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Biomedical subjects

L H Williams

Publications and source records attributed to L H Williams.

16 recordsLinked to original sources
PubMed2006

ST7-mediated suppression of tumorigenicity of prostate cancer cells is characterized by remodeling of the extracellular matrix.

Multiple lines of evidence have provided compelling evidence for the existence of a tumor suppressor gene (TSG) on chromosome 7q31.1. ST7 may be the target of this genetic instability but its designation as a TSG is controversial. In this study, we show that, functionally, ST7 behaves as a tumor suppressor in human cancer. ST7 suppressed growth of PC-3 prostate cancer cells inoculated subcutaneously into severe combined immunodeficient mice, and increased the latency of tumor detection from 13 days in control tumors to 23 days. Re-expression of ST7 was also associated with suppression of colony formation under anchorage-independent conditions in MDA-MB-231 breast cancer cells and ST7 mRNA expression was downregulated in 44% of primary breast cancers. Expression profiling of PC-3 cells revealed that ST7 predominantly induces changes in genes involved in re-modeling the extracellular matrix such as SPARC, IGFBP5 and several matrix metalloproteinases. These data indicate that ST7 may mediate tumor suppression through modification of the tumor microenvironment.

Base Sequence↗
PubMed1998

Side effects resulting from the use of growth hormone and insulin-like growth factor-I as combined therapy to frail elderly patients.

BACKGROUND: The objective of this study was to examine the relationship between serum IGF-I concentration and the incidence of side effects of therapy with recombinant human growth hormone (rhGH) and recombinant human insulin-like growth factor-I (rhIGF-I). METHODS: Thirteen high-risk, undernourished elderly males were started on a 15-day course of rhGH and rhIGF-I by subcutaneous injection. The dose of rhGH was held constant at .0125 mg/kg/day, whereas the dose of rhIGF-I was increased in a stepwise fashion from 10 micrograms/kg to the targeted dose of 40 micrograms/kg twice a day. RESULTS: Nine subjects completed the protocol and reached the full target dose of both hormones. Fluid retention, gynecomastia, and orthostatic hypotension were the most common complications. The hormone injections increased the serum concentration of IGF-I (from 72.7 +/- 40.9 to 483.7 +/- 251.4 eta g/ml, p = .001) and IGFBP-3 (from 1.82 +/- 0.66 to 2.72 +/- 1.18 mg/L, p = .012), and decreased serum albumin (from 34.3 +/- 5.5 to 31.4 +/- 4.6 g/L, p = .009). The magnitude of the initial increase in the serum IGF-I concentration was a powerful risk factor for severe orthostatic hypotension, diffuse myalgias, and drug-induced hepatitis. There was no association between the serum IGF-I concentration and fluid retention or gynecomastia. CONCLUSIONS: Treatment of the undernourished frail elderly with the anabolic agents rhGH and rhIGF-I at the specified dosages may produce undesirable side effects including fluid retention, gynecomastia, and orthostatic hypotension. Although these agents hold therapeutic promise, they must be used with caution in this high-risk population.

Aged↗
PubMed1989

Prenatal diagnosis of a red-cell enzymopathy: triose phosphate isomerase deficiency.

A child with triose phosphate isomerase deficiency was born to nonconsanguineous parents, and died at 13 months of age. The parents were both found to be heterozygous for this enzyme deficiency. At a subsequent pregnancy, analysis of fetal red blood cells obtained by cordocentesis at 19 weeks' gestation enabled prenatal diagnosis of the heterozygous state. This technique may allow diagnosis of other red-cell enzymopathies during the second trimester.

Carbohydrate Epimerases↗
PubMed1988

Long-term bone marrow culture as a model for host toxicity: the effect of methotrexate on hematopoiesis and adherent layer function.

Long-term bone marrow culture was used to examine the hematopoietic toxicity of the chemotherapeutic agent methotrexate. A dose-related suppression in myelopoiesis was seen when cultures were treated with 10(-3), 10(-4), or 10(-5) M methotrexate followed by folinic acid rescue. Differential counts revealed an initial decrease of postmitotic myeloid cells followed by mitotic precursors and myeloid colony-forming units (CFU-C). Myelopoiesis had disappeared by 7-10 days when 10(-3) M methotrexate was studied, by day 21 with 10(-4) M methotrexate, and by day 28 with 10(-5) M methotrexate. Although 10(-3) M methotrexate caused a predictable suppression in myelopoiesis, the effect of 10(-5) M methotrexate was more variable. In some studies this dose caused significant suppression of myelopoiesis, whereas in others less suppression occurred. This provides some evidence for varying host susceptibility to drug. Microenvironmental (adherent layer) cells were also affected by methotrexate. An increase in proliferation of these cells occurred in proportion to the dose of methotrexate added to culture. Methotrexate did not affect the ability of the adherent cells to produce colony-stimulating activity (CSA), but high doses did prevent the layer's ability to support the proliferation of adherent cell-free marrow. These results indicate that long-term bone marrow culture can be used to successfully predict and define chemotherapeutic host toxicity.

