Biomedical subjects

E John

Publications and source records attributed to E John.

At least 19 recordsLinked to original sources

PubMed1992

Structure of pentaamminechlororuthenium(III) bisulfate tetrahydrate.

[RuCl(NH3)5](HSO4)2.4H2O, M(r) = 487.88, triclinic, P1, a = 10.0422 (5), b = 14.1044 (7), c = 6.3273 (6) A, alpha = 100.369 (5), beta = 98.655 (6), gamma = 81.354 (4) degree, V = 864.5 (3) A3, Z = 2, Dm = 1.86 (1), D chi = 1.874 g cm-3, lambda(MO K alpha) = 0.71073 A, mu = 13.3 cm-1, F(000) = 498, T = 296 (1) K, R = 0.025 for 4622 unique reflections with I greater than 3 sigma(I). The structure contains (NH3)5RuCl2+ cations, bisulfate anions and solvate water molecules all linked by an extensive hydrogen-bonding network. Each Ru ion is coordinated in a distorted octahedral fashion by five ammonia molecules and a chloride ion. The Ru--Cl distance [2.3742 (5) A] is typical for RuIII--Cl linkages. The Ru--NH3 distances span a narrow range [2.096 (2)-2.119 (2) A] and provide no evidence for a trans effect.

Molecular Structure↗

PubMed1992

Evaluation of biological response modifiers in the enhancement of tumor uptake of technetium-99m labeled macromolecules. A preliminary report.

Imaging tumors with radioactive monoclonal antibodies remains attractive but continues to be challenging. With the hypothesis that the use of biological response modifiers (BRMs) may augment the tumor uptake, technetium-99m(99mTc)-labeled tumor necrosis factor (TNF) and nuclear histone specific TNT-1-F(ab')2 were evaluated in tumor bearing mice given a single dose of interferon (IFN). Ukrain or pokeweed mitogen as BRMs. As early as 1.5 h post injection (p.i.) of the radioactive macromolecules, the absolute tumor uptake (% administered dose/g) of each agent was enhanced (e.g., TNF, control = 1.8 +/- 0.4, Ukrain = 3.2 +/- 0.5, P = 0.006) and tumor to muscle ratios were elevated (e.g., TNF, control a 4.1 +/- 2.2, interferon 8.3 +/- 2.7, P = 0.01). The absolute tumor uptake remained practically unchanged at 4 h p.i. Generally with BRMs, the blood clearance was rapid and tumor/blood ratios and tumor/muscle ratios were higher than in the control group, increasing to greater than 200% for IFN as a BRM. The early enhancement in tumor uptake of macromolecules, leading to excellent delineation of tumors by scintigraphy is highly encouraging and warrants further studies to explore the full potential of BRMs.

Animals↗

PubMed1992

Recovery of tracheal epithelium following high frequency ventilation at low inspired humidity.

We used scanning electron microscopy (SEM) and light microscopy (LM) to study the recovery of tracheal epithelium in newborn lambs damaged by high frequency flow interrupted ventilation (HFFIV) at low inspired humidity (30%). Newborn lambs were mechanically ventilated for 6 h, allowed to recover and subsequently killed at 2, 7 or 14 days. The recovery of the trachea above and below the tip of the endotracheal tube (ETT) was studied at these time periods and compared to a control non-intubated group and a group killed immediately after 6 h of ventilation. Above and below the ETT, SEM and LM revealed deciliation to be greatest 2 days after ventilation. The damaged tracheal mucosa had converted to non-ciliated epidermoid squamous metaplastic cells. Recovery was not complete by 14 days, although the squamous cells had already differentiated into goblet and ciliated columnar epithelial cells. No difference was seen in the rate of recovery of the tracheal mucosa above or below the tip of the ETT.

Animals↗

PubMed1992

A synthetic analogue of melittin aggregates in large oligomers.

An analogue of melittin synthesized in the group of E. T. Kaiser (DeGrado, W. F., F. J. Keźdy, and E. T. Kaiser. 1981. J. Am. Chem. Soc. 103:679-681) was investigated by Raman spectroscopy and fluorescence anisotropy decay. In water, the analogue is completely alpha-helical and aggregates in large oligomers of about 50 monomers. In vesicle membranes, it undergoes orientational fluctuations similar to melittin. The most significant difference from melittin, therefore, is the formation of straight helixes and their aggregation in large oligomers in water. We interpret this as a consequence of the lacking proline residue in the analogue. We, furthermore, hypothesize that the increased tendency for aggregation causes the increased hemolytic activity of the analogue.

