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Biomedical subjects

L H Smith

Publications and source records attributed to L H Smith.

At least 19 recordsLinked to original sources
PubMed2005

Thyroid cancer in pregnancy.

OBJECTIVE: To compare stage at diagnosis, treatment and survival among pregnant women with thyroid cancer to non-pregnant women with thyroid cancer, and to assess the impact of treatment on maternal and perinatal outcomes. METHODS: A database containing maternal and newborn discharge records linked to the California Cancer Registry was queried to obtain information on all thyroid cancers from 1991-1999. Women with thyroid cancer occurring during pregnancy were compared to age-matched non-pregnant women with thyroid cancer. RESULTS: 595 cases of thyroid cancers were identified (129 antepartum and 466 postpartum). About 64% of thyroid cancers were diagnosed at stage 2 among pregnant women versus 58% among non-pregnant controls. The odds of thyroid cancer were 1.5 times higher among Asian/Pacific Islanders than among Non-Hispanic White women. Pregnancy had no significant effect on mortality after diagnosis of thyroid cancer. Thyroidectomy during pregnancy was not associated with adverse maternal or neonatal outcomes. CONCLUSIONS: Thyroid cancer discovered during or after pregnancy does not appear to have a significant impact on the prognosis of the disease.

Adenocarcinoma, Follicular↗
PubMed2003

Altered morphology in cultured rat intestinal epithelial IEC-6 cells is associated with alkaline phosphatase expression.

Non-transformed, rat intestinal epithelial cells (IEC-6), and human intestinal colonic carcinoma cells (CACO-2) have both been used to study processes of epithelial cell differentiation. However, only CACO-2 cells have been described as spontaneously expressing phenotypic changes of differentiation in culture. We report here that when IEC-6 cells are grown in post-confluent culture, they develop structural changes similar to those seen in cells induced to differentiate by culture on Englebreth-Holm-Swarm (EHS) extracellular matrix proteins. Correlated with this morphological change is loss of nuclear localization of c-myc protein and development of cell surface alkaline phosphatase (ALP) enzymatic activity. Messenger RNAs for liver and intestinal isoforms of ALP were expressed in both pre- and post-confluent cells. Inhibition of ALP activity in post-confluent cells by levamisole indicated the expressed ALP activity to be of the liver isoform. We suggest the expression of ALP activity, which occurs concomitantly with morphological alterations in post-confluent IEC-6 cells, represents increased expression and localization to the cell surface of the liver isoform of ALP. Cultured IEC-6 cells may provide a non-transformed, in vitro alternative to CACO-2 cells for study of epithelial cell differentiation.

Alkaline Phosphatase↗
PubMed2001

Cyclic AMP- and IL6-signaling cross talk: comodulation of proliferation and apoptosis in the 7TD1 B cell hybridoma.

Proliferation of the 7TD1 B cell hybridoma is dependent on the survival factor interleukin-6 (IL6). IL6 inhibits physiological cell death and allows expansion of populations of serum-stimulated cells. In this report, we demonstrate that cyclic AMP (cAMP)- and IL6-dependent signaling pathways can interact, controlling proliferation of 7TD1 cells through modulation of apoptosis. Cyclic AMP analogues inhibited proliferation, as well as other treatments that increased intracellular cAMP. The cAMP-induced inhibition could be reversed after 24 h by the removal of dibutyryl-cAMP from the culture medium and readdition of IL6. In the absence of IL6, cAMP induced a slow loss of viable cells. This decrease in viable cells in the presence of cAMP was accompanied by a marked increase in apoptosis. The increase in apoptotic cells after 48 h was preceded at 24 h by a parallel increase in DEVD-caspase activity after treatment with cell-permeable cAMP analogues. Increased DEVD-caspase activity and subsequent apoptosis could both be blocked by the addition of IL6. These coregulating actions may represent a cross-talk signaling mechanism modulating cytokine activation of cellular proliferation and survival.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed2001

Genetic diversity and transcriptional analysis of the bys1 gene from Blastomyces dermatitidis.

