{"title":"Therapeutic use of human growth hormone.","authors":"A S Mason","doi":"10.1136/jcp.s1-7.1.58","DOIUrl":"https://doi.org/10.1136/jcp.s1-7.1.58","url":null,"abstract":"A great deal is known about the therapeutic effect of human growth hormone (HGH) on short stature. Raben (1958) reported the acceleration of growth in hypopituitary subjects given HGH 18 years ago. The species specificity of growth hormone means that we must rely on hormone extracted from human pituitaries. It is likely to be a long time before HGH is synthesised and various 'soups' of digested ox pituitary have been of no avail. The only immediate hope for an alternative to HGH is the isolation and synthesis of the growth hormone releasing hormone. If the syndrome of isolated growth hormone deficiency is due to a lack of this hypothalamic hormone rather than an inability of the pituitary itself to secrete growth hormone the logical therapy is obvious. The amount of 'clinical grade' HGH available from human pituitaries obtained at necropsy will depend largely on the efficiency of the extraction procedures. Raben's (1959) method using acetonedried pituitaries yielded 4-4 IU per gland. The modification of Wilhelmi's method by Mills et al. (1969) obtained about 7-2 IU per gland. Methods using fresh frozen pituitaries vary from that of Roos et al. (1963) to the modern development by Lowry (1977) that produced monomer growth hormone at a yield of 16-0 IU per gland. The antigenicity of these products is of importance. The Raben preparation, widely used, promoted antibody formation in a number of patients. The preparations from frozen pituitaries seem less antigenic. The biological potency of each batch of HGH has to be assayed, because it varies considerably, and the potency of the finally ampouled material has to be checked.","PeriodicalId":75995,"journal":{"name":"Journal of clinical pathology. Supplement (Association of Clinical Pathologists)","volume":"7 ","pages":"58-61"},"PeriodicalIF":0.0,"publicationDate":"1976-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1136/jcp.s1-7.1.58","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12253030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Relationships of structure with function of the gonadotrophins.","authors":"W R Butt","doi":"10.1136/jcp.s1-7.1.12","DOIUrl":"https://doi.org/10.1136/jcp.s1-7.1.12","url":null,"abstract":"The gonadotrophins are an interesting group of hormones in which to study relationships of structure with function. They are glycoproteins with carbohydrate components which confer important properties of biological activity and they consist of subunits which bear interesting relationships with one another. Furthermore, they are easier to study than some other hormones because of the specific biological assay methods available which are relatively simple to carry out.","PeriodicalId":75995,"journal":{"name":"Journal of clinical pathology. Supplement (Association of Clinical Pathologists)","volume":"7 ","pages":"12-5"},"PeriodicalIF":0.0,"publicationDate":"1976-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1136/jcp.s1-7.1.12","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12253315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Management of acromegaly.","authors":"J D Nabarro","doi":"10.1136/jcp.s1-7.1.62","DOIUrl":"https://doi.org/10.1136/jcp.s1-7.1.62","url":null,"abstract":"was an accidental observation when the patient went to the doctor for some other condition. Surprisingly, less than 10% of the patients went actually complaining of a change in their appearance, but this reflects the very slow way in which the condition usually evolves. Most of the other presenting symptoms were due to local spread of the tumour or to recognised features or complications of acromegaly, although some were a little unusual-namely, presentation with hirsutism, goitre, nose blocked by nasal polyps,","PeriodicalId":75995,"journal":{"name":"Journal of clinical pathology. Supplement (Association of Clinical Pathologists)","volume":"7 ","pages":"62-7"},"PeriodicalIF":0.0,"publicationDate":"1976-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1136/jcp.s1-7.1.62","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12253031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cytochemical methods of hormone assay.","authors":"L Bitensky","doi":"10.1136/jcp.s1-7.1.22","DOIUrl":"https://doi.org/10.1136/jcp.s1-7.1.22","url":null,"abstract":"Initially polypeptide hormones were assayed by their biological activity. Such conventional bioassays, however, are remarkably insensitive. For example, the Lipscomb and Nelson (1962) bioassay of corticotrophin (ACTH) cannot measure a concentration of less than about 100 pg/ml, while the normal circulating levels of the bioactive form of this hormone range from about 5 to 60 pg/ml. The introduction of radioimmunoassay increased the sensitivity with which hormones could be assayed quite remarkably, that of ACTH being able to measure as little as 10 pg/ml. Moreover, the number of assays which could be done in unit time by radioimmunoassay was far greater than could be achieved by conventional bioassay. The fact that radioimmunoassay fundamentally measures the number of specific molecules (or antigenic determinants) present rather than the functional activity of the hormone might be regarded as an improvement on