PubMed Health⌕ Search

Biomedical subjects

J Weisz

Publications and source records attributed to J Weisz.

At least 19 recordsLinked to original sources
PubMed2001

Right prefrontal activation produced by arterial baroreceptor stimulation: a PET study.

This study was performed to test the hypothesis of greater right hemispheric involvement in the processing of baroreceptor stimuli. Carotid sinus baroreceptors were stimulated by rhythmically decreasing air pressure in a neck chamber, and under control conditions the thorax was stimulated in a similar manner. Changes in regional cerebral blood flow (rCBF) were measured by PET. Baroreceptor stimulation resulted in rCBF increase in the right anterior-inferior prefrontal cortex (Brodmann areas (BA) 10/44/47) and bilaterally in BA 6/8. We conclude that in at least some stages of baroreceptor information processing the right hemisphere plays a greater role than the left hemisphere.

Adolescent↗
PubMed2000

Nuclear localization of catechol-O-methyltransferase in neoplastic and nonneoplastic mammary epithelial cells.

Catechol-O-methyltransferase (COMT) plays both a regulatory and protective role in catechol homeostasis. It contributes to the regulation of tissue levels of catecholamines and catecholestrogens (CEs) and, by blocking oxidative metabolism of catechols, prevents endogenous and exogenous catechols from becoming a source of potentially mutagenic electrophiles. Evidence implicating CEs in carcinogenesis, in particular in the hamster kidney model of estrogen-induced cancer, has focused attention on the protective role of COMT in estrogen target tissues. We have previously reported that treating hamsters with estrogens causes translocation of COMT to nuclei of epithelial cells in the renal cortex, the site of CE biosynthesis and where the cancers arise. This finding suggested that nuclear COMT may be a marker of a threat to the genome by catechols, including CEs. It is postulated that CEs play a role in the genesis of breast cancer by contributing to a state of chronic oxidative stress that is presumed to underlie the high incidence of this disease in the United States. Therefore, here we used immunocytochemistry to re-examine human breast parenchyma for nuclear COMT. In addition to confirming previous reports of cytoplasmic COMT in mammary epithelial cells, we identified nuclear COMT in foci of mammary epithelial cells in histologically normal breast tissue of virtually all control (macromastia) and cancer patients and in breast cancer cells. There was no correlation between tissue histology and the numbers of cells with nuclear COMT, the size of foci containing such cells, or intensity of nuclear COMT immunostaining. The focal nature of the phenomenon suggests that nuclear COMT does not serve a housekeeping function but that it reflects a protective response to an increased local catechol load, presumably of CEs and, as such, that it may be a characteristic of the population of women studied who share the same major risk factor for developing breast cancer, that of living in the industrialized West.

Adolescent↗
PubMed2000

Attachment and culture. Security in the United States and Japan.

Attachment theorists maintain that cultural differences are relatively minor, and they focus on universals. Here the authors highlight evidence of cultural variations and note ways in which attachment theory is laden with Western values and meaning. Comparisons of the United States and Japan highlight the cultural relativity of 3 core hypotheses of attachment theory: that caregiver sensitivity leads to secure attachment, that secure attachment leads to later social competence, and that children who are securely attached use the primary caregiver as a secure base for exploring the external world. Attachment theorists use measures of sensitivity, competence, and secure base that are biased toward Western ways of thinking: The measures emphasize the child's autonomy, individuation, and exploration. In Japan, sensitivity, competence, and secure base are viewed very differently, calling into question the universality of fundamental tenets of attachment theory. The authors call for an indigenous approach to the psychology of attachment.

Adult↗
PubMed2000

Estrogen metabolism by conjugation.

