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Biomedical subjects

A Daniele

Publications and source records attributed to A Daniele.

53 records · Page 3Linked to original sources

Can residual lexical knowledge concern word form rather than word meaning?

We described a patient with a dramatic deficit of both word comprehension and naming but with good preservation of visual pictorial semantics. On word-picture matching, his performances were slightly better than expected based on the observed lexical semantic disorder; in addition, the patient, who maintained good preservation of his underlying phonology, showed a tendency to point to the picture phonologically related to the target. In order to interpret these data, we advanced the hypothesis that the patient, in spite of his virtually complete inability to name, would be able, in a word-picture matching task, to "covertly" (i.e., preverbally) retrieve the name from the picture and to use this name to attempt a match with the phonological form of the stimulus word. This mechanism, that we called "phonological" comprehension, would allow the identification of the correct target and would explain the choice of the phonologically related foil that was sometimes selected.

Aged↗

Mapping of human hexokinase 1 gene to 10q11----qter.

Two partial-length cDNAs encoding the type 1 human hexokinase (ATP:D-hexose 6-phosphotransferase) were isolated from a placenta cDNA library using a 50-bp oligonucleotide synthesized according to the known sequence of human HK1. Using the larger (1.8 kb) cDNA insert as a probe and a panel of human-hamster somatic cell hybrids, we were able to assign the HK1 gene to the long arm of chromosome 10.

Animals↗

Cloning and expression of a new human polypeptide which regulates protein phosphorylation in Escherichia coli.

A 1,820 bp full-length clone encoding for a new human protein was isolated from a lambda gt11 placental cDNA library using anti-human hexokinase antibodies. The cDNA complete sequence includes a 12 bp 5' non-coding region, a single open reading frame encoding a protein of 55 KDa (HP-10) and a 177 bp non-coding with two putative polyadenylation signals upstream of 3' poly(A)tail. The deduced amino acid sequence reveals a sequence of 492 amino acids that contains a stretch of 7 glutamic acid from position 169 and one potential glycosylation site at position 274. Although antibodies against hexokinase recognize the fusion protein and antibodies against the fusion protein recognize hexokinase, HP-10 is not human hexokinase, by a number of criteria including the alignment of determined amino acid sequences. In searching for a possible functional role of HP-10 its cDNA was inserted into a procaryotic vector which allows the expression of the non-fused protein. Bacteria expressing the HP-10 encoded protein were isolated and found to have a dramatic increase in endogenous phosphorylated proteins. Since HP-10 does not have a protein kinase activity per se it should be considered a new regulatory phosphorylation protein which is active in E. coli.

Amino Acid Sequence↗

Dissociation between knowledge of living and nonliving things in dementia of the Alzheimer type.

Patients who survive herpes simplex encephalitis (HSE) sometimes present a category-specific disorder for living things. Since HSE specifically involves the temporolimbic structures of both hemispheres, these structures could play a critical role in processing and storing information about living things. If this were the case, a category-specific disorder for the same items should also be observed in the early stages of dementia of the Alzheimer type (DAT) as the temporolimbic structures are often severely affected in this condition. To test this hypothesis, we administered to 15 DAT patients and to 10 normal controls a confrontation-naming task and a verbal associates recognition task, with both living and nonliving items as stimuli. The hypothesis was confirmed, since DAT patients performed worse with living than with nonliving items, and scored worse than normal controls on the living but not the nonliving items.

Alzheimer Disease↗

Cloning of cDNA for a novel mouse membrane glycoprotein (gp42): shared identity to histocompatibility antigens, immunoglobulins and neural-cell adhesion molecules.

A full-length clone encoding a murine membrane glycoprotein, gp42, was selected from a mouse fibroblast cDNA expression library by screening with a polyclonal antiserum. The deduced amino acid (aa) sequence indicates that gp42 is a transmembrane protein of 273 aa with a large N-terminal portion exposed outside the cell and a short cytoplasmic domain. Computer assisted analysis shows that gp42 is distinct from previously characterized proteins, but shares a number of structural features with the class II histocompatibility antigens. The sizes of the extracellular domains of gp42 and of class II histocompatibility antigens are similar, the position of four cysteines and the location of several aa residues are conserved. Some of these conserved residues are also present in immunoglobulins (Ig) and in the neural-cell adhesion molecule, thus indicating that gp42 is a new member of the Ig superfamily.

