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Biomedical subjects

A Katz

Publications and source records attributed to A Katz.

At least 235 records · Page 13Linked to original sources
PubMed1993

Radiation-associated hyperparathyroidism: comparison of adenoma growth rates, inferred from weight and duration of latency, with prevalence of mitosis.

In sporadic parathyroid adenomas, the birth rate of new cells, based on the proportion of S-phase cells at the time of surgical excision, is much too low to account for growth of the tumor from a single cell, as is required by monoclonal origin, even if the mutation occurred in utero, indicating that the rate of cell proliferation has slowed down during the course of the disease. In radiation-associated hyperparathyroidism, the age at irradiation provides a more accurate upper limit to the age of the tumor. The purpose of this study was to relate this age to the prevalence of mitosis as an alternative index of current cell proliferation. In 56 such patients, the geometric mean for the minimum cell birth rate needed for growth from a single cell to the observed size in the time available was 54.4%. In 44 patients, including 31 of the previous 56 and an additional 13, sampling an average of 220,000 cell profiles, 15 mitoses were found, an overall prevalence of 0.15/10(5), which corresponds to a cell birth rate of 2.7%/yr, assuming the duration of mitosis to be 0.5 h. If cases with no mitosis were assigned a value of half the detection limit, the geometric mean mitotic index was 0.360/10(5), and the corresponding cell birth rate was 6.4%/yr. This is more than 8 times smaller than the minimum birth rate required and 20 times smaller than the cell birth rate in meningiomas, suggesting that such extreme reduction of cell birth rate is a unique feature of parathyroid adenomas, rather than a general feature of all benign tumors. The data support the set-point hypothesis, which reconciles the earlier concept of focal hyperplasia with monoclonal origin and provides an alternative nonneoplastic mechanism of etiology for the usual nonprogressive form of the disease.

Adenoma↗
PubMed1993

Phosphofructokinase activity in human skeletal muscle: effects of euglycaemic hyperinsulinaemia and fasting.

Euglycaemic (approximately 5.5 mmol l-1) hyperinsulinaemic (60 mU [m2]-1 min-1) clamps were performed for 2 h after a 10 h and after a 72 h fast on man. Biopsies were obtained from the quadriceps femoris muscle before and after each clamp and analysed in vitro for phosphofructokinase (PFK) activity under optimal (pH 8.2) and regulatory conditions (pH 7.0 and low substrate concentrations). Insulin stimulated, and fasting inhibited basal and insulin stimulated muscle glycolysis in vivo. However, PFK activity, measured in vitro, was not altered by any of the treatments (at pH 8.2: basal [10 h] = 102 +/- 5 mmol kg-1 dry wt min-1, clamp [10 h] = 104 +/- 6; basal [72 h] = 107 +/- 6, clamp [72 h] = 110 +/- 4 (at pH 7.0: basal [10 h] = 10.7 +/- 0.9, clamp [10 h] = 10.7 +/- 1.7; basal [72 h] = 11.7 +/- 2.4, clamp [72 h] = 9.7 +/- 1.6). Similarly, the activity ratio (7.0/8.2) was also not significantly altered by any of the treatments. Euglycaemic hyperinsulinaemia did not increase and fasting did not decrease the contents of activating hexose phosphates in muscle. The activity ratio increases after administration of epinephrine in rabbit muscle and the increase is thought to be mediated through a combination of increased hexose phosphates and adenine nucleotides (cyclic AMP) (Mansour TE. J Biol Chem 1972; 247: 6059-66). We confirmed that 2 h of epinephrine infusion also increased the activity ratio and hexose phosphates (but not fructose 2,6-P2) in human muscle.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

PSA density (PSAD). Role in patient evaluation and management.

Prostate Specific Antigen (PSA) is the most accurate serum marker for cancer of the prostate. However, sensitivity and specificity are suboptimal, especially at the intermediate levels between 4.1 and 10.0 ng/ml (monoclonal). For intermediate PSA levels, prostate specific antigen density (PSAD) provides unique information regarding the need for biopsy and the likelihood of prostate cancer. This article summarizes the utility of PSAD in diagnosing and treating prostate cancer.

