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Biomedical subjects

J Conroy

Publications and source records attributed to J Conroy.

At least 37 records · Page 2Linked to original sources

Carnitine palmitoyl transferase deficiency in malignant hyperthermia.

The activity of carnitine palmitoyl transferase, an enzyme that catalyzes the transport of long-chain acylcarnitines into mitochondria, was quantitated in EB-virus-transformed lymphoblasts from 7 patients with susceptibility for malignant hyperthermia. Immunoreactive enzyme protein was also measured using an enzyme-linked immunosorbent assay. Cell lines derived from patients with carnitine palmitoyl transferase deficiency of muscle and from normal individuals were used as positive and negative controls, respectively. One patient with malignant hyperthermia had a deficiency in the enzyme activity which was comparable with that of the known carnitine palmitoyl transferase deficient patients. This individual's lymphoblasts were also deficient in immunoreactive enzyme protein. All of the remaining patients with malignant hyperthermia were deficient only when the backward assay for carnitine palmitoyl transferase was used for quantitation. It is likely that a subset of individuals with a malignant hyperthermia phenotype have a primary deficiency of carnitine palmitoyl transferase and that others have a milder enzyme deficiency secondary to the primary defect in malignant hyperthermia.

Carnitine O-Palmitoyltransferase↗

A novel polymerase chain reaction method for detection of human immunodeficiency virus in dried blood spots on filter paper.

A method for detection of proviral human immunodeficiency virus DNA in dried blood spots on filter paper by direct polymerase chain reaction (PCR) has been developed. To develop the method, a standard system was used which was prepared from cells each containing a single integrated provirus and titrated with normal donor blood. This rapid procedure provides virtually quantitative yields of nuclear DNA and exploits most of the standard methodology described for blood specimens. A nested PCR using SK38-SK39 gag as the internal primer pair was also designed; this PCR detected a single copy of provirus per filter at near theoretical frequency with SK19 probe. The utility of the procedure was demonstrated with clinical specimens. Blood spot filters from human immunodeficiency virus-infected and uninfected individuals were readily and unequivocally discriminated. The method is designed for ultimate use with large (1.5-ml) sample preparation tubes that are compatible as PCR tubes with thermal cyclers. This will permit convenient, direct single-tube PCR of dried blood specimens on filters. It should be adaptable to analysis of dried blood spots for a variety of infectious or genetic diseases.

Base Sequence↗

High-dose cytosine arabinoside and etoposide in the treatment of relapsed or refractory adult leukemia.

Thirteen patients with leukemia were treated with a combination of cytosine arabinoside (ara-C) (3 g/m2 by 1-h infusion every 12 h for 12 doses) and etoposide (100 mg/m2 daily over 1 h for 3 doses). Toxicity of the regimen consisted of severe hematologic suppression, moderate abdominal colic with vomiting and diarrhea, and occasionally severe central nervous system (CNS) toxicity. Two patients received the regimen as consolidation for acute myelogenous leukemia in remission. Of the remaining 11 patients with chronic myeloid leukemia (CML)-blast crises or relapsed/refractory acute myeloid leukemia (AML), nine patients (82%) obtained CR (or chronic phase) and two patients obtained partial remission (PR). High-dose ara-C and etoposide is an effective but toxic regiment for the treatment of relapsed or refractory myeloid leukemias.

Adult↗

Influence of host environment on growth of clonal CD5+B (Lyl+B) cells.

Autoimmune NZB mice have increased percentages of CD5+B (Lyl+B) cells in both the spleen and peritoneum. We have previously reported that as NZB mice age they develop a clonal population of hyperdiploid CD5+B cells in the spleen. These cells can readily be transplanted into unirradiated recipients. The growth characteristics of such transplanted hyperdiploid NZB spleen cells were examined in different recipient strains to determine if the immunological status of the host environments affected the growth of the clonal CD5+B cells. Young NZB and NZB.xid recipients (lacking hyperdiploid CD5+B cells) allowed growth and expansion of unpassaged CD5+B cells derived from primary NZB mice. Similarly, (NZBxDBA/2) and (NZBxBALB/c) F1 recipients allowed for expansion of CD5+B cell clones from primary sources. In a separate experiment, T cell-depleted NZB spleen cells containing a hyperdiploid CD5+B cell clone were transferred to SCID mice. The SCID environment supported the growth of the primary clone. None of these recipients normally have elevated CD5+B cells, yet these recipients allowed growth of primary transferred hyperdiploid cells. However, a difference in the ability of these recipient strains in their ability to expand multiply passaged CD5+B cell clones was observed. These results indicate that while hyperdiploid CD5+B cells are difficult to be maintained in culture, they can readily be passaged in vivo. The host environment may provide growth factors or signals for endogenous growth factors. Although the CD5+B clones arise initially in a hyperactive autoimmune environment, a hyperimmune environment is not necessary to support their growth. Transferred CD5+B cells affect the recipient environment and reduce the percentages of normal B cells.

Animals↗

In vivo effects of hyperdiploid Ly-1+ B cells of NZB origin.

