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Biomedical subjects

P Giraud

Publications and source records attributed to P Giraud.

At least 19 recordsLinked to original sources
PubMed1992

Ontogeny of prolyl endopeptidase, pyroglutamyl peptidase I, TRH, and its metabolites in rat pancreas.

We demonstrate that two enzymes, soluble unspecific pyroglutamyl peptidase I and prolyl endopeptidase, able to degrade thyrotropin-releasing hormone (TRH) in vitro were present in pancreas at the early stage of rat development. Specific particulate pyroglutamyl peptidase II remained undetectable during ontogenesis. Pyroglutamyl peptidase I specific activity increased until day 3 and decreased after day 5. Furthermore, prolyl endopeptidase specific activity rose slightly to a peak on postnatal day 20. A good correlation between immunoreactive TRH and deaminated TRH (TRH-OH) was found in the 1st wk after birth. However, His-Pro diketopiperazine (DKP) levels were stable and low during development. We show that hot acidic extraction conditions could artefactually generate His-Pro DKP. In vivo, active site-directed inhibitors of pyroglutamyl peptidase I and prolyl endopeptidase enzymes do not show any TRH-deamidating and/or pyroglutamyl peptidase I pathways in neonatal rat pancreas. The data suggest that these two enzymes are not involved in intra- or extracellular control of TRH levels in neonatal rat pancreas and that pancreatic TRH content appears to be principally regulated by biosynthetic steps. Nevertheless, low levels of endogenous His-Pro DKP and TRH-OH identified in neonatal rat pancreas suggest that TRH or TRH-like peptides may be metabolized in this tissue in intact rats, albeit at low rates.

Aging↗
PubMed1992

Assignment of the beta-thyroid hormone receptor to 3,5,3'-triiodothyronine-dependent inhibition of transcription from the thyrotropin-releasing hormone promoter in chick hypothalamic neurons.

Thyroid hormone, T3, is essential to the normal development and metabolism of vertebrates. Fine tuning of circulating levels of T3 is critical and involves feedback inhibition of the TRH and TSH genes by T3 at the hypothalamic and hypophyseal levels. However, the molecular basis of T3 inhibition of TRH gene expression in the hypothalamus is not known. The actions of T3 on target gene expression are mediated through nuclear receptor proteins, TR alpha and TR beta. To examine their effects on T3-dependent transcription from the rat TRH promoter, we used a gene transfer technique to express TR alpha and TR beta in cultured embryonic chick hypothalamic cells. Transcription from the TRH promoter construct transfected into these cultures was depressed in the presence of 10(-9) M T3. Cotransfecting TR alpha or TR beta activated transcription from the TRH promoter. However, only TR beta-dependent TRH transcription was differentially modulated by T3. Physiological concentrations of T3 decreased TR beta-dependent TRH transcription 4-fold. Thus, when T3 levels increase, TR beta mediates inhibition of TRH expression, a key step in down-regulating the hypophyseal-thyroid axis. This study demonstrates for the first time a T3-dependent differential regulation of the TRH promoter by TR beta and not TR alpha. Thus, the negative regulation of the TRH promoter in transiently transfected primary embryonic chick hypothalamic neurons provides a useful system for studying the molecular actions of thyroid hormone receptors.

Animals↗
PubMed1992

[Investigation of phosphorus calcium metabolism after oral phosphorus supplementation].

Effects of oral administration of phosphorus on phosphorus and calcium parameters and on bone metabolism hormones were investigated in two studies: in the first, 12 young female adults and 8 females over 50 years of age took a single oral load dose of 780 mg elemental phosphorus, whereas in the second study assays were performed 5 and 15 days after initiation of twice-daily phosphorus supplements in 19 young adults, 14 subjects above 50 years of age who were free of osteoporosis, and 12 patients with osteoporosis also over 50 years of age. The phosphorus load was associated with an increase in intact parathyroid hormone levels (iPTH 1-84), which was more marked in subjects above 50 years of age than in younger adults. On the 15th day of phosphorus supplementation, there was no significant increase in baseline iPTH and no change in baseline dihydroxyvitamin D or osteocalcin levels; during the Nordin tests, the fractional calcium excretion index (CaU/CrU) and the fractional hydroxyproline excretion index (OH Pro/CrU) remained unchanged. In contrast, the phosphorus load was followed by a decrease in the maximum phosphorus reabsorption threshold (TMP/DFG), which was more marked on the 5th day than on the 15th day; a slight fall in serum phosphorus levels was also seen on the 15th day. These findings suggest that phosphorus supplementation should be intermittent rather than continuous. Analysis of subjects aged 50 to 69 years failed to disclose any significant differences between patients with and without osteoporosis.

Administration, Oral↗
PubMed1992

[Initial stability and pelvic deformation in cemented and non-cemented acetabular components].

