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Biomedical subjects

L A Fitzpatrick

Publications and source records attributed to L A Fitzpatrick.

137 records · Page 8Linked to original sources
PubMed1986

Calcium-controlled secretion is effected through a guanine nucleotide regulatory protein in parathyroid cells.

Calcium regulates parathyroid secretion through mechanisms yet to be elucidated. We have investigated this phenomenon through use of pertussis toxin which catalyzes ADP-ribosylation and inactivation of a guanine nucleotide regulatory protein, possibly Ni or No. Calcium inhibition of PTH release is blocked in cells treated with pertussis toxin, and there is concomitant ADP-ribosylation of a 40-kilodalton protein. The ionophore A23187 inhibits secretion in toxin-treated as well as in control cells. We conclude that a guanine nucleotide regulatory protein is involved in calcium regulation of PTH secretion at a locus proximal to the intracellular site effecting inhibition of secretion.

Adenosine Diphosphate Ribose↗
PubMed1986

Secretory dysfunction in parathyroid cells from a neonate with severe primary hyperparathyroidism.

We report a patient with neonatal severe primary hyperparathyroidism whose parathyroid cells were markedly refractory to regulation by calcium in vitro. He showed life-threatening hypercalcemia (4.8-5.2 mM vs. normal of 2.1-2.7 mM). A sibling had been treated previously for an identical disorder. At age 6.5 months, four hyperplastic parathyroid glands were removed, and portions of one were immediately grafted into the forearm. Serum calcium again became elevated post-operatively and then fall to the normal range after excision of grafted parathyroid tissue. Dispersed parathyroid cells from the first operation showed no suppression of PTH secretion by 2 mM calcium; however, there was normal maximal suppressibility at 4 mM calcium with half-maximal suppression at 2.53 mM (the calcium set point). This contrasts with much lower set points previously established for suppressible cells from normal (1.02 +/- 0.10 mM, mean +/- 1 SD), from primary hyperplastic (1.10 +/- 0.14 mM), or from adenomatous (1.26 +/- 0.14 mM) parathyroid glands. The strikingly high set point may not be unique because a small number of glands previously classified as nonsuppressible (by the criterion of failing to suppress below 50% maximum at calcium concentration up to 2-3 mM) might have shown similarly high set points if tested at higher calcium concentrations. We conclude that an unusual abnormality of PTH secretory control accounts, in large part, for both the marked hypercalcemia and for its refractoriness to surgical treatment in this patient.

Calcium↗
PubMed1985

Computerized technetium/thallium scans and parathyroid reoperation.

Twenty-three consecutive patients who underwent reoperation for persistent primary hyperparathyroidism were studied with computerized technetium/thallium scans to evaluate it as a localization test. Prospective and blinded retrospective readings of the scans were correlated with findings at surgery. Computerized technetium/thallium scanning detected 52% of the parathyroid adenomas found at surgery. Forty-two percent of adenomas were localized exactly. There were no false positive scans. No normal parathyroid glands were imaged. No mediastinal glands were imaged. The study was not observer dependent. We conclude that computerized technetium/thallium scanning is helpful in patients undergoing parathyroid reoperation. If positive, it can accurately localize adenomas. If negative, we recommend more invasive studies.

Adenoma↗
PubMed1984

A human myeloma immunoglobulin G binding four moles of calcium associated with asymptomatic hypercalcemia.

A calcium-binding immunoglobulin G (IgG1 lambda RUP) was identified in the serum of a patient with multiple myeloma, asymptomatic hypercalcemia, and a normal ionized serum calcium. Calcium binding by IgGRUP was confirmed by two-dimensional electrophoresis with calcium-45 and equilibrium dialysis. Amino acid analyses indicated an unusually high number of glutamic (or glutamine) residues in the L chain and Fab fragment but no detectable gamma-carboxyglutamic acid. As determined by equilibrium dialysis with 45Ca, the intact IgGRUP and its Fab fragments bound calcium at an optimum pH of 7.4. There was minimal binding of calcium to H chains and no binding by L chains or the Fc fragment. Recombination of H and L chains partially restored the binding activity. By Scatchard analysis, the binding affinity (Kd) of IgGRUP was 1.7 X 10(-3) M and the binding capacity was 4 mol of calcium/mol of IgG. The binding of 4 mol of calcium/mol of IgG is twice that reported previously for two other calcium-binding myeloma proteins and suggests unique properties of IgGRUP.

Aged↗
PubMed1981

Acute aflatoxicosis in calves fed peanut hay.

Acute aflatoxicosis was believed to be the cause of death of 12 to 90 drought-stricken Hereford calves fed peanut hay on the southern Darling Downs in Queensland. Jaundice, photosensitisation, diarrhoea, anorexia and depression were seen before death. Serum levels of enzymes of hepatic origin and bilirubin were elevated. After death haemorrhage, hepatocyte damage, bile ductule proliferation were found. Total aflatoxin levels up to 2230 microgram/kg were detected in the peanut hay with most toxin concentrated in nut-in-shell.

