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Biomedical subjects

R Goodman

Publications and source records attributed to R Goodman.

At least 37 records · Page 2Linked to original sources

A twin study of hyperactivity--I. An examination of hyperactivity scores and categories derived from Rutter teacher and parent questionnaires.

In a representative sample of 570 13-yr-old twins, higher hyperactivity scores from parent and teacher ratings were associated with male sex, lower intelligence, inattention, specific learning problems, and behavioural deviance (mainly antisocial). This pattern of correlates also characterized all three hyperactivity categories: to a marked degree in pervasive hyperactivity; less markedly in school hyperactivity; and least markedly in home hyperactivity. Children with pervasive hyperactivity had more attentional and educational problems than non-hyperactive children who were pervasively antisocial. By contrast, children with school or home hyperactivity resembled non-hyperactive children who were situationally antisocial. These findings cast doubt on the validity of combining situational and pervasive hyperactivity into a single diagnostic category such as Attentional Deficit Disorder with Hyperactivity (ADDH).

Adolescent

A twin study of hyperactivity--II. The aetiological role of genes, family relationships and perinatal adversity.

In a large representative sample of 13-year-old twins, monozygotic pairs were more alike than same-sex dizygotic pairs on objective measures of attentiveness and on parent and teacher ratings of hyperactivity. Comparison of recognized and unrecognized monozygotic pairs indicated that parents and teachers rated twins more similarly when the twins were perceived as "identical" rather than "non-identical". After allowing for this stereotyping, genetic effects accounted for approximately half of the explainable variance of hyperactivity and inattentiveness. Data from mixed-sex pairs did not support a 2-threshold genetic explanation for the male excess of hyperactivity. The link between adverse family factors and hyperactivity was weak. Perinatal adversity was not related to later hyperactivity.

Adolescent

Neuronal misconnections and psychiatric disorder. Is there a link?

Brain damage can induce anomalous neuronal connections in experimental animals, which can sometimes result in maladaptive behaviour, particularly when damage occurs early in development. Anomalous patterns of neuronal connection can also arise from genetic disorders. In humans, neuronal misconnections could be involved in a variety of psychiatric disorders. For example, they may account for the link between hyperkinesis and childhood hemiplegia, and for the link between schizophrenia and 'alien tissue' lesions of the temporal lobes. Predictions from misconnection hypotheses can potentially be tested in neuropathological, neurophysiological, and clinical studies.

Brain

Successive unfolding of two different collagen vascular diseases in the same patient.

Genetic factors may be important in the development of autoimmune disease. We describe the development of fulminant systemic lupus erythematosus in a patient 5 years after recovery from polymyositis. The successive unfolding of different autoimmune diseases in the same individual is suggestive of sequential gene activation.

Antibodies, Antinuclear

Kinetic analysis of an E.coli phenylalanine-tRNA synthetase mutant.

A mutation in the pheS gene, encoding phenylalanyl-tRNA synthetase, in E. coli NP37 confers temperature-sensitivity on the organism. A five-fold increase in tRNA(phe) levels complements the mutation. Analysis of the kinetic properties of the mutant enzyme indicates that the KM is 20-fold higher than the wild-type and the dissociation constant of the tRNA(phe)-synthetase complex for the mutant is at least 10-fold higher. These results indicate that the mutation in E. coli NP37 directly affects the tRNA(phe) binding site on the cognate synthetase.

Amino Acyl-tRNA Synthetases

Radiotherapy for the prevention of local-regional recurrence in high risk patients post mastectomy receiving adjuvant chemotherapy.

