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Biomedical subjects

D C Hammond

Publications and source records attributed to D C Hammond.

At least 19 recordsLinked to original sources

The effect of occlusion on the survival of an isolated dorsal skin flap in the rat.

Previous studies have documented that maintenance of a moist environment can increase flap survival in the rat model. However, the distal aspect of the dorsal rat flap can survive as a graft, a fact that masks the behavior of this tissue as a flap, thereby making previous studies difficult to interpret. Using a dorsal rat flap model designed to control for the skin graft variable, the effect of occlusive dressings on flap survival was determined. In two groups of rats (n = 10), treatment with a semipermeable occlusive dressing was compared with no treatment. In both groups, 2 x 7-cm flaps based caudally were raised on the dorsum of each rat and the wound closed beneath the flap to prevent take of the flap as a graft. No significant difference in surviving flap surface area was noted (p greater than 0.2). We conclude that, although a moist environment may enhance wound healing, it will not improve the survival of an ischemic flap.

Animals

The L protein of vesicular stomatitis virus transcription complexes is specifically photolabelled by 5-azido-uridine 5'-triphosphate, an analogue of the RNA polymerase substrate uridine 5'-triphosphate.

A photoactive nucleotide analogue of UTP, 5-azido-uridine 5'-triphosphate (5-N3UTP), has been demonstrated to interact with the RNA polymerase of the vesicular stomatitis virus (VSV) transcription complex. Kinetic studies indicated that 5-N3UTP served as an efficient replacement for UTP in in vitro polymerase reactions. The Km for the azido analogue was 27 microM and that of the natural substrate, UTP, was 7 microM. Photolysis of [gamma-32P]5-N3UTP in the presence of VSV transcription complexes resulted in selective radio-labelling of the L protein. This photolabelling was saturable with an apparent Kd of 28 microM. The L protein was protected from [gamma-32P]5-N3UTP-mediated photolabelling by competing natural substrates (UTP, CTP, ATP, GTP). The stoichiometry of photoprobe incorporation into the transcription complex was close to unity with respect to the L protein. These data provide evidence that the nucleotide-binding domain of the VSV RNA polymerase contains amino acid residues of the L protein.

Affinity Labels

Identification and characterization of serine/threonine protein kinase activity intrinsic to the L protein of vesicular stomatitis virus New Jersey.

A photoaffinity analogue of ATP, 8-azido-adenosine 5'-triphosphate (8-N3ATP), was used to probe ATP-binding sites in native transcription complexes of vesicular stomatitis virus (VSV) (New Jersey serotype). The analogue was found to be a substrate for a serine/threonine protein kinase that phosphorylated both the NS and L proteins of native complexes. The analogue failed to interact with the RNA polymerase, another ATP-utilizing activity associated with the transcription complex. Kinetic analyses of both ATP and 8-N3ATP utilization by the protein kinase yielded biphasic saturation curves. Photolysis of 8-N3ATP in the presence of VSV transcription complexes resulted in selective labelling of the L protein. The photolabelling of L was saturable and apparently biphasic. Photolabelling of the L protein was significantly reduced by competition with ATP whereas other nucleoside triphosphates (GTP, UTP and CTP) were ineffective competitors. The stoichiometry of photolabelling was 0.2 at 10 microM-8N3ATP and 1.3 at 100 microM-ATP. These data provide chemical evidence for a virus-encoded serine/threonine protein kinase which resides on the L protein.

Adenosine Triphosphate

Management of acute and chronic vascular injuries to the arm and forearm. Indications and technique.

Acute arterial injuries of the upper extremity account for half of civilian arterial injuries in the United States. The great majority of these injuries are due to penetrating trauma, with stab wounds and gunshot wounds being the most common cause. The history of the injury and a careful physical examination will identify most injuries. Arteriography should be performed when a vascular injury is suspected but not confirmed by physical examination. Reconstruction of critical vascular lesions is essential for restoration of flow distally. Noncritical lesions may be repaired in most cases, with long-term patency rates averaging 50% to 68%. Although amputation is uncommon after upper-extremity vascular injury, long-term disability can be significant in those patients with concomitant nerve injury. Chronic upper-extremity ischemia may be secondary to atherosclerotic occlusive disease, aneurysms, or arteriovenous fistulas. Angiography will delineate the diseased or occluded arterial segment, allowing bypass to be successful in more than 90% of cases. With careful attention to proper diagnosis and treatment, good to excellent long-term relief of symptoms can be obtained.

Acute Disease

Hypnosis for postpolio syndrome & Type-A behavior.

