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Biomedical subjects

W Jones

Publications and source records attributed to W Jones.

At least 145 records · Page 8Linked to original sources

Growth factor interactions between mouse mammary cell lines cocultured in collagen gels.

Three related mouse mammary cell lines were cultured in collagen gels and assayed for growth factor responsiveness and interaction via soluble factors. The CL-S1 cell line is nontumorigenic and grows poorly in collagen gel culture. The +SA and -SA cell lines exhibit different degrees of malignant behavior in vivo and have different growth properties in vitro. In collagen gel culture, +SA growth was stimulated by serum but not by epidermal growth factor (EGF), whereas both serum and EGF were required for optimal growth of -SA cells of early passage number as well as CL-S1 cells. -SA cells of later passage repeatedly exhibited a change so as to no longer require serum while retaining EGF responsiveness. [125I]EGF binding analyses indicated that CL-S1 cells bound EGF with less affinity than did -SA cells whereas +SA cells bound almost no ligand. When cell lines were maintained in separate collagen gels but shared the same culture medium, growth of +SA or -SA cells was slightly enhanced in the presence of CL-S1 cells and -SA cell growth was enhanced by the presence of +SA cells. Using the normal rat kidney fibroblast line NRK (clone 49F) as an indicator, serum-containing conditioned media from each cell line and from each pair of cell lines cultured in collagen gels were tested for transforming growth factor (TGF) activity. Both the -SA and CL-S1 lines tested positive for TGF-alpha production and possibly released a TGF-beta activity. These results suggest mechanisms by which cell populations in and around tumors can modify one another's growth characteristics.

Animals↗

Intraperitoneal cisplatin and etoposide in the treatment of refractory/recurrent ovarian carcinoma.

To determine the efficacy of a 6-month course of combination intraperitoneal (IP) chemotherapy with cisplatin and etoposide in patients with refractory or recurrent advanced ovarian carcinoma, 67 patients were entered into this prospective, nonrandomized, single-institution trial. Cisplatin at 100 mg/m2 and etoposide at 200 mg/m2 were administered IP on day 1 every month for 6 months. Exploratory laparotomy was performed before protocol entry and was planned after the completion of 6 months of IP therapy to surgically document response. All patients had received prior intravenous (IV) chemotherapy with a cisplatin-based regimen. At protocol entry, 18 (27%) patients had surgically defined residual tumor (maximal tumor diameter) greater than 2.0 cm, 17 (25%) patients greater than 0.5 cm - less than or equal to 2.0 cm, and 32 (48%) patients less than or equal to 0.5 cm. Sixteen patients (24%) who had experienced a treatment-free interval of more than 1 year prior to study entry were considered as having recurrent disease and the remaining 51 (76%) patients were considered as having refractory disease. Toxicity was tolerable: four patients (6%) had nadir fever, three (4%) had culture-documented bacterial peritonitis, five (7%) had IP catheter-related complications, and 27 (40%) had an increase in serum creatinine greater than 1.5 mg/dL. Among the 57 patients who are fully evaluable for response, the overall surgically defined response rate, complete (CR), and partial response (PR), was 40% (23/57), and the CR rate was 21% (12/57). Among the patients with recurrent disease, eight of 13 (62%) responded, with responses seen among all categories of residual disease. Among the patients with refractory disease, 15 of 44 (34%) had surgically documented responses. However, responses were more frequent in patients with residual disease less than 0.5 cm; 11 of 20 (55%) versus four of 24 (17%) with residual greater than 0.5 cm, P = .019 (chi 2, one degree of freedom, Yates correction). The duration of the CRs ranges from 4 to 18+ months. Longer follow-up is needed to determine if there is any impact on survival.

Adult↗

Pneumatic otoscopy in the diagnosis of middle ear effusion: the use of video as a teaching aid.

