Beyond conventional physical examination in hepatology: POCUS.

Point-of-care ultrasound (POCUS) refers to the use of ultrasound imaging through pocket-sized sonographic devices at the patient's bedside, to make a diagnosis or direct a procedure and immediately answer a clinical question. Its goal is to broaden the physical examination, not to replace conventional ultrasound studies. POCUS has evolved as a complement to physical examination and has been adopted by different medical specialties, including hepatology. A narrative synthesis of the evidence on the applications of POCUS in hepatology was carried out, describing its usefulness in the diagnosis of cirrhosis of the liver, metabolic dysfunction-associated steatotic liver disease (MASLD), decompensated cirrhosis, and portal hypertension. The review also encompasses more recent applications in the hemodynamic evaluation of the critically ill patient with cirrhosis of the liver, patients with other liver diseases, as well as in the ultrasound guidance of procedures. POCUS could make up part of the daily clinical practice of gastroenterologists and hepatologists, simplifying the initial evaluation of patients and optimizing clinical management. Its accessibility, ease of use, and low adverse event profile make POCUS a useful tool for the properly trained physician in the adequate clinical setting. The aim of this review was to describe the available evidence on the usefulness of POCUS in the daily clinical practice of gastroenterologists and hepatologists.

Evaluation and management of emergencies in the patient with cirrhosis.

The approach to and management of critically ill patients is one of the most versatile themes in emergency medicine. Patients with cirrhosis of the liver have characteristics that are inherent to their disease that can condition modification in acute emergency treatment. Pathophysiologic changes that occur in cirrhosis merit the implementation of an analysis as to whether the overall management of a critically ill patient can generally be applied to patients with cirrhosis of the liver or if they should be treated in a special manner. Through a review of the medical literature, the available information was examined, and the evidence found on the special management required by those patients was narratively synthesized, selecting the most representative decompensations within chronic disease that require emergency treatment.

Improving collected rainwater quality in rural communities.

The country of Mexico is facing serious problems with water quality and supply for human use and consumption in rural communities, mainly due to topographic and isolation. In Mexico the average annual precipitation is 1,500 cubic kilometers of water, if 3% of that amount were used, 13 million Mexicans could be supplied with drinking water that they currently do not have access. Considering the limited infrastructure and management in rural communities, which do not receive services from the centralized systems of large cities, a modified pilot multi-stage filtration (MMSF) system was designed, developed, and evaluated for treating collected rainwater in three rural communities, Ajuchitlan and Villa Nicolas Zapata (Morelos State) and Xacxamayo (Puebla State). The efficiencies obtained in the treatment system were: colour and turbidity >93%. It is worth mentioning that the water obtained for human use and consumption complies with the Mexican Standard NOM-127-SSA1-1994.

Microvesicles: ROS scavengers and ROS producers.

This review analyzes the relationship between microvesicles and reactive oxygen species (ROS). This relationship is bidirectional; on the one hand, the number and content of microvesicles produced by the cells are affected by oxidative stress conditions; on the other hand, microvesicles can directly and/or indirectly modify the ROS content in the extra- as well as the intracellular compartments. In this regard, microvesicles contain a pro-oxidant or antioxidant machinery that may produce or scavenge ROS: direct effect. This mechanism is especially suitable for eliminating ROS in the extracellular compartment. Endothelial microvesicles, in particular, contain a specific and well-developed antioxidant machinery. On the other hand, the molecules included in microvesicles can modify (activate or inhibit) ROS metabolism in their target cells: indirect effect. This can be achieved by the incorporation into the cells of ROS metabolic enzymes included in the microvesicles, or by the regulation of signaling pathways involved in ROS metabolism. Proteins, as well as miRNAs, are involved in this last effect.

Evidence that fungal MEP proteins mediate diffusion of the uncharged species NH(3) across the cytoplasmic membrane.

