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Biomedical subjects

J Grenier

Publications and source records attributed to J Grenier.

At least 91 records · Page 5Linked to original sources

Aberrant recombination events in B cell lines derived from a kappa-deficient human.

We have analyzed the structure of Ig kappa chain genes in B cell lines derived from a human individual who cannot synthesize any kappa chains, and whose Igs all contain lambda chains (1). We have characterized secondary DNA recombination events at two kappa alleles which have undergone misaligned V-J recombinations. One such secondary recombination has joined the flanking sequences of a V kappa and a J kappa 2 gene segment as if it were the reciprocal product of a V-J kappa 2 recombination, and resulted in the displacement of the recombined VJ kappa 1 gene segments from the C kappa locus. The non-rearranged form of the V kappa fragment which had recombined with the J kappa 2 flank was cloned. Nucleotide sequencing of this fragment identified a V kappa gene that differed by at least 38% from all previously sequenced human V kappa genes. The other V-J kappa segment analyzed has undergone a secondary recombination at a different site from that described above, at a site within the intervening sequence between the J kappa and C kappa gene segments, similar to the location of secondary recombinations which have occurred in lambda + B cell lines from mice and humans (2,3). These results prove that multiple recombinations can occur at one J kappa-C kappa locus.

B-Lymphocytes↗

[Haloperidol. Plasma monitoring and hormonal effects of treatment].

Therapeutic plasma monitoring of haloperidol, a major neuroleptic, measured by radioimmunoassay, has shown a rather good correlation between plasma level and dosage but with large interindividual variation in children as in adults; age seems not to have any effect on haloperidol metabolism. 80% of subjects present a concomitant prolactin levels variation, whereas in 20% no prolactin response is found. During acute kinetics of either a 10 mg oral haloperidol administration or a 250 mg intramuscular haloperidol decanoate injection, a parallel elevation of prolactin, cortisol, immunoreactive bêta-endorphin and bêta-lipotropin plasma levels occur, at the same time as haloperidol plasma levels. Those rise with a good equivalence between the two doses of the two forms.

Administration, Oral↗

Edinger-Westphal nucleus: cholecystokinin immunocytochemistry and projections to spinal cord and trigeminal nucleus in the cat.

Immunocytochemical methods were used to determine the distribution of cells with cholecystokinin-like immunoreactivity (CCK-LI) in the cat Edinger-Westphal complex (EW). Numerous cells with CCK-LI are found throughout the length of EW. The distribution and frequency of such cells are similar to the pattern of EW neurons that show substance P-like immunoreactivity (SP-LI). Companion retrograde transport experiments reveal that EW neurons which project to spinal cord or the region of the caudal trigeminal nucleus are found throughout the length of EW, and that some EW neurons which project to spinal cord also show CCK-LI.

Animals↗

Beta-2-microglobulin in myeloma: optimal use for staging, prognosis, and treatment--a prospective study of 160 patients.

Previous reports have shown that serum beta-2-microglobulin (S beta2M) is a reliable marker of presenting tumor mass, response to chemotherapy, and prognosis of patients with multiple myeloma (MM). In order to more thoroughly evaluate the optimal use of S beta2M in plasma cell dyscrasias (PCD), S beta2M levels were serially measured in 160 patients with MM, in comparison with 37 normal controls (NC) and 28 patients with monoclonal gammopathy of undetermined significance (MGUS). In MGUS, S beta2M did not differ significantly from that of NC, but was significantly lower than that of MM (p less than 0.001), including low cell mass MM (p less than 0.02). In MM, S beta 2M was highly correlated with the total body burden of myeloma cells as derived from the staging of Durie and Salmon, both at diagnosis and in remission (residual tumor mass) (p less than 0.001). During the plateau phase, S beta 2M remained very stable and was always within the normal range for patients with greater than or equal to 75% tumor regression. The most striking finding was that S beta 2M gave an extremely reliable fit for survival prediction at (1) diagnosis, (2) remission, and (3) early relapse, with higher S beta 2M levels in each instance being in favor of poorer prognosis. We conclude that S beta 2M is an extremely useful marker in initial stratification and follow-up of patients with MM.

Humans↗

Serum beta2 microglobulin and survival duration in multiple myeloma: a simple reliable marker for staging.

