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Biomedical subjects

D C Young

Publications and source records attributed to D C Young.

At least 19 recordsLinked to original sources

Collisionally induced dissociation in the study of A-ring hydroxylated vitamin D type compounds.

Collisionally induced dissociation (CID) is often used to determine the structure of ions based on comparison with the CID spectra of known ions. The latter are generated from judiciously selected compounds taking into account basic principles of ion chemistry. We report here on the use of this approach toward determination of the site of A-ring hydroxylation of vitamin D. Although not intrinsically an aromatic compound, vitamin D gives rise in its mass spectrum to an aromatic methylstyryl cation at m/z 118. A-ring hydroxylated metabolites of vitamin D would thus incorporate the extra OH group on the ion at m/z 118, shifting it to m/z 134. The position of substitution of the extra OH group on a metabolite could then be ascertained by comparing the CID spectrum of its m/z 134 fragment to those of the four possible (hydroxymethyl)styryl cations generated from synthesized authentic compounds. Because of their propensity to polymerize, these cations were generated in situ via the McLafferty rearrangement of the corresponding (hydroxyphenyl)ethanols. For optimum differentiation of isomeric ions, preparation of permethylated derivatives of vitamin D was necessary. The validity of the hypothesis was verified using 1,25-dihydroxy-vitamin D3 as a test compound. This method provides a viable approach for the characterization of A-ring hydroxylated metabolites of vitamin D as well as for related aromatic compounds.

Binding Sites

Superficially invasive squamous cell carcinoma of the cervix.

The microscopic pathologic features of early invasive squamous cell cervical carcinoma are used as determinants for the treatment of these lesions. This study is a retrospective review of 180 patients with squamous cell cervical carcinoma with invasion to a depth of 5 mm or less. Invasion of less than or equal to 1 mm, greater than 1 but less than or equal to 3 mm, greater than 3 but less than or equal to 5 mm was noted in 37, 84, and 59 patients, respectively. The median follow-up was 6.5 years. Four (2.2%) patients developed carcinoma in situ of the vagina and four (2.2%) patients progressed to invasive squamous carcinoma. Pelvic lymph node metastases were rare (1%). No patient has died from recurrent disease. Analysis of numerous clinical and pathological variables identified no risk factors for recurrence. Most (54/68) patients with tumor invading beyond 3 mm or with tumor demonstrating vascular invasion were treated by traditional "radical" methods. This limited a meaningful analysis of the risk of conservative treatment. The reliability of using the existing definitions of microinvasive disease for the guidance of treatment remains controversial. Further clarification may be rendered only with prospective clinical-pathologic studies performed by cooperative groups.

Adult

Substrate and endocrine responses during exercise at selected stages of pregnancy.

To determine whether the concomitant effects of pregnancy and exercise yield substrate and endocrine patterns different from those expected during exercise alone, we compared the responses of glucose, lactate, free fatty acids, insulin, epinephrine (EP), norepinephrine (NE), human chorionic gonadotropin (HCG), human placental lactogen (HPL), estriol, and progesterone (P) in nonpregnant women (NP; n = 7) and pregnant women in the second (TR2; n = 6) and third trimester (TR3; n = 8) of pregnancy, before, during, and after 30 min of bicycle ergometer exercise at heart rates of 130-140 beats/min. In general, all substrates and hormone concentrations increased with exercise (P less than 0.05), except insulin, which decreased (P less than 0.05), and HCG, which did not change (P = 0.08). Differences in selected hormone concentrations (P, estriol, HCG, and HPL) among groups were already present at rest because of the different stages of pregnancy. Differences among groups at rest were also found in insulin and NE (P less than 0.05). Significantly different responses to exercise (i.e., group x time interactions) were as follows. NP vs. TR2:P, estriol, HCG, HPL, EP, and NE (P less than 0.05); NP vs. TR3: glucose, EP, and NE (P less than 0.05); TR2 vs. TR3: lactate, EP, and NE (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Analysis of risk factors for postoperative pulmonary complications in head and neck surgery.

Preoperative pulmonary function tests (PFTs) are unproven in their predictive value for postoperative pulmonary complications. There is a lack of prospective outcome studies upon which to form an opinion, particularly regarding noncavitary surgery. Seventy-three head and neck surgery patients were prospectively evaluated with preoperative PFTs, arterial blood gas analysis (ABG), medical history, and physical examination. Age, anesthesia duration, forced expiratory volume in 1 second (FEV1), peak flow (PF), PaO2, Roizen class, and pack years of smoking were significantly correlated with postoperative pulmonary complications. As similar studies in head and neck surgery patients have not been previously taken, it is hoped that these results will serve as a basis for future endeavors.

