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Biomedical subjects

M Shapiro

Publications and source records attributed to M Shapiro.

At least 19 recordsLinked to original sources
PubMed1992

Intracranial pressure and cerebral perfusion pressure in experimental streptococcus pneumoniae meningitis.

Clinical studies have demonstrated the prognostic importance of increased intracranial pressure in central nervous system infections. To delineate development of intracranial pressure in meningitis experiments were carried out in rabbits. Meningitis was induced by injecting streptococcus pneumoniae bacteria into the cisterna magna and blood, and intracranial pressures were continuously recorded. In the experimental model, three stages were seen: incubation period (0-8 h)--in which CSF becomes positive for the infecting organism and biochemical changes occur, but there are no hemodynamic or intracranial pressure changes; stage of slowly increasing intracranial pressure - because blood pressure remains normal, cerebral perfusion pressure is maintained adequate for cerebral metabolic need (9-24 h); terminal stage (greater than 25 h)--with hemodynamic collapse, critical reduction of cerebral perfusion pressure, cerebral ischemia, and death of the experimental animals. It is suggested that a similar sequence occurs in human disease. The clinical implication stresses the need for early recognition and treatment of intracranial hypertension as an important adjunct to antibiotic treatment of the infecting organism.

Animals↗
PubMed1992

Molecular basis of virulence and growth of hepatitis A virus in cell culture.

The ability of engineering variants of hepatitis A virus (strain HM175) to replicate in cell culture or to cause disease in marmosets was evaluated. Virus variants were encoded by chimeric genomes constructed from infectious cDNA clones of two viruses (wild type and cell-culture-adapted) which differed in their ability to grow in vitro and to cause acute hepatitis in marmosets. Transfection and infectivity assays indicated that virus growth in vitro could be enhanced by subcloning the cell substrate prior to infection or by introducing multiple combinations of two or more mutations into the wild type genome. Various chimeric viruses induced liver enzyme elevations in marmosets, indicating that attenuation of virulence also required multiple mutations.

Animals↗
PubMed1992

cDNA clone of hepatitis A virus encoding a virulent virus: induction of viral hepatitis by direct nucleic acid transfection of marmosets.

Direct inoculation of marmoset livers with an in vitro transcription mixture containing cDNA and full-length genomic RNA transcripts of hepatitis A virus resulted in acute viral hepatitis. Elevations in serum levels of liver enzymes were correlated with appearance of antibody to hepatitis A virus. Genomes of infectious hepatitis A virus isolated from the feces of transfected marmosets contained the same mutation as the cDNA template used for transfection. Liver biopsies confirmed that the virus encoded by the cDNA clone induced histopathological changes equivalent to those caused by virulent wild-type virus.

Animals↗
PubMed1992

Pancreatic disease: findings on state-of-the-art MR images.

Recent technical innovations have made MR imaging a useful technique for imaging the pancreas. The potential impact of MR imaging on the management and outcome of cases can be determined only by controlled prospective comparative studies; however, these cannot be performed adequately until the normal and abnormal appearances of the pancreas on state-of-the-art MR images are understood. This pictorial essay is presented to further this intermediate goal.

Adenocarcinoma↗
PubMed1992

Relation between hospital experience and in-hospital mortality for patients with AIDS-related Pneumocystis carinii pneumonia: experience from 3,126 cases in New York City in 1987.

There is marked debate about whether outcomes of care, particularly mortality, vary as a function of hospital and physician experience with a disease. This issue is especially important with respect to AIDS because greater than 200,000 individuals have now been diagnosed with this disease. We analyzed discharge data for 3,126 persons with AIDS who had Pneumocystis carinii pneumonia and who were treated at one of 73 New York City hospitals in 1987. In-hospital mortality was 25%. Factors associated with higher chances of short-term death were older age, being black, not having private health insurance, and being severely ill. A logistic regression model indicated that after controlling for differences in patient and hospital characteristics, the chances of death decreased when care was given at hospitals with higher caseloads of patients with Pneumocystis carinii pneumonia. Our findings suggest that hospital experience may decrease mortality in this subset of patients with human immunodeficiency virus disease, although it is unknown whether this is due to differences in quality of care.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Attempts to transmit hepatitis B virus to chimpanzees by arthropods.

Bedbugs (Cimex lectularius L.) were fed on an infective blood-hepatitis B virus (HBV) mixture. Further bedbugs and tampan ticks (Ornithodoros moubata [Murray]) were fed on HBV-carrier chimpanzees. After a 10-13 day interval for oviposition, tests done on samples of individual arthropods showed that 53-85% of the bugs were HBsAg-positive and none HBeAg-positive, while 100% of the ticks were HBsAg-positive and 88% HBeAg-positive. The remaining arthropods were fed on 3 susceptible chimpanzees, which had failed to develop HBV infection after 11 months, indicating no transmission had occurred. Subsequently the presence of viable virus in the original infective meals was confirmed by inoculation of the relevant donor sera directly into the 3 still susceptible chimpanzees. HBV infections quickly followed in each animal. It is concluded that, while mechanical transmission of HBV is most unlikely after a 10-13-day interval between feedings in bedbugs and tampans, it is still possible that mechanical transmission between humans might occur during interrupted feeds.