From 1977 to 1986, 63 patients at high risk for isolated local-regional recurrence following mastectomy and adjuvant chemotherapy received post-operative radiotherapy. All patients had operable primary tumors (T1-3a). For entire group the mean and median number of positive nodes were 10 and 8, respectively. Radiotherapy consisted of 4500 to 5000 rad to the chest wall and regional nodes. Chemotherapy consisted of CMF +/- prednisone (45 patients), CAF (16 patients), and other variable regimens (2 patients). Relapse occurred in 23 patients with only two patients experiencing an isolated local-regional recurrence. In 3 patients local-regional recurrence appeared simultaneously with or following distant metastases and in 18 patients the pattern of failure was distant metastases alone. With a median follow-up of 28 months (range 9-87 mo.), 40 patients are alive without disease, 9 are alive with disease, and 14 have died with disease. The 4-year actuarial overall survival is 67% and the 4-year actuarial disease-free survival is 47%. The 4-year actuarial probability of an isolated local-regional recurrence is 5%. Complications related to the radiation included a 9% incidence of moderate to severe arm edema. This study demonstrates the ability of radiation to reduce the incidence of local-regional recurrence in a previously identified high risk group of patients and has produced encouraging survival results with minimal morbidity.

Actuarial Analysis

Genomic organization and deduced amino acid sequence of a putative sodium channel gene in Drosophila.

The deduced amino acid sequence of a Drosophila gene isolated with a vertebrate sodium channel complementary DNA probe revealed an organization virtually identical to the vertebrate sodium channel protein; four homologous domains containing all putative membrane-spanning regions are repeated in tandem with connecting linkers of various sizes. All areas of the protein presumed to be critical for channel function show high evolutionary conservation. These include those proposed to function in voltage-sensitive gating, inactivation, and ion selectivity. All 24 putative gating charges of the vertebrate protein are in identical positions in the Drosophila gene. Ten introns interrupt the coding regions of the four homology units; introns with positions conserved among homology units bracket a region hypothesized to be the selectivity filter for the channel. The Drosophila gene maps to the right arm of the second chromosome in region 60D-E. This position does not coincide with any known mutations that confer behavioral phenotypes, but is close to the seizure locus (60A-B), which has been hypothesized to code for a voltage-sensitive sodium channel.

Amino Acid Sequence

In vitro effects of thymosin and lithium on lymphoproliferative responses of normal donors and HIV seropositive male homosexuals with AIDS-related complex.

The in vitro effects of thymosin fraction 5 (TF5) and lithium chloride (LiCl) on the ability of peripheral blood mononuclear cells (PBMC) obtained from 37 normal male donors and 33 male patients with AIDS-related complex (ARC) to respond to alloantigenic stimulation (mixed leukocyte reaction, MLR) and to produce interleukin 2 (IL-2) in response to mitogens were studied. TF5 significantly increased MLR responses in normal donors (P less than 0.01) and in a group of 33 ARC patients with depressed cellular immunity (P less than 0.05). Similar effects were observed when LiCl was added to the MLR assays in both the normal and the ARC patient groups. Furthermore, TF5 and LiCl exhibited additive immunoenhancing properties. In 10 normal donors TF5 enhanced phytohemaggutinin (PHA)-induced IL-2 production as well as IL-2 production in response to pokeweed mitogen (PWM) (P less than 0.02). TF5-mediated enhancement of IL-2 production by PBMC obtained from ARC patients was observed in response to both mitogens, i.e., PHA and PWM. Additionally, LiCl increased PHA-induced IL-2 production in both normal subjects and ARC patients. LiCl and TF5 together had an additive effect in the enhancement of IL-2 production in both groups of subjects. Our data extend previous observations regarding the immunoregulatory activities of TF5 and LiCl and provide evidence that PBMC obtained from ARC patients have the potential to respond in vitro to these agents. The significance of these findings is discussed.

AIDS-Related Complex

An evaluation of total nodal irradiation as treatment for stage III A Hodgkin's disease.

Between April 1969 and December 1974, 37 patients with surgically staged III A Hodgkin's disease were treated with total nodal irradiation (TNI). Their probability of relapse-free survival at 7 years is 51% and overall survival 82% with the majority of patients remaining disease free after retreatment with MOPP (10 of 16). In contrast, 21 stage III B patients treated with TNI and MOPP chemotherapy over the same time period have a relapse-free survival of 74% and overall survival of 91%. Because of superior results in treating stage III B patients with combined modality treatment, we fell that a relapse-free survival of 51% may not justify continuation of TNI as the only modality of treatment for patients with stage III A disease, and we have initiated a trial of combined radiation therapy and MOPP chemotherapy in these patients. The most effective treatment of stage III A Hodgkin's disease, however, remains uncertain and depends both on the ultimate risk of combined modality treatment and the success of retreatment following relapse after radiation.