Methylammonium and ammonium (MEP) permeases of Saccharomyces cerevisiae belong to a ubiquitous family of cytoplasmic membrane proteins that transport only ammonium (NH(4)(+) + NH(3)). Transport and accumulation of the ammonium analog [(14)C]methylammonium, a weak base, led to the proposal that members of this family were capable of energy-dependent concentration of the ammonium ion, NH(4)(+). In bacteria, however, ATP-dependent conversion of methylammonium to gamma-N-methylglutamine by glutamine synthetase precludes its use in assessing concentrative transport across the cytoplasmic membrane. We have confirmed that methylammonium is not metabolized in the yeast S. cerevisiae and have shown that it is little metabolized in the filamentous fungus Neurospora crassa. However, its accumulation depends on the energy-dependent acidification of vacuoles. A Deltavph1 mutant of S. cerevisiae and a Deltavma1 mutant, which lack vacuolar H(+)-ATPase activity, had large (fivefold or greater) defects in the accumulation of methylammonium, with little accompanying defect in the initial rate of transport. A vma-1 mutant of N. crassa largely metabolized methylammonium to methylglutamine. Thus, in fungi as in bacteria, subsequent energy-dependent utilization of methylammonium precludes its use in assessing active transport across the cytoplasmic membrane. The requirement for a proton gradient to sequester the charged species CH(3)NH(3)(+) in acidic vacuoles provides evidence that the substrate for MEP proteins is the uncharged species CH(3)NH(2). By inference, their natural substrate is NH(3), a gas. We postulate that MEP proteins facilitate diffusion of NH(3) across the cytoplasmic membrane and speculate that human Rhesus proteins, which lie in the same domain family as MEP proteins, facilitate diffusion of CO(2).

Two-site immunoenzymometric assays for serum IgG subclass infant/maternal ratios at full-term.

Improvements were made in the range, precision, convenience, automation, and reliability of our previously published two-site immunoenzymometric assays using mouse monoclonal antibodies specific for human IgG and its subclasses. The serum concentration ratios for these immunoglobulin isotypes were measured in neonatal/maternal paired sera from 119 normal full-term deliveries. These ratios are significantly different than 1.0 (P = 0.001) for total IgG, IgG1, and IgG2 (show non-equality of paired neonatal/maternal sera concentrations) but are not significantly different than 1.0 for IgG3 and IgG4. On average, IgG1 is elevated 61%, and IgG2 is depressed 11% in the full-term neonate with respect to its own mother. In some pregnancies, active transport of IgG1 may be selectively enhanced by low material IgG1 concentration and selectively inhibited by high levels.

Microsurgical treatment of intractable hemifacial spasm.

Ten patients with intractable hemifacial spasm were treated by posterior fossa exploration and microsurgical technique. These patients have been followed 1 to 5 years. The spasmodic motor disorder was related to compression of the 7th nerve or its exit zone at the brain stem by a dolichoectatic anterior inferior cerebellar artery in eight patients and to kinking and ectasia of the basilar or vertebral artery in two patients. In five patients, there were prominent arachnoidal adhesions in the cerebellopontine angle, and an arachnoid cyst was a component of the lesion in another patient. Additional conditions associated with hemifacial spasm included geniculate neuralgia, facial paresis, vertigo, hearing loss, and trigeminal neuralgia. The surgical morbidity and postoperative results are discussed.

[Intelligence, memory and malingering: correlation between scales]. / Inteligencia, memoria y simulación: correlaciones entre instrumentos de medida.

OBJECTIVES: To validate the test of memory malingering (TOMM), and to study the influence of intelligence and memory on its performance in brain injury patients. PATIENTS AND METHODS: A total of 30 patients with traumatic head injury were included in the study. All patients were assessed with the Complutense verbal learning test, the Visual Reproduction subtest of the Wechsler memory scale-revised, the Boston naming test, two fluency tests (FAS, and animals), the Wechsler adult intelligence test-III, and with the TOMM. Cognitive results below 1 standard deviation (SD) from normative data were considered 'abnormal'. A parametric correlation between TOMM scores and cognitive tests was used to detect whether memory and intelligence were affecting TOMM performance. Statistical significance was set up at p<0.05. RESULTS: Between 46.1% (Boston) and 81.4% (WAIS-III performance IQ) of the sample presented cognitive deficits. Up to 83.3% of the patients scored above the cutoff point suggestive of malingering in the TOMM (45/50). Significance correlations were found between TOMM scores and memory or intelligence indexes. DISCUSSION: The TOMM is a useful tool to detect malingering in head injured patients. Effects of low intelligence coefficients, as well as memory deficits should be considered in clinical practice when evaluating patients with TOMM scores suggestive of malingering.

