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Biomedical subjects

J Brooks

Publications and source records attributed to J Brooks.

At least 109 records · Page 6Linked to original sources
PubMed1992

T cell recognition of Epstein-Barr virus associated lymphomas.

Epstein-Barr virus, a lymphotropic herpesvirus of humans, has potent B cell growth transforming activity yet persists in the lymphoid tissues of most individuals as a lifelong asymptomatic infection. Virus induced B cell growth transformation in vitro is associated with the expression of a limited set of viral genes encoding six nuclear antigens (EBNA 1, 2, 3A, 3B, 3C and LP) and two latent membrane proteins (LMP 1, 2). Healthy virus carriers possess strong EBV specific CTL memory that can be reactivated in vitro. Here, we summarize experiments in which the antigenic specificities of these HLA class I restricted memory CTL responses have been mapped in a range of individuals with different HLA backgrounds. Of the known EBV latent proteins, EBNA 3A, 3B and 3C are frequently the dominant targets for such responses, but examples of responses directed against epitopes of EBNA 2, EBNA-LP or the LMP have been identified; by contrast, CTL responses against epitopes of EBNA 1 have not been observed. Epstein-Barr virus is associated with at least three malignancies of lymphoid origin--immunoblastic lymphomas of the immunosuppressed, endemic Burkitt's lymphoma and a subset of Hodgkin's disease. The immunoblastic lymphomas express the complete spectrum of EBV coded latent proteins and a cellular phenotype similar to that of in vitro transformed B lymphoblastoid cell lines; accordingly, they remain sensitive to EBV specific CTL recognition. Endemic BL cells are not recognized by such CTL, and at least three consistent features of this tumour could contribute to immune escape: (a) allele specific downregulation of HLA class I antigen expression, (b) absence/low expression of cellular adhesion molecules and (c) restriction of EBV latent protein expression to EBNA 1 only. The relative importance of these three features of the BL cell phenotype with regard to sensitivity to CTL recognition is re-interpreted in the light of recent results. Finally, the pattern of virus latent protein expression in EBV positive Hodgkin's disease is described, and the possibility of EBV specific CTL control against this tumour is discussed.

Antigens, Viral↗
PubMed1992

Use of nonlinear, mixed-effects modeling for population analysis of ofloxacin: effects of age on oral drug pharmacokinetics.

To compare the effect of age on pharmacokinetics of orally administered ofloxacin, two separate studies were reanalyzed using mixed-effect modeling with the program NONMEM. Subjects were male volunteers, 36 age 65 years or greater and 24 age 18-40 years. The younger group received three 100-mg tablets and the older group received two 200-mg tablets of ofloxacin. Serial blood samples obtained throughout dosing were assayed for drug concentrations using high-performance liquid chromatography. A pharmacostatistical model was developed for the data using mixed-effect modeling with NONMEM. A one-compartment open model with first-order absorption, which included the covariables weight and age, best fit the data. Mean (SE) population values were clearance/F 0.219 (0.009) L/hr/kg, volume of distribution/F 1.50 (0.071) L/kg, and absorption rate constant 2.26 (0.048) hr-1. Older subjects had a 29% lower clearance and 13% lower volume of distribution then the younger subjects.

Administration, Oral↗
PubMed1991

Using neural networks to diagnose cancer.

While artificial brains are in the realm of science fiction, artificial neural networks (ANNs) are scientific facts. An artificial neural network is a computational structure modeled somewhat on the neural structure of the brain; both have many highly interconnected processing elements. These biologically inspired processing elements are taught by feeding examples until the results are acceptable. In the past 5 years, neural networks have become successful in providing meaningful second opinions in clinical diagnosis. In our research, a prototype artificial neural network was trained on numeral ultrasound data of 52 actual cases and then correctly identified renal cell carcinoma from renal cysts and other conditions without diagnostic errors. Our nonlinear artificial neural network was trained on software using the standard backpropagation paradigm on a 80386 microcomputer. Our ANN learned from ultrasound data in 52 cases (17 malignant, 30 cysts, and 5 other) at a Memphis hospital. The trained prototype performed without error on 47 cases which were not in the data used for training. This prototype must be validated by extending this study to more cases.

Carcinoma, Renal Cell↗
PubMed1991

Localization of the sites of synthesis and action of prolactin by immunocytochemistry and in-situ hybridization within the human utero-placental unit.

While the fetal pituitary synthesizes and releases prolactin, it is also produced within the utero-placental unit during pregnancy in women and has been localized in the amnion, chorion and decidua. However, it is not clear whether prolactin is synthesized within all these non-fetal pituitary tissues. We have investigated prolactin production and its gene expression using tissue culture, immunocytochemistry and in-situ hybridization techniques. Prolactin was immunolocalized not only in the decidua but also in amnion and trophoblast cells. In contrast, the in-situ hybridization results showed that silver grains, formed by specific hybridization of a prolactin cDNA probe to prolactin mRNA, were confined to decidual cells of early and term pregnancy. The results from tissue cultures correlated well with those of in-situ hybridization, that is that only the decidua made detectable prolactin, while it was undetectable in the culture medium from trophoblast tissue, irrespective of the stage of pregnancy. This study, for the first time, establishes that only decidualized cells are involved in biosynthesis of prolactin; other prolactin-containing cells in the amnion and trophoblast appear to sequester prolactin, possibly via receptors, suggesting that prolactin may play an important paracrine role within the amnion and syncitio- and cytotrophoblast of the utero-placental unit.

