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Biomedical subjects

D W Johnson

Publications and source records attributed to D W Johnson.

At least 19 recordsLinked to original sources

Massive epithelium-lined inclusion cysts after scleral buckling.

Two patients with massive epithelium-lined inclusion cysts of the orbit became symptomatic five and 16 years after scleral buckling. Each patient described diplopia and displacement of the previously treated eye. An orbitotomy in the first patient disclosed a loculated epithelium-lined inclusion cyst that extended posteriorly from the insertion of the inferior rectus muscle nearly to the apex of the orbit. In the second patient, a loculated epithelium-lined inclusion cyst extended into the superior nasal portion of the orbit from its origin near the insertions of the superior and medial recti muscles. We speculated that epithelial cells of the conjunctiva were shed at the time of scleral buckling and became lodged in the exposed sulcus created by the surgical retraction of Tenon's capsule. Here they proliferated and formed the large epithelium-lined cysts. In each patient, removal of the cyst was followed by a decrease in diplopia as the displaced globe returned toward its normal position.

Aged

Novel molecular species of sphingomyelin containing 2-hydroxylated polyenoic very-long-chain fatty acids in mammalian testes and spermatozoa.

Polyenoic very-long-chain fatty acids (VLCFA) have been shown to be localized in unusual molecular species of sphingomyelin in the testes and spermatozoa of the ram, bull, rat, and boar and in the spermatozoa of man. The composition of polyenoic VLCFA-sphingomyelin was comparable in the testes and spermatozoa of each mammalian species; however, the sphingolipid was more concentrated in spermatozoa. The composition of testicular and spermatozoan polyenoic VLCFA-sphingomyelin differed considerably between animal types. Human spermatozoa mainly contained n-6 polyenoic VLCFA with two to four double bonds and even-carbon chain lengths up to 32. In ram and bull testes and spermatozoa, n-3 and n-6, tetra-, penta-, and hexaenoic VLCFA with even-carbon chain lengths up to 34 predominated. In rat and boar testes and spermatozoa, the polyenoic VLCFA were mainly n-6 derivatives with three to five double bonds and even- and odd-carbon chain lengths up to 34. The testes and spermatozoa of the latter two animal species contained 2-hydroxylated, in addition to non-hydroxylated, polyenoic VLCFA in sphingomyelin. This is the first time that 2-hydroxylated polyenoic VLCFA have been recognized in biological systems. Non-hydroxylated polyenoic VLCFA were initially observed in the sphingomyelin of rat testes 25 days after birth, followed by 2-hydroxylated derivatives at 30 days. The total amount of polyenoic VLCFA associated with rat testicular sphingomyelin increased dramatically from 25 to 40 days of postnatal life and then remained constant to 60 days (sexual maturity). The ratio of 2-hydroxylated to non-hydroxylated polyenoic VLCFA increased during this period. Polyenoic VLCFA-sphingomyelin seems to occur exclusively in the testes and spermatozoa of mammals, and it is postulated that this lipid plays a role in reproduction.

Animals

Very long-chain fatty acids in peroxisomal disease.

Fatty acids with from 24 to 28 carbon atoms (very long-chain fatty acids, VLCFA) are present in small amounts in all mammalian tissues. Even longer chain fatty acids with from 30 to 38 carbon atoms (ultra-long-chain fatty acids, ULCFA) are found in certain specialized tissues including retina, brain, and spermatozoa. In patients with inherited defects in peroxisomal structure and/or function, there is an accumulation of VLCFA in most tissues, while VLCFA and ULCFA levels are increased in brain. The most pronounced changes occur in those patients who have defects in peroxisomal assembly (Zellweger syndrome, infantile Refsum's disease, and neonatal adrenoleukodystrophy). In the brain of these individuals, ULCFA are distributed largely in molecular species of phosphatidylcholine with penta-, hexa-, and heptaenoic acids. In contrast, patients with X-linked adrenoleukodystrophy have increased levels of phosphatidylcholine with monoenoic rather than polyenoic ULCFA. A defect in a peroxisomal VLCFA CoA synthetase or ligase has been reported for these patients, but assembly of their peroxisomes is apparently normal. We speculate that ULCFA are normal products of carbon chain elongation. We have confirmed this by demonstrating the elongation of [1-14C]hexacosatetraenoic acid (26:4n-6) by rat brain in vivo to a series of longer chain tetraenoic acids with carbon chain lengths up to 34. Elongation to ULCFA can occur as well in non-neural tissues as shown by detection of labeled saturated and monoenoic fatty acids with up to 32 carbon atoms after incubation of normal and Zellweger syndrome fibroblasts with [2-14C] acetate. Increased labeling of VLCFA and ULCFA is observed in cells from patients with peroxisomal disorders. Our data suggest that ULCFA with up to at least 32 carbon atoms are formed normally, as a part of the elongation process in most mammalian tissues, and that control of carbon chain elongation is a major function of peroxisomes. Impairment of this function as occurs in peroxisomal disease results in the accumulation of VLCFA and ULCFA. The relative enrichment in normal tissues of ULCFA such as 32:6n-3 in ram and bull spermatozoa and 36:4n-6 in human and rat brain suggests a probable physiological role for this class of fatty acids in these tissues.

