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Biomedical subjects

P Johnson

Publications and source records attributed to P Johnson.

At least 433 records · Page 24Linked to original sources

Isolation, experimental transmission, and characterization of causative agent of Potomac horse fever.

Potomac horse fever, a disease characterized by fever, anorexia, leukopenia, and occasional diarrhea, is fatal in approximately 30 percent of affected animals. The seasonal occurrence of the disease (June to October) and evidence of antibodies to the rickettsia Ehrlichia sennetsu in the serum of convalescing horses suggested that a related rickettsia might be the causative agent. Such an agent was isolated in cultured blood monocytes from an experimentally infected pony. This intracytoplasmic organism was adapted to growth in primary cultures of canine blood monocytes. A healthy pony inoculated with these infected monocytes also developed the disease. The organism was reisolated from this animal which, at autopsy, had pathological manifestations typical of Potomac horse fever. Cross serologic reactions between the newly isolated agent and antisera to 15 rickettsiae revealed that it is related to certain members of the genus Ehrlichia, particularly to Ehrlichia sennetsu. Since the disease occurs in other parts of the United States as well as in the vicinity of the Potomac River, and since it has also been reported in Europe, the name equine monocytic ehrlichiosis is proposed as being more descriptive.

Animals↗

Paraneoplastic cerebellar disease. Remission with excision of the primary tumor.

We describe two patients with paraneoplastic cerebellar syndromes who gained clinically useful neurologic remissions following radical excision of the primary cancer. In both patients the syndrome was characterized by the rapid onset of gait ataxia, nausea, postural vertigo, central positional nystagmus, and saccadic oscillations. These observations encourage radical treatment of the primary cancer in patients with advanced malignant neoplasms who are disabled by cerebellar dysfunction, and lend support to a current hypothesis that paraneoplastic cerebellar degeneration is due to anticerebellar Purkinje cell antibodies elaborated by the primary cancer.

Adenocarcinoma↗

Purification, chain separation and sequence of the MRC OX-8 antigen, a marker of rat cytotoxic T lymphocytes.

The MRC OX-8 antigen is a marker of the rat cytotoxic T lymphocytes that consists of disulphide-linked chains of mol. wts. 37 and 32 kd. It is thought to be equivalent to the human T8 and mouse Lyt2,3 antigens (all now called CD8 antigens). MRC OX-8 antigen was purified from thymocytes using a monoclonal antibody column and because antigenicity was retained after reduction and alkylation the two polypeptide chains could be separated by a subsequent affinity chromatography step. Peptides were isolated from each chain and their sequences determined. A cDNA probe coding for the mouse CD8 antigen (pLY2C-1 provided by Dr L. A. Herzenberg) was used to obtain rat cDNA clones from which the sequence of the equivalent rat molecule was determined. Peptides from the 32-kd chain were identified in this translated sequence whereas peptides from the 37-kd chain were not. The 32-kd polypeptide sequence consisted of 210 amino acids and had one possible N-linked glycosylation site. The N-terminal part of the sequence was surprisingly different from both its mouse and human counterparts but, as in the other two species, it showed a clear relationship to Ig V domains.

Amino Acid Sequence↗

Inheritance of amphetamine-induced thermoregulatory responses in inbred mice.

Two inbred strains of mice, DBA/2 and C57BL/6, differ in their responses to d-amphetamine-induced alteration of core temperature. At low doses of amphetamine (e.g., 2 mg/kg IP), both strains become markedly hypothermic within 10-20 minutes. High doses (e.g., 20 mg/kg IP) induce significant hyperthermia (+1.8 degrees C) in DBA/2 mice but have only a slight hyperthermic effect (+0.2-0.3 degrees C) effect on C57BL/6 mice. The phenotype of the F1 hybrid strain derived by crossing C57BL/6 by DBA/2 is indistinguishable from its C57BL/6 parent at a dose of 20 mg/kg IP, i.e., reduced responsiveness to amphetamine-induced hyperthermia is dominant. Analysis of the thermoregulatory responses of recombinant inbred derivatives (lines BXD-9, 11, 15, 19, 20, 21, 23, 27, 28, 30) suggest that the relative responses to amphetamine-induced hyperthermia is inherited in a simple Mendelian fashion. These results differ from other pairs of inbred mouse strains which have been compared. These findings identify yet another neuropharmacological difference between mouse strains C57BL/6 and DBA/2 and are reviewed in terms of neuroregulatory mechanisms effecting thermoregulation.

