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Biomedical subjects

S Kay

Publications and source records attributed to S Kay.

At least 19 recordsLinked to original sources
PubMed2000

Release from apoptosis correlates with tumor progression in the AKR lymphoma.

Disturbance of apoptosis is an established factor in tumorigenesis. The role of apoptosis in tumor progression is not yet clear. In the present study we compared the tendency to spontaneous apoptosis (and the proliferative capacity) of tumor cells derived from primary (PT) and metastatic tumor (MT) cells of several AKR lymphoma variants. Apoptosis-related gene expression was also compared. Our results indicate that release from apoptosis has a role in the tumor progression of this T cell lymphoma. At the cellular level, a markedly lower apoptotic tendency was observed in MT than in PT cells. The existence of macrophages only in PT also supports the presence of apoptotic cells in local but not in MTs. By contrast, proliferative capacity does not determine tumor aggressiveness in this system. At the molecular level, we found a higher staining intensity for bcl-2 in MT than in PT cells, suggesting that bcl-2 might be responsible for the reduced apoptosis in MT compared to PT cells. Evidence for p53 overexpression was found in the MT cells of one of the variants but in none of the PT. Comparison of Fas receptor, unexpectedly showed an increased expression in MT versus PT cells, possibly indicating resistance to Fas-induced apoptosis in the MT cells.

Animals↗
PubMed2000

Sensitivity to macrophages decreases with tumor progression in the AKR lymphoma.

Resistance to immune reactions, innate or acquired, may be one of the mechanisms responsible for the progression of tumors. We have, indeed shown higher numbers of macrophages surrounding low- as compared to high-malignancy cells. In the present study we examined the level of cell surface molecules known to determine sensitivity to macrophages, namely galactose (GAL) and sialic acid (SA) residues. A histochemical assay for identification of SA by electron microscopy showed a higher cell surface content on metastatic (MT) than on primary (PT) tumor cells. The FACS data seen with fluorescent lectins showed a higher binding of Sambucus nigra agglutinin, which identifies SA attached to terminal GAL in -2.6 or -2.3 linkage, in MT than in PT cells. Binding of Maakia amurensis lectin (MAL-1), which identifies SA at position 3 of GAL, showed that the MT cells contain two subpopulations, one binding more MAL-1 and another less. Cell sorting showed a more aggressive behavior of the first population. The comparison of Peanut agglutinin (PNA) binding, which identifies GAL, demonstrated a decreased amount of PNA receptors in MT as compared to PT cells. Western blot analysis of the membranal proteins with different lectins, identified 3 sialylated glycoproteins. The 88 kDa glycoprotein had no significance for metastatic potential. The 130 kDa glycoprotein was higher in MT than on PT cells. The 220 kDa glycoprotein was practically present only on MT cells. The tendency observed was of a higher level of membranal glycoconjugates terminally sialylated with subterminal galactose residues, inMT cells as compared to PT cells. This may explain the recently found decrease in apoptotic cell death with increasing aggressiveness of the AKR lymphoma and suggests a lower sensitivity to macrophages with tumor progression. Treatment based on the reduction in sialic acid content might render the tumor cells more vulnerable to macrophages. We found, indeed, that Wheat germ agglutinin (WGA) injected in vivo, exerted an inhibitory effect on growth of the lymphoma. We found moreover that WGA-treated tumor cells were more sensitive than nontreated cells to macrophages in vitro.

Animals↗
PubMed1999

Revisiting the role of routine retropleural drainage after repair of esophageal atresia with distal tracheoesophageal fistula.

