Subtypes of Depression—Diagnosis and Medical Management

Depression is both a common and a greatly undertreated illness in the United States today. The focus of this review is a definition of the characteristics of four subtypes of depression which appear to be differentially sensitive to four different classes of medications. The tricyclic antidepressants should be used for patients with unipolar depression and vegetative symptoms. Lithium appears to be most effective for bipolar depressives. The monoamine oxidase (MAO) inhibitors are best used for patients with atypical depression. Antipsychotic medications appear to be useful for depressed patients with psychotic symptoms or agitation. Recent pharmacokinetic and biochemical data, including serum lithium levels, plasma tricyclic levels, and the predictive ability of pretreatment urinary 3-methoxy-4-hydroxyphenylglycol (MHPG) levels are also reviewed.     

Penetrating chest wound: a case report.

An unusual penetrating chest injury was caused by a ball-point pen. Because of apparent penetration of the heart, preparations were made for an emergency open-heart procedure before emergency thoracotomy was undertaken, with the pen still in situ. The pen had bruised the epicardium but had not penetrated the pericardial sac. After removal of the pen, the wound was closed and a chest tube left in place. Recovery, apart from minor degrees of basal atelectasis, pleural effusion and wound infection, was uneventful. The outcome was consistent with that associated with current aggressive management of penetrating chest injuries. Management is based on three approaches. The primary one is intercostal thoracostomy tube drainage and fluid and blood replacement. In cases of massive hemorrhage or air leak, thoracotomy is necessary. The third approach is to prevent post-traumatic pulmonary insufficiency by using fine, high-efficiency filters during blood transfusion, avoiding excessive administration of intravenous fluids, performing tracheostomy after prolonged endotracheal intubation, and using a volume respirator with positive end-expiratory pressure. The average mortality for penetrating wounds of the heart is 25%.     

Comparison of ribosomes from Coxiella burnetii and Escherichia coli by gel electrophoresis, protein synthesis, and immunological techniques.

Ribosomes and postribiosomal supernatant fluid (S-100) were isolated from Coxiella burnetii. The ribosomes functioned in polyuridylic acid-directed polyphenylalanine synthesis in the presence of S-100 from either C. burnetii or Escherichia coli. C. burnetii S-100 promoted translation with E. coli ribosomes. Antisera against E. coli elongation factor G and ribosomal proteins L7/L12 cross-reacted with rickettsial S-100 and ribosomes, respectively. Ribosomal proteins were analyzed by two-dimensional gel electrophoresis.     

Indoleamine 2,3-dioxygenase. Purification and some properties.

Indoleamine 2,3-dioxygenase was purified from rabbit small intestine to apparent homogeneity as judged by polyacrylamide gel electrophoresis and analytical ultracentrifugation. The native enzyme was a monomeric protein of a molecular weight of 41,000 +/- 1,000 with an s020,w value of 3.45 S. It had a relative abundance of hydrophobic amino acids such as valine, leucine, and isoleucine, and contained approximately 5% carbohydrate by weight. The estimated content of sugar residues per mol of enzyme was: galactose, 1.2; mannose, 2.6; N-acetylglucosamine, 5.2; and sialic acid, 0.8. One mole of enzyme had 0.8 mol of protoheme IX as a prosthetic group. However, copper was not detected in a significant amount and the ratio of copper to heme was less than 0.03. EPR spectra of the nitric oxide complex of the ferrous enzyme indicated that a nitrogen atom, possibly in an imidazole group, might be coordinated as the fifth ligand of the heme coenzyme. The anisotropic g values were gx = 2.08, gy = 1.98, and gz = 2.01. A single enzyme protein catalyzed the oxygenative ring cleavage of D- and L-tryptophan, D- and L-5-hydroxytryptophan, tryptamine, and serotonin. In addition, the purified enzyme had a peroxidase activity with guaiacol and potassium iodide as hydrogen donors, but not a catalase activity.     

Neurohypophyseal hormone-responsive renal adenylate cyclase. IV. A random-hit matrix model for coupline in a hormone-sensitive adenylate cyclase system