Amphetamine↗

A single gene difference determines relative susceptibility to caffeine-induced lethality in SWR and CBA inbred mice.

Inbred mouse strains SWR and CBA differ markedly in their relatively susceptibility to the acute toxic effects of intraperitoneally administered caffeine. At a dose of 187 mg/kg, SWR mice survive a stress-potentiated lethality test apparently related to the generation of tonic seizures; in contrast, CBA mice usually die in less than 30 seconds after this dose. Progeny from several different genetic crosses were characterized to determine the genetic basis underlying this phenotypic difference in caffeine sensitivity. F1 progeny from reciprocal crosses of the parental strains were uniformly sensitive to caffeine-induced lethality, i.e., caffeine responsiveness behaves like an autosomal dominant trait. Self-crossing of F1 individuals produced both progeny which were resistant to caffeine-induced lethality (26% of the total) and those which were susceptible (74%). Backcrosses of the F1 animals to the CBA parent produced no (0/19) resistant progeny. In contrast, backcrosses of F1 animals to SWR produced 54% resistant progeny. These data indicate that the difference in susceptibility to caffeine-induced lethality between these strains is determined by a single pair of autosomal alleles in which susceptibility (responsiveness) to this methylxanthine is dominant to resistance (nonresponsiveness).

Animals↗

Management of chronic sternal osteomyelitis.

The management of 2 patients in whom chronic sternal osteomyelitis developed after apparently uncomplicated coronary artery bypass operations is described. Each patient had become totally disabled because of chronic, draining sinus tracts. Eradication of the infection required total sternectomy and excision of all infected costal cartilage. Subsequent reconstruction was accomplished by using bilateral pectoralis major myocutaneous advancement flaps without any maneuvers to stabilize the anterior chest wall. Both patients have resumed full activity and have returned to work with only minimal residual compromise of pulmonary function.

Aged↗

Use of influenza A virus vaccines in seronegative children: live cold-adapted versus inactivated whole virus.

We report the safety and antigenicity of influenza A vaccines in seronegative children one to seven years of age. A natural H1N1 challenge that occurred shortly after completion of the vaccination program permitted an evaluation of efficacy. Twenty-eight subjects were inoculated with live cold-adapted (ca) influenza A/Washington/897/80 (H3N2), 29 with ca influenza A/California/10/78 (H1N1), 24 with inactivated whole-virus influenza A/Bangkok/79 (H3N2), and 30 with a placebo. The ca vaccines were well tolerated, whereas the inactivated vaccine caused adverse reactions in about one-third of the children. Fifty-seven percent of the ca H1N1 recipients showed serological responses, contrasted with 84% and 100% of subjects receiving the ca or inactivated H3N2 vaccines, respectively. None of the 16 children with induced H1N1 antibody developed clinically apparent influenza-like illness, compared with eleven of the 51 initially seronegative children who did not receive the ca H1N1 vaccine and with four of the 12 who failed to respond. Results of the efficacy field trial suggest protection against infection and symptomatic illness in children inoculated with ca H1N1, despite its failure to stimulate high levels of hemagglutinin-inhibiting antibody.

Antibodies, Viral↗

Traumatic fistula between the descending thoracic aorta and the left main pulmonary artery.

A patient sustained a low-velocity gunshot wound to the left chest which resulted in a clinically silent traumatic fistula between the descending thoracic aorta and the left main pulmonary artery. The bullet remained in the aorta and embolized to the left popliteal artery, from which it was removed 2 days after thoracotomy. Lateral repair of the aorta and pulmonary artery was performed as well as reinforcement of the posterior aortic wall which was weakened by the bullet as it ricocheted within the aorta. This appears to be the first reported case of a traumatic aorta to pulmonary artery fistula involving the descending thoracic aorta.

Adult↗

Autoimmune hemolytic anemia associated with a hypernephroma.

This report describes a case of warm-antibody-mediated hemolytic anemia associated with a hypernephroma. Only four patients with renal cell carcinoma and Coombs'-positive hemolytic anemia have been reported previously. Although rare, the occurrence of autoimmune hemolytic anemia in association with a hypernephroma should be considered one of the possible hematologic complications of this tumor.

Aged↗

Some anticonvulsant drugs alter monoamine-mediated behaviour in mice in ways similar to electroconvulsive shock; implications for antidepressant therapy.

