Circular dichroism and 1H and 31P nuclear magnetic resonance spectroscopy have been used to investigate complex formation between cytochrome c and the flavodoxins from Azotobacter vinelandii and Clostridium pasteurianum. Such complexes are known to be involved in the mechanism of electron transfer between these two redox proteins. A large increase in ellipticity in the Soret band of the cytochrome heme was observed upon formation of the Clostridium flavodoxin complex, whereas much smaller changes were found for the complexes with either Azotobacter flavodoxin or an 8 alpha-imidazolyl-FMN-substituted Clostridium flavodoxin analogue. Similarly, the magnitudes of the perturbations of the contact-shifted heme proton resonances obtained upon complexation of cytochrome c by Azotobacter flavodoxin were much smaller than those previously shown for Clostridium flavodoxin [Hazzard, J. T., & Tollin, G. (1985) Biochem. Biophys. Res. Commun. 130, 1281-1286]. 31P nuclear magnetic resonance measurements were also consistent with differences in the interactions between the components in the complexes of the two flavodoxins with cytochrome c. It is suggested that these spectral changes are due to a loosening or opening of the heme crevice upon Clostridium flavodoxin binding, which allows closer contact between the heme and flavin prosthetic groups and results in a faster rate of electron transfer. The implications of these observations for biological oxidation-reduction processes are considered.

Azotobacter↗

PubMed1987

Magnetic resonance imaging of the thoracic aorta.

Forty-one patients with a variety of suspected aortic lesions underwent magnetic resonance imaging (MRI) of the thoracic aorta. Patients were separated into 2 groups: Group A included 19 patients who underwent MRI after arteriography for comparison purposes and were evaluated retrospectively. Surgical confirmation was obtained in 9 of these patients. Group B included 22 patients who were studied prospectively because of abnormal chest x-ray, ultrasound or computerized tomographic findings and did not undergo arteriography before MRI. Two patients from this group had surgery. In group A, MRI correlated with the surgical or angiographic findings in 18 of 19 patients (95%). In group B, MRI was considered of diagnostic quality in all patients and no other invasive or noninvasive imaging modalities were needed for diagnosis and treatment. Thus, MRI will replace arteriography in a large proportion of patients with suspected thoracic aortic lesions.

Aorta, Thoracic↗

PubMed1987

Diagnostic imaging techniques in lung carcinoma.

For the early detection of lung cancer at a stage when it is localized and hence resectable, persons in a high-risk group should be screened periodically with sputum cytologic studies and chest radiographs. For determination of the intrathoracic extent of a lesion, posteroanterior and lateral chest radiographs should be followed by computerized tomography to evaluate the hila, mediastinum, pleura, and chest wall. Computerized tomographic examination of the chest should be extended to include the upper abdomen. The adrenal glands can be evaluated by such examination, but adequate examination of the liver requires both precontrast and postcontrast computerized tomography scans. The radiologic workup for assessing distant metastases to the liver, brain, or bone should be performed only when clinical and biochemical findings suggest such metastases. For detection of recurrent carcinoma following treatment, computerized tomograms of the chest are more sensitive than routine radiographs. Magnetic resonance imaging may prove useful in the future for initial staging and for differentiating posttreatment fibrosis from recurrent bronchogenic carcinoma.

Adrenal Gland Neoplasms↗

PubMed1987

Respiratory tract deposition of sodium cromoglycate is highly dependent upon technique of inhalation using the Spinhaler.

Sodium cromoglycate deposition has been studied following delivery of the drug by inhalation to six normal volunteers and two groups of ten patients using the Spinhaler. Plasma concentrations of the drug, and its urinary excretion have been related to the inhalation technique used for its delivery. An early peak concentration of sodium cromoglycate occurred in the plasma, thereafter the plasma concentration declined mono- or bi-exponentially with a terminal T1/2 of approximately 100 minutes in both patients and normal subjects. There was a marked between-subject variability in the plasma concentrations of sodium cromoglycate achieved, and in the areas under the plasma concentration-time curves of the drug. This reflects the variability between subjects in the amount of drug delivered to the respiratory tract. Most of this variability was due to differences in inhalation technique particularly with regard to inspiratory flow rate achieved and duration of breath-holding after inhalation. Thus careful instruction of patients is required to derive optimal dosing with sodium cromoglycate. It is recommended that patients inhale through the Spinhaler as rapidly as possible and then breath-hold for 10 seconds. These data provide a valuable background against which to study the relationship between the disposition of sodium cromoglycate, its site of action and its efficacy.

Administration, Inhalation↗

PubMed1987

Extrapulmonary effects of maintenance corticosteroid therapy with alternate-day prednisone and inhaled beclomethasone in children with chronic asthma.