Periacetabular surface deformation of the pelvis and micromotion between implant and bone were measured in three cementless acetabular components. Pelvic deformation was greater in cementless implants than in cemented ones-independent of the stiffness of the implant. The results of micromotion measurements confirmed the function of certain of anchorage concepts, but they also illustrated the limitations of such measurements in single locations.

Acetabulum↗
PubMed1991

Evidence for pyroglutamyl peptidase I and prolyl endopeptidase activities in the rat insulinoma cell line RINm 5F: lack of relationship with TRH metabolism.

Thyrotropin-Releasing hormone (TRH)-degrading pyroglutamyl peptidase I (PGP I) and prolylendopeptidase (PE) activities have been demonstrated in rat insulinoma RINm 5F cell line. These two enzymes catalyze the conversion of TRH to Histydyl-Proline-Diketopiperazine and to acid TRH respectively. After cell fractionation, we found all the PGP I and PE activities in the cytosolic fraction. The membrane-bound PGP II activity is not detectable in the RINm 5F cells. Further investigations on these two cytosolic enzymes show that pyroglutamyl- and proline-containing peptides are inhibitors of each TRH-degrading enzyme. Gel filtration chromatography on Sephadex G100 shows that PGP I and PE activity have an apparent molecular mass of about 18 kDa and 57 kDa, respectively. Kinetic analysis with TRH as substrate, gives a Km of 44 microM and 235 microM, and a Vmax of 1.49 and 8.80 pmol/min/micrograms protein for PGP I and PE, respectively. Immunoreactive TRH, His-Pro-Diketopiperazine and acid TRH levels in the cell line extracts are 2.2 +/- 0.9, 22.5 +/- 11.1 and 28.7 +/- 14.6 pg/1O6 cells, respectively. When cells have been incubated for 2 to 72 hours with a P.E. inhibitor (Z-Gly-Pro-CHN2) at 5 x 10(-7) M, both cell PGP I and PE activities are inhibited. No change in the cellular content of immunoreactive TRH, His-Pro-Diketopiperazine and acid TRH have been observed in treated cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma, Islet Cell↗
PubMed1991

Striatal proenkephalin turnover and gene transcription are regulated by cyclic AMP and protein kinase C-related pathways.

Preproenkephalin metabolism, in the rat, was studied in primary striatal neurons maintained in a chemically defined medium. Acute treatment (30 min) with forskolin (10(-5) M) or phorbol 12 myristate 13 acetate (10(-7) M) resulted, respectively, in a two- and seven-fold increase in methionine-enkephalin secretion. Chronic treatment with forskolin or phorbol 12 myristate 13 acetate (24 h) induced a 100% increase in methionine-enkephalin content (forskolin) and on the other hand a 50% decrease in methionine-enkephalin (phorbol 12 myristate 13 acetate). Both treatments increased preproenkephalin mRNA levels in a time-dependent manner, this augmentation being observable after 180 min by Northern blot analysis and in situ hybridization. These data indicate that under chronic stimulation, with either forskolin or phorbol 12 myristate 13 acetate, proenkephalin turnover is accelerated. However, after stimulation with phorbol 12 myristate 13 acetate, the more potent methionine-enkephalin secretagogue, increased peptide synthesis is not sufficient to replenish methionine-enkephalin intracellular stores. Preproenkephalin gene transcription was analysed by introducing the preproenkephalin gene promoter fused to the bacterial acetyl chloramphenicol transferase reporter gene into primary neurons. Chronic stimulation (48 h) by forskolin (10(-5) M) or phorbol 12 myristate 13 acetate (10(-7) M) of striatal neurons transfected with this fusion gene increased chloramphenicol acetyltransferase activity six-fold and the two effects were additive. These data suggest that the cyclic AMP and the protein kinase C pathways directly activate preproenkephalin gene transcription.

Animals↗
PubMed1991

Telematic transmission of computerized blood glucose profiles for IDDM patients.

OBJECTIVE: To improve the analysis of self-monitoring of blood glucose (SMBG) and its communication between patients and physicians by a telematic transmission of computerized SMBG and to study the consequences of its use on glucose control of insulin-dependent diabetic (IDDM) patients. RESEARCH DESIGN AND METHODS: A prospective randomized crossover trial with two 3-mo periods, one with SMBG recorded on traditional booklets (booklet period) and another with computerized SMBG transmitted to a central data base through a telematic network (telematic period), comprised the study. During the latter phase, patients could receive computerized SMBG analysis on individual terminals connected to the telephone network (Minitel system). Blood glucose recordings and HbA1c were measured at inclusion and end of each period. Eleven pairs of IDDM patients on intensified insulin therapy were randomized within each pair to start with the telematic period (group A) or the booklet period (group B). RESULTS: Telematic transmissions were successful (less than 1% failure rate). Although initial HbA1c was low (6.7%), it declined during the telematic period (delta = -0.41%) compared with the booklet period (delta = +0.37%, P = 0.05). The percentage of low (less than 3.3 mM) blood glucose values correlated with HbA1c changes during the telematic period (r = 0.714, P = 0.0014) but not the booklet period. The patients favored the telematic tool to analyze SMBG. CONCLUSIONS: Telematic transmission of SMBG is feasible. It can improve SMBG analysis and perhaps glucose control, therefore offering a new way of communication between diabetic patients and their physicians.

