Female-to-male transmission of HIV.
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Female↗
Biomedical subjects
A Johnson
Publications and source records attributed to A Johnson.
[Patient-controlled analgesia after major back surgery].
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Analgesia, Patient-Controlled↗
Naturally acquired CD8+ cytotoxic T lymphocytes against the Plasmodium falciparum circumsporozoite protein.
In rodent malaria model systems, protective immunity induced by immunization with irradiated sporozoites is eliminated by in vivo depletion of CD8+ T cells, and adoptive transfer of CTL clones against the circumsporozoite protein protects against malaria. We recently demonstrated that volunteers immunized with irradiated Plasmodium falciparum sporozoites produce CTL against peptide 368-390 of the P. falciparum circumsporozoite protein. To determine whether natural exposure to malaria induced similar CTL, we studied 11 adult, male, life-long residents of a highly malarious area of Kenya, who were selected because their lymphocytes had been shown to proliferate after stimulation with peptides 361-380, 371-390, or 368-390 and because nine had been resistant to malaria in previous studies. In four of the 11 individuals there was peptide-specific, genetically restricted, CTL activity. In all four individuals, this activity was unaffected by depletion of CD4+ T cells. In three volunteers the activity was eliminated or reduced by depletion of CD8+ T cells; in the fourth volunteer the CD8+ T cell depletion was uninterpretable. This first demonstration of CD8+ T cell, genetically restricted, Ag-specific CTL against a malaria protein among individuals exposed to endemic malaria provides a foundation for studying the relationship between circulating CTL and resistance to malaria infection.
Amino Acid Sequence↗
B----Z DNA conformational changes induced by a family of dinuclear bis(platinum) complexes.
The reactions of bis(platinum) complexes of general formula [(PtClm(NH3)3-m)2(NH2(CH2)nNH2)]2(2-m)+ were studied with poly(dG-dC).poly(dG-dC), poly(dG-m5dC).poly(dG-m5dC) and poly(dG).poly(dC). When m = 0 (Complexes II, n = 2,4) the complexes are saturated 4+ cations capable only of electrostatic interactions with the polynucleotide. Where m = 1 the complexes contain two monodentate platinum coordination spheres with the chloride trans to the diamine bridge (Complexes I, n = 2,4, 1,1/t,t). Complexes I give CD spectra characteristic of a 'Z-like' conformation upon reaction with poly(dG-dC).poly(dG-dC) and poly(dG-m5dC).poly(dG-m5dC) but not poly(dG).poly(dC). The B----Z transition appears independent of interplatinum diamine chain length. As little as 1 bis(platinum) complex per 25-30 base pairs is sufficient to observe the Z-like spectrum. Covalent binding is however not a prerequisite for Z-DNA formation because the polyvalent cations II are also very effective in inducing the B----Z transition in either poly(dG-dC).poly(dG-dC) or poly (dG-m5dC).poly(dG-m5dC). In these cases, the concentrations of II required are significantly lower than analogous monomeric agents such as [Co(NH3)6]3+. The possible biological consequences of the Z-DNA induction by bis(platinum) complexes are discussed.
Circular Dichroism↗
Prevalence and pathologic features of sickle cell nephropathy and response to inhibition of angiotensin-converting enzyme.
