POTENTIAL USES OF HUMAN PANCREATIC GROWTH HORMONE-RELEASING FACTOR 1-44 AMIDE

A family of growth hormone releasing peptides have been isolated and characterized from human pancreatic islet cell tumours. We have compared the growth hormone release in normal volunteers and patients with various hypothalamo-pituitary disorders, following direct stimulation of the pituitary using 50μg of the most potent homologue, hp GRF 1-44 amide i.v. with that following indirect stimulation using oral clonidine 0-15 mg/m², which depends on intact hypothalamic mechanisms. These tests both produced a wide variation in GH response in normal volunteers, considerable GH release following hp GRF 1^44 amide but little after clonidine in idiopathic GH deficiency, and indistinguishable, negligible responses in patients with craniopharyngiomas and pituitary tumours associated with GH deficiency. Two untreated acromegalics showed GH increments in the normal range despite elevated basal levels. It is concluded that hp GRF 1-44 amide is of limited diagnostic value by itself, but may be of considerable therapeutic use in patients with idiopathic GH deficiency.     

d· Ala5 analog of the elastin polypentapeptide. Physical characterization

The d ° Ala₅ analog, (l · Val₁-l · Pro₂-Gly3-l · Val₄-d · Ala₅)_n, of the polypentapeptide (PPP) of elastin is synthesized and characterized by a series of physical methods. Carbon-13 and proton nuclear magnetic resonance spectroscopies are used to verify purity and, by means of solvent dependence of peptide C -O chemical shift and of temperature dependence of peptide NH chemical shift, to establish by comparison with the PPP of elastin the presence and increased stability of the Type II Pro₂-Gly₃ β-turn. The temperature dependence of aggregation in water to form a viscoelastic phase called the coacervate is reported for several concentrations. Comparison of carbon-13 nuclear magnetic resonance spectra obtained under identical conditions for the coacervate states of the PPP of elastin and the d · Ala₅ analog shows the effect of replacing the Gly₅ residue by a d · Ala_s residue to be one of greatly restricting mobility of the polypeptide chain. Scanning electron micrographs, of the coacervate alone and of the coacervate cross-linked and compounded to a Dacron fabric before and after stress-strain studies, are reported which show the d · Ala₅ PPP matrix to rupture during the stresses of drying and of stretching while wet. Thus, the effect of adding a methyl moiety to the Gly₅ residue of the PPP of elastin is to decrease markedly the mobility of the polypeptide chain and to destroy elasticity. The results are presented as a test of the proposed librational entropy mechanism of elasticity of the PPP of elastin.     

RELATIONSHIPS BETWEEN THE CIRCADIAN RHYTHMS OF TSH, PROLACTIN AND CORTISOL IN SURGICALLY TREATED MICROPROLACTINOMA PATIENTS

Pharmacological doses of glucocorticoids inhibit TSH release both in vivo and in vitro and since the circadian rhythms of TSH and cortisol show a reciprocal relationship, the hypothesis has been advanced that changes in cortisol levels may be a primary determinant of circadian TSH changes. We have tested this hypothesis by studying the relationship between circadian cortisol and TSH rhythms in subjects before and during blockade with metyrapone. Seven patients were studied during their routine post-operative assessment following selective transethmoidal adenomectomy for microprolactinomas. PRL levels were restored to normal (less than 420 mU/l) in all patients by surgery (pre-op: 930-2752 mU/l, post-op: 33-376 mU/l) and the patients also had normal pituitary function in other respects. Blood was sampled hourly for 24 h before and on the third day of treatment with metyrapone (250 mg, 2 hourly). In order to compare circadian rhythms, hormonal data were subjected to cosinor analysis which involved fitting of the data with a cosine function using the method of least squares. The 6% cross reactivity of the cortisol antibody with 11-deoxycortisol was taken into account during the calculation of results. All subjects showed a normal cortisol rhythm which was strikingly blunted during metyrapone treatment. Group mean (+/- SD) TSH mesors, amplitudes and acrophases for control and metyrapone treated subjects were 1.5 +/- 0.26, 1.29 +/- 0.48; 0.46 +/- 0.26, 0.23 +/- 0.13 and -49 degrees +/- 9.8 degrees; -62 degrees +/- 2.7 degrees respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cow's Milk Allergy as a Cause of Infantile Colic: Immunofluorescent Studies on Jejunal Mucosa

