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Biomedical subjects

J S Daniels

Publications and source records attributed to J S Daniels.

13 recordsLinked to original sources
PubMed2003

Ectopic lingual thyroid: a case report.

A rare case of lingual thyroid of massive size is being reported in a 28-year-old female patient who presented with dysphonia, fullness in the throat, dysphagia and breathing difficulties. Fibre-optic nasopharyngoscopy revealed a sessile mass occupying the whole of the oro and hypopharynx. The mass was excised and histopathological examination was reported as thyroid tissue. Postoperatively the patient remained euthyroid and did not require thyroxine supplements since the hypoplastic thyroid gland in the prelaryngeal region remained functional.

Adult↗
PubMed2001

Redox-activated, hypoxia-selective DNA cleavage by quinoxaline 1,4-di-N-oxide.

Quinoxaline 1,4-dioxide (4) is the historical prototype for modern heterocyclic N-oxide antitumor agents such as 3-amino-1,2,4-benzotriazine 1,4-dioxide (tirapazamine, 1) and 3-amino-2-quinoxalinecarbonitrile 1,4-dioxide (11). Early experiments in bacterial cell lines suggested that enzymatic, single-electron reduction of quinoxaline 1,4-dioxides under low-oxygen (hypoxic) conditions leads to DNA damage. Here the ability of quinoxaline 1,4-dioxide to cleave DNA has been explicitly characterized using in vitro assays. The hypoxia-selective DNA-cleaving properties of 4 reported here may provide a chemical basis for understanding the cytotoxic and mutagenic activities of various quinoxaline 1,4-dioxide antibiotics.

Antibiotics, Antineoplastic↗
PubMed2000

Pyrimido[1,2-alpha]purin-10(3H)-one: a reactive electrophile in the genome.

Malondialdehyde and base propenal react with deoxyguanosine residues in DNA to form an exocyclic adduct, pyrimido[1, 2-alpha]purin-10(3H)-one (1), that has been detected at high levels in genomic DNA of healthy humans. Previous studies have shown that tris(hydroxymethyl)aminomethane adds to 1 at elevated pH, forming an enaminoimine (2), but it is uncertain whether 1 reacts directly or hydrolyzes under basic conditions to N(2)-(3-oxo-1-propenyl)deoxyguanosine (3) prior to amine addition. We report that 1 reacts at neutral pH with hydroxylamines to form oximes. The rate of reaction of 1 with hydroxylamines at pH 7 is at least 150 times faster than the rate of hydrolysis of 1 to 3. Thus, 1 is directly reactive to nucleophiles. These observations indicate that 1 is an electrophile in the human genome that may react with cellular nucleophiles to form novel cross-linked adducts.

DNA Adducts↗
PubMed1998

Direct evidence for bimodal DNA damage induced by tirapazamine.

The ability of tirapazamine (1, 3-amino-1,2,4-benzotriazine 1, 4-dioxide, SR4233) to fix DNA radical lesions is demonstrated by studying the reaction between the antitumor drug and an oligonucleotide radical that is independently produced at a defined site within a biopolymer. Using beta-mercaptoethanol as a competitor, it was determined that tirapazamine traps a C1'-nucleotide radical with a rate constant of approximately 2 x 10(8) M-1 s-1. Product and isotopic labeling studies suggest that tirapazamine reacts with the radical via covalent adduct formation, resulting primarily from reaction at the N-oxide oxygen. Intermediate covalent adducts could not be observed, but are postulated to decompose to the alkaline labile 2'-deoxyribonolactone lesion. These experiments affirm recent proposals suggesting that tirapazamine can serve as a surrogate for O2 in converting DNA radicals into toxic strand damage events.

Anaerobiosis↗
PubMed1984

The pathogenesis of obesity.

This article clarifies current understanding of the etiology and pathogenesis of obesity, the most common metabolic disorder in humans. Among the factors covered are adipocyte hyperplasia and hypertrophy, setpoint hypothesis, disorders of energy intake, disorders of energy expenditure, thermic effect of food, adaptive thermogenesis, and biochemical defects resulting in obesity.

Adipose Tissue↗
PubMed1978

Purification, characterization, and amino acid sequence of rat anaphylatoxin (C3a).

C3a anaphylatoxin derived from the third component of complement has been isolated from rat serum and its complete amino acid seuqence determined. A three-step purification procedure was employed that consisted of gel filtration on Sephadex G-100, followed by chromatography of the anaphylatoxin-containing pool on carboxymethylcellulose. A subsequent separation on DEAE-Sephadex resolved C3a from minor contaminating peptides. Biological studies have shown that purified rat anaphylatoxin is approximately twice as active as human or porcine C3a when tested for smooth-muscle contraction. In addition to the active form of rat anaphylatoxin, a serum carboxypeptidase B inactivated form of C3a (C3ades-Arg) was purified from rat serum and utilized in subsequent structural studies. Sequence analysis of rat C3a was facilitated by a long automated Edman degradation which established the first 55 residues of the anaphylatoxin. Overlapping peptides were generated by cyanogen bromide and trypsin, and the resultant fragments were sequenced by either automated or manual Edman procedures. The primary structure of rat C3a is 70% identical to the previously determined structures of human and porcine anaphylatoxin. Antisera raised to the purified rat peptide do not cross-react immunologically by Ouchterlony analysis with either human or porcine C3a.

Amino Acid Sequence↗
PubMedDate not supplied

Abnormal nerve conduction in impotent patients with diabetes mellitus.

The etiology of impotence in the diabetic population has not been clearly defined. To assess this problem, 24 impotent diabetic subjects, 21 nonimpotent diabetic subjects, and 10 subjects with psychogenic impotence were compared with nocturnal monitoring of penile tumescence and rigidity, penile arterial blood flow, and nerve conduction of the pudendal nerve. There was no statistical difference in mean age or duration of diabetes among the various study groups. All diabetic subjects who presented with complaints of impotence had severe abnormalities on nocturnal erection monitoring. There was no significant difference in the mean penile brachial index between impotent and nonimpotent diabetic subjects (P = .335). In contrast, there was a significant difference in bulbocavernosus-reflex latency times (P less than .001) between impotent (mean latency 48.4 ms) and nonimpotent (mean latency 38.7 ms) diabetic subjects. This study strongly suggests that impotence in the diabetic population is secondary to functional abnormalities of pelvic nerves and that the bulbocavernosus-reflex latency time is an excellent diagnostic test for assessing function of pelvic nerves in the diabetic individual.

Diabetes Complications↗