Search PubMed⌕ Search

Biomedical subjects

D Carter

Publications and source records attributed to D Carter.

At least 127 records · Page 7Linked to original sources

Hypoxanthine-guanine phosphoribosyltransferase as a therapeutic target in protozoal infections.

The auxotrophy of parasitic protozoa for purines makes purine acquisition from the host a nutritional necessity for the survival and growth of these pathogens. The parasite hypoxanthine-guanine phosphoribosyltransferase (HGPRT) enzyme has been implicated as a critical enzyme in this purine salvage process. Moreover, the HGPRT enzyme in some parasites can also initiate the metabolism of purine base analogs that have little effect on the mammalian host. This implies that either inhibitors or substrates of HGPRT might serve as efficacious and selective agents for the treatment of parasitic diseases. This commentary provides an overview of recent molecular and biochemical studies on HGPRT proteins from parasitic protozoa and a discussion of the potential of HGPRT as a rational target for the chemotherapeutic manipulation of parasitic diseases.

Amino Acid Sequence↗

Changes in the telephone calling patterns of adolescent girls.

It is commonly believed that adolescent girls now call adolescent boys on a regular basis and this represents a change in behavior from previous generations. The purpose of this study was to test the hypothesis that during the last 40 years the incidence has increased. A sample of current students from a Southern urban commuter university was interviewed to determine their telephone use patterns. The changes in calling behavior among this sample indicates a transition period between a time when adolescent girls perceived their parents as disapproving of their calling boys (they placed few calls) to a time when adolescent girls perceived their parents as approving (they evidenced many such calls). Based on the current age of respondents, the transition period was calculated to be from 1964 to 1981. The results are discussed in relation to changes in adolescent female gender roles in the United States beginning in 1964.

Adolescent↗

Reproducibility of major diagnoses in a binational study of lung cancer in uranium miners and atomic bomb survivors.

A binational panel of four Japanese and four American pathologists examined 208 pulmonary neoplasms, according to the World Health Organization (WHO) recommendations, second edition, for the histologic typing of lung tumors. The study design included independent evaluations by pathologists working alone, followed by group reviews. The individual evaluations, and their implications for reproducibility of the WHO recommendations, are reported. Consensus (agreement by six or more pathologists) with respect to major (ie, first digit) diagnosis was obtained for 76.4% of the cases. Consensus was obtained for 72.5% of the cases with any major diagnosis of small cell cancer; the comparable figures for adenocarcinoma and squamous cell carcinoma were 56% and 48%, respectively. American pathologists were twice as likely as Japanese pathologists to diagnose large-cell cancer, the only significant national difference. Consensus was far less frequent with the minor (ie, second digit) diagnosis categories. This study shows that lung cancers continue to be difficult to classify reproducibly.

Carcinoma↗

Over-expression of oxytocin in the testes of a transgenic mouse model.

The bovine oxytocin gene has been expressed in the testes of two independent transgenic mouse lines. Hybridization and RNase protection analysis showed that the oxytocin transgene was transcribed from the normal functional promoter in the Sertoli cells of the seminiferous tubules in a developmentally regulated manner. Immunohistochemistry indicated that both oxytocin and neurophysin epitopes were expressed together in the Sertoli cells at stages I-V and X-XII of the cycle of the seminiferous epithelium. Furthermore, analysis with high-performance liquid chromatography showed that there was a tenfold increase in the amount of amidated oxytocin present in testicular extracts from the transgenic mice. However, there appeared to be no detectable effect of this overproduction of hormone on testicular morphology or fertility parameters. A significant decrease by 50% was detected only in the levels of intratesticular testosterone and dihydrotestosterone. The results point to a local paracrine role for oxytocin in the modulation of Leydig cell function.

Animals↗

Local recurrence versus new primary: clinical analysis of 82 breast relapses and potential applications for genetic fingerprinting.

PURPOSE: The purpose of this study was to perform a detailed clinical pathological analysis of breast relapses in patients treated with conservative surgery and radiation therapy in an effort to classify those relapses as true local recurrences or second primary tumors, and to assess the prognostic and therapeutic implications of such a classification system. METHODS AND MATERIALS: Of 990 patients treated with conservative surgery and radiation therapy at our facilities prior to December 1987, 82 patients have experienced a relapse in the conservatively treated breast as the primary site of failure. Patients were classified as having new primary tumors if they fulfilled any one of the following criteria: a) breast relapse occurring at a site distinctly removed from the original tumor; b) histology of the breast relapse compared with the original tumor consistent with a new primary; or c) DNA flow cytometry converting from an aneuploid primary to a diploid relapse. RESULTS: As of 2/92, with a median follow-up of 5.4 years from the time of breast relapse, the overall 5-year survival rate following breast relapse was 55%. Forty-seven patients were classified as true recurrences and 33 patients were classified as new primaries. Patients classified as true recurrences had a shorter median time to breast relapse than patients classified as new primaries (3.16 years vs. 5.42 years, p < .05) and an inferior post breast recurrence survival rate compared to patients classified as new primaries (36% vs. 89%, p < .05). Residual disease outside of the recurrent tumor bed was also noted to be more frequent in patients classified as true recurrences compared to patients classified as new primaries (48% vs. 16%, p < .05). CONCLUSION: Based on the clinical and pathological criteria outlined, it appears that a significant portion of patients experiencing a relapse in the conservatively treated breast may have new primary tumors as opposed to true local relapses. Distinction between a true recurrence and a new primary tumor may have significant prognostic implications. Uncertainties associated with the clinical and pathological criteria are presented and further investigations with genetic fingerprinting techniques to establish the clonality of breast relapses are presented and discussed.