Blastomyces dermatitidis, a pathogenic fungal organism, is able to exist in two different morphologies, a multicellular mycelium or a unicellular yeast, according to temperature, 25 degrees C and 37 degrees C respectively. The switching between morphologies must be accompanied by a cascade of signaling events in which expression of genes responsible for the change of morphology is increased or decreased. bys1, a gene from B. dermatitidis isolate #58, is expressed at high levels in the unicellular yeast, but gradually diminishes as the temperature is lowered and the organism converts to the mycelial phase where there is no transcription of bys1. We explored if bys1 homologs are found in other B. dermatitidis isolates and if the transcription of the homologs were regulated by temperature. bys1 was identified in all B. dermatitidis isolates tested and could be grouped into two classes by Southern blot, PCR, and DNA sequence. Although the bys1 transcripts of both classes were regulated by temperature, transcription rates varied between the three isolates tested.

Amino Acid Sequence↗
PubMed2001

Phenotypic expression of primary hyperoxaluria: comparative features of types I and II.

BACKGROUND: The primary hyperoxalurias are autosomal recessive disorders resulting from deficiency of hepatic alanine:glyoxylate aminotransferase (PHI) or D-glycerate dehydrogenase/glyoxylate reductase (PHII). Marked hyperoxaluria results in urolithiasis, renal failure, and systemic oxalosis. A direct comparison of PHI and PHII has not previously been available. METHODS: Twelve patients with PHI and eight patients with PHII with an initial creatinine clearance of greater than or equal to 50 mL/min/1.73 m2 underwent similar laboratory evaluation, clinical management, and follow-up. Diagnosis of PHI and PHII was made by hepatic enzyme analysis (N = 11), increased urinary excretion of glycolate or glycerate (N = 7), or complete pyridoxine responsiveness (N = 2). Six PHI and five PHII patients had measurements of calcium oxalate crystalluria, urine supersaturation, and urine inhibition of calcium oxalate crystal formation. RESULTS: PHI and PHII did not differ in age at the onset of symptoms, initial serum creatinine, or plasma oxalate concentration. Urine oxalate excretion rates were higher in PHI (2.19 +/- 0.61 mmol/1.73 m2/24 hours) than PHII (1.61 +/- 0.43, P = 0.04). Urine osmolality, calcium, citrate, and magnesium concentrations were lower in PHI than PHII (P = 0.001, P = 0.019, P = 0.0002, P = 0.03, respectively). Crystalluria scores and calcium oxalate inhibitory activity of the urine did not differ between PHI and PHII. Calcium oxalate supersaturation in the urine was less in PHI (7.3 +/- 1.9) compared with PHII (14.0 +/- 3.3, P = 0.002). During follow-up of 10.3 +/- 9. 6 years in PHI and 18.1 +/- 5.6 years in PHII, stone-forming activity and stone procedures were more frequent in PHI than PHII (P < 0.01 and P = 0.01, respectively). Four of 12 PHI compared with 0 of 8 PHII patients progressed to end-stage renal disease (P = 0.03). CONCLUSION: The severity of disease expression is greater in type I primary hyperoxaluria than in type II. The difference may be due to greater oxalate excretion and lower concentrations of urine citrate and magnesium in patients with PHI compared with PHII.

Adolescent↗
PubMed2001

Obstetrical deliveries associated with maternal malignancy in California, 1992 through 1997.

