A simple program to integrate differential equations is given. The program is written in BASIC and has been devised to be used on small computers. The program has been used to integrate the differential equations corresponding to a single reaction-single enzyme, a bireaction-single enzyme and a four reaction-four substrate-single enzyme mechanism; it has been used also for studying the interconversions among various molecular forms of a single enzyme, viz. monomer - dimer - trimer - tetramer. The program has proven to be very effective in these models and its time consumption comparable with that of other longer programs. The BASIC version is shown, and the FORTRAN VS version is available upon request to the authors.

Computers↗

PubMedDate not supplied

Synthesis and some pharmacologic properties of five novel V1 or V1/V2 antagonists of AVP.

Based on [1-(1-mercaptocyclohexaneacetic acid),2-(O-ethyl-D-tyrosine),4-valine]-8-arginine-vasopressin as a model, five new analogues of arginine-vasopressin (AVP) were designed and synthesized. Four of them have in position 1 a large lipophilic substituent, whereas the fifth contains pchloro-D-phenylalanine at position 2. We found that the anti-antidiuretic potency with 1-mercapto-4-methycyclohexaneacetic acid is higher than with 1-mercaptocyclohexaneacetic acid (model peptide) in position 1 and this analogue is among the most potent antagonists of the antidiuretic response to AVP known to date. Upon further increase of the size of substituents, antagonistic potency was significantly decreased or totally eliminated. As for the substitution of p-chloro-D-phenylalanine in position 2, we conclude that this modification leads to substantial decrease of the V2 antagonistic potency.

Animals↗

PubMedDate not supplied

Graphical analysis of data from pharmacology experiments.

Dose-response curves are often used in the study of the interaction of hormones and receptors. From these plots, IC50 or EC50 values are calculated. In these pharmacological assays it is implicitly assumed that a single receptor predominates in a tissue. In this paper the interaction of a ligand with two receptors is studied from a theoretical point of view. It is assumed that the responses mediated by these receptors are qualitatively or quantitatively different. The theoretical direct and Scatchard plots display a high variety of shapes depending upon the difference in potency of the effect of the drug acting in both receptors and upon the magnitude and sign of the individual response. When dose-response curves taken from the literature have been transformed into direct or Scatchard plots new information has become available. With respect to this, it is shown that agonists of purinergic receptors seem to interact with two different populations of receptors. We claim that carefully designed experiments must provide valuable information concerning the number of subtypes of receptors present in a given system and the kind of response mediated by them.

Adenosine↗

PubMedDate not supplied

Discrete cis-active genomic sequences dictate the pituitary cell type-specific expression of rat prolactin and growth hormone genes.

The anterior pituitary gland, which is derived from a common primordium originating in Rathke's pouch, contains phenotypically distinct cell types, each of which express discrete trophic hormones: adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH), prolactin, growth hormone, and follicle stimulating hormone (FSH)/luteinizing hormone (LH). The structurally related prolactin and growth hormone genes, which are evolutionarily derived from a single primordial gene, are expressed in discrete cell types--lactotrophs and somatotrophs, respectively--with their expression virtually limited to the pituitary gland. The pituitary hormones exhibit a temporal pattern of developmental expression with rat growth hormone and prolactin characteristically being the last hormones expressed. The reported co-expression of these two structurally related neuroendocrine genes within single cells prior to the appearance of mature lactotrophs, in a subpopulation of mature anterior pituitary cells, and in many pituitary adenomas raises the possibility that the prolactin and growth hormone genes are developmentally controlled by a common factor(s). We now report the identification and characterization of nucleotide sequences in the 5'-flanking regions of the rat prolactin and growth hormone genes, respectively, which act in a position- and orientation-independent fashion to transfer cell-specific expression to heterologous genes. At least one putative trans-acting factor required for the growth hormone genomic sequence to exert its effects is apparently different from those modulating the corresponding enhancer element(s) of the prolactin gene because a pituitary 'lactotroph' cell line producing prolactin but not growth hormone selectively fails to express fusion genes containing the growth hormone enhancer sequence.

Animals↗

PubMedDate not supplied

A c-erb-A binding site in rat growth hormone gene mediates trans-activation by thyroid hormone.

The substance 3,5,3-triiodothyronine (T3) stimulates growth hormone gene transcription in rat pituitary tumour cells. This stimulation is thought to be mediated by the binding of nuclear T3 receptors to regulatory elements 5' to the transcriptional start site. Understanding of the mechanism by which thyroid hormone activates gene transcription has been limited by failure to purify nuclear T3 receptors because of their low abundance, and by the absence of defined T3 receptor-DNA binding sites affecting T3 regulation. Recently, human and avian c-erb-A gene products have been shown to bind thyroid hormone with high affinity and to have a molecular weight and nuclear association characteristic of the thyroid hormone receptor. In the present report, we describe the development of an avidin-biotin complex DNA-binding assay which can detect specific, high-affinity binding of rat pituitary cell T3 receptors to the sequence 5'CAGGGACGTGACCGCA3', located 164 base pairs 5' to the transcriptional start site of the rat growth hormone gene. An oligonucleotide containing this sequence transferred T3 regulation to the herpes simplex virus thymidine kinase promoter in transfected rat pituitary GC2 cells, and specifically bound an in vitro translation product of the human placental c-erb-A gene. The data provide supporting evidence that the human c-erb-A gene product mediates the transcriptional effects of T3 and also that GC2 cell nuclear extracts contain additional factors that modify the binding of pituitary T3 receptors to the rat growth hormone gene T3 response element.