[Anoxic encephalopathy. Clinical description, prognosis and neuroimaging]. / Encefalopatía anóxica. Descripción clínica, pronóstico y neuroimagen.

OBJECTIVES: To describe the clinical profile (neuropsychological, psychopathological, functional and neuroimaging), as well as the evolution of patients with anoxic encephalopathy. PATIENTS AND METHODS: Nine patients with anoxic encephalopathy attending our Service were included in the study. All patients were assessed with a broad range of neuropsychological tests, checklists of psychopathological symptoms, and several functional scales. A CT/MRI or a positron emission tomography (PET) were performed in five patients. Five patients were admitted to a multidisciplinary rehabilitation program. RESULTS: All patients showed problems in orientation, executive functions, verbal learning an immediate and long-term verbal memory, in association with diffuse cognitive changes in other functions. Psychopathologically, all patients showed apathy-indifference, and eight subjects showed anosognosia. All subjects have an important dependence in daily activities. CT/MRI were normal or showed subcortical changes whereas the PET showed a predominantly cortical hypometabolism with specific patterns. There were no significant improvements after rehabilitation in treated patients. CONCLUSION: In the absence of a unique clinical profile, our patients with anoxic encephalopathy showed similarities in their symptoms (diffuse cognitive deficits with predominance of amnesic and executive impairments; presence of apathy and anosognosia; complete functional dependence; and poor response to the rehabilitation). Functional neuroimaging could be a useful tool for a better understanding of these encephalopathies.

Esófago de Barrett: revisión de la literatura / Barrett's esophagus: review

El Esófago de Barrett (EB) es una patología adquirida producto del reflujo gastroesofágico crónico que provoca la lesión de la mucosa esofágica normal y su reemplazo por mucosa metaplásica. La importancia clínica del EB radica en que constituye un factor de riesgo para el desarrollo de adenocarcinoma esofágico. La incidencia del adenocarcinoma esofágico se encuentra en aumento y su diagnóstico se realiza generalmente en etapas avanzadas, teniendo un pronóstico sombrío. Actualmente el objetivo es detectar el cáncer en etapas iniciales y eventualmente tratables, para lo cual se han planteado distintos protocolos de vigilancia y numerosas alternativas de tratamiento del epitelio metaplásico del esófago de Barrett. En el siguiente artículo se revisan los conceptos más recientes de manejo.

Barrett's esophagus is an acquired disease caused by chronic gastroesophageal reflux causing the injury of normal esophageal mucosa and its replacement by metaplastic mucosa. The clinical significance of Barrett's esophagus is that it constitutes a risk factor for the development of esophageal adenocarcinoma. The incidence of esophageal adenocarcinoma is increasing and its diagnosis is usually done in advanced stages, with grim prognosis. Currently the goal is to detect cancer in early, treatable stages. Different protocols have been proposed, numerous alternatives for monitoring and treating metaplastic epithelium of Barrett's esophagus. In the following article the latest management concepts are reviewed.