Adolescent

Monoenoic fatty acids in human brain lipids: isomer identification and distribution.

The carbon chain length distribution and the double bond positional isomer composition of the monoenoic fatty acids of the lipids of total human brain tissue have been determined using gas chromatography and gas chromatography/mass spectrometry of the fatty acid methyl and picolinyl esters. The even chain length monoenoic C16 to C28 fatty acids contain predominantly two positional isomer series, the n-7 and n-9 cis homologues, whose relative proportion varies significantly with chain length. The odd chain length long-chain fatty acids consist of n-8 and n-10 isomers, whereas the odd chain length very long-chain (more than 22 carbon) fatty acids are n-7 and n-9 isomers.

Adolescent

The Anticarsia gemmatalis nuclear polyhedrosis virus polyhedrin gene region: sequence analysis, gene product and structural comparisons.

The genomic region of the Anticarsia gemmatalis multiple nucleocapsid nuclear polyhedrosis virus (AgMNPV) strain 2D encoding the polyhedrin gene was cloned and mapped, and a 2085 bp SphI-PstI fragment containing the gene was sequenced. The polyhedrin polypeptide of the parental isolate AgMNPV was manually sequenced, and the amino acid sequence obtained agreed with that deduced from the DNA coding region sequence. AgMNPV and Orgyia pseudotsugata MNPV (OpMNPV) are similar in terms of promoter structure and polyhedrin primary sequence, and the polyhedrin gene of both viruses is transcribed in the anti-clockwise direction in relation to their physical maps. The region upstream from the polyhedrin gene of AgMNPV, OpMNPV, Bombyx mori NPV and Autographa californica MNPV (AcMNPV) was compared and this showed that the open reading frame (ORF) common to all four viruses (ORF 5) has sequence homology with the AcMNPV 25K gene. The sequences between ORF 5 and the polyhedrin gene were found to be variable among the polyhedrin gene loci compared. Additionally, conserved elements in the promoters of the very late genes encoding polyhedrin and granulin, and those encoding two p10 proteins were found to share sequence homology and positional similarity with consensus regions in the conserved boxes A and C, responsible for binding transcription factors to eukaryotic 5S ribosomal RNA genes, and to box C of tRNA genes.

Amino Acid Sequence

Hypertension with hemodilution prevents multifocal cerebral hypoperfusion after cardiac arrest in dogs.

BACKGROUND: Improved neurological outcome with postarrest hypertensive hemodilution in an earlier study could be the result of more homogeneous cerebral perfusion and improved O2 delivery. We explored global, regional, and local cerebral blood flow by stable xenon-enhanced computed tomography and global cerebral metabolism in our dog cardiac arrest model. METHODS: Ventricular fibrillation cardiac arrest of 12.5 minutes was reversed by brief cardiopulmonary bypass, followed by life support to 4 hours postarrest. We compared control group I (n = 5; mean arterial blood pressure, 100 mm Hg; hematocrit, greater than or equal to 35%) with immediately postarrest reflow-promoted group II (n = 5; mean arterial blood pressure, 140-110 mm Hg; hypervolemic hemodilution with plasma substitute to hematocrit, 20-25%). RESULTS: After initial hyperemia in both groups, during the "delayed hypoperfusion phase" at 1-4 hours postarrest, global cerebral blood flow was 51-60% of baseline in group I versus 85-100% of baseline in group II (p less than 0.01). Percentages of brain tissue voxels with no flow, trickle flow, or low flow were lower (p less than 0.01) and mean regional cerebral blood flow values were higher in group II (p less than 0.01). Global cerebral oxygen uptake recovered to near baseline values at 3-4 hours postarrest in both groups. Postarrest arterial O2 content, however, in hemodiluted group II was 40-50% of that in group I. Thus, the O2 uptake/delivery ratio was increased (worsened) in both groups at 2-4 hours postarrest. CONCLUSIONS: After prolonged cardiac arrest, immediately induced moderate hypertensive hemodilution to hematocrit 20-25% can normalize cerebral blood flow patterns (improve homogeneity of cerebral perfusion), but does not improve cerebral O2 delivery, since the flow benefit is offset by decreased arterial O2 content. Individualized titration of hematocrit or hemodilution with acellular O2 carrying blood substitute (stroma-free hemoglobin or fluorocarbon solution) would be required to improve O2 uptake/delivery ratio.