Adolescent

The significance of mediastinal involvement in early stage Hodgkin's disease.

Between April 1969, and December 1974, 111 consecutive surgically staged I A and II A patients with supradiaphragmatic Hodgkin's disease were treated at the Joint Center for Radiation Therapy. Patients received 3600--4400 rad to mantle and para-aortic--splenic pedicle regions. Median follow-up was 56 months (30--96). Fourteen patients developed relapsing Hodgkin's disease and three patients died of possible treatment-related causes, two with acute myocardial infarctions and one with radiation pneumonitis. Patients with mediastinal enlargement greater than one third of the chest diameter have a significantly higher risk (p less than 0.01) of developing relapse (9 of 18) than patients with lesser or no mediastinal disease (5 of 93). Of the 18 patients with large mediastinal disease, six relapsed in the mediastinum and two in the lung. There continue to be no pelvic extensions in the entire group. There is a 92% relapse-free and 97% overall survival in the 93 patients without extensive mediastinal disease. We continue to recommend mantle and para-aortic--splenic pedicle irradiation for these patients. In view of the large number of relapses in patients with extensive mediastinal disease, we are now treating this subgroup of patients with MOPP chemotherapy in addition to mantle and para-aortic irradiation.

Adolescent

Nerve growth factor-mediated induction of tyrosine hydroxylase in a clonal pheochromocytoma cell line.

We have established a clonal cell line, PC-G2, from an experimentally induced rat pheochromocytoma. Administration of nerve growth factor to PC-G2 causes a 4- to 8-fold induction in the specific activity of tyrosine hydroxylase [tyrosine 3-monooxygenase; L-tyrosine,tetrahydropteridine:oxygen oxidoreductase(3-hydroxylating); EC 1.14.16.2]. The response is elicited in a dose-dependent fashion, at concentrations above 0.1 microgram/ml. Antiserum to nerve growth factor inhibited the induction of tyrosine hydroxylase. Dexamethasone enhances the nerve growth factor-mediated elevation of tyrosine hydroxylase. After 3--4 days of exposure to nerve growth factor the maximal induction of tyrosine hydroxylase is seen, although a significant increase can be observed after 24 hr. In contrast to the PC-12 cell line (derived from the same tumor), in which neurite outgrowth occurs in response to nerve growth factor, there is no morphological change or alteration in growth rate of PC-G2 cells after exposure to nerve growth factor.

Cell Line

Glucocorticoid induction of tyrosine hydroxylase in a continous cell line of rat pheochromocytoma.

We have established a continous cell line (G1) in which the tyrosine hydroxylase specific activity is increased as much as 50-100-fold in response to dexamethasone. This response is specific for the glucocorticoid class of steroid hormones; it is elicited by dexamethasone, corticosterone, and triamcinolone, but not by estradiol, testosterone, progesterone, or deoxycorticosterone acetate. The increase in tyrosine hydroxylase specific activity is likely to be due to the increased synthesis of new enzyme protein rather than an activation of existing protein molecules, inasmuch as this increase is completely blocked by cycloheximide.

Adrenal Gland Neoplasms

Stages I--III Hodgkin's disease in children: results of staging and treatment.

Fifty-two children with clinical stages I-III Hodgkin's disease were evaluated for disease extent between April 1969 and March 1975. All underwent laparotomy and splenectomy. Two patients with liver involvement were excluded. Thirty of 31 patients with pathologically staged IA-IIA disease have been continuous complete remission after mantle and para-aortic irradiation. There have been no extensions into the untreated pelvis. Fourteen of 15 patients with pathologic stages IIB and IIIB disease show no evidence of relapse after TNI and MOPP. Three of four patients with stage IIIA disease developed nodal relapse after irradiation; all are alive without evidence of disease after re-irradiation (3) and MOPP (2). Thus 45 of 50 patients (90%) have remained continuously free of disease after completion of the planned treatment, and overall 49 of 50 (98%) are alive, without evidence of disease. Such results justify continuation of our staging and treatment philosophy in children with Hodgkin's disease.

Adolescent