The effects in mice of administration of the anticonvulsants, progabide, sodium valproate, diazepam, carbamazepine and phenytoin on 5-hydroxytryptophan (5-HTP)-induced head-twitch, apomorphine-induced locomotion, clonidine-induced sedation, and beta-adrenoceptor and 5-HT2 receptor number have been examined. Repeated progabide administration (400 mg kg-1, i.p. twice daily for 14 days) enhanced the head-twitch response the effect lasting for over 8 days after the last dose, and also increased 5-HT2 receptor number in frontal cortex. Progabide (400 mg kg-1, i.p.) enhanced the head-twitch response when given once daily for 10 days and when given intermittently (5 times over 10 days) but not after 1 day of administration. Repeated Na valproate (400 mg kg-1, i.p.) also increased the 5-HTP-induced head-twitch response and 5-HT2 receptor number in the frontal cortex when given twice daily for 14 days, but no behavioural enhancement was seen after 10 days' treatment. Diazepam (1.25 mg kg-1, i.p.) twice daily for 14 days increased the head-twitch response and 5-HT2 receptor number. Repeated progabide and valproate (but not diazepam) administration attenuated the sedation response to the alpha 2-adrenoceptor agonist, clonidine (0.15 mg kg-1) but neither drug altered beta-adrenoceptor number in the cerebral cortex. No changes in apomorphine-induced locomotor behaviour were seen after progabide, valproate or diazepam. Repeated carbamazepine (20 mg kg-1) or phenytoin (40 mg kg-1) administration failed to alter any of the biochemical or behavioural parameters listed above. Like repeated electroconvulsive shock (ECS), progabide altered the head-twitch response, clonidine-induced sedation response and 5-HT2 receptor number. Unlike repeated ECS, it did not alter beta-adrenoceptor number or the apomorphine-induced locomotor response. These data suggest that ECS may produce some changes in monoamine function by altering GABA metabolism as has previously been postulated.

5-Hydroxytryptophan↗

Uptake, accumulation, and egress of erythromycin by tissue culture cells of human origin.

The ability of erythromycin A base to penetrate and accumulate in tissue culture cells of human origin was investigated. The antibiotic was highly concentrated by early passage cells of normal bronchus, kidney, liver, lung, and skin and by cancer cells derived from breast, liver, and lung. Intracellular levels 4 to 12 times that of the extracellular milieu were obtained in both early-passage and transformed cells. The total quantity of erythromycin accumulated depended on the extracellular concentration of antibiotic, but the cellular/extracellular ratios were, for the most part, independent of the initial extracellular drug concentration. In all cell types tested, the accumulated antibiotic rapidly egressed when cells were incubated in antibiotic-free medium. Bioactivity assays demonstrated that the expelled drug was unmetabolized, fully active antibiotic. The concentration of erythromycin by a variety of human cell types probably accounts, in part, for the effectiveness of the antibiotic against intracellular parasites such as Legionella and Chlamydia spp.

Cells, Cultured↗

Bone and muscle atrophy with suspension of the rat.

A modification of the Morey tail suspension model was used to determine atrophic responses of rat bone and muscle with 14-90 days unloading of the hindlimbs. Bone uptake of methylene diphosphonate followed a phasic pattern similar to changes in bone formation rate in immobilized dogs and rats. Increased uptake at 60 days (P = 0.01, femur) indicated an increased bone metabolism. Regional densitometry demonstrated a preferential loss of bone mineral in the trabecular mass (P = 0.02) at 30 days and in the cortical shaft by 90 days (P = 0.03). Maximal muscle atrophy occurred within 14-30 days. The gastrocnemius was less severely affected by suspension than by immobilization techniques, whereas the soleus atrophied (by weight) similarly, suggesting that muscle atrophy in the suspension model is distinctly different from immobilization atrophy. One significant response of skeletal muscle to suspension was an altered blood distribution. Muscle blood distribution changes reflect the hypodynamic state of muscle that continues to contract but probably at an altered rate in response to altered functional demands.

Animals↗

Measurement of platelet ionized calcium.

