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Biomedical subjects

J Fernandes

Publications and source records attributed to J Fernandes.

At least 55 records · Page 3Linked to original sources

[Assisted circulation to the right ventricle through pulmonary counterpulsation using a biological method].

PURPOSE: To study the hemodynamic effects of latissimus dorsi dynamic pulmonaroplasty in open chest animals. METHODS: Six anesthetized mongrel dogs were subjected to diastolic counterpulsation using electrically stimulated latissimus dorsi muscle flap wrapped around the aortic and pulmonary arteries roots and gated to the surface electrocardiogram. Aortic and Pulmonanary pressures as well as cardiac output and cardiac index were measured. RESULTS: Diastolic counterpulsation resulted in a significant increase in cardiac output (from 2.35 +/- 0.26 to 2.45 +/- 0.28 l/min) (p < 0.005) and cardiac index (from 0.108 +/- 0.020 to 0.113 +/- 0.020 l/min/kg) (p < 0.05). The diastolic pulmonary arterial efficiency index showed a significant increase when latissimus dorsi stimulation was on (from 8.37 +/- 0.60 to 11.65 +/- 0.83 mmHg); (p < 0.005). CONCLUSION: Latissimus dorsi dynamic pulmonaroplasty provides an effective means of arterial counter pulsation in open chest dogs.

Animals↗

Muscle development in the four-winged Drosophila and the role of the Ultrabithorax gene.

BACKGROUND: In the fruitfly Drosophila melanogaster, segment identity is specified by the homoeotic selector genes of the bithorax and Antennapedia complexes. The functions of these genes in the segmental specification of the Drosophila ectoderm have been well studied, but their roles in muscle development have been relatively poorly investigated. Recent experiments have strongly suggested that homeotic selector genes are directly involved in one aspect of mesodermal patterning during Drosophila embryogenesis. But muscle development is a complex process, requiring for its completion the correct positioning of the epidermis, the nervous system and the developing muscles in a segment-specific manner. Many aspects of homeotic selector gene function in this process remain to be understood. RESULTS: In flies that are homozygous for three mutant alleles (anterobithorax, bithorax3, postbithorax) of the Ultrabithorax gene, the third thoracic segment (T3) is transformed towards the second (T2). The adults have two pairs of wings, but the homeotically transformed T3 (HT3) has only rudimentary indirect flight muscles. We used the 'four-winged' fly to study the role of homeotic selector genes in the development of the indirect flight muscles, which we classify into four 'events'. First, the determination of the segment-specific pattern of myoblasts in the larval thorax; second, the specific pattern of migration of myoblasts during metamorphosis; third, the fusion of myoblasts to form adult indirect flight muscles and fourth, the development of the branching pattern of adult motor innervation. Our study shows that the segmental identity of the epidermis determines the segment-specific pattern and number of myoblasts on the larval discs, and the pattern of their migration during metamorphosis. The segmental identity of the mesoderm, however, is crucial for the fusion of myoblasts to form indirect flight muscles, and also influences the branching pattern of innervation of indirect flight muscles. CONCLUSIONS: Segmental information expressed in the ectoderm, and the autonomous function of homeotic selector genes in the mesoderm, are both required for the complete development of indirect flight muscles.

Alleles↗

Binding of reovirus to receptor leads to conformational changes in viral capsid proteins that are reversible upon virus detachment.

A conformational change was detected in reovirus upon its attachment to mouse L fibroblasts. Specifically, the capsid proteins of cell-bound virions became more resistant to pepsin digestion. Similar observations were made using glutaraldehyde-fixed cells or plasma membranes instead of live cells, indicating that virus internalization was not necessary for this effect. This conformational change was totally reversible, since bound virions reverted back to the pepsin-sensitive state upon release from the cell surface. Not unexpectedly, a conformational change was also detected in the reovirus cell attachment protein sigma 1 when it alone bound to cells. The alteration was mapped, by deletion mutagenesis, to a region proximal to the N-terminal (virion-anchoring) end of the protein and was also found to be reversible. Structural changes in sigma 1 were also detectable following its interaction with sialic acid (conjugated to bovine serum albumin) shown previously to the minimal receptor determinant recognized by reovirus. These results suggest that upon cell attachment, a signal is transmitted from the C-terminal receptor-binding region of sigma 1 to the N terminus in a ripple-like progression that eventually leads to conformational changes in the other reovirus capsid proteins. An altered conformational state may be necessary for subsequent viral entry and programmed disassembly of viral capsids inside susceptible cells.

