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Biomedical subjects

K L Smith

Publications and source records attributed to K L Smith.

At least 235 records · Page 13Linked to original sources

Long-term results of treatment of children and adolescents with Hodgkin's disease.

Fifty-four children and adolescents with Hodgkin's disease Stages I--IV were treated with chemotherapy plus radiotherapy from 1967 to 1972. Thirty-eight patients (70%) remain in continuous complete remission. Nine patients have died, four of progressive disease, three of pneumonitis, one with probable pneumococcal sepsis, and one of acute myelocytic leukemia. Significant retardation of height and crown-rump length occurred, particularly in boys who received at least mantle or abdominal radiotherapy when younger than age 16 years. Five women have amenorrhea and no patient has clinical evidence of hypothyroidism. The major long-term effects of therapy in this group of patients has been growth retardation. Future studies to minimize long-term effects of therapy are necessary but must be carefully designed so that present cure rates are not jeopardized.

Adolescent↗

Value of serum copper levels and erythrocyte sedimentation rates as indicators of disease activity in children with Hodgkin's disease.

Initial and serial serum copper levels (SCL) and erythrocyte sedimentation rates (ESR) of 29 children with Hodgkin's disease were reviewed to determine the relationship of these features to disease activity. Only six of 10 patients who relapsed had SCL greater than adult upper normal levels. Although correction for age increased this to 7, it also increased the number of patients with false positive results to 9 of 19. Although 9 of the 10 patients at relapse had an increase in SCL over the preceding value, almost one-fifth of patients in remission had increases in consecutive SCL greater than the average increase of patients who relapsed. We conclude that SCL, even when age corrected and consecutively followed, are not useful as indicators of disease activity in children with Hodgkin's disease. Although the ESR increased to greater than 20 mm/hour in 9 of 10 patients who relapsed, this determination could not be considered a useful early indicator of disease recurrence since it was so frequently elevated in patients who were free of disease (62 of 109 determinations). The extremely nonspecific nature of SCL and ESR in childhood renders these tests unreliable, particularly in the individual child.

Adolescent↗

Cultural, morphological, cell membrane, enzymatic, and neoplastic properties of cell lines derived from a Hodgkin's disease lymph node.

A neoplastic cell line (designated HuT11) has been established in continuous culture from an involved lymph node of a patient with Stage IIA Hodgkin's disease of the mixed cellularity type. The HuT11 line has been morphologically heterogeneous, consisting of mononucleate lymphoid-like cells, polygonal epithelioid cells, and mono-, bi-, and multinucleate giant cells. Four clones initiated from isolated binucleate giant cells of the HuT11 line also have been successfully established as continuous cell lines. The cloned lines have been morphologically distinct and more homogeneous, although typical giant cells have consistently appeared throughout the long-term culture of each. The HuT11 lines have grown as monolayers in McCoy's Medium 5A supplemented with 10% fetal calf serum, with generation times of 12 to 14 hr and high saturation densities. Cytogenetic studies showed that early and later passages of HuT11 cells were aneuploid, and all cell lines were successfully heterotransplanted in the hamster cheek pouch. Repeated indirect immunofluorescence examinations have shown each cell line to be negative for Epstein-Barr virus nuclear antigen. Indirect immunofluorescence tests in which monospecific immunoglobulins were used revealed positive membrane reactions for the gamma (heavy)-chain and kappa (light)-chain of human immunoglobulin G in approximately 20% of viable cells in each line; however, direct immunofluorescence with anti-human immunoglobulin G F(ab')2 reagent failed to confirm these reactions. Rosette tests for B- and T-lymphocyte and macrophage membrane receptors yielded negative results. All cell lines were strongly phagocytic for latex particles and neutral red dye. Cytochemical stains of the monolayers revealed abundant esterase, fluoride-resistant nonspecific esterase, acid phosphatase, and leucine aminopeptidase activities, while lysozyme assays were negative. Although some properties of the HuT11 lines have suggested a macrophage derivation, an undifferentiated lymphoid cell origin of the Hodgkin's neoplastic cell remains a possibility.

Aneuploidy↗

Comparison of the clinical course of Hodgkin's disease in children and adolescents.

