PubMed HealthSearch

Biomedical subjects

P Cancilla

Publications and source records attributed to P Cancilla.

18 recordsLinked to original sources

A 35-year experience with the post-sophomore fellowship in pathology: analysis of its effectiveness as a recruitment resource.

Recent reports have indicated a shortage of pathologists coming out of training programs over the next few years. This is due, in part, to a decrease in the number of medical students entering pathology and an overall decline in the popularity of the field as a specialty choice. Medical students electing to spend a year in a post-sophomore fellowship in pathology would be expected to enter the field at a higher than average rate. In this study, the specialty choices of 140 former student fellows were analyzed. The students included in the study were enrolled in a year-long University of California, Los Angeles post-sophomore fellowship in pathology between 1953 and 1988. Twenty-seven of the 140 students (19.3%) ultimately chose pathology as a career. This represents a 9- to 10-fold increase over the average percentage of medical students entering pathology through the match (less than 2%) for any given year. Of all students from the University of California, Los Angeles who entered pathology, 75% did not elect to spend a year in fellowship. Eighty percent of the former fellows chose some other field, medicine and surgery being the most popular choices.

Cohort Studies

Blood-brain barrier: interface between internal medicine and the brain.

The blood-brain barrier separates brain interstitial space from blood and is formed by brain capillary endothelial cells that are fused together by epithelial-like tight junctions. Study of the blood-brain barrier traditionally has been a relatively arcane field, even for neurobiologists. However, advances over the last 10 years in understanding the transport physiology and cell biology of the brain capillary endothelial cell now provide insights into the pathogenesis of such problems as brain glucopenia, hepatic encephalopathy, therapeutic efficacy of alpha-methyldopa, brain edema in diabetic ketoacidosis, Alzheimer's disease, brain tumors, and lupus cerebritis.

Animals

Giant axonal neuropathy: normal protein composition of neurofilaments.

A 14-year-old boy had progressive weakness and ataxia since two years of age with tightly curled hair, facial diplegia, distal weakness and hypaesthesia, cerebellar syndrome and normal intelligence. He also had distal renal tubular acidosis manifested by metabolic acidosis. Sural nerve ultrastructure showed numerous giant axons packed with neurofilaments. The neurofilament major proteins of 68 000, 160 000 and 210 000 daltons found in normal sural nerve were also present in the diseased nerve indicating that the protein composition of neurofilaments which accumulates in this disorder has not been appreciably altered. The amount of 68 000 dalton neurofilament protein was two times higher in giant axonal neuropathy nerve than in the control nerve. Our results suggest that the neurofibrillary pathology in giant axonal neuropathy is due to a build-up of normal neurofilaments.

Acidosis, Renal Tubular

Alterations in creatine kinase in fresh muscle and cell cultures in Duchenne dystrophy.

Creatine kinase (CK) (total and isoenzymes) was measured in cultures obtained by dissociation and subsequent plating of cells from biopsied quadriceps muscle of 10 patients with Duchenne muscular dystrophy (DMD) and 20 controls. The total cellular CK and CK-MM reached highest values around 21 days in both DMD and control cultures, suggesting that DMD cultures do not show delayed myoblast fusion. There was a significant decrease of total cellular CK in DMD cultures at all stages, but the maximum differences were noted for the peak values. The CK isoenzyme pattern in DMD cultures demonstrated a higher percentage of CK-BB and CK-MB and a lower percentage of CK-MM than was observed in cultures from the controls. Addition of cytosine arabinoside after myoblast fusion to muscle cell cultures did not induce significant changes of CK isoenzyme pattern. There was no difference in the CK levels in culture medium from controls and DMD patients. The alterations of cellular CK were similar in fresh muscle and cell cultures from DMD patients.

Cells, Cultured

Partial purification and characterization of a folate-binding protein from human choroid plexus.

A folate-binding protein (binder) from human choroid plexus was solubilized with Triton X-100 and partially purified in three steps: (1) affinity chromatography, (2) Sephadex G-200 column chromatography, and (3) polyacrylamide gel electrophoresis. When the partially purified binder was subjected to sodium dodecyl sulfate--polyacrylamide gel electrophoresis, the binding activity was located in the region of the gel with a molecular weight between 45,000 and 60,000. The specific activity of the binder after the three purification steps was 1.2 mu g folic acid/mg protein, a 316-fold purification. Binding activity of the partially purified binder decreased below pH 6.0 and above pH 8.0, was unaffected by treatment with ribonuclease or deoxyribonuclease, but was abolished with trypsin, chymotrypsin, or protease (Streptomyces griesus). The binding of folic acid to the human binder was inhibited by folate Greater Than H4-folate Greater Than methyl-H4-folate approximately dihydrofolate approximately pteroic acid Greater Than methotrexate approximately aminopterin.

Carrier Proteins

Altered protein synthesis and creatine kinase in breast muscle cell cultures from dystrophic chick embryos.