Animals

The use of vaccines in renal failure.

Renal insufficiency is characterised by impaired host defences, which are compromised further by each of the 3 modes of renal replacement--haemodialysis, continuous ambulatory peritoneal dialysis (CAPD) and renal transplantation. Reduced renal clearance of unknown toxins, possible development of nutritional deficiencies and administration of immunosuppressive medications lead to aberrant immune regulation early in the course of renal failure. This results subsequently in increased frequency and severity of infection. Vaccination plays an important role in attenuating this infection risk, but impaired cell-mediated and humoral immunity contraindicates the use of live vaccines and engenders suboptimal and short-lived antibody responses to inactivated vaccines. Reinforced vaccination schedules, increased vaccine dosage and concomitantly administered adjuvant immunomodulators have variably improved the defective antibody responses to certain vaccines. Immunisation against hepatitis B virus has resulted in a significant decrease in prevalence and incidence of this infection in haemodialysis units. Similarly, the inoculation of influenza vaccine in patients with uraemia and of polyvalent pneumococcal vaccine in special risk circumstances has been recommended because of perceived reductions in morbidity and mortality from infection with these agents. Cytomegalovirus (CMV) vaccine may attenuate CMV disease severity in recipients of renal allografts. Staphylococcus aureus vaccine, on the other hand, is ineffective in preventing peritonitis or exit site infections in patients receiving CAPD. Other killed vaccines have not been comprehensively studied, but generally have the same indications for use as in normal individuals. However, the protection that these vaccines afford may be either inadequate or transient, so that other infection control strategies should be simultaneously implemented.

Bacterial Infections

Effects of compensatory growth on some body component weights and on carcass and noncarcass composition of growing lambs.

A trial was conducted in 1983 and repeated in 1984 to measure effects of restricted feed intake and realimentation on weights of organs and on carcass and noncarcass composition. A total of one hundred six weaned lambs from two breeds (Timahdit and D'man) and a breed cross (Ile de France x D'man) were used in both years. Lambs were allotted to one of six feed intake regimens: HH (ad libitum access to feed from 21 to 30 kg); HM (ad libitum access to feed from 21 to 26 kg then 70% ad libitum to 30 kg); MH (70% ad libitum from 21 to 26 kg then ad libitum to 30 kg); MM (70% ad libitum from 21 to 30 kg); LH (restricted to lose weight from 21 to 17 kg then ad libitum to 30 kg); and LM (restricted to lose weight from 21 to 17 kg then 70% ad libitum to 30 kg). Weights of visceral organs and mesenteric and kidney fat showed dramatic responses to alteration of feed allowances. After recovery from 20% live weight loss, weight of liver equaled or exceeded that of both the ad libitum and 70% refed lambs. Mesenteric and kidney fat did not. Refeeding was accompanied by an increase in water (P less than .05) and a decrease in fat (P less than .01) of both carcass and noncarcass components. These results indicate that weight loss of lambs incurred during feed shortage was largely in internal organ weights, and that these lambs can recover these losses during realimentation and undergo compensatory growth with better feed efficiency and lean carcasses.

Adipose Tissue

Effects of undernutrition and refeeding on weights of body parts and chemical components of growing Moroccan lambs.

Forty-four intact, male lambs (20 Timahdit and 24 D'man) were used to assess the effects of 22% (from approximately 25 to approximately 20 kg) and 31% (from approximately 25 to approximately 17 kg) live weight loss and the subsequent refeeding to initial BW on changes in body components. Body composition was determined using a serial slaughter technique at 17, 20, and 25 kg live weight during normal growth, weight loss, and refeeding phases. Reduction in live weight from 25 to 20 kg was associated with greater loss of visceral organs (30%) and internal fat (75%) than carcass loss (19%). Further body weight loss (from 20 to 17 kg) involved carcasses to a greater extent than internal organs. The composition of BW loss consisted of 53% water, 28% fat, and 15% protein. Refeeding was associated with a rapid increase in organ weights and less fat regeneration. Although total internal organs recovered only 90% of their original weight, liver and kidneys regained all their weight. At the same slaughter weight, carcass and noncarcass components of refed lambs were leaner because of lower fat content in these components.