Blood Glucose↗
PubMed1991

[Role of beta thyroid hormone receptor in the modulation of the TRH transcription].

Two genes coding for thyroid hormone (T3) receptors (THR) have been identified: THR alpha and THR beta. To determine their transcriptional effects we transfected reporter genes expressing chloramphenicol acetyl transferase (CAT) alone or with vectors coding for THR alpha or THR beta in primary cultures of embryonic chick hypothalami. Transcription from a promotor containing a T3 Response Element (T3RE-CAT), was activated in the presence of tri-iodo thyronine (T3) and much reduced in the absence of the hormone. In contrast, in the absence of T3, transcription from the Thyrotropin releasing hormone (TRH) promoter (TRH-CAT) was much greater than in cultures grown with T3. In cotransfection experiments where THR alpha or THR beta was expressed with the TRH promoter construct, THR beta-dependent transcription, but not THR alpha-dependent transcription, was significantly reduced in the presence of T3.

Animals↗
PubMed1991

[A study of primary mooring and deformation of the peri-acetabular area under static load].

We propose a method to study the primary stability and the periacetabular deformation under static load, with and without cemented and cement-free acetabular implants, using a biomechanical model that stimulates the balance mechanism described by Pauwels. The biomechanical model uses whole pelvises of recently frozen corpses. We have imitated the gluteus medius and minimus muscles on the pelvis with cables and pulleys. The loading device comprises a metallic frame, on which a hydraulic press is set up for static testing, and a prototype femoral prosthesis made of two main parts: one on which the gluteal muscles are inserted, and another one on which the femoral head is attached. The pelvis is fixed to the metallic frame by a plate attached to the sacrum and allowing movements in all planes of space. The measurement method utilizes: for primary stability, four transducers, including three three-directional ones, in the three planes of space outside the pelvis, only one being located inside the pelvis with a 16 degrees orientation relative to the vertical; for deformation, a transducer located in three different places in the periacetabular region. We have used ten freshly frozen pelvises with six different implants (two with and four without cement) and eighteen implantations.

Acetabulum↗
PubMed1991

Thyroliberin (TRH) and TRH free acid (TRH-OH) present in milk do not originate from local synthesis in mammary gland.

UNLABELLED: Hypothalamic hormones represent a peculiar group of hormones present in milk in surprisingly high concentrations. High levels of these neuropeptides raised the question of their origin. The hypothesis suggesting local synthesis of TRH in the mammary gland was, therefore, tested. Acid extracts of human milk contained TRH and TRH-OH immunoreactivity. RIA determinations at various purification steps revealed that only a part of the immunoreactivity may represent authentic peptides. No high molecular weight TRH precursor could be demonstrated upon a sequential enzymatic treatment of human milk and rat mammary gland extracts. Exploration of rat mammary gland tissue for TRH mRNA showed that the TRH gene is not expressed in the mammary gland. Rat mammary gland homogenates were able to deamidate exogenous TRH to TRH-OH. CONCLUSION: TRH is not synthesized in the mammary gland via a high molecular weight precursor. It is likely that the TRH-free acid in milk (demonstrated for the first time in this product) originates from TRH deamidation in mammary gland cells during TRH transport from the blood.

Breast↗
PubMed1990

Characterization of an alpha-amidating activity in a human pancreatic tumour secreting vasoactive intestinal peptide (VIP).

A case of watery diarrhoea hypokalaemia achlorhydria (WDHA) syndrome due to a pancreatic tumour and identified by VIP plasma level, VIP immunocytochemistry, and ultrastructural analysis of tumour sections, is reported. Since VIP is the mediator of the syndrome and is biologically active under its amidated form, the enzymatic alpha-amidating activity was investigated and characterized in tumour extract; using the synthetic substrate D-Tyr-Val-Gly, the enzyme displayed an optimal activity at pH 7.0, under aerobic conditions and with 35 microM CuSO4 and 3 mM ascorbate as co-factors. The Kmax and Vmax values of the enzymatic activity were 133.7 microM and 26.9 pmol/h/micrograms protein respectively. Its molecular weight, determined by molecular sieving, was close to 36 kDa. Other tumours of the human endocrine pancreas were also investigated for the enzymatic activity. The clinical interest of studying the regulation of the alpha-amidating activity in such tumours is discussed.

