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Biomedical subjects

L F Harris

Publications and source records attributed to L F Harris.

At least 19 recordsLinked to original sources

Molecular dynamics simulations in solvent of the glucocorticoid receptor protein in complex with a glucocorticoid response element DNA sequence.

We investigated protein/DNA interactions, using molecular dynamics simulations computed in solvent, between the glucocorticoid receptor (GR) DNA binding domain (DBD) amino acids and DNA of a glucocorticoid receptor response element (GRE). We compared findings obtained from a fully solvated 80 Angstrom water droplet GR DBD/GRE model with those from a 10 Angstrom water layer GR DBD/GRE model. Hydrogen bonding interactions were monitored. In addition, van der Waals and electrostatic interaction energies were calculated. Molecular dynamics simulations from both models yielded similar findings; amino acids of the GR DBD DNA recognition helix formed both direct and water mediated hydrogen bonds at cognate codon/anticodon nucleotide base sites within the GRE right major groove halfsite. Likewise GR DBD amino acids in a beta strand structure adjacent to the DNA recognition helix formed both direct and water mediated hydrogen bonds at cognate codon/anticodon nucleotide base and backbone sites. We also investigated protein/DNA interactions with a 10 Angstrom water layer model consisting of the same GR DBD as above but with a predicted alpha helix attached to the carboxyl terminus of the GR DBD docked at the same GRE as above with additional flanking nucleotides. In this model, the interactions between amino acids of the DNA recognition helix and beta strand and nucleotides within the GRE right major groove halfsite were at cognate codon/anticodon nucleotide sites as found in the two models above. In addition, amino acids within the predicted alpha helix located on the carboxyl terminus of the GR DBD interacted at codon/anticodon nucleotide sites on the DNA backbone of the GRE flanking nucleotides. These interactions together induced breakage of Watson-Crick nucleotide base pairing hydrogen bonds, resulting in bending of the DNA, strand elongation and unwinding events similar to those described for helicases.

Amino Acid Sequence

Disc space infection.

Disc space infection or discitis, an infection of the intervertebral disc with contiguous subchondral vertebral osteomyelitis, most frequently follows prior intervertebral disc surgery or arises by hematogenous dissemination. The majority of cases are located in the lumbosacral spine and are caused by staphylococci. Clinical findings include localized spinal pain and fever. The diagnosis is suggested by radiologic studies (plain x-ray, bone scan, CT scan and MR imaging) and confirmed by culturing blood or material obtained from the involved disc space. Treatment consists of antimicrobial therapy, spinal immobilization and surgical intervention in selected circumstances. Discitis is associated with a good prognosis but residual back pain, limited spinal mobility and neurologic deficit may occur.

Adolescent

Hospitalized tornado victims.

We reviewed the clinical findings of 59 patients admitted to Huntsville's three hospitals during the first 24 hours after the November 15, 1989, tornado and as a result of injury caused by the tornado. Fracture of a bone was the most common injury followed by soft tissue trauma and infection. A variety of non-traumatic conditions also were encountered. Fractures were more frequent above the waist than below and five fractures became infected resulting in osteomyelitis. Infections most often involved the urinary tract and bone and were caused primarily by aerobic gram-negative bacilli. The hospital mortality rate was 7%.

Adolescent

Aquatic hazard Mycobacterium marinum infection.

We describe two patients with Mycobacterium marinum infection and review the pertinent literature. M. marinum infection follows trauma, often trivial, in water or from marine life. Clinical manifestations include superficial cutaneous lesions which are either solitary or multiple in a sporotrichoid distribution, involvement of the deeper structures of the hand and wrist and disseminated disease. Biopsy of infected tissue reveals a mixed suppurative-granulomatous reaction with sparse to absent acid-fast bacilli. Definitive diagnosis is achieved by growing the organism from appropriate specimens. Suggested therapeutic regimens consist of rifampin and ethambutol for advanced disease and infection invading the deeper structures of the hand and wrist and one of the tetracyclines or trimethoprim-sulfamethoxazole for early or minimal disease. Surgical debridement is advised when there is persistent pain, a discharging sinus or previous local injection of corticosteroids.

Adult

Staphylococcus aureus endocarditis in community hospitals.