Adipose Tissue

The cost of quality assurance/quality control.

Good Manufacturing Practice Guidelines have an inherent philosophy to maintain high standards and to promote uniformity within trading areas. Reaching these standards in some countries and maintaining them in others is costly. The Cost of Quality is regarded as a significant indicator of business performance. Quality costs are increasing as demands for improved accuracy and precision are made on the industry. The paper also details actual costs for validating a modern biological production facility and establishing biological quality control facilities. Bench mark quality control testing costs for a typical large and small animal vaccine are given.

Animals

Quick blots and nonradioactive detection of DNA probes for the identification of mosquitoes.

The quick blot protocol is an improved technique for preparing crude insect homogenates for hybridization to nucleic acid probes. Individual insects are ground in wells of a microtiter plate and transferred to a dot blot manifold. This allows preparation of multiple filters and provides uniformity and an orderly arrangement of samples. The high background detection resulting from use of crude insect homogenates with nonradioactive detection systems was eliminated by incubating quick blot filters in a laundry stain remover containing proteases. We used mosquito species-specific DNA probes to demonstrate the effectiveness of nonradioactive DNA labeling systems with quick blots.

Animals

Herpes simplex type 1 infections in group day care.

To characterize patterns of herpes simplex virus type 1 infection, illness and transmission among children in group day care, the data for 115 children who had been followed longitudinally from early infancy in a research day care center were examined. By 5 years of age 37% of study children had evidence of herpes simplex virus type 1 infection as demonstrated by virus isolation and/or seroconversion. The incidence of infection was highest among children 1 to 2 years old. Four small clusters of primary infections were observed over the 12-year study period but no cluster involved more than 6 children. Fifty-five percent of primary infections occurred during these small outbreaks; the remainder were sporadic. Gingivostomatitis was observed in 26% of children with primary culture-proved infections; no child with infection identified solely by serologic means had a history of gingivostomatitis. The occurrence of gingivostomatitis did not appear to be associated with increased transmission of herpes simplex virus type 1 infection in this day-care setting.

Antibodies, Viral

Effects of U74006F on multifocal cerebral blood flow and metabolism after cardiac arrest in dogs.

Lipid peroxidation reactions during reperfusion after cardiac arrest may contribute to postischemic cerebral hypoperfusion, which in turn can contribute to permanent neurological dysfunction. We designed this study to determine whether the aminosteroid U74006F, a putative inhibitor of lipid peroxidation, mitigates cerebral multifocal hypoperfusion after cardiac arrest. We used our established dog model of ventricular fibrillation cardiac arrest (no blood flow) of 12.5 minutes, reperfusion by cardiopulmonary bypass of less than or equal to 5 minutes, and control of extracerebral variables during 4 hours postarrest. Cerebral blood flow was monitored by the stable xenon computed tomography method. Changes in cerebral oxygen consumption were obtained from mean blood flow values of coronal slices and the cerebral arteriovenous (sagittal sinus) oxygen content difference. A treatment group (n = 5) received U74006F starting with reperfusion (1.5 mg/kg i.a. plus 1.5 mg/kg i.v.) and three additional (graded) doses over 4 hours (total dose 4.5, 7.5, or 14.5 mg/kg). The U74006F-treated group showed the same postarrest transient hyperemia and protracted hypoperfusion in terms of global (computed tomography slice), regional, and local (multifocal) cerebral blood flow values and the same global cerebral oxygen consumption pattern as a concurrent control group (n = 5). At 1-4 hours postarrest, in both groups there was mismatching of global cerebral oxygen consumption, which reached baseline values, in relation to global cerebral blood flow and oxygen delivery, which remained at 50% of baseline. We conclude that treatment with U74006F after prolonged cardiac arrest causes no deleterious side effects and does not seem to alter multifocal postarrest cerebral blood flow and oxygen consumption.

Animals

Exogenous opioids increase plasma prolactin in Holstein calves primarily via a dopaminergic mechanism.