In this study the clinical features and response to therapy of 34 children, 4--10 years of age, and 54 adolescents, 11--20 years of age, were compared. The therapeutic response in patients in this series entered on a formal protocol was compared with nonstudy patients. The 2 age groups had similar sex ratios, characterized by male predominance, and age was not a determining factor in the extent of disease at diagnosis. By contrast, the distribution of histopathology varied between children and adolescents: mixed cellularity was most prevalent in the 4--10-year group (14/34), while nodular sclerosis predominated the older patients (23/55). Remission induction and duration were not age dependent, but remission duration did differ between study and nonstudy patients. Forty-five of 57 patients in the former group remain in continuous complete remission compared to 7 of 31 in the latter group. From these results we conclude that the clinical course of Hodgkin's disease is similar in children and adolescents and that the agressive therapy combined with careful staging used so successfully in adults should be adhered to in younger patients.

Adolescent↗

Changes in lactoferrin, immunoglobulin G, bovine serum albumin, and alpha-lactalbumin during acute experimental and natural coliform mastitis in cows.

An experimentally induced Escherichia coli infection of a bovine mammary gland resulted in a 30-fold increase in lactoferrin (Lf) concentration in the mammary secretion by 90 h postinoculation and a 4-fold increase in total daily production of Lf by 264 h postinoculation in the infected quarter. A simultaneous rise and fall of bovine serum albumin (BSA) and immunoglobulin G (IgG) concentrations occurred during the acute phase of the infection. Peak BSA and IgG levels were reached 36 h before peak Lf levels. BSA concentrations declined rapidly after the acute phase, whereas IgG and Lf levels remained elevated and decreased slowly as the infection subsided. A decline in alpha-lactalbumin concentration by 48 h postinoculation indicated decreased synthetic capability. The increased Lf production may be a result of a specific response of secretory tissue to inflammatory agents and thus the infectious process. Analogous changes in Lf, IgG, and BSA were observed during a natural coliform infection. Sephadex G-200 chromatography of mastitis skim milk showed that Lf approximated the monomer (molecular weight 77,100) early in infections progressed and abated, the apparent molecular weight of Lf increased to approximately that of the trimer and subsequently decreased to about 1.5 times that of the monomer.

Acute Disease↗

In vitro growth inhibition of mastitis-causing coliform bacteria by bovine apo-lactoferrin and reversal of inhibition by citrate and high concentrations of apo-lactoferin.

Bovine apo-lactoferrin (apo-Lf) was added to in vitro cultures of eight strains of coliform bacteria associated with bovine mastitis. As little as 0.02 mg of APO-Lf per ml resulted in marked inhibition of growth of all coliforms. Growth inhibition was lost if saturated Lf or iron plus apo-Lf was added to the synthetic medium. The inhibition of growth increased as the concentration of apo-Lf increased from 0.02 to 0.2 mg/ml for Klebsiella pneumoniae (OARDC-A1), Klebsiella spp. (K1-21), and Aerobacter aerogenes (55-12222) and 2 mg/ml for A. aerogenes (76-2414-1), Escherichia coli (60-Lilly), E. coli (66-S16), and Klebsiella spp. (K6-24). As the concentration of apo-Lf was increased above 0.2 or 2 mg/ml, there was less inhibition of growth except for E. coli (33-C4). Apo-Lf at 20 mg/ml was bactericidal for E. coli (33-C4). Results are compatible with the hypothesis that coliform bacteria respond to low-iron environments by production of iron-sequestering agents that complete effectively with apo-Lf for free iron. Addition of apo-Lf plus citrate resulted in loss of growth inhibition. The molar ratio (citrate to apo-Lf) was found to be more important than the absolute concentration of either component. A ratio of 75 resulted in 50% growth inhibition, whereas ratios of 300 and greater resulted in less than 10% growth inhibition. These results suggest that the ratio of citrate to Lf would be important in evaluating Lf as a nonspecific protective factor of bovine mammary secretions.

Animals↗

Lactoferrin concentration during involution of the bovine mammary gland.

Electroimmunodiffusion assay was used to quantitate changes in lactoferrin concentration in mammary secretions during involution of the bovine mammary gland. Concentration of lactoferrin began to increase 2 to 4 days after cessation of regular milking and continued to increase linearly at a rate of 1.15 mg/ml per day as a result of increased net synthesis of lactoferrin during the first 14 to 21 days of involution. Maximum lactoferrin concentration (approximately 20 mg/ml) was attained after 3 to 4 wk of involution. These changes represent a 100-fold increase in lactoferrin concentration over that in normal milk. Maximum lactoferrin concentration was variable between cows. In some cows, the concentration of lactoferrin plateaued at less than 10 mg/ml after 10 days of involution. In others, much higher lactoferrin concentrations of 75 to 100 mg/ml were measured. Lactoferrin concentration decreased markedly prior to parturition and onset of lactation. The increase in lactoferrin concentration during mammary gland involution appeared to be related closely to the process of involution.