Extrapulmonary effects of alternate-day prednisone and inhaled beclomethasone dipropionate therapy were examined in 24 and 32 children with asthma, respectively. Early morning serum cortisol values were significantly lower among patients receiving alternate-day prednisone than among patients receiving inhaled beclomethasone dipropionate and control subjects at 24 hours but not at 48 hours after an alternate-day prednisone dose. Urinary-free cortisol output during the second 24 hours of the alternate-day prednisone regimen were similar to values among patients receiving inhaled beclomethasone and were significantly lower than among control subjects for both groups. Mean heights among patients before being placed on maintenance corticosteroids were at the thirty-fifth percentile and were similar for both regimens. This was significantly lower than initial measurements for control subjects who, on average, were near the fiftieth percentile for both children with asthma not requiring maintenance corticosteroids and normal healthy Iowa children. Mean heights for both corticosteroid-treated groups remained at the thirty-fifth percentile after more than a 2-year average duration of follow-up. Heights of children with chronic asthma not requiring maintenance corticosteroids were initially significantly higher (fifty-first percentile) than the patients who subsequently required maintenance corticosteroids and increased significantly to the sixty-first percentile during a mean 2.7-year follow-up. Heights of healthy Iowa children remained near the fiftieth percentile during a mean 7-year follow-up. Disproportionate weight gain, although it was not consistently present, was significantly more likely with the alternate-day prednisone. Other extrapulmonary effects of the corticosteroid regimens appeared not to be of clinical importance during the time period of the study.

Administration, Inhalation↗

PubMed1987

Risk factors for alcohol hepatotoxicity among male alcoholics.

Alcoholic liver cirrhosis is a leading cause of morbidity and mortality in alcohol dependence. A common precursor to cirrhosis is alcoholic hepatotoxicity evident clinically by elevated serum liver enzymes. In this study 50 male patients with significant (greater than two times upper limits of normal) elevation of liver enzymes attending a veterans inpatient alcohol treatment center were matched by age and time since last drink to 50 male veterans without elevated liver enzymes. Patients with elevated liver enzymes were found to be more likely to be daily drinkers, less likely to indulge in binge drinking patterns or have alcoholic blackouts, and showed a trend towards a less severe pattern of alcoholism. Significant gamma glutamyl transferase (GGT) elevations were found in patients consuming an average of 7 beers/day for 5 years, and significant aspartate aminotransferase (AST) elevations were found in patients consuming a threshold of 12 beers/day for 10 years. These findings are consistent with current research suggesting alcoholic cirrhosis is a result of a threshold exposure to alcohol in alcoholics with an additional environmental or genetic risk factor.

Adult↗

PubMed1987

The pharmacokinetics of nedocromil sodium, a new drug for the treatment of reversible obstructive airways disease, in human volunteers and patients with reversible obstructive airways disease.

1. The plasma concentrations and urinary excretion of nedocromil sodium have been determined following single dose administration in six healthy volunteers dosed orally (1 mg kg-1) and intravenously (0.2 microgram kg-1 for 30 min). Similar parameters were measured in six volunteers and twelve asthmatic patients dosed by inhalation (4 mg). Multiple dose kinetic measurements were also made. 2. The intravenous data demonstrated that nedocromil sodium is a high clearance drug (10.2 +/- 1.3 ml min-1 kg-1). The data were fitted by a two compartment model with very rapid elimination from the central compartment (k10 = 0.088 +/- 0.021 min-1; beta = 0.013 +/- 0.002 min-1). 81% of the dose was excreted in the urine. 3. Oral absorption was low (2-3% of the dose) and contributed negligibly to the plasma profile after inhalation. 4. After inhalation of single doses of 4 mg in volunteers and patients plasma concentration rose rapidly, plateaued and then fell monoexponentially with a half-life of approximately 2 h. The data fitted a 'flip-flop' model with two absorption components. The extent of absorption was up to 6% of the dose with less in patients. 5. After multiple dosing with 4 mg four times daily for 7 days in volunteers negligible accumulation was observed. The pattern was similar in patients treated with 4 mg four times daily after 1, 6 and 12 months.

Administration, Inhalation↗

PubMed1987

The effect of molecular size on the nasal absorption of water-soluble compounds in the albino rat.