Many of the hundreds of thousands of survivors of polio are now developing postpolio syndrome. Symptoms include progressive muscle weakness, fatigue, decreased endurance, joint and muscle pain, weight gain, respiratory difficulties, and sleep disturbance, often precipitated or exacerbated by a Type-A Personality pattern. A postpolio patient with Type-A Personality was taught self-hypnosis as a vital component of treatment. Pre-post testing included the Profile of Mood States, the State-Trait Anxiety Inventory, the State-Trait Anger Inventory, and the Personal Orientation Inventory; the patient's spouse was interviewed during the follow-up. At the 6-month follow-up, improvements were documented in pain level, depression, self-regard, self-acceptance, capacity for intimate contact, time competence (living in the present), confusion, anxiety, insomnia, and in trait and state anger. Only a mild improvement occurred in fatigue, and no improvement was found in weight control. Follow-up at 12 months confirmed the maintenance of improvements. Self-hypnosis training may prove extremely helpful for postpolio patients and may prove helpful in modifying central characteristics of Type-A Personality.

Autosuggestion

Malignant degeneration of dermal cylindroma.

Dermal cylindroma is a rare tumor of the cutaneous appendage system, which can undergo aggressive malignant transformation. Clinically this change can manifest as ulceration. The histological features of malignant degeneration are well defined. When these changes occur, prompt excisional biosy or reexcision with clear surgical margins is indicated.

Aged

Controlled tissue expansion of a groin flap for upper extremity reconstruction.

A large upper extremity defect in an 8-year-old girl was resurfaced with an expanded groin flap. Tissue expansion allowed complete coverage of the defect while minimizing the donor deformity. Pretransfer expansion of pedicled flaps offers an alternative to free-flap reconstruction of complex upper extremity defects. This is especially valuable in the pediatric patient, in whom donor-site morbidity can be significant.

Child

1989 ARRS President's Award. The validity and utility of sonography in the diagnosis of appendicitis in the community setting.

Two hundred six patients with suspected appendicitis were examined with sonography over a 6-month period in three community teaching hospitals. Of 41 patients in whom the surgeons judged the clinical findings severe enough to warrant immediate surgery (group A), 34 (83%) had appendicitis, and sonography had a sensitivity of 0.76, a specificity of 0.71, and an accuracy of 0.76. Of 165 patients in whom the surgeons judged the clinical findings severe enough to warrant hospitalization for observation but not immediate surgery (group B), 51 (31%) had appendicitis at subsequent surgery. Sonography had a sensitivity of 0.96, a specificity of 0.94, and an accuracy of 0.95. Of 49 surgeons surveyed, the mean testing threshold (i.e., the probability of appendicitis below which they would send the patient home without further tests or observation) was 0.11, and the mean treatment threshold (i.e., the probability of appendicitis above which they would operate immediately) was 0.82. The posttest probability of appendicitis with findings indicating appendicitis present on sonography was 0.93 in group A and 0.88 in group B, and with findings absent on sonography it was 0.62 in group A and 0.02 in group B. We conclude that in group A patients, the use of sonography remains controversial in the diagnosis of appendicitis, but in group B patients it is both valid and useful.

Appendicitis

Endoscopic tattooing of the colon. An experimental study.

Methods of "tattooing" the colon endoscopically were evaluated in a series of studies on dogs. Injections were performed through a sigmoidoscope using a 25-gauge sclerotherapy needle. The first phase showed excellent staining with methylene blue; however, after 24 hours the stain had completely diffused and was no longer visible. In the second phase, eight agents were evaluated for durability at the site of injection. Only indocyanine green and india ink remained visible on the serosal surface of the bowel after 48 hours. While indocyanine green showed no adverse tissue reaction, india ink caused a significant inflammatory infiltrate with microhemorrhage and thrombosis. The final phase confirmed the staining qualities of indocyanine green. The dye persisted for seven days, and no adverse reactions were noted, either macro- or microscopically. Based on our findings, indocyanine green is an excellent agent for use in tattooing the colon to facilitate intraoperative localization of small colonic lesions. Clinical trials to evaluate the efficacy and safety of this agent in humans are warranted.

Animals

Inhibited sexual desire in women.

A multifaceted study was conducted to identify differences in biopsychosocial characteristics between a clinical group of 59 married women who complained of inhibited sexual desire (ISD) and 31 married women who expressed normal sexual desire (non-ISD). Areas of examination included personality, endocrine, relationship, and sexual dimensions. Instruments of data collection included the MMPI, Dyadic Adjustment Scale, radioimmunoassay of testosterone and prolactin levels, and a questionnaire which focused on demographic, relationship, and sexual information. Statistical analyses indicated nonsignificant between-group differences on demographic characteristics, personality variables, and hormonal evaluation. Statistically significant differences were found between the two groups with regard to sexual history and several marital and sexual dimensions. The ISD group reported significantly greater dissatisfaction with these areas than the non-ISD group. Implications for clinical practice and research are discussed.

