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Biomedical subjects

M Hartman

Publications and source records attributed to M Hartman.

At least 37 records · Page 2Linked to original sources

Sex and sociocultural correlates of urinary incontinence in Israeli preschool children.

Urinary incontinence in children aged 2 to 6 years whose mothers varied in ethnic descent, in level of education, and in immigration status was studied in Israel. Mothers of 302 children were interviewed in well-baby clinics regarding primary and secondary urinary incontinence of their children. A significant age trend was found for attaining primary urinary continence. However, various interactions between mothers' ethnic descent, mothers' level of education, and mothers' immigration status were associated with different rates of primary and secondary urinary incontinence in their children. Moreover, sex differences in rates of primary and secondary urinary incontinence were also associated with mothers' ethnic descent and level of education. It is suggested that different levels of maternal emotional availability to the child in the various subgroups can account for most of the findings.

Child↗

Common sense, insight, and neuropsychological test performance in schizophrenia patients.

We report an exploratory study examining the interrelationships among common sense, insight into psychosis, and performance on a battery of neuropsychological tests in 32 patients with schizophrenia evaluated at the time of discharge from involuntary hospitalization at a State psychiatric hospital. Common sense, as measured by the Social Knowledge Questionnaire, was associated with better performance across tests measuring parietal lobe functioning and vocabulary. In addition, patients with more common sense were more likely to say that they were ill and needed treatment. A global measure of insight, the Insight and Treatment Attitudes Questionnaire (ITAQ), was related to performance on a test of left parietal lobe function. However, the responses to the ITAQ item that may best reflect current awareness of mental illness in patients at the time of discharge ("After you are discharged, is it possible you may have mental problems again?") were related to performance on tests of the functioning of the prefrontal lobes and the right and left parietal lobes. These results add to the growing evidence that some of the deficits in awareness of illness among patients with schizophrenia are related to the neuropsychological dysfunction commonly seen in patients with this disorder.

Adult↗

Hyaluronan in human cerebrospinal fluid.

We studied the concentration of hyaluronan in cerebrospinal fluid (CSF) in various diseases and attempted to define its reference interval. A radioassay utilizing cartilage proteins with affinity for hyaluronan was used in determining the concentration of 200 lumbar and 27 ventricular CSF specimens and 11 brain cyst fluids. Molecular weight distributions were determined by gel chromatography and localization in brain tissue by histochemistry. The hyaluronan level of lumbar CSF showed an increase with age; comparatively healthy children had (mean +/- SD) 50 +/- 41 micrograms/L (n = 40) and adults 166 +/- 77 micrograms/L (n = 9); i.e. significantly different values. The highest level was recorded in a patient with meningitis (> 8000 micrograms/L). More than 4000 micrograms/ L was noted in a patient with tumour metastasis in the cerebellum. Significantly elevated levels were especially found with spinal stenosis, head injury and cerebral infarction, but also in inflammatory medical disorders, hydrocephalus and encephalitis. We found no significant increase in multiple sclerosis and some other neurological diseases. Ventricular CSF of adults contained significantly less hyaluronan (53 +/- 73 micrograms/L; n = 16) than lumbar CSF. Hyaluronan in cyst fluids varied from 31 to 25,000 micrograms/L. Weight average molecular weight of hyaluronan in CSF was 2.9-3.0 x 10(5) and in brain tumour cyst fluid 2.4 x 10(6). In search for the origin of hyaluronan in CSF it was found that its concentration in the choroid plexus and leptomeninges was low, but that hyaluronan was accumulated in the superficial layer of the cerebral cortex. Continued screening for hyaluronan in CSF may be valuable in cases of inflammatory diseases, tumours and obstruction to CSF flow.

Adolescent↗

Divided attention and indirect memory tests.

Attentional state during acquisition is an important determinant of performance on direct memory tests. In two experiments we investigated the effects of dividing attention during acquisition on conceptually driven and data-driven indirect memory tests. Subjects read a list of words with or without distraction. Memory for the words was later tested with an indirect memory test or a direct memory test that differed only in task instructions. In Experiment 1, the indirect test was category-exemplar production (a conceptually driven task) and the direct test was category-cued recall. In Experiment 2, the indirect test was word-fragment completion (a data-driven task) and the direct test was word-fragment cued recall. Dividing attention at encoding decreased performance on both direct memory tests. Of the indirect tests, category-exemplar production but not word-fragment completion was affected. The results indicate that conceptually driven indirect memory tests, like direct memory tests, are affected by divided attention, whereas data-driven indirect tests are not. These results are interpreted within the transfer-appropriate processing framework.

Adult↗

Coexpression of platelet-derived growth factor alpha and beta receptors on medulloblastomas and other primitive neuroectodermal tumors is consistent with an immature stem cell and neuronal derivation.

