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Biomedical subjects

Z L Olkowski

Publications and source records attributed to Z L Olkowski.

At least 19 recordsLinked to original sources
PubMed1998

Mutant AP endonuclease in patients with amyotrophic lateral sclerosis.

Among the more frequent oxidative DNA injuries is the formation of abasic sites (AP sites) resulting from removal of purine or pyrimidine bases, estimated to occur at a rate of 1 x 10(4)/genome/24 h. A defect in DNA repair at this level could account for the accumulation of mutations and subsequent genome instability. We have identified missense mutations in the APE gene coding for a multifunctional DNA repair enzyme, AP endonuclease in eight of 11 patients with amyotrophic lateral sclerosis (ALS) and familial ALS. These mutations could affect the repair of abasic sites leading to the accumulation of mutations in neurons, resulting in their degeneration and death. Our findings implicate mutated AP endonuclease in the pathogenesis of ALS.

Amino Acid Sequence↗
PubMed1997

Prevalence of high serotonin uptake in lymphocytes of abstinent alcoholics.

An impairment in serotonergic neurotransmission may be associated with alcoholism. We recently identified a high-affinity serotonin transporter (5-HTT) in human peripheral blood lymphocytes (PBLs). Moreover, molecular analysis of RNA samples of human lymphocytes using reverse transcription, coupled with polymerase chain reaction, enabled us to confirm the expression of a 5-HTT identical to the one reported in neuronal tissues, as evidenced by hybridization and sequence analysis. In this investigation, we measured the serotonin (5-HT) uptake in PBLs of recovering alcoholics (N = 10) with long-term abstinence (2-10 years) and non-alcoholic controls (N = 10). 5-HT uptake was measured by incubating 1 x 10(7) cells of PBLs with [3H]5-HT (3-1000 nM; sp. act. 23 Ci/mmol) for 10 min at 37 degrees. The results of this preliminary study revealed that abstinent alcoholics had significantly (P < 0.01) increased uptake of 5-HT (43.6 +/- 5.70 pmol/10(7) cells) as compared with controls (23.33 +/- 2.50 pmol/10(7) cells). An enhanced uptake of 5-HT in PBLs of abstinent alcoholics agrees with previously reported observations of increased 5-HT uptake in brain and platelets of former alcoholics and their descendants. This suggested that a serotonergic mechanism may be linked to the heredity of alcoholism.

Adult↗
PubMed1995

A cocaine-sensitive active dopamine transport in human lymphocytes.

Human lymphocytes possess a cocaine-sensitive high-affinity transport system for [3H]dopamine. [3H]Dopamine uptake was saturated with increasing dopamine concentrations and followed Michaelis-Menten kinetics. The uptake was temperature, sodium, and chloride dependent and was affected by the co-addition of ouabain, phloridzin, potassium cyanide, gramicidin, and other metabolic inhibitors. The uptake of dopamine was blocked significantly in a concentration-dependent manner by cocaine and its congeners. Furthermore, preliminary evidence is presented linking the possible relationship between decreased lymphocyte [3H]dopamine uptake and chronic cocaine abuse in humans.

Adult↗
PubMed1994

Expression of a high-affinity serotonin transporter in human lymphocytes.

This study was undertaken to assess the capability of lymphocytes to actively transport serotonin (5-HT). The data we obtained showed that lymphocytes isolated from the blood of normal human subjects contained a high-affinity uptake system for [3H]5-HT. Kinetic analysis of the uptake data as computed by regression analysis from Lineweaver--Burk plots, yielded a Km of 180 +/- 20 nM and Vmax of 94 +/- pmole/10(7) cells. The uptake of [3H]5-HT was temperature, sodium and chloride dependent and was potently inhibited by the antidepressants clomipramine, imipramine, fluoxetine and fluvoxamine, which are specific for the 5-HT transporter. Compounds that are more selective for norepinephrine and dopamine transporters such as mazindol, desipramine, and GBR 19209 had a lower inhibitory effect on the uptake of [3H]5-HT in human lymphocytes. The expression of a 5-HT transporter in human lymphocytes that resembles 5-HT uptake by platelets and brain synaptosomes may provide insights into the potential role of 5-HT in immune function and its relationship to the neurobiology of affective and addictive disorders.

Adult↗
PubMed1994

Active [3H]-dopamine uptake by human lymphocytes: correlates with serotonin transporter activity.

The main objective of the present investigation was to determine whether the uptake of [3H]-dopamine in human lymphocytes is mediated through a serotonin transporter. This was examined by studying the effects of various monoamine uptake inhibitors on the uptake of [3H]-dopamine in human lymphocytes. Among the compounds tested, indatraline, imipramine and fluoxetine, selective inhibitors of neuronal serotonin transporter, were the most potent inhibitors of [3H]-dopamine uptake in lymphocytes. The 50% inhibiting concentration (IC50) for these inhibitors was in the range of 3.5-17 nmol/l. Bupropion, GBR 12909, nomifensine and xylamine, selective inhibitors of dopamine and norepinephrine transporters, had low affinity for the dopamine uptake system in human lymphocytes with IC50 values ranging between 1,000 and 40,000 nmol/l. These findings provide supportive evidence for the participation of a serotonin transporter in the uptake of [3H]-dopamine in human lymphocytes. The existence of a high affinity transport system for dopamine and serotonin in human lymphocytes may serve as a readily accessible model to detect changes in the neuronal uptake of dopamine and serotonin in addictive and psychiatric disorders.

