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Biomedical subjects

L Walker

Publications and source records attributed to L Walker.

At least 145 records · Page 8Linked to original sources
PubMed1989

Association of a Ras-related protein with cytochrome b of human neutrophils.

Activation of the superoxide generating system in human neutrophils is thought to involve the interaction or assembly of cytochrome b with other cytosolic and membrane proteins. We have now co-isolated by conventional purification procedures a protein of relative molecular mass 22,000 with cytochrome b. This Ras-related protein is not a fragment of either of the subunits of cytochrome b, and its primary structure, as determined by the sequencing of its complementary DNA, is identical to that predicted from a recently cloned ras-related gene, rap1 (also termed Krev-1). Immunoaffinity purification on anti-cytochrome and anti-Ras immunoaffinity matrices indicates an association between cytochrome b and the Ras-related protein. The association of a Ras-related GTP-binding protein with cytochrome b of human neutrophils could indicate a role for such a protein in the transduction, regulation or structure of the superoxide generating system.

Amino Acid Sequence↗
PubMed1989

Three hundred admissions to the Waikato Hospital intensive therapy unit--survival, costs, and quality of life after two years.

Three hundred consecutive admissions 13 years of age and above who entered the Waikato Hospital intensive therapy unit, were followed up after two years. Their degree of illness was similar to that in other intensive care units. At two years, 26% of the patients were dead. Maori admissions and death rates more than doubled those of the nonMaori. Once admitted, the proportion dying was identical in both groups. The average stay in ITU was 6.3 days. The average stay in hospital including ITU, was 28 days. One hundred and fifty-nine people (168 admissions) were traced and questioned about their quality of life. Seventy-four percent had a good quality, 19% were affected, and 7% had a severely affected quality of life. Preliminary estimates of cost suggest that the average ITU cost per patient is about $9500, and the average total hospital cost for any patient entering ITU is about $20,000.

Adolescent↗
PubMed1989

Study of human epithelial cell detachment and damage: development of a model.

Detachment of epithelial structures from underlying basement membrane (BM) represents an important component of a number of human disease processes e.g. airway and alveolar diseases, gastrointestinal ulceration, and retinal diseases. This study describes a method of evaluating human epithelial cell detachment from BM that is simple, rapid, inexpensive, quantifiable and which, because it utilizes BM rather than tissue culture plastic, more closely mimics the in vivo situation than other methods. In this model human amnionic epithelial cells attached to their underlying BM are isolated from fresh placentae and mounted in a multi-well chemotaxis assembly. These membranes can be studied with the epithelial cell monolayer intact. Protease-induced detachment of the epithelial cells from the underlying BM was readily quantifiable using light microscopy and spectroscopy. Following removal of the native amnionic epithelial cells, immunoperoxidase staining for the BM attachment proteins laminin, fibronectin, and type IV collagen demonstrated that these molecules remain intact. The BM could also be used as an attachment surface to reconstitute other epithelial cell monolayers. Cultured human amnionic cells and human respiratory epithelial cells were both able to attach to the denuded BM in the absence of serum (% attachment = 85 +/- 15% and 92 +/- 8% respectively, P = 0.8). Natural BM was a better substrate for epithelial cell attachment than tissue culture plastic in that, in the absence of serum, cultured epithelial cell attachment to tissue culture plastic was 20 +/- 4% of the value for BM (P less than 0.05). Furthermore, cells attached to plastic adhered less effectively than to BM in that trypsin concentrations required to induce 50% cell detachment were 0.72 +/- 0.4 for plastic and 62 +/- 13 BAEE U/ml for BM (P less than 0.001). In view of the complex protein interactions known to be involved in the anchorage of human epithelial cells to BM, it is likely this model will be a useful tool for evaluating the mechanisms underlying human epithelial cell attachment and detachment in a variety of normal and disease situations.

Amnion↗
PubMed1989

Maternal milk and plasma glucose and insulin levels: studies in normal and diabetic subjects.