BACKGROUND: Nephropathy may develop in patients with sickle cell disease. We determined the prevalence of proteinuria and renal insufficiency in a group of patients with sickle cell disease and investigated the renal pathologic changes and the effects of an angiotensin-converting-enzyme inhibitor (enalapril) on protein excretion in patients found to have nephropathy. METHODS: We prospectively screened 381 patients with sickle cell disease for the presence of proteinuria and renal insufficiency. Renal biopsy and measurements of glomerular filtration rate, effective renal plasma flow, and urinary protein excretion were performed in 10 patients with mild nephropathy before and after the administration of enalapril, and again two to three weeks after its discontinuation. RESULTS: Of the 381 patients with sickle cell disease, 26 (7 percent) had serum creatinine concentrations above the normal range and 101 (26 percent) had proteinuria of at least 1+. The renal lesions in the 10 patients who had biopsies consisted of glomerular enlargement and perihilar focal segmental glomerulosclerosis. The mean (+/- SD) glomerular area in these patients was 28.7 +/- 4.1 x 10(3) micron 2, as compared with 15.8 +/- 4.3 x 10(3) micron 2 in 10 control patients without renal disease who had died of trauma (P less than 0.0001). During the administration of enalapril, the mean 24-hour urinary protein excretion decreased 57 percent (range, 23 to 79 percent) below the base-line value (P less than 0.001), and it increased to 25 percent below the base-line value after enalapril was discontinued. The glomerular filtration rate and effective renal plasma flow did not change significantly. CONCLUSIONS: Approximately 25 percent of patients with sickle cell disease have proteinuria. Treatment with enalapril reduces the degree of proteinuria in these patients, suggesting that glomerular capillary hypertension may be a pathogenic factor in sickle cell nephropathy.
Adult↗
Metal-ceramic bridges from commercial dental laboratories: alloy composition, cost and quality of fit.
The quality of construction of fixed bridge prostheses directly affects their long-term survival. The cost, alloy composition and marginal fit of bridges made by 30 commercial dental laboratories is assessed. Duplicate models of a three unit bridge preparation were sent to 30 different laboratories, as if required for a patient receiving treatment under the General Dental Service. Material was sent via general dental practitioners, requesting metal-ceramic bridges made from 45% Au alloy, precious metal or non-precious metal. Proximal contacts were overbuilt at 65% of sites and pontic tissue contacts were excessive in all but one bridge. Eight laboratories did not use alloys corresponding to the request made. The mean marginal gaps of non-precious metal bridges (145 microns) were significantly greater than those for 45% gold alloy (106 microns). Marginal fit was poor and a number of factors have been observed, with other postulated, which may have contributed to this problem.
Ceramics↗
Corynebacterium jeikeium meningitis and transverse myelitis in a neutropenic patient.
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Adult↗
alpha-Conotoxin GI produces tetanic fade at the rat neuromuscular junction.
The ability of the marine snail toxin, alpha-conotoxin GI, to produce blockade of singly evoked twitches and to produce tetanic and train-of-four fade has been determined in the isolated rat hemidiaphragm preparation. Results were compared to those obtained with a reversible (vecuronium) and an irreversible (alpha-bungarotoxin) nicotinic acetylcholine antagonist and have been interpreted in terms of relative effects on post- and prejunctional nicotinic acetylcholine receptors at the neuromuscular junction. alpha-Conotoxin GI (0.5-2 microM) produced a concentration-dependent, readily reversible, decrease in the peak amplitude of single twitches and 50 Hz tetani, and an increase in tetanic and train-of-four fade. alpha-Conotoxin GI was consistently 2-3-fold more potent than vecuronium with respect to all of the measured tension parameters. Both alpha-conotoxin GI and vecuronium were approximately 2-fold more potent in producing tetanic fade and in blocking tetanic contractions than in blocking single twitches. In contrast to both alpha-conotoxin GI and vecuronium, alpha-bungarotoxin (0.13 microM) reduced the peak amplitude of both single twitches and 50 Hz tetani to the same extent without the appearance of a large degree of tetanic or train-of-four fade. Based on a comparison of the in vitro time course of neuromuscular block and of the relative effects of vecuronium, alpha-conotoxin GI and alpha-bungarotoxin on twitches, tetani and trains-of-four, we conclude that alpha-conotoxin GI has both pre- and postjunctional activity at the neuromuscular junction. In this respect, alpha-conotoxin GI resembles the clinically used competitive neuromuscular blocking drugs rather than the irreversible snake alpha-neurotoxins.
Animals↗
Vascular catheter-related sepsis: diagnosis and prevention.