Adult↗
PubMed1991

Binding of [3H]-dopamine to human lymphocytes: possible relationship to neurotransmitter uptake sites.

Freshly isolated human lymphocytes from 11 healthy subjects had specific binding sites for dopamine which were dependent on time, temperature and sodium, and appeared to follow Michaelis-Menten kinetics. The apparent affinity constant (KD) of human lymphocytes for dopamine and the maximal number of binding sites (Bmax) were 109 +/- 21 nM and 2.66 +/- 1.75 pmol/10(7) cells, respectively. Dopamine binding was markedly affected by cocaine (IC50 = 150 nM) and other inhibitors of biogenic amine uptake. The relatively high potency of cocaine in competing for dopamine binding suggested that human lymphocytes may serve as a readily accessible model to detect changes in the neuronal uptake of dopamine and perhaps other monoamine neurotransmitters.

Adult↗
PubMed1978

Effects of combined immunotherapy with levamisole and Bacillus Calmette-Guérin on immunocompetence of patients with squamous cell carcinoma of the cervix, head and neck, and lung undergoing radiation therapy.

Patients with squamous cell carcinoma of the head and neck, squamous cell carcinoma of the cervix, and lung carcinoma were treated with radiation therapy (RT) prior to being randomly assigned either to a group receiving no further treatment or to a group treated with combined adjuvant immunotherapy (bacillus Calmette-Guérin and levamisole). A battery of in vitro immunologic evaluations in addition to skin tests was used to evaluate these patients prior to RT, immediately following RT, and at regular intervals thereafter. Mean percentages and levels of circulating T lymphocytes were significantly lower in all three types of patients prior to RT than in normal healthy controls. B-lymphocyte percentages and levels, however, were not significantly different from controls except for lower B-cell levels in the lung group. Following completion of RT, circulating levels of both T and B lymphocytes were significantly lower than pretreatment values although the percentages were not significantly changed. Mitogenic responses of patient lymphocytes to both phytohemagglutinin and pokeweed mitogen were significantly lower prior to RT than were healthy control responses. A further depression of blastogenesis following RT was statistically significant. Preliminary data at intervals following RT indicate a gradual recovery of depressed immune parameters (T- and B-lymphocyte levels and mitogenic responses) both in patients treated with adjuvant immunotherapy and in those receiving no further treatment. Although not statistically significant in preliminary data, there is a suggestion that recovery of these immune parameters is slower in the group receiving immunotherapy. Plasma sialic acid levels were elevated in patients when compared to healthy controls and remained elevated throughout the study with little fluctuation. Lymphocyte cytotoxic activity against tumor target cells was variably affected by RT, but was generally increased at 8 weeks following RT when compared to previous values.

B-Lymphocytes↗
PubMed1978

Cytological and quantitative cytochemical studies of post-radiation dysplasia.

A total of 60 vaginal smears from 19 women treated with ionizing radiation for malignancies of the genital tract in the past seven years in the Division of Radiation Therapy of Emory University School of Medicine were studied for the presence of post-radiation dysplasia (PRD) by means of Feulgen cytospectrophotometry and cytological analysis. PRD was diagnosed on the basis of the presence of dysplastic cytological changes, absence of clinically detectable lesions, and presence of aneuploid DNA values in the dysplastic cells. PRD was detected in 21% of the studied cases. Uniform criteria for PRD, describing premalignant and malignant post-radiation lesions, diagnosed on the basis of aneuploid DNA values, as well as cytological observations is suggested.

Adult↗
PubMed1977

Immunocompetence of cancer patients treated with Levamisole.

Nineteen outpatients with malignant melanoma and squamous cell carcinoma of the head and neck, who had surgical resection for complete removal of the tumor and no demonstrable metastases following surgery, were administered Levamisole (p.o., 150 mg per day, two days per week) and maintained on this dose for at least six months. Of this group, drug therapy was discontinued in four patients because of severe "flu-like" syndromes leaving a group of 15 patients for detailed analysis. T-lymphocyte percentages and levels, cAMP levels in the lymphocytes and a battery of skin tests for recall antigens were evaluated following surgery and at various intervals during immunotherapy. Patients who responded well to the treatment showed increased levels of T-lymphocytes and increased cAMP levels, whereas non-responders had low T-cell levels and low cAMP levels. Also positive skin test reactions were observed in most patients who responded well to immunotherapy, although this was the least reliable indicator of patient response. Eight of the nine patients in the melanoma group have responded well clinically, whereas five of the six squamous cell carcinoma patients have developed recurrences.

Carcinoma, Squamous Cell↗