Chondrocytes of the adult rat express mRNA for insulin-like growth factor binding protein-4 (IGFBP-4).
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Animals↗
Biomedical subjects
K Hall
Publications and source records attributed to K Hall.
Somatization in patients with dissociative disorders.
OBJECTIVE: This study attempted to determine the prevalence of somatic symptoms, somatization disorder, and medical interventions in patients with dissociative disorders. METHOD: Fourteen psychiatric inpatients with a DSM-III dissociative disorder were matched for age and gender with a comparison group of inpatients who reported few dissociative symptoms. All subjects were interviewed in a blind manner with the Dissociative Disorders Interview Schedule (this semistructured interview schedule includes a section on somatization disorder), and their hospital charts were reviewed to determine somatic symptoms and medical histories. RESULTS: Sixty-four percent of the patients with dissociative disorders met DSM-III criteria for somatization disorder and reported an average of 12.4 somatic symptoms. None of the comparison patients met DSM-III criteria for somatization disorder, and these patients reported an average of 3.1 somatic symptoms. These differences between the two groups were significant. Significant differences were also found in the number of medical hospitalizations and consultations between the two groups. A significant correlation was found between the degree of dissociation and degree of somatization in patients with dissociative disorders. CONCLUSIONS: The authors conclude that somatization disorder is a frequent and serious comorbid disorder among patients with dissociative disorders.
Adult↗
Serum insulin-like growth factor-I in 1030 healthy children, adolescents, and adults: relation to age, sex, stage of puberty, testicular size, and body mass index.
Serum levels of insulin-like growth factor-I (IGF-I) increase with age and pubertal development. The large variation in circulating IGF-I levels in adolescence makes it difficult to use the IGF-I value of a single child in the assessment of his growth status. In addition, the interference of IGF-binding proteins in many IGF-I assays contributes to this problem. We measured IGF-I in acid-ethanol-extracted serum from 1030 healthy children, adolescents, and adults, employing a RIA that reduces interference of IGF-binding proteins by using monoiodinated Tyr31-[125I]des-(1-3)IGF-I as radioligand. Mean serum IGF-I concentrations increased slowly in prepubertal children from 80-200 micrograms/L with a further steep increase during puberty to approximately 500 micrograms/L. After puberty, a subsequent continuous fall in circulating IGF-I levels was apparent throughout adulthood to a mean of 100 micrograms/L at the age of 80 yr (P < 0.0001). Girls had maximal IGF-I levels at 14.5 yr of age, whereas boys had peak IGF-I levels 1 yr later. This is almost 2 yr later than average peak height velocity. The large variation in serum IGF-I levels during puberty was diminished when data were separated according to sex and Tanner stage of puberty. Interestingly, we found a significant variation with age within the Tanner stages; there was an increase in serum IGF-I concentrations with age in the early pubertal stages and a decrease in the late stages (P < 0.05). Serum IGF-I increased concomitantly with increasing testicular volume. Multiple regression analysis revealed that serum IGF-I levels predicted height velocity in the following year (r = 0.33; P < 0.0001). Body mass index did not correlate significantly with serum IGF-I in prepubertal children in a multiple regression analysis. In conclusion, there was a significant variation in serum IGF-I levels with age within a given Tanner stage of puberty in addition to the well known increase with increasing age or pubertal stage. Accordingly, the effects of sex, age, and puberty on serum IGF-I cannot be separated into simple additive components when studying 1030 children in a cross-sectional design. Thus, the age-, sex-, and puberty-corrected IGF-I values may, in fact, improve the use of serum IGF-I as a diagnostic tool to distinguish between a child with retarded puberty and a GH-deficient individual.
Adolescent↗
Fasting affects serum insulin-like growth factors (IGFs) and IGF-binding proteins differently in patients with noninsulin-dependent diabetes mellitus versus healthy nonobese and obese subjects.