OBJECTIVE: This study aims to characterize the rate of occurrence and nature of outcomes associated with obstetrical deliveries in women with malignant neoplasms among 3,168,911 women who delivered in California in 1992 through 1997. DESIGN: The study is a population-based retrospective review of infant birth and death certificates and maternal and neonatal discharge records. Cases of malignant neoplasms associated with obstetrical delivery were attributed to 1 of 3 categories, depending on the earliest documented hospital discharge diagnosis, as follows: "prenatal" if the diagnosis was first documented by hospitalization within 9 months preceding delivery, "at delivery" if the diagnosis was established from the delivery hospitalization, or "postpartum" if the diagnosis was first documented by hospitalization within 12 months after delivery. METHODS: Computer-linked infant birth and death certificates and maternal and neonatal discharge records were used to identify cases and outcomes. Cases of malignant neoplasms were identified by using International Classification of Diseases, Ninth Revision codes (140-208). Noninvasive neoplasms and carcinoma in situ neoplasms were excluded. In analysis of outcomes, the Mantel-Haenszel estimate for adjusted odds ratios was used. RESULTS: Among 3,168,911 obstetrical deliveries over the 6-year span, a total of 2247 cases of primary malignancy were identified. The observed rate of occurrence for primary malignant neoplasms was 0.71 per 1000 live singleton births. Most cases (53.3%) were first documented in the postpartum period as follows: prenatal, 587 cases (0.18 per 1000); at delivery, 462 cases (0.15 per 1000); and postpartum, 1198 cases (0.38 per 1000). The most frequently documented primary malignant neoplasms associated with obstetrical delivery were breast cancer (423 cases, 0.13 per 1000), thyroid cancer (389 cases, 0.12 per 1000), cervical cancer (266 cases, 0.08 per 1000), Hodgkin's disease (172 cases, 0.05 per 1000), and ovarian cancer (123 cases, 0.04 per 1000). Odds ratios for a variety of demographic factors identified maternal age as the most significant risk factor for development of malignant neoplasms (age greater than 40 vs 20-25, odds ratio 5.7, CI 4.6-6.9). Age-adjusted odds ratios for maternal cancer of any type suggested significantly elevated risks for cesarean delivery (odds ratio 1.4, CI 1.3-1.6), blood transfusion (odds ratio 6.2, CI 4.5-8.5), hysterectomy (odds ratio 27.4, CI 20.8-36.1), and maternal postpartum hospital stay greater than 5 days (odds ratio 30.6, CI 27.9-33.6), but not for postpartum maternal death (odds ratio 0.8, CI 0.6-1.0). Odds ratios also suggested significantly elevated risks for premature newborn (odds ratio 2.0, CI 1.8-2.2), very low birth weight (odds ratio 2.9, CI 2.2-3.8), and newborn hospital stay longer than 5 days (odds ratio 2.6, CI 2.4-3.0), but not for neonatal death (odds ratio 1.6, CI 0.8-3.1) or infant death (odds ratio 1.2, CI 0.5-3.3). However, several types of malignant neoplasms did confer significant elevations in risk for neonatal death. Hospital charges for both maternal and neonatal care were significantly elevated in the maternal malignant neoplasm group. CONCLUSION: A lower than expected occurrence rate of obstetrical delivery associated with maternal malignancy was seen when compared with previously published hospital-based reports. Malignant neoplasms associated with obstetrical delivery were most frequently first documented in the postpartum period. Maternal and neonatal morbidity were significantly increased, yet the risk of in-hospital maternal death was not significantly elevated. A significant increase in risk of neonatal death for infants of mothers with cervical cancer was found.

Adult↗
PubMed2000

A gene expression database for the molecular pharmacology of cancer.

We used cDNA microarrays to assess gene expression profiles in 60 human cancer cell lines used in a drug discovery screen by the National Cancer Institute. Using these data, we linked bioinformatics and chemoinformatics by correlating gene expression and drug activity patterns in the NCI60 lines. Clustering the cell lines on the basis of gene expression yielded relationships very different from those obtained by clustering the cell lines on the basis of their response to drugs. Gene-drug relationships for the clinical agents 5-fluorouracil and L-asparaginase exemplify how variations in the transcript levels of particular genes relate to mechanisms of drug sensitivity and resistance. This is the first study to integrate large databases on gene expression and molecular pharmacology.