Tratamiento endoscópico del cáncer de colon: revisión de la literatura / Endoscopic treatment of colon cancer: review of the literature

Surgery has long been the only available treatment for colorectal cancer (CRC) even for those detected in early stages. Follow-up studies suggest that endoscopic resection (ER) in carefully selected patients with CRC may be curative. Endoscopic mucosal resection (EMR) in Japan is indicated in the treatment of colorectal adenomas and intramucosal and superficial submucosa CRC commitment, due to the low risk of lymph node metastasis and excellent clinical results. In treating large lesions, tumors of lateral extension, depressed lesions and those with no mark elevation, endoscopic submucosal dissection (ESD) appears as a safe and less invasive alternative, allowing for block resection and also facilitating analysis by the pathologist. In skilled hands, ER may be performed on outpatients obtaining similar results to the surgical treatment, however, a variety of complications have been described, including stricture formation, bleeding and perforations. It is essential to identify those patients who will benefit from endoscopic therapy, carefully evaluating the indications of endoscopic treatment of CRC. A new challenge is to establish a systematic training program for colorectal ESD and to develop improvements in the design of instruments, equipment and solutions for injection to facilitate and increase its use around the world. On the other hand, endoscopy in CRC has a palliative role providing tools for the control of hemorrhage or palliative recanalization of luminal obstruction, including local treatment or colonic stent.

La cirugía ha sido por mucho tiempo el único tratamiento disponible para el cáncer colorrectal (CCR) incluso para aquellos detectados en etapas tempranas. Los estudios de seguimiento sugieren que la resección endoscópica (RE) en pacientes con CCR cuidadosamente seleccionados puede ser curativa. La resección mucosa endoscópica (RME) en Japón está indicada en el tratamiento de adenomas colorrectales y CCR intramucoso y con compromiso de la submucosa superficial debido al escaso riesgo de metástasis ganglionar y a los excelentes resultados clínicos. En el tratamiento de lesiones de mayor tamaño, tumores de extensión lateral, lesiones deprimidas y aquellas con signo de no elevación, la disección endoscópica submucosa (DES) aparece como una alternativa segura, menos invasiva y efectiva que permite la resección en bloque y facilita el análisis por el patólogo. En manos experimentadas, la RE se puede realizar en pacientes ambulatorios, obteniendo resultados similares al tratamiento quirúrgico, sin embargo, una variedad de complicaciones se han descrito, incluyendo la formación de estenosis, hemorragia y perforaciones. Es fundamental identificar aquellos pacientes que se beneficiarán del tratamiento endoscópico, evaluando cuidadosamente las indicaciones de tratamiento endoscópico del CCR. Un nuevo desafío es establecer un programa de entrenamiento sistemático para DES colorrectal, además de desarrollar mejoras en el diseño de los instrumentos, equipamiento y soluciones para inyección para facilitar y aumentar su realización en el mundo. Por otra parte, la endoscopia en CCR tiene un rol paliativo, aportando herramientas para el control de hemorragia o la recanalización paliativa de una obstrucción luminal, que incluye el tratamiento local o la instalación de stent colónicos.

Osmotic signal transduction to proU is independent of DNA supercoiling in Escherichia coli.

proU expression has been proposed to form part of a general stress response that is regulated by increased negative DNA supercoiling brought about by environmental signals such as osmotic or anaerobic stress (N. Ni Bhriain, C. J. Dorman, and C. F. Higgins, Mol. Microbiol. 3:933-944, 1989). However, we find that although proU-containing plasmids derived from cells grown in media of elevated osmolarity were more supercoiled than plasmids from cells grown in standard media, they did not activate proU expression in vitro. The gyrA96 mutation and anaerobic conditions are known to affect DNA supercoiling but did not alter proU expression. Finally, the gyrase inhibitors coumermycin and novobiocin did not reduce in vitro proU expression. Therefore, this evidence rules out regulation by changes in DNA superhelicity for proU in Escherichia coli.

Secretion can proceed uncoupled from net plasma membrane expansion in inositol-starved Saccharomyces cerevisiae.

