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Biomedical subjects

R C Jones

Publications and source records attributed to R C Jones.

At least 145 records · Page 8Linked to original sources

Multimodality treatment of locally advanced breast carcinoma.

Forty patients with 41 locally advanced breast lesions at stages IIIA and IIIB and the inflammatory stage were treated with combined-modality therapy from July 1980 to August 1985. Treatment included induction chemotherapy consisting of three cycles of fluorouracil, doxorubicin hydrochloride, and cyclophosphamide, followed by mastectomy in those patients whose lesions were operable (n = 28), and resumption of chemotherapy. Nine patients received postoperative radiation therapy. The mean follow-up was 34 months. Greater than 50% reduction in tumor size was achieved in 72% of patients after three cycles of chemotherapy. Overall, local control was achieved in 85% of patients with 59% survival and 53% disease-free survival, while 10% of patients developed local recurrences. Excluding lymphedema of the upper extremity (n = 2) and inflammatory carcinomas (n = 4), local control was achieved in 96% of patients, with 75% survival and 68% disease-free survival, while 4% of patients developed local recurrences. The rate of disease-free survival was 71% in patients with partial response to chemotherapy, contrasted with 43% in patients who did not respond or only minimally responded to chemotherapy. Actuarial five-year survival, based on life-table analysis, was calculated to be 46% for the group overall, 58% for the group excluding lymphedema of the upper extremity and inflammatory carcinoma, and 56% for the 28 patients undergoing mastectomy.

Adult↗

Inhibition of aminoimidazoquinoxaline-type and aminoimidazol-4-one type mutagen formation in liquid-reflux models by the amino acids L-proline and/or L-tryptophan.

Laboratory models were used to study the inhibition of mutagen formation by Maillard-type reactions during cooking of meats or fish. The amino acid L-proline (L-pro) was an effective, dose-dependent inhibitor of the development of mutagenicity (Ames test) in a liquid-reflux model of glucose + glycine + creatine known to produce IQ-type mutagens (MeIQx and 7,8-DiMeIQx). L-pro also inhibited formation of mutagens in a reflux model of threonine + creatine, developed in our laboratory, which yields a novel class of IQ-"like" aminoimidazol-4-one mutagens. A mixture of L-pro and L-tryptophan (L-trp) at lower concentrations of each yielded increased inhibition, compared with the findings when each inhibitor was tested by itself.

Animals↗

Pathogenesis of experimental reovirus tenosynovitis in chickens: influence of the route of infection.

Four groups of specific pathogen-free, day-old chicks were infected experimentally with an avian arthrotropic reovirus strain R2 by four different routes:--oral, subcutaneous, foot-pad and intra-articular. These groups were followed sequentially to study: pathological changes in the hock joints and liver; cloacal virus shedding and the presence of virus in hock joints; serological responses as determined by enzyme linked immunosorbent assay (ELISA), agar gel precipitation (AGP) and virus neutralization tests. All 4 infected groups developed arthritis or tenosynovitis with synovial hyperplasia and lymphocytic infiltration. Foot-pad and intra-articular routes of infection were found to advance the disease process by 2 to 3 weeks after infection by these routes were associated with superficial degenerative changes in articular cartilage. Antibodies were detected at 2 to 3 weeks p.i. by all 3 methods, but there were no significant differences between the patterns of serological response in the infected groups. Injection into the foot-pad appears to be the most convenient and effective parenteral route of experimental infection.

Animals↗

L-tryptophan inhibits formation of mutagens during cooking of meat and in laboratory models.

The formation of mutagens and carcinogens of the 2-amino-3-methylimidazo[4,5-f]quinoline and -quinoxaline type, formed during the frying or broiling of meats and in liquid-reflux laboratory models, was inhibited by L-tryptophan in a dose-dependent fashion. Addition of 75 mg (1.04 mg/cm2 surface area) of L-tryptophan per side in a sauce to ground beef patties prior to cooking significantly blocked the formation of mutagens observed in control patties treated identically with sauce but without L-tryptophan. The sauce itself did not have a significant inhibitory effect. When a mixture of 35 mM glucose, 70 mM glycine, and 70 mM creatinine in diethylene glycol-water (95:5) was heated in a liquid-reflux model for 2 h at 150 degrees C, the addition of 1.75-105 mM L-tryptophan gave a dose-related inhibition of mutagen formation, that reached 100% inhibition with 105 mM L-tryptophan.