Animals↗

Localization of a new type of X-linked liver glycogenosis to the chromosomal region Xp22 containing the liver alpha-subunit of phosphorylase kinase (PHKA2).

We describe here a new type of X-linked liver glycogen storage disease. The main symptoms include liver enlargement and growth retardation. The clinical and biochemical abnormalities of this glycogenosis are similar to those of classical X-linked liver glycogenosis due to phosphorylase kinase deficiency (XLG). However, in contrast to patients with XLG, the patients described here have no reduced phosphorylase kinase activity in erythrocytes and leukocytes, and no enzyme deficiency could be found. Linkage analysis of four families with this X-linked type of liver glycogenosis assigned the disease gene to Xp22. Lod scores obtained with the markers DXS987, DXS207, and DXS999 were 3.97, 2.71, and 2.40, respectively, all at 0% recombination. Multipoint linkage analysis localized the disease gene between DXS143 and DXS989 with a maximum lod score of 4.70 at theta = 0, relative to DXS987. As both the classical XLG gene and the liver alpha-subunit of PHK (PHKA2) are also located in Xp22, this variant type of XLG may be allelic to classical XLG, and both diseases may be caused by mutations in PHKA2. Therefore, we propose to classify XLG as XLG type I (the classical type of XLG) and XLG type II (the variant type of XLG).

Adolescent↗

Effect of acute lactulose administration on serum acetate levels in cirrhosis.

Lactulose has been used successfully in the treatment of portal-systemic encephalopathy but its exact mechanism of action is not known. The aim of this study was to observe the systemic effects of the colonic fermentation of an acute lactulose dose in cirrhotics and normal subjects. Six cirrhotic patients and 6 normal subjects were placed on 2 identical 2-d metabolic diets, 1 of which was supplemented with lactulose (1 g/100 kcals to a maximum of 28 g/d). Lactulose increased colonic fermentation in cirrhotic and normal subjects as evidenced by higher breath hydrogen and serum acetate levels. The increase in serum acetate levels after lactulose compared to control was similar in cirrhotic compared to normal subjects. However, the mean serum acetate concentration in the cirrhotics was significantly greater than that in the control subjects (p = 0.039), indicating increased endogenous production, or decreased peripheral utilization of acetate by the cirrhotic liver, or both. No change was observed in blood ammonia, glucose, insulin, or free fatty acid levels with lactulose.

Acetates↗

Bioavailability of residues of diazepam and its metabolites.

The present study was performed to determine the metabolic fate of the residues of diazepam and its metabolites in an in vivo model and using two different animal species, guinea pigs and rats, successively. Guinea pigs were orally dosed with diazepam at 100 mg/kg bw and 10 mg/kg bw. After 2 h the animals were sacrificed and their livers were removed. Rats were fed these livers and sacrificed 8 h later after having ingested the portion given. Blood, kidney, and liver of rats were collected to quantify drug residues. Oxazepam and demethyldiazepam were identified by HPLC-UV in liver and kidney rat extracts and also in some blood samples. Temazepam was only found in liver from rats that had eaten guinea pig liver dosed at the highest level. The identity of demethyldiazepam was confirmed in rat liver extracts by GC-MS. This study demonstrates the bioavailability of diazepam metabolites in a second animal (rat simulating a consumer) following a diazepam administration to a first animal (guinea pigs simulating a target animal). Residue concentrations were reduced from 9.7 and 243 micrograms in consumed guinea pig liver to 3.75 and 455 ng/g in rat liver for parent drug and oxazepam, the lowest and highest residues found, respectively.

Animals↗

Hypoglycaemia: principles of diagnosis and treatment in children.

The diagnostic approach to children with suspected hypoglycaemia is facilitated by the fact that two clinically distinct groups exist with little overlap: 1. Hypoglycaemias characterized by a fuel deficit only. 2. Hypoglycaemias in which the fuel deficit is overshadowed by symptoms of intoxication. This differentiation is used when taking the medical history, performing the physical examination, and planning the laboratory investigations. The latter may encompass tolerance tests, a fasting test or the use of a non-radioactive glucose isotope. Protocols for such tests are given.

Child↗

Combined antitumor therapy with the chemotherapeutic drug doxorubicin and an anti-transferrin receptor immunotoxin: in vitro and in vivo studies.