PURPOSE: The aim of this study was to review routine retropleural drainage in esophageal atresia with distal tracheoesophageal fistula (TEF). METHODS: The charts of 52 patients diagnosed with TEF between 1987 and 1997 were reviewed. Data collected included gestational age, birth weight, associated congenital anomalies, respiratory status, operative technique and timing, size of gap, tension on the anastomosis, complications related to the drain, and esophageal anastomotic leak (incidence, diagnosis, and treatment). RESULTS: A total of 52 cases of TEF were identified. Data on sex, gestation age, birth weights, and malformations are summarized. Forty-seven patients underwent a single-stage extrapleural repair. Only one leak was identified in the single-stage group on routine day 7 esophagogram: a Waterson C patient who was clinically well with minimal drainage. The only other leak was in a class C patient who had undergone a staged repair because of an initial long gap. None of the favorable Waterston class patients suffered a leak. CONCLUSIONS: A routine retropleural drain placed near the anastomosis may not be necessary in all cases of TEF. Good prognosis patients (Waterston class A and B) who undergo an uncomplicated extrapleural repair without undue tension do not appear to benefit from having a chest drain in place, and there is potential for complications. In complicated cases, however, retropleural drainage remains a reasonable adjunct.

Anastomosis, Surgical↗
PubMed1999

Prenatal percutaneous needle drainage of cystic sacrococcygeal teratomas.

Prenatal ultrasound (US) permits in utero diagnosis of sacrococcygeal teratoma (SCT), follow-up of tumor size, and the early identification of complications, allowing for a more timely and appropriate delivery. The recommended management of large SCTs is delivery by cesarean section (CS) to prevent dystocia, tumor rupture, hemorrhage, and death. However, even delivery by CS can be difficult, necessitating a large hysterotomy that adds to maternal morbidity. The authors report two cases of cystic SCTs in which prenatal percutaneous drainage allowed for an uncomplicated vaginal delivery. In the first case, a large unilocular cystic SCT was diagnosed at 31 weeks' gestation on prenatal US. The fetal presentation was breech, and the mass was steadily increasing in size, preventing spontaneous version. At 37 5/7 weeks, the cyst was percutaneously drained under US guidance allowing for successful external version. Repeat drainage just before induction of labor permitted a successful vaginal delivery. In the second case, the cystic SCT was percutaneously drained just before induction of labor at full term, again allowing for an uncomplicated vaginal delivery. Prenatal percutaneous needle drainage of cystic SCTs offers an alternative to CS that results in decreased risks for both mother and fetus.

Adult↗
PubMed1999

A patient preference study comparing raltitrexed ('Tomudex') and bolus or infusional 5-fluorouracil regimens in advanced colorectal cancer: influence of side-effects and administration attributes.

Current chemotherapy regimens used in advanced colorectal cancer (ACRC) are similar in terms of efficacy, but differ importantly in terms of side-effects and administration profiles. These differences may impact significantly on patients' lives. We have evaluated patient preferences between raltitrexed ('Tomudex') and 5-fluorouracil-based chemotherapy regimens, with regard to side-effect attributes (raltitrexed and Mayo regimens) and administration attributes (raltitrexed, Mayo, De Gramont and Lokich regimens) in a study based on 82 patients with ACRC. Patients completed a series of rating tasks on how 'upsetting' these attributes were to them using a visual analogue scale (VAS) in a structured interview conducted by a research nurse. Mucositis and asthenia were the most and least upsetting side-effects, respectively. The side-effect profile of raltitrexed was clearly preferred by 78% of patients versus 14% for Mayo (P < 0.001). When side-effects and administration attributes were combined into an overall profile, 91% of patients selected raltitrexed as their clearly preferred regimen, versus 6% for Mayo (P < 0.001). The administration regimen of raltitrexed was ranked most acceptable (mean rank score 1.5 compared with Mayo 2.6, De Gramont 2.7, and Lokich 3.3). Given similar palliative effects, patients with ACRC exhibit preferences for raltitrexed over other regimens, based on administration and/or side-effect attributes. Such preferences should constitute an important part of decisions relating to the choice of chemotherapy regimen in ACRC.

Adult↗
PubMed1999

Isoflavones from red clover improve systemic arterial compliance but not plasma lipids in menopausal women.