The involvement of estrogens in carcinogenic processes within estrogen-responsive tissues has been recognized for a number of years. Classically, mitogenicity associated with estrogen receptor-mediated cellular events was believed to be the mechanism by which estrogens contributed to carcinogenesis. Recently, the possibility that estrogens might contribute directly to mutagenesis resulting from DNA damage has been investigated. That damage is apparently a result of the formation of catechol estrogens that can be further oxidized to semiquinones and quinones. Those molecules represent reactive oxygen species and electrophilic molecules that can form depurinating DNA adducts, thus having the potential to result in permanent nucleotide mutation. Conjugation of parent estrogens to sulfate and glucuronide moieties; of catechol estrogens to methyl, sulfate, and glucuronide conjugates; and of catechol estrogen quinones to glutathione conjugates all represent potential "detoxification" reactions that may protect the cell from estrogen-mediated mitogenicity and mutagenesis. In this chapter, the biochemistry and molecular genetics of those conjugative reaction pathways are discussed. When applicable, the involvement of specific enzymatic isoforms is presented. Finally, the activity of many of these conjugative biotransformation reactions is subject to large interindividual variation--often due to the presence of common nucleotide polymorphisms within the genes encoding those enzymes. Functionally significant genetic polymorphisms that might contribute to variable conjugation of estrogens and catechol estrogens are also discussed.

Breast Neoplasms↗
PubMed2000

Expression of BAX in plasma cell dyscrasias.

Several studies demonstrate that the BCL-2 and BCL-XL antiapoptotic genes are variably expressed in plasma cells of patients with multiple myeloma (MM). However, the plasma cell expression of BAX protein, their major proapoptotic partner, has not been investigated. Our initial Western blot analysis of myeloma cell extracts also suggested patient variability in the expression of BAX, which was not altered by exposure to interleukin 6. To further investigate the significance of BAX expression, we performed immunohistochemistry on archival bone marrow biopsies and compared BAX staining to BCL-2 immunostaining. Expression was first evaluated in 104 patients with reactive plasmacytosis, monoclonal gammopathy of undetermined significance/smoldering MM, or active MM. An increase (P < 0.05) in expression of both BAX and BCL-2 was detected in MM patients compared with patients with reactive plasmacytosis. Patients with monoclonal gammopathy of undetermined significance/smoldering MM had intermediate values. For correlations with outcome, expression was assessed in 43 patients at diagnosis who were treated with melphalan and prednisone; 30 at diagnosis who were treated with vincristine, Adriamycin, and dexamethasone; and 29 at relapse who were treated with second-line therapy. There was no correlation between BAX or BCL-2 expression and response to chemotherapy or duration of response or between BCL-2 expression and survival. However, patients who demonstrated extremely low plasma cell BAX expression had significantly increased survival. This was true for patients initially treated with melphalan and prednisone or vincristine, Adriamycin, and dexamethasone, as well as patients studied at relapse. BAX expression did not correlate with expression of proliferating cell nuclear antigen used as a marker of proliferation. These data indicate a myeloma-specific increase in BAX expression in plasma cells and suggest that low BAX expression identifies a cohort of patients with long survival, which is not specifically associated with low proliferating cell nuclear antigen expression.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

An improved histochemical method for measuring nitric oxide synthase activity.

The previous quantitative histochemical method for measuring nitric oxide synthase (NOS) activity in tissue sections involved the loss of about 15 per cent of the NOS, presumably from the section into the reaction medium. Two changes are now described. The first is concerned with the preparation in the laboratory of the active reagent, lead ammonium citrate/acetate (LACA). The second change involves an improvement of the procedure for measuring NOS activity. The new method appears to retain all the measurable NOS activity inside the section.

Acetates↗
PubMed1999

The context of depression in clinic-referred youth: neglected areas in treatment.

OBJECTIVE: To review the empirical, methodological, and conceptual limitations of psychotherapy and pharmacotherapy for childhood and adolescent depression and to present descriptive data on key characteristics of a depressed sample to illustrate gaps in treatment. METHOD: Interview-based assessment of psychiatric features and psychosocial functioning, family psychopathology and marital adjustment, and child and parent stressful life events was performed in a sample of 43 depressed youngsters seeking outpatient treatment. RESULTS: The empirical and conceptual review indicated that treatments based on downward extensions of adult procedures are limited in number and success. Also, the treatments generally neglect the following characteristics revealed in the descriptive data: depressed youngsters have high rates of recurrent depression and comorbid conditions, impaired academic and social functioning, exposure to high rates of parental psychopathology, parental assortative mating, severe marital dysfunction, and high rates of severe stressors. CONCLUSIONS: Treatments need to be informed by and address the actual characteristics of depressed youngsters and their environments, which are highly dysfunctional.

