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Biomedical subjects

D Carter

Publications and source records attributed to D Carter.

At least 37 records · Page 2Linked to original sources

Patterns of presentation of breast disease over ten years in a specialised clinic.

A clinic specialising in breast disease has been surveyed over a decade. Detailed information has been collected on 3,500 women with benign breast disorders and 950 with breast cancer. Over this time, the demand for and utilisation of this facility has increased steadily. Over the ten years, there has been a trend for a higher proportion of breast cancers to be smaller in size and for fewer cancers to be locally advanced or metastatic at presentation. Critical appraisal of referral and consultation patterns indicates that the original aims of establishing this clinic have not been maintained. Paradoxically, this is a result of the success of the exercise. Measures which might lead to a higher proportion of patients with breast cancer being managed at the Breast Clinic rather than a General Surgical Outpatient Clinic are discussed.

Adult

The cytokine CSF-1 (M-CSF) expressed by endometrial carcinomas in vivo and in vitro, may also be a circulating tumor marker of neoplastic disease activity in endometrial carcinoma patients.

Endometrial epithelial cell expression of CSF-1 and FMS antigens was studied in vivo and in vitro in 24 human endometrial carcinoma and 11 benign endometrial biopsy specimens. Twenty-one of 24 adenocarcinomas and 4 of 11 benign lesions stained positively (by IHC) with rabbit anti-human CSF-1 antibodies, while all 24 carcinomas and 3 out of 11 benign lesions (all secretory endometrial specimens) showed significant IHC staining (1+ or greater) of epithelial elements and tissue macrophages with a mouse anti-FMS (CSF-1 receptor) monoclonal antibody. CSF-1 levels in plasma from endometrial carcinoma patients (85 samples, 24 patients) were also found to be markedly elevated (some greater than 100 ng/ml) in patients with active or recurrent disease. In vitro, several endometrial carcinoma cell lines were shown to express FMS complementary transcripts and FMS antigen which were very similar if not identical to those expressed in choriocarcinoma cell line positive controls. Autocrine and paracrine effects mediated by tumor or stromally produced CSF-1 and a tumor epithelial cell CSF-1 receptor may therefore contribute to the biological behavior of endometrial neoplasms in vivo and in vitro.

Adenocarcinoma

Primary malignant melanoma of the lower respiratory tract. Report of a case and literature review.

The authors report a case of primary bronchial malignant melanoma, occurring in a 34-year-old woman presenting with persistent cough. At bronchoscopic examination, a polypoid mass was found to occlude the left mainstem bronchus. Biopsies showed a malignant epithelioid tumor resembling an atypical carcinoid. Histochemistry, electron microscopic study, and immunohistochemistry confirmed the diagnosis of melanoma. Physical examination and additional clinical history to exclude other possible primary sites were negative. The patient underwent thoracotomy with left pneumonectomy. Nineteen months after resection she was found to have a histologically similar tumor involving her left adrenal gland. Review of the literature shows that melanoma of the lower respiratory tract has been reported only in adults and has a tendency to present as a central polypoid growth that may be responsive to surgical resection.

Adult

Benign mixed tumors (pleomorphic adenomas) of the breast.

Six cases of benign mixed tumors of the female breast are described. The tumors were found in three settings: (a) as a de-novo lesion arising from breast parenchyma, (b) as single or multiple nodules arising in a background of benign proliferative epithelial elements, and (c) in association with breast carcinoma. The tumors ranged from 1 to 4 cm in diameter, and were histologically characterized by the admixture in various proportions of benign glandular epithelial and myoepithelial elements and cartilaginous or myxoid components. Immunohistochemical staining supported this interpretation. One of the cases was remarkable for the presence of abundant tyrosine-like crystals, a feature described in benign mixed tumors of salivary glands. None of the tumors has recurred during a follow-up period of 1-7 years. Mixed tumors of the breast are considered to be similar to their dermal and salivary gland counterparts.

Adenoma

Hepatoblastoma: detection of tumor vascularity with duplex Doppler US.

