Biomedical subjects

R L Hall

Publications and source records attributed to R L Hall.

At least 37 records · Page 2Linked to original sources

PubMed1995

The effect of inhibitors on the growth of the entomopoxvirus from Amsacta moorei in Lymantria dispar (gypsy moth) cells.

Within the family of Poxviridae, the entomopoxviruses are the most distant relatives of the more well-known and intensively studied orthopoxviruses (vaccinia and variola). The growth of the entomopoxvirus from Amsacta moorei (AmEPV) has been characterized in cell culture and compared to that of vaccinia virus (VV), the prototypic orthopoxvirus. The overall characteristics of infected cell cultures were generally similar between the two viruses. One striking difference noted was the apparent absence of proteolytic processing of late AmEPV viral proteins, a hallmark of vertebrate poxvirus infections associated with viral morphogenesis. AmEPV, like VV, was found to be sensitive to all the inhibitors of viral infection tested including phosphonoacetic acid, 1-beta-D-arabinofuranosylcytosine, and isatin-beta-thiosemicarbazone (IBT), a compound associated with the rather specific inhibition of vertebrate poxviruses. While both VV and AmEPV are inhibited by IBT, the inhibition of AmEPV, unlike that of VV, is not accompanied by either a breakdown of ribosomal RNA or a global inhibition of late viral protein synthesis. Instead, in the presence of IBT, AmEPV enveloped, immature virions form devoid of a well-differentiated core, which unlike mature virions fail to insert into occlusion bodies.

Animals↗

PubMed1995

Toxicity of the protein kinase C inhibitor safingol administered alone and in combination with chemotherapeutic agents.

Safingol [(2S,3S)-2-amino-1,3-octadecanediol] potentiates the toxicity of doxorubicin (DOX) and cisplatin (CIS) against tumor cells in vitro and in vivo. The present studies were conducted in rats and dogs to evaluate safingol toxicity when administered i.v. as a single agent and to evaluate safingol's ability to potentiate the toxicity of established chemotherapeutic agents to normal tissues in vivo. In an escalating dose study, dogs were administered safingol i.v. at 5, 10, 20, 30, 40, and 75 mg/kg on Days 1 through 6. Necropsies were performed on Day 7. Red urine was observed at 10 mg/kg and higher. Icterus was observed following 40 mg/kg with additional signs of hypoactivity and anorexia occurring after 75 mg/kg. Clinical and microscopic pathology revealed marked hepatotoxicity, venous degeneration and necrosis at injection sites, and evidence of intravascular hemolysis. Doses of 5, 20, or 40 mg safingol/kg were utilized in single i.v. dose rat and dog studies. No evidence of adverse systemic toxicity was seen up to 20 mg/kg in either species [for rats: Cmax = 12,600 (males) or 17,133 (females) ng/ml, AUC = 3853 (males) or 4365 (females) ng x hr/ml; for dogs: Cmax = 2533 ng/ml, AUC = 2851 ng x hr/ml (no sex differences)]. Local effects of venous irritation or intravascular hemolysis were observed at all doses in rats and at 20 and 40 mg/kg in dogs. A dose of 40 mg/kg [for rats: Cmax = 31,233 (males) or 91,300 (females) ng/ml, AUC = 11,519 (males) or 18,620 (females) ng x hr/ml; for dogs: Cmax = 9033 ng/ml, AUC = 11,094 ng x hr/ml (combined sex)] was associated with clinical pathologic and renal histomorphologic changes considered consequent to intravascular hemolysis in both species, lethality and testicular toxicity in rats, and clinical biochemical changes indicative of hepatobiliary injury in dogs. Studies indicated that hemolysis occurred during infusion, was not caused by circulating levels of safingol, and was a function of dose concentration and vein of delivery. Safingol at 10 or 20 mg/kg was administered i.v. to rats 30-60 min prior to myelosuppressive i.v. doses of DOX, CIS, or cyclophosphamide (CYP). Hematology, plus renal function and morphology for CIS-treated animals, was assessed 4 and 14 days later.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1995

FEMA GRAS--a GRAS assessment program for flavor ingredients. Flavor and Extract Manufacturers Association.