Adult↗

Relationship between breast histopathology and family history of breast cancer.

BACKGROUND: The relationship between breast cancer histology and a number of epidemiologic risk factors associated with breast cancer was examined in 4071 histologically confirmed breast cancer cases aged 20 to 54 years from the Cancer and Steroid Hormone Study. METHODS: The distribution of risk factors, which included a family history of breast cancer, age at onset of breast cancer, laterality, race, age at menarche, age at menopause, history of benign breast disease, parity, number of livebirths and number of stillbirths, and age at first childbirth, were examined by histologic subgroup. To determine whether histology is associated with familial risk of breast cancer, a Cox proportional hazards model was used, modeling time to onset of breast cancer among mothers and sisters. RESULTS: Cases with medullary carcinoma were found to be significantly younger than cases with other tumor types in these data. In addition, medullary carcinoma was reported more frequently among black cases than among white cases. Cases with lobular carcinoma in situ were significantly more likely to have a mother and/or sister affected with breast cancer than cases with other tumor types and were also more likely to be bilateral, although few of these cases were both bilateral and reported a family history of breast cancer. The highest reported rates of benign breast disease occurred in cases with carcinoma in situ (both ductal and lobular) and tubular carcinoma. The remaining risk factors showed no association with histology. CONCLUSIONS: The current study clarifies the extent and nature of the relationship between breast cancer histology and epidemiologic risk factors including a family history of breast cancer.

Adult↗

The influence of interleukin-2 on vasopressin and oxytocin gene expression in the rodent hypothalamus.

There is growing evidence of interactions between the central nervous system and the immune system. We present evidence that the cytokine interleukin-2 (IL-2) influences expression of the genes encoding the neuropeptides vasopressin (VP) and oxytocin (OT) in the hypothalamus of the nude mouse. A single injection of recombinant mouse IL-2 (rmIL-2) caused a significant increase in VP and OT mRNA levels in the hypothalamus of nude mice. This effect was specific to the nude mouse. These observations stress the potential value of the nude mouse for studying interactions between the central nervous system (CNS) and the immune system.

Animals↗

Radiation pneumonitis. Bronchoalveolar lavage assessment and modulation by a recombinant cytokine.

A common side effect of radiotherapy is the development of fibrosis in the irradiated tissue. To study the mechanisms of this fibrogenic response, we developed a model system of whole-lung radiation in the rat and studied the evolution of injury by assessment of the cells and protein recovered by lavage. Once the pattern of injury was known, we attempted to modulate this reaction by administering the cytokine interferon-gamma (IFN-gamma). Rats received 15 Gy radiation to the whole thorax and were studied by lung lavage at intervals of 1 to 35 days after radiation. The effect of radiation was an initial (24 h) leak of protein, unaccompanied by cellular alterations, that resolved by 48 h. This was followed 2 wk later by a phase of inflammatory cell recruitment and more significant protein leak. A third phase of increase in inflammatory cells and further increase in protein flux was noted at Day 35. A significant cellular infiltrate was seen in lung sections obtained from animals treated in parallel experiments. IFN-gamma was given by osmotic pump from Day 0 to Day 35. This treatment significantly attenuated the PMN recruitment and protein leak (p < 0.002 and 0.01, respectively) at Days 25 and 35. Histologic sections demonstrated reduced alveolar cellularity and exudate at Day 25 (p < 0.05); however, significant numbers of inflammatory cells and exudate were present in irradiated and IFN-gamma-treated animals at Day 35. These data indicate that inflammatory cell recruitment may play a role in the lung injury following radiation. Furthermore, these preliminary data indicate that a cytokine blocks this reaction.

Animals↗

Treatment variables and intellectual outcome in children with classic phenylketonuria. A single-center-based study.