The total protein synthesis (TPS), myosin synthesis (MS) and creatine kinase (CK) levels in muscle cell cultures obtained from 400 normal (strain 454) and 400 dystrophic chick embryos (strain 455) were investigated. The cultures were obtained from breast muscles of 12 day chick embryos by dissociation in 0.25% trypsin, preplating and plating of 5 x 10(5) floating cells on gelatin coated dishes in Minimal Essential Medium, 10% horse serum and 2% chick embryo extract. After 6 days, when electron-microscopic studies demonstrated good muscle differentiation, cell cultures were labeled with [3H]leucine. TPS and MS, respectively, showed 85% and 65% increases in breast muscle cell cultures from dystrophic chick embryos. The half-life times for total protein and myosin from dystrophics were 19 and 32 hr, respectively as compared with 36 and 48 hr from controls. Noncollagen protein content (NCP) showed 27% decrease in postfusion stage (12 days) of cell cultures from dystrophics. The CK level showed 30% lower values in the cells from dystrophics but 50% higher values in their culture medium. The addition of leupeptin plus pepstatin (50 microgram/ml) to these cultures resotred NCP content, total protein and myosin turnover to normal values and significantly increased TPS and MS. The addition of diphenylhydantoin (DPH) (20 microgram/ml) to cell cultures from dystrophics did not change the NCP content nor the turnover for total protein and myosin but significantly increased TPS, MS and CK while medium CK significantly decreased. The addition of leupeptin plus pepstatin or DPH to muscle cell cultures from normal chick embryos also significantly stimulated TPS and MS.

Animals

Is idiopathic dementia a regional vitamin deficiency state?

We hypothesize that some cases of idiopathic dementia are due to a gradual undernourishment of the brain with water-soluble vitamins. This occurs because the choroid plexus and possibly other transport loci in the central nervous system become unable to transport water-soluble vitamins from blood into the central nervous system in adequate amounts. If this testable hypothesis is correct, direct injections of vitamins into the ventricular cerebrospinal fluid should ameliorate the development of dementia.

Ascorbic Acid

Methyl alcohol poisoning. II. Development of a model for ocular toxicity in methyl alcohol poisoning using the rhesus monkey.

Rhesus monkeys were intoxicated with methyl alcohol, using an initial dose of 2 gm/kg and subsequent doses were administered in order to maintain an attenuated and prolonged state of intoxication. Arterial blood samples were drawn for methyl alcohol, formate, PO2, PCO2, and pH, which were monitored periodically throughout the course of the experiment. With the use of these procedures monkeys developed metabolic acidosis with the accumulation of formic acid in the blood and a corresponding decrease in blood bicarbonate. These animals served as models, which allowed for ocular evaluation for early signs related to methyl alcohol poisoning. A mechanism to explain toxicity is proposed and discussed.

Acidosis

Methyl alcohol poisoning III. Ocular toxicity.

The ocular toxicity of methyl alcohol has been investigated in six rhesus monkeys. All the animals developed fundus changes within 43 to 171 hours after its ingestion. The only fundus lesion seen was optic disc edema and associated changes, usually of a marked degree. Fluorescein fundus angiography confirmed the findings. The retinal and choroidal circulations, including the retinal capillary bed, were normal. Ophthalmoscopically and angiographically, optic disc edema in methyl alcohol poisoning was indistinguishable from that seen in raised intracranial pressure, except that no increased intracranial pressure was observed. It is postulated that optic disc edema in methyl alcohol poisoning is due to an axoplasmic flow stasis.

Animals

Protein synthesis in muscle cultures from patients with myotonic dystrophy. Influence of A23187 ionophore and calcium: preliminary investigation.

Muscle samples for cultures were obtained from the tibialis anterior by open biopsy under local anesthesia in 12 patients with myotonic dystrophy and 15 controls. Total protein synthesis in muscle cultures from patients with myotonic dystrophy showed a nonsignificant increase in (3H)-leucine incorporation. Addition of A23187 ionophore significantly stimulated the protein synthesis in muscle cultures from patients with myotonic dystrophy, but had an inhibitory effect in the cultures from controls. Myosin heavy chain synthesis was measured and found normal in all patients with myotonic dystrophy.

Anti-Bacterial Agents

Cultured skin fibroblasts in storage disorders. An analysis of ultrastructural features.

Electron microscopic studies were performed on cultured fibroblasts from patients with metachromatic leukodystrophy, Fabry's, Gaucher's, Niemann-Pick's (Type A and C), Sanfilippo's (Type A and B) disease, chondroitin-4-sulfate mucopolysaccharidosis, lipofuscinosis (Spielmeyer-Vogt's disease) and ceroid-lipofuscinosis (Batten's disease with curvilinear bodies). Specific cytoplasmic inclusions with a limiting membrane were identified in Fabry's disease, Niemann-Pick syndrome, chondroitin-4-sulfate mucopolysaccharidosis and Sanfilippo's Type B disease. In Fabry's disease, the lipid inclusions tended to form stacks of parallel and concentric membranes. In Niemann-Pick syndrome, the lipid inclusions were made of wavy, loosely packed membranes. In chondroitin-4-sulfate mucopolysaccharidosis and Sanfilippo B, the lysosomes were enlarged and contained a reticular matrix with little electron-dense material. No specific ultrastructural changes were observed in Gaucher's, Sanfilippo's (Type A) disease, metachromatic leukodystrophy (sulfatidosis) and Batten's disease.

Biopsy