Adolescent↗
PubMed1999

Visual event-related potentials evoked by using a virtual reality display.

This study aimed at investigating whether a virtual reality display (VRD) is an appropriate tool for evoking visual event-related potentials (VEPs). VEPs evoked by VRD stimuli were highly similar in form to VEPs evoked by using a computer monitor, both having two dominant peaks, labeled P100 and N200. Monitor and VRD N200 latencies and amplitudes were highly correlated. However, peak latencies were longer and the peaks were broader when stimuli were presented on the VRD. Besides, VRD P100 amplitude was smaller, and an N75 peak could be seen usually only on monitor VEPs.

Adult↗
PubMed1998

BCL-X expression in multiple myeloma: possible indicator of chemoresistance.

Because murine myeloma plasma cells and normal human lymph node plasma cells express BCL-X, we evaluated BCL-X expression in malignant human plasma cells. BCL-X expression was detected in several human myeloma cell lines, as well as in CD38-sorted bone marrow cells obtained from some patients. Only the antiapoptotic long form of BCL-X (BCL-X-L), was detected. Because BCL-X-L expression can protect tumor cells from apoptotic death induced by chemotherapeutic agents, we tested the clinical relevance of expression in 55 archival bone marrow biopsies. The biopsies were stained by immunohistochemistry, and BCL-X expression was correlated with the subsequent response to treatment. BCL-X expression in malignant plasma cells strongly correlated with decreased response rates in patient groups treated with either melphalan and prednisone or vincristine, Adriamycin, and dexamethasone. Response rates were 83-87% in non-BCL-X-expressing cases and 20-31% in BCL-X-expressing cases. In addition, BCL-X expression was more frequent in specimens taken from patients at relapse (77%), when compared to those at initial diagnosis (29%). Further support for the association of drug resistance with BCL-X-L expression came from studies of the 8226 dox-40 cell line. This line, which expresses p-glycoprotein and serves as a model of multidrug resistance in multiple myeloma cells, demonstrated an up-regulated expression of BCL-X-L, which was relatively specific, in that BCL-2 or BAX expression was not altered. In addition, dox-40 cells demonstrated a generalized resistance to apoptosis that was induced by several different agents. These results indicate that malignant plasma cells can express BCL-X-L and that such expression may be a marker of chemoresistant disease.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Induction of nuclear catechol-O-methyltransferase by estrogens in hamster kidney: implications for estrogen-induced renal cancer.

Catecholestrogens are postulated to contribute to carcinogenesis by causing DNA damage mediated by reactive oxygen species generated during redox cycling between catechol and quinone estrogens, and by quinone estrogens that can form depurinating adducts. The above hypothesis is based principally on studies of the cancers that develop in renal cortex of hamsters treated with primary estrogens: Hamster kidney can catalyze 2- and 4-hydroxylation of estrogens and support their redox cycling, and the kidneys of estradiol-treated hamsters show evidence of oxidative cellular and DNA damage. Here we used immunocytochemisty to test the postulate that catechol-O-methyltransferase (COMT), the enzyme that can prevent oxidation of catecholestrogens to their quinone derivatives, would be induced in renal cortex of hamsters treated with estradiol or ethinyl estradiol. In kidneys of control hamsters, COMT was localized in cytoplasm of epithelial cells of proximal convoluted tubules, predominantly in the juxtamedullary region where the estrogen-induced cancers arise. After 2- or 4-weeks of treatment with either estrogen, COMT was seen in epithelial cells of proximal convoluted tubules throughout the cortex, and many cells also showed intense nuclear COMT immunoreactivity. Estradiol-induced renal cancers were negative for COMT, but were surrounded by tubules with intense cytoplasmic and nuclear immunostaining. The nucleus-associated COMT was shown by immunoblot analysis to be the soluble form of the enzyme. Using reverse transcription-polymerase chain reaction amplification, hamster kidney COMT was shown to lack the putative nuclear localization signal sequence present in human COMT. A second phase II enzyme, CuZn-superoxide dismutase (CuZnSOD), was shown by immunocytochemistry to remain extranuclear in proximal convoluted tubules of estrogen-treated hamsters, which indicates entry of COMT into the nucleus to be selective. The findings are consistent with the catechol/quinone estrogen hypothesis of estrogen-induced cancer, while the translocation of the enzyme to the nucleus following estrogen treatment suggests a response to a threat to the genome by electrophilic products of catechols.