bioassay, representing a precise chemical rather than a biological analytical tool. However, so long ago as 1967 it was recognised that immunoassays measure a composite of antigenic activity which is not necessarily related to the biological activity of the hormone. A special committee, convened by the World Health Organization, noted a need for 'micro-bioassays' which would have at least the same sensitivity as radioimmunoassay and which could be done in parallel with it (World Health Organization, 1975). Since then reports concerning the dissociation of immunoactivity and bioactivity (for example, Besser et al., 1971) have increased alarmingly. Thus gastrin has been shown to occur in a number of forms which show various biological activities (Yalow, 1974). Apart from this problem of assaying molecules which may have little or no biological activity, the sensitivity of radioimmunoassay may be insufficient to measure low normal circulating levels of some hormones or pathologically low levels that might occur in some diseases. Thus the population survey of Tunbridge et al. (1976) and the other studies of Petersen et al. (1975) clearly show that the circulating level of TSH in a considerable proportion of normal people may be below 1.0 ,uU/ml or even below 0.5 ,uU/ml. Yet this is the sensitivity level of even the best radioimmunoassays currently available for this hormone. Therefore there is clearly a need for a functional (that is, biological) assay system at least 10 times more sensitive than the current radioimmunoassays. Such bioassays could be performed in parallel with the more conventional radioimmunoassays to test whether the molecules detected by the latter were functional. Their greater sensitivity would also be of value when only small samples were obtainable, as in investigations ofhormones in neonates (Holdaway et al., 1973) or when many serial samples were required (Daly et al., 1974a), and when the hormonal levels were below the limits of precise measurement by radioimmunoassay.","PeriodicalId":75995,"journal":{"name":"Journal of clinical pathology. Supplement (Association of Clinical Pathologists)","volume":"7 ","pages":"22-5"},"PeriodicalIF":0.0,"publicationDate":"1976-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1136/jcp.s1-7.1.22","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"11417640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Purification of anterior pituitary and hypothalamic hormones.","authors":"P J Lowry, C McLean, R L Jones, N Satgunasingam","doi":"10.1136/jcp.s1-7.1.16","DOIUrl":"https://doi.org/10.1136/jcp.s1-7.1.16","url":null,"abstract":"Pure preparations of pituitary and hypothalamic hormones are needed mainly for (1) their chemical characterisation, which increases our understanding of their biochemistry and makes their synthesis possible; (2) replacement therapy, in which contamination with other pituitary hormones is undesirable; and (3) the development of specific diagnostic assays.","PeriodicalId":75995,"journal":{"name":"Journal of clinical pathology. Supplement (Association of Clinical Pathologists)","volume":"7 ","pages":"16-21"},"PeriodicalIF":0.0,"publicationDate":"1976-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1136/jcp.s1-7.1.16","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"11245643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Pituitary and hypothalamic physiology.","authors":"G M Besser","doi":"10.1136/jcp.s1-7.1.8","DOIUrl":"https://doi.org/10.1136/jcp.s1-7.1.8","url":null,"abstract":"Professor P. M. Daniel has described in the first paper the nervous pathways connecting the hypothalamus to the posterior pituitary and how the posterior pituitary merely stores the hormones vasopressin, oxytocin (which has no clearly defined function in man), and neurophysin, the large molecule or molecules which bind the other hormones. For many years the anterior pituitary was thought to be very different but recently it has been realised that conceptually it is quite similar.","PeriodicalId":75995,"journal":{"name":"Journal of clinical pathology. Supplement (Association of Clinical Pathologists)","volume":"7 ","pages":"8-11"},"PeriodicalIF":0.0,"publicationDate":"1976-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1136/jcp.s1-7.1.8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"11245644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Disorders of gonadotrophin secretion.","authors":"S L Jeffcoate","doi":"10.1136/jcp.s1-7.1.42","DOIUrl":"https://doi.org/10.1136/jcp.s1-7.1.42","url":null,"abstract":"In recent years, particularly since the advent ofradioimmunoassay, the regulation of pituitary gonadotrophin secretion has been extensively studied in man and in animals (Greep et al., 1976). I shall not comprehensively catalogue the different diseases and syndrome complexes associated with disordered gonadotrophin secretion. These are systematically covered in several textbooks and reviews (London, 1975; James et al., 1976). Instead I shall consider the more practical situation of a pathologist or other clinician faced with the result of a serum gonadotrophin measurement and discuss the factors that need to be borne in mind when interpreting that result. This will lead me to some conclusions about the optimal use of these assays in clinical practice.","PeriodicalId":75995,"journal":{"name":"Journal of clinical