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Biomedical subjects

D D Johnson

Publications and source records attributed to D D Johnson.

At least 91 records · Page 5Linked to original sources

Familial pericentric and paracentric inversions of chromosome 1.

We investigated 33 individuals (21 carriers) from one family with a pericentric inversion involving a large part of chromosome 1 (1p36.1----1q32). In addition, we investigated 15 individuals (10 carriers) from another family with a paracentric inversion of a small part of chromosome 1 (1p32----1p36.1). In each family, the index patient was ascertained because three miscarriages had occurred. Each carrier of these inversions was phenotypically normal. If the miscarriages of the index patients are excluded, the frequency of recognized miscarriages among the carriers of childbearing age was 9% (4 of 46) for the family with pericentric inversion and 17% (4 of 23) for the family with paracentric inversion. One of the pericentric inv(1) carriers had had a stillborn daughter. The carriers of the pericentric inversion who were of childbearing age had 41 children; carriers of the paracentric inversion who were of childbearing age had 19 children. No live-born children with birth defects were observed in either family. This evidence, together with the low frequency of miscarriages, suggests that crossover within the inversion loop occurs much less frequently than might be expected from the large size of this inversion. Our investigation suggests that the risk of recognized miscarriages, stilbirths, and live-born children with recombinant chromosomes who have birth defects may be much lower for inv(1) carriers than previously reported. The risk of having a malformed child because of a recombinant chromosome is probably less than 3% for carriers of the pericentric inversion and less than 6% for the carriers of the paracentric inversion.

Chromosome Banding↗

Combined rotavirus and K99 Escherichia coli infection in gnotobiotic pigs.

Fifty nine 3-day-old gnotobiotic pigs were randomly assigned to 4 experimental groups: 14 pigs were orally inoculated with rotavirus (RV), 14 were orally inoculated with enterotoxigenic Escherichia coli (ETEC), 18 were orally inoculated with both agents, and 13 were controls. Pigs inoculated with RV plus ETEC were given the RV inoculum at 3 days of age and then, 24 hours later, were given the ETEC inoculum. Three pigs inoculated only with RV, 3 pigs inoculated only with ETEC, 4 pigs inoculated with RV plus ETEC, and 3 pigs in the control group were euthanatized at 5 and 7 days of age. Two pigs in each of the 4 experimental groups also were euthanatized at 9 days of age. Intestinal segments from 6 sites in the small intestine were examined by virologic, bacteriologic, and histologic procedures. For 10 days after inoculation, the remaining pigs in each group were observed clinically to monitor severity and duration of diarrhea, mortality, and shedding of RV or ETEC. Pigs inoculated with the combined RV plus ETEC inoculum developed more severe diarrhea, compared with pigs inoculated with the single agents; all dually inoculated pigs died between 3 and 6 days after inoculation. There was no mortality in pigs inoculated with either RV or ETEC. Lesions were restricted to the small intestine in pigs inoculated with RV plus ETEC and in pigs inoculated with RV or ETEC. There was no difference in the severity of the villus atrophy between the dually inoculated pigs and pigs inoculated only with RV.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Benzodiazepine antagonist Ro 15-1788 (flumazepil) attenuates the anticonvulsant activity of diazepam in epileptic fowl.

The ability of the imidazobenzodiazepine Ro 15-1788 to displace diazepam from brain membranes in vitro and to antagonize the anticonvulsant activity of diazepam in vivo was determined in epileptic fowl. At doses of 1.0 mg/kg and higher, Ro 15-1788 significantly attenuated the anticonvulsant action of diazepam (1.0 mg/kg) in epileptic chickens. Ro 15-1788 alone exerted no anticonvulsant activity even in doses as high as 10 mg/kg. Specific binding of 10 nM [3H]diazepam to whole homogenate fractions prepared from cerebral hemispheres of epileptic fowl was inhibited by Ro 15-1788 with an IC50 of 8.5 nM and the Ki was determined to be 4.25 nM. These results suggest that Ro 15-1788 competes directly with diazepam for a binding site involved in producing anticonvulsant activity.

Animals↗

Omental pedicle graft in the management of infected ascending aortic prostheses.

Two patients had mediastinal infections with chronic draining sinus tracts that involved a vascular prosthesis in the ascending aorta. In 1 patient, a false mycotic aneurysm developed and in the other, a beginning rupture of the proximal suture line. In both patients, the infection was cured by replacing the infected aortic prosthesis combined with wrapping the new prosthesis with a pedicled omental graft. An omental graft was used to protect the vascular prosthesis and minimize the risk of recurrent infection.

Adult↗

Duplication of 7q31.2----7qter and deficiency of 18qter: report of two patients and literature review.

