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Biomedical subjects

D Katz

Publications and source records attributed to D Katz.

At least 109 records · Page 6Linked to original sources
PubMed1990

Development of non-Hodgkin lymphoma in a cohort of patients with severe human immunodeficiency virus (HIV) infection on long-term antiretroviral therapy.

OBJECTIVE: To describe the incidence of non-Hodgkin lymphoma in a group of patients with symptomatic human immunodeficiency virus (HIV) infection receiving long-term dideoxynucleoside antiretroviral therapy. DESIGN: We examined the records of all patients with the acquired immunodeficiency syndrome (AIDS) or severe AIDS-related complex who were entered into three long-term phase I trials of zidovudine (azidothymidine, AZT) or zidovudine-containing regimens at the National Cancer Institute between 1985 and 1987. SETTING: The Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland. PARTICIPANTS: Fifty-five HIV-infected patients with AIDS or severe AIDS-related complex. MEASUREMENTS AND MAIN RESULTS: Eight of fifty-five patients (14.5%; 95% CI, 6.5% to 26.7%) developed a high-grade non-Hodgkin lymphoma of B-cell type, a median of 23.8 months (range, 13 to 35 months) after starting antiretroviral treatment. Using the method of Kaplan and Meier, the estimated probability of developing lymphoma by 30 months of therapy was 28.6% (CI, 13.7% to 50.3%) and by 36 months, 46.4% (CI, 19.6% to 75.5%). The patients who developed lymphoma had less than 100 T4 cells/mm3 for a median of 17.8 months (range, 7 to 35 months) and less than 50 T4 cells/mm3 for a median of 15.3 months (range, 5.5 to 35 months) before the diagnosis. All patients presented with non-Hodgkin lymphoma in extranodal sites, and two developed primary brain involvement in the setting of Toxoplasma infection. CONCLUSION: Patients with symptomatic HIV infection who survive for up to 3 years on antiretroviral therapy may have a relatively high probability of developing non-Hodgkin lymphoma. Prolonged survival in the setting of profound immunosuppression with substantial T4-cell depletion is probably an important factor in the development of these lymphomas. However, a direct role of therapy itself cannot be totally discounted. As improved therapies for the treatment of HIV infection and its complications result in prolonged survival, non-Hodgkin lymphoma may become an increasingly significant problem.

AIDS-Related Complex↗
PubMed1990

Treatment of osteoporosis with human parathyroid peptide and observations on effect of sodium fluoride.

OBJECTIVE: To evaluate the need for a randomised study of treatment of spinal osteoporosis with human parathyroid peptide in the secondary prevention of crush fractures; to study the effect of human parathyroid hormone peptide 1-34 plus sex hormones on vertebral body cancellous bone; and, separately, to determine the effect of relatively low doses of sodium fluoride plus calcium on spinal bone mineral density. DESIGN: Open study of patients with primary or postmenopausal osteoporosis. All patients had serial bone densitometry of the spine by quantitative computed tomography and dual photon absorptiometry as well as serial densitometry of the radial midshaft (cortical) and radial distal (trabecular) bone by quantitative computed tomography. Changes in the spinal bone not forming the spongiosa of the vertebral bodies ("cortical" bone) were determined from the difference between the two axial measurements, after correction to the same units of measurement. SETTING: Northwick Park Hospital and Medical Research Council Clinical Research Centre. PATIENTS: 24 Patients who fulfilled the conventional criteria for type 1 (vertebral) osteoporosis not secondary to recognised causes other than sex hormone deficiency and with at least one crush or wedge vertebral fracture and a spinal bone density (quantitative computed tomography) less than 80 mg/cm3 or two or more fractures. Twelve patients received human parathyroid peptide and 12 sodium fluoride; they were not randomised. MAIN OUTCOME MEASURES: Trends in axial and peripheral bone mass values determined by linear, time dependent regression analyses. RESULTS: The patients receiving the peptide showed a substantial increase in vertebral spongiosa (mean 25.6 mg/cm2 two years after the start of treatment). No significant changes were seen in spinal cortical or radial bone density. The patients receiving sodium fluoride showed roughly equal increases in cancellous and cortical bone over the same period (mean increase in vertebral spongiosa 16.1 mg/cm3). No significant changes were seen in radial bone. CONCLUSIONS: Treatment of postmenopausal women with human parathyroid peptide selectively increases spinal cancellous bone density by amounts that may prove useful in secondary prevention. Peptide treatment should now be tested in a randomised study in which the important end point is prevention of fractures as the usefulness of sodium fluoride in this context is doubtful.

