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Biomedical subjects

C E Smith

Publications and source records attributed to C E Smith.

At least 271 records · Page 15Linked to original sources

Local or regionally recurrent carcinoma of the breast: results of therapy in 121 patients.

Local or regional recurrence after primary surgical management for carcinoma of the breast was retrospectively evaluated by presenting stage and management in 121 patients. None had evidence of systemic disease. Management consisted of surgical removal only in 11 patients, removal followed by irradiation in 25, biopsy only followed by irradiation in 43, hormonal therapy after biopsy in 30, and chemotherapy after biopsy in 12. Mean and median follow-up for all patients was 46.9 and 31.5 months, respectively. Patients experiencing a recurrence within 24 months of primary surgical management experienced the worst overall and disease-free survival. The group of 42 patients with residual disease who received systemic therapy after biopsy had improved disease-free and overall survival at 5 years in comparison to the group of 43 patients who received local therapy after biopsy (p less than or equal to 0.05). Radiation therapy produced more frequent and durable control of local disease than did systemic therapy. Patients who had a complete response to applied therapy had significant improvement in overall survival.

Biopsy↗

Hyperthyroidism due to thyrotropin-secreting pituitary tumors. Diagnostic and therapeutic considerations.

Hyperthyroidism may be caused by the inappropriate secretion of thyroid-stimulating hormone (TSH) from a pituitary tumor. Of 33 reported cases, 17 have occurred in women and 16 have occurred in men. All patients had large tumors, and secretion of a second hormone (growth hormone or prolactin) has been common. Diagnosis requires the detection of TSH in the serum when patients are clinically and biochemically hyperthyroid. Ancillary tests supporting the diagnosis include an alpha-subunit to TSH molar ratio greater than 1.0, an absent TSH response to protirelin, suppression of serum TSH (but not alpha-subunit) by glucocorticoids, and a lack of suppression of serum TSH by dopaminergic agonists. Successful treatment of this disorder requires pituitary surgery and/or pituitary irradiation.

Adolescent↗

Patterns of periovulatory oviductal motility and progesterone in the unanesthetized rabbit.

Pairs of miniature extraluminal force transducers were chronically implanted on the isthmus of 26 rabbits without disturbing reproductive function. No alterations were noted in the transducer-bearing animals in the numbers of corpora lutea, uterine implants, or viable conceptuses, or in fertility, pregnancy rates, rates of ovum transport, or peripheral plasma levels of progesterone (P) or estradiol (E2). Using these devices, isthmic motility was recorded in 14 unanesthetized rabbits throughout the 72 h following human chorionic gonadotropin injection (hCG) (75 IU) and coitus. This activity was comprised of distinct bursts (B) of intense contractile activity, interspersed with periods (IB) of relative quiescence. Although the basic pattern of B and IB periods persisted throughout this interval, significant changes were noted in the duration of its components. During this period, B durations increased, with all values greater (P less than 0.01) than estrus from 24 h following the ovulatory stimuli. IB durations diminished somewhat at 24 h, but were markedly prolonged at 60 and 72 h. The proportion of time spent in bursting activity was maximal and significantly greater than estrus (P less than 0.01) at 24 h, a time at which ova were retained at the ampullary-isthmic junction. This proportion was minimal, on the other hand, at 60 and 72 h, when ova were moving rapidly through the isthmus and uterotubal junction. Plasma P surged from estrus to a peak at 6 h, fell until 24 h, and gradually increased through 72 h. All post-stimulus P values were greater (P less than 0.01) than at estrus. The B and IB durations at 72 h were both positively correlated with the P levels at 6 h. These findings suggest the importance of specific patterns of isthmic motility in ovum transport and of P in its regulation.

Animals↗

Pathogenicity and histopathology of an unusually intense infection of white grubs (Posthodiplostomum m. minimum) in the fathead minnow (Pimephales promelas).