Blotting, Northern↗
PubMed1991

Quality assurance in MRI.

"With the prospect of the federal government waiting in the wings to mandate and oversee quality assurance in radiology, managers should waste no time in establishing adequate quality assurance programs for MRI, the latest new technology," declare the authors. Determining standards for quality assurance is certainly a difficult task, considering all the stakeholders involved, say the authors. They focus on evaluating the appropriateness of the imaging test and insuring the accuracy of the diagnosis as the key elements to be monitored.

Centers for Medicare and Medicaid Services, U.S.↗
PubMed1991

Congruence between nursing education and nursing service: a common conceptual/theoretic framework for nursing units.

The results of the incorporation of a conceptual/theoretic framework in this nursing service setting have been an improvement in the service to consumers of nursing, an effective restructuring of the environment of the health care agency advantageous for the client and for nursing staff, and the differentiation of practice roles according to education, experiences, and client needs. It has fostered understanding, acceptance, and support of the contribution of theory development and nursing research to nursing and health care. It brought together nurse leaders in education and service to the benefit of both and with maximum benefit to the consumer of nursing services. The specification of the philosophy, outcome behaviors, and conceptual/theoretic frameworks has allowed nurses to have control over nursing. It has incorporated nurses in setting the pace for the future of nursing practice, promoted the development of peer activity and review, and demonstrated how nursing can make a difference. The benefit for the nurse includes increased job satisfaction, enhanced professional and personal development, increased self-esteem, and the realization that the service of nursing is a valued and valuable service to consumers. Promotion of the image of the nurse was another outcome, as was the realization that nurse educators and nurse supervisors share common goals. The timeframe may be different in that educators see a finished product years ahead while nurse supervisors see client outcomes on a daily basis. The gap between these two efforts is bridged by the use of common conceptual/theoretic frameworks for the design and administration of both the nursing education and nursing service units.(ABSTRACT TRUNCATED AT 250 WORDS)

Consultants↗
PubMed1991

Explicit criteria for determining inappropriate medication use in nursing home residents. UCLA Division of Geriatric Medicine.

Increasing attention is being paid to inappropriate medication use in nursing homes. However, criteria defining the appropriate or inappropriate use of medication in this setting are not readily available and are not uniform. We used a two-round survey, based on Delphi methods, with 13 nationally recognized experts to reach consensus on explicit criteria defining the inappropriate use of medications in a nursing home population. The criteria were designed to use pharmacy data with minimal additional clinical data so that they could be applied to chart review or computerized data sets. The 30 factors agreed on by this method identify inappropriate use of such commonly used categories of medications as sedative-hypnotics, antidepressants, antipsychotics, antihypertensives, nonsteroidal anti-inflammatory agents, oral hypoglycemics, analgesics, dementia treatments, platelet inhibitors, histamine2 blockers, antibiotics, decongestants, iron supplements, muscle relaxants, gastrointestinal antispasmodics, and antiemetics. These criteria may be useful for quality assurance review, health services research, and clinical practice guidelines. The method used to establish these criteria can be used to update and expand the guidelines in the future.

Aged↗
PubMed1990

A phase I and pharmacokinetic study of trimetrexate using a 24-hour continuous-injection schedule.

Trimetrexate (TMTX) is an analog of methotrexate and a potent inhibitor of the enzyme dihydrofolate reductase. In this phase I study, TMTX was given intravenously to 32 patients as a constant infusion over 24 hours every 28 days. The maximum-tolerated dose of TMTX was 200 mg/m2, with myelosuppression as the dose-limiting toxicity. Other toxicities included nausea and vomiting, stomatitis, erythema and phlebitis at the site of infusion, rash and skin hyperpigmentation, and elevated serum hepatic enzymes. Two drug-related deaths occurred secondary to leukopenia and sepsis. Twenty-six patients were evaluable for antitumor response. Twenty-one patients had progressive disease, while three patients had disease stabilization. There were two partial responses observed--one in a patient with breast cancer and a second in a patient with nasopharyngeal carcinoma. TMTX pharmacokinetics were studied in 15 patients. The drug had a mean terminal half-life of 13 hours. Steady-state was not achieved during the 24-hour infusions. Only 6% of the parent compound was excreted unchanged in the urine, and CSF levels averaged less than 2% of simultaneously measured plasma levels. A dose of 150 mg/m2 is recommended for phase II trials of TMTX using this 24-hour infusion schedule.

Adult↗
PubMed1990

Comparison of antiprogestin stimulation of uterine prostaglandin synthesis in vitro.