Amino Acid Sequence↗
PubMed1997

Focal nuclear hepatocyte response to oxidative damage following low dose thioacetamide intoxication.

Rats were treated with low doses of the hepatocarcinogen thioacetamide. Forty-eight hours following this treatment, microscopic foci of hepatic injury were observed, which were surrounded by a peripheral rim of histologically normal hepatocytes. These peripheral hepatocytes generally contained enlarged nuclei, and showed nuclear staining for 4-hydroxynonenal-protein adducts, indicative of nuclear oxidative damage. In these same hepatocytes, we also observed specific focal nuclear induction of mu-class glutathione-S-transferase and alcohol dehydrogenase I, two enzymes which are important in metabolism of 4-hydroxynonenal. Of particular interest was the concurrent nuclear induction of APE/ref-1, a multifunctional DNA repair enzyme which can function as a redox factor, and of the transcription factor Jun, whose DNA binding is facilitated by APE/ref-1. These results document an orchestrated focal nuclear response to oxidative damage produced by thioacetamide administration, and may relate to the permanent effects produced by this treatment.

Alcohol Dehydrogenase↗
PubMed1996

Expression of aromatase protein and messenger ribonucleic acid in tumor epithelial cells and evidence of functional significance of locally produced estrogen in human breast cancers.

The expression of aromatase by breast cancer cells and the role of locally produced estrogen in the stimulation of tumor growth has been controversial. The present study was performed to determine the site of aromatization in human breast cancers, using both immunocytochemistry and in situ hybridization. The functional significance of locally produced estrogens on growth of the tumor was addressed by measuring aromatase activity and a marker of proliferation (PCNA score). In addition, histocultures of some tumors were carried out to investigate whether testosterone aromatization could stimulate tumor proliferation. Of the 19 tumors investigated, 10 (52.6%) showed significant immunoreactivity to antiaromatase antibody in the cytoplasm of tumor epithelial cells and in surrounding stromal cells. The presence of aromatase mRNA detected by ISH was also located in tumor epithelial cells and stromal cell, and the pattern of expression was the same as with immunocytochemistry. In the ten tumors that showed immunoreaction to aromatase, the average aromatase activity measured in cryosections was 286.5 +/- 18.6 (SE) fmol estrogen/mg protein.h, whereas in nine tumors with weak aromatase immunoreaction, the enzyme activity was 154.7 +/- 19.3 (SE) fmol estrogen/mg protein-h (P < 0.05). The mean PCNA score was 33.8 +/- 5.1 (SE)% in strongly stained tumors and 20.8 +/- 2.0 (SE)% in weakly stained tumors (P < 0.05). Aromatase activity level and PCNA score were significantly correlated. In histoculture of four tumors, estradiol increased the incorporation of [3H]-thymidine into DNA. In two of these tumors, aromatase activity was high and [3H]-thymidine incorporation into DNA was also stimulated by testosterone. In the other two tumors that had low aromatase activity, no such stimulation occurred with testosterone. The results indicate that aromatase is expressed mainly in tumor epithelial cells and that sufficient amounts of estrogen are synthesized by the tumor to produce a proliferative response. It is concluded that estrogen synthesis by cancer cells could play a important role in promoting growth in a significant proportion of breast tumors.

Aromatase↗
PubMed1996

Focal altered compartmentation of repetitive B2 (Alu-like) sequences in rat liver following hepatocarcinogen exposure.