Amino Acid Sequence↗

Contralateral and ipsilateral tactile extinction in patients with right and left focal brain damage.

Heilman has suggested that right hemisphere lesions produce neglect both in the spaces contralateral and ipsilateral to the damaged hemisphere. To test this hypothesis, we studied the incidence of contralateral and ipsilateral tactile extinctions in 44 right and 59 left brain-damaged patients, by means of a standard test of a double tactile simultaneous stimulation of symmetrical and asymmetrical parts of the two sides of the body and of ipsilateral body parts. Results did not confirm Heilman's hypothesis; while contralateral tactile extinction was more frequent and severe in right than in left brain-damaged patients, no hemispheric difference was found when the number of ipsilateral extinctions was taken into account. Furthermore, ipsilateral tactile extinction was significantly related to aspecific factors (such as age, severity of sensorimotor impairment and widespread mental deterioration), irrespective of the hemispheric side of lesion.

Brain Diseases↗

Gonadal steroids modulate human monocyte interleukin-1 (IL-1) activity.

Interleukin-1 (IL-1), a monocyte and macrophage product, is the mediator of a wide variety of immune responses, including fever, and increases during the luteal phase of the menstrual cycle, concomitantly with progesterone (P). These studies were undertaken to assess the possible relationship between steroidogenesis and IL-1 activity elaborated by human peripheral monocytes. IL-1 was measured with the D-10 thymocyte stimulation bioassay and dose response curves as a function of both estradiol (E2) and P were established. Low concentrations of both E2 (10(-9) M-10(-10) M) and P (10(-8) M-10(-9) M) resulted in maximal IL-1 stimulation. At higher concentrations of both E2 (10(-7) M) and P (10(-7) M-10(-5) M) there was a significant reduction (P less than 0.05) in IL-1 activity. However, neither E2 nor P production by human granulosa-luteal cells cultured with increasing amounts of human IL-1 (0 to 20 IU/ml) was affected in either the absence or presence of human chorionic gonadotropin (hCG, 5 IU/ml). Thus, human peripheral monocyte IL-1 activity appears to be modulated by gonadal steroids; however, a reciprocal relationship between IL-1 and gonadal steroidogenesis was not observed.

Animals↗

Hunter syndrome: presence of material cross-reacting with antibodies against iduronate sulfatase.

Polyclonal antibodies were obtained from rabbits by injection of iduronate sulfatase purified 35,000-fold from human placenta, after elution of the enzyme from sodium dodecyl sulfate (SDS) polyacrylamide gels. The specificity of these antibodies towards iduronate sulfatase was demonstrated by immunoprecipitation of enzyme activity; the level of other lysosomal hydrolases and sulfatases remained constant. Immunoblot of iduronate sulfatase from various human sources showed that the antibody recognises a polypeptide of mol. wt. 72,000 daltons in placenta and serum, and a form of mol. wt. 60,000 daltons in fibroblasts. No immunoprecipitable peptide was found in urine or in the culture medium of fibroblasts. Polypeptides of the same molecular weight were recognised in serum and in fibroblasts of Hunter patients. The presence of altered proteins in these patients was also shown by competition experiments. The addition of Hunter proteins alters the binding of normal enzyme to the antibody.

Animals↗

Ovulation induction with human menopausal gonadotropin compared to human urinary follicle-stimulating hormone results in a significant shift in follicular fluid androgen levels without discernible differences in granulosa-luteal cell function.

