Biomedical subjects
Publications and source records attributed to J Levine.
Posterior radial head dislocation without fracture of the ulna in an adult is extremely rare. A case is presented in which immediate closed reduction, a short period of immobilization, and early active range of motion resulted in a very good outcome. Early detection by thorough physical examination and careful radiographic analysis is crucial for a good final result.
That physiological effects are directly related to concentration at the site of action has been validated for only a few classes of drugs. For opiates, a direct correlation is known to exist between concentration and magnitude of analgesia, but has not been shown for duration of analgesia. These experiments in rats, using opiates whose elimination half-lives differ by a factor of 2 1/2, in a range of doses that produce 10-90% of maximal analgesic effect, show that duration is not dependent on dose or rate of elimination of opiate analgesics. The data suggest that analgesic duration is not determined by the pharmacokinetics of opiates at the receptors where these drugs act to elicit analgesia.
Fodrin is an actin/calmodulin-binding protein with similarities to spectrin (erythrocytes) and TW 260/240 (brush border). It is concentrated beneath the plasma membranes of neurons and other cells. We have observed translocations of fodrin in both neurons and lymphocytes. Newly synthesized, radiolabeled fodrin moves down axons at a maximum velocity (about 50 mm/day) that is slower than the most rapidly axonally transported proteins (group I). A portion of fodrin appears to move more slowly at velocities (1-10 mm/day) resembling those of actin and myosin (group IV) and tubulin and neurofilament proteins (group V). In lymphocytes, when certain surface antigens are induced by cross-linking agents to migrate to one pole of the cell and form a cap, fodrin redistributes beneath the membrane and forms a subcap. The movements of fodrin in lymphocyte capping and in the axonal transport of group IV polypeptides have certain similarities. In both cases, the redistribution of fodrin is accompanied by concomitant redistributions of actin, myosin, and calmodulin, and both processes proceed at similar velocities. We consider the possibilities that these two processes are related, both being driven by a submembrane force-generating system comprising in part actin, myosin, and fodrin, and that fodrin serves to link various organelles or proteins to this system.
A multiple stepwise logistic regression analysis shows that histologic regression is more likely to be found in a malignant melanoma that is level III or less, more than 10 mm in diameter, associated with solar elastosis, located on an anatomic area other than the head or neck, and when there are areas of whiteness clinically. Although patients with malignant melanomas displaying signs of regression histologically have a slightly better 5-year disease-free survival, this may be attributed to a difference in tumor thickness.
Fodrin, a protein composed of two polypeptides with molecular weights of 250,000 and 240,000, is concentrated in the cortical cytoplasm of neurons, and moves down the axons by the process of axonal transport. We have used immunofluorescence techniques to determine whether fodrin antigens also move in non-neuronal cells when cell surface ligands are induced to redistribute by crosslinking them. A redistribution of fodrin antigens occurred in the following instances: (i) when 3T3 cells were incubated with concanavalin A and anti-concanavalin A, surface concanavalin A receptors formed aggregates and fodrin antigens formed corresponding intracellular aggregates; (ii) when B lymphocytes were incubated with anti-Ig, the surface Ig formed caps and fodrin antigens formed intracellular subcaps; (iii) when T lymphocytes were treated with anti-H-2 followed by a secondary antibody, the H-2 antigen formed caps and fodrin formed corresponding subcaps. These observations show that fodrin antigens can move within non-neuronal cells, as well as in axons, and that their organization can be regulated by interaction between surface proteins and environmental stimuli. They also raise the possibility that fodrin, together with other proteins that form subcaps in lymphocytes (e.g., actin, myosin, and alpha-actinin) is a component of the cellular machinery responsible for the capping process. We consider whether the similarities between the movements of fodrin in lymphocyte capping and axonal transport may indicate that certain aspects of these two processes are related.
The developmental levels of three samples of paranoid and nonparanoid schizophrenic patients who manifested hallucinations, delusions, or both symptoms were compared. The patient sample consisted of 432 men and 207 women. Developmental level was assessed by the Zigler-Phillips Social Competence Index. Patients who manifested delusions were found to be at a higher developmental level than those who suffered hallucinations. The social competence of patients having both symptoms tended to fall between the levels of the single symptom groups. Females had higher competence scores than males, and paranoid patients had higher scores than nonparanoid patients. The results were discussed in terms of the significance of developmental level as a pervasive dimension of the individual which relates to the expression of specific symptoms and other facets of psychiatric disorder.
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The paper reviews studies of the effectiveness of antidepressants in acute depression and variables accounting for nonresponsiveness. Data supporting continuation and maintenance therapy are presented. The authors discuss nonspecific psychotherapeutic components of drug management and also review studies of the usefulness of antidepressant and psychotherapy, alone and in combination.