Although catheter-related sepsis (CRS) is an important cause of nosocomial infection and the major complication of intravenous catheter use, there is, as yet, no consensus concerning either a useful definition of CRS or the optimal method of catheter management and prevention of infection. Semiquantitative culture of catheter tips is a useful method of diagnosis of CRS but other techniques such as quantitative catheter blood cultures and Gram staining of the catheter have roles in selected patients. The most significant impact on the prevention of CRS is made by the introduction of an intravenous therapy team. The site and method of catheter insertion, type of dressing and antisepsis, catheter flushing and use of prophylactic antibiotics are also important issues. Techniques such as guide-wire exchange and catheters such as triple lumen and total implantable venous access devices have their own infection problems. Many new and interesting approaches to the prevention of CRS are being formulated. To facilitate further progress, a standardized definition for diagnosis, and revised recommendations for prevention of CRS would be helpful.
Anti-Bacterial Agents↗
Glutaric aciduria type 1 an atypical presentation together with some observations upon treatment and the possible cause of cerebral damage.
This report describes an infant diagnosed aged twenty-five months as having glutaric aciduria Type 1 (GA 1). Initial presentation was with isolated macrocephaly at four months of age. Severe hypertonia, and dystonia, within 24 hours of minor head injury occurred at nineteen months of age. Serial cranial imaging showed subdural fluid collections, and increasing underlying cerebral atrophy, mainly frontal and temporal. Confirmation of the clinical diagnosis required repeated blood and urine analysis by high performance liquid chromatography and gas chromatography/mass spectrometry; diagnosis was later confirmed enzymologically. Treatment with riboflavin, L-carnitine, vigabatrin and baclofen, produced some symptomatic relief; a low protein diet, nitrazepam and sodium valproate appeared of less obvious use. The rationale for these attempts at treatment is discussed. The possible role of quinolinic acid in the genesis of the fronto temporal and striatal atrophy is discussed and measurement of the quinolinate concentration in cerebrospinal fluid (CSF) of this case and age-related controls is presented.
Amino Acid Metabolism, Inborn Errors↗
A new ventilator converter with the Siemens Servo Ventilator--evaluation in a lung model.
A ventilator converter device (Anmedic) for connecting a non-rebreathing ventilator (Servo Ventilator 900 B; Siemens-Elema) to a circle anaesthesia system was evaluated in a lung model. Recorded minute ventilation was slightly lower than dialled in most cases. We furthermore found inadequate expiratory expansion of the ventilator converter bellows, with progressive loss of tidal volume and consequently recorded minute volume, when fresh gas flow to the circle system was low (1 l.min-1), expiratory time was short (less than 40%) and respiratory obstruction was present.
Airway Obstruction↗
Influence of intrathecal morphine and naloxone intervention on postoperative ventilatory regulation in elderly patients.
Thirty elderly patients undergoing major hip surgery under spinal analgesia were randomly allocated in a double-blind manner into three groups. The aim was to evaluate the influence of intrathecal morphine and postoperative naloxone infusion on the regulation of ventilation. The Bupivacaine Group received spinal analgesia with 20 mg bupivacaine intrathecally. The Morphine Group received spinal analgesia with 20 mg bupivacaine + 0.3 mg morphine intrathecally. The Naloxone Group received spinal analgesia with 20 mg bupivacaine + 0.3 mg morphine intrathecally + postoperative naloxone infusion intravenously (1 microgram/kg/h over 12 h, 0.25 micrograms/kg/h over the next 12 h). Evaluation of resting ventilation and the ventilatory responses to hypercarbia and hypoxaemia was made on three occasions: before surgery, and 8, and 24 h after the intrathecal injection. Intrathecal morphine had no significant effect on ventilatory regulation in elderly patients undergoing major hip surgery performed under bupivacaine spinal analgesia. Postoperative administration of opioids or sedatives after intrathecal morphine as well as postoperative blood loss associated with a fall in blood pressure appeared to increase the risk of developing respiratory depression. Naloxone infusion seemed to reduce the risk of developing respiratory depression. Furthermore, one third of the elderly had a poor response to hypoxaemia before surgery.
