Similar T-cell immune responses induced by group M consensus env immunogens with wild-type or minimum consensus variable regions.

Consensus HIV-1 genes can decrease the genetic distances between candidate immunogens and field virus strains. To ensure the functionality and optimal presentation of immunologic epitopes, we generated two group-M consensus env genes that contain variable regions either from a wild-type B/C recombinant virus isolate (CON6) or minimal consensus elements (CON-S) in the V1, V2, V4, and V5 regions. C57BL/6 and BALB/c mice were primed twice with CON6, CON-S, and subtype control (92UG37_A and HXB2/Bal_B) DNA and boosted with recombinant vaccinia virus (rVV). Mean antibody titers against 92UG37_A, 89.6_B, 96ZM651_C, CON6, and CON-S Env protein were determined. Both CON6 and CON-S induced higher mean antibody titers against several of the proteins, as compared with the subtype controls. However, no significant differences were found in mean antibody titers in animals immunized with CON6 or CON-S. Cellular immune responses were measured by using five complete Env overlapping peptide sets: subtype A (92UG37_A), subtype B (MN_B, 89.6_B and SF162_B), and subtype C (Chn19_C). The intensity of the induced cellular responses was measured by using pooled Env peptides; T-cell epitopes were identified by using matrix peptide pools and individual peptides. No significant differences in T-cell immune-response intensities were noted between CON6 and CON-S immunized BALB/c and C57BL/6 mice. In BALB/c mice, 10 and eight nonoverlapping T-cell epitopes were identified in CON6 and CON-S, whereas eight epitopes were identified in 92UG37_A and HXB2/BAL_B. In C57BL/6 mice, nine and six nonoverlapping T-cell epitopes were identified after immunization with CON6 and CON-S, respectively, whereas only four and three were identified in 92UG37_A and HXB2/BAL_B, respectively. When combined together from both mouse strains, 18 epitopes were identified. The group M artificial consensus env genes, CON6 and CON-S, were equally immunogenic in breadth and intensity for inducing humoral and cellular immune responses.

New form of X-linked dominant hereditary nephritis in dogs.

OBJECTIVE: To determine features of a new form of hereditary nephritis (HN) in dogs. ANIMALS: Parents and 16 first-generation offspring (8 males, 8 females). PROCEDURE: Adolescent dogs that developed renal failure were euthanatized and necropsied. Unaffected dogs were monitored until they were at least 2 years old. Studies included light and electron microscopy of kidneys obtained from affected and unaffected dogs and immunolabeling for collagen-IV chains in renal and epidermal basement membranes (BM). The nucleotide sequence of a portion of exon 35 of the COL4A5 gene was determined in genomic DNA isolated from affected and unaffected males. RESULTS: 7 of 8 male and 2 of 8 female offspring had proteinuria and juvenile-onset chronic renal failure, which progressed more rapidly in the males. Labeling for alpha3-alpha6(IV) chains was completely absent in renal BM of affected males and segmentally absent in affected females. Expression of alpha1-alpha2(IV) chains in glomerular BM (GBM) of affected dogs was increased. Labeling for alpha5-alpha6(IV) chains in epidermal BM was absent in affected males and segmental in affected females. Ultrastructural changes characteristic of HN were observed in GBM of affected dogs. The sequence of exon 35 of COL4A5 was normal in affected dogs. CONCLUSIONS: This renal disease is an example of X-linked dominant HN, with typical abnormalities of GBM ultrastructure and alpha(IV) chain expression. CLINICAL RELEVANCE AND IMPLICATIONS FOR HUMAN MEDICINE: Dogs with this naturally acquired progressive renal disease can be used to investigate the pathogenesis and treatment of similar disorders in human beings and dogs.

Tratamiento quirúrgico de emergencia del vólvulo Hospital Clínico Viedma 1988-1994 / Emergency surgical treatment of volvulos at Viedma Hospital

El vólvulo de sigmoide es causa frecuente de consulta en emergencia del Hospital Clínico Viedma: tratandose de un centro que atiende a la mayoria de la población Cochabambina. En el periódo comprendido entre 1988 a 1994: fueron sometidos a cirugía de emergencia 189 pacientes con el diagnóstico de vólvulo de sigmoides. El sexo masculino fue el mas afectado 62.6 por ciento y 27.4 por ciento del sexo femenino. Mas del 60 por ciento de los pacientes acudio a emergencia durante las primeras 48 hrs de iniciado el cuadro el cual favorecio en el diagnóstico precoz y tratamiento precoz. Se solicito placa simple de abdomén en el 73.5 por ciento; restosigmoidoscopia en el 72.5 por ciento; procedimientos que coadyuvarón en el diagnóstico precoz. La irritación peritoneal en mas de 50 por ciento de los casos fue la indicación para el tratamiento quirúrgico de emergencia. De los 189 pacientes intervenidos quirúrgicamente en el 78.8 por ciento se encontro compromiso de la vitalidad intestinal, solo en el 21.2 por ciento se encontro asa viable. La operación de Hartman fue la opción quirúrgica que mayor preferencia tuvo en el 71.9 por ciento tanto en pacientes con asa comprometida y en los casos con asa viable. La mortalidad postquirúrgica fue del 25.4 por ciento y la mortalidad del 9.5 por ciento.

