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Biomedical subjects

M Valentini

Publications and source records attributed to M Valentini.

At least 37 records · Page 2Linked to original sources

The blockage of the human transferrin receptor by a monoclonal antibody, EA.3, induces growth inhibition in leukemia cell lines.

In our program to produce monoclonal antibodies against hemopoietic functional antigens we have obtained an hybridoma cell line EA.3 reacting with human transferrin receptor. This monoclonal antibody is an IgM that displays "in vitro" antiproliferative activity against leukemic cells due to its competition with transferrin on the receptor. Cell cytotoxicity was demonstrated either with the blockage of BrdU incorporation in HL-60 cells and with leukemic CFU inhibition. In contrast, K562 cells were insensitive to the blockage of the transferrin receptor induced by this MAb.

Antibodies, Monoclonal

Inhibition of NK binding to K562 cells induced by MAb saturation of adhesion molecules on target membrane.

Cell to cell interaction play a major role in the induction of a immune response. NK cells represent a special lymphoid subset which displays its cytotoxic function without the engagement of MHC system. In order to investigate the role of different adhesion molecules in the mechanism of binding of the NK cell to the classic tumor target K562 cell, we have employed different unclustered mAbs of the Adhesion session (5th "CD" Workshop, Boston 1993) mostly of the CAM (cell adhesion molecule) subpanel. After their reactivity characterization both on lymphocytes and K562 cells, those that demonstrate reactivity against the tumor target were tested in the binding assay. The target was pretreated with the monoclonal in order to block a possible reacting molecule for the effector. Then, after the incubation of lymphocytes with PE-labelled anti CD16 mAb, their ability to bind to the target was tested in flow. While the majority of the mAbs did not induce any significant change in the binding capacity of the NK subset, few of them did, and precisely anti-CD58 (LFA-3) and anti-CD54 (ICAM-1) which showed different level of inhibition, particularly drastic with S002, S083 and S100. Other mAbs, such as the S011 (anti-CD59), due to the presence of the PI-linked glycoprotein recognized on both target and effector membranes, and to its capacity to stimulate NK activity, produced a total binding of the NK population. The coincubation of targets with anti-CD54 and anti-CD58 allowed to reduce at the lowest level this function. This data seem to support the hypothesis of specific surface molecules involved in the binding process of the NK cell, after recognition of the target.

Antibodies, Monoclonal

Effect of short- and long-term treatment with omeprazole on cell cycle distribution in the gastric mucosa. Results of a flow cytometric study.

Omeprazole may exert an effect on gastric mucosal proliferation by inhibiting gastric acid secretion and increasing serum gastrin levels. It may also influence the kinetics of endocrine cells and the oxyntic mucosa. The aim of the present study was to evaluate the cell cycle in different gastric compartments following short- (1 month) and long-term (6 months) administration of two different dosages of omeprazole by means of a flow cytometric method. We also determined serum gastrin levels at the same time. No differences in cell cycle distribution of the antrum, body, and fundus were found in the two different dosage groups after 1 month of therapy, considering the synthetic phase (S-phase) of the cell cycle. A statistically significant increase in S-phase was reported after long-term therapy in the mucosa of the fundus and body of the stomach in both groups. Gastrin levels showed no clear correlation with cell cycle distribution variables. We postulate a proliferative adaptation of the oxyntic mucosa to long-term drug administration not mediated by gastrin influence.

Adult

Changes in autonomic nervous function over a 5-year period in non-insulin-dependent diabetic patients.

One hundred and eight non-insulin-dependent diabetic patients who had been tested for autonomic dysfunction in 1984/85 were re-evaluated 5 years later. Autonomic function was assessed by means of four cardiovascular tests (heart rate variation during deep breathing and standing, and blood pressure variation after standing and sustained handgrip). Eighteen subjects were lost to follow-up; in the 90 patients who completed the study, both the deep breathing and the handgrip test significantly worsened (respectively from 13.7 +/- 7.8 to 11.6 +/- 6.3 beats min-1 p < 0.01, and from 16.9 +/- 8.2 to 12.7 +/- 7.1 mmHg, p < 0.001), whereas both the 30:15 ratio and the variation of blood pressure on standing did not change. The impairment of a comprehensive evaluation score (from 2.5 +/- 1.7 to 3.0 +/- 1.5; p < 0.05) also confirmed the gradual deterioration of autonomic function over the study period.

Autonomic Nervous System

Adjuvant therapy for primary breast cancer in a female patient affected by autoimmune liver disease: does it cure breast cancer and primary biliary cirrhosis?

