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Biomedical subjects

J L Bennett

Publications and source records attributed to J L Bennett.

At least 19 recordsLinked to original sources

Synthesis of 2-alkyl- and 2-carboxy-p-tert-butylcalix[4]arenes via the lithiation of tetramethoxy-p-tert-butylcalix[4]arene.

[reaction: see text]. Tetramethoxy-p-tert-butylcalix[4]arene reacts readily with n-butyllithium to give a putative monolithiated intermediate that is substituted with alkyl halides and carbon dioxide to give in 60-75% yield conformationally mobile calix[4]arenes monosubstituted at the methylene bridge (2-position). 2-Alkyl- and 2-benzyl-substituted tetramethoxycalix[4]arenes are converted in 62-68% overall yield to the corresponding tetrahydroxy-p-tert-butylcalix[4]arenes by treatment with boron tribromide. The tetrahydroxy-p-tert-butylcalix[4]arenes exist in the cone conformation at room temperature in CDCl3 as judged by NMR spectroscopy.

Journal Article↗

Stability and reproductive fitness of Schistosoma mansoni isolates with decreased sensitivity to praziquantel.

These studies are focused on schistosomes derived from human infections not cured by three successive doses of praziquantel that also produced infections in mice that were significantly more difficult to cure than infections with control worms. Half (three of six) of these isolates retained their decreased response to praziquantel after multiple passages through the life-cycle in the absence of therapeutic pressure. Two of the isolates, including the one initially least sensitive to praziquantel; reverted, to a sensitivity not significantly different from controls. For example, the EE6 isolate initially required 680 mg/kg praziquantel to affect a 50% reduction in worm load in murine infections, but after only six passages through the life cycle over 5 years this was reduced to 113 mg/kg, not different from control infections. The stability of some of the isolates and the reversion of others indicates that the biological or genetic factors conferring decreased praziquantel response varies among the isolates. The three isolates that retained decreased sensitivity to praziquantel all showed compromises in reproductive fitness in the laboratory, expressed most frequently as a decreased cercarial production from snails infected with those isolates compared to controls. For example, the total cercarial production of snails infected with the EE10 isolate was only 57% that of controls. The reversion of some of the isolates to a praziquantel sensitive state and the decreased reproductive fitness of those that did not revert suggest that there is some biological cost associated with the relative praziquantel insensitivity of these worms, which could help limit the impact of such isolates in the field. Infections with the less sensitive isolates also produced significantly less circulating schistosomal antigen in mice, suggesting that a decrease in the host immune response elicited by these worms could be one of the factors contributing to the diminished praziquantel efficacy.

Animals↗

Praziquantel-induced tegumental damage in vitro is diminished in schistosomes derived from praziquantel-resistant infections.

The aggressive use of praziquantel to combat schistosomiasis in Egpyt raises concern about the possible emergence of resistance. Eggs from Egyptian patients with praziquantel-resistant infections (not cured by 3 doses of praziquantel) have been used to establish infection-specific schistosome isolates in mice. The response of these worms to the drug was observed in vitro, in order to determine if the isolates obtained from these resistant infections were, in fact, less responsive to praziquantel. One of the hallmark effects of praziquantel on schistosomes in vitro is a disruption of the worm's outer surface, the tegument. Here, praziquantel-induced tegumental damage is observed in 3 distinct isolates, 2 derived from resistant infections and 1 from an infection cured by a single dose. The isolates from the resistant infections were less susceptible to praziquantel-induced tegumental damage in vitro, suggesting that the worms are in some way less responsive to the drug.

Animals↗

Oltipraz concentrations in plasma, buccal mucosa cells, and lipids: pharmacological studies.

Oltipraz is considered one of the most potent cancer chemoprevention agents, as shown in preclinical studies. Its pharmacological effects in humans have been associated with unusual toxicity affecting the fingers and toes. This study was designed to test intermittent dosing schedules using two dosage levels: 500 mg as a single weekly dose and 200 mg as a biweekly dose, each for 30 days. Fifteen men and women were studied in each dosing group. All were heavy smokers considered to be at high risk for developing lung cancer. Plasma, buccal mucosa cell, and lipoprotein concentrations were measured at different intervals corresponding to the time period when most of the adverse effects occur. No serious toxicities were observed using these doses and schedules. The plasma and buccal mucosa cell concentrations of Oltipraz showed substantial interindividual variations at each sampling. Some subjects had no detectable plasma or buccal mucosal cell Oltipraz concentrations. The distribution of Oltipraz incorporation into the lipid fractions and albumin was changed by the administration of different schedules of Oltipraz. The results of this study suggest that the intermittent dosing is well tolerated and does not result in steady state in plasma or buccal mucosa cells. The variation and lack of detectable Oltipraz concentration in plasma, buccal mucosa cells, and lipids may affect both the toxicity and the pharmacological effects when these doses and schedules are used.

Administration, Oral↗

Palsies of the third, fourth, and sixth cranial nerves.

