The Hypothalamic-Pituitary-Adrenocortical System—Clinical Evaluation by Pharmacologic Techniques

The hypothalamic-pituitary-adrenocortical system is a complex negative feed-back control mechanism. Under non-stress conditions it functions to maintain a circadian rhythm of adrenal steroid production which is secondary to a circadian fluctuation in the sensitivity to suppression of acth by hydrocortisone. Any stressful stimulus causes an augmentation of steroid production which is due in part to a decrease in sensitivity of acth to suppression. Aldosterone production is not primarily controlled by acth.The increased understanding of this system and of its pathologic alterations has led to the development of a number of pharmacologic techniques which have proved most valuable in evaluating its integrity. Hypothalamic-pituitary function can be assessed by the response to the administration of dexamethasone, methopyrapone, bacterial pyrogen and vasopressin. Adrenal cortical function can be assessed by the response to acth, dexamethasone and spironolactone.     

Applicants to Canadian Medical Schools for 1966-67

An examination of applicants to Canadian medical schools for 1966-67 revealed that 4534 applications were received for the approximately 974 available places. The number of Canadian applications was 2866 and these were made by 1815 individual applicants, an increase of 48 over 1965-66. United States applicants declined from 1143 to 1013.Evaluations made by the schools concerning the acceptability of the Canadian applicants disclosed that 55 applicants who rated as “acceptable” by one or more schools failed to gain admission to any medical school in 1966-67 (as compared to 36 in 1965-66). However, of those applicants who did find a place 76 were evaluated as “marginal” or “unacceptable”, while another 126 were rated as “acceptable” by one school but “marginal” and/or “acceptable” by one or more other schools.These results were interpreted to imply that the Canadian medical schools were still experiencing difficulty in attracting well-qualified applicants for study in medicine.     

Pheromone-mediated sexual selection in the mothUtetheisa ornatrix: Olfactory receptor neurons responsive to a male-produced pheromone

Male Utetheisa ornatrixhave a pair of eversible glandular brushes (coremata) which are displayed during precopulatory interactions with the female. Earlier studies have shown that a pheromone associated with the coremata, hydroxydanaidal (HD), is derived by the males from pyrrolizidine alkaloids (PAs) that they sequester as larvae from their foodplants (Crotalariaspp.) The PAs impart a distastefulness upon Utetheisathat protects both larvae and adults against predation. The receptor neurons specialized for detection of HD are housed in sensilla whose morphological features, as revealed by scanning electron microscopy, classify them as sensilla basiconica. The sensitivity and dynamic range of these receptor neurons were largely unaffected by whether the females were raised on an alkaloid-free diet or on a diet supplemented with Crotalariaseeds. Acetylation of the hydroxyl group of HD substantially reduced the activity of the molecule. None of the antennal sensilla examined contained receptor neurons sensitive to a PA (monocrotaline) or its N-oxide.     

Senior house officers and their training. II. Perceptions of service and training.

Aspects of teaching and learning at senior house officer level in South East Thames region were investigated by analysis of the responses of consultants, senior registrars, registrars, and senior house officers to a postal questionnaire. Responses to sections about who teaches senior house officers, how senior house officers learn, and the relation between the service and training elements of these posts varied significantly, according to the status of the respondents; certain grades commonly overestimated their own contribution when compared with the estimates of the other grades. Although the replies of senior house officers showed that they were taught by various grades, 47% of this group did not regard the consultant as their main teacher. Senior registrars and registrars rather than consultants were regarded by senior house officers as best at teaching (63% v 48% respectively). Consultants and registrars were considered to require more commitment to training, personal educational training, and to be more approachable. Inquiry about teaching methods used most by senior house officers showed absence of a systematic approach to training. Only about half of senior house officers cited ward rounds with consultants. Views on the relation between training and service were significantly different among grades, but there was general dissatisfaction. Overall, the findings disclosed the ineffectiveness of senior house officer training posts. This arises from lack of a clear distinction between training and service elements, of educational training for teachers, of a clear contractual obligation to teach im the consultant grade, and of allotted time for training and study for the teachers and senior house officers respectively. Reversal of these current trends is needed for senior house officer posts to fulfil their main training function.     