Medulloblastomas and related childhood primitive neuroectodermal tumors (PNET) are currently thought to originate from a multipotent stem cell that can give rise to a variety of different tumor types, representing different lines of differentiation and stages of maturation of the original stem cell. The proliferation and differentiation of different cell types in the central nervous system are influenced by growth factors, such as platelet-derived growth factor (PDGF). In this study, we investigated the expression of the two types of PDGF receptors, alpha and beta, on 14 cases of PNET by immunohistochemistry and in situ hybridization. To characterize the tumor cells according to their differentiation and maturation, we performed immunohistochemistry with Ab against several members of the intermediate filament family, such as neurofilament, glial fibrillary acidic protein, vimentin, and the embryonal marker nestin. For the cerebral PNET, we found that the phenotype of multidirectional differentiation (with coexpression of neurofilament, glial fibrillary acidic protein, vimentin, and in some cases nestin) was associated with the expression of both PDGF alpha and beta receptors on the tumor cells. Medulloblastomas (i.e., cerebellar PNET), however, often showed the phenotype of partially committed neuron-like precursor cells, and this was associated with the predominant expression of PDGF alpha receptors on the tumor cells. Our findings show that the PDGF alpha receptor, previously known to play a role in the normal development of cells of the glial lineage, either exclusively or in combination with the PDGF beta receptor, is expressed on tumor cells of neuronal derivation. This "aberrant" expression of PDGF alpha receptors on PNET may reflect a feature of the malignant phenotype of these tumors. Further studies are needed to study the biologic effects of PDGF-A and its receptor in PNET.

Brain Neoplasms↗

Detection of TP53 gene mutation in human meningiomas: a study using immunohistochemistry, polymerase chain reaction/single-strand conformation polymorphism and DNA sequencing techniques on paraffin-embedded samples.

Mutations in the TP53 tumor suppressor gene have been studied in different types of brain tumors. Little is known about this genetic event in human meningioma, a mostly benign tumor. To investigate the frequency of TP53 gene mutations in human tumors derived from meningeal tissues, paraffin-embedded tissues from 30 cases (including 2 malignant and 4 atypical meningiomas, as well as 2 hemangioblastomas and 3 hemangiopericytomas) were screened by immunohistochemistry. Polymerase chain reaction/single strand conformational polymorphism (PCR/SSCP) and direct DNA sequencing were thereafter performed in selected cases. Nuclear p53 staining was not seen in any of the 19 benign meningiomas tested, while atypical meningiomas, hemangioblastomas, and hemangiopericytomas displayed nuclear staining in a subpopulation of tumor cells in 4 out of 5, 2 out of 2, and 3 out of 3 cases, respectively. One malignant meningioma showed an intense nuclear staining and a band shift in SSCP. In this case, we identified a mutation in the TP53 gene at codon 161 changing GCC to ACC and resulting in an alteration of alanine to threonine in this position. Our results indicate that TP53 gene mutation may be considered as a marker for malignant transformation in meningioma. p53 immunoreactivity, even in the absence of detectable gene mutation, is also associated with atypia and does not appear in regular benign meningiomas.

Adult↗

Human CTL epitopes encoded by human papillomavirus type 16 E6 and E7 identified through in vivo and in vitro immunogenicity studies of HLA-A*0201-binding peptides.

Human papillomavirus type 16 (HPV16) is strongly associated with cervical carcinogenesis. The HPV16 E6 and E7 oncoproteins are constitutively expressed in the majority of cervical tumor cells and are, therefore, attractive targets for CTL-mediated immunotherapy. In mice, the outgrowth of a lethal dose of HPV16-induced tumor cells has been prevented by vaccination with a CTL epitope encoded by HPV16 E7, indicating the feasibility of peptide immunization to obtain antitumor CTL responses. In the present study, the immunogenicity of 9 HLA-A*0201-binding peptides encoded by HPV16 E6 and E7 was analyzed in vivo in HLA-A*0201Kb transgenic mice and in vitro in CTL cultures induced from PBMC of HLA-A*0201+ healthy donors. Four peptides with a good binding affinity were immunogenic in HLA-A*0201Kb transgenic mice, and three of them were also highly immunogenic in CTL induction experiments with PBMC of HLA-A*0201+ healthy donors. Human CTL clones specific for these three peptides were capable of lysing the HPV16 E7-containing HLA-A*0201+ cervical carcinoma cell line CaSki. These E7-derived peptides (11-20, YMLDLQPETT; 82-90, LLMGTLGIV; 86-93, TLGIVCPI), therefore, are likely to represent naturally processed human CTL epitopes of HPV16. Additionally, these three HPV16-encoded peptides have the highest affinity of binding to the HLA-A*0201 molecule. In this study, peptides with a lower binding affinity were less immunogenic. Therefore, our data illustrate that the HLA-binding affinity of a peptide has a major impact on its immunogenicity. In conclusion, we have identified immunogenic peptides encoded by HPV16 E6 and E7 that could be used in vaccines for the prevention and treatment of cervical carcinoma.

