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Biomedical subjects

M Phillip

Publications and source records attributed to M Phillip.

At least 73 records · Page 4Linked to original sources
PubMed1995

Fetal pseudohypoaldosteronism: another cause of hydramnios.

Pseudohypoaldosteronism (PHA) is a rare hereditary salt-wasting syndrome which is caused by decreased renal tubular responsiveness to aldosterone. The syndrome consists of hyponatremia, hyperkalemia, dehydration, failure to thrive and increased urinary salt loss. A case of PHA was previously described where fetal polyuria was the probable cause of hydramnios. We present four new cases of PHA, from two families, who were born after pregnancies complicated by severe hydramnios and premature labor. We suggest that PHA should be included in the differential diagnosis of hydramnios, since appropriate investigations might lead to the early diagnosis and treatment of a life-threatening disease.

Adult↗
PubMed1995

Modulation of insulin-like growth factor I (IGF-I) receptors and membrane-associated IGF-binding proteins in endometrial cancer cells by estradiol.

Insulin-like growth factor I (IGF-I) receptors and membrane-associated IGF-binding proteins (IGFBPs) were examined in Ishikawa endometrial cancer cells. Our findings suggest that about 95% of [125I]IGF-I is bound to membrane-associated IGFBPs rather than to IGF-I receptors. Specifically, [125I]IGF-I binding to cell membranes could be completely displaced by cold IGF-I or IGF-II, but not by insulin, suggesting that binding was primarily due to IGFBPs. This was confirmed by using [125I]des-(1-3)IGF-I as the ligand. Des-(1-3) IGF-I binds with high affinity to IGF-I receptors, but with markedly lower affinity to IGFBPs. [125I]Des-(1-3)IGF-I bound to Ishikawa cells was displaced by IGF-I, IGF-II, and insulin. These results suggest that measuring IGF-I receptor levels using labeled IGF-I may be misleading. Accordingly, we evaluated the differential binding of [125I]IGF-I and [125I]des-(1-3)IGF-I to study the involvement of the IGF system in the stimulation of Ishikawa cell growth by estradiol. IGF-I stimulates Ishikawa cell proliferation, but at low concentrations, and this stimulation is largely dependent on the presence of estradiol. Estradiol caused a 2.5-fold increase in IGF-I receptor levels. Moreover, estradiol reduced soluble IGFBP levels, presumably increasing the availability of IGFs for their receptors. This elevation in IGF-I receptor levels and the decrease in IGFBP levels were accompanied by a 3.5-fold increase in IGF-I receptor messenger RNA and a 2.5-fold decrease in IGFBP messenger RNAs. These experiments suggest that estradiol sensitizes endometrial cancer cells to the effects of IGFs by simultaneously elevating receptor levels and decreasing (potentially inhibitory) IGFBP levels.

Binding, Competitive↗
PubMed1995

Urinary cyclic adenosine 3',5'-monophosphate response in McCune-Albright syndrome: clinical evidence for altered renal adenylate cyclase activity.