In the present study we have 1) assessed how differences in insulin and GH status between obese patients with noninsulin-dependent diabetes mellitus (NIDDM) and healthy obese (OB) and nonobese (NOB) subjects are associated with different responses of insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs) to fasting, and 2) determined whether the IGF-I response to fasting in healthy subjects is secondary to changes in IGFBP-3. In patients with NIDDM, there was a lack of response of serum IGF-I concentrations to 4 days of fasting, contrasted with the significant decrease in IGF-I concentrations in NOB subjects (37%; P < 0.001) and the delayed and attenuated decrease in OB subjects (23%; P < 0.01). Insulin and the insulin-regulated IGFBP-1 were also unchanged during fasting in NIDDM, whereas insulin was decreased and IGFBP-1 was increased in both NOB and OB subjects. Insulin-resistant NIDDM patients, with high basal glucose and insulin, normal IGFBP-1, and low GH, had decreased prefasting serum IGF-I concentrations, similar to the values in fasted body mass index- and age-matched OB subjects. IGFBP-3, the major determinant of the IGF-I turnover rate in serum, was unchanged by fasting, as determined by RIA and Western ligand blot analysis. In accordance, no induction of IGFBP-3 proteolytic activity by fasting could be demonstrated. Serum IGF-II concentrations were also unchanged by fasting. Basal immunoreactive IGFBP-3 levels did not differ among the groups, whereas IGFBP-3 by Western ligand blot analysis was decreased in NIDDM in accordance with the finding of increased IGFBP-3 proteolysis in NIDDM. In conclusion, 1) differences in GH status and modulation of GH induction of IGF-I by insulin resistance could contribute to low basal IGF-I levels and lack of a IGF-I response to fasting in patients with NIDDM; and 2) the turnover rate of IGF-I in serum, which is largely determined by IGFBP-3, is not likely to be altered by short term fasting, suggesting that the decrease in serum IGF-I concentrations is a result of decreased IGF-I production.
Adult↗
Effect of insulin on the hepatic production of insulin-like growth factor-binding protein-1 (IGFBP-1), IGFBP-3, and IGF-I in insulin-dependent diabetes.
Insulin-like growth factors (IGFs) circulate attached to binding proteins (IGFBPs). Only the unbound form of IGF is suggested to be biological active. The main source of circulating IGF-I and IGFBP-1 is considered to be the liver, but that of circulating IGFBP-3 is not known. IGF-I and IGFBP-3 are GH dependent, whereas IGFBP-1 is insulin regulated. The aim of the present study was to examine the effect of insulin on the hepatic secretion of IGFBP-1, IGFBP-3, and IGF-I. Seven insulin-dependent diabetic patients in whom insulin was withheld for 12 h were studied in the overnight fasted state. Blood was sampled simultaneously from the hepatic vein, a peripheral vein, and an artery before and during insulin infusion for 3 h. The basal IGFBP-1 levels in the peripheral vein were several-fold elevated (249 +/- 44 micrograms/L) compared to those in healthy subjects (37 +/- 2 micrograms/L). Fasting IGFBP-1 concentrations were inversely correlated to the insulin levels (r = -0.918; P < 0.001). The mean IGF-I concentration (175 +/- 17 micrograms/L; -1.62 +/- 0.38 SD score) was decreased compared with that in age-matched healthy subjects. The basal IGFBP-3 levels in the peripheral vein (4.50 +/- 0.33 mg/L) were within the normal range. There was a significant correlation in the hepatic vein between fasting IGF-I and IGFBP-3 levels (r = 0.928; P < 0.001). Basal splanchnic IGFBP-1 production was 18 +/- 7 micrograms/min, whereas no basal net exchanges of IGF-I or IGFBP-3 were observed across the splanchnic area. Insulin inhibited splanchnic IGFBP-1 production within 120 min and glucose output within 20 min. Serum IGF-I, but not IGFBP-3, concentrations increased significantly during the insulin infusion. In summary, this study demonstrates the existence of considerable IGFBP-1 production from the liver during insulinopenia and the complete blocking of splanchnic IGFBP-1 production and increases in serum levels of IGF-I by insulin despite no effect on IGFBP-3 levels. Thus, insulin may play a role in determining the bioavailability of IGF-I.
Adult↗
Immunoreactive proinsulin-like growth factor-II levels in healthy subjects, patients with growth hormone deficiency, and patients with type 1 diabetes: effects of insulin-like growth factor-I and insulin.
Proinsulin-like growth factor-II (IGF-IIE), with an E-peptide elongation at the C-terminal, is found in the circulation and in different body fluids with mol wt between 10-16 kilodaltons compared to native 7.4-kilodalton IGF-II. Some tumors overexpress IGF-II and IGF-IIE with increased levels in patients serum, sometimes causing hypoglycemia (nonislet cell tumor-induced hypoglycemia). We have developed a RIA for a 15-amino acid part of the E-peptide. By using the E16-peptide as the labeled ligand, this RIA is unaffected by the presence of IGF-binding protein in the samples. Gel chromatography under acid and neutral conditions revealed that all IGF-IIE was detected without prior separation of serum. Using recombinant IGF-IIE21 as standard, we determined normal levels in 70 males and 67 females between 20-70 yr of age. The average was 46.6 +/- 1.1 micrograms/L, and the 95% confidence interval was between 21.4-71.9 micrograms/L. A significantly higher level was found in males (49.0 +/- 1.6 micrograms/L) compared to females (44.2 +/- 1.3 micrograms/L). In two nonislet cell tumor-induced hypoglycemia patients, levels of immunoreactive (ir) IGF-IIE were 2.5-3 times normal levels. GH-deficient patients had normal levels, but daily sc injections of recombinant human IGF-I decreased serum irIGF-IIE by 40%. Insulin-dependent diabetic patients undergoing liver venous catheterization had normal basal levels of irIGF-IIE in peripheral blood. A 180-min insulin infusion decreased the levels significantly in the vena hepatica, but no splanchnic gradient was observed.