Aged↗
PubMed1993

[Thrombolysis for evolving myocardial infarction in a rural primary care clinic].

Early thrombolytic therapy gives maximum benefit in acute myocardial infarction. In remote rural areas with no mobile intensive care service there is a significant delay between onset of symptoms and administration of thrombolytic therapy which has a critical impact on revascularization. Thrombolytic therapy with streptokinase 1,500,000 U was given in a primary care rural clinic to 2 patients with evolving myocardial infarction 45-50 minutes from onset of symptoms. In both patients, who were transported to hospital after the therapy, there were clinical signs of reperfusion. There were no complications during treatment or transportation. We conclude that thrombolytic therapy given for evolving myocardial infarction in a rural primary care clinic is possible and safe.

Aged↗
PubMed1993

The prognostic importance of two easily obtainable noninvasive markers after intravenous thrombolytic therapy in acute myocardial infarction.

The predictability of left ventricular function, short- and long-term prognosis, assessed by means of two easily obtainable noninvasive markers, was prospectively studied in 110 consecutive patients undergoing thrombolytic therapy for acute myocardial infarction. Positive noninvasive markers were defined as follows: a) > 50% reduction in ST segment elevation within 120 min of initiating therapy, and b) early peak of creatine kinase (CK) activity < 12h after the start of thrombolysis. Seventy-five (68%) of the patients had two positive markers and are classified as the responder group. The nonresponder group consisted of 35 patients (32%) who had 0-1 positive markers. Left ventricular function was assessed 6-12 weeks after therapy by equilibrium radionuclide ventriculography. Left ventricular ejection fraction (LVEF) and survival rates at 1 month and 36 months were significantly higher in the responder group compared to the nonresponder group (54 +/- 12% vs. 43 +/- 11%, P < 0.05; 99% vs. 89%, P < 0.06; and 95% vs. 80%, P < 0.05 respectively). Thus, the combined analysis of two easily obtainable noninvasive markers can predict post-treatment preservation of left ventricular function and survival up to 36 months in patients with acute myocardial infarction undergoing thrombolytic therapy.

Adult↗
PubMed1993

Destructive spondyloarthropathy in a patient on continuous ambulatory peritoneal dialysis for 13 years.

Since 1984 there have been reports of a destructive spondyloarthropathy occurring in patients on long-term hemodialysis. The primary abnormality appears to be an accumulation of beta 2-microglobulin, which is not adequately removed by dialysis, and forms amyloid deposits in articular and periarticular tissues. We report a case of this disease in a patient treated only by peritoneal dialysis. While this form of treatment may delay the development of arthropathy, as compared to hemodialysis, it does not prevent it. An increasing incidence of this disorder may be expected, since increasing numbers of patients have been on long-term peritoneal dialysis.

Aged↗
PubMed1992

Activation of phospholipase C by alpha 1-adrenergic receptors is mediated by the alpha subunits of Gq family.

