the presence of both myelinated and unmyelinated nerve fibres. 4. Electrical stimulation of the nerve explant in preparations autografted for more than 2 months resulted in the contraction of bundles of muscle fibres. Endplate potentials of similar amplitudes were recorded intracellularly in some muscle fibres of such preparations when stimulating either the nerve explant or the cutaneous pectoris nerve. When two stimuli were paired by gradually reducing the interval of time between them, the second response was gradually facilitated. This confirmed that nerve fibres stimulated through the explant corresponded to new neuritic processes resulting from motor nerve sprouting. 5. Pieces of perineural tissue and segments of peripheral nerve killed by alcohol treatment or by repeated freezing and thawing were used as controls. They did not induce any nerve sprouting. 6. The results indicate that cells surviving in a segment of peripheral nerve trunk actively induce intact axons to sprout both from their terminals and intramuscular nodes of Ranvier; moreover these cells promote attraction and proliferation of growing neurites. The possibility of release of a diffusible factor by glial cells is discussed.
The effect of age (over 70 yr) on the pharmacokinetics and pharmacodynamics of edrophonium was evaluated in seven patients aged 76-87 yr and in seven patients aged 27-57 yr. When elderly patients were compared with younger controls, the elderly exhibited a statistically significant decreased plasma clearance (5.9 +/- 2 versus 12.1 +/- 4 mL.kg-1.min-1) and a prolonged elimination half-life (84.2 +/- 17 versus 56.6 +/- 16 min). Pharmacodynamically, a higher concentration of edrophonium is required in elderly patients to produce the same effect as in the younger controls. This observation may be explained in part by changes in neuromuscular transmission that are a function of the aging process. In addition, even though plasma concentrations were significantly greater at every sampling point in the elderly than the younger group, there was no difference between either the maximum duration or the total duration of action of edrophonium in the two groups. The maximum duration of action of edrophonium in both groups was very brief (1.3-2.2 min). These results contrast with a previous study of the anticholinesterases neostigmine and pyridostigmine, in which the action of these drugs was significantly prolonged in elderly patients. Explanations for the observed differences between edrophonium and other anticholinesterases may relate to differences in chemical structure and the possibility that edrophonium produces antagonism of neuromuscular blockade by a different mechanism than neostigmine or pyridostigmine.
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A full-length cDNA for vWF has been cloned from a human lung cDNA library and a fragment of this cDNA has been modified to allow its expression in E. coli. This fragment, which corresponds to Val 449-Asn 730 of vWF and includes the GPIb-binding domain and binding sites for collagen and heparin, was subcloned into an expression vector containing an inducible lambda PL promoter. On induction, the expressed recombinant vWF subfragment migrated with a mol wt of around 38,000 after SDS-PAGE. It was identified as a vWF fragment by Western blotting using either a polyclonal or a monoclonal antibody which inhibits the binding of vWF to GPIb. Following solubilization in urea, the bacterial extract inhibited ristocetin-induced platelet aggregation and bound to ristocetin-treated platelets, to collagen and to heparin.