We describe two male patients with a 46,XY,-18,+der(18),t(7;18) (q31.2;q23)mat karyotype. Previously, 22 other patients with dup(7q) have been described, but only four of them had duplication of segment 7q31----7qter. The two patients in this study were ascertained independently and lived in different states. However, because of the rarity of this translocation, the patients were suspected to be related. The families were investigated extensively, and the patients were found to be third cousins once removed. Both patients had severe hypospadias, large fontanelles, cleft palate, and minor facial anomalies (square and prominent forehead, short, downslanting palpebral fissures, long eyelashes, long philtrum, short nose, thin vermilion border with downcurved upper lip). Their phenotypes were compared with those of previously described patients. One of the two patients described here is alive at 23 months and is the oldest known living patient with this chromosome abnormality. Apneic spells often are present and may be secondary to severe brain abnormalities, such as those identified in our two patients.

Abnormalities, Multiple↗

A comparison of methods for removal of endogenous GABA from brain membranes prepared for binding assays.

Two commonly used procedures for removing endogenous GABA from brain homogenates were evaluated by measuring residual GABA using high performance liquid chromatography (HPLC). The effect of these treatments on [3H]muscimol binding to the GABA receptor was also determined. Membranes subjected to osmotic lysing and eight washes with Tris-citrate buffer contained significant quantities of residual GABA whereas lysing and incubation with Triton X-100 followed by three buffer washes resulted in GABA levels below the limits of detection. The apparent affinity for [3H]muscimol was significantly higher in the Triton X-100 treated membranes and this was probably a result of the lower amount of GABA present in these membranes. The effect of Triton treatment or buffer washing on residual levels of glutamate, glutamine, aspartate, and taurine were also determined.

Animals↗

Necropsy of sheep and goats.

In this article, diseases will be discussed by system. Common differential diagnoses that may be associated with gross lesions are pointed out, and practical laboratory tests are presented that may help establish a specific diagnosis.

Animals↗

Necropsy of the suckling calf.

In this article, diseases will be discussed by system and comments will be made on gross lesions, their interpretation, and various tests available to confirm or rule out differential diagnoses.

Animal Population Groups↗

Photically-induced retinal damage in diabetic rats.

The present study examines the interaction of light damage to the retina and streptozotocin (SZ)-induced diabetes in male and female rats during the early development of the disease, when changes occur in the blood-retinal barrier and in pigment cell membranes. Exposure of rats to low illuminance was used to determine the relationship between photically-induced cell death and diabetes. Other groups of animals were exposed to a greater illuminance for shorter time periods (24 hours) in attempts to identify a specific post-treatment day for the effect of diabetes. Blood glucose levels were monitored to indicate the severity of the diabetes. Morphometric analyses and histopathologic observations demonstrated that the outer nuclear layer (ONL, photoreceptor nuclei) was reduced significantly in thickness in female rats exposed to light during a 9 day period after SZ injection, but was unchanged from the control groups when exposed beginning at 12 days after SZ treatment. Removal of the pituitary gland prior to SZ treatment and light exposure resulted in the survival of more photoreceptor cells and prevented the differential in ONL thickness observed between control and diabetic intact animals. Attempts to establish a period of greatest susceptibility of the diabetic retina to photic damage were unsuccessful, but results indicate that prior light history and/or shipment stress might be related to retinal damage from light exposure.

Animals↗

Pancreatic amylase, plasma glucose, and insulin responses to propionate or monensin in sheep.

Yearling wethers fitted with reentrant bile-pancreatic duct cannulae were in a two-part study of effects of duodenal propionate infusions or increased ruminal propionate caused by dietary monensin on pancreatic alpha-amylase secretion and glucose and insulin in blood plasma. Continuous duodenal infusion of propionate increased concentrations of glucose and insulin in blood plasma of wethers fed alfalfa. Results supported a direct response of insulin secretion to propionate. Amylase secretion was not affected. Addition of monensin (22 ppm) to an 80% corn diet reduced the ratio of acetate:propionate in rumen, but bile-pancreatic flow and amylase activity were unaffected. Monensin supplementation had little influence on glucose and insulin in blood plasma. Pancreatic alpha-amylase secretion of ruminants seems to be a complex phenomenon that is not regulated strictly by fluctuations of glucose or insulin.

Amylases↗

T-lymphocytes with 7;14 translocations: frequency of occurrence, breakpoints, and clinical and biological significance.