The possibility that the heightened cardiovascular risk associated with the menopause can be reduced by increasing dietary isoflavone intake was tested in 17 women by measuring arterial compliance, an index of the elasticity of large arteries such as the thoracic aorta. Compliance diminishes with age and menopause. An initial 3- to 4-week run-in period and a 5-week placebo period were followed by two 5-week periods of active treatment with 40 mg and then 80 mg isoflavones derived from red clover containing genistein, daidzein, biochanin, and formononetin in 14 and 13 women, respectively, with 3 others serving as placebo controls throughout. Arterial compliance, measured by ultrasound as a pressure (carotid artery) and volume (outflow into aorta) relationship, was determined after each period; plasma lipids were measured twice during each period. Urinary output of isoflavones was also determined. Arterial compliance rose by 23% relative to that during the placebo period with the 80-mg isoflavone dose and slightly less with the 40-mg dose (mean +/- SEM: placebo, .197 +/- .015; 40 mg, .237 +/- 0.007; 80 mg, .244 +/- .014). In the three women receiving continuous placebo, compliance was .16 +/- .022, similar to that during the run-in period for the remaining subjects (.17 +/- .021) [corrected]. ANOVA showed a significant (P = < 0.001) difference between treatments; by Bonferroni multiple comparisons and by paired t test, differences were significant between placebo and 40- and 80-mg isoflavone doses (by paired t test: P = 0.039 for placebo vs. 40 mg; P = 0.018 for placebo vs. 80 mg). Plasma lipids were not significantly affected. An important cardiovascular risk factor, arterial compliance, which diminishes with menopause, was significantly improved with red clover isoflavones. As diminished compliance leads to systolic hypertension and may increase left ventricular work, the findings indicate a potential new therapeutic approach for improved cardiovascular function after menopause.

Adult↗
PubMed1999

Microsurgical reconstruction in abnormalities of children's hands.

Microsurgical reconstruction offers unique opportunities for improving function and appearance in children's hands affected by congenital anomalies or following trauma. Strong parallels exist between the surgery for congenital and post-traumatic defects. This article defines some of the methods used in replacement of skin, the creation of new digits, and the transfer of muscles.

Amputation, Traumatic↗
PubMed1999

Developing shared understanding through simulation.

In this article relevant key findings of a review of selected published work are used to provide a foundation for a new approach to developing a shared understanding of aspects of health care delivery. The new approach makes use of simulation models. It is hoped that this approach will provide support for improved decision-making and for the development of more appropriate enabling tools.

Community Health Services↗
PubMed1999

Constructing scenarios for validating the electronic health care record architecture.

The CEN TC 251 Electronic Health Care Record Architecture is the first part of a four part communication prestandard intended to facilitate the safe communication of clinical information, irrespective of circumstances related to time, distance, and responsibility. The work has important implications for a diversity of stakeholders and must embody clinical principles if it is to succeed. The issue at hand is how to enable clinicians to validate the reference architecture, which is necessarily a technical document, so that they have confidence that it can meet the clinical requirement for safe communication. A model of communication that has been used to ground the architecture is shown to be useful in creating relevant clinical scenarios to permit the first steps towards coherent validation in a systematic way.

Computer Communication Networks↗
PubMed1999

Architecture models to facilitate communication of clinical information.

This is an account of the development and use of a context model for facilitating the communication of clinical information. Its function is to articulate the principle of context within a reference architecture for the Electronic Health Care Record (EHCR). The work required a re-examination of established models of communication, the purpose being to use them to support an architecture that could be reasonably expected to accommodate future, and by definition unforeseeable, developments in EHCR communication. The Context Model is built upon seven recognized constituents of communication. These constituents, although having their origin in the engineering of signal communication, have been found to be useful for explication both in the verbal and textual communication of narratives between people. The electronic health care record architecture supported by the model is the European prestandard ENV13606-1.