The recent finding of an activating mutation in the Gs alpha protein, the protein that couples receptors to stimulation of adenylate cyclase, from endocrine and nonendocrine tissues of patients with McCune-Albright syndrome (MAS) suggests that alterations in adenylate cyclase activity may account for the clinical abnormalities in these patients. Many patients with MAS have hypophosphatemia. This may result from the presence of the activating Gs alpha mutation in proximal renal tubules or the elaboration of a phosphaturic factor from fibrous dysplasia. We, therefore, sought to characterize renal cAMP generation and phosphate handling in MAS patients. Intravenous infusion of PTH is a classic clinical test used to evaluate hormonal responsiveness of renal proximal tubule adenylate cyclase and examine PTH-dependent phosphate clearance. We performed PTH infusion in 6 MAS patients, 10 normal subjects, and 6 patients with pseudohypoparathyroidism (PHP). The basal urinary cAMP (UcAMP) level in the MAS group [5.5 +/- 2.6 nmol/dL glomerular filtration (GF)] was elevated (P < 0.05) compared to those in both normal subjects (3.2 +/- 1.2 nmol/dL GF) and patients with PHP (1.9 +/- 0.6 nmol/dL GF). However, PTH-stimulated peak UcAMP (15.0 +/- 7.0 nmol/dL GF) and the peak/basal UcAMP ratio (3.1 +/- 1.7) in MAS were significantly lower than the respective values in normal subjects (30.8 +/- 16.9 nmol/dL GF and 9.3 +/- 2.9; P < 0.05 for both) and were statistically similar to the blunted levels in PHP (respectively, 3.1 +/- 1.5 nmol/dL GF and 2.0 +/- 1.7). By contrast, the PTH-induced phosphaturic response in MAS patients was similar to that in the normal subjects. Our study provides clinical evidence that MAS patients have altered renal adenylate cyclase activity, manifested by an elevated basal UcAMP, but a blunted UcAMP response to PTH stimulation. These observations are presumably due to a mutation in the Gs alpha protein in the renal tubules. Despite the blunted UcAMP excretion, the phosphaturic response to PTH in MAS patients is intact.

Adenylyl Cyclases↗
PubMed1995

Snake bite by Cerastes vipera in children: report of two cases.

Two children, ages 2 and 4 years, envenomed by the snake Cerastes vipera are presented. Both children suffered from local pain and swelling of the hand that spread up to the shoulder in the 2-year-old and up to the elbow in the 4-year-old. A hemorrhagic blister was noted on the bitten finger in the younger patient. Urinary retention, tachycardia, and a slight prolongation of prothrombin time was noted in the 2-year-old, whereas hypertension and fever were observed in the 4-year-old. In both cases, the swelling receded gradually and the patients were discharged from the hospital after several days without any complications and in a good condition.

Animals↗
PubMed1995

High prevalence of thyroxine-binding globulin deficiency among Bedouin infants in southern Israel.

A high prevalence of thyroxine-binding globulin deficiency was found among Bedouin newborns in the Negev area (southern Israel) during a study lasting 2 years. This prevalence is significantly higher than those reported in other populations. Moreover, thyroxine-binding globulin deficiency was found to be more common than congenital hypothyroidism among the Bedouin. The results of thyroxine-binding globulin analysis in four patients may suggest the coexistence of at least two different mutations among the Bedouin population.

Ethnicity↗
PubMed1995

Obesity among Jewish and Bedouin secondary school students in the Negev, Israel.

BACKGROUND: Obesity, which is a common problem, may be associated with many pathological conditions. In this study we compare the prevalence of obesity among Jewish and Bedouin 11th and 12th grade students. METHODS: Five secondary schools were chosen in the Beer Sheva region. The health charts of school infirmaries of all 512 students attending high classes were reviewed. Birth weight, and weight at ages 6-7, 14-15, and 17-18 were abstracted together with height at 17-18 y, as these data were available to us. Triceps skinfold thickness measurements (TST) were made in a subsample of 243 students. Obesity was defined by comparing the individual weight and height (W-H) and the TST to standard norms for age and sex. RESULTS: The differences between the prevalence rates of obesity among Jewish and Bedouin students were not significant (13.7% vs. 11.0%; 9.9% vs. 6.2%, using the W-H and the TST methods, respectively). Obesity at the ages 6-7 and 14-15 is a significant risk factor for obesity at 17-18 y. (RR = 5.8 and 12.1 respectively with 95% CI = 4.0-12.7 and 7.0-21.9, respectively). No significant differences were found between the rates of obesity obtained by the W-H and the TST methods (13.3% vs. 8.6%).

Adolescent↗
PubMed1994

High glucose and insulin decrease fetal lung insulin receptor mRNA and tyrosine kinase activity in vitro.