Aflatoxins↗
PubMedDate not supplied

Epidemiology and clinical features of osteoporosis in young individuals.

Due to the lack of epidemiologic data on osteoporosis in the young, we identified all 22 Olmsted County, MN, residents aged 20-44 years when first diagnosed with established osteoporosis in 1976-1990. The overall age- and sex-adjusted incidence rate was 4.1 per 100,000 person-years (95% CI 2.4-5.9) with a female to male ratio of age-adjusted rates of 1.2:1. The majority represented secondary osteoporosis (12 steroid-induced, 3 postmenopausal, 2 delayed puberty, 2 anticonvulsant-induced, 2 gastrointestinal disease, 2 alcoholism, 1 anorexia nervosa, and 7 other etiologies; some individuals had more than one factor present) but two had idiopathic osteoporosis (incidence 0.4 per 100,000 person-years, 95% CI 0-0.9). To further characterize the patients with idiopathic osteoporosis, we also reviewed the entire Mayo Clinic experience with such patients from 1976 to 1990, regardless of residency. A total of 56 patients (30 female/26 male) were identified with a median age at diagnosis of 34 years. Only 8% were hypercalciuric at presentation. There was a preponderance of cancellous bone fractures (vertebral 81%, rib 37%, wrist 13%), although 13% did have hip fractures. Transiliac bone biopsies were available in 18 patients. As compared to age- and sex-matched controls, the osteoporotic subjects had a significant reduction in trabecular bone volume, cortical thickness, and mean wall thickness, the latter suggesting an abnormality in osteoblast function in these individuals.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗
PubMedDate not supplied

Site-specificity of bone mineral density and muscle strength in women: job-related physical activity.

We proposed that there are significant correlations between muscle strength and bone mineral density in premenopausal women and that these correlations are site-specific. To test this hypothesis, we examined the relationships among site-specific bone mineral density, physical activity, and muscle strength in a group of 96 healthy premenopausal Caucasian women. Bone mineral density was measured at the lumbar spine and at three sites in the proximal femur (trochanter, femoral neck, and Ward's triangle) with dual-energy x-ray absorptiometry and at the mid-radius with single-photon absorptiometry. The muscle strength of hip and spinal muscle groups was determined with a strain gauge isodynamometer, and grip strength was measured with the JAMAR dynamometer. The strength of shoulder girdle muscle groups was evaluated with the use of free weights. Physical activity was determined by surveying the subjects and by using a standardized scale. Data analysis revealed significant linear correlations of muscle strength with bone mineral density at the mid-radius (r = 0.31; P = 0.002) and at the hip (r = 0.26; P = 0.01). Grip strength was significantly correlated with bone mineral density of both the spine and the femur (r = 0.24, r = 0.34; P < 0.05 for both). Back extensor strength correlated with bone mineral density of the hip (Ward's triangle; r = 0.23; P = 0.023). However, there was no significant positive correlation between the strength of the spinal flexor or extensor muscles and the site-related bone mass (lumbar spine). Only one of the three components of the physical activity score (job) positively correlated with vertebral bone mineral density (r = 0.21; P = 0.04). Physical activity negatively correlated with age (r = 0.24; P = 0.02). We conclude that in premenopausal women, the effect of muscle strength on bone mass is more systemic than site-specific. A positive correlation between vertebral bone mass and components of physical activity demonstrates that even job-related physical activity is an important factor in maintaining adequate bone mass.

Adult↗
PubMedDate not supplied

Trial introduction of the Willis dropped ovary technique for spaying cattle in northern Australia.

OBJECTIVE: To compare the Willis dropped ovary technique with traditional spaying methods in extensive beef cattle herds in northern Australia. PROCEDURE: Three field trials were conducted simultaneously at different sites in northern Australia in 1996-97. Brahman and Brahman-Shorthorn cross heifers (n = 219, 2 years, 250 to 378 kg) and cows (n = 211, 3 to 16 years, 256 to 540 kg) were allocated by stratified randomisation to three treatments: spaying using the Willis dropped ovary technique (WDOT); spaying using traditional paralumbar and vaginal methods; and unspayed. Following these procedures, these nonpregnant, nonlactating cattle were then exposed to bulls (4 per 100 females) under extensive rangeland conditions for 12 months during which time weight, body condition, pregnancy and ovarian function were monitored and compared. RESULTS: Pregnancy rates varied from 60 to 90% for entire heifers and 80 to 100% for entire cows depending on site. The traditional spay methods were 100% successful in preventing pregnancy; the WDOT was 92 to 97% effective, depending on operator experience. The number of deaths was the same or higher in Willis spayed animals than other groups. Weight changes were similar in all groups at the three sites over the trial period. The time taken to spay using the WDOT was similar to or less than that required for the traditional methods. Uterine abnormalities were not observed in animals spayed with the WDOT, there were however 30 (12.4%) animals where excision of the ovary was incomplete; the still-attached ovarian remnant presumably accounting for the three pregnant animals in this group. CONCLUSION: The WDOT suffers from requiring a high degree of skill in transrectal ovarian manipulation. There were more deaths and more pregnancies than with traditional spay methods. More experienced operators can be expected to achieve lower mortalities, better contraception and higher processing rates. Pregnancy will occur as a consequence of ovarian remnants unless care is taken to ensure removal of the entire ovary.