The evaluation of pediatric abdominal masses commonly includes computed tomography, ultrasound (US), and, more recently, magnetic resonance imaging. A previous study suggested that duplex US is of use in further tissue characterization of hepatic lesions in adults. The authors describe the Doppler signals arising from hepatoblastomas in three infants. Peak systolic Doppler frequency shifts in the neoplasms of these three patients were all equal to or greater than 4 kHz, well above the normal range for hepatic arteries. Each neoplasm also exhibited antegrade diastolic flow. The detection of high Doppler frequency shifts associated with neovascularity may prove useful in future evaluation of pediatric hepatic masses.

Carcinoma, Hepatocellular

Dopaminergic mediation of physiological changes in proopiomelanocortin messenger ribonucleic acid expression in the neurointermediate lobe of the rat pituitary.

POMC mRNA levels in the intermediate lobe of the pituitary are known to be regulated by osmotic stimuli. Salt loading with 2% saline causes a decrease in POMC mRNA levels in the IL without affecting levels in the anterior lobe. We have investigated possible mediators of this effect and attempted to elucidate the mechanism by which the changes in mRNA levels are brought about. The dopamine D2 receptor antagonist domperidone blocked the inhibitory effect of salt load on POMC mRNA in the neurointermediate lobe, while the D2 agonist bromocriptine mimicked the effect of salt load. Pharmacological agents affecting D1 receptors, beta-adrenoceptors, and endogenous serotonin levels did not block the decrease in POMC mRNA levels after a salt load. The level of transcription of the POMC gene in the neurointermediate lobe was investigated using a nuclear run-on transcription assay. Transcription of POMC was found to be unchanged after a salt load, indicating that an osmotic stimulus does not decrease POMC mRNA levels by a specific change in the level of transcription.

Actins

Vasopressin gene expression in the rodent hypothalamus: transcriptional and posttranscriptional responses to physiological stimulation.

The neuropeptide vasopressin (VP) is expressed in the supraoptic nucleus, a discrete group of neurons in the hypothalamus that respond to osmotic stimuli. In the rat the pattern of expression of VP mRNA changes in two ways as a consequence of the physiological stimulation of these neurons. Firstly, there is an accumulation of VP mRNA, and secondly, the poly(A) tail of the VP mRNA increases in length. We asked whether the increase in VP mRNA level is a consequence of transcriptional or posttranscriptional mechanisms. We present evidence from nuclear run-on assays that increases in the transcription of the rat VP gene are sufficient to account for the accumulation of VP mRNA observed in chronically stimulated animals. However, we note that in acutely stimulated animals there are rapid and relatively large increases in VP gene transcription that do not correlate with increases in the VP mRNA level, but coincide with the appearance of a homogeneous class of VP mRNAs with elongated poly(A) tails. We suggest that immediately after the onset of an acute osmotic stimulus, there is a rapid destruction of preexisting VP mRNAs and their replacement with new transcripts bearing longer poly(A) tails. We have also addressed the question of the function of the elongated VP mRNA poly(A) tail. It is unlikely that the poly(A) tail extension is involved in RNA stability; the transcriptional changes observed are sufficient to account for the increase in VP mRNA level, and we show that in the mouse similar increases in VP mRNA level are observed without concomitant changes in poly(A) tail length. We did not observe a change in the polysome distribution of the VP mRNA after osmotic stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Synaptic connections made by axons regenerating in the central nervous system of adult mammals.

The restoration of connections in the injured central nervous system (CNS) of adult mammals is hindered by the failure of axons to grow back to their natural fields of innervation. Following transection of the optic nerve of adult rodents, the guided regeneration of retinal ganglion cell (RGC) axons along a transplanted segment of peripheral nerve (PN) has shown that these neurones retain their capacities to form well-differentiated synapses in both normal and abnormal targets. The main aim of this review is to describe the anatomical and functional characteristics of some of these connections and to suggest that their terminal distribution and morphology may be the result of a persistence in these targets of molecular determinants that influence normal connectivity in the intact animal.

Afferent Pathways

Ovarian adenocarcinomas express fms-complementary transcripts and fms antigen, often with coexpression of CSF-1.

