Group Of pH Research Articles

Prospective molecular monitoring of BCR/ABL transcript in children with Ph+ acute lymphoblastic leukaemia unravels differences in treatment response.

Children with Philadelphia-chromosome-positive (Ph+) acute lymphoblastic leukaemia (ALL) represent a subgroup at very high risk for treatment failure, despite intensive chemotherapy. However, recent retrospective studies showed that Ph+ childhood ALL is a heterogeneous disease with regard to treatment response. We have prospectively monitored, by reverse transcription polymerase chain reaction (RT-PCR) during follow-up, the presence of the BCR/ABL fusion transcript in Ph+ ALL children diagnosed in the Italian multicentre Associazione Italiana Ematologia Oncologia Pediatrica ALL-AIEOP-95 therapy protocol. To our knowledge, this is the first report on the evaluation of minimal residual disease (MRD) in childhood Ph+ ALL prospectively enrolled in an intensive, Berlin-Frankfurt-Munster (BFM)-type treatment protocol. Twenty-seven of 36 (75.0%) Ph+ patients consecutively enrolled into the high-risk group of the AIEOP-ALL protocol between May 1995 and October 1999 were successfully analysed. Twenty were good responders to the pre-phase of prednisone/intrathecal methotrexate treatment (PGR) and seven were poor responders (PPR). Within the PPR group, the RT-PCR monitoring constantly showed positivity for the BCR/ABL fusion transcript and all the patients died of disease progression. In contrast, highly sensitive qualitative RT-PCR monitoring revealed heterogeneity within the PGR group of Ph+ childhood ALL patients. Three different subgroups could be defined, according to the clearance of Ph+ cells within the first 5 months of treatment. This provides useful information on the capability of chemotherapy to reduce the leukaemic clone, with prognostic implications.

Infrared spectra of the H-bound and π-bound isomers of the phenol–argon cation

Infrared photodissociation spectra of the phenol–argon cation (Ph +–Ar) are recorded in the vicinity of the O–H stretch vibration ( ν 1) of bare Ph +. Two isomers are identified by their characteristic complexation-induced frequency shifts, Δ ν 1. In H-bound Ph +–Ar, the Ar atom forms an ionic hydrogen bond with the O–H group of Ph + leading to a significant red shift, Δ ν 1∼−70 cm −1. In the π-bound Ph +–Ar isomer, the Ar atom is attached to the π-electron system of Ph +, resulting in a much smaller shift, Δ ν 1∼+2 cm −1. The Ph +–Ar complexes are produced in an electron impact ion source. The relative ν 1 band intensities of both isomers depend strongly on the source conditions and reveal that H-bound Ph +–Ar is the global minimum, while the π-bound structure is a local minimum. Ab initio calculations at the UMP2/6-311G(2df,2pd) level predict binding energies of D e∼660 and ∼400 cm −1 for the H-bound and π-bound minima, with an isomerization barrier of V b∼150 cm −1 from π-bound toward H-bound Ph +–Ar.

Enhancing effect of switching iontophoresis on transdermal absorption of glibenclamide

Glibenclamide(GLI) is widely used as an oral hypoglycemic drug in the treatment of non-insulin dependent diabetes mellitus (NIDDM). We investigated The enhancing effect of switching iontophoresis on the transdermal absorption and reduction of skin irritation to develop a transdermal dosage form of GLI. The 0.1% of Gli suspensions in 0.2 M tris-HCl buffer of pH 7.4, 8.0 and 8.5 were prepared as donor solutions. We examined drug permeation through the excised rat abdominal skin, drug absorption in rats and reduction of skin irritation after application of switching iontophoresis for 1 h using DC 10 V. The solubility of GLI in 0.2 M tris-HCl buffer increased with a rise in pH. In the permeation study, GLI was permeated continuously and the cumulative amount of permeated GLI increased using an alkaline donor solution. In the drug absorption study, the application group of pH 8.5 gave higher plasma concentration levels than those of pH 7.4 and 8.0 groups. The skin irritation evoked by the application of iontophoresis was pathologically studied. A total irritation score (TIS) was estimated as a judging standard for the skin damage. The TIS value increased dependently with a rise in pH. However, it was considered that the skin irritations were not serious and small matters. The results demonstrate the possibility of iontophoretic transdermal administration of GLI and the effect of drug solubility in the donor solution on the absorption of GLI.

AgNOR quantity as a prognostic tool in hyperplastic and neoplastic parathyroid glands.