Bone Marrow↗
PubMed1986

Evaluation of the effect of age on hematopoiesis in the C57BL/6 mouse.

The effect of age on hematopoiesis was studied in young (six-month) and old (24-month) C57BL/6 mice. In addition, studies were performed on very old (42-month) mice, housed either singly or in groups of five animals per cage. Although a reduction in hematocrit was found in the older mice, red cell mass was normal in both old and very old single-caged mice. A detailed evaluation of erythropoiesis that included plasma- and erythron-iron turnover (PIT and EIT), red cell survival, and quantitation of the marrow erythroid progenitor and differentiated cells demonstrated no age-related change in single-caged animals. Similarly, quantitation of marrow myeloid precursors was identical in these groups. These results indicate that no age-related change in basal hematopoiesis can be demonstrated even in animals approaching maximal life expectancy. When very old mice were routinely housed in groups of five per cage, however, a decrease in hematocrit was found which was accompanied by significant alterations in hematopoiesis, including reductions in total differentiated erythroid cells, erythroid burst-forming units (BFU-E), erythroid colony-forming units (CFU-E), and colony-forming-unit culture (CFU-C) levels. It is likely that in very old animals, group housing constitutes a sufficient stress to compromise hematopoiesis. These findings indicate that basal hematopoiesis is unaltered by aging, although the bone marrow's reserve capacity is markedly compromised.

Aging↗
PubMed1984

Massive pericardial effusion in a hypothyroid child.

A child with Down's syndrome and long standing severe hypothyroidism had a massive pericardial effusion without cardiac tamponade. The effusion completely resolved with medical treatment without pericardiocentesis.

Adolescent↗
PubMed1983

Pancreatitis during sodium valproate treatment.

A girl aged 1 year died of acute haemorrhagic pancreatitis while taking sodium valproate. Necropsy showed widespread vascular disease that may have contributed to the onset of pancreatitis. Previous reports of pancreatitis in children receiving valproic acid are reviewed and although the association is rare, a causal relation between pancreatitis and valproic acid seems to have been established.

Acute Disease↗
PubMed1982

Correlation of amylase and lecithin sphingomyelin ratios in amniotic fluid samples.

The use of amniotic fluid amylase (AF amylase) has been proposed as a screening test to determine fetal maturity. We reviewed data from 944 amniotic fluid samples analyzed by our laboratory for amylase and lecithin sphingomyelin (L/S) ratio between 1975 and 1980. AF amylase shows poor overall correlation with L/S ratios (r = 0.256). Retrospective analysis of AF amylase as a screen to determine the need for L/S ratios showed an overall sensitivity of 57%, and an overall specificity of 86% for AF amylase. Three groups were studied: a low amylase group (amylase less than 200 U/L), a middle group (amylase 200-300 U/L), and a high amylase group (amylase greater than 300 U/L). Only 55% of the low amylase group had an immature L/S ratio. The high amylase group had the best correlation between AF amylase and L/S ratio, but 13% of these samples had an immature or borderline L/S ratio. We conclude that AF amylase cannot be used as a screening test to determine the need to perform L/S ratios.

Amniotic Fluid↗
PubMed1981

Elevated amniotic fluid creatinine.

Amniotic fluid creatinine has been used to evaluate fetal maturity, but there is evidence that maternal diseases may affect amniotic fluid creatinine levels. We report a case of a pregnant woman with renal insufficiency who had markedly elevated amniotic fluid creatinine. Review of data from 9 patients with elevated serum and amniotic fluid creatinine levels showed a statistically significant relationship between maternal serum creatinine and amniotic fluid creatinine. Review of data from 19 patients with amniotic fluid creatinine levels higher than 3 mg/dl showed no relationship between the amniotic fluid creatinine and fetal weight. We conclude that amniotic fluid creatinine in women with elevated serum creatinine is an unreliable predictor of fetal maturity.

Adolescent↗