We measured ionized cytoplasmic calcium in human blood platelets by two techniques: one based on the fluorescence of intracellular Quin 2 and the other based on the luminescence of the calcium sensitive photoprotein, aequorin. Platelet activation (shape change, aggregation, secretion) induced by thrombin, ADP, epinephrine, collagen, A23187, or phorbol ester was invariably preceded or accompanied by a rise in platelet free calcium indicated by aequorin, but in some cases Quin 2 failed to detect the elevation of calcium concentration. Aequorin appears to be sensitive to localized changes in cytoplasmic calcium levels, while Quin 2 reflects average or diffuse calcium values. Failure of Quin 2 to indicate a rise in free calcium levels in association with a platelet activity does not establish the process as "calcium independent".

Aequorin↗

Primary hormonal therapy of advanced breast cancer with megestrol acetate: predictive value of estrogen receptor and progesterone receptor levels.

Estrogen (ER) and progesterone receptor (PR) levels in human breast cancer have been shown to have value in predicting response to a variety of hormonal therapies. However, the relationships between steroid receptor levels and tumor response and survival in patients treated with progestational agents for primary hormonal therapy have not been clearly defined. Forty-three advanced breast cancer patients, whose tumors had been assayed for ER and PR were treated with megestrol acetate as initial hormonal therapy. Twenty-five patients had ER and PR levels greater than 10 femtomole/mg cytosol protein, and the median ER and PR levels for the entire group were 114 fmol/mg and 100 fmol/mg, respectively. The overall response rate (complete and partial) was 46%, with a median duration of response of 66 weeks. Seventy percent of patients whose ER and PR were greater than 10 fmol/mg responded: Step-wise discriminant analysis showed that ER and PR were significantly related to response and that PR was the best predictor of response (P = .0034). Similarly, both ER and PR were significantly related to survival (P = .0001 for PR and P = .021 for ER). These data indicate that megestrol acetate is effective primary hormonal therapy in advanced breast cancer patients, and that ER and PR levels were significantly related to response and to survival duration. PR proved to be the best predictor of response in this group of patients.

Aged↗

Unusual compound of small molecular weight in the serum of horses with acute grass sickness.

An unusual compound of small molecular weight has been detected in serum from horses with acute grass sickness by solvent extractions and thin-layer chromatography. The substance has not been detected in the serum of normal horses or cases of equine colic and apparently disappears from grass sickness serum after two to three days of clinical illness. Although this compound is found in sera which are known to possess in vivo neurotoxicity, this property could not be demonstrated in either the total chloroform extract which contains the compound or in the hydrophilic serum components remaining after extraction. These findings suggest that, although the compound may be related to the neurotoxin present in the original serum, the toxicity is inactivated during the extraction procedure or that the emulsion necessary for administration precludes absorption of an active toxin.

Acute Disease↗

Continuous, noninvasive measurement of fetal oxygen and carbon dioxide levels in labor by use of mass spectrometry.

Clinical evaluation of the continuous, simultaneous measurement of fetal scalp surface oxygen and carbon dioxide partial pressures by mass spectrometry was undertaken for 52 labors. The mass spectrometer (MM8-80, V.G. Gas Analysis, Winsford, England) was easy to operate and had good long-term stability. The mean drifts for both oxygen and carbon dioxide over the study periods were less than 2 mm Hg. The mean (+/- SD) cervical dilatation at the time of transducer application was 6.1 (+/- 1.9) cm and the mean (+/- SD) duration of the studies was 169 (+/- 122) minutes; 10.5% of the transducer applications were unsuccessful. Falls in fetal scalp surface oxygen levels and rises in carbon dioxide levels were more frequent with late than with variable and with variable than with early fetal heart rate decelerations and with increasing severity and frequency of decelerations. Fetal scalp surface pressure changes also occurred with fetal heart rate variability changes, including some related to behavioral state changes. There was not a constant reciprocal relationship between oxygen and carbon dioxide changes, and fetal heart rate patterns were not related to actual blood gas levels. Fetal scalp surface measurements were related to both fetal blood sample and umbilical artery results. Trends in both oxygen and carbon dioxide levels during the course of labor were compared and related to other fetal variables, and most of the time the scalp surface measurements were an accurate guide to systemic blood gas levels. Maternal oxygen administration resulted in significant increase in fetal scalp surface oxygen levels, and on two of eight occasions it also led to decreases in fetal carbon dioxide levels. Scalp surface gas measurement by means of mass spectrometry is a powerful new method of intrapartum fetal monitoring, which should increase the precision of fetal surveillance as well as allow the accurate assessment of both established and new methods for optimizing labor and delivery.

Carbon Dioxide↗