Amino Acid Sequence↗

PubMed1992

Necrotizing enterocolitis in a perinatal centre.

Thirty-five neonates developed radiologically proven necrotizing enterocolitis (NEC) over a 40 month period. They were 28 +/- 2 weeks gestation, and weighted 1094 +/- 411 g at birth. Eighteen infants (51%) required surgery and three (8.5%) died. The incidence was 6.7% in the very low birthweight (VLBW) infants. A large proportion of NEC (60%) presented beyond 10 days of life. An inverse relationship between gestation and age of onset was observed. The age of presentation was 22 +/- 13 days (range 10-53 days) for the 18 infants less than or equal to 28 weeks compared with 7 +/- 5 days for those over 28 weeks (P less than 0.01). Five NEC infants had bacteraemia which occurred 2-7 days prior to gastrointestinal symptoms of NEC, and four were staphylococcal. Compared with infants controlled for gestation, there was no significant differences observed in perinatal events or feeding history. We concluded that an immature gastrointestinal system is vulnerable to NEC even beyond the early neonatal period.

Enterocolitis, Pseudomembranous↗

PubMed1992

Treatment with hypertonic dextrose and insulin in severe hyperkalaemia of immature infants.

Over a three-year period, 12 infants received dextrose/insulin infusions for severe hyperkalaemia from a mean age of 24 h. The infants were born after 24 to 26 weeks of gestation and weighed 730 +/- 172 g (mean +/- SD) at birth. Serum potassium concentration ranged from 7.4 to 8.4 mmol/l (7.7 +/- 0.4 mmol/l; mean +/- SD). Four had cardiac arrhythmias. All infants showed an initial response, serum potassium concentration decreased below 6.5 mmol/l in 5 +/- 2 h. In two infants, rebound hyperkalaemia occurred and was resistant to treatment; both infants died, one during an exchange transfusion. In the other 10 infants, infusions were ceased at a mean postnatal age of 53 h. Hyperglycaemia was the major problem during infusion and was resistant to increases in insulin concentrations. Normoglycaemia was achieved in 10 infants. The hypertonic solution consisted of a dextrose/insulin ratio of 2.2 +/- 0.6 g/IU, which delivered glucose at a rate of 0.46 +/- 0.15 g/kg/h, in addition to the pre-existing stable maintenance glucose intake.

Blood Glucose↗

PubMed1991

Biosensors based on membrane transport proteins.

We propose a novel class of biosensors based on membrane bound receptors or transport proteins as the sensing element. The protein is incorporated in a planar lipid bilayer which covers the transducer. The transducer may detect an electric current, a voltage, or a change in fluorescence. A prototype lactose sensor is presented which consists of a quartz slide covered by a lipid membrane containing the protein lactose permease from Escherichia coli. This protein is a lactose/H+ cotransporter, hence lactose in the external medium initiates lactose/H+ cotransport across the lipid membrane. This leads to a rise in proton concentration in the small volume between the lipid membrane and the quartz surface which can be detected by a pH-sensitive fluorescence dye.

Arylsulfonates↗

PubMed1991

Tracheal damage following conventional and high-frequency ventilation at low and high humidity.