Female↗
PubMed1990

[Urinary excretion of albumin and lipid abnormalities in hypertensive insulin-dependent diabetics].

Patients with insulin dependent diabetes mellitus (IDDM) often suffer from cardiovascular diseases as renal failure occurs. Elevated albumin excretion rate (AER) is a predictive value of this event. Relations between AER, blood pressure, serum lipids and apoproteins concentrations in 100 patients with IDDM have been surveyed. Twenty one hypertensive patients (HT group) were compared to 21 patients without hypertension (n HT group), matched for sex, age, diabetes duration, and metabolic control, assessed by glycosylated haemoglobin. Comparison of both groups showed HT group had elevated systolic blood pressure (137 +/- 12 vs 126 +/- 20 mmHg; p less than .05), elevated diastolic blood pressure (80 +/- 7 vs 71 +/- 8 mmHg; p less than .001), increase in AER (27 range 3-4023 vs 6 range 2-51 mg/day; p less than .001), slightly elevated serum creatinine (95 +/- 32 vs 78 +/- 15 mumol/l; p less than .05). In HT group, serum lipid composition showed: raise in total cholesterol (251 +/- 43 vs 221 +/- 41 mg/dl; p less than 0.5), elevated apoprotein B (130 +/- 30 vs 99 +/- 21 mg/dl; p less than .001) elevated apoprotein B/apoprotein A1 ratio (.91 +/- .32 vs .66 +/- .27; p less than .001), elevated triglycerides (157 +/- 53 vs 98 +/- 43 mg/dl; p less than .005) and elevated LDL-cholesterol (170 +/- 42 vs 143 +/- 33 mg/dl; p less than .05). Levels of apoprotein A1 and HDL-cholesterol were not significantly different. Body mass index, daily insulin requirement and tobacco usage were similar in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Ontogenetic expression of peptidyl-glycine alpha-amidating monooxygenase mRNA in the rat pancreas.

Qualitative and quantitative expression of m.RNA coding for Peptidyl-Glycine alpha-Amidating Monooxygenase (PAM) in the developing rat pancreas was investigated by Northern and dot blot hybridization, with a bovine PAM c.DNA probe (0.7 kb fragment). A specific hybridization signal was evidenced for a 3.7 kb m.RNA species. Measurement of PAM m. RNA rate during the rat pancreas ontogenesis revealed a biphasic profile which appeared corelated with that of gastrin and TRH m.RNA respectively. On the other hand, streptozotocin-treatment resulted in a 50% decrease of PAM m.RNA levels.

Aging↗
PubMed1989

Thyrotropin releasing hormone in the pancreas of newborn rats from streptozotocin-treated mothers.

The effect of maternal diabetes (induced by i.p. injections of 40-50 mg/kg BW Streptozotocin on the day of mating) on TRH in the pancreas of newborn rats was studied. Determination of peptide alpha amidation activity and TRH precursor level on the day of birth revealed decreased biosynthesis of TRH resulting in profoundly (10 times) lower pancreatic TRH and TRH-OH concentrations in pups of diabetic rats. Pancreatic His-Pro-diketopiperazine (His-Pro-DKP) remained unaffected by maternal diabetes. The depression of pancreatic TRH was less profound 24 h later, and even elevated TRH was measured in the pancreas of pups of diabetic mothers on postnatal day 5. Short term postnatal starvation or nursing of intact pups by the diabetic foster mother did not affect pancreatic TRH. It could be postulated that postnatal TRH development in the rat pancreas is retarded by maternal diabetes, while His-Pro-DKP remains unaltered.

Aging↗
PubMed1988

Ontogeny of enkephalin- and VIP-containing neurons in dissociated cultures of embryonic mouse spinal cord and dorsal root ganglia.

The ontogeny of vasoactive intestinal polypeptide (VIP), and Met-enkephalin in primary cultures of spinal cord/dorsal root ganglia from 12-day mouse embryos was examined by radioimmunoassay and immunohistochemistry. Met-enkephalin levels rose from less than 5 to 700 pg/culture over 26 days and were half maximal by day 16-18 in culture. VIP levels rose from less than 1 to 30 pg/culture over the same period, but were already half maximal by day 9. Met-enkephalin immunoreactivity was localized in multipolar medium sized neurons while VIP immunoreactivity was visualized both in neurons with extensively branched processes and in bipolar cells some of which appeared to be dorsal root ganglion cells. Tetrodotoxin (TTX)-sensitive spontaneous release of both peptides developed in parallel with the ability to stimulate peptide release with elevated potassium. Factors affecting the ontogeny of neuropeptide expression in, and release from, spinal cord neurons can now be examined in vitro in a strictly defined neurochemical environment.

Animals↗