Specific insulin binding by the fetal lung insulin receptor is reduced in vitro by a combination of high glucose and insulin. Using 19-22 day fetal rat lung, we studied the effect of culture for 48 hours under conditions of low (10mM) and high (100mM) glucose with and without added insulin on insulin receptor tyrosine kinase activity, mRNA abundance, and glucose uptake. Culture in high glucose + insulin reduced tyrosine kinase activity to 77.2 +/- 5.2% of control values (p < .001); high glucose or insulin alone had no effect. Insulin-receptor mRNA abundance was reduced by high glucose + insulin to 37 +/- 6% of control values (p < .05). Again, no significant differences were seen with high glucose or insulin alone. Uptake of 3H-2-deoxy-glucose by explants cultured under high glucose + insulin conditions was also significantly reduced. These data indicate that down-regulation of fetal lung insulin receptors by high glucose + insulin occurs at the pre-translational level and that glucose transport is adversely affected under these conditions. Down-regulation of lung insulin receptors late in fetal life may limit the availability of glucose as substrate for surfactant synthesis in the perinatal period and may partially explain the increased incidence of respiratory distress syndrome in infants of poorly controlled diabetic mothers.

Animals↗
PubMed1994

Differential accumulation of insulin-like growth factor-I in kidneys of pre- and postpubertal streptozotocin-diabetic rats.

Nephropathy, one of the major complications of diabetes mellitus, is characterized by an early increase in kidney size. In experimental models of diabetes, this event is preceded by a rapid and transient rise in kidney IGF-I levels, at least in adult animals. Since diabetes-associated renal changes are uncommon in young patients, we investigated the early changes in the components of the IGF system following induction of diabetes in prepubertal and postpubertal rats. The rationale for this study was the evaluation of potential differences which could lead to kidney complications only at adult stages. Unlike the situation in the postpubertal kidney, in which there was a transient accumulation of extractable IGF-I 24-48 h after streptozotocin (STZ) administration, there was a decrease of approximately 12-fold in the level of IGF-I in the prepubertal kidney over the same period of time. Paradoxically, kidney IGF-I mRNA levels were reduced by approximately 50% in the postpubertal rat 24 h after STZ treatment, whereas in the prepubertal kidney IGF-I mRNA levels were unaltered. Furthermore, the levels of IGF-I receptor mRNA and 125I-labelled IGF-I binding to kidney membranes of postpubertal diabetic rats were similar to the levels in control kidneys. On the other hand, both the levels of IGF-I receptor mRNA and 125I-labelled IGF-I binding were increased (approximately 2.5-fold (after 24 h) and approximately 3-fold (after 48 h) respectively) in prepubertal animals. In addition, increased expression of IGF-binding protein (IGFBP)-1 mRNA was seen early in diabetes in both pre- and postpubertal rats. The results of this study suggest that the transient accumulation of IGF-I in the kidney of the postpubertal diabetic rat may not be due to an increase in the local synthesis of IGF-I, but rather to an increase in IGF-I uptake from the circulation due to non-membrane-associated IGFBP-1. The lack of accumulation of IGF-I in the prepubertal kidney probably reflects the approximately 10-fold lower levels of circulating IGF-I in young as compared with adult diabetic rats.

Age Factors↗
PubMed1993

Plasma integrated concentration of growth hormone after recombinant human growth hormone injection. Implications for determining an optimal dose.