Animals↗
PubMedDate not supplied

Synchronising oestrus with oestradiol benzoate after using a two-dose prostaglandin treatment to synchronise luteolysis in dairy heifers.

OBJECTIVE: To compare the reproductive performance and pattern of onset of oestrus in dairy heifers in which oestrous cycles were synchronised with two doses of prostaglandin (PG) F2alpha and oestrus was synchronised with oestradiol benzoate (ODB). PROCEDURE: Dairy heifers in two herds (herd A, n = 192; herd B, n = 267) were treated with two doses of an analogue of PGF2alpha (cloprostenol, 375 microg, IM) 12 days apart. Heifers not detected in oestrus 48 h after the last dose of PGF2alpha were either left untreated (No ODB, n = 147) or treated with ODB (0.75 mg IM, n = 126). Onset of oestrus was monitored at 0, 24, 48, 80, 96 and 120 h after the last dose of PGF2alpha Heifers were inseminated on detection of oestrus. RESULTS: After the last dose of PGF2alpha, oestrous detection rates at 80 h (43.5 vs 72.6%, P < 0.001), 96 h (74.1 vs 84.9%, P =0.025) and 120 h (78.2 vs 86.3%, P = 0.082) were less in the No ODB compared to the ODB heifers, respectively. Conception rates (percentage pregnant that were inseminated) were greater in the No ODB compared to the ODB heifers (64.3% vs 47.6%, respectively; P = 0.006), while pregnancy rates (percentage pregnant that were treated) were also greater in the No ODB compared to the ODB heifers, but differences were not significant (50.3% vs 41.1%, respectively; P = 0.068). CONCLUSION: Administration of ODB to heifers not in oestrus 48 h after a two-dose PGF2alpha treatment increases the percentage of heifers detected in oestrus by 80 h, 96 h and 120 h after treatment, by an estimated 29%, 11% and 8%, respectively. However, administration of ODB decreases conception rates by an estimated 17%, and may decrease pregnancy rates (estimated 9% difference). Results are consistent with the hypothesis that ODB can increase submission rates but reduce conception rates following a two dose treatment with PGF2alpha.

Animals↗
PubMedDate not supplied

Altered response to thyroid hormones by breast and ovarian cancer cells.

BACKGROUND: In this study, L-thyroxine (T4), 3',3,5-triiodo-L-thyronine (T3), 3,5-diiodo-L-thyronine (T2), reverse T3; 3',5',3-triiodo-L-thyronine (RT3) and transferrin were added to breast cancer cell lines Hs 578T, MDA-MB-231, MDA-MB-468, and T-47D and ovarian cancer cell line OVCAR-3 to test the response to cell proliferation. MATERIALS AND METHODS: Breast and ovarian cancer cell lines were placed in serum-free medium prior to addition of effector. Proliferation was determined by thymidine incorporation. For Northern analysis, RNA was isolated and c-fos, cjun and TIEG expression assessed. RESULTS: No compound provided uniform results across all cell lines. T2 inhibited proliferation in Hs 578T and MDA-MB-468, had no effect in MDA-MB-231 and OVCAR-3, and stimulated proliferation in T-47D cells. T3 inhibited proliferation in all cell lines except T-47D in which two-state behavior occurred, with increased proliferation at low concentrations (< or = 10(-6) M) and decreased proliferation at high concentrations (> or = 10(-5) M). RT3 inhibited proliferation in Hs 578T, MDA-MB-231, and T-47D but had no effect in MDA-MB-468 and OVCAR-3. T4 inhibited proliferation in Hs 578T, MDA-MB-231, and MDA-MB-468 and had two-state behavior in T-47D and OVCAR-3. Finally, transferrin increased proliferation only in OVCAR-3 cells. Protooncogene expression was increased by both transferrin and T4 in the cell lines tested. CONCLUSIONS: Correlation of iodines and proliferative responses were used to determine "essential" iodines necessary to produce the observed effect. Interaction between these cancer cells and non-physiological concentrations of thyroid hormone can be explained by thyroid hormone receptors with altered binding properties. Thus, interaction of thyroid hormones and cancer cells may differ from what occurs with normal cells.

Breast Neoplasms↗