Fourteen infants and children who had suffered from infantile “colic” and related symptoms were diagnosed as being allergic to cow's milk because of their response to cow's milk exclusion and then to repeated challenge with cow's milk. The parents of these children frequently were allergic themselves and very frequently refused to drink cow's milk. Small bowel biopsy specimens were taken on these children, but only seven had biopsies both while taking cow's milk and when on a milk free diet. The mucosae were all histologically normal with normal disaccharidase levels. However, on immunological study it has been shown that significantly higher numbers of IgE containing plasma cells were present in the mucosal specimens when these infant? were taking cow's milk, than when they were on a milk-free diet.     

Tympanoplasty and Eustachian tube function*

In an attempt to assess the value of preoperative tubal testing in the selection of cases most likely to respond favourably to surgery, 100 ears with a central perforation following chronic otitis media were investigated. Tubal function was tested manometrically with different known tests. Postoperatively the healing and hearing results were correlated with the preoperative test results. No positive correlation was found between healing or hearing and tubal function. Postoperatively 50 ears were re-tested in a pressure chamber with a flow volume technique. It was found that the tubal function improves postoperatively in spite of no visible pathological changes in the aural end of the tube. Possible explanations are offered.     

Linkage relationships between the three phosphoglucomutase loci PGM1, PGM2 and PGM3

1. Phosphoglucomutase phenotypes have been studied in several generations of the family of an individual heterozygous at each of the three loci, PGM₁, PGM₂, and PGM₃. 2. PGM₁ and PGM₂ phenotypes were determined using red cells. Fibroblasts grown in tissue culture were used for PGM₃ phenotyping. 3. The family results support the genetical hypothesis based on the analysis of dizygotic twin pairs that the PGM₃ isozyme patterns found in the placenta are determined by two alleles, PGM¹₃ and PGM²₃. 4. Locus PGM₃ is not closely linked to locus PGM₂ 5. The data also support the previous findings that locus PGM₁ is not closely linked to PGM₂ or PGM₃.     

Anthropometric Characteristics of Mohawk Children Aged 6 to 11 Years: A Population Perspective

OBJECTIVE: Recent studies have concluded that Native North American children have higher proportions of overweight and obesity than children from the general North American population. This study presents anthropometric data on a representative sample of children from the Mohawk Nation that can be used for comparison with other Native American populations. DESIGN: This is a cross-sectional study comparing distributions of anthropometric characteristics of Mohawk children to the corresponding age and gender data from the Second National Health and Nutrition Examination Survey (NHANES II). Weight, height, triceps and subscapular skinfold thickness, and waist and hip circumferences were measured in 527 children. SUBJECTS/SETTING: All children in grades 1 to 6 (aged 6 to 11 years) in the 3 elementary schools of 2 Mohawk communities in Canada, for whom parental consent was obtained, were enrolled in the present study. There were no exclusion criteria. With a participation rate of 83%, the 527 children enrolled in this study represent an unbiased sample of the population from 2 Mohawk territories. RESULTS: Compared with children studied in NHANES II, Mohawk children were similar in height and triceps skinfolds but were generally heavier, had thicker subscapular skinfolds, and had greater waist and hip circumferences. These differences were greater in older children. Mohawk children who had extreme-high weight values compared with their population means were heavier than their NHANES II counterparts. APPLICATIONS/CONCLUSIONS: Results indicated that, on average, Mohawk children seem to be slightly heavier than children in NHANES II. Except for those with extreme overweight values, Mohawk children show less variation of weight and body mass index than children in NHANES II. Finally, overweight Mohawk children seem to be more likely to carry their excess body fat truncally, compared with overweight children from NHANES II. Health practitioners working with Native American populations should be careful when assessing childhood obesity. Simple comparisons of weight or body mass index with NHANES standards may lead to inappropriate risk assessments.