Afección Pulmonar en pacientes con artritis reumatoidea

El presente estudio se realizo con el fin de determinar la incidencia de afección pulmonar en pacientes con artritis reumatoidea y su relación con la actividad de la enfermedad. Se estudiaron 25 pacientes con artritis reumatoidea con >4 criterios de la A.R.A. de 1987 y se les realizó historia clínica completa, determinación de factor reumatóideo, radiografía estandar de torax y póstero anterior de manos con carpos, espirometria y gasometría arterial en reposo. El 36 por ciento (9/25) de pacientes presentó afección pulmonar y de estos 66,6 por ciento eran sintomáticos. 71,4 por ciento presentaron alteración espirométrica, 77,7 por ciento presentaron hipoxia arterial en reposo. La afección pulmonar mostró una relación directamente proporcional con la clase funcional de la enfermedad con una diferencia estadisticamente significativa p<0.005. No tuvo relación con el nivel del factor reumatoideo, duración de la enfermedad, presencia de nódulos y estadío radiológico de la Artritis Reumatóidea. Por lo tanto se puede afirmar que la afección pulmonar en la artritis reumatoidea no es infrecuente y su incidencia se relaciona directamente con la clase funcional de la enfermedad.

Uncertainties and ambiguities: measuring how medical students cope.

To develop psychometric measures specific to the ambiguities encountered in medicine and determine their value in predicting medical students' attitudes towards patients and their choice of residency, we administered to senior and first-year medical students a 25-item Likert-type questionnaire to assess their intolerance of ambiguity (ITA). Factor analysis yielded two dimensions that were converted to scales: 'Aversion to uncertainties in clinical medicine' (ITA1) and 'Preference for highly structured training environs' (ITA2). First-year students scored higher on ITA1 and lower on ITA2 than seniors. An excessive reliance on high-technology medicine, a negative orientation toward psychological problems, and Machiavellianism predicted ITA1. ITA1 was the best predictor of senior medical students' negative attributional style toward hypochondriac, geriatric and chronic pain patients. The following rank order of seniors' career choice was predicted by ITA1 scores: internal medicine, psychiatry and family medicine (lowest); radiology, surgery and anaesthesiology (highest). And by ITA2 scores: surgery, obstetrics and gynaecology, and surgical subspecialties (lowest); radiology, psychiatry and anaesthesiology (highest). We concluded that personality traits and role characteristics which predict 'Aversion to uncertainties in clinical medicine' are maladaptive to managing many primary care patients, and this mismatch is reflected in seniors' residency choice.

Machiavellianism in medical students.

To be more responsive to the nation's health needs, medical educators should identify those personal qualities associated with effective primary medical care. For this research Machiavellianism was chosen as a tracer character trait opposed to the characteristics embodied in an ideal family physician. A survey was conducted of 167 freshmen from one medical school and 823 seniors from four medical schools, with Machiavellianism scores used to predict their professional role characteristics, attributional style toward patients, and choice of a career specialty. Results showed that 15% of all students scored positively on the Machiavellianism scale. Mean Machiavellianism scores for seniors did not differ from those for freshmen. Men had higher Machiavellianism scores than women. Those students with high Machiavellianism scores relied excessively on high-tech medicine and were externally controlled, intolerant of ambiguity, and authoritarian. Seniors' high Machiavellianism scores predicted a negative attributional style toward geriatric and hypochondriac patients, thereby validating the use of Machiavellianism to measure medical students' indifference to patients and their problems.