Adult↗
Valid measurements of total IGF concentrations in biological fluids. Recommendations from the 3rd International Symposium on Insulin-like Growth Factors.
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Body Fluids↗
Risk of nonshunt abdominal operation in the patient with cirrhosis.
BACKGROUND: The hazards of operative treatment for variceal hemorrhage and intractable ascites in patients with cirrhosis are well known. Much less information is available on the morbidity and mortality in these patients after abdominal operations not directly related to the sequelae of portal hypertension. STUDY DESIGN: We reviewed the records of 77 consecutive histologically proved cases of cirrhosis in patients undergoing 85 general surgical, abdominal procedures during a ten year period. Logistic regression analysis was done on 32 preoperative and intraoperative variables with relation to postoperative outcome. RESULTS: There were 47 men and 30 women, with a mean age of 61 years (range of 28 to 86 years). The 30-day mortality rate was 18 percent (15 of 77 patients). Emergent operation was associated with a mortality rate of 32 percent (11 of 35 patients) compared with 8 percent (four of 50 patients) after elective procedures (p < 0.05). Extensive complications occurred in 28 percent of patients (24 patients; 14 percent after elective operative treatment and 49 percent after emergent procedures). The mortality rate was greatest after gastric procedures (38 percent). Other factors of statistical significance (p < 0.05) associated with poor postoperative outcome included cachexia, preoperative transfusion of fresh frozen plasma, and intraoperative platelet transfusion. Surprisingly, operative blood loss, presence of ascites, and operative time were not associated with increased complications or death. CONCLUSIONS: We conclude that elective, nonshunt abdominal operations can be performed with acceptable morbidity and mortality rates in selected patients with cirrhosis.
Abdomen↗
Novel heterotrimeric kinesin-related protein purified from sea urchin eggs.
Kinesin heavy chain and kinesin-related polypeptides (KRPs) comprise a family of motor proteins with diverse intracellular transport functions. Using pan-kinesin peptide antibodies that react with these proteins, we have previously purified from sea urchin eggs a trimeric microtubule-binding and bundling protein, KRP (85/95) (ref. 8) comprising subunits of M(r) 115,000 (115K), 95K and 85K. We report here that kinesin-related genes encode the 85K and 95K subunits, and that the protein can be immunoprecipitated from cytosol as a trimeric complex using an 85K monoclonal antibody. We also find that purified KRP(85/95) directs movements towards the 'plus' ends of microtubules. To our knowledge, this protein is the first kinesin-related motor to be purified from its natural host cell in a native multimeric state.
Amino Acid Sequence↗
Directional coronary atherectomy of saphenous vein graft narrowings: multicenter investigational experience.
Directional coronary atherectomy (DCA) of saphenous vein graft lesions was performed at 21 centers between June 1988 and September 1990, which represents the multicenter investigational experience. A total of 318 procedures were performed and 363 vein graft lesions were treated. Angiographic success with DCA was achieved in 86% of lesions and clinical success was achieved in 85% (269 of 318) of patients. Major complications occurred in 2.5% of patients, with Q wave myocardial infarction (MI) in 1.3%, death in 0.9%, and urgent bypass surgery in 0.9%. Other complications included non-Q wave MI in 4.4%, distal embolization in 7.2%, coronary occlusion in 1.9%, and vessel perforation in 0.6%. Although there was a trend toward lower success rates with ostial vein graft lesions (82% vs 88% for other graft sites) and with diffuse (length > 20 mm) graft lesions (75% vs 87% for shorter lesions), the differences were not significant. Baseline clinical and angiographic factors did not identify predictors of lower success or more frequent complications in the study group. Overall restenosis rate in the 149 patients with angiographic restudy was 57%. The restenosis rate was significantly lower with primary vein graft lesions (38%) compared with a 75% restenosis rate for grafts with prior restenosis, p < 0.001. This initial multicenter investigational experience indicates that directional coronary atherectomy is a safe and effective therapy for selected saphenous vein graft disease. Although the overall restenosis rate is relatively high, the restenosis rate following DCA of primary vein graft lesions is significantly lower than for vein grafts having had prior intervention.(ABSTRACT TRUNCATED AT 250 WORDS)
Atherectomy, Coronary↗
Ligand blot analysis: validation of quantitative capabilities and utilization for measurement of truncated insulin-like growth factor regulation of Hep-G2 insulin-like growth factor binding protein-1 production.
