Endemic infection of a cat colony with a feline calicivirus closely related to an isolate used in live attenuated vaccines.

We have typed three feline calicivirus (FCV) isolates obtained over a 5-month-period from an endemically infected cat colony. Sequence analysis from variable region E of the capsid gene from these isolates strongly suggests they are minor variants of a single FCV strain, and that this strain is closely related to the one used in many live-attenuated FCV vaccines. Such a vaccine was last used approximately 2 months before the first of the isolates in this study was obtained. Sequence differences between the 'colony isolate' and the vaccine virus suggest that the colony virus has evolved from the vaccine virus and was persisting in the colony. The extent to which vaccine virus may contribute to the continued high prevalence of FCV needs to be determined.

Selective estrogen receptor modulators and postmenopausal women's health.

Selective estrogen receptor modulators represent an alternative approach to the use of estrogen replacement therapy or hormone replacement therapy for decreasing postmenopausal bone loss, as well as for reducing the incidence of serious cardiovascular disease in this population. Of particular interest is raloxifene, a benzothiophene compound, which binds with high affinity to the estrogen receptor and produces effects similar to estrogen on the skeleton and cardiovascular system but behaves as a complete estrogen antagonist in the uterus and the breast. The pharmacologic profile of raloxifene, a discussion of a possible mechanism of action, and the potential role of this drug in women's postmenopausal health are the subjects of this review.

Naphthyridinomycin-DNA adducts: a molecular modeling study.

Monocovalent groove binding complexes of antitumor antibiotic naphthyridinomycin and its analogs with DNA sequence d(ATGCAT)2 have been studied by molecular mechanics to understand which enantiomer of the drug and what chirality at C(7) of the drug are preferred for forming better drug-DNA adducts. The effect of hydroquinone intermediate and the substitution at C(11) on drug-DNA interactions have also been investigated. The results indicate that the enantiomer that forms the best adduct is different from the one reported earlier in the literature. The drug with an R configuration at C(7) is preferred for binding. The hydroquinone models do not necessarily provide a given analog of the drug with additional favorable DNA interactions. The substitution at C(11) by OH provides the best binding model. This finding agrees well with the results from previous biochemical studies. The sequence specific studies indicate that the sequence d(ATGCAT)2 is slightly preferred over others.

Structural, conformational, and theoretical binding studies of antitumor antibiotic porfiromycin (N-methylmitomycin C), a covalent binder of DNA, by X-ray, NMR, and molecular mechanics.

X-ray, NMR, and molecular mechanics studies on antitumor antibiotic porfiromycin (C16H20N4O5), a covalent binder of DNA, have been carried out to study the structure, conformation, and theoretical interactions with DNA. The crystal structure was solved by direct methods and refined to an R value of 0.052. The configurations at C(9), C(9a), C(1), and C(2) are S, R, S, and S, except for the orientation of the aziridine ring and (carbamoyloxy)methyl side chain. The five-membered ring attached to the aziridine ring adopts an envelope conformation. The solution conformation is similar to that observed in the solid state except for the (carbamoyloxy)methyl side chain. Monovalent and cross-linked models of the drug bound to DNA have been energetically refined by using molecular mechanics. The results indicate that, in the case of monocovalent binding, the drug clearly prefers a d(CpG) sequence rather than a d(GpC) sequence. In the case of the cross-linked model there is no clear-cut preference of d(CpG) over d(GpC), indicating that the binding preference of the drug may be kinetic rather than thermodynamic.

Structural and conformational analysis of pentostatin (2'-deoxycoformycin), a potent inhibitor of adenosine deaminase.

X-ray, NMR and molecular mechanics studies on pentostatin (C11H16N4O4), a potent inhibitor of the enzyme adenosine deaminase, have been carried out to study the structure and conformation. The crystals belong to the monoclinic space group P21 with the cell dimensions of a = 4.960(1), b = 10.746(3), c = 11.279(4)A, beta = 101.18(2) degrees and Z = 2. The structure was solved by direct methods and difference Fourier methods and refined to an R value of 0.047 for 997 reflections. The trihydrodiazepine ring is nonplanar and adopts a distorted sofa conformation with C(7) deviated from the mean plane by 0.66A. The deoxyribose ring adopts a C3'-endo conformation, different from coformycin where the sugar has a C2'-endo conformation. The observed glycosidic torsion angle (chi = -119.5 degrees) is in the anti range. The conformation about the C(4')-C(5') bond is gauche+. The conformation of the molecule is compared with that of coformycin and 2-azacoformycin. 1 and 2D NMR studies have been carried out and the dihedral angles obtained from coupling constants have been compared with those obtained from the crystal structure. The conformation of deoxyribose in solution is approximately 70% S and 30% N. Molecular mechanics studies were performed to obtain the energy minimized conformation, which is compared with X-ray and NMR results.

Molecular structure, conformation and interactions of antitumor antibiotic cyanonaphthridinomycin, a covalent binder of DNA.

X-ray, NMR and molecular modeling studies on cyanonaphthridinomycin (C22H26N4O5), a DNA binding antibiotic, have been carried out to study the structure, conformation and interactions with DNA. The crystals belong to the space group P21 with the cell dimensions of a = 5.934(1)b = 20.684(4), c = 16.866(3)A, gamma = 90.9 degrees and Z = 4(two molecules/asymmetric unit). The structure was solved by direct methods and difference Fourier methods and refined to an R value of 0.087 for 4061 reflections. The conformation of the molecule is compared with that of naphthridinomycin. There are differences in the orientation of the methoxyl group and the saturated oxazole ring. 1 and 2D NMR studies have been carried out and the dihedral angles obtained from coupling constants have been compared with those obtained from the crystal structure. Molecular mechanics studies were carried out to obtain the energy minimized structure and its comparison with X-ray and NMR results. Molecular modelling studies were performed to propose models for drug-DNA interactions. Both partial intercalation and groove-binding models have been proposed.

Lupus nephritis. Experience with 230 patients in a private practice from 1950 to 1980.

Nephritis developed in 230 of 609 private patients with systemic lupus erythematosus (SLE) (38 percent) followed up from 1950 to 1980. Eighty-seven percent of patients with nephritis were female; 71 percent were Caucasian. They were observed a mean of 10 years. Five- and 10-year survival rates were 80 percent and 65 percent, with improvement to 86 percent and 76 percent in the last decade. Normalization of urinary sediment and protein levels, blood pressure and serum albumin levels correlated with improved survival and tended to occur during the first year. Life-threatening complications of SLE were more common after the onset of nephritis but decreased as renal function worsened. Infection was the most frequent cause of death in the last decade. Forty-four patients received nitrogen mustard; 55 percent of the courses were followed by significant improvement in renal function and reduced steroid dosage. Control of the disease was associated with improved long-term survival of patients with SLE.

Familial systemic lupus erythematosus.

Pedigrees were obtained from 340 patients with systemic lupus erythematosus (SLE). Two hundred ten (62%) of the patients were from the wards of Lupus Clinic at the Los Angeles County-University of Southern California Medical Center, and 130 (38%) were from a private practice. Forty-one (12%) of the 340 patients with SLE had affected relatives: five had two and 36 had one affected relative. Ten (30%) of the 33 male patients and 31 (10%) of the 307 female patients had relatives with SLE. Examination of the individual pedigrees included examples of possible autosomal dominant, autosomal recessive, and sex-linked dominant and recessive inheritance. When all the pedigrees were considered as a group, multifactorial inheritance was suggested.