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Biomedical subjects

M Brand

Publications and source records attributed to M Brand.

At least 91 records · Page 5Linked to original sources

Characterization of LHI- and LHI+ Rhodobacter capsulatus pufA mutants.

The NH2 termini of light-harvesting complex I (LHI) polypeptides alpha and beta of Rhodobacter capsulatus are thought to be involved in the assembly of the LHI complex. For a more detailed study of the role of the NH2-terminal segment of the LHI alpha protein in insertion into the intracytoplasmic membrane (ICM) of R. capsulatus, amino acids 6 to 8, 9 to 11, 12 and 13, or 14 and 15 of the LHI alpha protein were deleted. Additionally, the hydrophobic stretch of the amino acids 7 to 11 was lengthened by insertion of hydrophobic or hydrophilic amino acids. All mutations abolished the ability of the mutant strains to form a functional LHI antenna complex. All changes introduced into the LHI alpha protein strongly reduced the stability of its LHI beta partner protein in the ICM. The effects on the mutated protein itself, however, were different. Deletion of amino acids 6 to 8, 9 to 11, or 14 and 15 drastically reduced the amount of the LHI alpha protein inserted into the membrane or prevented its insertion. Deletion of amino acids 12 and 13 and lengthening of the stretch of amino acids 7 to 11 reduced the half-life of the mutated LHI alpha protein in the ICM in comparison with the wild-type LHI alpha protein. Under the selective pressure of low light, revertants which regained a functional LHI antenna complex were identified only for the mutant strain deleted of amino acids 9 to 11 of the LHI alpha polypeptide [U43 (pTPR15)]. The restoration of the LHI+ phenotype was due to an in-frame duplication of 9 bp in the pufA gene directly upstream of the site of deletion present in strain U43(pTPR15). The duplicated nucleotides code for the amino acids Lys, Ile, and Trp. Membranes purified from the revertants were different from that of the reaction center-positive LHI+ LHII- control strain U43(pTX35) in doubling of the carotenoid content and increase of the size of the photosynthetic unit. By separating the reaction center and LHI complexes of the revertants by native preparative gel electrophoresis, we confirmed that the higher amount of carotenoids was associated with the LHI proteins.

Amino Acid Sequence↗

Fecal carriage of Streptococcus bovis and colorectal adenomas.

An association between fecal carriage of Streptococcus bovis and colorectal carcinoma has been reported. A relationship between S. bovis and colorectal adenomas has also been suggested. In the present study, the relationship between S. bovis and adenomas was investigated. Two of 18 current adenoma patients (11%) were found to have S. bovis in their stool compared with 12 of 84 controls (14%). Six of 38 patients who had ever had a diagnosis of adenoma (16%) had S. bovis compared with 8 of 64 controls (13%). These results rule out a strong association between fecal carriage of S. bovis and adenomas; however, because of the relatively small sample size, a weak to moderate association cannot be excluded.

Adenoma↗

Drug utilization in very premature infants in neonatal intensive care units.

Neonatal drug utilization in very premature infants (gestational age (GA) 24-29 weeks), requiring intubation and mechanical ventilation at birth was registered as part of a multicenter controlled clinical trial of high-dose versus low-dose bovine surfactant (initial doses 100 mg/kg birth weight (b.w.) versus 50 mg/kg b.w.). Drug utilization during 4 weeks after birth was analyzed in 164 infants (mean GA 27.2 +/- 1.2 (SD) weeks, b.w. 970 +/- 145 g (SD)). More than half of the study infants received antibiotics (98.8%), sedatives and analgesics (91.5%), sodium bicarbonate (78%), solutions for volume replacement (62.8%), methylxanthines (56.7%) and catecholamines (52.4%). It may be concluded that the pattern of drug usage indicates a high incidence of proven or suspected infections and circulatory and respiratory disorders reflecting the high-risk state of study infants.

Dose-Response Relationship, Drug↗

Altered pulmonary surfactant in uncomplicated and septicemia-complicated courses of acute respiratory failure.