Aged↗
Attenuated ventilatory response to hypoxaemia at vecuronium-induced partial neuromuscular block.
The effect of a partial neuromuscular block on the ventilatory response to hypercarbia and to hypoxaemia was studied in 11 non-anaesthetized male subjects. Respiratory frequency, tidal volume, minute volume, respiratory timing and drive were measured during air breathing and during stimulation by hypercarbia and hypoxaemia. The ventilatory response was defined as the ratio between, respectively, tidal volume and minute volume during ventilation stimulated by hypercarbia and hypoxaemia compared to measurements during air breathing. The ventilatory measurements were repeated on three separate occasions: before neuromuscular block was established, during an infusion of vecuronium aiming at a mechanical adductor pollicis train-of-four (TOF) ratio of 0.70, and after the infusion had been stopped and the neuromuscular block had spontaneously recovered to a TOF ratio of > 0.90. Resting ventilation during air breathing remained with minor variations throughout the experiment. The ventilatory response to hypercarbia was not affected at a TOF ratio of 0.70 as compared to measurements before vecuronium and at a TOF ratio of > 0.90. In contrast, the ventilatory response to hypoxaemia was markedly reduced at a TOF ratio of 0.70. We conclude that a mechanical TOF ratio of 0.70 following vecuronium may be associated with an inadequate ventilatory response to hypoxaemia.
Adult↗
An association between hypocholesterolaemia and colorectal carcinoma in an Irish population.
A group of 114 Irish patients with primary adenocarcinoma of the large bowel had significantly lower serum cholesterol concentrations than an age and sex matched group drawn from the general population. The hypocholesterolaemiac trait was manifest in male and female patients. Rigorous control procedures established that it was neither an artefact of nutritional compromise nor of preoperative bowel preparatory protocols. The data suggested that the appreciable hypocholesterolaemia observed was not influenced by the pathological stage or degree of differentiation of the tumour.
Adenocarcinoma↗
Twin pregnancies: accuracy of first-trimester abdominal US in predicting chorionicity and amnionicity.
A first-trimester transabdominal ultrasound (US) study was performed on twin pregnancies to determine the utility of US in predicting chorionicity and amnionicity. Among 85 dichorionic-diamniotic (DC-DA) twin pairs, a thick membrane was present in 78 (92%). Four of the DC-DA cases without a thick membrane had two distinct placental sites, allowing 82 DC-DA pregnancies (96%) to be predicted. Among 16 monochorionic-diamniotic (MC-DA) twin pairs, a thin membrane was present in 14 (88%). None of the four monochorionic-monoamniotic (MC-MA) cases had an identifiable membrane. The lambda sign had no value in this evaluation and was actually misleading, while a thick membrane or the identification of two separate placentas was always predictive of DC-DA twinning. However, a thin membrane, while usually predictive of an MC-DA pregnancy, did not exclude a DC-DA gestation. When no membrane is present, an MC-MA gestation is probable; however, a diamniotic pregnancy may still be present, and further evaluation is suggested.
Amnion↗
Dextran sulfate and heparin sulfate inhibit platelet-activating factor-induced pulmonary edema.
