PubMed Health⌕ Search

Biomedical subjects

A G Charles

Publications and source records attributed to A G Charles.

At least 19 recordsLinked to original sources
PubMed2001

Taxol-induced ceramide generation and apoptosis in human breast cancer cells.

PURPOSE: Taxol has emerged as a valuable antimitotic chemotherapeutic agent, particularly in advanced breast and ovarian cancers. Although much is known about cytotoxic mechanisms, the effectiveness of Taxol cannot be solely explained by microtubular interaction. This study was undertaken to determine whether ceramide generation plays a role in Taxol-induced apoptosis. METHODS: Hormone-independent MDA-MB-468 and hormone-dependent MCF-7 breast cancer cell lines were employed, and ceramide metabolism was characterized using [3H]palmitic acid as lipid precursor. RESULTS: Exposure of cells to Taxol resulted in enhanced formation of [3H]ceramide. Ceramide increased nearly 2-fold in MDA-MB-468 cells exposed to 50 nM Taxol, and more than 2.5-fold in MCF-7 cells exposed to 1.0 microM Taxol. These concentrations mirrored the EC50 (amount of drug eliciting 50% cell kill) for Taxol in the two cell lines. Use of cell-permeable C6-ceramide as a medium supplement revealed that MDA-MB-468 cells were 20-fold more sensitive to ceramide than MCF-7 cells (P < 0.001). Ceramide was generated as early as 6 h after exposure to Taxol in MDA-MB-468 cells, whereas the earliest signs of apoptosis were detected 12 h after treatment, and by 24 h the apoptotic index was six times that of untreated cells. Both fumonisin B1, a ceramide synthase inhibitor, and L-cycloserine, a serine palmitoyltransferase inhibitor, blocked Taxol-induced ceramide generation, whilst sphingomyelin levels remained unchanged, indicating a de novo pathway of ceramide formation. L-Cycloserine reduced Taxol-induced apoptosis by 30% in MDA-MB-468 cells and totally blocked Taxol-induced apoptosis in MCF-7 cells. CONCLUSIONS: These results suggest that Taxol-induced apoptosis is, in part, attributable to ceramide and sphingoid bases. This is of relevance to drug mechanism studies, as ceramide is a known messenger of apoptosis. Clinical use of Taxol with ceramide-enhancing agents may maximize cytotoxic potential.

Antineoplastic Agents, Phytogenic↗
PubMed1997

Chlamydia trachomatis infection during pregnancy: can it cause an intrauterine infection?

In an attempt to prove the presence of intrauterine fetal chlamydial infection, sera from 26 laboring women, who tested positive for cervical chlamydial antigen in the first half of their pregnancies, and from 43 laboring women with no evidence of such infection, and sera from the cord of their delivered infants were tested for chlamydial IgA-, IgG- and IgM-specific antibodies. Nine (34.6%) of the 26 women with positive cervical infection and 5 (11.6%) of the 43 women with no identifiable cervical infection had significant antibody levels at the time of the delivery. Three of the 26 (11.5%) babies born to the mothers with positive cervical chlamydial infection early in the pregnancy and high antibody titer at delivery were found to have anti-chlamydial antibodies in their cord serum, indicating intrauterine infection; cord sera from the other 43 babies were negative for these antibodies. These findings suggest a low but possible risk of intrauterine infection in the presence of lower genital infection during pregnancy.

Adult↗
PubMed1989

Estrogen replacement after menopause. When is it warranted?

As longevity increases, so will the number of women living for many years beyond menopause. The estrogen deprivation that occurs at menopause results in many degenerative changes in a woman's body, some of which cause unpleasant or disabling symptoms. To maintain good health and vitality in menopausal and postmenopausal women, serious consideration should be given to appropriate estrogen replacement therapy. Although such therapy has some risks, the benefits appear to exceed the risks.

Aged↗
PubMed1982

Promethazine hydrochloride therapy in severely Rh-sensitized pregnancies.

Seventeen severely Rh-sensitized women were treated with promethazine hydrochloride (Phenergan) in 18 pregnancies, according to a protocol described by Gusdon et al. There was an unequivocal amelioration of the disease process in 10 of the pregnancies. In 9 of these 10 pregnancies, the infant survived. In 4 of the pregnancies, promethazine proved an unnecessary therapy as the infants were Rh negative. Promethazine may or may not have been helpful in 2 pregnancies, both of which resulted in live-born infants. One pregnancy resulted in intrauterine fetal death subsequent to an intrauterine transfusion. This infant was later shown to have multiple congenital anomalies incompatible with life. In a subsequent pregnancy, the mother was again treated with promethazine and had a normal infant who survived after exchange transfusions. The one loss of a live-born infant resulted from a cardiac arrest during an exchange transfusion. On the basis of these observations, the authors agree with Gusdon et al that promethazine does have an ameliorating effect on Rh-sensitized pregnancies.

Abnormalities, Drug-Induced↗
PubMed1980

Female epispadias: report of a case and review of the literature.

Female epispadias is a congenital anomaly representing a mild form of the spectrum of exstrophy of the bladder. Unrecognized an untreated, the handicap associated with the physical malformation can create overwhelming clinical and psychological problems for the affected female. Radiographic findings of spinal dysrhaphism with diastasis of the public bones are often associated with, and can afford the first clue to, the physical findings of absent clitoris, ununited labia and patulous and foreshortned urethra.

Child, Preschool↗
PubMed1978

Obstetric and psychological effects of psychoprophylactic preparation for childbirth.

Medical records, personal interviews about the childbirth experience, and self-administered attitudinal and socioeconomic data were obtained 1 to 3 days post partum in a large metropolitan hospital, for 249 women, 95 of whom had taken psychoprophylaxis training for childbirth prior to delivery. When controlled by parity, psychoprophylactic preparation was not related to any obstetric differences except for lower levels of anesthesia for both primiparas and multiparas and lower levels of analgesia among multiparas only. Preparation was significantly related to lower levels of pain and higher levels of enjoyment during childbirth, and these psychological benefits did not diminish when controlled for parity, socioeconomic status, and four sets of psychological and attitudinal characteristics.

Adult↗