OBJECTIVES: To compare the degree of tracheobronchial damage in newborn lambs ventilated for 6 hrs with relative humidities of 30% or 90% and continuous positive airway pressure breathing, conventional mechanical ventilation of 25 and 60 breaths/min, or high frequency flow-interrupted ventilation at 600 breaths/min. BACKGROUND AND METHODS: Tracheobronchial damage secondary to mechanical ventilation remains a major iatrogenic lesion of the newborn despite substantial advances in both mechanical design and ventilatory techniques. A histologic scoring system was used to compare the damage noted in the tracheobronchial epithelium of newborn lambs after 6 hrs of conventional mechanical ventilation or high-frequency flow-interrupted ventilation at two relative humidities. Three groups of animals were ventilated for 6 hrs with an FIO2 of 0.21 at 36.0 degrees C and relative humidity of 90%. The first group received continuous positive airway pressure of 4 cm H2O, the second group received slow rate, conventional mechanical ventilation at 25 breaths/min, and the third group received fast rate, conventional mechanical ventilation at 60 breaths/min. Two other groups of animals were ventilated for 6 hrs with an FIO2 of 0.21 at 36.0 degrees C and relative humidity of 30%. The first group was ventilated with high-frequency flow-interrupted ventilation at 600 breaths/min and the second group with slow rate, conventional mechanical ventilation at 25 breaths/min. Two additional groups served as nonintubated controls; one group was killed immediately after sedation and the other group was killed after 6 hrs of sedation. RESULTS: The damage was mild but significantly different from controls when 90% humidity was used and there was no difference in the histology score between continuous positive airway pressure breathing and conventional mechanical ventilation at 25 or 60 breaths/min. Significant inflammation, erosion, necrosis, and blistering occurred with both conventional mechanical ventilation at 25 breaths/min and high-frequency flow-interrupted ventilation at 600 breaths/min when 30% humidity was used. The damage was only found 5 mm below the tip of the endotracheal tube and not at 3.5 cm beyond the endotrachea tube in the trachea nor in the right main bronchus. CONCLUSION: These data indicate that endotracheal intubation and mechanical ventilation, regardless of the method of ventilation, cause damage to the tracheal mucosa, but that poorly humidified inspired gases cause significantly greater damage.

Animals↗

PubMed1991

Effect of short-term muscle relaxation on neonatal plasma volume.

OBJECTIVES: To study the effect of pancuronium-induced muscle relaxation on circulating plasma volume. DESIGN: A prospective, controlled study. Consecutive infants who were paralyzed with pancuronium and a comparative group who were not paralyzed during mechanical ventilation were studied. SETTING: Neonatal ICU of a regional referral university-affiliated hospital. PATIENTS: Newborn infants weighing greater than 1700 g who required respiratory assistance within 24 hrs of birth and who were free of congenital heart disease, sepsis, or blood loss were eligible for entry into the study. Infants who received colloid infusions during the study period were excluded. A total of 17 consecutive infants (nine paralyzed and eight nonparalyzed control infants) were studied. Four paralyzed infants and one nonparalyzed infant received colloid infusions before the completion of the study and were excluded from the final analysis. MEASUREMENTS: Plasma volume was measured three times in the paralyzed infants: a) immediately before the first dose of pancuronium, b) after 12 to 24 hrs, and c) greater than or equal to 12 hrs after the return of muscle activity, but before extubation. Plasma volume in the nonparalyzed, control infants was measured at the time of intubation, 12 to 24 hrs after commencing mechanical ventilation, and 12 hrs after extubation. Plasma volume was measured using the Evans blue dye dilution technique. RESULTS: There were no changes in the plasma volume or blood volume in the three measurements among both the paralyzed and nonparalyzed infants. CONCLUSION: Pancuronium-induced muscle relaxation in mechanically ventilated newborn infants weighing greater than 1700 g did not alter circulating plasma volume in 24 hrs.

Evans Blue↗

PubMed1991

Cost efficiency of neonatal nurseries: the significance of unit size.

The cost of neonatal intensive care is high, and human and financial resources are finite. It is therefore essential to provide such care efficiently in terms of costs while still maintaining standards of care. We looked at the relationship of unit size to cost and determined the optimum and minimum size of the unit in terms of cost efficiency. Our data suggest that units with fewer than 6 ventilator cots were less cost-efficient than those with more cots while those with 12 ventilator cots were the most efficient. The calculations were done only up to 16 ventilator cots. Similarly, level II units were most cost-efficient when attached to an intensive care unit and had over 16 cots.

Australia↗

PubMed1990

Epithelial damage beyond the tip of the endotracheal tube.

The effects of ventilator rate and inspired humidity on the large airway epithelium of newborn lambs have been studied using scanning electron microscopy. Significant deciliation, denudation and necrosis occurred at both high and conventional rates if the inspired gas had low humidity. The damage observed was mild in the high humidity groups.

Animals↗

PubMed1990

Biochemical and morphological characterization of the intra-acrosomal antigen SP-10 from human sperm.