Secretion of acid phosphatase and invertase was examined in an inositol-requiring ino1 mutant of the yeast Saccharomyces cerevisiae. Inositol starvation is known to block plasma membrane expansion, presumably due to restricted membrane phospholipid synthesis. If membrane expansion and extracellular protein secretion are accomplished by the same intracellular transport process, one would expect secretion to fail coordinately with cessation of plasma membrane growth in inositol-starved cells. In glucose-grown, inositol-starved cells, plasma membrane expansion and acid phosphatase secretion stopped coordinately, and intracellular acid phosphatase accumulated. In sucrose-grown, inositol-starved cells, plasma membrane growth halted, but secretion of both acid phosphatase and invertase continued until the onset of inositol-less death. Although glucose-grown and sucrose-grown cells differ in their ability to secrete when deprived of inositol, they exhibited the same disturbances in phospholipid synthesis. Phosphatidylinositol synthesis failed, and its precursors phosphatidic acid and CDP-diglyceride accumulated equally in both cultures. Sucrose-grown yeast cells appear to accomplish normal levels of extracellular protein secretion by an inositol-independent mechanism. In glucose-grown yeasts, both plasma membrane expansion and secretion are inositol dependent.

Nonrandomly-associated forward mutation and mitotic recombination yield yeast diploids homozygous for recessive mutations.

We have employed the analysis of spontaneous forward mutations that confer the ability to utilize L-alpha-aminoadipate as a nitrogen source (alpha-Aa+) to discern the events that contribute to mitotic segregation of spontaneous recessive mutations by diploid cells. alpha-Aa- diploid cells yield alpha-Aa+ mutants at a rate of 7.8 +/- 3.6 x 10(-9). As in haploid strains, approximately 97% (30/31) of alpha-Aa+ mutants are spontaneous lys2-x recessive mutations. alpha-Aa+ mutants of diploid cells reflect mostly the fate of LYS2/lys2-x heterozygotes that arise by mutation within LYS2/LYS2 populations at a rate of 1.2 +/- 0.4 x 10(-6). Mitotic recombination occurs in nonrandom association with forward mutation of LYS2 at a rate of 1.3 +/- 0.6 x 10(-3). This mitotic recombination rate is tenfold higher than that of a control LYS2/lys2-1 diploid. Mitotic segregation within LYS2/lys2-x subpopulations yields primarily lys2-x/lys2-x diploids and a minority of lys2-x aneuploids. Fifteen percent of lys2-x/lys2-x diploids appear to have arisen by gene conversion of LYS2 to lys2-x; 85% of lys2-x/lys2-x diploids appear to have arisen by mitotic recombination in the CENII-LYS2 interval. lys2-1/lys2-1 mitotic segregants of a control LYS2/lys2-1 diploid consist similarity of 18% of lys2-1/lys2-1 diploids that appear to have arisen by gene conversion of LYS2 to lys2-1 and 82% of lys2-1/lys2-1 diploids that appear to have arisen by mitotic recombination in the CENII-LYS2 interval.(ABSTRACT TRUNCATED AT 250 WORDS)

In vitro reconstitution of osmoregulated expression of proU of Escherichia coli.

Osmoregulated expression of proU has been reconstituted in a cell-free system. proU encodes an osmotically inducible, high-affinity transport system for the osmoprotectant glycine betaine in Escherichia coli. Previously, a proU-lacZ fusion gene had been cloned, resulting in plasmid pOS3. In vivo osmoregulation of this extrachromosomal proU-lacZ fusion gene at low copy number showed that the plasmid-encoded fusion contained all the necessary sequences in cis for correctly receiving osmoregulatory signals during induction by osmotic stress and repression by glycine betaine. Using a cell-free (S-30) extract, plasmid pOS3 was then used to program protein synthesis in vitro. The ionic compound potassium glutamate specifically stimulated proU-lacZ expression in a concentration-dependent manner. Potassium acetate also induced some proU expression, but other salts were ineffective, thereby ruling out ionic strength as the stimulatory signal. High concentrations of sucrose, trehalose, or glycine betaine did not induce proU expression in vitro either, eliminating osmolarity per se as the stimulus. Reconstitution in a cell-free system rules out osmoregulatory mechanisms that depend on turgor, trans-membrane signaling, or trans-acting regulators synthesized after osmotic upshock.

[Intelligence and prognosis in severe traumatic brain injury: a neuropsychological study with the Wechsler adult intelligence scale (WAIS-III)]. / Pronóstico e inteligencia en los traumatismos craneoencefálicos graves: estudio neuropsicológico mediante el test de inteligencia de Wechsler para adultos (WAIS-III).