Bone Density↗
PubMed1990

Rapid periarticular bone loss in rheumatoid arthritis. Possible promotion by normal circulating concentrations of parathyroid hormone or calcitriol (1,25-dihydroxyvitamin D3).

For approximately 2 years, bone loss was measured in women with early stages of rheumatoid arthritis (RA) and in control subjects, using serial computed tomography and dual photon absorptiometry. Rapid trabecular bone loss from the distal radius was observed in the RA patients but not the controls. The bone loss correlated with initial plasma levels of parathyroid hormone and 1,25-dihydroxyvitamin D3 (calcitriol) concentrations. It has been suggested that these humoral factors may interact with cytokines or other mediators produced in the adjacent wrist joint. Losses of the cortical bone of the radial midshaft and the lumbar spine were modest and were comparable in the 2 groups. Indices relating to both bone formation and bone resorption predicted bone loss at these 2 sites, but changes in the parathyroid hormone and calcitriol concentrations did not.

Absorptiometry, Photon↗
PubMed1990

Serologically defined linear epitopes in the E2 envelope glycoprotein of Semliki Forest virus.

A set of 41 overlapping peptides, representing the complete sequence of SFV-E2 protein were synthesized and analyzed in the ELISA test against murine anti-SFV sera. No single peptide was recognized by all antisera. Eight peptides were found to be highly reactive with hyperimmune anti-SFV sera. Six out of the eight peptide sequences coincide with the most hydrophilic regions of SFV-E2. Out of these, four peptides (amino acid positions 16-35, 61-80, 166-185, 286-305) that contain the least number of alphavirus conserved residues were selected. This panel constitutes the minimal number of peptides necessary and sufficient for specific recognition of hyperimmune mouse anti-SFV sera.

Antigens, Viral↗
PubMed1990

[Bilateral claw deformity of the fingers due to fasciitis with eosinophilia (Shulman's syndrome). Apropos of a case].

Shulman's syndrome or fasciitis with eosinophilia is a disease of unknown origin with unclear relations with scleroderma, characterised by thickening of the fascia superficialis associated with blood eosinophilia. This diagnosis should be considered in a patient presenting with a lesion of the anterior surface of the forearms, which have an "armoured" appearance, associated with claw deformity of the wrist, hand and fingers. The diagnosis is based on cutaneo-muscular biopsy and treatment consists of corticosteroids. The clinical course is generally favourable, although recovery is sometimes incomplete. There is generally no visceral or systemic involvement apart from rare cytopenic forms which must be identified.

Adrenal Cortex Hormones↗
PubMed1990

Enhanced susceptibility to histamine-induced cardiac arrhythmias in spontaneously hypertensive rats.

To clarify mechanisms underlying an enhanced susceptibility to cardiac rhythm disturbances in hypertension and myocardial hypertrophy, we evaluated the vulnerability to histamine-induced arrhythmias of isolated left ventricles from spontaneously hypertensive rats (SHR) and age-matched controls (Wistar-Kyoto rats, WKY). Before drug administration, left ventricle-to-body weight ratios, spontaneous firing rates, and the incidence of arrhythmias (including delayed afterdepolarizations) were significantly increased in SHR ventricles versus WKY. In addition, action potential duration (APD) was prolonged in SHR at all levels of repolarization. In WKY but not SHR hearts, histamine (10(-7)-10(-4) M) increased spontaneous firing rates; the incidence of arrhythmias was increased in all hearts, but the response to histamine was most pronounced and occurred at lower threshold drug levels in SHR. After potentials and triggered activity were observed only in SHR. The H2-receptor blocker cimetidine (10(-5) M) and the Ca2(+)-channel antagonist verapamil (10(-6) M) each attenuated the arrhythmogenic influence of histamine in SHR and WKY preparations. Neither chlorpheniramine nor propranolol had any effect. The enhanced vulnerability to arrhythmogenesis observed in SHR myocardium may reflect elevated intracellular calcium levels, which may in turn be potentiated by local ischemia and/or intracardiac histamine release.

Action Potentials↗
PubMed1990

Pathology of temporal lobe foci: correlation with CT, MRI, and PET.