Cells with increased chromosome number and DNA content have been found in the spleens of old NZB mice. These hyperdiploid cells are of clonal origin and demonstrate discrete IgH chain gene rearrangements by Southern blot analysis. In this report, hyperdiploid cells were analyzed by three-color flow cytometric techniques and found to be Ly-1+ B cells which were dull for Ly-1 and bright for surface IgM. These cells, unlike typical diploid Ly-1+ B cells, were negative for B220/6B2 and surface IgD. Hyperdiploid Ly-1+ B cells were found to be the predominant splenic subpopulation in animals receiving a spleen cell transfer from donors which possessed hyperdiploid Ly-1+ B cells. (NZB x DBA/2)F1 recipients of NZB spleen cells demonstrated a 10- to 1000-fold increase in Ly-1+ B cells in the spleen but showed no increased levels of Ly-1+ B cells in the peritoneum. Nearly all the splenic Ly-1+ B cells were hyperdiploid with the phenotype of the NZB parent. Cytogenetic analysis revealed that all the hyperdiploid cells were NZB donor cells. These findings suggest that the increase in splenic Ly-1+ B cells in the F1 recipients was due to expansion of injected splenic hyperdiploid Ly-1+ B cells of NZB origin. All of the F1 recipients of NZB hyperdiploid Ly-1+ B cells demonstrated a significant decrease in endogenous B cells as well as decreased serum IgM and anti-ssDNA autoantibodies. These studies suggest that hyperdiploid Ly-1+ B cells are different from typical peritoneal Ly-1+ B cells both in the lymphoid organs to which they home and in their proliferative capacity. NZB hyperdiploid Ly-1+ B cells, which may arise as a natural consequence of hyperactive Ly-1+ B cells, may play an immunoregulatory role in the spleen.

Animals↗

Clonal expansion of abnormal B cells in old NZB mice.

The spleens of old NZB mice have an abnormal population of B cells with extra chromosomes. These hyperdiploid B cells manifest increased proliferative capacity; they grow in (NZB X DBA/2)F1 spleens after intravenous injections. Molecular analysis of individual old NZB and F1 passaged spleens demonstrate that hyperdiploid cells represent a clonal or oligoclonal expansion of B cells. All spleens with at least 10% hyperdiploid cells demonstrated both heavy and kappa light chain immunoglobulin gene rearrangements by Southern blot hybridization. None of the hyperdiploid spleens from old NZB mice had lambda rearrangements and only one of five showed evidence of clonal rearrangement of the TCR-beta gene. One also had a VK10 clonal rearrangement. Elevated p53 oncogene protein was observed in NZB hyperdiploid spleen cells; however, no p53 or other oncogene rearrangements or amplifications were seen. Hyperdiploid cells were IgM-bright, IgD-dull, Ia+, dull B220, Thy-1-, and Ly-1-dull. Spleens with hyperdiploid B cells had increased percentages of Ly-1 B cells. The data suggest that hyperdiploid cells in old NZB mice represent clonal expansion of B cells and that they may represent an intermediate stage between autoimmunity and malignancy.

Aging↗

ICRF-159 (razoxane) in patients with advanced adenocarcinoma of the endometrium. A Gynecologic Oncology Group Study.

Twenty-seven patients with advanced adenocarcinoma of the endometrium were accessioned into this Phase II study evaluating the efficacy of ICRF-159 (razoxane) as second-line chemotherapy between February 1981 and September 1983. One patient was ineligible because of an undocumented primary. One patient was invaluable because of concurrent use of adjunctive therapy and one patient had an inadequate trial. Twenty-four evaluable patients with measurable disease were given ICRF-159 orally at a starting dose of 1.5 g/m2 weekly until response could be determined. Grade 4 hematologic adverse effects were the only significant toxicity. There was no evidence of tumor response in any of the patients. Fourteen patients had stable disease and 10 had progressive disease. No activity was noted in advanced adenocarcinoma of the endometrium with ICRF-159 administered in the above dose and schedule.

Adenocarcinoma↗

Oral controlled-release delivery of ivermectin in cattle via an osmotic pump.

Ivermectin, a potent antiparasitic agent with activity against internal and external parasites, was delivered to cattle at a controlled zero-order rate for 35 d via orally administered, specially weighted, ALZET 2ML4 osmotic pumps. The osmotic pumps delivered the drug consistently over the trial period. Steady-state levels in plasma were achieved in 7-14 d, and plasma concentration depletion curves were observed to start at approximately day 35, the theoretical delivery lifetime of the osmotic pumps. Bioavailability was estimated to be 40%, and dose rate-plasma steady-state interrelationships were shown to be linear.

Animals↗

Attitudes of superintendents of institutions for the mentally retarded towards deinstitutionalization: a cross-cultural perspective.

A cross-cultural study was conducted on the attitudes of superintendents of institutions regarding deinstitutionalization in the United States and in Israel. The attitudes of 29 superintendents from Israel were compared with the attitudes of 181 American superintendents. The most general finding was that in spite of important legislative and demographic differences, in both countries the attitudes were neither highly in favor nor strongly against deinstitutionalization. Most respondents in both countries believed that the parents of the mentally retarded do not generally support deinstitutionalization.