Follicular fluid estradiol, progesterone, testosterone, and androstenedione levels were compared in 2 groups of spontaneously ovulatory women undergoing ovulation induction with human menopausal gonadotropin (hMG; which contains equal amounts of LH and FSH) or human urinary FSH (huFSH). The results were correlated with the ratios of embryo cleavage and pregnancy. Although significantly more FSH [1268 +/- 38 (+/- SEM) vs. 953 +/- 38 IU; P less than 0.05] was required for equivalent hyperstimulation in hMG compared to huFSH cycles, the number of oocytes retrieved and fertilized and the number of embryos transferred were similar for the 2 ovulation induction protocols. Forty-two follicles from 21 women stimulated with hMG and 38 follicles from 15 women stimulated with huFSH were examined and found to be representative of the total cohort of aspirated follicles. Follicular fluid estradiol and progesterone levels were similar, but hMG-stimulated follicles contained significantly more testosterone [7.83 +/- 0.52 (+/- SEM) vs. 6.30 +/- 0.42 ng/ml; P less than 0.03] and less androstenedione (24.4 +/- 3.6 vs. 37.8 +/- 5.0 ng/ml; P less than 0.03) than did huFSH-stimulated follicles. Embryonic cleavage rates were similar for all fertilized oocytes from both hMG- and huFSH-stimulated cycles, although pregnancy rates were significantly higher in huFSH cycles (40% vs. 9.5%; P less than 0.05). In addition, aromatase activity, progesterone production, and [125I]hCG-binding activity were compared in granulosa-luteal cells isolated from some of these women. Cells from 21 follicles from 9 women stimulated with hMG and 24 follicles from 9 women stimulated with huFSH were studied. There were no significant differences in aromatase activity, progesterone production, or [125I]hCG binding. Thus, the presence or absence of exogenous LH during ovulation induction with FSH has little direct effect on granulosaluteal cell function. However, the presence of LH during ovulation induction with FSH does appear to alter thecal androgen metabolism, resulting in higher testosterone and lower androstenedione levels in follicular fluid. Such a shift in androgen milieu may impair oocyte development and successful implantation.

Adult↗

Iduronate sulfatase from human placenta.

The major enzyme component of iduronate sulfatase from human placenta was purified 30 000-fold by a five-step procedure. Sucrose gradient centrifugation of the native enzyme gave a molecular weight estimate of 80 000 +/- 10 000. Electrophoresis in sodium dodecyl sulfate of the enzyme reduced with mercaptoethanol showed a protein band of Mr 82 000. We suggest that the enzyme is composed of a single polypeptide chain of Mr 80 000-90 000.

Female↗

Biosynthesis of alpha-N-acetylglucosaminidase in cultured human kidney carcinoma cells.

The biosynthesis of alpha-N-acetylglucosaminidase was studied in cultured human kidney carcinoma cells by labeling cells with 35S-methionine, isolation of the enzyme by immunoprecipitation and analysis on gel electrophoresis of the denatured polypeptide(s) and analysis of the native enzyme on linear sucrose gradient centrifugation. The enzyme is synthesized as precursor forms of apparent molecular weight 82,000-86,000. Processing of these precursors yields a polypeptide of apparent molecular weight of 80,000. The precursor-product relationship was indicated by pulse-chase as well as endocytosis experiments. Sucrose gradient centrifugation of the native enzyme shows that, extracellularly, the molecule is present with a molecular weight of 80,000; intracellularly, 80-90% of the enzyme is present with an apparent molecular weight of 240,000. We suggest that this is a polymeric form and that polymerization of alpha-N-acetylglucosaminidase is a late event of the maturation process.

Acetylglucosaminidase↗

Statistical analysis of clinical breast cancer by computer.

At the moment we still lack a clear correlation of clinical staging and pathology with therapy and prognosis in breast cancer patients. More studies need to be conducted dealing with the relationships of breast cancer to previous diseases, hormonal balance, conservative therapy and type of surgical therapy. These evaluations may be very important in supporting a less serious prognosis, a clearer clinical staging and a more certain choice of the right therapy. With computer help we have evaluated data from 500 patients with breast cancer. We have considered: age; previous breast diseases with particular regard to therapy; hormonal balance; obstetrical relevant past history; morphological and functional aspects of the breast; the histology of the tumour and metastases; and the results of therapy.

Breast Neoplasms↗

Neuroanatomical correlates of category-specific semantic disorders: a critical survey.

Previous studies of category-specific semantic disturbances have focused their attention on the intrinsic cognitive structure of these disorders. The present survey aims to evaluate the relationships between disrupted semantic category and localisation of the underlying brain damage, in order to establish whether the injured brain areas house just those neurophysiological mechanisms that should have critically contributed to the acquisition of the disrupted semantic categories. We took into account in our review two double dissociations concerning respectively: (1) the impairment of a specific linguistic category--we contrast those disorders selectively affecting verbs (action names) with those selectively affecting nouns (object names); (2) the impairment of a specific conceptual/semantic domain--we contrast disorders selectively affecting living beings with those preferentially affecting man-made artefacts. The hypothesis that different categories of knowledge may be closely intertwined with different sources of sensory-motor information, was substantially confirmed. The lesion preferentially encroached on the left frontal lobe when the category "verbs" was selectively affected; it involved the left temporal lobe and the posterior association areas when the category "nouns" was preferentially disrupted; it involved bilateral temporo-limbic structures and inferior temporal lobes when the category "living beings" was selectively disrupted; it usually encroached on the left fronto-parietal areas when man-made artefacts and body parts were preferentially affected. These data support the hypothesis that: (a) action schemata may critically contribute to the development of the semantic representation of verbs, (b) mechanisms of sensory integration may play an important role in establishing the semantic representation of nouns; (c) high-level visual processing and multi-modal sensory convergency may critically contribute to organising the semantic representation of living beings; (d) motor-kinaesthetic integration may play a leading role in developing the semantic representation of man-made artefacts.