Medical Records Systems, Computerized↗
PubMed1998

Coexisting kinetically distinguishable forms of dialkylglycine decarboxylase engendered by alkali metal ions.

The pyridoxal phosphate (PLP) dependent enzyme dialkylglycine decarboxylase (DGD) specifically binds alkali metal ions near the active site. Large ions (Rb+, K+) activate the enzyme while smaller ones (Na+, Li+) inhibit it. Crystallographic results have shown that DGD undergoes a metal ion size dependent structural switch [Hohenester, E., Keller, J. W., and Jansonius, J. N. (1994) Biochemistry 33, 13561], but no evidence for multiple conformations in crystalline DGD was obtained. Here, evidence is presented that DGD-K+ in solution exists in two conformations differing in catalytic competence. Initial rate traces for DGD-K+ exhibit a high degree of curvature due to decreasing activity over time. DGD remains tetrameric under the assay conditions as demonstrated by gel filtration experiments, arguing against the possibility of subunit dissociation as the source of activity loss. Likewise, the mass spectrum of DGD shows a single covalent form. A hysteretic model that assumes two slowly interconverting enzyme forms accounts well for the initial rate data when kinetic parameters from biphasic pre-steady-state kinetics are employed. The fit of the model to the data yields an estimate of 59 +/- 1% for the fast form. A cooperative model cannot account for the data. Double reciprocal plots for coenzyme binding to DGD exhibit two linear phases. Similarly, two kinetic phases are observed in PLP association kinetics. The substitution of Na+ or Rb+ for K+ alters the steady-state kinetic parameters of DGD. Preincubation of DGD-K+ with the competitive inhibitor 1-aminocyclopropane-1-carboxylate (ACC) lowers both kcat and KAIB apparently by drawing the enzyme toward the less active, tighter binding form observed in the pre-steady-state kinetics. These results suggest that the structure of the protein around the alkali metal ion determines the conformational distribution. The transamination reaction with l-alanine was coupled in the pre-steady-state to the LDH-catalyzed oxidation of NADH. This experiment yields an estimate of 68 +/- 4% for the fast form, in agreement with the hysteretic fit to the steady-state data. The reaction of DGD with dithiobis(nitrobenzoate) was used to probe the preexisting forms of DGD. Preincubation of DGD with ACC, like the exchange of Na+ for K+, shifts the conformational distribution, in agreement with the steady-state kinetics. These experiments clearly demonstrate that DGD is a hysteretic enzyme whose conformational distribution is controlled by the identity of the alkali metal ion bound near the active site, and that cooperativity does not play a role in catalysis or regulation.

Alanine↗
PubMed1998

Determinants of the selection of phosphatidylcholine molecular species for secretion into bile in the rat.

Certain phosphatidylcholine (PC) molecular species appear to be secreted into bile preferentially, but the mechanism for this selection remains obscure. We used multivariate analysis to examine the relationship between PC structure and the odds of secretion for individual PC species secreted into bile. PC was isolated from Folch extracts of bile and liver from rats, and individual molecular species of PC were quantified with reverse-phase high-performance liquid chromatography (HPLC). The odds of secretion for a given PC species were quantified as the ratio of its mole% in bile/mole% in liver. Regression analysis indicated that the odds of secretion were significantly related to length of both the sn-1 and sn-2 acyl chains (P < .0001 for both) and to relative hydrophobicity as determined by reverse-phase HPLC (P < .0001). In addition, the relationship between odds of secretion and sn-1 chain length was best described by a parabolic function. Considered together, these characteristics accounted for 88% of the observed differences in odds of secretion. This relationship between PC structure and odds of secretion was strikingly similar to the relationship between PC structure and affinity for bovine PC transfer protein. When multivariate models were used to predict both the odds of secretion and the affinity for PC transfer protein for a set of biologically plausible PC species, there was a linear relationship between the two. The likelihood of a given PC species being secreted into bile can be related to the structural characteristics of the acyl chains without having to postulate the existence of a special pool of PC destined for biliary secretion. Second, the structural characteristics that dictate selection of PC species for secretion into bile are similar to those that determine binding affinity for PC transfer protein, suggesting that the likelihood of a PC being secreted into bile is, in fact, closely related to its binding affinity for PC transfer protein (PC-TP).