Age Factors

The incidence of permanent upper and lower extremity profiles in active duty Army officers.

The records of 89,955 active duty Army officers were reviewed to determine their incidence of permanent upper and lower extremity profiles. Only 1,706 officers (1.897%) have permanent upper or lower extremity profiles. However, the incidence of such profiles varies with respect to rank, branch, and sex. Some officer groups have an incidence as high as 37%. Although the overall incidence of such profiles is quite low, the dramatically increased incidence in some officer groups demands scrutiny.

Cross-Sectional Studies

DNA ploidy and prostate-specific antigen as prognostic factors in clinically resectable prostate cancer.

Prostate-specific antigen (PSA) and DNA ploidy as measured by flow cytometry were compared with conventional prognostic indicators in 112 patients who underwent radical prostatectomy for clinically resectable prostate cancer. The variables examined included age, race, prostatic acid phosphatase (PAP), Gleason score of the radical prostatectomy specimen, and pathologic stage. No significant relationships were found between DNA ploidy and age, mean PAP value, and absolute PAP value. Of the 112 patients, 65 (58.0%) had disease limited to the prostate (pathologic Stages A and B); 47 (42.0%) had extraprostatic disease (pathologic Stages C and D1). The stage was related to the Gleason score (P less than 0.0001) where extraprostatic disease was associated with a Gleason score of 6 to 10. Nineteen (17.0%) patients had aneuploid tumors, and 93 (83.0%) had diploid tumors. DNA ploidy significantly correlated with pathologic stage (P = 0.04); aneuploidy was identified more frequently in patients with Stages C and D1 tumors. Aneuploid tumors occurred more frequently than diploid tumors in patients with a Gleason score of 6 to 10 (P = 0.034). Mean PSA values were higher in patients with aneuploid tumors (P = 0.078), extraprostatic neoplasms (P = 0.00001), and cancers with a Gleason score of 6 to 10 (P = 0.0004). Furthermore, PSA values greater than 10.0 ng/ml were associated with extraprostatic disease and a Gleason score of 6 to 10 (P less than 0.05 and P less than 0.001, respectively). Significant racial differences were found with respect to DNA ploidy, mean DNA indices, and mean PSA values. The 18 black patients had more DNA aneuploid tumors (P = 0.043), a higher mean DNA index (P = 0.017), and a higher mean PSA value (P = 0.043) than the 94 white patients. Both PSA and DNA ploidy analysis by flow cytometry appear to be valuable indicators in the evaluation of patients with prostatic carcinoma.

Acid Phosphatase

Structure and organization of the gas vesicle gene cluster on the Halobacterium halobium plasmid pNRC100.

Halobacterium halobium strain NRC-1 contains intracellular gas-filled vesicles (GVs) that confer buoyancy to the cells. Cloning of the major GV protein (GvpA)-encoding gene, gvpA, and analysis of GV-deficient mutants (Vac-) of H. halobium led to the identification of a region of a 200-kb plasmid, pNRC100, important for GV synthesis. We report here the nucleotide sequence of an 8520-bp region which, including gvpA, contains twelve open reading frames (ORFs) that are organized into two divergent transcription units, gvpAC oriented rightward, and gvpD, E, F, G, H, I, J, K, L, and M located upstream from gvpAC and oriented leftward. Insertions into the gvpA promoter and gvpD and E resulted in the Vac- phenotype. The overall gene organization is highly compact with the end of one ORF overlapping with the beginning of the next in most cases. The gene cluster is bracketed by two ISH8 element copies in inverted orientation, an organization suggestive of a composite transposon. Comparison of predicted amino acid sequences showed homology between GvpA, and the gvpJ and gvpM putative gene products. The putative gvpC gene product contains eight copies of an imperfectly repeated sequence with similarity to repeats in a cyanobacterial GvpC plus a highly acidic C-terminal region not found in the cyanobacterial homologue.

Amino Acid Sequence

Complications of a failed Bristow procedure and their management.