Animals↗

PubMedDate not supplied

The in vivo survival of human red cells with low oxygen affinity prepared by the osmotic pulse method of inositol hexaphosphate incorporation.

The purpose of this study was to determine the posttransfusion survival of low-affinity red cells (RBCs) containing the hemoglobin modifier, inositol hexaphosphate (IHP). An osmotic pulse technique was used to incorporate IHP, a compound that normally does not cross the RBC membrane. Two groups of six volunteers were studied. RBCs were treated under conditions that resulted in a relatively large increase in mean corpuscular volume (delta MCV = 11.8 +/- 4.0, 1 SD) in Group I, but a relatively small increase (delta MCV = 5.5 +/- 1.9) in Group II. The groups had a similar decrease in mean corpuscular hemoglobin (delta MCH = -3.8 +/- 0.9 for Group I and -3.1 +/- 1.1 for Group II). The 24-hour posttransfusion RBC survival, measured with 3 mL of 51Cr-labeled autologous RBCs, correlated with the induced change in oxygen affinity, and larger shifts were associated with poorer survival. An acceptable 75-percent 24-hour posttransfusion survival was achieved for p50 increases up to approximately 15 torr. Cells that survived 24 hours appeared to have a normal lifespan. This study is the first demonstration of adequate survival for human RBCs with a potentially long-lasting decrease in oxygen affinity.

Blood Transfusion↗

PubMedDate not supplied

The importance of individual optimization of tRNA aminoacylating conditions.

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Acylation↗

PubMedDate not supplied

[Tuberculous meningitis].

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Adolescent↗

PubMedDate not supplied

[Absence of bacteremia after dental extractions].

A study was made on 100 subjects of both sexes between the ages of 3 and 15 years to detect the presence of bacteria in the circulation after performing dental extractions. Two groups were formed of 42 and 57 subjects respectively. One of these groups was subjected to preoperative antisepsis of the region to be operated on, the rest of the conditions were similar for both groups. All the patients were submitted to a preoperative gingival smear and 5 c.c. of blood taken for cultures. Two postoperative blood cultures, one immediately after the operations and another 24 hrs. later were also done in all patients. All the extracted teeth presented severe infections at the root level and some showed complicated infection such as osteomyelitis. All blood cultures performed 24, 48, 72 hrs. and 21 days after the operation, were negative; therefore, there is no justification based on the study, to assume the existance of focal infection related to the presence of bacteremia.

Adolescent↗

PubMedDate not supplied

Expression of HECA-452 in parapsoriasis and mycosis fungoides.

We have investigated the HECA-452 expression in large plaque parapsoriasis (PP) and mycosis fungoides (MF) patients, evaluating the potential role of this biomarker in both cutaneous disorders. Skin specimens from 72 PP and 61 MF patients were selected in this study. We compared their actual histological diagnosis with their previous diagnosis and we found that all 72 PP patients had the same diagnosis as before (stable PP), while 26 out of 61 MF had a previous PP histological diagnosis (evolving PP). Our results show an increased expression of HECA-452 in MF compared to PP (p<0.01). Furthermore, evolving PP showed a significantly higher level of HECA-452 than stable PP (p<0.05). We conclude that HECA-452 expression increases during the natural history of Mycosis Fungoides. HECA-452 could be used as a biomarker for MF and predict which PP evolves to MF.

Antibodies, Monoclonal↗

PubMedDate not supplied

[Methacholine test in the study of non-specific bronchial reactivity in a group of patients allergic to pollen].

We have studied thirty subjects sensitive to pollens suffering from seasonal rhinitis and/or mild seasonal asthma. The patients were submitted to a preseasonal and to a seasonal evaluation of their bronchial reactivity by means of a metacholine provocation test in order to measure possible variations of their responsiveness. Our data shown that the metacholine provocation test is not substantially influenced by seasonal pollen stimulation; it is likely that in patients sensitive to pollens, aspecific bronchial reactivity is intermittent, so explaining the inconstant behaviour of responsiveness observed in our allergic patients.

Adolescent↗

PubMedDate not supplied

[Development of molecular probes for the diagnosis of mycobacteria].

The presence of a repetitive sequence in Mycobacterium bovis DNA was demonstrated. This sequence was also found in M. tuberculosis DNA but was absent in M. kansasii, M. flavescens, M. fortuitum, M. vaccae, M. leprae, M. phlei, M. smegmatis and M. marinum. This repetitive sequence was found to be polymorphic in M. tuberculosis but not in BCG. Dot hybridization analysis suggested that the repetitive sequence could be useful in the identification of pathogenic Mycobacterium in clinical samples.

DNA Probes↗