Records of 46 patients with classic phenylketonuria (PKU) were used to determine treatment variables associated with intellectual outcome. Patients comprised three groups: phenylalanine-restricted diet started 1) after 3 months and loss of diet control at a mean age of 7 years, 2) before age 3 months and loss of diet control at a mean age of 5 years, and 3) before age 3 months and through a mean age of 11 years. All underwent IQ testing during the diet; groups 1 and 2 were retested at a mean of six years off the diet. On the diet, groups 2 and 3 had higher IQs than group 1; group 3 IQ was also higher than IQ off diet in groups 1 and 2. After discontinuing the diet, group 2 IQs decreased significantly. Predictors of IQ in group 1 were age at loss of diet control and percentage of phenylalanine concentrations > 15 mg/dL; in group 2, mean phenylalanine concentrations and age at loss of diet control. Predictors of changes in group 1 IQs were global degree of dietary control and percentage of phenylalanine concentrations > 15 mg/dL; in group 2, phenylalanine concentrations of < 3 mg/dL and age at start of diet. Group 1 patients with phenylalanine concentrations < 3 mg/dL or > 15 mg/dL achieved no IQ gain by continuing the diet after age 7 years. Thus, intellectual prognosis is best for PKU patients who start a phenylalanine-restricted diet early and continue through age 12 years.

Adolescent↗

Losing ground.

Explore the source record for details and available documents.

Agriculture↗

Metastatic mature teratoma in lung following testicular embryonal carcinoma and teratocarcinoma.

We report seven cases of metastatic mature teratoma in the lung from testicular teratocarcinoma and embryonal carcinoma. The patients were between 19 and 58 years of age when orchiectomy was performed. The primary tumors each contained a prominent component of embryonal carcinoma as well as mature and immature teratoma in six patients and only embryonal carcinoma in one. In three patients metastatic pulmonary nodules were detected at the time of orchiectomy, and in three others pulmonary metastases occurred 4 and 8 months after orchiectomy. In one patient the interval was 1.5 years; however, chest roentgenography was not performed during that period. All the patients received chemotherapy or radiation therapy prior to removal of the pulmonary metastases. Thoracotomy was performed between 4 months and 9 years after detection of pulmonary metastases on chest roentgenograms. In one patient the procedure consisted of a lobectomy and in another a pneumonectomy. In the remaining five cases excision of the nodules was performed. The pulmonary metastases resected were grossly solitary lesions in five patients and multifocal in two. Microscopically, each tumor consisted entirely of mature teratoma. Cuboidal and mucin-secreting glandular epithelium predominated in the cystic areas; fibroconnective tissue was the predominant feature of the solid areas. In four patients the course has been indolent with no manifestations of the disease after at least 1 year; in two patients no follow-up was obtained; and one patient died, apparently of a septic process. We present a discussion of this interesting and unusual event.

Adult↗

Laryngeal chondrosarcomas.

Four cases of laryngeal chondrosarcoma are presented. The patients' ages ranged from 60 to 75 years; one was a man and three were women. Two of the tumors arose in the thyroid cartilage, one in the cricoid cartilage, and one in the left arytenoid cartilage. A rapid fatal course with pulmonary and cerebral metastases was observed for the tumor arising in the arytenoid cartilage that histologically corresponded to a myxoid chondrosarcoma. The other three cases corresponded to low-grade, well-differentiated chondrosarcomas of the hyaline type, and the patients were alive and free of recurrence or metastases 3 to 6 years following total and partial laryngectomy. A review of the literature on the topic and the importance of assessing histologic grade, size, and location in the evaluation of these neoplasms is discussed.

Aged↗

Radiation-associated lung cancer: a comparison of the histology of lung cancers in uranium miners and survivors of the atomic bombings of Hiroshima and Nagasaki.

A binational panel of Japanese and American pulmonary pathologists reviewed tissue slides of lung cancer cases diagnosed among Japanese A-bomb survivors and American uranium miners and classified the cases according to histological subtype. Blind reviews were completed on slides from 92 uranium miners and 108 A-bomb survivors, without knowledge of population, sex, age, smoking history, or level of radiation exposure. Consensus diagnoses were obtained with respect to principal subtype, including squamous-cell cancer, small-cell cancer, adenocarcinoma, and less frequent subtypes. The results were analyzed in terms of population, radiation dose, and smoking history. As expected, the proportion of squamous-cell cancer was positively related to smoking history in both populations. The relative frequencies of small-cell cancer and adenocarcinoma were very different in the two populations, but this difference was accounted for adequately by differences in radiation dose or, more specifically, dose-based relative risk estimates based on published data. Radiation-induced cancers appeared more likely to be of the small-cell subtype, and less likely to be adenocarcinomas, in both populations. The data appeared to require no additional explanation in terms of radiation quality (alpha particles vs gamma rays), uniform or local irradiation, inhaled vs external radiation source, or other population difference.

Adenocarcinoma↗