Animals↗

Hormone induced lactation in the bovine III. Dynamics of injected and endogenous hormones.

Three lactations were induced in two cows in two trials by twice daily subcutaneous injections for seven days. Each injection contained .05 mg/kg body weight of estradiol-17beta and .125 mg/kg body weight of progesterone. Included with the hormones in trial 1 was a combination of 233 muCi of [6,7-hydrogen-3] estradiol-17beta and 12 muCi of [4-carbon-14] progesterone. During trial 2,2050 muCi of [2,4,6,7 hydrogen-3] estradiol-17beta were incorporated with the hormones for one cow and 2344 muCi of [1,2,6,7 hydrogen-3] progesterone for the other. Radioactivity from hydrogen-3 and carbon-14 was detected in urine and feces but not in mammary secretion during trial 1. Isotope recovery from [hydrogen-3] estradiol-17beta was too low to quantify. By day 17, 90% of the carbon-14 from progesterone was accumulated in feces and 8.0% in urine. For trial 2, recoveries of radioactivity by day 28 from urine, feces, and mammary secretions were, respectively, 32.4, 56.2, and less than .002% from [hydrogen-3] estradiol-17beta and 6.0, 87.7, and .25% from [hydrogen-3] progesterone. Estrogen and progesterone in plasma averaged 1.83 and 2.61 ng/ml during days 2 to 7. Estrogen decreased more rapidly than progesterone post-treatment, but both had decreased by days 16 to 19 when average prolactin of plasma increased. Quantitative measures of estradiol 17-beta and progesterone absorption, whether in plasma or excreta, were correlated.

Animals↗

Hormone induced lactation in the cow. IV. Relationships between lactational performance and hormone concentrations in blood plasma.

Concentrations of progesterone, estrogen, and prolactin in plasma were compared among lactations induced in 29 cows by daily subcutaneous injections of .25 mg progesterone and .1 mg estradiol-17beta per kg body weight for 7 days. Superior, median, and inferior lactations were identified by ranking both weightage adjusted maximum milk yields in 7 consecutive days (average 144 +/- 9 kg) and days for milk yield to increase from 5 to 10 kg/day (15 +/- 3 days). Superior and inferior of the former averaged 189 and 101 kg, and their latter averaged 2 and 42 days. Plasma hormones were measured on day 0 before first treatment (day 1), and on days 7, 14, 17, 21, 24, 28, and 35. Superior lactations were associated with below-average progesterone and estrogen in plasma on day 0, rapid decreases in progesterone after day 7 and in estrogen after day 14, and increased prolactin after 7. In comparison, median lactations were associated with elevated progesterone and estrogen after day 17, but prolactin was similar to that of superior lactations. Inferior lactations were associated with decreased prolactin in plasma from days 21 to 35. We hypothesized that (a) first treatment should start 3 to 8 days after estrus, (b) daily doses of estradiol-17beta should be decreased with progesterone unchanged for the 7 days, and (c) estradiol-17beta alone should be continued for 7 days to improve hormonally induced lactations.

Animals↗

Concentration of lactoferrin in milk of normal lactating cows and changes occurring during mastitis.

The mean lactoferrin (Lf) concentration determined by electroimmunodiffusion (EID) assay of whey preparations from 80 quarters of 20 normal lactating cows was 0.35 mg/ml. The mean alpha-lactalbumin (alpha-LAC) and bovine serum albumin (BSA) concentrations were 2.01 mg/ml and 0.29 mg/ml, respectively. The mean was significantly related to cell count (P smaller than 0.01), BSA (P smaller than 0.05), stage of lactation (P smaller than 0.05), and milk production (P smaller than 0.05). The Lf-milk production relationship was the only negative correlation. In 11 cows with mastitis, there was a significant (P smaller than 0.01) increase in mean Lf concentration in infected quarters from 0.55 mg/ml on day 1 of the infection to 1.89 mg/ml by day 3. By day 15 clinical signs had subsided and mean Lf concentrations had decreased to near day 1 values. On day 3 quarters infected with coliform bacteria (clinical mastitis generally more severe) had mean Lf values more than twofold greater than those quarters infected with species of Staphylococcus or Streptococcus (milder clinical signs). Noninfected (control) quarters of cows having coliform bacteria-infected quarters had slightly increased mean Lf concentrations, where Lf concentration in contral quarters of cows having quarters infected with gram-positive organisms remained unchanged.

Animals↗