Pulmonary surfactant, which is crucial for alveolar stability, may also be involved in endogenous defense mechanisms of the lungs. Thus, alterations in pulmonary surfactant may promote infections, including pneumonia and septicemia. Because patients who have acute respiratory failure often develop pneumonia, thus septicemia, we investigated when surfactant is altered in these patients and whether there is a specific pattern of changes in surfactant phospholipid composition associated with septicemia in these patients. To answer these questions, we determined the phospholipid content and composition in lung washings obtained from alveolar sites (by bronchoalveolar lavage) and from tracheal sites (by aspiration). Both techniques were performed serially over a period of 18 days in 30 patients who had acute respiratory failure resulting from polytrauma, 18 of whom developed septicemia caused by pneumonia. We found that in lung washings obtained from the alveolar sites from all patients, the phosphatidylglycerol content was decreased and the phosphatidylinositol content was increased as early as 6 hr after trauma and normalized during recovery of the patients. In addition, alveolar phosphatidylcholine content was decreased 24 hr after trauma. In patients who developed septicemia during the observation time, but not in patients who had uncomplicated courses of acute respiratory failure, the concentrations of alveolar phosphatidylethanolamine (normally 4.8% of total phospholipids) and alveolar phosphatidylcholine (normally 62.8%) both approached the proportions found in the trachea (phosphatidylethanolamine 33.4%, phosphatidylcholine 35.6%), suggesting that surfactant phospholipid pool size had progressively decreased. Our results indicate that in patients who have acute respiratory failure, pulmonary surfactant is altered very early, and that when septicemia complicates the course of acute respiratory failure, the surfactant phospholipid pool size decreases progressively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Surfactant abnormalities in patients with respiratory failure after multiple trauma.

We present a prospective study, designed to evaluate surfactant abnormalities in severely injured patients during the course of post-traumatic pulmonary dysfunction. Serially obtained bronchoalveolar lavage fluids from noncontused lung areas (in total, 132 samples from 17 patients) were analyzed for alveolar phospholipid composition and surfactant function in vitro during the first 14 days after trauma. The data were compared with those of 29 lavage samples obtained from 10 healthy control subjects and correlated to severity of respiratory failure. In the traumatized patients, the total lavage phospholipid content was unchanged, but there was a progressive decrease in the relative amounts of phosphatidylcholine (%PC) and phosphatidylglycerol and an increase in phosphatidylinositol, phosphatidylethanolamine, and sphingomyelin. These alterations were paralleled by a marked decrease in the hysteresis area of the surface tension isotherm. The decrease in %PC and reduction of hysteresis area were significantly correlated. The alterations in alveolar phospholipid composition and in vitro surfactant function were more pronounced in patients with severe respiratory failure. There was a significant inverse correlation between severity of respiratory dysfunction and %PC or hysteresis area for all traumatized patients. Protein leakage into the alveolar space was significantly higher in patients with severe respiratory failure and appeared to precede surfactant abnormalities in such patients. The neutrophil content in the alveolar space was markedly increased in all patients with multiple injuries however, no significant correlation with the noted alterations in alveolar phospholipid composition or surfactant function was found. We concluded that surfactant abnormalities occur during the course of post-traumatic pulmonary dysfunction and are correlated with the severity of respiratory failure.

Adolescent↗

daughterless, a Drosophila gene essential for both neurogenesis and sex determination, has sequence similarities to myc and the achaete-scute complex.

daughterless (da) has multiple functions in Drosophila embryonic development: maternal da activity is necessary for proper sex determination, and zygotic da activity is necessary for formation of the peripheral nervous system. We have cloned the region containing da and have found that five recessive lethal da mutations map to a single transcription unit. A predicted protein product of this transcription unit has sequence similarities with the oncogene myc, with the gene MyoD1, which is involved in myoblast determination, and with the Drosophila achaete-scute complex, which is involved in neuronal precursor determination. The role of da as a gene controlling cell determination in multiple developmental pathways is discussed.

Amino Acid Sequence↗

Distribution and function of alveolar cells in multiply injured patients with trauma-induced ARDS.

To determine whether alveolar cells are involved in the pathogenesis of adult respiratory distress syndrome (ARDS), we assessed the distribution and function of alveolar cells from 30 polytraumatized patients with trauma-induced respiratory failure, 5 of whom also had lung contusion. Cells were obtained by bronchoalveolar lavage performed daily beginning on the day of trauma and continuing for 14 days. Neutrophils constituted about 60% of lavage cells in ARDS patients with lung contusion 0-2 days after polytrauma and about 50% in ARDS patients without lung contusion. In ARDS patients with lung contusion the neutrophil fraction decreased to 52% 3-6 days after trauma and to 40% 7-14 days after trauma. In patients without lung contusion the neutrophil fraction increased to 77% and then decreased to 60% at these times. Total cell counts in ARDS patients with lung contusion were more than twice as high as in patients without lung contusion 0-2 days after trauma. The difference in total cell counts decreased during days 3-6 and disappeared by day 7. In all patients morphologically altered alveolar cells were observed 4 days and more after trauma. In non-survivors significantly more altered cells were found. The chemiluminescence-response pattern of the alveolar cells was enhanced throughout the study and correlated with the neutrophil fraction (r = 0.6). The neutrophil fraction also correlated with the pulmonary vascular resistance during the first two days after trauma (r = 0.53). We conclude that alveolar cells are involved in the pathogenesis of trauma-induced ARDS and that the alveolar cell distribution is different in patients with and without lung contusion during the development of posttraumatic respiratory failure.