In earlier studies of oncogene expression in ovarian and endometrial neoplasms, the authors reported that high tumor levels of fms-complementary transcripts correlate with high histologic grade and advanced clinical stage presentations. In this communication, they pursue these initial clinicopathologic investigations to demonstrate by in situ hybridization and immunohistochemistry that malignant epithelial cells of 14 of 14 invasive adenocarcinomas of the ovary express fms-complementary transcripts. By Northern blotting and by reverse transcription, followed by polymerase chain reaction amplification, the authors also were able to demonstrate fms transcript expression in several ovarian and endometrial carcinoma-derived cell lines. Because about half (6/14) of the invasive adenocarcinoma specimens were shown to coexpress fms and colony-stimulating factor 1, the authors propose that the expression of this lymphohematopoietic cytokine and its receptor by ovarian adenocarcinomas could contribute to their proliferative and invasive characteristics in vivo.

Adenocarcinoma

Conservative surgery and radiation therapy in breast carcinoma: local recurrence and prognostic implications.

Conservative surgery with radiation therapy has been used with increasing frequency at Yale-New Haven Hospital since the late 1960's, resulting in a minimum evaluable follow-up time of 5 years on 278 patients treated prior to 1982. The radiation therapy technique generally encompassed treatment to the breast and regional lymph nodes of 4600 cGy with an electron beam boost to the tumor bed of 6400 cGy. Axillary dissection was performed in 19%, adjuvant chemotherapy in 7.3%, and adjuvant hormonal therapy in 5.7%; 65% were clinical Stage I and 35% were clinical Stage II. As of July 1987, with a minimum evaluable follow-up of 5 years and a median follow-up of 7.46 years, the actuarial 5- and 10-year survival for all 278 patients was 83% and 67%, respectively. The breast recurrence-free rate was 91% at 5 years and 80% at 10 years. Whereas the 5-year survival was significantly greater for clinical Stage I patients (91% vs 68%, p = .01), the breast recurrence-free rates did not significantly differ between clinical Stage I & II (93% vs 88%). There were 31 patients who failed in the breast alone as the first site of failure; 67% were at or near the primary site whereas 33% were distinctly removed from the primary site. Salvage mastectomy was performed in 25 patients, repeat wedge resection in two patients, and biopsy only in four patients. Axillary nodes were positive in five (33%) of 15 evaluable patients undergoing axillary dissection at the time of recurrence. The 5-year actuarial survival following local recurrence for the 31 patients was 48% at a mean follow-up of 5.06 years. The local recurrences were further subclassified into localized breast recurrences (LBR), defined clinically as greater than 3 cm and/or with dermal involvement. The 22 patients experiencing localized breast recurrences tended to occur later (median time to recurrence 4.3 years) than the nine patients experiencing a diffuse breast recurrence (median time to recurrence 2.9 years). At last follow-up, three (14%) of the 22 localized breast recurrences had subsequently failed distantly and none had subsequent local failure, whereas four (44%) of nine diffuse breast recurrences had subsequent distant failure and five (55%) of the nine diffuse breast recurrences experienced further local disease. The 5-year actuarial survival following salvage treatment was 90% for the localized breast recurrences and only 13% for the diffuse breast recurrences.

Breast Neoplasms

Circulating levels of CSF-1 (M-CSF) a lymphohematopoietic cytokine may be a useful marker of disease status in patients with malignant ovarian neoplasms.

We have previously reported our observations of epithelial tumor cell expression of transcripts and protein antigens of CSF-1 and transcripts of a protein closely related--if not identical--to the CSF-1 receptor in ovarian and endometrial neoplasms in vivo and in vitro. In the present communication, we extend these investigations to analyze the clinical utility of determinations of plasma CSF-1 concentrations in 125 samples from 33 patients with ovarian neoplasms and one patient with benign endometriosis. We observed that plasma CSF-1 levels in patients with active and recurrent neoplastic disease were markedly elevated and follow changes in disease status in individual patients. These and other results presented in this communication suggest that not only could CSF-1 be a useful circulating tumor marker in ovarian carcinoma patients, but also that in combination with measurements of other markers--such as CA-125--determinations of plasma CSF-1 levels might actually improve the accuracy of "tumor marker"-based assessments of disease status in patients with malignant ovarian neoplasms.