The management of patients who have a failed Bristow reconstruction of the shoulder is very complex. In order to determine the complications that occur when a Bristow procedure fails, and how they should be managed, we retrospectively evaluated forty shoulders in thirty-nine patients who had been treated by the senior one of us for a failed Bristow procedure from 1977 to 1987. The complications of the index Bristow procedures included recurrent painful anterior instability, injury to the articular cartilage, failure of the coracoid bone-block to unite with the glenoid, loosening of the screw, neurovascular injury, and posterior instability. The primary etiology of failure of the index Bristow procedure was excessive laxity of the capsule in thirty-two shoulders (80 per cent) that were affected by chronic, painful anterior or posterior instability. An untreated Perthes-Bankart lesion was present in the remaining eight shoulders (20 per cent). The use of anterior reconstruction for the revision of a failed Bristow procedure is a difficult operation that necessitates meticulous technique. As our over-all plan of treatment resulted in a good or excellent outcome in only 50 per cent of the patients, we do not recommend the Bristow procedure for primary treatment of symptomatic anterior instability of the shoulder.

Adolescent

Non-union of fractures of the mid-shaft of the clavicle. Treatment with a modified Hagie intramedullary pin and autogenous bone-grafting.

We reviewed a series of fifty patients who had a non-union of a fracture of the clavicle. Twenty-one patients (42 per cent) who had a symptomatic non-union of the middle of the shaft of the clavicle were treated with open reduction, internal fixation with a modified Hagie intramedullary pin, and autogenous bone-grafting, and those patients form the basis for the report. The average duration of follow-up was thirty-five months (range, five months to eleven years). Healing occurred in twenty (95 per cent) of the twenty-one patients. Intramedullary fixation has several advantages compared with other treatments, such as fixation with a plate and screws. It can be performed through a cosmetically acceptable incision in the Langer line; less dissection of the soft tissues is needed; and, after healing, the pin can be removed through a small incision under local anesthesia.

Adult

Gas chromatography-mass spectrometry of conjugated dienes by derivatization with 4-methyl-1,2,4-triazoline-3,5-dione.

The dienophile 4-methyl-1,2,4-triazoline-3,5-dione forms stable adducts with conjugated dienes by generating Diels-Alder cycloaddition products. The reaction is rapid, highly selective for conjugated dienes and the derivatives are suitable for analysis by gas chromatography. Their mass spectra are marked by their simplicity and by the presence of abundant fragment ions diagnostic of the diene position in the parent compound.

Alkenes

Immunological effects of flavone acetic acid.

Flavone acetic acid (FAA) enhances natural killer and lymphokine-activated killer (LAK) cell activity in mice. We examined the immunological effects of FAA on human blood cells both in vivo and in vitro. Peripheral blood natural killer and LAK activity and lymphocyte subsets were evaluated in cancer patients after receiving 3-h infusion of FAA at either 8.5 or 10 g/m2 with alkalinization. Natural killer cell activity and the number of Leu-19 (CD56) positive cells decreased at 24 h after infusion; significant changes in LAK activity and the number of Leu-1 (CD5), Leu-3 (CD4), Leu-2 (CD8) cells were not observed. Peripheral blood mononuclear cells and peripheral blood lymphocytes collected from healthy volunteers were exposed in vitro to FAA, interleukin 2, and FAA plus interleukin 2. FAA, alone or in combination, failed to enhance LAK activity at any time point or concentration from peripheral blood mononuclear cells and peripheral blood lymphocytes. Concentrations of greater than or equal to 100 micrograms/ml antagonized the generation of LAK activity from interleukin 2 treated peripheral blood lymphocytes. These data suggest that FAA may not be useful in enhancing immunological responses in humans.

Adult

Improving diagnostic accuracy of cervical metastases with computed tomography and magnetic resonance imaging.

Elective neck dissection in patients with head and neck cancer continues to be controversial. The management of these patients would be greatly facilitated by improvements in predicting cervical metastases. Recent investigations have suggested that computed tomography and magnetic resonance imaging are more sensitive in detecting cervical metastases than physical examination. The Department of Otolaryngology at the Ohio State University Hospitals, Columbus, undertook a prospective study to compare the preoperative sensitivities of physical examination, computed tomography, and magnetic resonance imaging with pathologic findings in 27 patients undergoing neck dissections for head and neck cancer. The results indicate that computed tomography and magnetic resonance imaging were more sensitive (84% and 92%, respectively) than physical examination (75%), although the results did not achieve statistical significance. The sensitivity of combined computed tomography and magnetic resonance imaging was 90%.

Head and Neck Neoplasms

Prognostic factors in patients with primary transitional cell carcinoma of the upper urinary tract.