Polychemotherapy (CMF or CMF-like regimens) is the treatment of choice in premenopausal breast cancer patients with 1-3 positive nodes. In clinical practice, patients with abnormal biochemical tests of liver function are usually excluded from this potentially curative methotrexate-containing regimen in order to avoid worsening of hepatic damage. On the other hand, recent reports have shown a beneficial effect of methotrexate in a particular autoimmune liver disease such as primary biliary cirrhosis. We discuss the case of a female patient with breast cancer and primary biliary cirrhosis whose biochemical tests of liver function and the titer of antimitochondrial antibody persistently improved after treatment with 3 cycles of CMF. In conclusion, we suggest that the CMF regimen is potentially useful in patients with breast cancer and primary biliary cirrhosis.

Antineoplastic Combined Chemotherapy Protocols

[Picotamide: use in chronic obliterative arteriopathies of the lower limbs].

In the present study the authors evaluated treatment efficiency and patient compliance of medium-term therapy with Picotamide, given in doses of 900 mg/die for the first 15 days, and 600 mg/die up to the completion of a three-month period, to 50 patients affected by vaso-occlusive arterial disease of the lower limbs. At follow-up visits the following controls have been carried out: CW Doppler sonography of the lower limbs, Maximum Walking Distance (M.W.D.), Red blood cell count, White blood cell count, Platelet count, Haemoglobin and Fibrinogen levels. At the end of the three-month therapy period the Ankle-Arm parameters remained unchanged.

Aged

Doppler ultrasound studies of the uterine arteries in spontaneous and IVF stimulated ovarian cycles.

The changes of uterine artery blood flow in women were studied throughout normal and in vitro fertilization (IVF) stimulated cycles. The obtained data showed that uterine blood flow variations are correlated to spontaneous or induced hormonal changes. Furthermore, Doppler investigation may be very important in predicting the pregnant state at a very early stage in patients enrolled in an IVF program.

Adult

Intra-uterine growth retardation is associated with increased levels of magnesium in amniotic fluid.

Magnesium (Mg) and zinc (Zn) levels were measured in amniotic fluid of 30 normal pregnancies between the 16th and the 42nd week of amenorrhea and in 15 cases of intra-uterine growth retardation (IUGR) at 30-38th week of pregnancy. While Zn levels were stable throughout physiological pregnancy, the Mg concentration decreased progressively from 1.09 +/- 0.31 mg/100 ml (mean +/- SD) at the end of the second trimester to 0.75 +/- 0.20 (p less than 0.02) at term. In the case of IUGR, Mg levels (1.22 +/- 0.28) were higher than in controls (0.89 +/- 0.27, p less than 0.01) matched for gestational age. No differences in Zn levels were found between the two groups. Although the mechanisms leading to Mg accumulation in the amniotic fluid of growth-retarded fetuses remain unknown, these data support the role played by Mg in fetal growth.

Amniotic Fluid

Octatropine-methyl-bromide and sulglycotide salt in the short-term treatment of active duodenal ulcer. A double blind endoscopic study of 40 outpatients.

Forty outpatients with endoscopically confirmed duodenal ulcers were entered in a double blind trial. They were randomly allocated to octatropine-methyl-bromide and sulglycotide salt (GVP) or placebo. The results show that the combination of the two drugs is less efficacious than the two constituent substances taken separately, is not more efficacious than placebo in ulcer healing, and is ineffective with regard to ulcer pain.

Anti-Ulcer Agents

Premenstrual increase of intracellular magnesium levels in women with ovulatory, asymptomatic menstrual cycles.

Intracellular magnesium (Mg) levels regulate several enzymatic reactions and the hypoactivity of Mg has been involved in different pathological states. In addition to other factors, gonadal hormones, too, have been found to interfere in Mg balance. This study evaluates the changes in Mg in women throughout the normal menstrual cycle and those measured at weekly intervals in males. Magnesium and potassium (K) levels were measured in the plasma, red blood cells (RBC), lymphocytes (LC) and polymorphonucleated cells (PMN) of 11 normal menstruating women, in different periods of their menstrual cycle. Blood samples were collected every 4th day. According to the time and LH, progesterone and estradiol levels, they were classed as follicular (Foll), periovulatory (OV), luteal (Lut) or premenstrual (PM). The Menstrual Distress Questionnaire completed by the subjects revealed that no significant symptomatology was present. Four blood samples were also collected from 4 normal males, at weekly intervals. Mg and K were determined by atomic absorption spectrophotometry. LC and PMN were purified by centrifugation on a Ficoll discontinuous gradient. No differences were found in males versus females in the Mg or K contents in the different compartments. In the 4 periods tested, the K levels were constant, in both females and males. The same applies for Mg contents in males. In females, Mg contents, as well as the Mg/K ratio in LC and PMN, showed a significant increase in the premenstrual period compared with the other periods of the cycle. On the contrary, plasma and RBC Mg levels were constant throughout the cycle.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

No gradient exists between lumbar and ventricular cerebrospinal fluid beta-endorphin.