We tested the hypothesis that dextran sulfate and heparin sulfate inhibit platelet-activating factor- (PAF) induced pulmonary edema in the isolated perfused guinea pig lung via a charge-dependent mechanism. Dextran sulfate prevented the changes in pulmonary capillary pressure (Ppc, 7.8 +/- 0.9 vs. 14.0 +/- 0.7 cmH2O), lung weight gain (dW, +0.48 +/- 0.29 vs. +8.41 +/- 2.07 g), and pulmonary edema formation or wet-to-dry weight ratio [(W-D)/D, 6.5 +/- 0.3 vs. 13.2 +/- 2.6] occurring 60 min after PAF infusion (10(-11) M) into an isolated lung. The unsulfated form of dextran had no protective effect [Ppc, dW, and (W-D)/D, 11.9 +/- 1.4 cmH2O, +5.33 +/- 2.18 g, and 11.2 +/- 3.2, respectively]. The unrelated anionic compound, heparin sulfate, also inhibited the PAF response [Ppc, dW, and (W-D)/D, 7.0 +/- 0.5 cmH2O, +0.61 +/- 0.32 g, and 6.1 +/- 0.2, respectively], whereas the partially desulfated form of heparin was not effective in inhibiting PAF-induced edema [Ppc, dW, and (W-D)/D, 15.1 +/- 0.7 cmH2O, +6.07 +/- 1.58 g, and 10.0 +/- 1.2, respectively]. When the metachromatic dye crystal violet was used as an indicator of charge interactions, the sulfated compounds interacted with PAF in vitro. The data indicate that PAF-induced pulmonary edema is inhibited by sulfated polysaccharides, possibly via a charge interaction between negatively charged compounds and PAF.
Animals↗
TNF-alpha augments pulmonary vasoconstriction via the inhibition of nitrovasodilator activity.
We tested the hypothesis that tumor necrosis factor-alpha (TNF-alpha) increases pulmonary vasoconstriction by decreases in nitric oxide- (NO) dependent vasodilation. Lungs were isolated from guinea pigs 18 h after intraperitoneal injection of either TNF-alpha (1.60 x 10(5) U/kg) or control. U-46619 (365 mM/min) caused increases in pulmonary arterial and capillary pressures, pulmonary arterial and venous resistances, and lung weight. TNF-alpha augmented the U-46619-induced increases in pulmonary arterial and capillary pressures, pulmonary arterial and venous resistances, and lung weight. Methylene blue (1 microM), which inhibits the activation of soluble guanylate cyclase by NO, had an effect similar to TNF-alpha on the pulmonary response to U-46619 alone but was not additive to the effect of TNF-alpha. NG-monomethyl-L-arginine (270 microM), an inhibitor of NO generation, also enhanced the response to U-46619. Lung effluent levels of nitrite, the oxidation product of NO, were reduced after treatment with either TNF-alpha or NG-monomethyl-L-arginine compared with U-46619 alone. In addition, lungs isolated after TNF-alpha treatment showed decreased vasodilation in response to acetylcholine (10(-8)-10(-5) M) compared with control; however, vasodilation in response to L-arginine (10 mM) and nitroprusside (10(-6.3) and 10(-6) M), agents that promote NO release, was not decreased in TNF-alpha-treated lungs. The data indicate that TNF-alpha induces an increase in vascular constriction in response to U-46619 and a decrease in vasodilation in response to acetylcholine. The mechanism for the TNF-alpha-induced alteration in pulmonary vascular reactivity may be decreased generation of NO.
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
Complete deletion of the androgen receptor gene: definition of the null phenotype of the androgen insensitivity syndrome and determination of carrier status.
The molecular basis of androgen insensitivity was investigated in a family with the complete form of the syndrome. Polymerase chain reaction amplification and Southern blot analysis of genomic DNA revealed a deletion of the entire androgen receptor (AR) gene in affected individuals. The carrier status of female members of this family was examined using a HindIII restriction fragment length polymorphism associated with the AR gene. Obligate carriers were hemizygous for one of the two alleles at this locus, while heterozygosity for the polymorphic alleles, implying the presence of two copies of the AR gene, indicated noncarrier status. This conclusion was supported by gene dosage studies using comparative densitometric analysis of Southern blots hybridized simultaneously with an AR cDNA probe and a control cDNA probe from an unrelated gene. Finally, the pattern of inheritance of another X-linked DNA polymorphism allowed us to conclude that the original mutation had occurred in the germ line of the maternal great-grandfather of the index patient. Although rare, complete deletion of the AR gene is of particular importance in terms of correlation between molecular defect and phenotype, as it represents the quintessential form of complete androgen insensitivity, the null phenotype.
Alleles↗