Twenty-six patients with medically refractory complex partial seizures had temporal lobectomy after evaluation, which included prolonged scalp EEG recordings, positron emission tomography (PET), MRI, and x-ray CT. PET showed a region of focal interictal temporal hypometabolism corresponding to electrographic localization of seizure onset in 21. Five patients had a region of increased MRI signal intensity on the spin echo image in the region of the EEG focus, 2 had an abnormality ipsilateral to but distinct from the EEG focus, and 1 had bilateral findings. CT was abnormal in 3 cases; 2 had tumors. Three patients had low grade tumors (1 with a normal PET). PET can detect metabolic dysfunction associated with mild pathologic changes in epileptic foci, but increased signal intensity on MRI does not necessarily correlate with the degree of pathologic abnormality. Tumors may be less likely when both CT and MRI are normal.

Adolescent↗
PubMed1989

ICI 164,384, a pure antagonist of estrogen-stimulated MCF-7 cell proliferation and invasiveness.

Estrogen is known to stimulate the proliferation and basement membrane invasiveness of the MCF-7 human breast cancer cell line. We have compared the new steroidal antiestrogen ICI 164,384, the triphenylethylene 4-hydroxytamoxifen (OHT), and the benzothiophene LY 117018, for their effects on the proliferation and invasiveness of the MCF-7 cell line and its antiestrogen-resistant variant LY-2. While all three antiestrogens blocked the proliferative effects of 17 beta-estradiol on MCF-7 cells, OHT and LY 117018, but not ICI 164,384 stimulated their proliferation in the absence of estrogen. The proliferative effects of OHT and LY 117018 were blocked by ICI 164,384. Basement membrane invasiveness of MCF-7 cells was stimulated by 17 beta-estradiol and OHT, but not LY 117018 or ICI 164,384. Both ICI 164,384 and LY 117018 were able to block the invasiveness induced by either 17 beta-estradiol or OHT. The LY-2 antiestrogen-resistant variant of the MCF-7 cell line showed increased basal proliferation, and responded only slightly to estrogen. ICI 164,384, but not OHT or LY 117018 antagonized the effects of 17 beta-estradiol, but did not reduce proliferation below control levels. The LY-2 line was not resistant to the antiestrogenic effects of LY 117018 or ICI 164,384 on invasiveness, and was stimulated by LY 117018 for this parameter. Thus, ICI 164,384 is a pure antiestrogen for MCF-7 cell proliferation and invasiveness, and may offer clinical advantage over nonsteroidal antiestrogens which can stimulate these activities in tumor models in vitro.

Basement Membrane↗
PubMed1989

Histamine attenuates the arrhythmogenic effects of norepinephrine in hearts of spontaneously hypertensive rats.

A potential physiological role for cardiac histamine and its interaction with norepinephrine were investigated in isolated left ventricles from spontaneously hypertensive rats (SHR). Prior to drug administration, left ventricle-to-body weight ratios and spontaneous firing rates (beats per min) were significantly increased in SHR ventricles vs. age- and sex-matched controls (WKY). Also, action potential duration was significantly prolonged in SHR at all levels of repolarization. In all hearts, norepinephrine (10(-7)-10(-4) M) increased spontaneous rate and the percent incidence of arrhythmias. The H2-receptor antagonist cimetidine (10(-5) M) potentiated the rate and arrhythmogenic effects of norepinephrine in SHR and, to a lesser extent, in WKY preparations; propranolol (10(-6) M) reduced them. Histamine (10(-7) M) also inhibited the norepinephrine-induced increase in arrhythmias in SHR, but not in WKY. The attenuation of adrenergically induced rhythm disturbances by histamine and their potentiation by cimetidine in hypertensive hearts support the hypothesis that histamine plays a role as a postjunctional modulator of adrenoceptor function in a setting of hypertension and myocardial hypertrophy.

Action Potentials↗
PubMed1989

Race differences in pubic symphyseal aging patterns in the male.

A well-documented multiracial sample of 704 male pubic bones allows for rigorous testing for racial differences in pubic symphyseal metamorphosis. The relationship between estimated age (using a modified Todd six-stage system) and age is examined as a function of race (White, Black, Mexican). One set of analyses incorporates linear regression models, while a second set does not impose such structure on the relationship. The latter analyses incorporate analysis of variance and related procedures. Significant differences in age are found across racial groups; it is seen that Blacks and Mexicans with advanced pubic symphyseal patterns tend to have lower ages than Whites. We do not address the question of causality, which may involve genetic factors and/or environmental variables such as diet, alcoholism, or drug abuse.

