Nitroreductases and glutathione transferases that act on 4-nitroquinoline 1-oxide and their differential induction by butylated hydroxyanisole in mice.

These studies concern the initial steps in 4-nitroquinoline 1-oxide (4NQO) metabolism in relation to mechanisms of anticarcinogenesis. Butylated hydroxyanisole (BHA) administration by a protocol known to inhibit the pulmonary tumorigenicity of 4NQO in A/HeJ mice enhanced hepatic and pulmonary activities for 4NQO metabolism by two major pathways, conjugative detoxification and nitroreductive activation. High-performance liquid chromatography analysis showed approximate doubling of two types of glutathione transferase subunits with 4NQO-conjugating activity in livers of BHA-treated mice. Similar increases were observed in hepatic 4NQO-conjugating activity and in Vmax, while Km for 4NQO was 39 to 43 microM. Pulmonary 4NQO-glutathione transferase activity increased 24 to 29%. DT diaphorase activity toward 4NQO was elevated 3.3-fold in livers and 2.7-fold in lungs of BHA-treated mice. However, the predominant 4NQO reductase of liver and lung was dicumarol resistant, had a strong preference for NADH, and showed little if any response to BHA. This Mr 200,000 enzyme, partially purified from livers of Swiss mice, exhibited the stoichiometry of 2-NADH/4NQO expected for reduction of 4NQO to 4-hydroxyaminoquinoline 1-oxide. Its high affinity for 4NQO (Km, 15 microM) signified a much greater influence on 4NQO metabolism than DT diaphorase (Km, 208 microM). The dicumarol-resistant 4NQO reductase differed from several known cytosolic nitroreductases. The results suggest that protection by BHA may result from alteration of the balance between 4NQO activation and conjugation.     

Association of BRCA2 polymorphism at codon 784 (Met/Val) with breast cancer risk and prognosis.

PURPOSE: The association of BRCA2 polymorphisms at codon 372 [Asn (N)/His (H)]and codon 784 [Met (M)/Val (V)] with breast cancer risk was evaluated in Japanese women. In addition, the prognostic significance of these polymorphisms was studied in breast cancer patients. EXPERIMENTAL DESIGN: A case-control study was conducted to examine the association of the BRCA2 N/H372 polymorphism and M/V 784 polymorphism with breast cancer risk (cases = 149, controls = 154). The prognostic significance of these polymorphisms was evaluated in 139 patients with primary breast cancer. RESULTS: No significant association was observed between the N/H372 polymorphism and breast cancer risk. In contrast, a significant increase in breast cancer risk (odds ratio, 2.03; 95% confidence interval, 1.07-3.87) was observed in carriers of the variant allele (V784) of the M/V784 polymorphism as compared with noncarriers after adjustment for the classical risk factors, age, family history, parity, body mass index, and so forth. Among breast cancer patients, various clinicopathological parameters including menopausal status, tumor size, lymph node status, histological grade, and estrogen-receptor status were not significantly different between the carriers and noncarriers of the variant allele with regard to both N/H372 and M/V784 polymorphisms. The N/H 372 polymorphism was not significantly associated with patient prognosis. On the other hand, breast cancer patients carrying the variant allele of M/V784 polymorphism showed a significantly (P = 0.014) lower 3-year disease-free survival rate (63%) than noncarriers (92%). Multivariate analysis has revealed that the M/V784 polymorphism is a significant prognostic factor, being independent of the other conventional prognostic factors such as lymph node status and estrogen receptor status. CONCLUSION: These results suggest that the M/V784 polymorphism, but not the N/H372 polymorphism, would be useful in the selection of women at high risk for developing breast cancer and would also serve as a clinically useful prognostic factor in breast cancer patients.     

Disclosure of sexual abuse. The secret is out--what now?

The sexual abuse of a child is a well-kept secret. Disclosure creates difficulties for the child, the family, and sometimes for the professionals working with them. A multidisciplinary, multiagency model is one method to facilitate care and recovery for the child victim. Each agency and service has a different purpose and goal. Cooperative coordination and communication are the keys to case management with reduced psychological trauma for the child and family. Child psychiatric nurses can be effective members of the child abuse health team model. Advocacy roles also can be developed by nurses who work with sexual victimization through the avenues of media, writing, committee membership and research.     

Energetics and evolution: An emerging research domain

The study of energetics is important to human biology because the availability and utilization of food energy influence health, survival, and reproduction. Over the last decade, human biologists, biological anthropologists, and other evolutionary scientists have increasingly come to recognize the importance of energy dynamics in shaping evolutionary processes. Thus far, different lines of energetics research have been conducted largely in isolation from one another. This thematic collection examines topics of evolutionary energetics from several different perspectives, drawing together research from human paleontology, comparative primate and mammalian biology, human population biology, and mathematical modeling. It represents a starting point for further integrative research on human evolutionary energetics. Am. J. Hum. Biol. 14: 547–550, 2002. © 2002 Wiley‐Liss, Inc.     

Two unusual duplication anomalies of the urinary tract: use of percutaneous urography

We performed suprapubic percutaneous urography in two patients to diagnose unusual duplication anomalies of the urinary tract, since preoperative diagnosis was unclear after routine noninvasive studies. In both patients standard suprapubic puncture technique was employed. The procedure was used to confirm the diagnosis of duplication of the bladder in one case and to establish the site of origin of a ureterocele in the other. The technique employed in suprapubic cystography may be extended to the diagnosis of unusual cystic abnormalities in the pelvis that may be of urinary tract origin.     