The generally recognized as safe (GRAS) assessment program of the Flavor and Extract Manufacturers Association (FEMA) of the United States was initiated in 1959 to provide for the assessment of flavor ingredients as GRAS under the Food Additives Amendment to the U.S. Federal Food, Drug, and Cosmetic Act. FEMA sponsored the formation of an independent panel of experts to perform GRAS assessments and to provide their conclusions to the U.S. Food and Drug Administration, the food and flavor industries, and the public. The program was designed to account for the legal, regulatory, and scientific issues associated with GRAS assessments and has continued to incorporate changes in the law and in science. This review describes the legal and scientific foundation of the FEMA program.

Flavoring Agents↗

PubMed1995

Ankle arthroscopy in industrial injuries of the ankle.

Industry-related injuries to the foot and ankle are not uncommon. These cases are often difficult to evaluate with respect to degree of damage and even more difficult to quantitate with regard to functional impairment. This article represents an attempt to determine the role of ankle arthroscopy in the evaluation of ankle injuries that involve compensation or liability. A retrospective review was conducted. The study group consisted of 40 patients who underwent a total of 42 arthroscopic procedures. The patients were evaluated with regard to the mechanism of injury and clinical manifestations. Pain and swelling were the most common preoperative symptoms. The majority of patients had pain localized to the lateral and anterolateral ankle. There were a high percentage of positive bone scans that correlated well with bone pathology but poorly with soft-tissue pathology. Computed tomography (CT) scans were equivalent to tomograms in the demonstration of bone pathology. Follow-up was obtained in 24 patients. At least 50% of the patients had some improvement in their symptoms. Thirty-three percent believed there was no change, and 17% said they were worse. Over 70% of the patients were able to return to work, although 20% had to change their occupation. Fifteen percent were considered disabled. In patients without a specific diagnosis, ankle arthroscopy was helpful in establishing a diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Accidents, Occupational↗

PubMed1995

A new monoclonal antibody (3D3) generated with human respiratory mucins and directed against Lewis determinants.

We have prepared a monoclonal antibody (MAb), 3D3, raised against purified human respiratory mucins. This antibody recognized mucins and proteolytically derived glycopeptides. The epitope recognized by the antibody was destroyed by alpha-L-fucosidase, indicating that it was present on the carbohydrate moieties. Structural specificity was determined by adsorption on a variety of synthetic, insolubilized oligosaccharides. Several lines of evidence indicate that the 3D3 MAb reacted strongly with the Lewis (Leb) antigen, but also recognized Le(a) and Le(y) determinants. This antibody might be useful to study mucin secretion.

Adsorption↗

PubMed1995

Mucous and serous secretions of human bronchial epithelial cells in secondary culture.

Human bronchial surface epithelial cells were maintained in secondary culture on a collagen gel substrate in a defined, serum-free medium. These conditions have previously been reported to promote mucous cell differentiation. After 3 wk in culture, approximately 40% of the cells were stained by an antibody directed against human respiratory mucin. Analysis of media from cells cultured in the presence of the radioactive precursors [3H]glucosamine and [35S]sulfate revealed that the cells secreted high molecular weight glycoproteins with properties of typical respiratory mucins. In addition, hyaluronic acid and proteoglycans containing chondroitin sulfate and/or heparan sulfate glycosaminoglycans were identified in cell conditioned media. Finally, Western blot analyses showed that the cells secreted lysozyme and mucous proteinase inhibitor, proteins that are generally considered to be markers for submucosal gland serous cells. These results show that human bronchial cells from the surface epithelium in secondary culture secreted a range of glycoconjugates and proteins that were typical secretory products of both mucous and serous cells.

Bronchi↗

PubMed1995

Progressive retinal toxicity in neonatal rats treated with D,L-2-amino-3-phosphonopropionate (D,L-AP3).