High efficiency transient transfection of Cos-7 cells was previously used to establish the functional coupling between G alpha q/G alpha 11 and phospholipase C beta 1 (Wu, D., Lee, C-H., Rhee, S. G., and Simon, M. I. (1992) J. Biol. Chem. 267, 1811-1817). Here the same system was used to study the functional coupling between other guanine nucleotide-binding regulatory protein (G-protein) alpha subunits and phospholipases and to study which G alpha subunits mediate the activation of phospholipase C by the alpha 1-adrenergic receptor subtypes, alpha 1 A, alpha 1 B, and alpha 1 C. We found that G alpha 14 and G alpha 16 behaved like G alpha 11 or G alpha q, i.e. they could activate endogenous phospholipases in Cos-7 cells in the presence of AIFn. The synergistic increase in inositol phosphate release in Cos-7 cells after they were cotransfected with cDNAs encoding G alpha subunits and phospholipase C beta 1 indicates that both G alpha 16 and G alpha 14 can activate phospholipase C beta 1. The activation of phospholipase C beta 1 was restricted to members of the Gq subfamily of alpha subunits. They activated phospholipase C beta 1 but not phospholipase C gamma 1, gamma 2, or phospholipase C delta 3. The cotransfection of Cos-7 cells with cDNAs encoding three different alpha 1-adrenergic receptors and G alpha q or G alpha 11 leads to an increase in norepinephrine-dependent inositol phosphate release. This indicates that G alpha q or G alpha 11 can mediate the activation of phospholipase C by all three subtypes of alpha 1-adrenergic receptors. With the same assay system, G alpha 16 and G alpha 14 appear to be differentially involved in the activation of phospholipase C by the alpha 1-adrenergic receptors. The alpha 1 B subtype receptor gave a ligand-mediated synergistic response in the cells cotransfected with either G alpha 14 or G alpha 16. However, the alpha 1 C receptor responded in cells cotransfected with G alpha 14 but not G alpha 16, and the alpha 1 A receptor showed little synergistic response in cells transfected with either G alpha 14 or G alpha 16. The ability of the alpha 1 A and alpha 1 C receptors to activate phospholipase C through G alpha q and G alpha 11 was also demonstrated in a cell-free system.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

Subunits beta gamma of heterotrimeric G protein activate beta 2 isoform of phospholipase C.

The activation of heterotrimeric G proteins results in the exchange of GDP bound to the alpha-subunit for GTP and the subsequent dissociation of a complex of the beta- and gamma-subunits (G beta gamma). The alpha-subunits of different G proteins interact with a variety of effectors, but less is known about the function of the free G beta gamma complex. G beta gamma has been implicated in the activation of a cardiac potassium channel, a retinal phospholipase A2 (ref. 9) and a specific receptor kinase, and in vitro reconstitution experiments indicate that the G beta gamma complex can act with G alpha subunit to modulate the activity of different isoforms of adenylyl cyclase. Of two phospholipase activities that can be separated in extracts of HL-60 cells, purified G beta gamma is found to activate one of them. Here we report that in co-transfection assays G beta gamma subunits specifically activate the beta 2 and not the beta 1 isoform of phospholipase, which acts on phosphatidylinositol. We use transfection assays to show also that receptor-mediated release of G beta gamma from G proteins that are sensitive to pertussis toxin can result in activation of the phospholipase. This effect may be the basis of the pertussis-toxin-sensitive phospholipase C activation seen in some cell systems (reviewed in refs 13 and 14).

Adenylate Cyclase Toxin↗
PubMed1992

Expression of CD34 and platelet glycoproteins during human megakaryocytic differentiation.

Megakaryocyte (MK) progenitors express the CD34 antigen, but the precise stage along the MK differentiation at which the CD34 is turned off is not known. Purified marrow CD34+ cells give rise within 4 days in culture to rare mature MK, suggesting that some MK precursors bear the CD34 antigen. By multiparameter flow cytometry, CD34+ cells bearing platelet glycoproteins (GP) could be detected, but at a low frequency (less than 2% of the marrow CD34+ cells). We used an in vitro liquid suspension culture to selectively amplify MK differentiation. CD34+ cells were isolated after 6 days before a wave of mature MK. These cells gave rise within another 4 days in culture to numerous MK (up to 50%), showing that these CD34+ cells were greatly enriched in MK precursors. This was confirmed by ultrastructural studies that showed the presence of typical promegakaryoblasts. By flow cytometry, three populations of small cell size could be defined: CD34+ GPIIIa-, CD34+ GPIIIa+, and CD34- GPIIIa+ cells. The two GPIIIa+ populations were almost pure immature blastic MK. alpha-Granules were rare in the CD34+ GPIIIa+ cells, whereas they were more developed in the CD34- GPIIIa+ cells, which also exhibited demarcation membranes. Approximately 45% of the two GPIIIa+ cell populations were capable of undergoing at least one cell division and of giving rise to a polyploid progeny. However, proliferation and polyploidization capacities were higher in the CD34+ GPIIIa+ than in the CD34- GPIIIa+ cells. A small fraction of GPIIIa+ cells (about 10%) were able to give rise to MK colonies containing a maximum of 16 cells for the double-positive cells. GPIb was expressed on about sixfold less cells than GPIIIa, but was detected on a few CD34+ cells. Most double-stained (CD34+ GPIb+) cells were polyploid. CD34- GP+ cells (more mature) contained less polyploid MK than the CD34+ GP+ fraction. Altogether, these findings show that CD34 is still expressed on a polyploid transitional immature MK and that GPIIIa is present on some MK progenitors with low proliferative capacities. They also suggest that the expression of CD34 is related to the ability of the MK precursors to accomplish DNA synthesis (either cell division or endomitosis). Such a characterization will facilitate the investigation of the role of the different cytokines on MK differentiation.