Adult

Functional analysis of hypomethylation variants of the New Jersey serotype of vesicular stomatitis virus.

The ts mutant F1 of vesicular stomatitis virus, New Jersey serotype, directs the synthesis of undermethylated 5'-terminal cap structures in vitro. In order to determine the relationship between the ts and hypomethylation phenotypes, a spontaneous revertant rev(ts)F1 of the ts phenotype was analyzed. The revertant retained the hypomethylation phenotype. The four cap structures (GpppA, 7mGpppA, GpppAm, and 7mGpppAm) synthesized in mutant and revertant-directed reactions in the presence of low as well as high concentrations of AdoMet were resolved by HPLC. Quantitation of the data and analysis of cap substrate to product ratios revealed that despite apparent similarities between the two hypomethylation phenotypes, the functional lesions in F1 and rev(ts)F1 were different. F1 displayed an AdoMet concentration-dependent alteration in the GpppA----GpppAm reaction and an AdoMet concentration-independent alteration in the GpppA----7mGpppA reaction. In contrast, rev(ts)F1 displayed AdoMet concentration-dependent alterations in the reactions GpppA----7mGpppA and GpppAm----7mGpppAm.

Methylation

The fates of undermethylated mRNA cap structures of vesicular stomatitis virus (New Jersey) during in vitro transcription.

A dual label pulse-chase analysis employing S-adenosyl-L-[methyl-3H]methionine and [beta-32P]GTP has been devised to identify precursors to the cap structure 7mG(5')ppp(5')Am present on the 5'-termini of vesicular stomatitis virus mRNAs. Both monomethylated cap structures, 7mG(5')ppp(5')A and G(5')ppp(5')Am, have been detected in vitro in New Jersey serotype reactions containing suboptimal concentrations of S-adenosyl-L-methionine. The simultaneous chasing of both radiolabeled substrates allowed the determination of the transcriptive fate of each pulse-labeled cap structure in the total RNA population. Ten percent of the 7mG(5')ppp(5')A cap structure and 27% of the G(5')ppp(5')Am cap structure generated during the pulse were chased into 7mG(5')ppp(5')Am. These results suggested that while there may have been a preferred order of 5'-cap methylation, the order was not compulsory. The dual label analysis also revealed that only 34% of the pulse-labeled G(5')ppp(5')A cap structure could be chased into methylated cap structures. A nascent RNA chain length-dependent "methylation window" is proposed.

Base Sequence

S-(4-bromo-2,3-dioxobutyl)-CoA labels two distinct sites on citrate synthase.

The chemical nature of the inactivation of citrate synthase by S-(4-bromo-2,3-dioxobutyl)-CoA, an active site-directed irreversible inhibitor, has been investigated. Active site-directed inactivation leads to derivatization of either Lys22 by epsilon-amino Schiff base formation or Glu363 by apparent alkylation of the gamma-carboxyl group, respectively. Lys22 is labeled in the tight (catalytic) form of the enzyme while Glu363 is labeled in the open (product release) form. Glu363 and Lys22 are both located at or near the entrance to an active site in the crystal structure of citrate synthase (Remington, S., Wiegand, G., and Huber, R. (1982) J. Mol. Biol. 158, 111-152). Glu363 is in the sequence of the protomer forming the active site while Lys22 is in the sequence of the other polypeptide in the homodimer. Labeling in this region appears to inactivate the enzyme by preventing access of substrates to the active site. A distinct and separate labeling process involves derivatization of Asn192 in the tight (catalytic) form and Ser198 and/or Ser199 in the open (product release) form at a locus far removed from the active site. Labeling at the second site may simply identify chemically reactive residues, or it may identify the binding site for long chain acyl-CoA, which has been identified as a possible allosteric negative effector of citrate synthase (Caggiano, A. V., and Powell, G. L. (1979) J. Biol. Chem. 254, 2800-2806). This second labeling process apparently inactivates the enzyme by interfering with catalytically essential conformational changes.

Affinity Labels

Psychological characteristics of women with inhibited sexual desire.

A multifaceted study was conducted to identify differences in biopsychosocial characteristics between a clinical group of 59 married women who complained of inhibited sexual desire (ISD) and 31 married women who expressed normal sexual desire. This report focuses on the findings obtained from the groups' personality profiles generated by the Minnesota Multiphasic Personality Inventory (MMPI). Statistical analyses indicated no significant differences between the ISD and non-ISD groups with regard to two of the three validity and 10 primary clinical scales of the MMPI. Both group profiles were classified as subclinical with no evidence of serious psychological disturbance. The implications for this nonsignificant association between intrapsychic symptomatology and ISD are discussed.

Adult