The relationship between maternal glucose levels and the concentration of glucose and insulin levels in human milk from diabetic women has not been elucidated. In addition, the rate of appearance of intravenously injected insulin to the change in concentration of insulin in maternal milk has not been studied. To study this relationship of glucose levels in serum to glucose levels in milk, maternal milk and glucose levels were measured in diabetic lactating women (n = 7) and nondiabetic lactating women (n = 10). In addition, the change in milk concentration of insulin was studied after an intravenous injection of insulin. The maternal whole blood glucose in the seven diabetic women was stabilized at a baseline blood glucose of approximately 100 mg/dl and then elevated with an infusion of intravenous glucose to a level of three times baseline (approximately 300 mg/dl for up to 2 hours). The plasma glucose was then lowered back to baseline with intravenous insulin over 20 minutes. The baseline serum insulin and glucose levels were compared to nonlactating women who donated serum to measure insulin levels in normal controls. Maternal milk glucose levels rise following an increase of plasma glucose levels with a lag time to the peak glucose level of 40-90 minutes, and return to baseline following the return of plasma glucose to baseline with a lag time of 120-150 minutes. Baseline milk insulin levels are elevated in hyperinsulinemic women and the levels of insulin in the milk will rise dramatically above baseline values after an intravenous injection of insulin with a lag time to the peak of concentration in milk of 60-80 minutes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Effects of formal support on mothers' adaptation to the hospital-to-home transition of high-risk infants: the benefits and costs of helping.

94 mothers were randomly assigned to a control group or to a group who received a formal support program designed to aid their adaptation to the transition from hospital to home care of high-risk infants. Mothers' predischarge need for support and the severity of infants' predischarge medical problems moderated program effects assessed 6 months after NICU discharge. Positive effects of the program on mothers' sense of competence, perceived control, and responsiveness were evident for mothers who had needed the most support. But at low levels of need for support, participation in the program had negative effects on these outcomes. A similar pattern was found for the effects of the program on mothers' positive mood as a function of the severity of infants' medical problems. Secondary findings suggest why some mothers may benefit from formal support after NICU discharge and others may experience at least temporary disruptions in their adaptation from such support.

Cost-Benefit Analysis↗
PubMed1989

Circumstances of sexual and physical victimization of black psychiatric outpatients.

A sample of 54 adult psychiatric outpatients, previously identified as victims of sexual or physical assault, were interviewed regarding their childhood and adult victimization experiences. Patients were questioned about the nature of the assaults, their relationship to the perpetrator(s), the number of assaults suffered in each relationship, and whether the assault(s) occurred before or after the onset of their mental illness. Eighty percent of the sample had experienced major physical assault as an adult and 59% had experienced major physical assault as a child; 37% and 31%, respectively, reported major sexual assault as a child and as an adult. Women were more likely than men to report physical and sexual assault as an adult and sexual assault as a child. Childhood assault most often occurred before the onset of the patient's mental illness; whereas, adult sexual assault for women and physical and sexual assault for men was as likely to occur after the onset of the psychiatric disorder, suggesting an increased vulnerability to victimization for the adult mentally ill.

Adult↗
PubMed1988

Intravesical chemotherapy: combination with dimethyl sulfoxide does not enhance cytotoxicity in vitro.

There is evidence that dimethyl sulfoxide (DMSO) can increase the anticancer activity of chemotherapeutic drugs. As DMSO is instilled into the bladder for interstitial cystitis, it could be readily adopted in clinical practice if it was found to enhance the effectiveness of the drugs used for intravesical chemotherapy. The purpose of this study was to investigate, using a human bladder cancer cell line, the hypothesis that DMSO enhances the activity of these agents. However, the addition of 4% DMSO to the four drugs most frequently used for intravesical chemotherapy (adriamycin, epodyl, mitomycin-c, thiotepa) did not increase tumour cell kill in vitro.

Administration, Intravesical↗
PubMed1988

Occult primary seminoma: eighteen-year delay in presentation.

Primary retroperitoneal seminoma is well documented. A case is reported in which a patient presented with a seminoma of testis eighteen years after removal of a retroperitoneal seminoma. Histologic appearance of the testis was identified to the original pathology, and it is proposed that this represents recurrence of an occult testicular seminoma.

Adult↗
PubMed1988

Sequence homology and immunologic cross-reactivity of human cytomegalovirus with HLA-DR beta chain: a means for graft rejection and immunosuppression.

