PubMed HealthSearch

Biomedical subjects

T Holloway

Publications and source records attributed to T Holloway.

10 recordsLinked to original sources

Characterization of 20q deletions in patients with myeloproliferative disorders or myelodysplastic syndromes.

Deletions of the long arm of chromosome 20 are associated with several myeloid malignancies. We have analyzed the structure of the del(20q) in 30 patients and two cell lines. Twenty-one of the patients presented with a myeloproliferative disorder and nine with a myelodysplastic syndrome. Two categories of deletions were identified. Eighteen patients had a large deletion with loss of both G(+) bands from the long arm of chromosome 20. Twelve patients had small deletions with loss of one G(+) band from the long arm of chromosome 20. A chromosome paint was generated from a del 20q marker carrying a small deletion. This probe was hybridized to normal metaphases (reverse chromosome painting) and also to metaphases from patients with a del 20q (comparative reverse chromosome painting). All six small deletions analyzed were characterized by loss of the proximal G(+) band (q12) and retention of the distal G(+) band (q13.2). These data define a minimal deleted region extending from 20q11.2-20q13.1.

Adult

B-cell non-Hodgkin's lymphoma cell line (Karpas 1106) with complex translocation involving 18q21.3 but lacking BCL2 rearrangement and expression.

A B-cell non-Hodgkin's lymphoma (B-NHL) cell line (Karpas 1106) with an unusual three-way translocation involving 18q21.3 has been derived from a patient with mediastinal lymphoblastic B-NHL. Although conventional cytogenetics showed a derivative 18q-identical to that seen in cases with t(14;18)(q32.3;q21.3), no translocations of either chromosome 14 could be detected. Instead fluorescent in situ hybridization analysis using a chromosome-18 paint showed that the segment 18q21.3-18qter had become sandwiched on a derivative chromosome X between segments Xqter-c-Xq28 and 13q12-qter, with the centrometric site of 18q21.3 subband juxtaposed to the X sequences. Pulsed-field DNA blots failed to detect rearrangement of the BCL2 gene. Conventional DNA blots using a variety of restriction digests and both 5' and 3' BCL2 and FVT 1 probes also failed to detect rearrangement in Karpas 1106. A rearranged fragment seen only in HindIII digests with 5' BLC2 probes may represent a local microalteration, which is either a mutation or small deletion involving the HindIII site as seen in other cases of B-NHL. Neither BCL2 RNA nor BCL2 protein expression were detected. These and other data suggest that genes at 18q21.3, other than BCL2 and FVT1, may be targets for translocation in certain subgroups of B-NHL.

Adult

Philadelphia-negative chronic myeloid leukaemia: detection by FISH of BCR-ABL fusion gene localized either to chromosome 9 or chromosome 22.

Dual-colour FISH has been used to study two patients with chronic myeloid leukaemia (CML) associated with a normal karyotype. Co-localization of signals from BCR and ABL cosmids was observed in interphase nuclei from both patients. In one patient, analysis of metaphase spreads showed that the 3' region of the ABL gene was deleted from one chromosome 9 and inserted into chromosome 22. In a second patient 5' BCR sequences were missing from one copy of chromosome 22, and co-localized with 3' ABL sequences on chromosome 9. These results demonstrate the molecular heterogeneity of Ph-negative CML. In addition, they illustrate the potential usefulness of dual-colour FISH on interphase nuclei for monitoring the response to treatment of patients with Ph-negative CML.

Blotting, Southern

Platelet monoamine oxidase activity in alcoholics, alcoholics with drug dependence, and cocaine addicts.

The main objective of this investigation was to study the influence of drug dependence on platelet monoamine oxidase (MAO) activity in the presence and absence of alcoholism. One hundred and thirteen admissions to alcohol and drug treatment facilities participated in the study. Twenty-six met the criteria for alcoholism (group I), seventy-eight subjects were alcohol-/cocaine- and cannabis-dependent (group II), and the remaining nine were patients with DSM-III-R diagnosis of cocaine addiction (group III). MAO activity was assayed radiochemically with [14C]tyramine as a substrate (221 microM). The results of this study showed that platelet MAO activity [nmol of product formed x (mg protein)-1 x hr-1] (mean +/- SE) was significantly (p < 0.01) lower in all of these subjects (group I, 5.50 +/- 0.80; group II, 3.90 +/- 0.50; group III, 4.3 +/- 1.60) as compared with controls (14.85 +/- 1.13). Measurements of platelet MAO activity may provide us with a reliable biochemical marker for alcoholism and perhaps addiction to other substances of abuse (i.e., cocaine).

Adolescent

Elevated concentrations of dopamine sulfate in plasma of cocaine abusers.

This study investigated the effect of cocaine abuse on peripheral catecholamines. Specifically, we measured the concentration of free dopamine, dopamine sulfate, free norepinephrine, norepinephrine sulfate, free epinephrine and epinephrine sulfate in plasma samples obtained from the blood of a group of patients with cocaine addiction (N = 15). The concentrations of free and sulfoconjugated catecholamines in plasma were measured by a radioenzymatic technique. The results of this study revealed significant (P < 0.0001) elevation in plasma dopamine sulfate (8926 +/- 1204 pg/mL) of cocaine addicts upon admission to an in-patient treatment facility when compared with the level of this dopamine metabolite in plasma of control subjects (2356 +/- 121 pg/mL). Furthermore, there was a significant (P < 0.0001) relationship between elevation in plasma dopamine sulfate levels and severity of cocaine use among these patients, and in the majority of cases the plasma levels of dopamine sulfate declined appreciably in time with abstinence from cocaine. In contrast, no appreciable difference was observed in the concentrations of either free or sulfate-conjugated norepinephrine and epinephrine in plasma of cocaine addicts as compared with controls. Differences in plasma dopamine sulfate among these patients versus controls may be interpreted as a reflection of activation of extracellular dopamine metabolism associated with chronic cocaine exposure in humans.

Adult

The effect of cocaine abuse on plasma levels of sulfated dopamine and salsolinol in alcoholics.

This study investigated the effect of cocaine abuse on peripheral dopamine and its tetrahydroisoquinoline metabolite salsolinol in chronic alcoholics. Specifically, the concentration of dopamine sulfate and salsolinol sulfate was measured in plasma samples obtained from the blood of a group of alcoholics (n = 40) and alcoholics with cocaine dependence (n = 55). The concentrations of sulfoconjugated dopamine and salsolinol were measured by a radioenzymatic technique. The results of this study showed that chronic alcoholics (627 +/- 195 pg/ml) and alcoholics with cocaine addiction (409 +/- 76 pg/ml) had significantly (p < 0.05) elevated levels of salsolinol sulfate (mean +/- SEM) in their plasma as compared to controls (99.5 +/- 7.5 pg/ml). However, alcoholics with cocaine dependence produced significantly (p < 0.01) higher concentration of dopamine sulfate in their plasma (7520 +/- 1299 pg/ml) as compared to chronic alcoholics (3896 +/- 438 pg/ml) and controls (2124 +/- 104 pg/ml). Differences in plasma dopamine sulfate among alcoholics with cocaine dependence vs. alcoholics without cocaine dependence may be interpreted as a reflection of increased extracellular dopamine metabolism associated with chronic cocaine exposure.

Adolescent