Adolescent↗
PubMed1989

Transforming growth factors type beta 1 and beta 2 are equipotent growth inhibitors of human breast cancer cell lines.

At least one member of the TGF-beta family, TGF-beta 1, has been previously shown to inhibit the anchorage-independent growth of some human breast cancer cell lines (Knabbe et al., 1987; Arteaga et al., 1988). Members of the TGF-beta family might, therefore, provide new strategies for breast cancer therapy. We have studied the inhibitory effects of TGF-beta 1 and TGF-beta 2 on the anchorage-independent growth of the oestrogen receptor-negative cell lines MDA-MB-231, SK-BR-3, Hs578T, MDA-MB-468, and MDA-MB-468-S4 (an MDA-MB-468 clone not growth inhibited by EGF) and the estrogen receptor-positive cell lines MCF7, ZR-75-1, T-47D. TGF-beta 1 and TGF-beta 2 caused a 75-90% growth inhibition of MDA-MB-231, SK-BR-3, Hs578T, and MDA-MB-468 cells and a 50% growth inhibition of ZR-75-1 and early passage (less than 100) MCF7 cells. T-47D cells responded to TGF-beta only in serum-free conditions in the presence of IGF-1 or EGF. The growth of MDA-MB-468-S4 cells and late passage (greater than 500) MCF7 cells was not inhibited by TGF-beta 1 or TGF-beta 2. TGF-beta-sensitive MCF7 and MDA-MB-231 cells did not respond to Muellerian inhibiting substance (MIS), a TGF-beta-related polypeptide. TGF-beta 1 or TGF-beta 2 were mutually competitive for receptor binding with a similar affinity (Kd 25-130 pM, 1,000-13,000 sites per cell). To determine the time course of the TGF-beta effect, an anchorage-dependent growth assay was carried out using MDA-MB-231 cells. Growth inhibition occurred at 6 days, and cell-cycle changes were seen 12 hr after the addition of TGF-beta. Cells accumulated in the G1 phase and were thus inhibited from entering the S-phase. These data indicate that TGF-beta is a potent growth inhibitor in most breast cancer cell lines and provide a basis for studying TGF-beta effects in vivo.

Anti-Mullerian Hormone↗
PubMed1989

Structural requirements for anthracycline-induced cardiotoxicity and antitumor effects.

By employing rat cardiac myocytes in culture and mouse L-1210 leukemia cells, we have compared different anthracycline analogs with respect to their ability to kill cardiac myocytes and tumor cells. Anthracyclines induced a decrease in cellular ATP and glutathione from both cardiac myocytes and L-1210 cells in a time- and concentration-dependent fashion. Moreover, the decrease in ATP in cardiac myocytes was followed by release of the cytoplasmic enzyme lactic acid dehydrogenase and of adenine nucleotides after anthracycline treatment. At very low concentrations of anthracyclines, at which ATP and glutathione were not affected, the drugs induced complete cessation of the growth of L-1210 cells. Some structural alterations in the anthracycline molecule resulted in parallel changes in antitumor activity and in cardiotoxicity. But other structural alterations resulted in dissimilar changes in antitumor activity and cardiotoxicity. Although the results indicate that the structural requirements for inducing cardiotoxicity and antitumor activity may be different, they also indicate that the mechanisms by which anthracycline causes cell death in tumor cells and cardiac myocytes may be the same.

Animals↗
PubMed1989

A rapid method for in situ hybridization for viral DNA in brain biopsies from patients with AIDS.

Brain biopsy is often necessary in the diagnosis of neurological complications found in AIDS patients. We describe here a rapid method of tissue preparation and in situ DNA hybridization for detecting JC virus DNA in frozen brain biopsy sections which allows the diagnosis of progressive multifocal leukoencephalopathy to be established on the day of surgery. Once the diagnosis is established, therapeutic and management decisions can be made more easily. The commercial availability of biotinylated probes for several of the DNA viruses most frequently encountered in brain infections of AIDS patients will provide wide application of these techniques to patient management.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Expression of the BZLF1 latency-disrupting gene differs in standard and defective Epstein-Barr viruses.