The human sperm protein SP-10 was previously defined as a "primary vaccine candidate" by a World Health Organization Taskforce on Contraceptive Vaccines. By one- and two-dimensional immunoblots, we show that SP-10, extracted from ejaculated human sperm, demonstrated a polymorphism of immunogenic peptides from 18 to 34 kDa, a pattern that was conserved from individual to individual and was not altered by reducing agents. The majority of the antigenic peptides possessed isoelectric points of approximately 4.9. Immunocytochemistry on testis sections indicated that SP-10 was localized to round spermatids and spermatozoa within the adluminal compartment of the seminiferous epithelium. Immunofluorescence showed that SP-10 was not associated with the surface of acrosome-intact, ejaculated sperm. Light and electron microscopic immunocytochemistry localized SP-10 throughout the acrosome, and electron microscopic evidence demonstrated a bilaminar array in association with the inner aspect of the outer acrosomal membrane and the outer aspect of the inner acrosomal membrane. After induction of the acrosome reaction with the ionophore A23187, SP-10 remained displayed on the sperm head in association with the inner acrosomal membrane and equatorial segment. The results indicate that the MHS-10 monoclonal antibody may be used as a marker of acrosome development in the human and as a probe to evaluate acrosome status. The results also support the hypothesis that inhibition of sperm-egg interaction by anti-SP-10 monoclonal antibody may occur as a result of antigen exposure following the acrosome reaction.

Acrosome↗

PubMed1990

Identification of human acrosomal antigen SP-10 in primates and pigs.

The intra-acrosomal human sperm protein SP-10 was previously designated a "primary vaccine candidate" by a World Health Organization Taskforce on Contraceptive Vaccines. In the present study, a monoclonal antibody to SP-10 (MHS-10) was employed on Western blots to identify immunoreactive SP-10 in sperm extracts from baboon (Papio cyanocephalus anubis) and two macaques (Macaca mulatta and Macaca fascicularis). In each of these primates, the MHS-10 monoclonal antibody recognized a polymorphic pattern of immunoreactive peptides similar to that in humans. Immunoreactive SP-10 was also demonstrated in pig sperm. Using purified preparations of the previously described intra-acrosomal molecules acrosin and sperminogen in the pig, we observed that the MHS-10 monoclonal antibody did not react with these proteins, indicating SP-10 is distinct from these known acrosomal components. Sperm from several common species including the rabbit, bull, rat, guinea pig and cat did not immunoreact with the MHS-10 monoclonal antibody. By use of a radioactive probe spanning 628 nucleotides of the open reading frame for SP-10 on Northern blots of poly A + RNA obtained from testes of Macaca fascicularis, Papio papio, and Papio cyanocephalus anubis, a 1.35-kb mRNA of identical size to the mRNA from human testes was identified. These results indicate that baboons, macaques, and pigs may be appropriate models for testing an SP-10-based contraceptive vaccine.

Acrosome↗

PubMed1990

Cloning and sequencing of cDNAs coding for the human intra-acrosomal antigen SP-10.

cDNAs coding for the intra-acrosomal protein SP-10 were cloned and characterized as a first step in understanding the expression of this antigen during spermatogenesis. Three overlapping SP-10-specific cDNAs were isolated from a human testes cDNA expression library. These cDNAs hybridized to a 1.35-kb mRNA that was present in human testes but was not found in liver or placenta. Complete sequencing of these cDNAs, designated SP-10-5, SP-10-8, and SP-10-10, produced an 1117-bp sequence containing a 265-amino acid-coding region for the SP-10 protein. Hydrophobicity plots generated from the deduced amino acid sequence showed a very hydrophobic amino terminus characteristic of a signal peptide. Sequence data showed that three different amino acid repeats occurred a total of 16 times in the central third of the SP-10 protein. Interestingly, cDNA SP-10-10 has an internal 57-base pair (19 amino acids) in-frame deletion that is not present in SP-10-5, suggesting that alternative splicing generates more than one SP-10 mRNA. The SP-10 protein appears to be a unique acrosomal protein, based on previous immunohistological data and the observation that SP-10 cDNA sequences did not show any significant homology to other sequences found in the Genbank, National Biomedical Research Foundation, or Swiss sequence banks. A recombinant SP-10 fusion protein was produced in an Escherichia coli expression vector and used to generate a polyclonal antiserum. This antiserum stained the acrosomal cap in situ and reacted with a similar set of peptides on Western blots as did a monoclonal antibody to SP-10.