Progesterone has an inhibitory effect on prostaglandin synthesis in urine tissue and this effect is reversible with progesterone receptor antagonists. Although antiprogesterone steroids such as RU486 (Mifepristone) are effective at inducing abortion in women they have an improved efficacy when used with exogenous synthetic prostaglandin. In the guinea-pig such antagonists sensitize the uterus but do not result in increased myometrial activity and therefore may not induce endogenous PG synthesis. In this study the effects of antiprogestins on a preparation of rat uterus perifused with progesterone were studied. ZK98 734 caused a rapid and sustained increase in 6-oxoPGF synthesis which rose within the first 90 minutes. This rapid response suggested that some mechanism other than the induction of fresh protein synthesis was involved. A similar increase was not seen with pregnant guinea-pig myometrium/decidua perifused in a similar manner, suggesting that some other mechanism was responsible for the relatively low PG production in pregnancy. However increases in 6-oxoPGF in response to antiprogestins were recorded when pregnant guinea-pig decidua/myometrium was incubated for 4 hours. In these experiments 1 microM ZK98 734 and 1 microM ZK98 299 (Onapristone) gave a 2.7 fold increase in PG production whereas RU486 gave a 1.6 fold increase. Both 1 microM ZK98 734 and 1 microM ZK98 299 also gave a significant increase in PGE production but no increase in PGF was observed. These findings suggest that some antiprogestins might have a better effect on the stimulation of endogenous PG synthesis or on the rate of catabolism of prostanoids.

Animals↗
PubMed1990

The child with simultaneous stridor and wheezing.

We describe 25 patients with simultaneous stridor and wheezing. Twelve patients presented to the emergency department of The Children's Hospital of Denver over a two-year period; we found an additional 13 in a review of the literature. A combination of two disorders produced stridor and wheezing in six patients, with one condition in the extrathoracic airway and one in the intrathoracic airway. The remaining 19 patients had single lesions, nine with obstruction of the extrathoracic airway and 10 with obstruction of the intrathoracic airway. The causes of stridor and wheezing in these 19 patients fell into three general categories: (1) congenital lesion affecting the airway (eight patients); (2) foreign body in the airway or esophagus (nine patients); and (3) acquired lesion affecting the airway (two patients). All eight patients with congenital lesions developed symptoms by four months of age. All nine patients with an airway or esophageal foreign body were between five and 30 months of age. The history may be misleading, and the physical examination often cannot discriminate among the various likely diagnoses. However, the addition of four plain x-ray views (lateral neck, posteroanterior and lateral chest, and forced expiratory chest) located the site of obstruction in 18 of 25 patients. Barium swallow identified the two patients with vascular rings. Four patients underwent endoscopy to determine the site of obstruction. We make recommendations for evaluation of these patients.

Adolescent↗
PubMed1990

Autologous bone marrow transplantation with 4-hydroperoxycyclophosphamide purged marrows for children with acute non-lymphoblastic leukemia in second remission.

Although autologous bone marrow transplantation (ABMT) following purging with 4-hydroperoxycyclophosphamide (4HC) has been effective for some adults with acute non-lymphoblastic leukemia (ANLL), there are few data on ABMT for children. We have performed ABMT for 13 patients (median age, 5 years) with ANLL in second remission. Bone marrow was treated ex vivo with 4HC to kill residual leukemic cells. In order to enhance the anti-leukemic effect of 4HC, exogenous red blood cells were eliminated from the marrow/4HC mixture. All patients were conditioned for transplantation with busulfan (16 mg/kg) and cyclophosphamide (200 mg/kg), followed by infusion of the 4HC treated marrow. Eleven of 13 patients had complete hematologic reconstitution; there were no transplant-related deaths. Five patients relapsed at 2, 4, 5, 6 and 6 months post-BMT. Eight patients are disease-free survivors; the median time for survival is 24 months, with a projected disease-free survival of 61%. ABMT is a safe and efficacious treatment modality for children with ANLL in second remission. Our results suggest that the disease-free survival for pediatric patients may be superior to that seen in adults.

Actuarial Analysis↗
PubMed1989

The nucleotide sequence of a mouse renin-encoding gene, Ren-1d, and its upstream region.

The renin-encoding genes have been cloned from high (Ren-1d, Ren-2d)- and low (Ren-1c)-renin-producing strains of mice (DBA/2J and C57BL/10). Each of the genes is approx. 9.6 kb in length and consists of nine exons and eight introns. The entire nucleotide sequence of the Ren-1d gene has been determined and the 5'-flanking regions of the three genes, Ren-1c, Ren-1d and Ren-2d, have been compared. The significance of several potential regulatory signals found in the DNA is discussed.

Amino Acid Sequence↗
PubMed1989

The value of speech-language assessment in the diagnosis of child abuse.

Language deficits and developmental delays may be helpful clues in the diagnosis of child abuse and neglect. Speech-language assessment of 27 children burned through abuse or neglect identified 22 (81%) with language delays. Other significant trends included a decreased attention span, inappropriate affect, irritability, and withdrawn behavior. We recommend speech-language assessment for all burned children suspected to be victims of abuse or neglect as part of the abuse team investigation and to identify children who may benefit from intervention.

Affect↗