31P NMR studies on the effect of phosphite on Phytophthora palmivora

31P NMR spectra were obtained from perchloric acid (PCA) and KOH extracts of Phytophthora palmivora mycelium. Signals indicating the presence of large amounts of short-chain polyphosphate were observed in the spectra of PCA extracts of mycelia grown under both low (0.1 mM) and high (10 mM) phosphate conditions. The mean chain length of polyphosphate was calculated from the relative areas of signals arising from terminal and internal P nuclei in the polyphosphate chain. The small amount of polyphosphate evident in the KOH extract had an average chain length similar to PCA-soluble polyphosphate. 32P tracer studies indicated that phosphorus in the PCA fraction accounted for between 50 and 60% of total phosphorus, the bulk of the remainder being divided between the lipid and KOH extracts. The presence of the fungicide phosphorous acid markedly reduced the average chain length of acid-soluble polyphosphate. This reduction occurred both under low-phosphate conditions, in which treatment with phosphorous acid retards growth, and under high-phosphate conditions, in which no significant growth retardation is observed. Treatment with phosphorous acid perturbed phosphorus distribution and lipid composition under low-phosphate conditions.     

The expression of sarcomeric muscle-specific contractile protein genes in BC3H1 cells: BC3H1 cells resemble skeletal myoblasts that are defective for commitment to terminal differentiation

The BC3H1 cell line has been used widely as a model for studying regulation of muscle-related proteins, such as the acetylcholine receptor, myokinase, creatine kinase, and actin. These cells, derived from a nitrosourea-induced mouse brain neoplasm, have some of the morphological characteristics of smooth muscle and have been shown to express the vascular smooth muscle isoform of alpha-actin. To provide further information about the contractile protein phenotype of BC3H1 and to gain additional insights into the possible tissue of origin of these cells, we have examined the expression of a battery of contractile protein genes. During rapid growth, subconfluent BC3H1 cells express the nonmuscle isoform of alpha-tropomyosin (alpha-Tm) and the nonsarcomeric isoforms of myosin heavy and light chains (MHCs and MLCs, respectively), but do not express troponin T(TnT). However, when BC3H1 cells differentiate in response to incubation in serum-deprived medium or upon approaching confluence, they express TnT as well as sarcomeric muscle isoforms of MHC, MLC 2 and 3, alpha-Tm, and alpha-actin. These results suggest that BC3H1 is a skeletal muscle cell line of ectodermal origin that is defective for commitment to terminal differentiation.     

Expression of the neural cell adhesion molecule NCAM in endocrine cells

We examined the expression of the neural cell adhesion molecule NCAM in a number of endocrine tissues of adult rat and in an endocrine tumor cell line. NCAM was found by immunoelectron microscopy to be present on the surface of all endocrine cells in the three lobes of the hypophysis, although staining was relatively less intense in the intermediate lobe, and in pancreatic islets. Pituicytes, hypophyseal glial cells, were also labeled for NCAM. A rat insulinoma cell line (RIN A2) also expressed NCAM as judged by immunocytochemistry. Analysis of NCAM antigenic determinants (Mr 180, 140, and 120 KD) revealed large variations in the relative proportions of NCAM polypeptides present in the different tissues. Although all tissues and cell lines expressed NCAM-140, NCAM-180 was not detected in the adenohypophysis, pancreas, or adrenal medulla, and NCAM-120 was found in none of the endocrine tissues or cell lines except at low levels in the neurohypophysis. The tumor cell line expressed significant levels of NCAM-180, which was most abundant in the neurohypophysis. These results show that NCAM expression appears to be a general property of endocrine cells, although the antigenic composition differs markedly from that in brain tissue. These data are discussed with regard to the embryological origins of the different endocrine tissues, and possible functional implications are suggested.     

SSCP and segregation analysis of the human type X collagen gene (COL10A1) in heritable forms of chondrodysplasia.

Type X collagen is a homotrimeric, short chain, nonfibrillar collagen that is expressed exclusively by hypertrophic chondrocytes at the sites of endochondral ossification. The distribution and pattern of expression of the type X collagen gene (COL10A1) suggests that mutations altering the structure and synthesis of the protein may be responsible for causing heritable forms of chondrodysplasia. We investigated whether mutations within the human COL10A1 gene were responsible for causing the disorders achondroplasia, hypochondroplasia, pseudoachondroplasia, and thanatophoric dysplasia, by analyzing the coding regions of the gene by using PCR and the single-stranded conformational polymorphism technique. By this approach, seven sequence changes were identified within and flanking the coding regions of the gene of the affected persons. We demonstrated that six of these sequence changes were not responsible for causing these forms of chondrodysplasia but were polymorphic in nature. The sequence changes were used to demonstrate discordant segregation between the COL10A1 locus and achondroplasia and pseudoachondroplasia, in nuclear families. This lack of segregation suggests that mutations within or near the COL10A1 locus are not responsible for these disorders. The seventh sequence change resulted in a valine-to-methionine substitution in the carboxyl-terminal domain of the molecule and was identified in only two hypochondroplasic individuals from a single family. Segregation analysis in this family was inconclusive, and the significance of this substitution remains uncertain.