D,L-2-amino-3-phosphonopropionate (D,L-AP3) has complex pharmacologic activity at central nervous system metabotropic glutamate receptors important in excitatory neurotransmission and development. Previous studies have described retinal and optic nerve atrophy in adult rats after postnatal treatment with D,L-AP3. Using neonatal male Sprague-Dawley rats, the present studies examined normal postnatal retinal development (n = 20) and the progression of retinal toxicity induced by D,L-AP3 (n = 30). Retinal development was examined by light microscopy on postnatal days (PNDs) 5, 9, 12, 16, and 22. Between PNDs 5 and 16, the retina underwent considerable postnatal differentiation. A prominent neuroblastic layer evident on PND 5 differentiated into outer retinal layers by PND 16. To examine the effects of D,L-AP3, neonatal rats were treated intraperitoneally with sterile water or 400 mg/kg/day D,L-AP3 on PNDs 3-6. On PNDs 5, 7, 10, 15, and 20, retinas were examined by light and electron microscopy. On PNDs 5 and 7, cells with swollen, pale cytoplasm were evident in the more differentiated inner nuclear layer and in the middle of the developing neuroblastic layer. Retinal toxicity rapidly progressed after treatment, because developing outer retinal layers had cytoplasmic swelling, nuclear pyknosis, and necrosis on PND 10. By PNDs 15 and 20, retinal dystrophy was severe and involved primarily outer layers. This study showed that early postnatal treatment with D,L-AP3 initiates rapidly progressing retinal toxicity, thus implicating metabotropic glutamate receptors in the postnatal retinal development of rats.

Alanine↗

PubMed1995

Acute rupture of the extensor hallucis longus tendon.

A 40-year-old man with a history of previous cheilectomy and two steroid injections for first metatarsophalangeal degenerative joint disease sustained an acute rupture of the extensor hallucis longus tendon. He was treated successfully with delayed primary repair of the tendon.

Adult↗

PubMed1995

Isolated weakness of the extensor hallucis longus in a patient with hereditary spherocytosis.

A 24-year-old woman with a history of hereditary spherocytosis and oral contraceptive use presented with a spontaneous, isolated loss of great toe extension. She had clinical and electrodiagnostic evidence of a localized lesion affecting the nerve supply to the extensor hallucis longus (EHL). Full clinical recovery was apparent within 6 months with nonoperative therapy. Isolated EHL weakness may occur as a rare neurologic complication of procedures such as high tibial osteotomies, but, to our knowledge, this has not been reported in the absence of trauma or surgery. While the coexistence of hereditary spherocytosis and a peripheral neuropathy may have been purely coincidental, it is plausible that the isolated lesion in this patient was due to ischemic changes from underlying rheologic conditions, possibly in association with a variation in the neural or nutrient vessel supply to the EHL.

Adult↗

PubMed1995

Gout as a source of sesamoid pain.

Isolated gout of a great toe sesamoid has not been described previously. We present a case of gout of the medial sesamoid in a young athlete. Because a diagnosis is often elusive in patients with sesamoid pain, it is possible that other cases of gout of a hallucal sesamoid have gone unrecognized. Consideration of this diagnosis might lead to curative medical therapy precluding the need for surgical intervention.

Adolescent↗

PubMed1995

Geographic variation of native people along the Pacific Coast.

Data gathered by Boas in the 1890s from 1749 adult males and 1056 adult females were subjected to anthropometric analyses to investigate possible effects of climatic adaptation. The subjects were native people from California, Oregon, Washington, the panhandle of Alaska, and British Columbia. They were categorized by their tribe's latitude and longitude (the center point of tribal distribution) and by habitat (characterized as coastal, western lowlands, and interior). Multiple R regressions were used to determine complex relationships between age, habitat, latitude, rainfall, mean January temperature, mean July temperature, and blood quantum, all of which affected some anthropometric variables to statistically significant degrees in both the male and the female samples. Body size and proportional differences support other studies of Bergmann's and Allen's rules, and variation in the nasal index supports prior studies of selection of longer, narrower noses in cold and dry climates and broader noses in warmer, moister ones. Recent disruption in the central portion of the study area was detectable in reduced size of subjects in these regions. Other complicating factors, such as ethnicity and the possibility of prior migrations and intermarriage between populations, are discussed.

Adaptation, Physiological↗

PubMed1993

Expression of TRPM-2 during involution and regeneration of the rat liver.