Androgen-Binding Protein↗
PubMed1998

Anorectal disease in HIV-infected patients.

PURPOSE: Anorectal diseases are common in human immunodeficiency virus-infected individuals. The aim of this prospective study was to assess the cause and clinical presentation of anorectal disease in this human immunodeficiency virus-infected population. METHODS: A registry of all human immunodeficiency virus-seropositive patients with anorectal complaints who were referred to and followed up in the colorectal surgery clinic at a county hospital was maintained, with all data collected prospectively. All patients underwent examination under anesthesia with random cultures and biopsies, along with specific sampling of any suspicious lesions. RESULTS: Data from 180 consecutive human immunodeficiency virus-seropositive patients with anorectal symptoms were analyzed. Mean age of the population was 34 years, with a male-to-female ratio of 14:1. This group comprised homosexual and bisexual males (55 percent), injection-drug users (15 percent), heterosexuals (12 percent), and others (18 percent). The average lag time from diagnosis of human immunodeficiency virus to anorectal symptoms was 48 months. The average CD4 lymphocyte count was 160 cells/mm3. The most common symptom was anorectal pain (57 percent), followed by lumps or warts (28 percent), rectal bleeding (12 percent), discharge (11 percent), and pruritus (6 percent), with 24 percent of patients having multiple complaints. Anal condyloma was the most prevalent pathology observed (43 percent), of which 10 percent was associated with anal intraepithelial neoplasia. Wide-based anal ulcers were the most frequent noncondylomatous lesions, occurring in 32 percent of patients, with the majority (91 percent) presenting with the chief complaint of anorectal pain. Some of these ulcers were associated with viral infections: herpes simplex virus (12 percent) and cytomegalovirus (7 percent). However, most ulcers were idiopathic, with negative cultures and biopsies. Other lesions encountered included fistulas (14 percent), abscesses (12 percent), hemorrhoids (6 percent), and malignancy, with two cases of Kaposi's sarcoma, one case of non-Hodgkin's lymphoma, and one case of squamous-cell carcinoma. More than one anorectal condition was identified in 16 percent of the patients. CONCLUSIONS: Human immunodeficiency virus infection is associated with a wide spectrum of anorectal disease, of which the most common lesions are anal condylomata and painful ulcers. The majority of these anal ulcers gave negative culture and biopsy results. In addition, there seems to be a high incidence of anorectal neoplasia in this patient population.

Adolescent↗
PubMed1998

Biological behavior and cell properties of new AKR lymphoma malignancy variants.

The AKR lymphoma-leukemia is a T lymphocyte neoplasm, most suitable as a model for human T cell malignancies. We have been interested in the process of tumor progression in the AKR lymphoma system. In the present study, two newly isolated variants, the TAU-42 and TAU-44, were characterized with respect to their biological behavior, by comparing them to a previously studied low-malignancy variant, the TAU-39. While the TAU-44 variant formed large s.c. local tumors, the TAU-42 variant formed only small growths or none at all. The TAU-42 lymphoma was found to have the highest malignant potential: it displayed very marked dissemination to spleen, lymph nodes, liver and lungs. The TAU-44 variant had an intermediate degree of metastatic potential but presented a predilection for spread to lymph nodes and spleen and was sometimes found to metastasize to peculiar organs, such as heart and pancreas. Cells derived from the different lymphoma variants varied in their immunophenotype: the highly malignant variant cells expressed more CD4 antigen than the low-malignancy one. The opposite was observed with regard to CD8. The variant cells also differed in their migrating capacity, the more malignant one exhibiting a higher motile activity. Studies on the tumor progression model of AKR lymphoma might contribute to the elucidation of the features determining the aggressiveness of T lymphocytic malignancies.