OBJECTIVE: To evaluate the effect of a standard dose of injected recombinant growth hormone on the integrated concentrations of growth hormone and insulin. DESIGN: Integrated concentrations were studied in patients receiving growth hormone therapy before and on the day of injection. SETTING: Pediatric endocrine clinic and diagnostic unit. PATIENTS: Twelve growth hormone-deficient patients with poor linear growth and deficient growth hormone response to provocative stimulation and/or 24-hour integrated concentration. INTERVENTION: Patients received subcutaneous injections of 0.06 mg/kg of growth hormone three times a week in the evenings at approximately 8 PM. Integrated concentrations were measured again approximately 6 months after the start of therapy at the time of a growth hormone injection. MEASUREMENTS AND RESULTS: Mean growth hormone dose administered was 2.0 +/- 0.5 mg. Integrated concentration of growth hormone was 2.2 +/- 0.9 micrograms/L before therapy. The integrated concentration of growth hormone after treatment (14.6 +/- 4.2 micrograms/L) was significantly higher than that before treatment and that of normally growing children (P < .001). After injection, peak growth hormone level was 53.7 +/- 24.1 micrograms/L; time to peak growth hormone level, 4.8 +/- 1.2 hours; constant of elimination, 0.24 +/- 0.06 per hour; half life, 3.0 +/- 0.7 hours; area under the curve, 328 +/- 85 (microgram.h)/L; clearance rate, 107.6 +/- 34.3 mL/min (3.2 +/- 0.8 mL/min per kilogram based on weight, 95.2 +/- 24.2 mL/min per meter squared based on surface area). There was no relationship between integrated concentration of growth hormone or pharmacokinetic variables after treatment and the growth response to 6 months' therapy. Integrated concentration of insulin before treatment was 19.0 +/- 10.9 mU/L, which was significantly lower than that after injection of growth hormone (33.4 +/- 9.5 mU/L; n = 9, P < .0008). CONCLUSIONS: Integrated concentrations of growth hormone after an injection of 0.06 mg/kg of growth hormone are considerably higher than spontaneous integrated concentrations of growth hormone observed in normally growing children, and associated with a rise in insulin secretion. These changes may be pertinent in patients with underlying insulin resistance or when higher doses of growth hormone are used for therapy.

Adolescent↗
PubMed1993

The value of urinary growth hormone determination for assessment of growth hormone deficiency and compliance with growth hormone therapy.

OBJECTIVE: To compare the 24-hour integrated concentrations of plasma growth hormone with growth hormone levels in a simultaneously collected sample of urine. SETTING: Pediatric endocrine diagnostic unit. PATIENTS: Forty-six children (41 male and five female) aged 6 to 19 years underwent measurement of integrated concentrations of growth hormone and simultaneous urine collection. MEASUREMENTS AND RESULTS: Integrated concentration of plasma growth hormone was correlated with urinary growth hormone levels from both the 24-hour (r = .67; P < .0001) and 12-hour overnight (r = .52; P < .001) measurements. Peak growth hormone response to paired stimulation was not correlated with either the 24-hour (r = .26; P < .23; n = 28) or 12-hour (r = .16; P < .48; n = 28) urinary growth hormone levels. The mean 24- and 12-hour urinary growth hormone levels for the patients with normal integrated concentrations of growth hormone were significantly higher than those in patient groups having subnormal integrated concentrations of growth hormone (P < .05). However, there was considerable overlap in the 12- and 24-hour urinary growth hormone levels between the patients with normal and those with subnormal integrated concentrations of growth hormone. Only one patient who had subnormal integrated concentrations of growth hormone had a 24-hour urinary growth hormone level higher than 9 ng, and none had a 12-hour urinary growth hormone level higher than 7 ng. The mean 12- and 24-hour urinary growth hormone levels were significantly higher in patients who received growth hormone injection than in those with normal spontaneous integrated concentrations of growth hormone and had no overlap with patients who had subnormal integrated concentrations of growth hormone. CONCLUSIONS: (1) Urinary and integrated concentrations of plasma growth hormone are correlated; (2) patient diagnoses based on integrated plasma growth hormone levels exhibit a high degree of overlap of urinary growth hormone; and (3) urinary growth hormone levels can serve to monitor compliance with growth hormone therapy.

Adolescent↗
PubMed1993

Regulation of the growth hormone (GH) receptor and GH-binding protein by GH pulsatility.