Previous reports have shown serum beta2 microglobulin (SB2M) to be a reliable marker for evaluation of presenting tumour mass, response to chemotherapy and prognosis of patients with multiple myeloma (MM). In the current study, SB2M was evaluated and correlated by bivariate and multivariate regression analyses with the main presenting clinical features, response to chemotherapy and survival duration of 115 untreated myeloma patients. In the bivariate analysis, there was a clear correlation between SB2M and myeloma stage (P = 0.002). Other interesting correlations were between SB2M and creatinine values (P less than 0.001), SB2M and the likelihood of having lambda subtype (P less than 0.001), high SB2M and high uric acid (P less than 0.036), high SB2M and a low haemoglobin (P less than 0.001). In the multivariate regression analyses, SB2M alone completely substituted for the effect of initial staging and gave a very reliable fit for survival prediction. Particularly noteworthy was the dramatic difference in survival duration observed between patients with a high pre-treatment SB2M (greater than 6 micrograms/ml) and those with low SB2M: 26 months versus 52 months (P less than 0.0001). We conclude that SB2M is the major determinant of survival in MM and can be used alone for effective pretreatment stratification of myeloma patients.

Adult↗

[Plasma and intrafollicular hormone profiles in the late preovulatory phase. I. Spontaneous cycles].

The hormone state of development in the late preovulatory phase is described in its relationship to the start of the LH surge which occurs 37-39 hours before ovulation. No precise relationship has been found between the oestradiol (E2) peak in the plasma and that which occurs before ovulation. All the same, the succession of hormone events that have been observed in 77 spontaneous cycles is the following: the level of E2 suddenly rises between 35 and 30 hours before the ovulatory discharge and this rise is immediately followed by a rise in the level of LH. Then the plasma concentration of 17-hydroxyprogesterone (17-OHP) increases 5 hours before the LH surge. In the preovulatory follicle 5 hours after the start of the LH surge, a drop in the level of E2 and a rise in the level of progesterone is noted. Concentrations of androgens only lessen in the last 12 hours before ovulation whereas the level of 17-OHP stays stable. We have thus been able to work out the sequence of plasma hormone phenomena that occur in determining whether a preovulatory gonadotrophic surge will occur. We have described the hormone levels in follicular fluid immediately before spontaneous ovulation. These findings will be able to serve as a reference to evaluate the quality of the late preovulatory phase in abnormal cycles or in cycles that have been induced.

Adult↗

Serum beta-2-microglobulin in multiple myeloma: relation to presenting features and clinical status.

Serum beta-2-microglobulin (B2m) levels were measured in 78 patients with multiple myeloma (MM) and were compared with values for normal individuals and patients with benign monoclonal gammopathies (BMG). Serum B2m levels and values corrected for renal function were significantly higher in patients with MM at time of diagnosis than in normal individuals (P less than 0.001) and were highly correlated with the total body burden of myeloma cells as derived from the staging system of Durie and Salmon. However there were no significant differences between values for BMG and low-mass MM. For patients evaluated following induction chemotherapy, there was also a clear correlation between serum B2m levels and the magnitude of tumor regression or progression (P less than 0.05). During the plateau-phase, serum B2m levels remained very stable and highly correlated with the residual tumor mass (P less than 0.001). It was concluded that (1) B2m was not a reliable marker to distinguish between BMG and low-mass MM and (2) B2m was a valuable marker for assessing initial tumor mass of patients with MM and response to chemotherapy (especially the plateau-phase), above all in patients with urine or low-serum monoclonal component levels.

Antineoplastic Agents↗

Steroid hormone levels in peritoneal fluid during the periovulatory period.

In order to obtain further information on estradiol (E2) and progesterone (P) patterns during the periovulatory period, their levels were determined in peritoneal fluid (PF) and plasma obtained during 22 laparoscopies performed within the 58 hours following the luteinizing hormone surge-initiating rise (LH SIR) determined by plasma LH assays every 6 hours. E2 levels in plasma and PF did not differ before ovulation (n = 13) but differed after ovulation (n = 9, P less than 0.01). P levels were lower in plasma than in PF before ovulation, but there was an overlap of values. After ovulation the difference was significant (P less than 0.01). When plotted as a function of time following LH SIR, E2 levels increases in PF progressively (r = 0.70), whereas the P increase was discontinuous, with a dramatic rise after follicular rupture. These different patterns may be related to respectively divergent and convergent variations of steroid levels in blood and follicular fluid.