A total of 50 patients with primary transitional cell carcinoma of the upper urinary tract underwent deoxyribonucleic acid ploidy characterization by flow cytometric analysis of paraffin embedded specimens. The primary tumor was diploid in 29 patients (58%) and aneuploid in 21 (42%). Aneuploidy was identified more frequently in grade 3 than in grades 1 and 2 neoplasms (p = 0.001). Additionally, grade 3 neoplasms occurred more often with invasive (stages T2 to T3) compared to superficial (stages TA, TIS and T1) tumors (p = 0.002). However, deoxyribonucleic acid ploidy was not significantly associated with tumor stage. Among the 49 patients treated by a definitive operation the median survival free of disease and median over-all survival were 33.7 and more than 120 months, respectively. Variables examined included deoxyribonucleic acid ploidy, tumor grade, tumor stage, primary tumor site and type of operation. In the univariate analysis deoxyribonucleic acid ploidy was the only significant predictor of survival free of disease (p = 0.04). Aneuploid tumors had a median survival free of disease of 19 versus 59 months for diploid tumors. However, in the multivariate analysis of factors affecting survival free of disease, the type of operation performed was the only significant variable. Patients undergoing nephroureterectomy with en bloc bladder cuff excision had a favorable survival free of disease (p = 0.04). Tumor stage was the only significant factor associated with over-all survival in univariate and multivariate analyses (p = 0.02 and 0.005, respectively). Patients with superficial tumors had a median survival of more than 120 versus 72 months for patients with invasive tumors. The data suggest that deoxyribonucleic acid ploidy may be a useful parameter to identify risk groups and plan the management of patients with primary transitional cell carcinoma of the upper urinary tract.

Carcinoma, Transitional Cell

Self-catalyzed linkage of poliovirus terminal protein VPg to poliovirus RNA.

The poliovirus terminal protein, VPg, was covalently linked to poliovirus RNA in a reaction that required synthetic VPg, Mg2+, and a replication intermediate synthesized in vitro. The VPg linkage reaction did not require the viral polymerase, host factor, or ribonucleoside triphosphates and was specific for template-linked minus-strand RNA synthesized on poliovirion RNA. The covalent nature of the bond between VPg and the RNA was demonstrated by the isolation of VPg-pUp from VPg-linked RNA. A model is proposed in which the tyrosine residue in VPg forms a phosphodiester bond with the 5'UMP in minus-strand RNA in a self-catalyzed transesterification reaction. It appears that either the RNA, VPg, or a combination of both forms the catalytic center for this reaction.

Base Sequence

Interference with vaccinia virus growth caused by insertion of the coding sequence for poliovirus protease 2A.

Attempts were made to express noninfectious derivatives of full-length type 1 (Mahoney) and type 2 (Lansing) poliovirus cDNAs in live recombinant vaccinia viruses for vaccine purposes. Vaccinia virus (VV) would not tolerate insertions of polio cDNA containing the coding sequence for the polio protease 2A. However, polio cDNA with the 2A gene deleted either in vivo or in vitro could be inserted into VV and stably maintained. Genetic evidence indicated that expression of the polio 2A gene in trans from transfected plasmid DNA was deleterious to vaccinia virus within the same cell. The 2A product presumably interferes with VV growth by modifying the host translational machinery such that translation of host and vaccinia capped mRNAs is inhibited. Polio cDNA containing a mutated 2A gene whose product is no longer active in host protein shutoff could be inserted into VV. However, inserts containing the intact mutated 2A gene did not synthesize detectable poliovirus protein, although they did produce polio-specific RNA. Expression of polio-specific protein was detected from a VV-polio recombinant containing cDNA encoding the capsid proteins plus an incomplete 2A gene. These results have implications regarding possible vaccine construction, and suggest a mechanism for interference between polio and vaccinia viruses in mixed infection.

Animals

Radical neck dissection: is it enough?

This series of 307 patients who underwent radical neck dissection showed an overall recurrence rate of 19 percent. Clinical staging of disease was an accurate predictor of both recurrence and survival. Extranodal disease dramatically increased recurrence and decreased survival. Although our recurrence rate after radical neck dissection was lower than that previously reported for surgery alone, it was still significantly higher than that after adjuvant radiotherapy. We conclude that histologically proved neck disease should be treated by radical neck dissection, followed by adjuvant radiotherapy to decrease recurrence and, it is hoped, improve survival.

Aged