We compared 13 cases of Staphylococcus aureus endocarditis from community hospitals to previous series all of which originated from university or tertiary care hospitals. In our experience Staph. aureus was the third leading cause of endocarditis and accounted for 20% of cases. The infection presented as one of three syndromes: native valve endocarditis, prosthetic valve endocarditis and endocarditis in drug addicts. Laboratory data revealed leukocytosis; infiltrates, nodules, congestive heart failure and cardiomegaly were seen on chest x-ray; and echocardiography infrequently detected vegetations. Criteria which favored the diagnosis of endocarditis in staphylococcemic patients were: absence of a primary site of infection, community acquisition of infection, metastatic infectious sequelae and vegetations documented by echocardiography. Treatment requires prolonged intravenous administration of high dose bactericidal antimicrobial agents; commonly nafcillin or oxacillin combined for a variable period with gentamicin. The mortality rate in our series was 23% and complications occurred in 70% of cases.

Alabama

Viridans streptococcal endocarditis.

Although responsible for a declining proportion of cases of infective endocarditis, viridans streptococci remain the commonest cause and accounted for 30% of our cases seen in Huntsville, Alabama. Usually viridans streptococcal endocarditis is associated with dental manipulation or infection and underlying heart disease but both conditions were not common in our series. Similar to the experience of other investigators, our patients exhibited a subacute course with fever, dyspnea, weight loss and heart murmur. Echocardiography, reported useful in detecting vegetations in one series, was not a sensitive diagnostic tool in our patients. We confirmed the low relapse rate and mortality rate associated with earlier reports of viridans streptococcal endocarditis but observed a high rate of complications, as noted in a recent series.

Adult

The Nager syndrome.

The Nager syndrome was identified in a newborn infant and in a subsequent sib by prenatal ultrasonography. This report documents an autosomal recessive pattern of inheritance for this disorder.

Abnormalities, Multiple

Subdural empyema and epidural abscess: recent experience in a community hospital.

We treated 31 cases of localized central nervous system infection over a seven-year period in our community hospital. The causes included brain abscess in 18 cases (58%); cranial subdural empyema (CSE) in six cases (20%); spinal epidural abscess (SEA) in four cases (13%); cranial epidural abscess (CEA) in two cases (6%); and spinal subdural empyema (SSE) in one case (3%). Both CSE and CEA were often caused by sinusitis and manifested by fever, headache, altered sensorium, and focal neurologic signs. Treatment consisted of drainage by burr holes or craniotomy followed by long-term administration of parenteral antibiotics. Though all patients with CSE and CEA survived, half had severe residual neurologic deficits. Both SEA and SSE were manifested by fever, spinal pain, and loss of motor function, and both were treated by laminectomy drainage and antibiotic administration. One patient died and three of the other four had residual neurologic deficits or back pain. Diagnosis of CSE and CEA was facilitated by CT scanning, while clinical examination, CT scanning, and myelography were useful in diagnosing SEA; SSE was not suspected preoperatively.

Abscess

Intravenous antibiotics at home.

Intravenous antibiotics can be administered safely and effectively and at substantially less cost in a home environment. Patients who are candidates for this treatment must be in stable condition clinically, possess a ready venous access, and show the mental and physical capabilities required to administer intravenous medication. Antibiotics must be delivered promptly and retain their sterility and activity until infusion. Close monitoring of the patient during therapy is essential. Orthopedic infections, mainly osteomyelitis, septic arthritis, and bursitis, have thus far been our most frequently treated infections, with Staphylococcus aureus, aerobic gram-negative bacilli, and S epidermidis the most commonly encountered pathogens. Penicillins, cephalosporins and aminoglycosides have been given most often. Cure rates have exceeded 85%, and many patients resume usual activities during treatment. Complications are unusual, cost savings are substantial, and patient satisfaction is maximal.

Adult

Chronic mandibular osteomyelitis.

Chronic osteomyelitis of the mandible is an infrequently reported condition, but recent experience with six cases over a 14-month period suggests it is more common than appreciated. Chronic mandibular osteomyelitis results from odontogenic infection, postextraction complication, trauma, or irradiation to the mandible. Clinical findings include local pain and swelling and trismus, but constitutional symptoms are unusual. Radiologic examination discloses radiolucent areas, bony destruction, and sequestrum formation. Pathogenic organisms are normal oral flora, Staphylococcus aureus, and aerobic gram-negative bacilli. Chronic mandibular osteomyelitis must be differentiated from malignant disease involving the mandible. Diagnosis is accomplished by bone biopsy and culture. Treatment involves through surgical debridement and prolonged antimicrobial therapy. Osteoradionecrosis of the mandible is extremely recalcitrant to conventional therapy, but aggressive surgery and treatment have proven effective.

Adult