A recent survey has shown that the average general practitioner could expect to see 40 episodes of middle ear effusion in one year. It is an important condition because of its frequency, its insidious onset, and its persistence. It is presently associated with hearing loss, resulting in educational and social disadvantages. A more accurate diagnosis can be made over other conventional methods by the use of pneumatic otoscopy. It is a technique that is not widely used by general practitioners in this country. A videotape was produced to demonstrate the behaviour of the normal and abnormal eardrum during pneumatic otoscopy. This paper gives a review of how this was achieved.

Child↗

Intraperitoneal chemotherapy as treatment for ovarian carcinoma and gastrointestinal malignancies: the Memorial Sloan-Kettering Cancer Center experience).

Several different chemotherapy trials via either combined systemic and intraperitoneal or only via the intraperitoneal route were investigated. The administration of systemically and intraperitoneally infused 5-fluorouracil (5-FU) in patients with ovarial carcinoma did not shown in any patient a complete or partial remission, but showed severe side effects. In a patient with a metastasizing adeno carcinoma of the appendix this chemotherapy protocol led to a complete remission. Investigations with intraperitoneally infused cisplatin showed that 50% of all patients came into remission with tumor nodules less than 0.5 cm, but showed only 20% objective remissions in patients with tumor nodules greater than 0.5 cm. The intraperitoneal administration of mitoxantrone showed in several patients with cisplatin refractory ovarial carcinoma tumor remission with, however, severe local toxicity.

Antineoplastic Combined Chemotherapy Protocols↗

Bedside diagnosis of alcohol intoxication with a pocket-size breath-alcohol device: sampling from unconscious subjects and specificity for ethanol.

We describe a novel mouth-cup device for sampling breath from unconscious subjects and analysis with a hand-held breath-alcohol instrument, the "Alcolmeter SD-2." This equipment was evaluated in healthy volunteers after they drank a moderate dose of alcohol. Three kinds of breath were analyzed: (a) end-expired air from a conventional mouth-tube, (b) breath sampled from the mouth-cup, and (c) air from a nasal tube supplied with the breath analyzer. The ethanol concentration in breath from the mouth-cup was slightly less than in end-expired air but significantly greater than in nasal air. Results with mouth-tube and mouth-cup correlated highly with blood-ethanol concentration as determined by gas chromatography; nasal-tube air correlated less well. The Alcolmeter responded not only to ethanol but also to methanol, 1-propanol, and 2-propanol, whereas ethylene glycol gave no response. The time-response curve for methanol was different, and this might permit differential diagnosis of methanol poisoning.

Adult↗

Expression of the oncogenes mil and ras abolishes the in vivo differentiation of mammary epithelial cells.

Three carcinoma-associated oncogenes, two of which have been strongly implicated in human mammary tumorigenesis, have been introduced into a novel mouse mammary epithelial cell line, EF43, that retains many differentiated functions. The effect of oncogene expression upon classical transformation parameters as well as parameters specific for mammary epithelial cells such as growth in three-dimensional collagen matrices and the ability to repopulate the cleared mammary fat pad and to form alveolar structures in vivo has been investigated. Expression of v-myc in EF43 cells results in no obvious phenotypic changes, and does not confer tumorigenic potential upon the cells. Expression of v-Ha-ras confers upon EF43 cells the ability to grow rapidly, grow in an anchorage-independent manner, results in tumor formation in nude and syngeneic animals, abolishes their ability to repopulate the mammary gland and, instead, results in rapid induction of anaplastic tumors. The v-mil oncogene, an avian homolog of the mouse v-mht and human c-raf oncogenes, previously thought to be non-transforming in the absence of a co-operating oncogene, transforms EF43 cells, allowing them to grow in an anchorage-independent manner, form tumors in nude mice and abolishes their ability to repopulate the cleared mammary fat pad. In contrast to v-ras, however, the tumors arising from v-mil expression have a differentiated morphology, typical of adenocarcinomas. Thus, different oncogenes show varying degrees of inhibition of the differentiation of mammary epithelial cells in vivo.

Animals↗

Potential advances in combination chemotherapy for advanced testicular cancer.