Increased message levels of testosterone-repressed prostate message-2 (TRPM-2) have been associated with programmed cell death in many tissues. To study its involvement in the apoptotic elimination of hepatocytes during liver involution and regeneration, levels of TRPM-2 message were evaluated in situ and by the ribonuclease protection assay. Although significant increases in apoptotic bodies were observed in rats 96 h following treatment with lead nitrate and ethylene dibromide, an increase in TRPM-2 message was not detected. Therefore, the expression of TRPM-2 mRNA may be a poor indicator of the extent to which apoptosis occurs during liver involution.

Animals↗

PubMed1993

Identification of an Amsacta spheroidin-like protein within the occlusion bodies of Choristoneura entomopoxviruses.

Like baculoviruses, a characteristic feature of entomopoxviruses is the amalgamation of virions within environmentally stable occlusion bodies. It is this occluded form of the virus that is primarily responsible for dissemination to other insects. While the major protein (polyhedrin) of baculovirus occlusions is quite similar between viruses, it has been reported that the major occlusion body protein (spheroidin) of two group B entomopoxviruses, Amsacta moorei (AmEPV) and Choristoneura biennis (CbEPV) is quite different both in terms of amino acid sequence and coding capacity of the corresponding spheroidin genes (115 and 47 kDa for AmEPV and CbEPV, respectively). We report the discovery of a AmEPV spheroidin gene homolog in both CbEPV and a second Choristoneura virus, Choristoneura fumiferana (CfEPV). Antibodies directed against the AmEPV 115-kDa spheroidin reacted with the major protein of approximately 115 kDa found within the occlusion body preparation from both Choristoneura viruses. Direct protein microsequencing of small portions of the 115-kDa protein from CbEPV has resulted in peptide sequences identical to those of corresponding regions of the AmEPV spheroidin gene. We suggest that it is this Choristoneura gene which encodes spheroidin. All attempts, however, to find a homolog of the previously reported CbEPV spheroidin gene within AmEPV have been unsuccessful. We also show this newly identified Choristoneura homolog of the AmEPV spheroidin gene as well as the AmEPV spheroidin gene itself are both located at the 3' end of an NPH I gene and are highly homologous in all three viruses, indicating that this region of the genome in the three viruses is co-linear. These results and others suggest that while the insect viruses lack the traditional central core of conserved genes observed for the vertebrate poxviruses, the insect poxviruses may have also evolved an alternative central core of conserved genes, unique to the invertebrate poxviruses.

Amino Acid Sequence↗

PubMed1993

Anatomy of the calcaneus.

The calcaneus is the largest tarsal bone in the foot and is well designed to sustain high tensile, bending, and compressive forces. However, high instantaneous loads often result in fracture. Any treatment of calcaneal fractures requires a working knowledge of the anatomy. The major neurovascular structures are located medially and are well insulated by the medial soft tissues. These structures are at risk, however, during medial approaches to the calcaneus. Laterally, there are several bony landmarks that are palpable primarily because of the relative paucity of the soft-tissue elements. Lateral approaches to the calcaneus have been associated with the areas of skin necrosis that may be related to the arterial anatomy. The calcaneus has four articular surfaces. The congruity of these articular surfaces and their relationship to one another can be assessed roentgenographically. With adequate knowledge of the bony anatomy of the calcaneus and its soft tissue envelope, a rational approach in assessment and treatment of calcaneal fractures can be developed.

Calcaneus↗

PubMed1992

The de-endothelialized rat carotid arterial graft: a versatile experimental model for the investigation of arterial thrombosis.