Previous experiments using gene transfer of plasmids with heterologous promoters identified an Epstein-Barr virus (EBV) gene (BZLF1) whose product (ZEBRA) switches the virus from a latent to a replicative state. We have now studied expression of ZEBRA in lymphoid cells harboring either standard virus or a mixture of standard and defective (heterogeneous [het]) viruses. A high-titer rabbit antiserum to a TrpE-BZLF1 fusion protein was used to identify ZEBRA expressed from standard and het EBV DNA. These ZEBRA proteins could be distinguished from each other on the basis of their electrophoretic mobilities. ZEBRA could not be detected in cells latently infected with standard EBV. However, within 6 h after induction of replication by sodium butyrate, ZEBRA appeared and persisted long thereafter. Synthesis of ZEBRA was insensitive to phosphonoacetic acid or acycloguanosine, behavior characteristic of an early replicative protein. ZEBRA was constitutively expressed in cells containing both defective and standard EBV genomes. ZEBRA was made predominantly from the het genome but also from the standard genome. Control of BZLF1 expression appears to occur at the transcriptional level. No BZLF1-specific transcript was detected in cells containing only standard latent EBV. BZLF1 transcripts could be detected in these cells if virus replication was induced by treatment with butyrate. Cells bearing both standard and het genomes did not require addition of an exogenous inducing agent to transcribe the BZLF1 gene. The experiments suggest that regulation of transcription of the BZLF1 gene is a pivotal event in the control of EBV replication.

Burkitt Lymphoma↗
PubMed1989

The black thyroid: an unusual finding during neck exploration.

Black thyroid discolouration has been reported in post-mortem examinations on patients who have previously taken minocycline. The discovery of this phenomenon during neck exploration and a review of the possible mechanism of black thyroid discolouration are discussed in this paper.

Adult↗
PubMed1989

The effects of a constitutive expression of transforming growth factor-alpha on the growth of MCF-7 human breast cancer cells in vitro and in vivo.

It has been suggested that transforming growth factor-alpha (TGF-alpha) is a mitogenic autocrine growth factor for human breast cancer cells, responsible for mediating the mitogenic effects of 17 beta-estradiol (E2) in responsive cells. To test this hypothesis we have introduced eukaryotic expression vectors directing the expression of TGF-alpha mRNA into E2-responsive MCF-7 human breast cancer cells. Transfected cells produce levels of TGF-alpha equivalent to or greater than those produced by both E2-stimulated MCF-7 cells and hormone-independent MDA-MB-231 cells. One transfected clone (H8) secretes sufficient TGF-alpha to fully down-regulate EGF-R expression. However, both of the transfected clones that constitutively secrete elevated levels of TGF-alpha (A8 and H8) respond to E2 stimulation in vitro by increasing the rate of cellular proliferation and inducing PGR synthesis. The basal proliferative capacity of H8 and A8 cells is equivalent to that of the parental cells and to cells transfected only with the G418 (neomycin) resistance gene. Furthermore, the TGF-alpha cDNA-transfected clones do not form tumors in ovariectomized athymic nude mice without E2 supplementation. Thus, the precise role of TGF-alpha in mediating either the in vivo or the in vitro mitogenic effects of E2 in MCF-7 human breast cancer cells remains unclear. While TGF-alpha expression may be essential, it is not sufficient alone to induce the fully E2-independent phenotype. Thus, TGF-alpha may function in combination with other E2-induced growth factors to control breast cancer proliferation and tumorigenesis.

Breast Neoplasms↗
PubMed1989

The inter-relationships between ovarian-independent growth, tumorigenicity, invasiveness and antioestrogen resistance in the malignant progression of human breast cancer.

Among the processes contributing to the progressive acquisition of the highly malignant phenotype in breast cancer are ovarian-independent growth, antioestrogen resistance and increased metastatic potential. We have previously observed that increased invasiveness and development of ovarian-independent growth occur independently. In an attempt to define the inter-relationships between these processes further, we have compared the phenotypes of ovarian-independent, invasive and antioestrogen-resistant sublines of the ovarian-dependent human breast cancer cell line MCF-7. Cells acquiring ovarian-independent growth can retain sensitivity to anti-oestrogens. One clone of MCF-7 cells selected for stable antioestrogen resistance has become non-tumorigenic but its invasive potential remains unaltered. Thus, acquisition of some characteristics of the progressed phenotype can occur independently. This phenomenon of independent parameters in phenotypic progression could partly explain the considerable intra- and intertumour heterogeneity characteristic of breast tumours.

Animals↗