Quantitative evaluation of adhesive properties and drug-adhesive interactions for transdermal drug delivery formulations using linear solvation energy relationships.

This paper describes the results of the application of linear solvation energy relationships (LSERs) to quantitatively characterize the properties of adhesives and to evaluate the degree of drug-adhesive interaction in transdermal drug delivery formulations. Probe solutions were prepared in acetonitrile (ACN) for a set of probe compounds with different physicochemical properties, and were used to swell the adhesives for subsequent probe molecule-adhesive interactions. The degree of the interactions was measured by the 'sorbed' amount of probe molecules. Based on LSERs, the 'sorbed' amounts were linearly correlated with their properties. The corresponding coefficients reflect the differential interactions of these molecules with the adhesive and ACN, and are quantitative indications of the adhesive properties. Two different transdermal acrylate adhesives (isooctyl acrylate/acrylamide/vinyl acetate in the weight ratios of 75/5/20 and isooctyl acrylate/2-hydroxyethyl acrylate/vinyl acetate in the weight ratios of 58/20/18) were selected for the evaluation of the methodology. It is concluded that the first adhesive is more basic and hydrophobic, which is consistent with the use of acrylamide monomer and significant amount of isooctyl acrylate. The second adhesive is more acidic and polarizable due to a relatively high amount of the 2-hydroxyethyl acrylate. Additionally, the 'sorbed' amount can be regarded as an interaction parameter or index between a drug molecule and the adhesive. Finally, this parameter is expected to correlate with the thermodynamic properties of transdermal formulations such as drug solubility, diffusion coefficient, release rate, and maybe skin permeation rate.     

Penicillamine-Induced Degenerative Dermatoses: Report of a Case and Brief Review of Such Dermatoses

We describe a case of elastosis perforans serpiginosa with additional findings of degenerative skin changes. A 20-year-old man with hepatolenticular degeneration, under prolonged treatment with D-penicillamine, presented with a circular or serpiginous arrangement of nuchal papules. Histopathologically, transepidermal channels were accompanied by granulomatous reactions, with several giant cells engulfing elastic fibers. In addition to these findings of a typical elastosis perforans serpiginosa, we observed scar-like skin changes inside the circular arrangement of the papules. At the scar-like tissue, we found electron-microscopical evidence of randomly aggregated thin collagen fibers with no tendency toward systemic combined bundle formation, which is a characteristic feature of normal collagen fiber formation. Pseudoxanthoma-elasticum-like changes were observed on his neck. On his axillae and groin, slight skin thickening and wrinkling were detected. The diagnosis of elastosis perforans serpiginosa does not represent all of the manifestations or the pathological background described above. The skin manifestations described here represent not only an elastosis but also a total degenerative dermatosis with over-healed collagenosis. Thus, those dermatoses should be summarized as one entity, penicillamine-induced degenerative dermatosis. After considering the pathogenic background and clinical similarities, we further propose to simplify the penicillamine-induced skin manifestations to three categories: acute sensitivity reactions, bullous dermatoses, and degenerative dermatoses.     

Coexistence of cerebral aneurysm and angiographically occult AVM in the occipital lobe; a case report]

The authors report a case of an 8-year-old boy with coexistent aneurysm and arteriovenous malformation (AVM) at the periphery of the left middle cerebral artery. The patient was referred to our hospital because of intracerebral hematoma in the occipital lobe. Angiography revealed an aneurysm at the periphery of the left middle cerebral artery. A small AVM was found, adjacent to the aneurysm, by histological examination of the aneurysm and surrounding tissue resected by surgery. The patient was discharged uneventfully 17 days after surgery. The association of intracranial aneurysm with AVM is reported to be seen in 1.4% of patients with intracranial aneurysms, and 6.4% to 16.7% of patients with an intracranial AVM. Three hypotheses have been proposed in order to explain the association of an aneurysm with AVM: (1) Congenital multiple disorders of vascular development, (2) Hemodynamic stress resulting from the presence of an AVM, (3) Coincidence without any causal relationship between them. The coexistence of the two vascular lesions, adjacent to each other at the peripheral cerebral arteries is rare. Only 7 cases have been reported in the literature. Four of the 8 cases including ours were children, and 6 of the 8 cases were thought to have had a hemorrhage from the AVM. It is likely that the coexistence of the two lesions in our patient is of congenital origin, because the influence of hemodynamic stress from the AVM seemed little and coexistence of the lesions as found in our case is more frequently seen in childhood.     

Cocaine decreases self-control in rats: a preliminary report

Cocaine abuse is often associated with behavior that takes into account short-term, but not long-term consequences. However, there has been no empirical research concerning the effects of cocaine on self-control (choice of a larger, more delayed reinforcer over a smaller, less delayed reinforcer). In the present research, when food-deprived rats repeatedly chose between a larger, more delayed food reinforcer and a smaller, less delayed food reinforcer, chronic intraperitoneal injections of 15 mg/kg cocaine (but not 10 mg/kg fluoxetine) decreased the rats' choices of the larger, more delayed reinforcer. Cocaine can decrease rats' self-control.