Administrative Personnel↗

Fibre-optic assessment of tracheal tube position. A comparison of tracheal tube position as estimated by fibre-optic bronchoscopy and by chest X-ray.

The distance between the tip of a tracheal tube and the carina was measured in twenty five patients who required tracheal intubation and artificial ventilation of the lungs. Two methods of evaluation of this distance--limited-optic bronchoscopy and chest X-ray--were compared. There was no significant difference between the distance measured by either method. The advantages of checking tracheal tube placement by fibre-optic bronchoscopy are discussed.

Adult↗

Discovery, production and purification of the Na+, K+ activated ATPase inhibitor, L-681,110 from the fermentation broth of Streptomyces sp. MA-5038.

The maximum yield for the production of L-681,110 by Streptomyces sp. MA-5038 (ATCC 31587) was observed after 5 days' incubation at 28 degrees C and pH about 8.3. L-681,110 was isolated from the fermentation broth by acetone extraction of the mycelia, absorption to Amberlite XAD-2 resin and two separations by thin-layer chromatography. The structure of L-681,110 was found to consist of a sixteen-membered lactone with a new type of substitution. The inhibition of ATPase, activity against Caenorhabditis elegans and stimulation of gamma-aminobutyric acid release indicate that L-681,110 possesses some characteristics of both oligomycin and avermectin. L-681,110 was also active against tapeworm and ticks in an in vivo assay.

Animals↗

Phase II study of maytansine in the treatment of advanced or recurrent squamous cell carcinoma of the cervix. A Gynecologic Oncology Group study.

Twenty-nine patients with advanced or recurrent squamous cell carcinoma of the cervix who had failed standard therapy were treated with maytansine 1.2 mg/m2 intravenously once every 3 weeks. Only one partial remission was observed among the 29 patients (3%). There were no complete remissions. Stable disease was observed in 18 (62%) and progressive disease in 10 (35%). Adverse effects were infrequent and mild to moderate and consisted primarily of myelosuppression, weakness, and nausea and vomiting. This study shows that maytansine at the dose and schedule tested is essentially inactive in the treatment of advanced or recurrent squamous cell carcinoma of the cervix.

Adult↗

Bacteremia following dental cleaning in patients with and without penicillin prophylaxis.

The rate, type, and magnitude of bacteremia were studied in 56 patients undergoing dental cleaning with and without penicillin prophylaxis. Sixty-one percent of patients without penicillin prophylaxis were bacteremic 5 minutes following the procedure. Although a significant decrease in detectable bacteremia occurred in patients receiving penicillin prophylaxis, the recovery of streptococci was not significantly different in the two groups. Using the present sample of patients as a basis for statistical inference, the true rate of bacteremia in such patients could be between 41% and 79% with 95% certainty. The magnitude of bacteremia was low and positive quantitative pour plates occurred at 5 minutes and only in patients without penicillin prophylaxis. Of the 71 total bacterial isolates, 53 (74.6%) were anaerobes and 18 (25.4%) were aerobes. This study indicates that parenteral penicillin prophylaxis for dental cleaning decreased detectable bacteremia rates significantly and could be recommended for patients with valvular heart disease who are known to be vulnerable to endocarditis.

Adult↗

A matched comparison of the developmental growth of institutionalized and deinstitutionalized mentally retarded clients.

Seventy mentally retarded clients previously residing in a large state institution were matched with 70 clients who remained at the same institution. Clients were matched by sex, level of retardation, years institutionalized, self-care skills, age, and IQ. Developmental growth, operationally defined as adaptive behavior change using a research version of the AAMD Adaptive Behavior Scale, was measured for all clients at Time 1 and Time 2. Demographic and environmental factors that could be associated with adaptive behavior growth were explored. Only the deinstitutionalized clients displayed significant growth. They increased in adaptive behavior and showed no significant change in maladaptive behavior.

Adult↗

Early splenectomy in chronic myelogenous leukemia: surgical aspects.

A retrospective study was conducted to analyze the surgical aspects of the splenectomy in chronic myelogenous leukemia. Twenty patients, Philadelphia chromosome-positive, were initially treated with busulfan until remission was reached. Elective splenectomy was then performed and chromosomal studies repeated at four- and six-month intervals yielding the indication for cyclic intensive chemotherapy. There ws no mortality, one episode of gram-negative sepsis with shock, and five instances of minimal complications. The spleen weights averaged 265 g, ranging from 60 to 800 g. All patients had normal coagulation profiles at the time of surgery, but four of them developed a postoperative thrombocytosis without related complications. A specific correlation was noted between postoperative thrombocytosis and splenomegaly (average weight 570 g). Eleven patients showed a high postoperative leukemoid reaction (average 40,500 cells/cu mm). The interval between diagnosis and splenectomy was shorter (average 7.5 months) in this group than for the patients who had a lower granulocytosis (average 19.5 months).

Adult↗