Biomedical subjects

William Gossman

Publications and source records attributed to William Gossman.

4 recordsLinked to original sources

PubMed2003

A density functional theory investigation of Fe-N-O bonding in heme proteins and model systems.

We report the results of a series of density functional theory (DFT) calculations of the Mössbauer quadrupole splittings and isomer shifts in NO heme model compounds, together with the results of calculations of the Mössbauer quadrupole splittings, isomer shifts, and electron paramagnetic resonance hyperfine coupling constants in a model Fe(II)(NO)(imidazole) complex as a function of Fe-NO bond length and Fe-N-O bond angle. The results of the Mössbauer quadrupole splitting and isomer shift calculations on the NO heme model compounds show good accord between theory and experiment, with the largest errors being observed for structures having the largest crystallographic R(1) values. The results of the property surface calculations were then used to calculate Fe-NO bond length and Fe-N-O bond angle probability surfaces (Z-surfaces) for a nitrosyl hemoglobin, using, in addition, an energy filter. The results obtained yielded a most probable Fe-NO bond length (r) of 1.79 A and an Fe-N-O bond angle (beta) of 136 degrees -137 degrees. This bond length is somewhat longer than those observed in most model compounds but may be due, at least in part, to hydrogen bond formation with the distal His residue. Bond elongation was also observed in a geometry optimized Fe(II)(NO)(imidazole) complex hydrogen bonded to an imidazole residue, in which we find r = 1.76-1.78 A and beta = 137 degrees -138 degrees. The computed bond angles are close to the canonical approximately 140 degrees value found in most model systems. Highly bent Fe-N-O bond angles or very long Fe-NO bond lengths seem unlikely to occur in proteins, due to their high energies. We also investigated the molecular orbitals and spin densities in each of the six coordinate systems investigated and found the orbitals and spin densities to be generally similar those described previously for five coordinate systems. Taken together, these results show that Mössbauer quadrupole splittings and isomer shifts, in addition to electron paramagnetic resonance hyperfine coupling constants, can now be calculated for nitrosyl heme systems with relatively good accuracy and that the results so obtained can be used to determine Fe-N-O geometries in metalloproteins. The Z-surface approach is thus applicable to both diamagnetic (CO) and paramagnetic (NO) heme proteins with in both cases the metal-ligand binding geometries found in the proteins being very close to those seen in model systems.

Hemeproteins↗

PubMed2002

Quantitative structure--activity relations for gammadelta T cell activation by phosphoantigens.

gammadelta T cells help contribute to innate immunity and are activated by the natural phosphoantigens produced by the organisms responsible for causing, for example, tuberculosis, malaria, tularemia, and plague. They are also activated by synthetic phosphoantigens and are cytotoxic to tumor cells. Here, we show that it is now possible to accurately predict gammadelta T cell activation by both natural and synthetic phosphoantigens by using the quantitative structure-activity relationship (QSAR) techniques commonly used in drug design. This approach should be of use in developing novel immunotherapeutic agents as well as contributing to a better understanding of the immune system's response to infectious agents.

Antigens, Bacterial↗

PubMed2002

Gender differences in narcotic-induced emesis in the ED.

Narcotic analgesia is commonly given in the emergency department. Narcotic-induced nausea and vomiting is thought to be a common occurrence, but the gender incidence and associations are not well defined. The aim of this study was to document the sex-related complication of nausea and vomiting after opiate administration for pain relief in the ED. The study hypothesis was that men and women have the same rate of narcotic-induced emesis in the ED. A prospective, convenience study of the use of narcotic analgesic on patients in an innercity Level I Trauma Center was undertaken. Information concerning the reason for narcotics, complications, number of doses, and route of administration were studied. The emergency physicians were allowed clinical judgment to treat the patients with any narcotic agent in any dose increment. The data were entered into an SPSS program (Chicago, IL). Analysis between groups (men v women) was then conducted by an independent t test. We compared the 2 groups across 6 categories: cause of injury, presenting pain scale, first drug given, first dose given, first route of drug, and requires an anti-emetic. A Bonferroni procedure was used to correct for the higher probability of significant findings when multiple tests were performed. All findings that are significant are after Bonferroni. The study was Institutional Review Board (IRB) approved. A total of 325 consenting patients were studied from October 1996 to April 1998. The patients consisted of 174 men and 151 women, with an average of 35.8 years of age. The race of the patients was 70% African American and 20% Hispanic. Of the total of 325 patients, 20.3% (74) required an anti-emetic because of nausea and/or vomiting. A significant difference occurred in causes of pain for women (t = 2.79, P <.007). The causes of pain for women were general pain, fracture, abdominal, back pain, and other as compared with men with gun shot wounds, general, fracture, low back, and flank. Women showed no significant difference with regard to presenting pain scale (t =.122, P <.903), first drug given (t = 1.643, P <.101), and first dose given (t =.708, P <.408). The majority of patients received morphine (55.4%), followed by meperidine (24.3%), and hydrocodone (13.5%). The most frequent route of administration was intravenous (IV, 45.2%), intramuscular (IM, 35.7%), with oral being the least frequent route (19.1%). There was a difference for women with first route given (t = 2.543, P <.01) and requires anti-emetic (t = 3.06, P <.002). The majority of women received IM (58.6%) versus IV (37.7%), whereas the majority of men (62.3%) received IV versus IM (41.4%). A significant number of patients became nauseated and/or vomited from Emergency Department-administered narcotics. The nausea and vomiting was associated with female sex and the cause of pain. A comparative study of other pain medications versus narcotics for incidence of induced nausea and emesis would be useful.

Adolescent↗

PubMed2002

Patients' self-treatment with alternative treatment before presenting to the ED.

This study examined the frequency of patients using alternative medicine to treat their condition before presenting to an emergency department (ED). This was a prospective randomized, consecutive survey conducted at a level I 24-bed inner-city trauma center. Patients were eligible for enrollment if they were at least 18 years old and able to consent. Exclusion criteria included patients delivered by an ambulance and patients unable or unwilling to consent. The questionnaire collected information about sociodemographic variables, alternative treatment used, why was it used, who prescribed the treatment, route, treatment satisfaction, and past history of alternative treatment and medication use. A total of 189 patients were surveyed. Of these, 10.6% of the surveyed patients used alternative treatment. The most common reason for using alternative medicine was "I wanted to try the simplest treatment first" (55%). These treatment options were self-prescribed by 55%, advice from a friend or family member by 40% and other health professional in 5%. The alternative medicines included massage (35%), home remedies (20%), prayer (20%), chiropractor (15%), herbal medicines (5%) and other methods (5%). The treatment was administered orally (20%) or topically (80%). Most said that the alternative therapy was helpful (60%). The use of alternative therapy versus no use of alternative therapy was correlated with gender (P =.05), treatment (P =.025) and how it was administered (P =.021). A small but significant number of inner-city patients use alternative treatments before presenting to an ED. Emergency physicians need to consider the use of alternative treatment and medicine by patients presenting to the ED for treatment.

Adolescent↗