Diplopia is one of the most vexing problems to confront a physician. When diplopia is binocular, it commonly results from dysfunction of one or more of the ocular motor nerves. Ocular motor dysfunction may result from injury anywhere along the neuraxis, from the ocular motor nucleus to the myoneural junction. Identifying the location of the lesion is important for determining the etiology and prognosis of third-, fourth-, and sixth-nerve injuries. In this article, an anatomic approach is presented for the diagnosis and treatment of ocular motor nerve lesions. Emphasis is placed on the identification of associated neurologic and ophthalmologic findings that are critical for management of patients with acquired and congenital ocular motor palsies.

Abducens Nerve Diseases↗

Effect of temperature, pH, and ions on sweet taste.

The purpose of this experiment was to determine the effects of temperature (50 degrees C and 6 degrees C), pH (pH 3.0, 4.0, 5.0, 6. 0, and 7.0) and the addition of monovalent and divalent cations (5 mM Na(+), 5 mM K(+), and 5 mM Ca(2)+ ) on the sweetness intensity ratings of sweeteners ranging widely in chemical structure. A trained panel provided intensity evaluations for prototypical tastes (sweet, bitter, sour, and salty) as well as aromatic and mouth-feel attributes. The following sweeteners were included in this experiment: three sugars (fructose, glucose, sucrose), three terpenoid glycosides (monoammonium glycyrrhizinate, rebaudioside-A, stevioside), two polyhydric alcohols (mannitol, sorbitol), two dipeptide derivatives (alitame, aspartame), two N-sulfonylamides (acesulfame-K, sodium saccharin), one sulfamate (sodium cyclamate), one protein (thaumatin), one dihydrochalcone (neohesperidin dihydrochalcone), and one chlorodeoxysugar (sucralose). Two to five levels of each sweetener reflecting a range of sweetness intensities were tested, using formulae developed by DuBois et al. The main finding from this three-part study was that temperature, pH, and ions had little effect on perceived sweetness intensity. Even when significant differences were found in the temperature study, the effects were very small.

Calcium↗

Optic neuropathy associated with laser in situ keratomileusis.

PURPOSE: To report 4 cases of optic neuropathy following laser in situ keratomileusis (LASIK). SETTING: Tertiary Care ophthalmic practices. METHODS: In this retrospective observational case series, 4 patients who developed acute visual loss following LASIK are reported. All had clinical evidence of optic neuropathy. Two had optic disc edema and 2 had normal appearing optic discs initially. None of the patients experienced significant visual recovery, and all developed optic atrophy in the affected eye. RESULTS: All patients had evaluations for alternative etiologies of their optic neuropathy, with negative results. All patients were therefore presumed to have experienced an ischemic optic neuropathy following LASIK. CONCLUSIONS: Patients who have LASIK may experience an acute anterior or retrobulbar optic neuropathy. The etiology is unknown but may be related to the marked increase in intraocular pressure that occurs during a portion of the procedure.

Adult↗

Archaeology, science and forensic anthropology: a tribute to Dr T. Dale Stewart.

The name, T. Dale Stewart is synonymous with physical anthropology. To many members of the physical anthropology section, particularly those born in the latter half of this century, he is perhaps best known for his 1979 Essentials of Forensic Anthropology. Without a doubt, much of the foundation of this discipline rests upon his teachings and influence. Few knew him in the capacity that William M. Bass did, as T. Dale Stewart was a member of Bass doctoral committee. Bass was greatly influenced during the time he spent working with Dr. Stewart in the 1950's and the instruction and guidance Stewart instilled in Bass has and will continue to be passed on to subsequent generations. Research was Dale Stewart's main emphasis and he succeeded in demonstrating the value of investigation and how results were crucial in explaining many of the processes manifest on skeletal material. Clearly his hypothesis-based approach became essential to skeletal biology and numerous procedures and methods employed in the field are synonymous with the teachings of Dr. T. Dale Stewart. By reflecting on several recently completed interdisciplinary research projects, the far-reaching impact of his knowledge and instruction can be demonstrated.

Forensic Anthropology↗

Neuro-ophthalmologic manifestations of a paraneoplastic syndrome and testicular carcinoma.

The authors report two patients with testicular cancer who exhibited supranuclear gaze disorders as a manifestation of a paraneoplastic brainstem encephalomyelitis. In the first patient, neuro-ophthalmic dysfunction was accompanied by a prominent limbic encephalitis whereas in the second patient, an unusual, mixed pendular and jerk nystagmus was manifested. Neuroimaging revealed an enhancing hypothalamic mass in the first patient and was negative in the second. Blood from both patients contained an antibody previously reported in a patient with limbic encephalitis and testicular cancer.

Adult↗

Resistance to praziquantel: direct evidence from Schistosoma mansoni isolated from Egyptian villagers.