Acrosome↗

PubMed1990

Risk factors in progression beyond stage 2 retinopathy of prematurity.

Of the 96 babies born at less than 30 weeks gestation at Westmead Hospital between January 1986 and December 1987, 91 were studied. Of these 37 developed some form of retinopathy of prematurity (ROP), with eight babies having stage 3 or worse. We compared the clinical features of these eight babies to a control group of eight babies with stage 2 ROP, having matched for gestational age. Factors of statistical significance in progression beyond stage 2 were male sex and number of days of assisted ventilation. The presence of a patent ductus arteriosus, although not statistically significant, is a factor which we consider to be clinically important. The development of Plus disease is associated with a poor prognosis.

Australia↗

PubMed1989

Topical iodine-containing antiseptics and neonatal hypothyroidism in very-low-birthweight infants.

The thyroid function of very-low-birthweight (VLBW; below 1500 g) infants admitted to neonatal intensive-care units was studied at two hospitals; one routinely used topical iodinated antiseptic agents and the other used chlorhexidine-containing antiseptics. Serial monitoring of urinary iodine excretion and serum thyrotropin and thyroxine levels was undertaken from birth for the first 4 weeks of life. Urinary iodine excretion rose dramatically in the 54 iodine-exposed infants and was up to fifty times greater than in the 29 non-exposed infants. Within 14 days, 25% (9 of 36) of the infants exposed to iodine had serum thyrotropin levels above 20 mIU/l, compared with none of the control group. The mean serum thyroxine level in these 9 infants (44.1 nmol/l) was significantly lower than that in exposed infants with normal thyrotropin levels (83.1 nmol/l) and in the non-exposed control group (83.0 nmol/l); thyroxine levels fell before serum thyrotropin rose. These disturbances in thyroid function correlated positively with urinary iodine excretion and hence iodine absorption. Thyroid function had returned to normal by the time of discharge from hospital. It is concluded that iodine absorption, from topical iodine-containing antiseptics, may cause hypothyroidism during a critical period of neurological development in the newborn infant. The routine use of iodine antisepsis in VLBW infants should be avoided because of this effect.

Administration, Topical↗

PubMed1989

Structural characterization of a metal-based perfusion tracer: copper(II) pyruvaldehyde bis(N4-methylthiosemicarbazone).

Copper(II) pyruvaldehyde bis(N4-methylthiosemicarbazone), Cu(PTSM), has been obtained as a dark red crystalline solid from EtOH-DMSO solvent mixture and structurally characterized by x-ray crystallography. The molecule possesses the expected pseudo-square planar N2S2 metal coordination sphere; however, the copper center also interacts through its axial coordination site with the sulfur atom of an adjacent Cu(PTSM) molecule in the crystal lattice. The structure of this compound is compared with the structures of other metal complexes that have been proposed in the nuclear medicine literature as perfusion tracers.

Crystallography↗

PubMed1989

Surfactant therapy and spontaneous diuresis.

The effect of artificial surfactant therapy on renal function and the onset of spontaneous diuresis was prospectively evaluated in 19 infants with hyaline membrane disease in a double-blind, controlled study. Twelve infants were in the surfactant group; seven infants received placebo (0.9% saline solution). There was no difference in the time of onset of spontaneous diuresis (as defined by output greater than or equal to 80% of intake). The glomerular filtration rate, determined by endogenous creatinine clearance, was also similar in the surfactant- and placebo-treated infants during the first 3 days of life. The fractional excretion of sodium was significantly higher in the placebo group at 24 hours and 36 hours. Infants in the placebo group had a higher negative sodium balance than those in the surfactant group. Ventilatory status improved significantly soon after surfactant treatment, as evidenced by improvement in the alveolar/arterial oxygen pressure ratio and by a lower mean airway pressure. These data suggest that ventilatory status can be improved without diuresis; the factors that regulate diuresis are multiple and not fully understood.

Blood Gas Analysis↗