An interim analysis of the current EORTC studies in advanced testicular cancer indicates that (a) for low volume metastatic disease the addition of bleomycin (B) to etoposide (E) and cisplatinum (P) may not be necessary, and (b) for high volume metastatic disease the alternating schedule of PVB/BEP is not superior to treatment with BEP. Future studies will subdivide patients into 3 groups. Those with low volume metastatic disease will receive EP using 2 dose schedules for cisplatin. Those with high volume metastases will receive either BEP or etoposide, ifosfamide and cisplatinum (VIP). Those with ultra-high volume metastases will receive BOP/VIP, possibly randomised against another intensive chemotherapy schedule.

Antineoplastic Combined Chemotherapy Protocols↗

In vitro replication potential of serially passaged mammary parenchyma from mice with different reproductive histories.

Growth properties of multicellular units (organoids) of mouse mammary parenchyma have been analyzed. These intact units grew differently in collagen-matrix cultures than did dispersed cells prepared from them. The latter actively migrated in the collagen matrix and reorganized themselves into multicellular structures before producing three-dimensional protuberances in gel. Terminal unit (end-bud/alveoli)-enriched fractions grew more extensively than did ducts, as predicted from growth patterns in vivo. To assess the growth potential and the relationships between replication history in vivo and replication potential in vitro in mammary parenchyma, intact terminal units from mammary glands of mice of different ages and with different reproductive histories were isolated and their growth characteristics compared. Terminal-unit organoids were cultured in collagen gel matrix and passaged weekly for up to 5 weeks. Morphology, growth rates, and growth fractions were compared among organoids from young virgin, old virgin, monoparous, and multiparous mice. Morphologies observed in various passages of organoids from the groups of mice were similar. Organoids from old virgin and multiparous mice declined in growth rate for four passages and then growth rate increased again during the fifth passage. (However, fifth-passage organoids failed to form tumors if implanted in syngeneic mice in vivo.) Growth of organoids from either old or young virgin mice was less at any given passage than tissue from multiparous mice of similar age. Growth fractions of organoids from old parous mice were the same as those from old virgin mice but reached the same maximum fraction faster. Later passage organoids from the different mouse groups responded morphologically to the hormone combination of estrogen, progesterone, prolactin, and cortisone but not respond to cholera toxin. These results suggest that an animal's hormonal history (altered profoundly by pregnancy and lactation) may be as important as chronological age in determining subsequent growth potentials of mammary epithelium.

Aging↗

Epidemiological-environmental study of diesel bus garage workers: acute effects of NO2 and respirable particulate on the respiratory system.

Personal samples of nitrogen dioxide (NO2) and respirable particulate (RP) were collected over the shift on 232 workers in four diesel bus garages. Response was assessed by an acute respiratory questionnaire and before and after shift spirometry. Measures of exposure to NO2 and RP were associated with work-related symptoms of cough; itching, burning, or watering eyes; difficult or labored breathing; chest tightness; and wheeze. The prevalence of burning eyes, headaches, difficult or labored breathing, nausea, and wheeze experienced at work were higher in the diesel bus garage workers than in a comparison population of battery workers, while the prevalence of headaches was reduced. Mean reductions in forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV1), peak flow, and flows at 50 and 75% of FVC were not obviously different from zero. There was no detectable association of exposure to NO2 or respirable particulate and acute reductions in pulmonary function. Workers who often had respiratory work-related symptoms generally had a slightly greater mean acute reduction in FEV1 and FEF50 than did those who did not have these symptoms, but these differences were not statistically significant.

Adolescent↗

Epidemiological-environmental study of diesel bus garage workers: chronic effects of diesel exhaust on the respiratory system.