Antineoplastic Agents↗
PubMed2000

Dietary restrictions for patients with neutropenia: a survey of institutional practices.

PURPOSE/OBJECTIVES: To describe institutional practices related to dietary restrictions for patients with neutropenia to determine whether restrictions are used and when they are implemented and discontinued. DESIGN: Descriptive survey. SAMPLE: 156 institutions belonging to the Association of Community Cancer Centers. METHODS: Mailed survey. FINDINGS: Of the institutions surveyed, 78% (n = 120) placed patients with neutropenia on restricted diets. Participating institutions responded that patients were placed on restricted diets at a variety of different white blood cell and neutrophil counts, including neutrophils < 1,000 (43%) and < 500 (46%). The majority of institutions (92%) placed patients on restricted diets once neutropenia was documented, while only 9% of institutions restricted diets when cancer treatment was initiated. Of the participating institutions, 83% (n = 96) restricted diets only when patients were neutropenic rather than throughout the duration of the chemotherapy regimen. The most commonly restricted foods were fresh fruits and juices (92%), fresh vegetables (95%), and raw eggs (74%). Few institutions restricted tap water (12%). Wine was restricted at 39% of institutions, and beer was restricted at 40% of institutions. CONCLUSIONS: The role of diet in the development of infection in patients with neutropenia is unclear. This unclear role contributes to the variation in dietary restrictions among institutions. IMPLICATIONS FOR NURSING PRACTICE: Additional research should focus on dietary factors contributing to neutropenic infections and establishing criteria for implementation of specific dietary modifications. Nursing assessment should include nutritional status and risk factors for neutropenia and bacterial translocation. Nursing protocols for neutropenic dietary restrictions should be based on research findings.

Bacterial Infections↗
PubMed1999

MedMiner: an Internet text-mining tool for biomedical information, with application to gene expression profiling.

The trend toward high-throughput techniques in molecular biology and the explosion of online scientific data threaten to overwhelm the ability of researchers to take full advantage of available information. This problem is particularly severe in the rapidly expanding area of gene expression experiments, for example, those carried out with cDNA microarrays or oligonucleotide chips. We present an Internet-based hypertext program, MedMiner, which filters and organizes large amounts of textual and structured information returned from public search engines like GeneCards and PubMed. We demonstrate the value of the approach for the analysis of gene expression data, but MedMiner can also be extended to other areas involving molecular genetic or pharmacological information. More generally still, MedMiner can be used to organize the information returned from any arbitrary PubMed search.

Databases, Factual↗
PubMed1998

Measurement of atherosclerotic carotid plaque size in vivo using high resolution magnetic resonance imaging.

BACKGROUND: Current imaging modalities, such as contrast angiography, accurately determine the degree of luminal narrowing but provide no direct information on plaque size. Magnetic resonance imaging (MRI), however, has potential for noninvasively determining arterial wall area (WA). This study was conducted to determine the accuracy of in vivo MRI for measuring the cross-sectional maximum wall area (MaxWA) of atherosclerotic carotid arteries in a group of patients undergoing carotid endarterectomy. METHODS AND RESULTS: Fourteen patients scheduled for carotid endarterectomy underwent preoperative carotid MRI using a custom-made phased-array coil. The plaques were excised en bloc and scanned using similar imaging parameters. MaxWA measurements from the ex vivo MRI were used as the reference standard and compared with MaxWA measurements from the corresponding in vivo MR study. Agreement between the in vivo and ex vivo measurement was analyzed using the Bland-Altman method. The paired in vivo and ex vivo MaxWA measurements strongly agreed: the mean difference (in vivo minus ex vivo) in MaxWA was 13.1+/-6.5 mm2 for T1-weighted (T1W) imaging (mean MaxWA in vivo=94.7 mm2, ex vivo=81.6 mm2) and 14.1+/-11.7 mm2 for proton density-weighted (PDW) imaging (mean MaxWA in vivo=93.4 mm2, ex vivo=79.3 mm2). Intraobserver and interobserver variability was small, with intraclass correlation coefficients ranging from 0.90 to 0.98. CONCLUSIONS: MRI is highly accurate for in vivo measurement of artery WA in atherosclerotic carotid lesions. This imaging technique has potential application monitoring lesion size in studies examining plaque progression and/or regression.