In 8 patients, beta-lipotropin (beta-LPH), beta-endorphin (beta-EP), ACTH, protein and chloride concentrations were measured in cerebrospinal fluid (CSF) samples obtained simultaneously from the lumbar space and lateral ventricle. Albumin and IgG levels were significantly higher in lumbar than in ventricular CSF samples while no craniocaudal gradient was observed for neuropeptide concentrations. The importance of molecular weight in determining such a regional distribution is supported also by the similar lumbar and ventricular levels of chlorides. These data would validate the CSF approach through lumbar puncture as a tool for exploring neuropeptides in the central nervous system.

Adrenocorticotropic Hormone

Limiting-dilution analysis for the determination of leukemic cell frequencies after bone marrow decontamination with mafosfamide or merocyanine 540.

To stimulate a leukemia remission marrow, cell suspensions of normal human bone marrow were mixed with human acute lymphoblastic or myelogenous leukemic cells of the CCRF-SF, Nalm-6, and K-562 lines. The cell mixtures were incubated in vitro with mafosfamide (AZ) or with the photoreactive dye merocyanine 540 (MC-540). A quantity of 10(4) cells of the treated suspensions was dispensed into microculture plates, and graded cell numbers of the line used to contaminate the normal marrow were added. Limiting-dilution analysis was used to estimate the frequency of leukemia cells persisting after treatment with the decontaminating agents. Treatment with AZ or MC-540 produced a total elimination (ie, 6 logs or 5.3 logs respectively) of B cell acute leukemia cells (CCRF-SB), whereas nearly 1.7 logs and 2 logs of K-562 acute myelogenous blasts were still present in the cell mixtures after treatment with MC-540 and AZ, respectively. Treatment of the Nalm-6-contaminated cell mixtures with AZ resulted in 100% elimination of clonogenic cells, whereas nearly 80% decontamination was obtained with MC-540. Our results suggest that treatment with AZ could be an effective method of eliminating clonogenic tumor cells from human bone marrow. MC-540, shown by previous studies to spare sufficient pluripotential stem cells to ensure hemopoietic reconstitution in the murine model and in clinical application, has comparable effects and merits trials for possible clinical use in autologous bone marrow transplantation.

Bone Marrow

HLA compatibility for patients with thalassemia: implications for bone marrow transplantation.

In order to evaluate the possibility of a patient with thalassemia finding an HLA-identical sibling donor, we performed an analysis of HLA antigens in families of thalassemic patients. The pattern distribution was not significantly different from the expected ratio 25:50:25. When the siblings were subdivided according to the age of the patients (under or over 5 years), the above pattern remained unmodified for both the age groups. The average size of the 129 thalassemic families was 2.4. Thus, taking into account that thalassemic patients have an average of 1.4 siblings and that the HLA genotype distribution is expected as such, HLA-matched siblings are available for 33% of the patients. Because an additional 8.5% of the patients were found HLA-phenotypically identical to one parent, the chance for a patient with thalassemia to find a suitable donor for bone marrow transplantation would be increased to 41.5%. Our preliminary data cannot be extrapolated to the overall Italian thalassemic population; however, it can be inferred that for a patient with thalassemia, the chance of finding a suitable donor for bone marrow transplantation is not reduced.

Bone Marrow Transplantation

[The role of cytology by needle aspiration in the diagnosis of thyroid nodules. Examination of 179 cases].

Since May 1981, fine needle biopsies have been used for cytological examination of thyroid nodules that were barely or not recorded by scintiphotography. By February 1984, a total of 179 patients had been examined. The biopsies were repeated on 12 patients where the first sample produced no diagnostic material. In 57 cases, a histological control existed in the form of material removed surgically by enucleoresections, partial and total thyroidectomies. Histological examination confirmed the cytological diagnosis in 7 out of 8 cases (88%) of malignant neoplasias with varying degrees of differentiation. A cytological diagnosis of adenoma was reached in 80% of cases, and of nodular struma in 82% of cases. Microscopic aspects of the cases are described together with the consequent cytological diagnostic criteria, while the characteristics and importance of the technique are also discussed.

Adenoma

[Value of modern diagnostic technics in rupture of the spleen].

Personal experience is reported of the latest instrumental techniques used to diagnose ruptures of the spleen following a closed abdominal trauma. Particular interest was taken in patients with unclear clinical symptoms who were given a series of surgical and/or non-surgical tests in order to diagnose ruptured spleen in the asymptomatic phase. Tests analysed included: peritoneal injection-douche, laparoscopy, angiography, scintiphotography, echography and CAT scanning.

Accidents, Traffic