We have determined the in vitro and in vivo efficacy of the combination of doxorubicin and an anti-transferrin receptor-monoclonal antibody (MAb)-ricin A chain immunotoxin. These agents both possess antineoplastic activity and their differing mechanisms of action and toxicities suggest that they may work well in combination. In vitro cytotoxicity was assayed by the inhibition of both 3H-leucine and 3H-thymidine incorporation into H-MESO-1 human malignant mesothelioma cells. In vivo, tumoricidal activity was determined by the effect of treatment on the survival of nude mice bearing H-MESO-1 as an intraperitoneal xenograft. The effect of doxorubicin on the antitumor activity of immunotoxin was directly compared to that of monensin, a well-described immunotoxin potentiator. The coincubation of doxorubicin (1 microM) with immunotoxin in vitro produced no increase in cytotoxicity or rate of cell kill when compared to immunotoxin alone. The addition of monensin to immunotoxin produced a significant increase in both cytotoxicity and the rate of cell kill. In animal trials, all treated groups demonstrated a significant increase in median survival when compared to controls. Treatment with doxorubicin or immunotoxin produced a mean survival time (MST) of 22 and 23 days, respectively, vs. control MST of 10 days. The combination of immunotoxin and doxorubicin increased the MST to 31 days (p = 0.004 vs immunotoxin or doxorubicin alone). Immunotoxin combined with monensin emulsion produced an increase in survival equivalent to doxorubicin/immunotoxin. The use of all three agents produced an additional improvement in survival. Combinations of standard chemotherapeutic drugs and ricin A chain immunotoxins may have additive antitumor effects in the therapy of solid tumors.

Animals↗

Anomalous origin of the left coronary artery. Use of thallium perfusion scans in the evaluation of successful revascularization.

Thallium imaging was performed on a 2-month-old infant with a left coronary artery originating from the pulmonary artery. Imaging was performed before and after corrective surgery, which involved creating a new left coronary osteum from the ascending aorta. The radionuclide study documented successful revascularization postoperatively.

Coronary Vessel Anomalies↗

Maturation of rat spermatozoa: ESR spin labeling studies.

The ability of spermatozoa to reduce nitroxide spin--TEMPO has been used as a parameter to understand maturation, capacitation and calcium uptake of sperm obtained from Holstman strain rats. The rate of spin label reduction by sperm follows the trend--caput greater than cauda greater than corpus. With the increase in age, the electron donating capability shows first a gradual increase, for 60- to 85-day-old rats, peaking at 85 days (corresponding to puberty) and leveling off after 92 days. Calcium uptake takes place in two phases which corresponds to accumulation of and activation by calcium. The presence of polyclonal antibody which is known to cause agglutination, does not adversely affect the sperm activity.

Animals↗

Development of the indirect flight muscles of Drosophila.

We have followed the pupal development of the indirect flight muscles (IFMs) of Drosophila melanogaster. At the onset of metamorphosis larval muscles start to histolyze, with the exception of a specific set of thoracic muscles. Myoblasts surround these persisting larval muscles and begin the formation of one group of adult indirect flight muscles, the dorsal longitudinal muscles. We show that the other group of indirect flight muscles, the dorsoventral muscles, develops simultaneously but without the use of larval templates. By morphological criteria and by patterns of specific gene expression, our experiments define events in IFM development.

Animals↗

Drugs of abuse testing.

Modern medical technology has made available a complex array of testing methods for drugs of abuse. The gathering of the best information from these methods demands that the clinician be familiar with the different testing protocols. In this, the third article in a monthly series, the authors discuss the more common and useful tests and describe their use for optimal results.

Humans↗

Lyme borreliosis: detecting the great imitator.

Lyme disease is a common inflammatory disease of North America. It is caused by the spirochetal bacterium Borrelia burgdorferi, which is transmitted by the bite of a small tick, Ixodes dammini. The disease is inconsistent in its manifestation, mimicking a wide variety of maladies, many of which are noninfectious. Currently, there is no practical means for detection of the presence of the organism, and serologic studies offer the best diagnostic aid. High titers of either immunoglobulin G (IgG) or immunoglobulin M (IgM) antibodies to B burgdorferi antigens indicate disease, but lower titers can be misleading. The IgM antibodies may remain after the initial infection, and IgG antibodies may remain for years. Antibiotic therapy early in the infection may interfere with antibody production, but therapy later does not appear to have a significant effect on antibody levels. Because several methods are available for the detection of antibodies and several choices for antibody detected--IgM, IgG, or combinations--the clinical laboratory should provide guidance and advice in choosing and interpreting tests.

Diagnosis, Differential↗

Blood glucose monitors: technology for home healthcare.

Blood glucose self-monitoring offers several advantages. This article, the first in a series, focuses on the types of monitors currently marketed and their limitations. Because optimal patient care rests with operator training, this article also places emphasis on the need to properly train those who will be performing blood glucose monitoring.

Blood Glucose Self-Monitoring↗