The quantitative capabilities of Western "ligand" blot analysis (LBA) of insulin-like growth factor binding protein have been evaluated using iodine-labeled insulin-like growth factor-II (125I-IGF-II), purified amniotic fluid insulin-like growth factor binding protein-1 (IGFBP-1), and IGFBP-1 in conditioned medium (CM) from Hep-G2 cells. Optimal conditions were evaluated for analysis of IGFBP-1 using IGF-2-II as the ligand. IGFBP-1 ligand blot quantities were measured after autoradiography by one- (1D) and two (2D)-dimensional densitometry. The 2D method was found to exhibit higher linearity (IGF-I, r = 0.993; IGF-II, r = 0.984) over a wider range than the 1D method. Displacement curves for IGF-II against membrane-bound IGFBP-1 measured by LBA were similar to those obtained with IGFBP-1 solutions using antibody precipitation of IGFBP-1. Transfer of IGFBP-1 from sodium dodecyl sulfate-polyacrylamide gel electrophoresis gels to nitrocellulose membranes was linear across the range 3.1-400 ng with both the 0.45- and the 0.2-micron pore sizes tested. The 0.2-micron size, however, showed nearly quantitative binding of IGFBP-1 trapping 20% more of this binding protein than the larger pore size. LBA was used to measure IGFBP-1 in CM from control and des1-3IGF-I (trIGF-I)-treated Hep-G2 cells and the results were compared with those obtained by a specific IGFBP-1 radioimmunoassay. IGFBP-1 concentrations measured by both assays were similar and both demonstrated nearly identical sensitivities. Each assay confirmed the previously noted trIGF-I suppression of IGFBP-1 secretion by Hep-G2 cells.
Animals↗
Force-velocity relationships in kinesin-driven motility.
Kinesin is a microtubule-based motor protein that uses energy released from Mg-ATP hydrolysis to generate force for the movement of intracellular membranes towards the fast-growing (plus) ends of microtubule tracks in cells. Kinesin-driven microtubule movement can be visualized and quantified using light microscope motility assays but our understanding of how kinesin generates force and motion is incomplete. Here we report the use of a centrifuge microscope to obtain force-velocity curves for kinesin-driven motility and to estimate that the maximal isometric force generated per kinesin is 0.12 +/- 0.03 pN per molecule.
Adenosine Triphosphate↗
A clinical therapeutic trial of cyclosporine in myasthenia gravis.
We randomly assigned 39 patients with steroid-dependent generalized myasthenia gravis to treatment with cyclosporine (5 mg/kg per body weight in divided doses) or placebo. Duration of treatment was 6 months. Patients were evaluated monthly. Primary measures of efficacy were quantified strength testing, antihuman acetylcholine receptor antibody titer, and dosage of corticosteroid medication. At the end of the study, patients in the cyclosporine group had significantly greater improvement in strength (p = 0.004) and a reduction in antireceptor antibody titer (p = 0.01). Percentage reduction of steroid medication was greater in the cyclosporine group, although the difference was not statistically significant (p = 0.12). There were no treatment failures, and there was one drug failure in the cyclosporine group. In the placebo group, there were three treatment failures. No significant nephrotoxicity was noted at this dosage during the first 6 months. During the subsequent 18 months of open-label therapy, continued reduction in steroid dosage occurred. Cumulative side effects, however, caused 35% of patients to discontinue the medication; 10% did so secondary to slowly progressive nephrotoxicity.
Adult↗
Diffuse pneumocephalus due to Clostridium septicum cerebritis in haemolytic uraemic syndrome: CT demonstration.
The computed tomography finding of diffuse pneumocephalus due to infection by gas-forming organisms is very unusual. We report such a case due to secondary infection by Clostridium septicum in a child with diarrhoea-associated haemolytic uraemic syndrome.
Brain Edema↗
Human cell lines as models for multidrug resistance in solid tumours.