Growth hormone (GH) secretion is pulsatile in man and every other mammalian species that has been studied. The magnitude of pulses, their frequency, and their regularity vary. The receptor, on its part, undergoes cycles of internalization and recycling that are in synchrony with the frequency of GH pulses. This sequence of events has been shown to be advantageous to growth. It is suggested that changes in GH secretion dynamics secondarily lead to most of the changes in GH receptor abundance and GH-binding protein (GH-BP) abundance. Across a wide scope of comparative studies, ontogenesis data, experimental systems, physiologic conditions, nutritional states, and disease situations, the pulsatility of serum GH is negatively correlated with cell membrane GH receptors and serum levels of GH-BP. It is suggested that these conditions regulate primarily the pattern of GH pulsatility, which in turn regulates the GH receptor/GH-BP, and thereby exert the specific effects on target cells to promote or suppress growth or to express distinct metabolic actions.

Adult↗
PubMed1993

The role of insulin-like growth factors in diabetic kidney disease.

Early renal manifestations of type I diabetes include kidney enlargement, increased glomerular filtration rate, and renal plasma flow. These hemodynamic changes may be caused by a number of factors, including growth hormone and/or insulin-like growth factor-I (IGF-I). Streptozotocin-induced insulinopenic diabetes in rats represents a model of human type I diabetes and is associated with the early hemodynamic changes in the kidney seen in poorly controlled type I diabetic patients. These changes are preceded by an accumulation of IGF-I peptide in the kidney. Insulin-like growth factor-I is not locally produced, but rather accumulates from circulating IGF-I, trapped by increased levels of IGF-binding proteins, particularly IGF-binding protein-1. The hemodynamic effects, reproduced by infusions of recombinant human IGF-I in normal rats, may be blocked by co-infusion of a kinin-receptor antagonist, suggesting that at least one of the mechanisms involved is the kallikrein-kinin system. These studies strongly support the notion that the IGF system may play a role in early hemodynamic manifestations of the diabetic kidney. Whether these effects lead to long-term diabetic renal disease remains to be studied.

Animals↗
PubMed1993

Plasma IGFBP-3 and its relationship with quantitative growth hormone secretion in short children.

OBJECTIVE: We assessed the relationship between serum IGFBP-3 levels with IGF-I and quantitative GH secretory status in poorly growing children. DESIGN: We studied the relationship between 24-hour integrated concentration of GH, peak GH to paired sequential stimulation tests, IGF-I and the IGFBP-3 serum levels. PATIENTS: One hundred and two children (82 males, 20 females, age 11.7 +/- 2.7 years) with short stature (height -2.6 +/- 0.7 SDS) were studied. MEASUREMENTS: Quantitative GH secretory status was assessed by the 24-hour integrated GH and by response to arginine and insulin stimulation. GH, IGFBP-3 and IGF-I were measured by radioimmunoassay. To adjust for age and gender, IGFBP-3 levels were converted to SD score. RESULTS: IGFBP-3 SDS was strongly correlated with IGF-I SDS (r = 0.64, P < 0.0001), and weakly with peak GH (r = 0.28, P < 0.0004), but not with the integrated GH concentration (r = 0.07, P < 0.46). IGFBP-3 SDS increased with pubertal maturation (P < 0.0001). There was no difference in mean IGFBP-3 SDS in subgroupings of the patients based on the results of their quantitative GH tests. CONCLUSION: In short children, IGFBP-3 levels increase with puberty, are strongly correlated with IGF-I levels, weakly correlated with peak response to GH stimulation tests, but not correlated with integrated GH. Consequently, diagnostic classifications of patients based on quantitative measurements of GH secretion and IGFBP-3 differ.

Adolescent↗
PubMed1993

Transient subcapsular cataract formation in a child with diabetes.

Transient cataracts in patients with insulin-dependent diabetes mellitus (IDDM) are rare and have been reported only in association with severe ketoacidosis or hyperosmolarity. We present an adolescent with transient bilateral posterior subcapsular cataracts, which developed after the recent onset of IDDM without ketoacidosis or severe hyperosmolarity.

Acute Disease↗
PubMed1992

Integrated plasma cortisol concentration in children with asthma receiving long-term inhaled corticosteroids.