OBJECTIVE: To evaluate the utility of the Wechsler adult intelligence scale III (WAIS-III) as a measure of intelligence after severe brain injury, and to elucidate prognostic factors associated with intelligence coefficients (IQs). METHODS: Forty-six patients (age: 27.4 +/- 12.8 years) attending our service after a severe head injury were included in our study (chronicity: 315.3 +/- 330 days after injury). All patients were assessed with the WAIS-III. WAIS-III IQs were correlated (Pearson and Spearman) with clinical and demographic data. A significance level of p < 0.05 was used in all comparisons. IQs between 1 and 2 standard deviation (SD) below normative data were considered "mild abnormal" while indexes below 2 SD were considered "abnormal". RESULTS: Only eleven patients (25 %) showed normal total IQ with predominance of manipulative (77.7 %) compared to verbal (64.5 %) impairment. Thirty-eight patients (95 %) had difficulties in speed processing, thirty-six (85.6 %) had problems with working-memory, twenty-five (62.5 %) showed impairments in perceptual organization, and twenty-six (62 %) had verbal comprehension deficits. WAIS-III IQs showed significant correlations with length of coma and posttraumatic amnesia duration (p < 0.05). CONCLUSIONS: The WAIS-III is a valid and sensible tool to detect cognitive deficits associated with brain injury. Almost all patients with severe brain injury show abnormal IQs with a slow processing speed as predominant symptom. Length of coma and posttraumatic amnesia seems to be the most relevant parameter related to intelligence in severe brain-injured patients.

The immunopathology of human Schistosomiasis-III. Immunoglobulin isotype profiles and response to praziquantel.

Immunoglobulin (Ig) isotype (IgG, IgG1, IgG2, IgG3, IgG4, IgM, IgD and IgE) levels were investigated, both pre- and post-treatment with praziquantel (PZQ), in 43 adults and children chronically infected with Schistosoma mansoni, by means of a two-site, isotype-specific immunoenzymometric assay. The patients were classified as responders (R) or non-responders (NR) on the basis of their circumoval precipitin test (COPT) results 12 months after treatment. In comparison with controls, pre-treatment R children showed significantly higher levels of IgG, IgG1, IgG4 (p < 0.001) and IgE (p < 0.01); and diminished IgG2 (p < 0.05), while NR children showed significantly elevated levels only of IgE (p < 0.05). Twelve months after therapy, R children maintained significantly lower levels of IgG2, but showed significantly decreased levels of IgG, IgG1, IgG4, and IgE, while the Ig isotype profile of NR children was unaltered. Adult R and NR showed similar isotype profiles before chemotherapy, with the exception of significantly elevated IgM levels in R. Twelve months after therapy, R adults showed significantly decreased levels of IgG, IgG1, and IgG4, while NR adults showed only diminished IgG4 levels. These results reveal different Ig isotype profiles in untreated adults and children chronically infected with S. mansoni. The results further show that the pre-treatment Ig isotype profile may be significantly modified after an effective R to chemotherapy, accounted for by down regulation of the IgG1 isotype in association with negative seroconversion of the COPT in R patients. The COPT reaction has been associated with the highly specific egg glycoprotein antigen omega 1, which shows a significant reduction in reactivity six months after treatment. IgG1 may thus play a main role in the response against the omega 1 antigen.

RPD3 (REC3) mutations affect mitotic recombination in Saccharomyces cerevisiae.