Acute Disease↗

[Differential diagnosis of pneumonia and pulmonary infarct based on lung scintigraphy].

The etiology of radiologic signs of circumscript parenchymatous lesions is multivarious. In some instances infarction of the lung has to be distinguished from pneumonia. The differential diagnosis has important therapeutic consequences for the patient. An important criterion for primary pneumonic infiltration is Xe-trapping within the area lacking perfusion, which can only be demonstrated by perfusion scintigraphy with Xe-133-NaCl. However, infarction of the lung lacks this pathologic feature. Pathophysiologically the various changes may occur as the result of obstruction of the vessel i.e. due to alveolar hypoxia and embolism. In order to improve the diagnostic methods a combination of perfusion scintigraphy using Xe-133-NaCl and Tc-99-macroaggregate and ventilation scintigraphy with Xe-127 was employed. We retrospectively evaluated 20 patients with the nuclear medical diagnosis of either pneumonia (n = 10) or infarction of the lung (n = 10). The following criteria were adopted: history, risk factors, X-ray of the chest, blood chemistry, ECG, phlebography, pulmonary angiography and histopathological diagnosis, as well as the course of the disease. According to our results the specificity of the scintigraphic diagnosis of pneumonia and infarction of the lung was 90%. However these results will have to be verified in a prospective study using pulmonary angiography as the reference method.

Aged↗

Mitochondrial phosphoenolpyruvate carboxykinase deficiency.

A 3-month-old girl presented with anorexia, failure to thrive and drowsiness. She was mildly icteric with hepatomegaly and peripheral oedema. Disordered liver function tests were associated with the biopsy appearances of a giant cell hepatitis and with a Fanconi syndrome. At the age of 16 weeks she collapsed with profound hypoglycaemia. Fasting also provoked hypoglycaemia with lactic acidaemia. She became increasingly irritable and hypotonic and, although initially liver and renal function improved, she deteriorated and died of hepatocellular failure and septicaemia. A post-mortem revealed massive fatty degeneration of the liver. The activity of phosphoenolpyruvate carboxykinase in her cultured skin fibroblasts was 16% of controls. Her brother died at the age of 4 weeks of sudden infant death syndrome.

Biopsy↗

Gastrointestinal bleeding in competitive runners.

Competitive runners have been shown to develop previously undescribed clinical conditions, including "runner's anemia." This has been shown to be an iron-deficiency anemia of several etiologies including gastrointestinal bleeding. Although 8-23% of runners have been shown to have guaiac-positive stools after a marathon, the incidence of significant and prolonged bleeding is unknown. We report four cases of competitive runners with iron-deficiency anemia, gastrointestinal bleeding coinciding with running, and no definitive gastrointestinal pathology despite extensive evaluation.

Adult↗

Effect of reduced temperature on glycoprotein (Ig, HLA) processing and transport in lymphoid cells.

Secretion of Igs and surface expression of HLA antigens was examined in lymphoid cells as a function of temp. Upon reducing the temp from 37 to 20 degrees C a progressive decrease in the secretion of Ig and surface expression of HLA antigens was noted. When the status of the oligosaccharides present on these glycoproteins was examined, conversion of high-mannose [endo-beta-N-acetylglucosaminidase-(Endo H) sensitive] to complex-type (Endo H resistant) oligosaccharides diminished with decreasing temp. At no time was an accumulation of Endo H resistant glycoproteins seen intracellularly. These results show that the phenomenon observed for synthesis and intracellular transport of viral glycoproteins in epithelial cells at reduced temp, namely intracellular accumulation of viral glycoproteins carrying complex sugar moieties, does not necessarily apply to glycoprotein transport in lymphoid cells. A difference in subcellular organization of epithelial and lymphoid cells may be responsible for this discrepancy.

Animals↗

[Aplasia of retinal vessels in congenital cytomegaly].

Case report on a premature male infant, born in the 34th week of pregnancy with bronchopulmonary dysplasia, bronchitis, hepatitis, marked cortical and subcortical atrophy of the brain with enlargement of the inner and outer subarachnoid space, with severe cerebral motility disorders and convulsions. Blood serology showed rapidly increasing cytomegaly titers, which were also elevated in the serum of the mother. The ophthalmological examination revealed a hypoplastic, white papilla in both eyes. Neither retinal arteries nor veins were seen. The macula and retinal periphery were normal. There were no signs of acute or passed retinochorioiditis. Temporary opacification of the cornea was observed. In connection with the pediatric findings the authors interpret the aplasia of the retinal vessels and the hypoplasia of the optic nerve as a result of a cytomegaly infection prior to the 4th month of pregnancy, which prevented normal development of the vessels. The temporary opacity of the cornea could be a reaction of the corneal endothelium against the virus.

Cytomegalovirus Infections↗