Arteriosclerosis↗
PubMed1997

Detection of serologic neutralizing antibodies against HPV-11 in patients with condyloma acuminata and cervical dysplasia using an in vitro assay.

This study was designed to investigate if neutralizing antibodies against HPV-11 are detectable in the serum of patients with condyloma acuminata (CA) or cervical intraepithelial neoplasia (CIN) using an in vitro infectivity assay for HPV-11. Purified HPV-11 virions were extracted from xenografted condyloma tissues implanted into athymic mice and used to infect cultured neonatal human foreskin keratinocytes (HFK) and an immortalized adult skin cell line (HaCaT). The presence of HPV-11-specific E1--E4 mRNA as detected by reverse transcriptase-polymerase chain reaction was indicative of early infection. Sera previously characterized for reactivity to HPV-11 and HPV-11 VLP (virus-like particles) by ELISA were tested for the ability to prevent HPV-11 in vitro infectivity. Neutralizing antibodies against HPV-11 were demonstrated when monoclonal antibodies or patient serum preincubated with HPV-11 virions prevented the infection of either of the two cell cultures, as shown by the absence of the E1--E4 mRNA transcript. Eleven (of 20) patients with CA were strongly ELISA reactive against HPV-11 virus-like particles. Five of these 11 patients also had detectable levels of neutralizing antibodies in their serum. It was also demonstrated that the neutralizing properties of the serum were titratable by endpoint dilution. None of 15 patients with CIN had detectable neutralizing antibodies against HPV-11. Neutralizing antibodies against HPV-11 can be detected in some patients with CA and the neutralizing effects of the patient sera can be titrated by endpoint dilution. The in vitro assay for the detection of neutralizing antibodies against HPV-11 may have utility for investigating the natural history of HPV infection and resolution, as well as assessing the efficacy of any putative HPV vaccine.

Animals↗
PubMed1997

Prophylactic chemoradiation of inguinofemoral lymph nodes in patients with locally extensive vulvar cancer.

OBJECTIVE: Primary surgical resection of locally advanced squamous cancer of the vulva may compromise the integrity of important midline structures such as the anus, clitoris, urethra, and vagina. Chemoradiation (synchronous radiation and cytotoxic chemotherapy) has been used as alternative initial treatment which may serve as definitive management for some patients, or may reduce the scope and functional sequelae of subsequent surgery in others. Inguinofemoral node dissection is associated with substantial risk of both acute and late morbidity, prompting consideration of elective inclusion of groin nodes within the irradiated volume and deletion of subsequent groin surgery. Concern that disease relapse in the groins is potentially fatal suggested the prudence of formal outcome assessment of our recent experience with prophylactic treatment of clinically uninvolved groin nodes in the context of concurrent chemoradiation for locally advanced primary vulvar cancer. METHODS: A review was conducted of 23 previously untreated patients with locally advanced squamous cancer of the vulva (2 T2, 20 T3, 1 T4) and clinically uninvolved groin nodes (1969 FIGO stages 14 N0, 4 N1, and 5 N2 with negative node biopsies) who were treated since 1987 with chemoradiation administered to a volume electively including bilateral inguinofemoral nodes. These patients did not undergo subsequent groin surgery. RESULTS: With follow-up from 6 to 98 months (mean, 45.3 months; median, 42 months), no patient has failed in the prophylactically irradiated inguinofemoral nodes. No patient has developed lymphedema, vascular insufficiency, or neurological injury in a lower extremity, and no patient has experienced aseptic necrosis of a femur. CONCLUSIONS: Elective irradiation of the groin nodes in the context of initial chemoradiation for locally advanced vulvar cancer is an effective therapy associated with acceptable acute toxicity and minimal late sequelae. It constitutes a sensible alternative to groin dissection in this patient population.