Prior research identified the recessive rec3-1ts mutation in Saccharomyces cerevisiae which, in homozygous diploid cells, confers a conditional phenotype resulting in reduced levels of spontaneous mitotic recombination and loss of sporulation at the restrictive temperature of 36 degrees C. We found that a 3.4-kb genomic fragment that complements the rec3-1ts/rec3-1ts mutation and which maps to chromosome XIV, is identical to RPD3, a gene encoding a histone de-acetylase. Sporulation is reduced in homozygous diploid strains containing the rec3-1ts allele at 24 degrees C, suggesting that this allele of RPD3 encodes a gene product with a reduced function. Sporulation is abolished in diploid strains homozygous for the rpd3Delta or rec3-1ts alleles, as well as in rpd3Delta/rec3-1ts heteroallelic diploids, at the non-permissive temperature. Acid-phosphatase expression has been shown to be RPD3 dependent. We found that acid-phosphatase activity is greater in diploid strains homozygous for the temperature-sensitive rec3-1ts allele than in RPD3/RPD3 strains and increased further when mutant strains are grown at 36 degrees C. We also tested the rpd3Delta/rpd3Delta strains for their effects on spontaneous mitotic recombination. By assaying a variety of intra- and inter-genic recombination events distributed over three chromosomes, we found that in the majority of cases spontaneous mitotic recombination was reduced in diploid rpd3Delta/rpd3Delta cells (relative to a RPD3/RPD3 control). Finally, although 90% of mitotic recombinant events are initiated in the G1 phase of the growth cycle (i.e., before DNA synthesis) we show that RPD3 is not regulated in a cell-cycle-dependent manner. These data suggest that mitotic recombination, in addition to gene expression, is affected by changes in chromatin architecture mediated by RPD3.

Plasma membrane expansion terminates in Saccharomyces cerevisiae secretion-defective mutants while phospholipid synthesis continues.

Phospholipid synthesis activity and plasma membrane growth have been studied in the Saccharomyces cerevisiae temperature-sensitive, secretion-defective mutants isolated by Novick and Schekman (Proc. Natl. Acad. Sci. U.S.A. 76:1858-1862, 1979; Novick et al., Cell 21:205-215, 1980). The mutants, sec1 through sec23, do not grow at 37 degrees C and exhibit lower rates of phospholipid synthesis than does the wild-type strain X2180. None of the mutants exhibits a decline in lipid synthesis rapid enough to explain secretion failure. Plasma membrane growth was assessed indirectly by examining the osmotic sensitivity of spheroplasts derived from cultures transferred from 24 to 37 degrees C. Spheroplasts from the normal-growing strain X2180 exhibited a small rapid increase in osmotic sensitivity and stabilized at a more sensitive state. Spheroplasts from the sec mutants exposed to the same temperature shift exhibited progressively increasing osmotic sensitivity. Cycloheximide treatment prevented progressive increases in osmotic fragility. These data are compatible with the hypothesis that plasma membrane expansion is restricted in the sec mutants. During incubation at 37 degrees C, the accumulation of intracellular materials within the no-longer expanding plasma membrane exerts osmotic stress on the membrane, increasing with time. The gene products defective in Novick and Schekman's sec mutants appear to be required for both extracellular protein secretion and plasma membrane growth in yeast cells.

Hypergammaglobulinemia associated with human immunodeficiency virus infection.

The serum concentrations of 11 Ig isotypes (IgG, IgG1, IgG2, IgG3, IgG4, IgA, IgA1, IgA2, IgM, IgD, and IgE) were measured in four relatively small groups of homosexual (or bisexual) males. All these patients were seropositive for HIV. Two of the groups (nonprogressors) were clinically stable for approximately 2 years and were characterized either as asymptomatic or with PGL. The third group (progressors) developed AIDS 2-38 months after blood specimens were taken. The fourth group had AIDS. A fifth group of anti-HIV-seronegative heterosexual males completed the study. The geometric mean IgA serum concentration was more markedly elevated over normal control sera than any of the other study groups and was the only Ig isotype that was significantly higher in the progressor than in the nonprogressor group. The geometric IgG1 serum concentration was significantly higher in asymptomatic nonprogressors, PGL-nonprogressors, progressors, and AIDS patient groups than that in HIV-seronegative normals. In contrast, the geometric mean IgG2 serum concentration is depressed in all the anti-HIV-seropositive patients (but not significantly with the AIDS group). Multivariate analysis showed the Ig-isotype assays to have much less predictive power for progression to AIDS than the T-helper cell assays.