Animals↗

Mechanisms of differential strain sensitivity in gastric carcinogenesis.

The genetically-controlled, distinct sensitivity of different rat strains to N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced cancer of the glandular stomach and duodenum was investigated. MNNG is activated through thiols, and the thiol content of the glandular stomach, duodenum, and liver of the BN rat tended to be slightly, but not significantly higher than that of the Wistar, Sprague-Dawley, Lewis, and Buffalo rats. The levels of the DNA repair system, O6-alkylguanine transferase (AGT), in sensitive Wistar strain rats had values similar to those in resistant Buffalo strain rats. Administration of 80 mg/liter of MNNG in the drinking water for six weeks up to the time of tissue collection yielded the same AGT levels. Of all the parameters examined to account for genetically-mediated sensitivity to gastrointestinal cancer induction, namely, N-denitrosation, thiol activation, AGT-related DNA repair, and cell duplication rates, the latter yielded the best association, although these factors acting together may be involved.

Animals↗

Inhibition of aminoimidazoquinoxaline-type and aminoimidazol-4-one-type mutagen formation in liquid reflux models by L-tryptophan and other selected indoles.

The essential amino acid L-tryptophan (L-Trp) was found to be an effective inhibitor of the development of mutagenicity (Ames test) in liquid-reflux models known to produce identified IQ-type mutagens, such as 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-3,7,8-trimethylimidazo[4,5-f]quinoxaline (7,8-DiMeIQx), and in reflux models recently developed in our laboratory that have been found to produce novel IQ-"like" mutagens (aminoimidazol-4-ones), which we have identified as 2-amino-1-methyl-5-propylideneimidazol-4-one (TCP-1), and 2-amino-5-ethylidene-1-methylimidazol-4-one (TCP-2 or ACP). Selected indoles other than L-Trp were also found to be effective inhibitors of mutagen formation in these same reflux models. A mechanism of inhibition of mutagen formation based on the preferential reaction of mutagen precursor aldehydes with the indole-ring nitrogen of these inhibitors, rather than with creatinine, is indicated, and a new "concerted condensation model" for the formation of IQ-type mutagens proposed.

Indoles↗

Altered artery mechanics and structure in monocrotaline pulmonary hypertension.

Pulmonary hypertension in rats, induced by an injection of monocrotaline, is associated with changes in the wall structure of the pulmonary arterial bed. We have studied the effects of this remodeling on mechanical properties of cylindrical pulmonary artery segments from rats 21 days after monocrotaline (MCT) injection. Resting and active (KCl induced) circumference-tension relationships were established for segments of extrapulmonary and intrapulmonary arteries isolated from the hilum and the fifth lateral branch from the axial pathway (all preacinar). The thicknesses of the vessel wall, the media, and adventitia were measured at several positions around the circumference of the artery by computerized analysis of histological cross sections of the segments fixed at a standard circumference. Resting and active stress were also calculated. The study shows that active circumferential tension and active stress are reduced in vessels from MCT-treated rats. Based on our findings, it is unlikely that altered contractile function of preacinar arteries contributes significantly to the increased vascular resistance seen in this model.

Animals↗

Distribution of 5 alpha-reductase in the epididymis of the tammar wallaby (Macropus eugenii) and dependence of the epididymis on systemic testosterone and luminal fluids from the testis.

The activity of 5 alpha-reductase was much higher in the caput and corpus epididymidis than in the cauda epididymidis. Orchidectomy caused a reduction in 5 alpha-reductase activity in the caput and corpus epididymidis, and regression of the epithelium and reduction in mass of all regions of the epididymis. Subsequent testosterone therapy caused a substantial increase in amount of epithelium and overall mass of the cauda epididymidis but showed little or no increase in any of the responses measured in the caput and corpus epididymidis. We concluded that the caput and corpus epididymidis of the tammar respond to factors other than testosterone, probably some constituent in the luminal fluid, and therefore are homologous with the initial segments of the epididymis in eutherians.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

Studies of fluid and spermatozoal transport in the extratesticular genital ducts of the Japanese quail.