A peptide (Leu-Gly-Arg-Pro-Asp-Glu-Asp-Ser-Ser-Ser-Ser-Ser-Ser-Ser-Cys) that was identical to residues 82 through 96 of a predicted protein of 208 amino acids from the immediate-early region (IE-2) nucleic acid sequence of human cytomegalovirus was chemically synthesized. By computer analysis, the first five amino acids of this peptide showed sequence homology to the beta chain of the human histocompatibility complex HLA-DR. The homologous amino acids, 53 through 57, were located in a region that is conserved between the human DR beta chain and the beta chain of the H-2 class II histocompatibility antigen for mice. The shared region between the IE-2 protein and DR beta chain were similar in both hydrophilicity and predicted beta-turn potential. The IE-2 viral peptide induced antibodies that specifically recognized the human DR beta chain. These observations describe a protein encoded by the IE-2 region of human cytomegalovirus that contains sequence homology and shows immunologic cross-reactivity with a conserved domain of HLA-DR and suggest a mechanism to explain how human cytomegalovirus infection contributes to graft rejection after transplantation.

Amino Acid Sequence↗
PubMed1988

Growth hormone stimulates insulin gene expression in cultured human fetal pancreatic islets.

The total body mass of the human fetus increases about 100-fold from 10-20 weeks of gestation, and peak serum GH concentrations occur at 20 weeks. Since insulin has an essential growth-promoting influence in the fetus, these experiments were designed to determine whether GH can function as a growth factor with insulin-releasing activity by stimulating insulin gene expression during embryogenesis. Pancreatic islets were isolated from human fetuses (n = 36) of 18-22 weeks gestational age. Insulin gene expression was quantified by measuring insulin mRNA by blot hybridization analysis using a [32P] cDNA probe encoding human insulin. We found that by 48 h of culture insulin gene expression was stimulated by 1.25 micrograms recombinant human GH/mL medium to 216% of the control value (n = 2). Insulin secretory capacity was expressed as a fractional stimulation ratio (FSR = F2/F1) of insulin release rates during two successive 1-h static incubations. After 48 h of culture 1.25 micrograms/mL GH stimulated the FSR value to 273% of the control value (n = 5). We conclude that recombinant human GH significantly enhances the steady state level of insulin mRNA concurrent with an increase in insulin secretory capacity, hence providing evidence for a regulatory function of GH on insulin gene expression during fetal development.

Gene Expression Regulation↗
PubMed1988

3H-cyclosporine internalization and secretion by human fetal pancreatic islets.

Human fetal pancreatic islets were isolated from 16- to 20-week-old fetuses by a collagenase technique and cultured 48 hr in RPMI 1640 containing 10% human adult serum and unlabeled 0 to 5 micrograms cyclosporine A (CsA)/ml. Insulin secretory capacity of human fetal islets was expressed as a fractional stimulatory ratio FSR = F2/F1 of the fractional secretion rates during two successive 1 hr static incubations first with 2 mM glucose (F1) to stabilize secretion followed by maximal stimulus, i.e., 25 mM glucose plus 10 mM L-leucine and 10 mM L-arginine (F2). Unlabeled CsA at the above concentrations had no significant effects on the insulin secretory capacity expressed by FSR-values. Studies of net uptake of 3H-CsA by islets cultured for varying periods up to 40 hr and expressed as picomole 3H-CsA per picomole islet insulin content demonstrated that uptake rate was slow and did not reach isotopic equilibrium over the 40 hr of culture. When isolated fetal islets were cultured for 48 hr in the presence of 3H-CsA and varying concentrations of unlabeled CsA it was found during two successive 1 hr static incubations that fetal islets secrete insulin concomitantly with 3H-CsA following maximal stimulus for secretion. An optimal secretory molar ratio of 3H-CsA to insulin of 4.0 +/- 1.3 (n = 7) was found after islets were cultured 48 hr in the presence of a saturating 2.128 micrograms 3H-CsA per milliliter culture medium. In three successive 30-min static incubations of 3H-CsA loaded islets, first with low glucose, followed by high glucose plus L-arginine and L-leucine, and finally with high glucose plus L-arginine and L-leucine and 10 mM theophylline, the proportional fractional secretion rates of insulin and 3H-CsA were of the same magnitude. It is concluded that human fetal pancreatic islets during 48 hr of culture in the presence of pharmacologically relevant concentrations of CsA can internalize the drug, which is compartmentalized and concomitantly secreted with insulin following maximal stimuli. Transplanted human fetal islets utilized as delivering units for CsA could be beneficial for the induction of immunotolerance to allografted fetal islets.

Cells, Cultured↗