Amino Acid Sequence↗

Aging and interference: evidence from indirect memory tests.

Four experiments examined age differences on indirect memory tests as a function of (a) the status of a stimulus as target or distractor and (b) the degree of predictability of a stimulus from context. No differences between young and old adults were found when targets were clearly designated as such. In this situation, participants showed priming for unexpected but not expected stimuli whether these words appeared as targets or distractors. In contrast, age differences emerged when there was initial uncertainty on each trial as to which stimulus was the target. It is concluded that aging is associated with a decrease in the efficiency of mechanisms involved in selection.

Adolescent↗

Expression of estramustine-binding protein in ependymomas and in human and developing rat ependymal cells.

The mainstays of primary treatment of ependymoma are aggressive surgery followed by radiotherapy. Although spreading occasionally occurs in the cerebrospinal pathways, chemotherapy is still not established and no ultimate drug has so far been found. Estramustine-phosphate (EMP), with a demonstrated effect on astrocytoma in vitro, has been shown to penetrate the blood-tumor barrier and to accumulate in human brain tumor tissue including ependymoma. It has been proposed that the cytotoxic effect of EMP depends on the presence of a binding protein, estramustine-binding protein (EMBP). In the present paper we have, for the first time, immunohistochemically demonstrated an EMBP-like protein in a series of ependymomas. Immunoreactivity was found within the cytoplasm of the tumor cells with a tendency to increase with increasing malignancy of the tumor. In addition, the occurrence of EMBP-like protein was demonstrated in human ependymal cells. In the rat brain, a weak immunoreactivity was detected in early fetal neuroepithelial cells while the staining intensity was increased in mature ependymal cells in late fetal, neonatal, and adult rat. Thus; immunoreactivity for an EMBP-like protein was demonstrated in ependymoma tissue, normal human ependyma and in the developing rat ependymal cells.

Adolescent↗

Psychological factors associated with chronic dizziness in patients aged 60 and older.

OBJECTIVE: To identify the prevalence and character of psychological disorders accompanying chronic dizziness in older patients. DESIGN: Case series of patients from a geriatric dizziness clinic, with comparison data from age- and sex-matched healthy community controls. Both cases and controls received screening psychological testing; all cases were evaluated by a clinical psychologist as part of the dizziness clinic evaluation. SETTING: Multidisciplinary Geriatric Dizziness Clinic. PARTICIPANTS: Fifty six consecutive patients with chronic dizziness, evaluated by a multidisciplinary Geriatric Dizziness Clinic, and 68 healthy volunteers whose age and sex distribution matched that of the dizziness clinic patients. MEASUREMENTS: Standardized questionnaire for medical, functional, and demographic data; the anxiety, depression, somatization, and phobic anxiety subscales of the Symptom/Checklist-90 (SCL-90-R); the Tinetti gait and motor screen; a physical therapy evaluation; selected laboratory tests; evaluation by a geriatrician; and a formal evaluation by a clinical psychologist, including a semistructured interview. Psychological diagnoses were assigned based on DSM-III-R criteria. MAIN RESULTS: Of these patients with chronic dizziness, 37.5 percent had a psychological diagnosis causing or contributing to their dizziness problem. Of these, only 3 were felt to have a primary psychological cause of their dizziness, and 18 had secondary psychological diagnoses. Anxiety disorders, depression, and adjustment reactions were the most common diagnoses. On multivariate analysis, factors predicting a psychological diagnosis were a positive response to hyperventilation testing, a high score on the SCL-90 anxiety subscale, and fatigue as a precipitant of dizziness. In addition, dizziness clinic patients scored significantly higher (P < 0.001) on all 4 subscales of the SCL-90 when compared with the healthy elderly, suggesting a greater degree of psychological distress among these elderly with chronic dizziness. CONCLUSIONS: Psychological disorders are rare as primary causes but are common as contributing or modulating factors in older persons with dizziness.

Age Factors↗

MR imaging in cerebral gliomas. Tissue component analysis in correlation with histopathology of whole-brain specimens.