A "random-hit" matrix model is proposed to account for the dynamic and steady state relationship between occupation of bovine renal medullary membrane receptors by [Lys8]vasopressin (LVP) and neurohypophyseal hormones (NHH) and the associated activation of membrane-bound adenylate cyclase. The model was developed by systematic introduction of specific rules concerning receptor coupling into a general structural model which consists of two square matrices of identical size, one composed of homogeneous R ("receptor") units, the second of homogeneous C ("cyclase") units. R units are either occupied (RO) or unoccupied (RU); C units are either active (CA) or inactive (CI). Hormone molecules are envisioned to "collide" with R units randomly; collision with RU leads to "binding", and occupation is maintained for a characteristic mean occupancy time, TO. In this structure, each R unit has an "interaction field" which consists of the "twin" unit in the "C" matrix, and the 4 nearest neighbor C units surrounding the twin. Occupation of an R unit leads to activation of all CI units in the interaction field of that R; CA units in the interaction field are refractory. Thus binding at a given R may "recruit" a variable number of inactive neighboring C units (5, 4, 3, 2, 1, or 0). The model requires that there be individual coupling delays between the moment of binding at a given R and subsequent activation of CI units (mean coupling delay (Td) approximately 10% To). Activation of C units persists as long as the "parent" R is occupied and is maintained for an additional short time interval (Tp) after RO reverts to RU, corresponding to hormone dissociation from receptor. The model accounts for the following previously demonstrated relations between LVP occupation of receptors and adenylate cyclase activation in bovine renal medullary membranes: 1) the shape of the nonlinear steady state relation between normalized (percentage maximal) receptor occupation (O) and cyclase activation (A), uniformly observed in different membrane preparations: 2) variable hormone concentration-dependent trajectories of approach to the final steady state A:O value (A:Oss) which may be either monophasic or biphasic; 3) the loss of intrinsic adenylate cyclase activity observed in bovine membranes for a series of NHH analogs with progressively diminishing affinity for receptors. The model represents an explicit theory of coupling where a successive series of temporal events are quantitatively related to each other and privide major constraints to any interpretation of the molecular organization of receptors and adenylate cyclase units in membranes. The model excludes a number of mechanistic proposals and suggests a new hypothesis for membrane coupling with features which may be generally applicable to other hormone-sensitive adenylate cyclase systems.     

Complement lysis: evidence for an amphiphilic nature of the terminal membrane C5b-9 complex of human complement

The terminal, membrane-derived C5b-9 complex of human complement (C) is an apparently hollow, cylindrical macromolecule vertically oriented on the target membrane. In the present study, an antiserum to the complex has been used to probe its immunobiochemical properties. "Neoantigenic" determinants characteristic of the complex have been detected, which are absent on native C5-C9 molecules. Evidence that the C5b-9 complex is an amphiphilic molecule that possesses apolar, detergent-binding surfaces has been obtained by using charge-shift crossed immunoelectrophoresis, and by direct demonstration of Triton X-100 binding to the complex in quantitative immunoelectrophoresis. By the same criteria, serum C5, C6, and C9 are hydrophilic molecules. The results indicate that assembly of C5-C9 into the terminal membrane C5b-9 complex is accompanied by conformational changes in the individual C components that lead to the exposure of apolar molecular regions in the complex. It is proposed that this constitutes the basis for the lipid-binding properties of the macromolecule, which enable it to become inserted into biologic and artificial lipid membranes with apparent generation of a transmembrane pore.     

Drilomermis leioderma n. gen., n. sp. (Mermithidae:Nematoda) parasitizing Cybister fimbriolatus (Say) (Dystiscidae-Coleoptera)

The nematode Drilomermis leioderma n. gen., n. sp. (Merrnithidae) is described from larvae of Cybister fimbriolatus (Say) (Dytiscidae: Coleoptera) in Louisiana. Diagnostic characters of the genus Drilomermis are: medium-sized nematodes with the cuticle appearing smooth (lacking cross fibers) under the light microscope, six cephalic papillae, without mouth papillae, six hypodermal cords at midbody, 2 extremely long spicules (longer than 10 times body width at anus) which are separate and parallel (not twisted), an S-shaped vagina, medium-sized amphids located near head papillae, and postparasitic juvenile with a tail appendage. D. leioderma possesses a ventrally displaced mouth, very long vagina, and male genital papillae arranged in 3 double rows in the vicinity of the cloacal opening. Even when containing multiple parasites, about 40% of the hosts sulwived emergence of the memithids and lived several more days. In nature, some of these hosts may be able to continue their development, which is unusual since most mermithid-parasitized hosts die soon after the nematode emerges.     

A comprehensive examination of protein sequences for evidence of internal gene duplication

Summary We have implemented a routine procedure for screening protein sequences for evidence of intragenic duplications. We tested 163 protein sequences representing 116 superfamilies of unrelated proteins. Twenty superfamilies contain proteins with internal gene duplications. The intragenic duplications detected can be divided into two major types. (1) One or more duplications of all or part of a gene produce a protein with two or several detectable regions of sequence homology. Sequences from 18 superfamilies contained this type of duplication. (2) Repeated reduplication of a small DNA segment can produce a protein that is repetitive over most of its length. Three superfamilies contain such repetitive sequences. We also investigated the limits of detection of ancient duplications using sequences derived by random mutation of a model sequence consisting of ten 10-residue repeats. The original repetitive nature of the sequence was usually detected after 250 point mutations even though the ancestral segment could not be accurately reconstructed.     

Studies on Tyzzer's disease in rats.

An outbreak of an epidemic disease occurred in a specified-pathogen-free (SPF) breeding colony of rats. The clinical signs and the post-mortem findings were characteristic for Tyzzer's disease. The causative agent, Bacillus piliformis, was demonstrated microscopically in ileum, liver and myocardium, and transmitted to mice where its pathogenicity appeared to be similar to that of another strain isolated from mice. B. piliformis from spontaneously-infected rats was demonstrated by indirect immunofluorescence technique. By means of the same technique it was found that the fluorescence antibody titre obtained of the individual sera from spontaneously-infected mice, rats and rabbits was the same, whether the antigen employed was organisms isolated from rats or mice. By testing sera from healthy rats in 3 different colonies by use of immunofluorescence technique, antibodies were found in several sera.