Adenocarcinoma

Vasopressin RNA in the neural lobe of the pituitary: dramatic accumulation in response to salt loading.

The peptides vasopressin (VP) and oxytocin are derived from preprohormone precursers encoded by highly homologous linked genes that are expressed in discrete groups of hypothalamic neurons. The mature hormones are released into the peripheral circulation from the neural (posterior) lobe of the pituitary and have also been implicated in the regulation of anterior lobe. We have used Northern blotting and in situ hybridization to RNA in tissue sections to describe the presence, anatomical localization, and regulation of VP and oxytocin RNAs in the pituitary gland itself. We were unable to detect VP transcripts in the anterior and intermediate lobes of the pituitary. Rather we found low levels of VP RNA in the neural lobe. Furthermore, the osmotic stimulation of a 2% (wt/vol) NaCl drinking diet resulted in a marked accumulation of VP RNA in the neural lobe. We suggest that VP, locally synthesized in pituicytes, may have paracrine effects on VP receptors in the neural lobe.

Animals

Ectopic pregnancy: duplex Doppler evaluation.

Of 398 patients in whom there was a clinical suspicion of ectopic pregnancy, 96 (24%) were found to have the condition. Of the 96, 70 underwent duplex Doppler imaging. A viable ectopic fetus was seen in 10 of 70 (14%), and an extrauterine sac without an identifiable fetus was seen in an additional 27, giving a sensitivity for imaging alone of 53%. Fetal heart activity was detected with Doppler in 13 (19%). High-velocity flow, which suggested the presence of an ectopic pregnancy, was detected in 38 of 70 (54%) patients (total preoperative sensitivity, 73%). In the 91 patients who did not have an ectopic pregnancy, duplex Doppler imaging of the intrauterine contents alone allowed an ectopic pregnancy to be excluded in 29 (32%) on the first examination and in a further 21 on the second scan (specificity, 55%). Nine vascular adnexal masses were falsely considered to be ectopic pregnancies (specificity, 90%). The positive predictive values were 47% for imaging alone and 85% for Doppler. The negative predictive values were 60% for imaging alone and 81% for Doppler.

Adult

Human breast carcinoma cell levels of MDR-1 (P-glycoprotein) transcripts correlate in vivo inversely and reciprocally with tumor progesterone receptor content.

Sixteen human breast carcinomas were subjected to molecular biological and biochemical analyses to determine tumor cell MDR-1 (P-glycoprotein) levels and progesterone receptor content. The results of these analyses disclosed a strong reciprocal and inverse correlation between levels of tumor cell-specific MDR-1 complementary hybrids and progesterone receptor content. These results suggest that the mechanisms which control expression of the P-glycoprotein gene and the progesterone receptor are interrelated and antagonistic, a result with obvious molecular biological, physiological, and clinical implications.

ATP Binding Cassette Transporter, Subfamily B, Mem

Oncogene structure, function, and expression in breast cancer.

The research of the past decade has made it clear that aberrant expression of genes that encode growth factors, their receptors, and other genes involved in normal cell growth and differentiation--so-called oncogenes--play important roles in determining the proliferative and invasive characteristics of malignant mammary neoplasms. The authors briefly review the topic of oncogenes and the relevance of oncogenes to breast carcinoma; also included is a description of current techniques commonly employed in the study of aberrant oncogene structure and function. Also presented is the authors' own work on oncogene expression in breast neoplasms, which implicates the neu, fms, PDGF-A and Ki-ras oncogenes in the control of mammary epithelial cell proliferation by autocrine and paracrine mechanisms.

Breast Neoplasms

Health visitors' perceptions of normal infant behaviour.

A survey of 50 health visitors revealed a wide range of views on the frequency of certain behaviour patterns associated with feeding, sleeping and crying in babies. The implications of this for health visitor training and client contact are discussed.

Child Behavior