Stereological studies of the spermatic ducts of the quail were carried out for comparison between different parts of the system and those of other species, and to provide a basis for future physiological studies. Duct length, surface areas and volumes of various components of the ducts were determined. Values were subsequently used to calculate net fluxes of fluid across the duct epithelium, spermatozoal velocity and the distribution of spermatozoa throughout the system. It was concluded that the extratesticular spermatic ducts are divided into 2 main parts: (1) the ductuli efferentes where spermatozoa spend a brief period (8 minutes) and which are adapted for considerable net fluid reabsorption (100 microliters/cm2/h), and (2) the connecting ducts, ductus epididymidis and ductus deferens where spermatozoa spend a longer period (24 hours) and which are involved in little net fluid transport (0.14-2.1 microliter/cm2/h). Most spermatozoa (92.3%) are located in the ductus deferens. The velocity of spermatozoal transport is much the same through the quail spermatic ducts (0.37 mm/min) as through the mammalian epididymis, the difference between classes in the duration of spermatozoal transport being due to differences in the distance that they travel. In a comparison between estimates of spermatozoal concentration using stereological methods and direct counts of spermatozoa in samples collected using micropuncture procedures it was concluded that both methods gave similar results.

Animals↗

Upper extremity fractures in the acute spinal cord injured patient.

Fifty-three long bone upper extremity fractures in 46 patients with recent spinal cord injuries were reviewed with reference to the outcome of operative versus nonoperative treatment. Twenty-four fractures had surgery and 29 fractures were treated nonoperatively. Criteria used in assessing outcome included range of motion, time to union, total rehabilitation time, and orthopedic and medical complications. Humeral fractures had similar outcomes with either operative or nonoperative treatment. Radial nerve injury occurring with humeral fractures prolonged the rehabilitation time. All three combined radial and ulnar fracture treated surgically developed synostosis whereas two of the three nonoperatively treated fractures had other orthopedic complications. Nondisplaced radial fractures responded appropriately to closed treatment. Displaced radial fractures treated nonoperatively had a high incidence of malunion. All ulnar fractures were treated operatively, and all achieved acceptable range of motion and fracture healing at the time of discharge. Medical complications such as deep venous thromboses and decubitus ulcers occurred more frequently in the nonoperatively treated group (28%) than in the operatively treated group (4%). Standard guidelines for upper extremity fracture care apply to the patient with a spinal cord injury. However, operative stabilization may be associated with a decreased risk of medical complications in these patients.

Adolescent↗

Mechanical properties and structure of isolated pulmonary arteries remodeled by chronic hyperoxia.

Normobaric hyperoxia is known to cause pulmonary hypertension with major restructuring of the walls of large and small pulmonary arteries. This study reports the effects of 21 days of exposure to 87% oxygen on the resting and active mechanical properties and structure of pulmonary arterial segments. Segments from the hilar region, extrapulmonary and proximal preacinar, and selected distal preacinar regions were studied. Resting and active (KCl-induced) tension:circumference curves were determined for each vessel. Morphometric measures were made of vessels fixed at a standard circumference using computerized planimetry. The areas of the media and adventitia as well as vessel wall thickness were increased in hyperoxic vessels. The walls of segments from the hypertensive rats demonstrated an increased stiffness based upon analysis of vessel resting tension:circumference relationships while the tangent modulus (a measure of stiffness normalized to tissue dimensions) was unchanged. Paradoxically, despite medial hypertrophy in the pulmonary vessels remodeled by hyperoxia, active tension was reduced. This study reveals that the resulting hypertensive state is not readily explained by an inherent increase in the maximal contractile capabilities of the remodeled vessel. Rather, obliteration of vessels in combination with increased resting stiffness appear to be the basis for pulmonary hypertension induced in hyperoxia.