Adult↗
PubMed1992

The G alpha q and G alpha 11 proteins couple the thyrotropin-releasing hormone receptor to phospholipase C in GH3 rat pituitary cells.

Thyrotropin-releasing hormone stimulates the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) in GH3 cell membranes. The stimulation of the phosphoinositide phospholipase C (PI/PLC) activity can be blocked by incubation of GH3 membranes with polyclonal antibodies directed against a peptide derived from the C-terminal region of G alpha q and G alpha 11. Antibodies directed against the C-terminal region of other G alpha-subunits had no detectable effect. The inhibition was specific since addition of the peptide that was used to prepare the antibody completely reversed the inhibition. Further evidence for the coupling of the TRH receptor to G alpha q or G alpha 11 comes from a reconstitution experiment in which human embryonic kidney cells were transiently transfected with cDNAs corresponding to the TRH receptor, G alpha q or G alpha 11. The PIP2 hydrolysis detected with membranes from cells that over-expressed the TRH receptor alone was low, however, co-expression with the G alpha q or G alpha 11 subunits produced a synergistic stimulation of PI-PLC activity. In contrast, co-expression of these alpha-subunits with the M2 muscarinic acetylcholine receptor induced a weak stimulation of PIP2 hydrolysis. The results presented here suggest that the TRH-dependent stimulation of PI-PLC in GH3 cells is mediated through the G-protein alpha-subunits, G alpha q and/or G alpha 11.

Animals↗
PubMed1992

Interleukin 6 gene transfection into Lewis lung carcinoma tumor cells suppresses the malignant phenotype and confers immunotherapeutic competence against parental metastatic cells.

To investigate the influence of interleukin 6 (IL-6) production on malignancy of tumor cells we transfected cells of the high-metastatic, low-immunogenic D122 clone of the Lewis lung carcinoma with a mammalian expression vector containing the human IL-6 complementary DNA. In vitro, IL-6 positive transfectants showed growth inhibition that was directly correlated with the levels of IL-6 production. The in vitro growth arrest did not seem to be a function of an autocrine system mediated via the secreted human IL-6 acting on the tumor cell surface receptors since neutralizing antibodies to human IL-6 did not prevent the growth inhibition. Neither did exogenous human recombinant IL-6 affect the growth of D122 cells. In vivo, IL-6 positive transfectants showed reduction of tumorigenicity and significant suppression of metastatic competence in syngeneic, immunocompetent mice. In mature T-cell deficient nude mice, the IL-6 transfectants showed some arrest of local growth but no suppression of lung metastasis. It seems therefore that the reduction of metastatic competence of IL-6 transfectants is primarily a function of stimulation by the transfectants of host T-cell immune responses. Immunization with inactivated high-positive IL-6 transfectants induced high levels of anti-tumor cytotoxic T-lymphocytes and protected mice against metastatic growth of a subsequent graft of parental tumor cells. Moreover, reduction of metastatic growth of parental highly metastatic D122 cells was also achieved when immunization of mice was begun after establishment of the primary parental tumors. Thus, inactivated IL-6 transfectants were effective when used as a cellular vaccine for experimental immunotherapy of metastasis.