We assessed the effect of long-term therapy with inhaled beclomethasone dipropionate (BDP) on the pituitary-adrenal axis, by measuring the integrated concentration (IC) of plasma cortisol in eight children with asthma (age, 6-16 years) who regularly used inhaled BDP in doses ranging from 8 to 26.5 micrograms/kg (200-450 micrograms/day) for 6 months to 4 years. The control group included six children (age, 6-16 years) who had the IC of plasma cortisol measured as part of an endocrinological evaluation and were found to be healthy. Cortisol concentration was measured in blood samples collected continuously over a 24-hr period. Mean IC of plasma cortisol in the study group was significantly lower than in the healthy controls (mean +/- SD, 4.9 +/- 3.3 vs 9.1 +/- 1.9 micrograms/mL; P less than 0.02). Cortisol response to 0.25 mg ACTH (iv) was abnormal in one of the eight BDP-treated patients. No correlation was found between IC of plasma cortisol and the BDP dose, severity of asthma, height percentile, or the Tanner stage. We conclude that long-term therapy, even with relatively conventional doses of inhaled BDP may cause reduction in the normal physiological secretion of cortisol. The clinical relevance of low IC of plasma cortisol is not clear, but it may reflect partial suppression of the pituitary-adrenal axis.

Administration, Inhalation↗
PubMed1992

Effect of testosterone on insulin-like growth factor-I (IGF-I) and IGF-I receptor gene expression in the hypophysectomized rat.

Circulating levels of insulin-like growth factor-I (IGF-I) increase during puberty, concurrent with an increase in the levels of GH and the gonadal steroids. The relationship between the changes observed in IGF-I and testosterone (T) levels are not understood. This study was designed to determine whether T has a direct effect on IGF-I serum levels, liver IGF-I gene expression, and epiphyseal growth plate IGF-I and IGF-I receptor gene expression. Hypophysectomized castrated rats were divided into four groups of six animals. The T group was treated with sc T for 5 days. The GH group was treated with a single dose of GH. The GH plus T group was treated with T for 5 days and with GH on the last day of treatment. The control group was injected for 5 days with vehicle alone. Serum IGF-I levels in the T group were not significantly different from those in the control group, and the levels in the GH plus T group were not significantly different from those in the GH group. There was an 11-fold increase in liver IGF-I mRNA abundance in the GH group compared to the control group (P less than 0.01). Liver IGF-I mRNA levels in the T group were not significantly different from those in the control group. When liver IGF-I mRNA levels in the GH plus T group were compared to those in the GH-treated group, no significant differences were found. In the epiphyseal growth plate region, there was a 12-fold increase in IGF-I mRNA levels in the GH group compared to those in the control group, but there was no statistical difference between the control and T groups. IGF-I mRNA levels in the GH plus T group were not significantly different from those in the GH-treated group. IGF-I receptor mRNA abundance was not significantly different in the T group compared to that in the control group. GH decreased IGF-I receptor mRNA by 2.3-fold, but T treatment before GH injection did not change this effect. We conclude that in castrated hypophysectomized rats, T does not stimulate IGF-I gene expression in the liver, nor does it increase IGF-I serum levels. T alone also does not have a stimulatory effect on IGF-I or IGF-I receptor gene expression in the epiphyseal growth plate region.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1990

Persistent hyperinsulinemic hypoglycemia of infancy ("nesidioblastosis"): autosomal recessive inheritance in 7 pedigrees.

Persistent Hyperinsulinemic Hypoglycemia of Infancy (PHHI) is a rare disease characterized clinically by persistent hypoglycemia with inappropriately elevated circulating insulin concentrations. Here we report on 7 pedigrees including 21 cases. The pedigrees are derived from 3 distinct ethnic groups, and include a very large Bedouin family, and Arab family, and 5 smaller pedigrees of Jewish families all of Eastern European origin. Data obtained from these families and from other families reported in the literature strongly suggest that PHHI is inherited as an autosomal recessive disorder.

Female↗