Aphasia, Broca↗

Apolipoprotein E genotype in sporadic early- and late-onset Alzheimer's disease.

The 84 isoform of apolipoprotein E (ApoE) has been proposed as a risk factor for Alzheimer's disease (AD), while the possible role of the epsilon2 allele in AD is controversial. We have studied the ApoE genotype in 38 patients with early-onset AD (EOAD) and in 43 patients with late-onset AD (LOAD). In the EOAD group we observed a significant increase of epsilon4 allele frequency as compared with normal controls, while there was a more than 3-fold decrease of epsilon2 allele frequency that did not reach statistical significance. In the LOAD group we found a highly significant increase of epsilon4 allele frequency as compared with normal controls, while there was a significant decrease of epsilon2 allele frequency. In both the EOAD and LOAD groups, no significant difference was observed between epsilon4 carriers and epsilon4 noncarriers as for age at disease onset, disease duration, and Mini-Mental State score at observation. However, in both EOAD and LOAD groups a statistical trend towards a longer disease duration was observed in epsilon4 carriers. In both the EOAD and LOAD groups, disease severity was compared in epsilon4 carriers versus epsilon4 noncarriers by means of analyses of covariance, with disease duration as covariate. No significant difference between epsilon4 carriers and epsilon4 noncarriers was observed in both EOAD and LOAD. The results of the present study confirm that epsilon4 allele seems to be associated with an increased risk for sporadic AD, while the significant decrease of epsilon2 allele frequency in the LOAD group supports the hypothesis of a possible protective role of epsilon2 allele in AD.

Age of Onset↗

Isolated amnesia with slow onset and stable course, without ensuing dementia: MRI and PET data and a six-year neuropsychological follow-up.

Patient EDS presented with an amnesic disorder of insidious onset (4 years) that remained stable and restricted to memory functions over a 10-year course. Repeated neuropsychological evaluations over 6 years showed a moderate-to-severe, stable impairment of long-term memory and of memory for public events, and a milder, stable impairment of autobiographic memory and of short-term memory. Language, perception, praxis and 'frontal' functions were fully preserved. MRI showed atrophy of the right hippocampus, of the right mammillary body and of the sylvian fissure (bilaterally, but more marked on the left). On PET scan, metabolic activity in the mesial temporal structures was significantly reduced on the right and was at lower normal levels on the left. The disorder observed in EDS is similar to that recently reported in other patients. Possible etiologies of the selective amnesia observed in EDS are considered and their implications discussed.

Age of Onset↗

MUC3 and MCA serum levels and steroid receptor content in breast cancer.

Mucins are an important class of complex glycoproteins expressed by many epithelial cells and their malignant counterparts. The aim of this study was to determine the serum levels of MUC3 and mucin-like carcinoma-associated antigen (MCA) in patients with primary breast cancer and to analyze the possible relationships between these two mucins and the steroid receptor status. The preoperative basal serum levels of MUC3 (ELISA assay with monoclonal antibody 1143/B7) and MCA (EIA assay with anti-MCA mouse monoclonal antibody b-12) were determined in 44 patients with breast cancer while estrogen receptor (ER) and progesterone receptor (PgR) levels were measured by the dextran-coated charcoal method in the cytosol of neoplastic tissue. MUC3 was expressed in 43/44 serum samples while high MCA serum levels were found in 16/44 only; the mean values of both markers did not correlate with menopausal status, tumor size, nodal involvement or ER. The only significant difference observed was a lower median value of MCA in patients with small tumors (T1-T2). No statistically significant correlation between MUC3 and MCA, MUC3 and ER or MCA and ER was observed; a statistically significant direct correlation between MUC3 and PgR+ status and a statistically significant inverse correlation between MCA and PgR+ were observed. Our results suggest that further investigations are necessary to establish whether progesterone can modulate MUC3 and MCA expression in breast cancer.

Adult↗