Traumatismo abdominal: Hospital Clínico Francisco Viedma, Departamento de Cirugía 1989-1993 / Abdominal trauma at Viedma Hospital

El traumatismo abdominal es causa frecuente de consulta en emergencia del Hospital Clínico Viedma; tratandose de un centro que atiende a la mayoria de la población cochabambina. En el periódo comprendido entre los años 1989-1993 se registraron 114 traumatismos abdominales. El sexo masculino fue el mas afectado con 92 casos (80.2 por ciento del sexo femenino. El mayor porcentaje se registro entre la segunda y cuarta década de la vida (85 por ciento); el arma blanca fue el agente casual mas utilizado con un porcentaje de (48.2), seguido de los accidentes de tránsito (21.2 por ciento). Solo en el (54 por ciento) de los casos se realizaron exámenes complementarios, en el (30.7 por ciento) de los casos se solicito rayos X, paracentesis abdominal en el (7.9 por ciento). Las vísceras mas afectadas resultaron ser el intestino delgado en el (28 por ciento) colon en el (17.5 por ciento) e hígado en el (12.3 por ciento) de los casos. El tratamiento quirúrgico mas frecuente fue realizado el el (57.7 por ciento) de los casos fue la rafia simple mas drenaje. Solo en el 22.8 por ciento de los casos se observó lesiones asociadas a otros sistemas.

Ontogenetic changes in the venom of the snake Lachesis muta stenophrys (bushmaster) from Costa Rica.

A comparative study was performed on some enzymatic and toxic activities of venoms collected from newborn, one-year old, two-years old and adult (more than five-years old) specimens of Lachesis muta stenophrys. There was an increase in lethal, hemorrhagic, edema-forming, myotoxic, proteolytic and phospholipase A2 activities of venoms as snakes aged. The venom of newborn specimens was almost devoid of toxicity. On the other hand, venom from newborn specimens showed the highest coagulant effect of human plasma. Electrophoretic and immunochemical results demonstrated conspicuous differences between venoms of different ages. Observations on the feeding behavior indicated that specimens of L. muta of different ages displayed a similar pattern, characterized by rapid strike and bite, holding the prey until they stopped their movements and swallowing them afterwards. It is concluded that venom of newborn L. muta has very low toxic and proteolytic activities and that it undergoes conspicuous changes during the first year of life.

Myonecrosis induced in mice by a basic myotoxin isolated from the venom of the snake Bothrops nummifer (jumping viper) from Costa Rica.

The mode of action of a basic myotoxin isolated from Bothrops nummifer venom was studied. This myotoxin is a basic polypeptide of 13,000 mol.wt, with a high content of lysine and aspartate, as well as of hydrophobic amino acids. It lacked phospholipase A2 activity when tested on several substrates at different pH values. Upon i.m. injection into mice, the toxin induced early morphological alterations typified by 'delta lesions' in the periphery of muscle fibers, an indication that the plasma membrane was the first cellular structure to be affected. Afterwards, necrotic cells had a clumped appearance, which then changed to a more hyaline histological pattern. Removal of necrotic material by phagocytes was followed by skeletal muscle regeneration, with the presence of myoblasts, myotubes and fully regenerated myofibers. The toxin induced a rapid and drastic drop in muscle creatine and creatine kinase contents of injected muscle, as well as an increase in serum levels of the enzymes lactic dehydrogenase and creatine kinase. Moreover, total muscle calcium increased significantly after toxin administration. Myotoxin induced a dose-dependent release of peroxidase entrapped in liposomes made from muscle phospholipids. The lack of phospholipase A2 activity in this toxin, together with the observation that it behaved as an amphiphilic protein in charge-shift electrophoresis, suggests that it might penetrate and disorganize muscle plasma membrane by means of a hydrophobic interaction.

An analysis of the magnitude of clinical-reasoning deficiencies in one class.

Clinical-reasoning ability is indispensable to a good doctor, but students are generally expected to "pick it up" in the course of their clinical clerkships. Concern by the University of Washington School of Medicine that some students did not master the concepts of clinical reasoning led to the formation of an ad hoc committee whose retrospective study on the class of 1981 is reported here by the authors. Nineteen students (11 percent of the graduating class) who were repeatedly noted by faculty members to have problems with clinical reasoning throughout their clinical clerkships were identified as a result of this study.

Purification of a carboxypeptidase B-like enzyme from the starfish Dermasterias imbricata.

A carboxypeptidase B-like enzyme which catalyses the hydrolysis of synthetic esters of lysine and arginine has been isolated from the starfish Dermasterias imbricata. This carboxypeptidase B-like enzyme has a molecular weight of approximately 34 000 and shares this and other properties with bovine pancreatic carboxypeptidase B. The existence of zymogen for this activity in the pyloric caeca of the starfish is demonstrated. This zymogen has a molecular weight near 40 000 and appears to be analogous to other monomeric procarboxypeptidases B. The zymogen possesses an intrinsic low-level activity toward synthetic substrates of carboxypeptidase B and is activated by trypsin.