Animals↗
PubMed1998

Transcription of Arabidopsis and wheat Cab genes in single tobacco transgenic seedlings exhibits independent rhythms in a developmentally regulated fashion.

Transcription of Cab genes has been previously shown to be regulated by a circadian oscillator coupled to the red light-absorbing plant photoreceptor phytochrome in various plant species. In addition, it has recently been suggested that rhythmic expression of the Cab genes could also be affected by a phytochrome-independent circadian oscillator in a developmentally regulated fashion. This study has shown that a red light-insensitive oscillator and a phytochrome-coupled circadian clock indeed coregulate the oscillating expression of individual Cab genes at the level of transcription at an early developmental stage. The study involved analysing the expression patterns of transgenes, containing short fragments of the Arabidopsis thaliana Cab2 or the wheat Cab-1 promoter fused to the firefly luciferase reporter gene, by a video-imaging system in single, etiolated tobacco seedlings. Germination and red/far-red light treatments applied between 12 and 36 h after sowing lead to the appearance of two independent circadian rhythms. These rhythms coexist, both exhibiting period lengths close to 25 h but phased differently. However, repeated red-light treatments given 60 h or later after sowing synchronize these free-running rhythms and induce a single new circadian oscillation. These data indicate that both oscillators regulate the expression of the Cab genes studied at the level of transcription and that the cis-acting element(s) of the wheat Cab-1 and A. thaliana Cab2 genes mediating these responses are located on short, 250 bp promoter regions. Furthermore, these red-light induced rhythms are also inducible by far-red light treatments alone. Therefore, in tobacco, the phytochrome-coupled oscillator is regulated, at least partially, by the very low fluence response of phytochrome A.

Animals↗
PubMed1998

Nutritional rickets in suburbia.

OBJECTIVE: Vitamin D deficiency continues to be a problem in pediatrics. This report presents four children, one Caucasian male and three African-American females aged 4 to 24 months who were treated for vitamin D deficiency rickets. METHODS: One female was diagnosed in the Emergency Department during evaluation of a viral syndrome, another presented with hypocalcemic seizures and the third was a self-referral for evaluation of widened wrists. The male had biochemical rickets discovered incidentally during a hospitalization for pneumonia. All were breastfed without formula supplements. The 24-month female had severe cow and soy protein allergies and received multivitamin supplements intermittently. Birth order was from third to sixth child. Two families practiced Islam and the mothers wore veils. The females had a weight deficit for height. The females demonstrated a rachitic rosary, widening of the wrists and leg bowing. At diagnosis the serum calcium was 5.0-8.6 mg/dl, the inorganic phosphorus was 1.5-3.9 mg/dl and the alkaline phosphatase was 408-3324 U/L. The serum intact parathormone levels and the vitamin D levels were measured at Nichols Laboratories. The 25-OH vitamin D levels were 2-22 ng/ml and the 1,25(OH)2 vitamin D levels were 14-122 pg/ml. All had elevated parathormone levels. The three females had roentgenographic evidence of rickets. Two of the children also demonstrated iron deficiency. RESULTS: All patients responded to Vitamin D supplements, beginning at 2000 IU for the male and 8,000-10,000 IU daily for the females. Two children were also given calcium supplements. The three females all showed complete healing of the rickets radiologically within six months. The serum intact parathormone demonstrated an inverse correlation with the serum calcium during recovery (r=-0.669; p<0.05). CONCLUSION: Vitamin D deficiency does still occur. Breastfed children of multiparous mothers, with increased skin pigmentation, living in the higher latitudes are at increased risk and would benefit from vitamin D supplementation while breastfeeding.

Alkaline Phosphatase↗