In spite of our expanding knowledge on the molecular biology of cancer, relatively little progress has been made in improving therapy for the solid tumours which are major killers, e.g., lung, colon, breast. Significant advances over the past 10-15 years in chemotherapy of some tumours such as testicular cancer and some leukaemias indicates that, in spite of the undesirable side-effects, chemotherapy has the potential to effect cure in the majority of patients with certain types of cancer. Multidrug resistance, inherent or acquired, is one important limiting factor in extending this success to most solid tumours. In vitro studies described in this review are now uncovering a diversity of possible mechanisms of cross-resistance to different types of drug. Sensitive methods such as immunocytochemistry, RT-PCR or in situ RNA hybridisation may be necessary to identify corresponding changes in clinical material. Only by classifying individual tumours according to their specific resistance mechanisms will it be possible to define the multidrug resistance problem properly. Such rigorous definition is a prerequisite to design (and choice on an individual basis) of specific therapies suited to individual patients. Since a much larger proportion of cancer biopsies should be susceptible to accurate analysis by the immunochemical and molecular biological techniques described above than to direct assessment of drug response, it seems reasonable to hope that this approach will succeed in improving results for cancer chemotherapy of solid tumours where other approaches such as individualised in vitro chemosensitivity testing have essentially failed. Results from clinical trials using cyclosporin A or verapamil are encouraging, but these agents are far from ideal, and reverse resistance in only a subset of resistant tumours. Proper definition of the other mechanisms of MDR, and how to antagonize them, is an urgent research priority.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Serum albumin: a marker for morbidity in peritoneal dialysis patients.
This study was designed to determine if the serum albumin is a marker for morbidity or mortality in peritoneal dialysis (PD) patients. The impact of a low serum albumin on the risk of hospitalization, peritonitis, or death was examined in 71 patients. Blood urea nitrogen (BUN), cholesterol, age, and the presence or absence of diabetes were also examined. In independent analyses, the serum albumin was lower (32.7 +/- 5.6 v 36.3 +/- 4.3 g/L, P < 0.01), the diagnosis of diabetes was more frequent (41% v 7%, P < 0.01), and the number of episodes of peritonitis were greater (2.0 +/- 1.6 v 0.7 +/- 1.3, P < 0.01) in the group of patients hospitalized compared with those not hospitalized. When diabetics were excluded from analysis, the serum albumin remained significantly lower in hospitalized patients. Stepwise logistic regression analysis, excluding the 10 patients hospitalized only for treatment of peritonitis, confirmed that only a low serum albumin and the diagnosis of diabetes were independent predictors of increased morbidity as evident by the increased frequency of hospitalization. Every 10 g/L decrease in the serum albumin increased the odds ratio for hospitalization by 5.2. The diagnosis of diabetes resulted in a 10-fold increase in the odds ratio. We conclude that a low serum albumin serves as a marker of morbidity in PD patients, primarily as a marker of increased risk for hospitalization. The diagnosis of diabetes also greatly increases the likelihood of hospitalization. Peritonitis is a cause for hospitalization, but not an independent risk factor.
Adult↗
Cerebrospinal fluid neopterin levels in 159 neurologically asymptomatic persons infected with the human immunodeficiency virus (HIV-1): relationship to immune status.
Monocytes and brain macrophage-microglial cells are thought to play a crucial role in the neurologic dysfunction associated with HIV-1 disease. Since neopterin is produced by monocytes-macrophages, we asked whether cerebrospinal fluid (CSF) neopterin levels increase before the onset of HIV-1 neurologic disease and whether they correlate with other CSF and peripheral blood immunologic parameters. In this study, CSF neopterin levels from 159 neurologically asymptomatic HIV-positive persons were found to increase as the blood CD4+ T-cell count decreased and as CSF IgG, IgG synthesis, IgG index, and beta 2-microglobulin increased. Neopterin levels in the CSF exceeded those in the serum in 32% of patients, while 25% had CSF levels > 13.5 nmol/liter. CSF neopterin levels vary with immune status, may reflect intrathecal production, and can be elevated in asymptomatic HIV-positive patients with normal neurologic examinations. Long-term follow-up of this patient population should be able to define the clinical correlation between CSF neopterin levels during the asymptomatic phase of HIV-1 disease and the risk of subsequent neurologic disease.
Biopterins↗
Case report: alpha G-Philadelphia, beta O-Arab, and beta C globins present in a single patient.
The case of a 7-month-old Nigerian child who presented with anemia and microcytosis is described. Hemoglobin electrophoresis studies revealed a band with pronounced cathodic mobility. This represented a heterohybrid hemoglobin tetramer composed of an alpha-globin mutant, G-Philadelphia (alpha GPhil), and two variant beta-globin chains, beta C and beta O-Arab. The absolute amounts of alpha GPhil found in the propositus were less than expected for an alpha 2-globin gene product. It has not been established whether alpha G-Philadelphia interacting with beta O-Arab and beta C globin chains is the cause of the microcytosis.
Anemia↗