Adolescent↗
PubMed1992

The use of [35S]methionine as a target cell label in long term cytotoxic assays.

Cytotoxic killing assays represent an important experimental tool in immunology to determine specific and/or cross-killing activities of immune effector cells in vitro. To evaluate the killing capacity of effector cells using cytotoxic killing assays, target cells are prelabeled with a radioisotope. Present labeling methods, using 51chromium to prelabel target cells, are associated with some disadvantages. In this study, we tested the use of 35sulfur-methionine ([35S]methionine) to prelabel target cells in long term cytotoxic killing assays. Our results indicate that prelabeling of target cells with [35S]methionine allows the use of a smaller amount of target and effector cells and enables more accurate detection of target cell killing, compared to the presently used labeling methods.

Animals↗
PubMed1992

New modified heterocyclic phenylalanine derivatives. Incorporation into potent inhibitors of human renin.

Modified heterocyclic phenylalanine analogues designed as replacements for the P3-P4 region were synthesized and incorporated into renin inhibitors. These inhibitors were found to have significant activity versus human recombinant renin, as well as in vivo activity. The compounds proved to be very resistant to chymotrypsin degradation, as exemplified by compound 8, which remained greater than 60% intact after a 24-h exposure to chymotrypsin. In contrast, the Boc-Phe analogue was nearly completely degraded after 1 h. Compound 6 proved to be the most potent renin inhibitor with an IC50 = 8.9 nM. These stable cyclized phenylalanines should prove to be generally useful as a substitute for Boc-Phe in protease inhibitors.

Angiotensin I↗
PubMed1992

Localization of extratemporal epileptic foci during ictal single photon emission computed tomography.

We obtained single photon emission computed tomography (SPECT) scans with technetium-99M-hexamethyl-propylene-amine-oxime in 11 patients during 12 extratemporal partial seizures (9 simple partial, 3 complex partial). Ten ictal SPECT studies in 9 patients showed a focal region of hyperperfusion, which agreed with electrical seizure onset in 5 and with clinical seizure localization in 4 in whom ictal electroencephalography was not localized. Contralateral cerebellar and ipsilateral basal ganglia hyperperfusion was seen in 3 patients with a frontal lobe seizure focus. Ictal hyperperfusion was well circumscribed, unlike the diffuse hyperperfusion changes reported during temporal lobe seizures. This observation may indicate a different degree of seizure spread in temporal as opposed to extratemporal epilepsy. Because electroencephalographic localization is often elusive in extratemporal seizures, ictal SPECT may be very helpful for the localization of extratemporal foci.

Adolescent↗
PubMed1992

Imaging of human T-lymphotropic virus type I-associated chronic progressive myeloneuropathies.

We studied magnetic resonance imaging (MRI) of the head and cervical spine and CT of the head in 46 patients (14 men, 32 women) with chronic progressive myeloneuropathy. The findings were correlated with human T-lymphotropic virus type I (HTLV-I) serology, race, country of origin, and age. We found a female predominance of 2:1. Most patients were aged between 30 and 50 years, and most were Caribbean immigrants and black. There were 9 men and 17 women with blood antibody titers to HTLV-I and 7 men and 15 women with cerebrospinal fluid (CSF) titers. All patients with virus or antibodies in blood or CSF were Caribbean immigrants or black. T2-weighted cranial MRI showed scattered areas of high signal intensity in the cerebral white matter, usually in the periventricular and subcortical areas, but not in the posterior cranial fossa. Cranial CT revealed periventricular low density areas, ventricular enlargement, and atrophy MRI of the cervical spine showed atrophy of the cord. Myelography was normal in all 15 patients examined. No imaging differences were observed between the HTLV-I-positive and -negative patients. These findings, although consistent with demyelination, are not specific.

Adolescent↗