A novel model of arterial thrombosis was developed. A mechanical endothelium-denuding injury was created (using a scalpel blade) on harvested, freezer-stored rat carotid arteries. Vessel length of 5 mm. were grafted into the femoral arteries of recipient Sprague-Dawley rats using microvascular anastomotic technique. Patency rates in untreated animals were compared with those in animals receiving systemic aspirin or heparin. The control group patency after 2 hours of flow was 15%, while grafts in aspirin- and heparin-treated animals achieved 35% and 95% patency rates, respectively. Uninjured non-frozen carotid grafts in untreated animals yielded a 95% patency rate, while frozen grafts achieved an 80% patency. Therapeutic levels of aspirin, heparin, and urokinase were confirmed through tail bleeding and whole blood clotting tests, as well as platelet aggregation studies and scanning electron microscopy of the graft lumenal surfaces. A long-term series using syngeneic grafts placed in recipients (Lewis-to-Lewis) and employing systemic heparinization demonstrated maintenance of patency for 4 weeks. Scanning electron microscopy revealed good re-endothelialization, well advanced by one week. Histology confirmed the regrowth of endothelial cells, but showed sparse cellular repopulation of medial and adventitial layers. The mechanical injury model was compared to enzymatic de-endothelialization (using trypsin or collagenase), for which patency rates were similar (10% and 0%, respectively). Trypsin de-endothelialized vessels were tested in vitro for the amount of active trypsin remaining bound to the lumenal surface; no detectable activity was found when trypsin inhibitor was applied following trypsin treatment. The versatility of allowing both in vitro evaluation and in vivo patency assessment demonstrates the uniqueness and value of this new model, offering an avenue toward more direct investigations of surface-mediated thrombotic processes.

Anastomosis, Surgical↗

PubMed1992

Polypeptide N-acetylgalactosaminyltransferase activity in tracheal epithelial microsomes.

Pig tracheal epithelium, a site of extensive mucin biosynthesis, contained polypeptide N-acetylgalactosaminyltransferase activity directed towards L-threonine residues. The enzyme preparation was broadly similar in properties to preparations from other tissues, e.g. pig and bovine submaxillary glands, bovine colostrum, BW5147 mouse lymphoma and baby-hamster kidney cells. Enzyme was membrane-bound and was released from microsomal preparations by extraction with Triton X-100. Extracted enzyme had a pH optimum of 7.5, had a requirement for Mn2+ (10 mM) and was inhibited by Na2EDTA. The Km for UDP-N-acetylgalactosamine was 110 microM and that for an octapeptide acceptor (VTPRTPPP) was 3.0 mM at 37 degrees C. Using a range of synthetic peptides of known structure related to TPPP it was established that L-threonine residues were specifically O-glycosylated probably in the alpha-configuration. Synthetic peptides containing the TPPP sequence required a peptide length of five or more for significant acceptor activity. In VTPRTPPP the two threonine residues were similarly glycosylated, as revealed by tryptic cleavage of the glycosylated product and separation of the 3H-labelled fragments. The enzyme preparation also specifically catalysed the transfer of N-acetylgalactosaminyl residues from UDP-N-acetyl[1-3H]galactosamine to bovine submaxillary mucin core protein and to myelin basic protein.

Amino Acid Sequence↗

PubMed1992

Mapping and molecular characterization of a functional thymidine kinase from Amsacta moorei entomopoxvirus.

A thymidine kinase (TK) gene from the entomopoxvirus of Amsacta moorei (AmEPV) has been identified, mapped, cloned, and sequenced. The AmEPV TK was shown to be biologically functional as cloning of the gene into a TK-derivative of the orthopoxvirus vaccinia creates a TK+ virus. The gene has been localized to a 1.5-kb EcoRI-Q DNA fragment which maps to the far left end of the viral genome. Sequence analysis reveals an open reading frame (ORF) of 182 amino acids potentially encoding a polypeptide of 21.2 kDa. Amino acid homology comparisons indicate that the gene is most closely related to the TKs of a variety of poxviruses (approximately 45%) and less so to the TKs of vertebrates (approximately 40%). The TK from African swine fever virus (ASF) showed the least homology (31.4%) to the AmEPV TK gene, suggesting that these two viruses are not closely related although ASF shares some biological features of poxviruses, and both ASF and AmEPV can replicate within arthropod hosts.

Amino Acid Sequence↗

PubMed1992

Clinical pathology for preclinical safety assessment: current global guidelines.

Regulatory guidelines for preclinical safety assessment studies of new drugs, chemicals, and food additives exist in many large industrial countries. Current guidelines include recommendations or requirements for clinical pathology testing. Many of the testing requirements are similar for every country, but others are not. The similarities and differences among several of the guidelines are discussed, and specific instances of ambiguous or inappropriate testing requirements are cited.

Animals↗