Prediction of evolution of secondary hyperplasia and tumours of the parathyroid glands is still a problem in histopathology. To assess whether the quantity of silver-stained nucleolar organiser region (AgNOR) proteins might be used as a prognostic tool in parathyroid pathology, a standardised AgNOR analysis has been performed on 19 cases of parathyroid hyperplasia caused by secondary hyperparathyroidism (PH), 8 cases of adenoma (PA) and 10 cases of carcinoma (PC). Clinico-pathological data and follow-up information were available. On formalin-fixed and paraffin-embedded sections, the visualisation and quantification of AgNORs were achieved according to the 1995 guidelines of the Committee on AgNOR Quantification. Then, the mean area (square micrometres) of AgNORs per nucleus (NORA) was evaluated by means of an image analyser and specific softwares. After testing the normal distribution of NORA values, statistical parametric tests were utilised; Kaplan-Meier and Cox multivariate analyses were also performed. In parathyroid lesions, a progressive increase of mean NORA values was observed from PH (2.895 microm2; SE 0.171) through PA (3.638 microm2; SE 0.125) to PC (4.701 microm2; SE 0.179); these differences were highly significant (P<0.001), although some degree of overlap was found among single NORA values. A significantly higher mean NORA value was revealed in PC with distant metastases than was noted in cases with no current clinical evidence of disease progression. Furthermore, a significantly (P<0.001) higher mean NORA value was encountered in the group of PH with recurrences (3.600 microm2; SE 0.106) than in nonrecurrent PH (2.261 microm2; SE 0.087). Multivariate analyses indicated that the NORA value was an independent prognostic parameter determining the risk of recurrence in PH. We suggest that AgNOR quantity may be a promising additional tool for predicting the biological behaviour of parathyroid lesions.

Blood pressure reactivity to mental stress and aerobic fitness in normotensive young adult African–American males with parental history of hypertension

Hypertension (HT) is the leading health problem in the adult African–American (AA) community and is associated with risk factors of stress, physical inactivity, and family history. We examined the influences of aerobic fitness and parental history of HT on blood pressure (BP) reactivity to mental stress in 60 normotensive young adult AA males. A 5-min mental arithmetic test was used as a provocative stress. Measurements of peak oxygen uptake (V̇O2peak) were used to classify physically active and inactive subjects into groups of high and low aerobic fitness. A questionnaire was used to evaluate parental BP histories. Reactivity of BP was indexed by differences in values (delta) measured during baseline and stress testing periods. Subjects with a parental history of HT (PH+) had significantly higher baseline systolic BP and mean arterial BP (SBP, MABP) values than subjects with no parental history of HT (PH−). Among the group of PH+ subjects, BP reactivity to mental stress was as follows: the high aerobic fitness subgroup (V̇O2peak=54.6±1.2 ml/kg/min) (n=15) exhibited a 7.3±2.0 mmHg rise in SBP and a 3.2±2.0 mmHg rise in MABP, and the low aerobic fitness subgroup (V̇O2peak=37.1±0.7 ml/kg/min) (n=15) had a 15.8±2.0 mmHg rise in SBP and an 11.8±2.0 mmHg rise in MABP (p<0.05). Among the group of PH− subjects with high and low aerobic fitness (n=30, 15/group), no differences in BP reactivity to mental stress were found. These results suggest that a lifestyle of physical activity associated with a high level of aerobic fitness may attenuate BP reactivity to mental stress and reduce the risk of HT in AA men. Copyright © 2000 John Wiley & Sons, Ltd.

Gastric mucosal damage by bile acid

To investigate the effect of bile acid on gastric mucosa, we performed biologic test using Sprague-Dawley rat. Mixture solution of TDCA 15mM and HCl of pH 3 was given into stomach to one group and HCl of pH 3 was given into stomach to another group. The significant gastric mucosal change was vasodilatation and edema, that was disappeared progressively. These findings suggest the bile acid can damage gastric mucosa.

The bcr gene in Philadelphia chromosome positive acute lymphoblastic leukemia

In chronic myelogenous leukemia (CML) and in a percentage of childhood and adult acute lymphoblastic leukemia (ALL) the Philadelphia (Ph') chromosome is present in the leukemic cells of patients. This chromosome is the result of a reciprocal translocation between chromosomes 9 and 22. In CML the break on chromosome 22 occurs within the major breakpoint cluster region (Mbcr) of the bcr gene. In this study, we report on the examination of DNAs from nine Ph'-chromosome positive ALL patients for rearrangements within the bcr gene using Southern blot analysis. Of nine patients having a karyotypically identifiable Ph'-chromosome, only five exhibited rearrangements of the bcr gene. This could indicate that in ALL, chromosome 22 sequences other than the bcr gene are involved in the Ph'-translocation. Within the group of Ph'-positive ALL patients having a bcr gene breakpoint, a correlation appears to exist between the age of the patient and the location of the breakpoint within the gene: all or the vast majority of pediatric patients analyzed to date do not have a Mbcr breakpoint as found in CML and in adult ALL.

The bcr Gene in Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia

Abstract In chronic myelogenous leukemia (CML) and in a percentage of childhood and adult acute lymphoblastic leukemia (ALL) the Philadelphia (Ph′) chromosome is present in the leukemic cells of patients. This chromosome is the result of a reciprocal translocation between chromosomes 9 and 22. In CML the break on chromosome 22 occurs within the major breakpoint cluster region (Mbcr) of the bcr gene. In this study, we report on the examination of DNAs from nine Ph′-chromosome positive ALL patients for rearrangements within the bcr gene using Southern blot analysis. Of nine patients having a karyotypically identifiable Ph′-chromosome, only five exhibited rearrangements of the bcr gene. This could indicate that in ALL, chromosome 22 sequences other than the bcr gene are involved in the Ph′-translocation. Within the group of Ph′-positive ALL patients having a bcr gene breakpoint, a correlation appears to exist between the age of the patient and the location of the breakpoint within the gene: all or the vast majority of pediatric patients analyzed to date do not have a Mbcr breakpoint as found in CML and in adult ALL.