Adolescent↗
PubMed1995

Titration of HPV-11 infectivity and antibody neutralization can be measured in vitro.

Human papillomavirus type 11 (HPV-11), produced from the athymic mouse xenograft system, was shown to infect cultured neonatal human foreskin keratinocytes and the HaCaT keratinocyte cell line in vitro. Infection was documented by the appearance of HPV-11-specific spliced mRNA, detected by reverse transcriptase-polymerase chain reaction. Purified HPV-11 virions at concentrations of approximately 10(7) particles/ml could successfully evoke infection in this system. Infection was completely abrogated by preincubation of the HPV-11 inoculum with mouse anti-HPV-11 monoclonal antibodies, experimentally immunized animal sera, or sera of human patients with HPV infection. Concurrent detection of cellular mRNA for the beta-actin gene, also by reverse transcriptase-polymerase chain reaction, provided an internal control confirming RNA recovery and successful reverse transcriptase-polymerase chain reaction. Using this approach, it was possible to determine semiquantitative titers for test solutions of HPV-11-neutralizing antibodies. The in vitro system for HPV-11 infectivity and neutralization may be useful in the study of the immune response to HPV-11 infection or immunization in patients.

Actins↗
PubMed1995

Pumping iron.

Explore the source record for details and available documents.

Hemochromatosis↗
PubMed1994

Results of long-term treatment with orthophosphate and pyridoxine in patients with primary hyperoxaluria.

BACKGROUND: The prognosis for patients with primary hyperoxaluria has been ominous, with the expectation of renal failure, poor results with transplantation, and early death. METHODS: We studied the long-term effects of orthophosphate and pyridoxine therapy in 25 patients with primary hyperoxaluria who were treated for an average of 10 years (range, 0.3 to 26). Their mean age at the start of treatment was 12 years (median, 6; range, 0.5 to 32). We also studied the effect of orthophosphate and pyridoxine on urinary supersaturation with calcium oxalate, crystal inhibition using a seeded growth system, and crystal formation using scanning electron microscopy in 12 patients during three-day stays in the clinical research center. RESULTS: The mean (+/- SD) glomerular filtration rate at the start of treatment was 91 +/- 26 ml per minute per 1.73 m2. The median decline in glomerular filtration rates was 1.4 ml per minute per 1.73 m2 of body-surface area per year. The actuarial survival free of end-stage renal disease was 96, 89, 74, and 74 percent of 5, 10, 15, and 20 years, respectively. Treatment with orthophosphate and pyridoxine reduced urinary supersaturation with calcium oxalate from 8.3 +/- 3.0 to 2.1 +/- 1.7 kJ per mole at 38 degrees C (P < 0.001), increased the inhibition of calcium oxalate formation from 63 +/- 11 to 108 +/- 10 inhibitor units per 24 hours (P < 0.001), and improved the crystalluria score from 2.6 +/- 0.3 to 0.6 +/- 0.1 (P < 0.001). CONCLUSIONS: Treatment of patients with primary hyperoxaluria with orthophosphate and pyridoxine decreases urinary calcium oxalate crystallization and appears to preserve renal function.

Actuarial Analysis↗
PubMed1994

Molecular evidence that the myxozoan protists are metazoans.

The evolutionary origins of the protistan phylum, Myxozoa, have long been questioned. Although these obligate parasites are like protozoans in many features, several aspects of their ontogeny and morphology have implied a closer relationship to metazoan lineages. Phylogenetic analyses of 18S ribosomal RNA sequences from myxozoans and other eukaryotes, with the use of parsimony, distance, and maximum-likelihood methods, support the hypothesis that myxozoans are closely related to the bilateral animals. These results suggest that the Myxozoa, long considered an assemblage of protozoans, should be considered a metazoan phylum.

Animals↗