The nasal absorption of a range of water-soluble compounds with different molecular weights, 4-oxo-4H-1-benzopyran-2-carboxylic acid (mol. wt 190), p-aminohippuric acid (mol. wt 194), inulin (mol. wt 5200) and dextran (mol. wt 70,000), has been investigated in the male Wistar rat. Compounds were instilled into the nasal cavities of anaesthetized animals, and for comparison, similar doses were administered intravenously. Serial samples of bile and urine were collected for up to 6 h. Nasal absorption, estimated by comparison of the extent of excretion in bile and urine following intranasal and intravenous administration, was 100% for 4-oxo-4H-1-benzopyran-2-carboxylic acid (1 mg kg-1), 75% for p-aminohippuric acid (1 mg kg-1), 15% for inulin (0.1 mg kg-1) and 2.8% for dextran (0.25 mg kg-1). The log molecular weight gave a good linear correlation with the log per cent intranasally absorbed (correlation coefficient of -0.996). From the molecular weight relationship, these data infer aqueous channel mechanisms for the nasal absorption of water-soluble compounds.

Absorption↗

PubMed1987

Factors associated with motor vehicle accidents among male alcoholics.

Male alcoholics (N = 260) presenting for inpatient treatment were given a structured psychiatric interview that included questions about previous motor vehicle accidents while intoxicated. The histories of 57 patients who reported personal injury accidents were compared with those of 131 patients who did not report accidents. Patients reporting accidents were more severely ill and had an earlier onset of heavy drinking. Also, more patients with accidents belonged to a subgroup of alcoholics with antisocial personality. The identification of high-risk alcoholics may contribute to motor vehicle accident prevention.

Accidents, Traffic↗

PubMed1987

Cardiac tumors and thrombus: evaluation with MR imaging.

Thirty patients with a suspected cardiac or pericardial mass underwent MR imaging. Twenty-six also had two-dimensional (2D) echocardiography, and three also had CT; one patient had MR only. Overall, 18 (60%) of the 30 patients were found to have a mass lesion. The lesion was confirmed by biopsy, surgery, or unequivocal demonstration on CT, 2D echocardiography, and/or MR imaging. Fourteen of the lesions were soft-tissue or tumor masses, and four were thrombi. The findings on 2D echocardiography and MR were in agreement in 17 (65%) of 26 patients who had both studies. MR was equivocal or in error in two patients (7%), and 2D echocardiography was nondiagnostic in seven (27%). In all seven patients with equivocal 2D echocardiography, the diagnosis was made by MR. In the four patients who did not have 2D echocardiography, MR showed the mass clearly. MR imaging is useful in the diagnosis of cardiac mass lesions. It can be used effectively in addition to 2D echocardiography to increase the certainty of diagnosis, and it is useful when 2D echocardiography is equivocal or inadequate.

Adolescent↗

PubMed1986

Complete nucleotide sequence of the Escherichia coli recB gene.

The complete nucleotide sequence of the Escherichia coli recB gene which encodes a subunit of the ATP-dependent DNase, Exonuclease V, has been determined. The proposed coding region for the RecB protein is 3543 nucleotides long and would encode a polypeptide of 1180 amino acids with a calculated molecular weight of 133,973. The start of the recB coding sequence overlaps the 3' end of the upstream ptr gene, and the recB termination codon overlaps the initiation codon of the downstream recD gene, suggesting that these genes may form an operon. No sequences which reasonably fit the consensus for an E. coli promoter could be identified upstream of the proposed recB translational start. The predicted RecB amino acid sequence contains regions of homology with ATPases, DNA binding proteins and DNA repair enzymes.

Amino Acid Sequence↗

PubMed1986

Complete nucleotide sequence of recD, the structural gene for the alpha subunit of Exonuclease V of Escherichia coli.

Intracellular amplification of the Escherichia coli RecB and RecC proteins does not result in an increase in Exonuclease V activity unless the level of a third protein, encoded between the recB and argA genes, is also amplified. Nucleotide sequence analysis of this region reveals a 1,824 nucleotide open reading frame which would encode a protein of 608 amino acids with a calculated molecular weight of 66,973. This is assumed to be the structural gene for the alpha subunit of Exonuclease V, recently designated recD. The proposed initiation codon of the recD gene overlaps the termination codon of the upstream recB gene by one nucleotide, suggesting that these genes may form an operon. The deduced amino acid sequence of the RecD protein contains a region which is homologous to highly conserved sequences in adenine nucleotide binding proteins.

Amino Acid Sequence↗

PubMed1986

Complete nucleotide sequence of the Escherichia coli ptr gene encoding protease III.

The nucleotide sequence of a 3120 bp region of the E. coli chromosome that includes the entire ptr gene has been determined. The proposed coding region for Protease III is 2889 nucleotides long, which would encode a protein consisting of 962 amino acids with a calculated molecular mass of 107,719 daltons. The predicted primary structure of the protein includes a 23-residue signal sequence, cleavage of which would give rise to a mature protein of molecular mass 105,124 daltons. At its 3' end, the ptr gene overlaps the start of the recB coding sequence by 8 bases, suggesting that these genes may form part of an operon.

Amino Acid Sequence↗