Adult↗

Ultrastructural changes in the rat exocrine pancreas after jejunoileal bypass.

The influence of a 90% jejunoileal bypass on the rat exocrine pancreas was studied by morphometrical procedures. In sham-operated animals exocrine acinar cells accounted for 80.3% of the pancreas volume. These cells are composed of 9.9% nuclei, 8.4% mitochondria, 12.2% zymogen granules, 0.3% lipid droplets and 69.2% of a compartment ("ERGLS") composed of endoplasmic reticulum, ribosomes, Golgi areas, lysosomes and the cytoplasmic ground substance. Intestinal bypass did not change the volume density of exocrine cells nor that of nuclei in the cells during the three postoperative months. The means nuclear diameter was approximately the same in both groups. However, the volume density of secretory granules diminished by 50%. This was accompanied by a decrease in mean granular diameter, but not in their numerical density. The volume density of lipid droplets increased 10 fold, that of mitochondria increased slightly from the 15th postoperative day but significantly from the 45th day. The remaining cellular compartment composed of "ERGLS" was not modified by intestinal bypass. These findings suggest that a 90% jejunoileal bypass induces major changes in the composition of pancreatic acinar cells but not in their size.

Animals↗

Falsely elevated serum thyrotropin (TSH) in newborn infants: transfer from mothers to infants of a factor interfering in the TSH radioimmunoassay.

In a TSH screening program for congenital hypothyroidism we detected seven newborn infants with normal plasma T4 and T3 levels but high immunoassayable TSH. Similar findings were obtained in their mothers. Serial plasma dilution curves, with and without the addition of normal rabbit serum to the samples, showed that the result of TSH assay performed with antihuman TSH rabbit antiserum was falsely elevated in mothers and infants by an interfering factor. Follow-up of the infants demonstrated that the falsely elevated plasma TSH levels returned to normal within the first 6 months of life. On the contrary, plasma TSH levels remained high in the mothers. These results suggested a placental transfer of maternal antibodies. Indeed, the analysis of the mothers anamnesis revealed that all had previously received injections of a microbial vaccine cultured on a rabbit lung-containing medium. We conclude that placental transfer of a maternal antirabbit factor may cause an artefactual hyperthyrotropinemia in the newborn and the incorrect diagnosis of neonatal hypothyroidism. This can be avoided by the addition of normal rabbit serum or immunoglobulin to the TSH RIA tubes.

Animals↗

[Serum beta-2-microglobulin in multiple myeloma. Practical value].

The concentration of serum, beta-2-microglobulin (S beta 2m) and the ratio measured S 2m/theoretical S beta 2m M/TH were evaluated in 69 patients with multiple myeloma (MM) and compared with healthy subjects and with patients with a benign monoclonal gammapathy. The concentration of S beta 2m and the ratio S beta 2m M/TH are higher in multiple myeloma than in controls and are strongly correlated with the plasma cell mass On the other hand, no difference was noted concerning the S beta 2m and the ration S beta 2m M/TH between benign monoclonal gammopathy and multiple myeloma at stage I of Durie and Salmon. Under chemotherapy, the variations in concentrations of S beta 2m and of the ratio S beta 2m M/TH are strongly correlated with those of the tumour mass. Beta 2m is not very useful for the differential diagnosis between benign monoclonal gammapathy and multiple myeloma. Beta 2m is very useful in the prognosis of MM, permitting one to assess accurately the tumour mass and the response to treatment, particularly in cases of deficiency of the usual markers.

Beta-Globulins↗

[Recovery of preovulatory human oocytes (author's transl)].

Rapid radio-immune assaying of LH was carried out four times daily on 52 women in the preovulatory phase of the cycle. This method enables the precise detection of the LH surge and recovery of the mature oocyte by laparoscopic aspiration of the follicular content, just before ovulation, which is between 28 and 36 hours after the start of the LH surge. The oocytes was recovered in 27 out of 41 patients with a normal cycle (66%). The rate of recovery per follicle aspirated is comparable in a natural cycle to that after treatment with Clomid (80 to 84%).

Adult↗