A massive infection of metacercariae, particularly of the white grub (Posthodiplostomum m. minimum), was found in fathead minnows (Pimephales promelas) taken in November, 1979 from a commercial baitfish farm in Missouri. More than 2000 metacercariae were found in one fish 6 cm long. Low-grade mortality was occurring, and histologic sections showed that an intensive inflammatory response had resulted from the infection. The body cavity also contained a large volume of ascitic fluid with many blood cells, of which 92% were leucocytes. Moderate numbers of metacercariae caused a lesser inflammatory response.

Animals↗

Hyperthyroidism due to a thyrotropin-secreting pituitary adenoma. Studies of thyrotropin and subunit secretion.

A 58-year-old man had symptoms of hyperthyroidism and congestive heart failure. While hyperthyroid, his serum thyrotropin (TSH) level was inappropriately elevated at 6.1 microunits/mL. The molar ratio of alpha subunit to TSH was 2.5, suggesting the presence of a TSH-secreting pituitary tumor. Further evaluation disclosed an enlarged sella turcica with posterior erosion, and an intrasellar mass was visualized on computed tomographic scan. Neither serum TSH nor alpha subunit levels became elevated after administration of thyrotropin-releasing hormone, nor were they suppressed by a dopamine infusion. Serum TSH but not alpha subunit levels rose during antithyroid drug therapy. Estrogens produced a partial reduction in serum alpha subunit concentration (presumably reflecting the nontumorous gonadotroph contribution to circulating alpha subunit). Dexamethasone completely suppressed serum TSH level but had no effect on the alpha subunit level, suggesting a differential feedback of glucocorticoids on TSH and alpha secretion. The patient was treated with pituitary irradiation rather than surgery because of his underlying heart disease.

Adenoma↗

Hodgkin's disease in a community oncology center: ten years' experience.

A total of 77 cases of Hodgkin's disease have been evaluated and the patients treated at our institution during the past ten years. Advances in diagnostic technology and therapy have improved the outcome of the disease and overall survival. Therapy during this period has not been standardized. Radiation therapy was the primary initial treatment for stages I, II and III, with combined-modality therapy or chemotherapy alone used for more advanced stages. Five-year disease-free and overall survival for stage IA is 81 percent and 95 percent, respectively; 74 percent and 78 percent for stage IIA; 70 percent in both instances for stage IIB; 54 percent and 100 percent for stage IIIA; 75 percent and 100 percent for stage IIIB, and 57 percent and 69 percent for stage IV. Of 13 patients initially treated with chemotherapy, 77 percent have had a complete response. Of the 16 patients (88 percent) having a relapse, 14 have been salvaged with a variety of therapeutic approaches. Overall, five-year survival for 77 patients is 86 percent, with 70 percent having no relapse.

Adolescent↗

Normal valine disposal in obese subjects with impaired glucose disposal: evidence for selective insulin resistance.

Insulin has major effects on both glucose and branched chain amino acid metabolism. To determine whether the insulin resistance of obesity equally affects both glucose and branched chain amino acid metabolism, we measured the ability of obese and normal subjects to dispose of intravenous bolus dose of glucose (25 g) or L-valine (4 g). Basal plasma glucose levels were the same in the 18 normal and 17 obese (163 plus or minus 8% of ideal body weight) subjects, but basal plasma insulin levels were higher in the obese group (15 plus or minus 2 vs 6 plus or minus 1 microU/ml; p less than 0.001). The obese group had a slower glucose disappearance rate after glucose challenge (0.84 plus or minus 0.06 vs. 1.11 plus or minus 0.07 hr(-1); p less than 0.01) despite having a greater serum insulin response to the glucose load (26 plus or minus 4 vs 11 plus or minus 1 insulin area units; p less than 0.01), confirming insulin resistance. In contrast, disposal of a valine load was the same in normal and obese subjects, as assessed by initial and second phase exponential disappearance rates, metabolic clearance rates of valine, and volumes of distribution. In normal men, disposal rates of glucose and valine after simultaneous administration of both substances were slower than corresponding disposal rates determined when each substance was given alone. We conclude that obese subjects with impaired glucose disposal have normal valine disposal, suggesting that the insulin resistance of obesity can be selective in its effect on different metabolic systems. Glucose and valine also appear to mutually antagonize each other's disposal.