Among 11,915 consecutive patients and 37 normal controls who had chromosome analysis at the Mayo Clinic between 1978 and 1984, 83 had a single sporadic metaphase with a 7;14 translocation. In 81 of the translocations, the breakpoints were at 14q11 and either 7q34 (type I) or 7p13 (type II): type I translocations occurred in 42 patients, and type II, in 39. The two other translocations had different breakpoints: one was t(7;14)(q11;q32), and the other was t(7;14)(p13;q32). All type I and type II translocations occurred in phytohemagglutinin-stimulated lymphocyte cultures; their combined incidence was 4.88 X 10(-4) per metaphase (81 of 165,991 metaphases) in such cultures. No type I or II translocation was found among 6,713 fibroblast metaphases, 33,463 amniocyte metaphases, or 68,972 bone marrow and unstimulated peripheral blood metaphases. One variant 7;14 translocation occurred in a phytohemagglutinin-stimulated culture, and the other occurred in a fibroblast culture. We did not find a correlation of sporadic 7;14 translocations with any month or season of the year or with patient age or sex. Of the 83 patients, 78 had various clinical disorders, three had ataxia-telangiectasia, one was a normal control, and one was an artificial insemination donor. Follow-up studies on 64 (77%) patients indicate that, to date, none have developed any malignant process subsequent to chromosome analysis. Except for ataxia-telangiectasia, the occurrence of types I and II translocations in lymphocyte cultures may have little, if any, clinical significance. The biological significance of these translocations may be the association of genes in chromosome bands 14q11, 7p13, and 7q34 with the normal physiology of lymphocytes such as the alpha- and beta-chains for T-cell antigen receptor.

Adolescent↗

Phorbol ester inhibits myoblast fusion and activates beta-adrenergic receptor coupled adenylate cyclase.

Primary cultures of myoblasts, derived from embryonic chick pectoral muscle, were treated with phorbol ester (TPA) for 8-96 h. TPA treatment blocked the fusion of myoblasts along with the expression of the MM form of creatine kinase. Interestingly, TPA treatment markedly increased the activity of beta-adrenergic receptor coupled adenylate cyclase (AC) activity. The study suggests that TPA treatment augments the functional interaction between a coupling Ns protein and catalytic unit of AC. The likely significance of these results is briefly presented.

Adenylyl Cyclases↗

Deletions of chromosome 13 in malignant hematologic disorders.

Thirteen patients with a hematologic disorder and an interstitial deletion of part of a chromosome #13 were evaluated to determine if any specific clinical manifestations are associated with these cytogenetic anomalies. Our results suggest that these anomalies occur in approximately 1.7% of patients with a chromosomally abnormal clone and a hematologic disorder. They may occur as the sole chromosome anomaly (8 of our patients) or with other abnormalities (5 of our patients). The breakpoints are not always the same, but band 13q14 always seems to be lost. At the time of chromosome analysis, 5 patients had a history of myelofibrosis or agnogenic myeloid metaplasia, 2 had acute nonlymphocytic leukemia, 2 had a myelodysplastic syndrome, one had polycythemia vera, one had sideroblastic anemia, one had acute lymphocytic leukemia, and one had an undifferentiated myeloproliferative disorder.

Adult↗

Benzodiazepine receptors and seizure susceptibility in epileptic fowl.

Benzodiazepine binding to brain membrane preparations obtained from epileptic and nonepileptic carrier fowl was compared. [3H]Flunitrazepam binding to whole brain homogenates from 2-day-old chicks and [3H]diazepam binding to synaptosomal membranes and homogenates from adult chickens were determined. Scatchard analysis revealed no differences in either the number of receptors or their affinity for the ligands when the epileptics were sacrificed in the interictal state. Evoked seizures in adult epileptics had no effect on the number or affinity of binding sites using [3H]diazepam as the ligand. Moreover, the ability of gamma-aminobutyric acid to facilitate benzodiazepine binding was not different in epileptic fowl when compared with carriers.

Animals↗

Evidence for the pharmacological relevance of benzodiazepine receptors to anticonvulsant activity.

Each of a series of benzodiazepines was found to be effective in preventing convulsions evoked by intermittent photic stimulation of epileptic chickens. There was a high correlation between the anticonvulsant potencies (mean effective dosages) and the affinity of the agents for the putative benzodiazepine receptor as measured by displacement of [3H]diazepam from binding sites on chicken synaptosomal membranes. This correlation in a genetic model of epilepsy provides further evidence that benzodiazepines exert their anticonvulsant effects by interacting with the benzodiazepine receptor.

Animals↗

Pharmacology of methyl- and propyl-beta-carbolines in a hereditary model of epilepsy.

Intravenous administration of beta-carboline-3-carboxylate methyl ester (beta-CCM) produced convulsions at small doses (0.03 mg/kg) in adult chickens, homozygous for the epileptic gene. Nonepileptic heterozygote hatchmates (carriers) did not undergo seizures at doses of 1 mg/kg, and doses of 3-5 mg/kg produced only brief myoclonic responses. The convulsant effect of beta-CCM could be prevented by pretreatment with large doses of beta-carboline-3-carboxylate propyl ester (beta-CCP). beta-Carboline-3-carboxylate methyl ester displayed a higher affinity than diazepam in displacement studies on synaptosomal membrane preparations from brains of epileptic and carrier chickens.

Animals↗