Recent evidence suggest that resistance to praziquantel (PZQ) may be developing. This would not be surprising in countries like Egypt where the drug has been used aggressively for more that 10 years. The classic phenotype of drug resistance is a significant increase in the 50% effective dose value of isolates retrieved from patients not responding to the drug. In a previous publication, we reported that such phenotypes have been isolated from humans infected with Schistosoma mansoni. Since the action of PZQ may be dependent upon the drug and host factors, most notably the immune system, we analyzed the quantitative effects of PZQ on single worms that differed in their response to PZQ when maintained in mice. Our hypothesis was that the in vitro action of the drug would correlate with it in vivo action. We confirmed this hypothesis and conclude that the in vitro action of the drug is related to its in vivo action. Knowing this relationship will assist in our ability to detect or survey for the PZQ resistant phenotype in human populations.

Animals↗

The differentiation of traumatic and heat-related fractures in burned bone.

Interpretations of antemortem and perimortem trauma are complicated when dealing with cases involving extreme exposure to fire. This investigation attempts to discern the signatures of perimortem trauma from heat related trauma. Femora of domestic pig, sus scrofa, with minimal soft tissue and articulated patellae were subjected to varying traumatic forces. Skeletal elements were impacted with blunt and sharp forces, cut with varying instruments, subjected to torsional forces of shot. Bones were burned in various situations in conjunction with Knox County Rural/Metro Fire Department training exercises conducted in Knox County, Tennessee. Following recovery, fragments were subjected to radiographic, macroscopic, and microscopic analyses. Skeletal elements were reconstructed to permit accurate comparison with pre-fire visual records. In addition, fracture surfaces were examined under both transmitted light and scanning electron microscopy in an attempt to discern surface signatures of the causal fracture (trauma, heat, or situational). Results indicate that signatures of sharp force trauma remain evident following incineration. Furthermore, radiopaque spatter was not observed in any shot specimen. However, these initial findings suggest that the interpretation of blunt force and torsional trauma requires a rigorous examination and comparison of fracture patterns in conjunction with surface morphology.

Animals↗

Patterned expression of BDNF and NT-3 in the retina and anterior segment of the developing mammalian eye.

PURPOSE: The neurotrophins brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) are hypothesized to play an important role in vertebrate eye development because of their patterned expression in the developing and adult neuroretina, their regulated response to retinal and optic nerve injury, and the effects of altered neurotrophin signaling on retinal development. To further characterize the role of these neurotrophins in mammalian eye development and maintenance, the pattern of expression of BDNF and NT-3 was analyzed in the developing and mature mouse eye. METHODS: Using mouse strains in which the reporter gene lacZ, encoding the enzyme beta-galactosidase, was targeted to either the BDNF or NT-3 locus, the expression of BDNF and NT-3 in the eyes of mice heterozygous for these mutations was analyzed by enzyme histochemistry during embryogenesis, postnatal development, and adulthood. RESULTS: BDNF and NT-3 expression were first observed in the inner and outer segments of the developing optic cup at embryonic days 10.5 to 11.5. As the retina matured, BDNF expression was restricted to retinal ganglion cells and a subset of cells in the inner nuclear layer (INL), whereas NT-3 expression was confined to a small subset of cells in the INL and ganglion cell layer. Both neurotrophins were expressed within the developing retinal pigment epithelium. In the anterior segment, BDNF and NT-3 were expressed at high levels in the developing and mature ciliary epithelium. In the lens and cornea, however, these neurotrophins displayed distinct patterns of expression during development and adulthood. BDNF expression was found in the lens epithelium, immature trabecular meshwork, corneal endothelium, and corneal epithelium, whereas NT-3 expression was confined to the corneal epithelium. CONCLUSIONS: BDNF and NT-3 exhibit different, yet overlapping, patterns of expression during the development and differentiation of the mouse eye. In addition to the neuroretina, the spatiotemporal expression of BDNF and NT-3 may play an important role in the development and maintenance of the lens, ciliary body, trabecular meshwork, and cornea.

Animals↗

Positive identification of cremains recovered from an automobile based on presence of an internal fixation device.

We report on the use of a surgically implanted device, an EBI osteostimulator, as a means of establishing the identification of a homicide victim. The use of such an appliance for securing positive identification has not been previously reported. Additionally we stress the importance of intensive and accurate excavation at scenes involving intense burning where the potential for non-skeletal contaminants is high.

Adult↗

The value of cerebrospinal fluid antiviral antibody in the diagnosis of neurologic disease produced by varicella zoster virus.

We studied four patients with subacute to chronic varicella zoster virus (VZV) infection of the central nervous system (CNS). VZV infection was verified by detecting antibody to VZV in the cerebrospinal fluid (CSF). VZV caused myelitis in two patients and encephalitis in two patients. In one of the patients with VZV encephalitis, in addition to VZV IgM antibody, VZV DNA was found in the CSF. Among the four patients with VZV infection of the CNS, CSF antibody to VZV was the crucial diagnostic laboratory test which corroborated the clinical features, and indicated that VZV caused neurologic disease. In addition to looking for amplifiable VZV DNA in the CSF of patients with neurologic disease whose clinical and radiologic features suggest VZV infection, we also recommend a search for CSF antibody to VZV, particularly in patients with intervals of weeks to months between zoster and the onset of neurologic disease, or in those patients without rash in whom the tempo of illness is unknown.

AIDS-Related Opportunistic Infections↗