The authors sketch the development of antipsychotic-drug treatment for schizophrenic patients focusing on efficacy in acute treatment, prevention of relapse during maintenance treatment, and differential symptom response. They also describe current treatment strategies that attempt to reduce the amount of medication required through continuous dose reduction or through the use of intermittent treatment.
In a clinicohistopathologic study of 557 patients with primary cutaneous malignant melanoma, there were fewer metastases and/or deaths from melanoma when histologic evidence of a coexisting acquired melanocytic nevus was found. A total of 130 patients with melanocytic nevus and 427 cases of melanoma without histologic evidence of a nevus (denovo) were studied. Clinical follow-up evaluation for evidence of metastases and/or death was obtained. Only ten of the patients (7.7%) with nevus-associated melanoma had metastases and/or death v 78 (18.3%) with de novo melanoma. When stratified by lesion thickness, the logrank test for survival revealed a statistically significant difference between the two groups. An overall favorable outcome seen in patients with malignant melanomas associated with acquired melanocytic nevi was found, therefore, to be independent of lesion thickness as well as six other variables reported to be related to the biologic behavior of malignant melanoma. Thus, the presence of nevus cells in a specimen of malignant melanoma portends a better prognosis and may have important implications in the biology of this neoplasm.
This article describes a controlled clinical trial comparing nomifensine and amitriptyline in endogenously depressed inpatients. It is also the first trial of the ICPP-BLIPS, a computer based clinical trial data documentation system. Using strict methodological criteria, careful quality control and comprehensive and systematic data display and data analysis, we have been able to show clearcut efficacy differences between nomifensine and amitriptyline (favouring the later) and clearcut differences in the profile of side effects between these drugs. Future studies utilizing this methodology are recommended were definitive and documented results of clinical trials are desired.
Developmental changes in plasma dehydropiandrosterone (DHA) and in adrenal histology were studied in several marmoset species (Callithrix jacchus and Saguinus labiatus, nigricollis, and fuscicollis) to evaluate these primates as experimental models for the study of fetal adrenal zone regression. Newborn marmosets had a prominent fetal adrenal zone, plasma DHA levels above 1000 ng/dl, and plasma DHA sulfate (DHAS) levels of 140 micrograms/dl. The fetal zone regressed dramatically during the first week of life, paralleled by a marked decline in plasma DHA, the plasma DHA to cortisol ratio, and plasma DHAS. The adult marmoset, however, had no adrenal reticular zone and no evidence of adrenal DHA secretion; DHA levels in castrate adults were undetectable (less than 25 ng/dl). Thus, the marmoset represents the first example of a primate that has a regressing, DHA- and DHAS-secreting fetal adrenal zone but that does not subsequently develop a DHA-secreting adrenal reticular zone.
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Fodrin (formerly designated 26 and 27) comprises two polypeptides (250,000 and 240,000 mol wt) that are axonally transported at a maximum time-averaged velocity of 40 mm/d--slower than the most rapidly moving axonally transported proteins, but faster than at least three additional groups of proteins. In this communication, we report the intracellular distribution of fodrin. Fodrin was purified from guinea pig brain, and a specific antifodrin antibody was produced in rabbit and used to localize fodrin in tissue sections and cultured cells by means of indirect immunofluorescence. Fodrin antigens were highly concentrated in the cortical cytoplasm of neurons and also nonneuronal tissues (e.g., skeletal muscle, uterus, intestinal epithelium). Their disposition resembles a lining of the cell: hence, the designation fodrin (from Greek fodros, lining). In cultured fibroblasts, immunofluorescently labeled fodrin antigens were arranged in parallel arrays of bands in the plane of the plasma membrane, possibly reflecting an exclusion of labeled fodrin from some areas occupied by stress fibers. The distribution of fodrin antigens in mouse 3T3 cells transformed with simian virus 40 was more diffuse, indicating that the disposition of fodrin is responsive to altered physiological states of the cell. When mixtures of fodrin and F-actin were centrifuged, fodrin cosedimented with the actin, indicating that these proteins interact in vitro. We conclude that fodrin is a specific component of the cortical cytoplasm of many cells and consider the possibilities: (a) that fodrin may be indirectly attached to the plasma membrane via cortical actin filaments; (b) that fodrin may be mobile within the cortical cytoplasm and that, in axons, a cortical lining may be in constant motion relative to the internal cytoplasm; and (c) that fodrin could serve to link other proteins and organelles to a submembrane force-generating system.
In a prospective study of 178 patients with malignant melanoma, a subset of 33 patients (18.5%) was identified to be at significantly higher risk for developing metastatic disease based on history of cigarette smoking. Patients in this high-risk group (current smokers with a greater than 15 pack-years of smoking history) had two-year disease-free survival rates of 74.2%. versus 92.3% for the remaining patients (p = 0.008). A possible explanation of this phenomenon is that chronic smoking diminishes host defense mechanisms and results in an adverse affect on the biologic behavior of established malignant melanomas.