Two hundred and eighty-three (283) male diesel bus garage workers from four garages in two cities were examined to determine if there was excess chronic respiratory morbidity related to diesel exposure. The dependent variables were respiratory symptoms, radiographic interpretation for pneumoconiosis, and pulmonary function (FVC, FEV1, and flow rates). Independent variables included race, age, smoking, drinking, height, and tenure (as surrogate measure of exposure). Exposure-effect relationships within the study population showed no detectable associations of symptoms with tenure. There was an apparent association of pulmonary function and tenure. Seven workers (2.5%) had category 1 pneumoconiosis (three rounded opacities, two irregular opacities, and one with both rounded and irregular). The study population was also compared to a nonexposed "blue-collar" population. After indirect adjustment for age, race, and smoking, the study population had elevated prevalences of cough, phlegm, and wheezing, but there was no association with tenure. Dyspnea showed a dose-response trend but no apparent increase in prevalence. Mean percent predicted pulmonary function of the study population was greater than 100%, i.e., elevated above the comparison population. These data show there is an apparent effect of diesel exhaust on pulmonary function but not chest radiographs. Respiratory symptoms are high compared to "blue-collar" workers, but there is no relationship with tenure.

Age Factors↗

Parathyroid hormone directly inhibits tubular reabsorption of bicarbonate in normocalcaemic rats with chronic hyperparathyroidism.

The hypothesis that chronic metabolic acidosis encountered in some patients with primary hyperparathyroidism is due to inhibition of proximal HCO3 reabsorption has recently been challenged. Indeed, this action of parathyroid hormone (PTH) has only been observed in acute studies, whereas in animal models of chronic hyperparathyroidism a metabolic alkalosis has been induced, probably owing to the release of alkaline salts from bone tissue, and to the stimulation of tubular acid secretion by hypercalcaemia. Studies were, therefore, performed to determine the effect of PTH on the renal handling of HCO3 in an animal model in which changes in plasma calcium and phosphate, and nephrocalcinosis, all known to affect tubular acidification, did not occur. Thyroparathyroidectomized (TPTX) rats were infused with synthetic bovine hormone fragment bPTH 1-34 via Alzet minipumps at the rate of 0.7 U h-1 to simulate normal endogenous production of PTH (group I) and at the three-fold higher rate of 2.1 U h-1 (group II). In order to prevent changes in serum calcium and phosphate, and nephrocalcinosis, animals of group II were fed a Ca- and P-free diet prior to TPTX (compared with a regular diet for group I) and both groups were treated with dichloromethylene-diphosphonate (Cl2MDP, 10 mg kg-1 day-1) and a Ca-free diet during PTH infusion. During the course of PTH infusion both groups of animals had stable and normal levels of plasma calcium and phosphate.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetates↗

Animal model of primary hyperparathyroidism.

An experimental model of hyperparathyroidism was developed in the rat to simulate primary hyperparathyroidism in humans. In this model thyroparathyroidectomized (TPTX) or parathyroidectomized (PTX) animals were infused for 6 days with an amount of bovine synthetic parathyroid hormone (PTH)-(1-34) fragment to restore plasma calcium levels to normal (0.7 U X h-1) or with PTH at twofold (1.4 U X h-1) or threefold (2.1 U X h-1) this basal level. Animals infused with 2.1 U X h-1 of bovine PTH-(1-34) exhibited hypercalcemia, hypophosphatemia, a reduction in theoretical renal threshold for phosphate and an increase in 1,25-dihydroxyvitamin D plasma levels that were approximately threefold the control value. In addition, these animals demonstrated nephrocalcinosis and changes of bone histology that were typical of the findings in patients with primary hyperparathyroidism. In contrast, in animals infused at 1.4 U X h-1, plasma calcium, phosphate, and theoretical renal threshold for phosphate remained within normal limits, but plasma 1,25-dihydroxyvitamin D was increased above control, suggesting that increased activity of 1 alpha-hydroxylase may be the most sensitive index of increased PTH levels. This animal model permits sustained elevation of PTH plasma levels at basal or pathologically elevated levels and should provide an effective means by which to evaluate the consequences of chronic hyperparathyroidism on epithelial function, bone, and other organ systems.

Acid-Base Equilibrium↗