A comparative analysis between MR examinations and histopathologic whole-brain sections regarding tumour components was performed in 5 brain specimens from patients with malignant glial brain tumours. All cases were examined with MR imaging in vitro and in 2 cases a close comparison with the MR examinations in vivo was also possible. The most homogeneous hypercellular area in malignant gliomas, giving the highest tumour grade, was not visualised on MR imaging as an isolated entity, either in vitro or in vivo. The most conspicuous tumour component, reflecting the heterogeneity of malignant gliomas, was necrosis. This feature was best depicted in the T2WI. In 4 of 5 cases, distant tumour spread of benign-looking tumour cells was found in areas visualised as normal on T2WI, outside the margins of the peritumoural oedema. In 2 cases, estimation of water content was performed immunohistochemically and a close correlation was found in each case between peritumoural and periventricular hyperintensity on T2WI and areas of pallor on the haematoxylin-eosin-stained whole-brain sections. These areas corresponded to microscopical oedema. MR imaging reflects underlying heterogeneous histopathology in malignant gliomas. The degree of malignancy of the lesion as a whole can thus be assessed by MR imaging. However, the method does not allow malignant gliomas to be correctly delineated.

Adult↗

Platelet-derived growth factor and its receptors in human glioma tissue: expression of messenger RNA and protein suggests the presence of autocrine and paracrine loops.

The expression of platelet-derived growth factor (PDGF) and its receptors was analyzed in 14 gliomas of various degrees of malignancy and compared with three gliosis cases by in situ hybridization and immunohistochemistry techniques. Expression of both PDGF A- and B-chains was higher in glioblastomas than in astrocytomas. The PDGF A-chain mRNA was predominantly found in cell-rich areas in glioblastomas. The cognate PDGF-alpha receptor (PDGFR-alpha) mRNA was heterogeneously distributed in gliomas of all grades, and PDGFR-alpha expression was higher in gliomas than in gliosis. Within some glioblastomas probed with PDGFR-alpha complementary RNA, cells heavily loaded with grains were intermingled with others containing low or moderate signals. The heavily labeled cells were often found in the vicinity of proliferating capillaries. Immunostaining with an anti-PDGF antibody and an affinity-purified antiserum against the PDGFR-alpha showed strong staining of most tumor cells with both antibodies in glioblastoma. In addition, the PDGFR-alpha antibodies yielded a strong staining of scattered cells, and the anti-PDGF antibody yielded staining of a few cells within the astrocytoma. Furthermore, high levels of the PDGF-beta receptor (PDGFR-beta) and PDGF B-chain mRNA as well as the beta receptor protein were found in hyperplastic capillaries. These results suggest the presence of autocrine and paracrine loops in glioma, activating the PDGFR-alpha in glioma cells and the PDGFR-beta in endothelial cells.

Adolescent↗

Ultrasound guided needle biopsy of brain tumors using an automatic sampling instrument.

All ultrasound (US) guided needle biopsies of brain tumors performed during an 8-year period were reviewed. Tissue samples were obtained in 112 of 115 biopsy procedures, and a histologic diagnosis was established in 99 cases (88.4%). The rate of major complications was 8.0%. The mortality is similar as in reports on stereotactic and CT-guided biopsy procedures while the morbidity is higher in our material. There are no large series available on US guided intracranial biopsy with adequate reports of complications. A modified biopsy technique is introduced here using a cutting needle and an automatic sampling instrument. The modified technique, which has been used in all cases since 1985, yielded diagnostic material in 91.5%. This method consistently provides a tissue core which is essential for a confident histopathologic diagnosis.

Biopsy, Needle↗

The use of semantic knowledge in Alzheimer's disease: evidence for impairments of attention.

The ability to access and use semantic knowledge was examined in 25 patients with Alzheimer's disease (AD) and 31 healthy controls. The AD patients exhibited intact automatic activation of semantic relationships on a semantic priming task. They also made active use of category information on a recognition memory test. However, the patients did not use semantic information to generate expectations on the semantic priming task and were inconsistent in their use of category information on the memory test. It is suggested that attentional deficits underlie the observed impairments and may in fact help explain the patterns of performance across tasks differing widely in their overt cognitive demands.

Adult↗

Aging and suppression: memory for previously relevant information.

In the 1st part of the experiment, older and younger adults read a series of high-cloze sentence frames, each missing its final word (e.g., "She ladled the soup into her____."). Subjects were instructed to predict the ending for each. For critical sentences, the predicted final word (bowl) was not shown. Instead, an unexpected but acceptable ending (lap) was provided as the target. On a subsequent indirect memory test in which subjects generated endings to medium-cloze sentences, older adults showed reliable retention of both the disconfirmed (bowl) and target (lap) endings. Younger adults showed retention of only the targets. Results are consistent with the Hasher and Zacks (1988) view that the impaired inhibitory mechanisms of older adults impede the abandonment of no-longer-relevant thoughts.

Adolescent↗