Rats were treated with low doses of the hepatocarcinogens dimethylnitrosamine or thioacetamide, and livers were examined 48 h later. These treatments are known to produce altered RNA compartmentation, wherein a class of repetitive RNA sequences normally restricted to the nucleus appears in the cytoplasm. Reverse transcription-PCR amplifications demonstrated that the sequences showing altered compartmentation consisted largely of a subfamily of the rodent B2 sequence family, the counterpart of human Alu sequences involved in retrotransposition. Northern blot analyses showed that these B2 sequences were found in cytoplasmic RNA as 170- to 360-nucleotide "sense" transcripts, and competition hybridization experiments established that B2 sequences represented most (if not all) of the sequences showing altered compartmentation. The major increase in B2 transcriptions in cytoplasmic RNA was not associated with any change in B2 transcription by RNA polymerase III. In situ hybridizations showed that the altered compartmentation of B2 sequences occurred in well-delineated foci within the rat liver; these foci consisted of a central region containing a prominent infiltrate of macrophages admixed with small hepatocytes and a peripheral region of histologically normal hepatocytes that showed evidence of oxidative damage. Altered compartmentation of B2 sequences may represent an important focal initiatory change in a subset of hepatocytes, whereas subsequent retrotranspositional events (associated with Alu-like sequences) could predispose initiated cell foci to alterations in promotion/progression phases.

Animals↗
PubMed1995

Effects of hemi-thalamic damage on K-complexes evoked by monaural stimuli during midafternoon sleep.

Polygraphic recording of midafternoon sleep were made in two patients with unilateral hemorrhagic infarction in the thalamus. One patient had massive signs of reduced attention in the contralesional space following right lateral thalamic lesion. The other patient had infarction centered in the left posterior ventrolateral thalamus with no signs of hemineglect. In both cases, waking and sleep records showed symmetric background EEG at C3 and C4. In contrast, monaural sounds (clicks) elicited bilaterally symmetrical K-complexes only in the second patient. In the other patient with right thalamic lesion, both left- and right-ear clicks failed to elicit K-complexes in the right cerebral hemisphere, whereas normal K-complexes continued to appear at C3 as well as at Fz. In neither patient did the frequency of evoked K-complexes depend on the side of the stimulated ear. Unlike K-complexes, sleep spindles were bilaterally absent in patient 1. The right hemisphere does not seem to have a special role in control of circuits generating K-complexes.

Acoustic Stimulation↗
PubMed1995

Measurement of nitric oxide synthase activity in sections of rat liver.

In the previous communication we described a histochemical method for measuring soluble guanylate cyclase (sGC) activity in sections of rat liver. In theory, this method could be used to assess nitric oxide synthase (NOS) activity by the increased sGC activity induced by the additional presence of the substrates for NOS activity. We found that this was correct provided that the concentration of the colloid stabilizer in the reaction medium was decreased to just below the concentration required to fully stabilize the guanylate cyclase activity in the sections. This was related to the fact that the site of NOS activity was different from that of the sGC activity in the hepatocytes, so that the NO generated had to diffuse from the Kupffer cells to the hepatocytes as could occur only in partially unstabilized sections. Optimal concentrations of arginine and of NADPH have been determined for demonstrating NOS activity; the increased reaction was shown to be largely inhibited by methyl-arginine.

Animals↗
PubMed1995

Histochemistry of guanylate cyclase activity.

Guanylate cyclase liberates pyrophosphate from guanosine triphosphate (GTP). In studies published previously, this phosphate is trapped by lead ions even though it is known that free lead ions inactivate a considerable proportion of this enzymatic activity. To overcome the damaging effects of fixation, this study used fresh cryostat sections stabilized with a sufficient concentration of a collagen-derived polypeptide to ensure no measurable loss of guanylate cyclase activity. To avoid the damaging influence of free lead ions, we used a hidden metal capture reagent, i.e., a complex of lead ammonium citrate/acetate that does not react with GTP but which rapidly forms a precipitate with the pyrophosphate liberated by the enzyme. The lead precipitate is then converted into the colored sulfide which is measured in individual cells by microdensitometry. This system was used to measure guanylate cyclase activity in individual cells in unfixed sections of rat liver.

Animals↗