Blood Glucose↗

Ultrastructural localization of coenzyme A phosphatase (CoA-Pase) activity to the GERL system in secretory ameloblasts of the rat incisor.

Enzymatic hydrolysis of the monoester phosphate group from coenzyme A (CoA) was studied in rat incisor ameloblasts by incubating specimens from glutaraldehyde-fixed teeth in a cytochemical medium prepared with acetyl-CoA as substrate and lead ions as capture agent for phosphate. Ameloblasts incubated for 1 hr at 37 degrees C and at pH 5.0 in this medium showed reaction product localized almost exclusively along the trans (mature) aspect of the Golgi apparatus within a network of small granules and interconnecting tubular channels that comprise the GERL system in this cell. Reaction product was otherwise seen in trace amounts only within some Golgi saccules, a few lysosomal dense bodies and, in rare instances, within an occasional focal area of the endoplasmic reticulum. No selective staining of the GERL system was seen in control ameloblasts incubated at either pH 7.2 or pH 9.0 with acetyl-CoA as substrate, or incubated at pH 5.0 with dephospho-CoA as substrate. Control experiments at pH 5.0 also revealed that reaction product selectively stained the GERL system in ameloblasts when other molecules resembling CoA were used as substrate (e.g., crotonyl-CoA, 3'-NADP+), but not when adenosine 3'-monophosphate (3'-AMP) was used as substrate. That is, ameloblasts incubated at pH 5.0 with 3'-AMP showed heavy deposits of reaction product at many sites throughout the cell, including most lysosomal dense bodies, the Golgi saccules, the GERL system, most secretory granules, the nucleus, and extensively throughout the endoplasmic reticulum. These findings suggest that the GERL system of ameloblasts contains a CoA-specific phosphatase activity that may function to convert CoA to dephospho-CoA at acid pH. Biochemical studies included with this investigation further indicate that CoA-Pase activity saturates at exceptionally low concentrations of substrate (KM = 30 microM CoA) compared to other acid-dependent phosphatases.

Acid Phosphatase↗

Correlated biochemical and cytochemical studies of nicotinamide adenine dinucleotide phosphatase (NADPase) activity in ameloblasts using structural analogues of NADP.

The effects of altering the molecular structure of nicotinamide adenine dinucleotide phosphate (NADP) on enzymatic hydrolysis of the monoester phosphate group was examined at pH 5.0 in rat incisor ameloblasts using eight analogues of the oxidized form of the beta-isomer of NADP (beta-NADP+) modified in either the nicotinamide or adenine regions, or at the site for attachment of the monoester phosphate group to the molecule. Biochemical studies with whole homogenates of unfixed enamel organs revealed that the Michaelis-Menten constant (KM) and the maximum rate of dephosphorylation (Vmax) were different for these analogues relative to values estimated with beta-NADP+ as substrate. For example, the KM value was 3-fold higher and the Vmax value was lower by about 1/2 with the reduced form of the molecule as substrate. The KM value was about 2-fold higher but the Vmax value was about the same with an analogue lacking the nicotinamide group as substrate, while both the KM and the Vmax values were about 2-fold higher with an analogue containing an ethylene group covalently linked to adenine as substrate. In contrast, the KM value was markedly reduced (1/15) and the Vmax value was elevated (4-fold) using an analogue as substrate which contained the phosphate group attached at the 3'-position (3'-NADP+), rather than the 2'-position as in beta-NADP+ and other analogues. Cytochemical studies with glutaraldehyde-fixed enamel organs revealed that reaction product from hydrolysis of beta-NADP+ and other analogues containing the phosphate group attached at the natural 2'-position was localized within the intermediate saccules of the ameloblast Golgi apparatus. Reaction product from hydrolysis of 3'-NADP+, however, was localized at a different site, that is, within granules and membranous connections of the GERL system in the cell. Hence, 3'-NADP+ was not hydrolyzed by NADPase but by another enzyme tentatively identified as Coenzyme A phosphatase.

Ameloblasts↗