Animals↗

The effect of a luteinizing hormone-releasing hormone antagonist on experimental endometriosis in the rat.

The effect of a Salk LRH analogue (Antagonist I) on growth of endometrial explants in the intact female rat was studied. Subcutaneous injection of the analogue was begun 3 weeks after transplantation of a section of endometrium to the peritoneal wall. The animals were laparotomized and the volume of the explant (length X width X height) in mm was measured with calipers on day 1 of treatment. The animals were injected daily for 3 weeks with 50, 250 or 500 micrograms of Antagonist I at which time the animals were again laparotomized and the volume of the explant measured. Eight weeks after cessation of treatment the animals were sacrificed and the volume of the explant measured. The degree of inhibition of explant growth was directly correlated with the amount of Antagonist I administered; a significant inhibition was obtained with doses of 250 or 500 micrograms. Eight weeks after cessation of treatment all explants demonstrated renewed growth, although explants in rats which had been treated with 250 or 500 micrograms had returned to only 51 and 61% of their initial volume, respectively. The results of this study demonstrate the LRH antagonists may be useful in the treatment of endometriosis although at doses considerably higher than those of the super agonists.

Animals↗

Changes in protein composition of the luminal fluids along the epididymis of the tammar, Macropus eugenii.

Micropuncture samples of luminal fluid were collected from the rete testis and along the epididymis. Quantitative analyses showed that the ductuli efferentes reabsorb about half the protein leaving the testis. Considerable protein is secreted by the caput epididymidis (initial segment) and there is a net loss of protein from the corpus and cauda epididymidis. Denatured, polyacrylamide gel electrophoresis showed that there are 5 proteins in rete testis fluid which are not present in blood (Mr of 14,700, 22,800, 24,100, 43,000 and 44,800). One of these proteins (Mr 14,700) is lost from plasma in the ductuli efferentes and 2 (Mr 43,200 and 44,800) are lost in the corpus epididymidis. Twelve proteins appear in the epididymal plasma and are not present in rete testis fluid or blood: 6 appear in the caput epididymidis (Mr 30,000, 31,000, 32,300, 17,400, 18,700 and 21,400), 3 in the corpus epididymidis (Mr 12,800, 39,800 and 90,600) and 3 in the cauda epididymidis (Mr 10,900, 56,300 and 63,000). A protein with the same molecular weight as a blood protein (149,500) accumulates in the corpus and cauda epididymidis. None of the samples of luminal fluid contained particulate matter other than spermatozoa, indicating that the tammar is a useful animal for micropuncture studies.

Animals↗

Regulation of the elemental composition of the epididymal fluids in the tammar, Macropus eugenii.

Micropuncture, microanalytical and microelectrode techniques were used to study electrochemical aspects of 7 elements and fluid in the ductuli efferents and ductus epididymidis of the tammar. Rete testis fluid was isosmotic with blood and had a lower pH. It also contained lower concentrations of bicarbonate, sodium, calcium, magnesium, phosphorus and sulphur and higher concentrations of potassium and chloride than blood. The luminal fluid was acidified further during passage through the sperm ducts and all of the elements which were studied moved in or out of the lumen, usually against an electrochemical gradient. The ductuli efferents reabsorbed 87% of the fluid leaving the testis without changing the intraluminal concentrations of sodium, potassium and calcium, but the concentrations of magnesium, phosphorus and sulphur increased. The caput epididymidis reabsorbed about half the fluid entering it: sodium concentrations decreased and those of potassium and phosphorus increased. There was also some fluid reabsorption and an increase in the values of potassium and phosphorus in the corpus epididymidis. There was little net transport of fluid in the cauda epididymidis; sodium, chloride, magnesium and phosphorus concentrations decreased and potassium values increased. Studies involving filtration through a dialysis membrane of blood and fluid from the rete testis and cauda epididymidis showed that, whilst some of the calcium, magnesium, phosphorus and sulphur was associated with high molecular weight compounds in blood, the association was not significant in the reproductive fluids.

Animals↗