pathology. Supplement (Association of Clinical Pathologists)","volume":"7 ","pages":"42-5"},"PeriodicalIF":0.0,"publicationDate":"1976-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1136/jcp.s1-7.1.42","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12253028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The posterior pituitary and diabetes insipidus.","authors":"C G Beardwell","doi":"10.1136/jcp.s1-7.1.68","DOIUrl":"https://doi.org/10.1136/jcp.s1-7.1.68","url":null,"abstract":"SYNTHESIS Vasopressin is synthesised in hypothalamic neurones, predominantly concentrated in the supraoptic and paraventricular nuclei, which appear to be separate from those concerned in oxytocin synthesis. After synthesis, which may begin with the formation of a high molecular weight, biologically-inactive precursor molecule (Sachs and Takabatake, 1964), the vasopressin is packaged together with one or more neurophysins into neurosecretory granules (Sachs et al., 1969). These then pass down the axons of the neurons to reach the secretory terminal where vasopressin is released after appropriate stimulation. Secretory terminals are found not only in the posterior pituitary but also in the region of the median eminence. Because of the relatively wide anatomical extent of the vasopressin-producing system diabetes insipidus rarely results from disease of the pituitary itself. It is much more commonly seen arising either in the absence of any clinically or radiologically obvious cause or as a result of primary or secondary neoplasms (especially from breast) involving the hypothalamus. It may also be associated with granulomatous lesions of the hypothalamus-for example, histiocytosis X or sarcoidosis. Craniopharyngiomas or large suprasellar extensions of pituitary tumours may interfere with vasopressin release or synthesis, but more commonly diabetes insipidus results from the trauma associated with the treatment of such lesions.","PeriodicalId":75995,"journal":{"name":"Journal of clinical pathology. Supplement (Association of Clinical Pathologists)","volume":"7 ","pages":"68-71"},"PeriodicalIF":0.0,"publicationDate":"1976-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1136/jcp.s1-7.1.68","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12253034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Secretion of pituitary-like peptides by the human placenta.","authors":"L H Rees","doi":"10.1136/jcp.s1-7.1.31","DOIUrl":"https://doi.org/10.1136/jcp.s1-7.1.31","url":null,"abstract":"STRUCTURE Ascheim and Zondek (1927) first demonstrated the presence of gonadotrophic substances in the urine of pregnant women. Such urine injected into infantile mice induced premature oestrus with follicle ripening and luteinisation. hCG is a glycoprotein structurally related to the pituitary hormones TSH, FSH, and LH and comprises two subunits (Reichert et al., 1970; Pierce and Liao, 1970). The a-subunit (92 amino-acids) shows extensive structural sequence homology with FSH, LH, and TSH, and the fsubunit (145 amino-acids) is similar to that of LH apart from an extra 30 C-terminal amino-acids (Swaminathan and Bahl, 1970). The carbohydrate content comprises over 20% of the molecule (Diczfalusy and Troen, 1961) and is essential for biological activity (Whitten, 1948). Isolated aand fl-subunits possess very little intrinsic biological activity but, because of the close structural similarities, an a-subunit of hCG can be combined with the fl-subunit of LH or TSH with restoration of a high degree of biological activity appropriate to the fl-subunit (Pierce, 1971). Interestingly, the fl-subunits of all the glycoprotein hormones show a significant degree of homology, suggesting that they evolve from a common ancestral gene (Pierce. 1971; Acher, 1976) (Fig. 1).","PeriodicalId":75995,"journal":{"name":"Journal of clinical pathology. Supplement (Association of Clinical Pathologists)","volume":"7 ","pages":"31-5"},"PeriodicalIF":0.0,"publicationDate":"1976-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1136/jcp.s1-7.1.31","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"11417642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Radioimmunoassay of IgE and IgE antibody and its clinical application.","authors":"S G Johansson","doi":"10.1136/jcp.s1-6.1.33","DOIUrl":"https://doi.org/10.1136/jcp.s1-6.1.33","url":null,"abstract":"For more than 50 years it has been known that some patients with asthma, allergic rhinitis and eczema possess antibodies with skin-sensitizing properties, so-called reagins. It is now well established that the reagins belong to a unique immunoglobulin class, IgE (Ishizaka and Ishizaka, 1967; Johansson and Bennich, 1967). The isolation of IgE and the raising of antibodies against IgE made possible the development of immunological assays for IgE and allergenspecific IgE antibody. The aim of this paper is to discuss the methodological aspects of the determination of IgE and IgE antibody as well as their clinical application.","PeriodicalId":75995,"journal":{"name":"Journal of clinical pathology. Supplement (Association of Clinical Pathologists)","volume":"6 ","pages":"33-7"},"PeriodicalIF":0.0,"publicationDate":"1975-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1136/jcp.s1-6.1.33","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"11990528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}