A study was conducted to determine whether exogenous opioids increase prolactin (PRL) secretion in Holstein heifer calves via a dopaminergic mechanism. Twenty-four Holstein heifer calves ranging in age from 5 to 7 mo were assigned to one of four treatment groups (six/treatment): 1) injection of saline (SAL); 2) injection of a synthetic enkephalin (D-Ala2, N-Me-Phe4, Met(O)5-ol enkephalin; DAMME); 3) injection of DAMME after pretreatment with the long-acting dopamine agonist 2-bromo-alpha-ergocryptine; or 4) injection of thyrotropin-releasing hormone (TRH) after pretreatment with 2-bromo-alpha-ergocryptine. Calves were equipped with indwelling jugular cannulas on d 1, and baseline plasma PRL concentrations were established. Animals receiving 2-bromo-alpha-ergocryptine were injected s.c. 3 h after the last baseline sample was drawn on d 1. On d 2, calves assigned to receive SAL, DAMME, or TRH were injected 2 h after the start of sampling, and sampling was continued for an additional 4.5 h. Basal plasma PRL was lower (P less than .01) on d 2 in calves injected with 2-bromo-alpha-ergocryptine than baseline levels on d 1. Plasma PRL was higher (P less than .01) in calves not pretreated with 2-bromo-alpha-ergocryptine after DAMME injection on d 2 but was not different after DAMME injection in calves pretreated with 2-bromo-alpha-ergocryptine. In contrast, plasma PRL increased (P less than .01) after TRH injection on d 2 in calves pretreated with 2-bromo-alpha-ergocryptine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Non-small cell lung cancer: treatment results at a USAF referral center.

The treatment results of 197 consecutive patients with non-small cell carcinoma of the lung managed at David Grant USAF Medical Center between January 1978 and September 1985 were reviewed. Patients were staged according to 1983 AJCC criteria as follows: 52 stage I, 28 stage II, and 117 stage III. Five-year survival and freedom from relapse (FFR) were 24% and 32%, respectively, for the entire population. Survival and FFR by stage were: stage I, 68% and 77% (5-year); stage II, 32% and 43% (5-year); and stage III, 10% and 10% (3-year), respectively.

Adult

Metabolism of hexacosatetraenoic acid (C26:4,n-6) in immature rat brain.

Rat brain was recently found to contain polyenoic very-long-chain fatty acids (VLCFA) belonging to the n-3 and n-6 series with four, five and six double bonds and even-carbon chain lengths from 24 to 38 [Robinson, Johnson & Poulos (1990) Biochem. J. 265, 763-767]. In the present paper, the metabolism in vivo of hexacosatetraenoic acid (C26:4,n-6) was studied in neonatal rat brain. Rats were injected intracerebrally with [1-14C]C26:4,n-6 and the labelled metabolites were examined after 4 h. Radioactivity was detected mainly in non-esterified fatty acids, with smaller amounts in other neutral lipids and phospholipids. Radiolabelled fatty acid products included C28-36 tetraenoic and C26-28 pentaenoic VLCFA formed by elongation and desaturation of the substrate, and C14-24 saturated, C16-24 monoenoic, C18-24 dienoic, C18-22 trienoic and C20-24 tetraenoic fatty acids formed from released [1-14C]acetate either by synthesis de novo or by elongation of endogenous fatty acids. The data suggest that polyenoic VLCFA are synthesized in brain from shorter-chain precursor fatty acids and undergo beta-oxidation.

Animals

Unique molecular species of phosphatidylcholine containing very-long-chain (C24-C38) polyenoic fatty acids in rat brain.

Rat brain has been shown to contain polyenoic very-long-chain fatty acids (VLCFA) belonging to the n-3 and n-6 series with four, five and six double bonds and even-carbon chain lengths from 24 to 38. These fatty acids are almost exclusively located in unusual molecular species of phosphatidylcholine at the sn-1 position of the glycerol backbone, whereas saturated, monoenoic and polyenoic fatty acids with less than 24 carbon atoms are present at the sn-2 position. Polyenoic VLCFA phosphatidylcholine in neonatal rat brain is enriched with n-6 pentaenoic and n-3 hexaenoic VLCFA with up to 36 carbon atoms, whereas the corresponding phospholipid in adult rat brain mainly contains n-6 tetraenoic and n-3 pentaenoic VLCFA with up to 38 carbon atoms. The total amount of polyenoic VLCFA associated with phosphatidylcholine is highest in the brain of immature animals. Polyenoic VLCFA phosphatidylcholine appears to be predominantly confined to nervous tissue in rats, and it is envisaged that this phospholipid is of physiological significance.

Animals