Animals↗
PubMed1991

Genetic mapping in the mouse of four loci related to the jun family of transcriptional activators.

Southern blot analysis of DNAs from somatic cell hybrids and the progeny of an intersubspecies backcross were used to identify and chromosomally map four loci in the mouse containing sequences cross-reactive to members of the jun family of transcriptional activators. The murine homolog of v-jun, Jun, was mapped to chromosome (Chr) 4, and a locus containing jun B-related sequences (Junb) was mapped to Chr 8. Probes for jun D identified two genetic loci; one, Jund-1, is near Junb on Chr 8, and a second, previously unidentified locus termed Jund-2, was mapped to Chr 2.

Animals↗
PubMed1991

Mutant tryptophan aporepressors with altered specificities of corepressor recognition.

The Escherichia coli trpR gene encodes tryptophan aporepressor, which binds the corepressor ligand, L-tryptophan, to form an active repressor complex. The side chain of residue valine 58 of Trp aporepressor sits at the bottom of the corepressor (L-tryptophan) binding pocket. Mutant trpR genes encoding changes of Val58 to the other 19 naturally occurring amino acids were made. Each of the mutant proteins requires a higher intracellular concentration of tryptophan for activation of DNA binding than wild-type aporepressor. Whereas wild-type aporepressor is activated better by 5-methyltryptophan (5-MT) than by tryptophan, Ile58 and other mutant aporepressors prefer tryptophan to 5-MT as corepressor, and Ala58 and Gly58 prefer 5-MT much more strongly than wild-type aporepressor in vivo. These mutant aporepressors are the first examples of DNA-binding proteins with altered specificities of cofactor recognition.

Apoproteins↗
PubMed1991

Islet cell responses to glucose in human transplanted pancreas.

Postsurgery, pancreas transplantation results in alterations of carbohydrate metabolism. Additionally, immunosuppressive therapy impacts on glucose regulation. We evaluated the hormonal and metabolic responses of pancreas allografts, utilizing the hyperglycemic clamp technique coupled with the tritiated glucose methodology, in 11 volunteers who had received simultaneous pancreas-kidney transplantation (P-K) with systemic drainage. Their responses were compared with seven volunteers who had received only a kidney (K) graft and with seven normal control (C) volunteers. Although basal glucose and hepatic glucose output were similar in all three groups, basal insulin, C-peptide, glucagon, and pancreatic polypeptide were highest in the P-K group and lowest in normal subjects. During hyperglycemia, all groups showed a similar characteristic, initial complete suppression of hepatic glucose production, with recovery followed by a later suppression. Peripheral glucose uptake was similar in P-K and C subjects but decreased in K patients. Systemic insulin levels were fourfold higher in the pancreas transplant patients than in healthy subjects. Thus, under basal and hyperglycemic stimulation, 1) hepatic glucose homeostasis is regulated normally, even with pancreatic drainage into the systemic circulation; 2) overall glucose disposal is normal in P-K patients because of marked hyperinsulinemia; and 3) there is loss of tonic inhibition of endocrine pancreatic function secondary to pancreatic denervation.

Adolescent↗
PubMed1991

Relationship of the human protooncogene CBL2 on 11q23 to the t(4;11), t(11;22), and t(11;14) breakpoints.

A probe identifying CBL2, the human cellular homolog of the murine oncogene v-cbl and murine cellular protooncogene Cbl-2, and panels of rodent X human somatic cell hybrids were used to study the relationship of this protooncogene to translocations associated with acute leukemia, lymphoma, and Ewing sarcoma. CBL2 was mapped to 11q23 and found to translocate from chromosome 11 to 4 in an acute leukemia cell line possessing a t(4;11)(q21;q23) and from chromosome 11 to 14 in a B-cell lymphoma with a t(11;14)(q23;q32). In an Ewing sarcoma cell line with a t(11;22)(q23;q12), however, CBL2 remained on chromosome 11. Additional studies of other genes in the region of 11q23 allowed the following ordering of these genes and breakpoints: 11cen--q23--NCAM--CD3(E-D-G)--[t(11;14), t(4;11)]--(THY1, CBL2, ETS1)--t(11;22)--11qter. The gross structure of the CBL2 sequences examined was not altered by either of the flanking breakpoints. Given that the 5' and 3' ends of the CBL2 gene are not known and are probably not evaluated by the v-cbl probe, these results do not rule out the possibility of CBL2 involvement in the pathogenesis of a subset of acute leukemias possessing a t(4;11), B-cell lymphomas possessing a t(11;14), or Ewing sarcomas possessing a t(11;22).

Animals↗
PubMed1991

Stabilization of F-actin prevents cAMP-elicited Cl- secretion in T84 cells.

T84 cells, a human intestinal epithelial cell line, serve as a model of electrogenic Cl- secretion. We find that cAMP-elicited Cl- secretion in T84 cells is accompanied by a marked redistribution of F-actin in the basolateral portion of the cell. To prevent this F-actin redistribution and thereby assess its importance to Cl- secretion, we have defined simple conditions under which this model epithelium can be loaded with nitrobenzoxadiazole (NBD)-phallicidin. This reagent binds F-actin with high affinity thus stabilizing the F-actin cytoskeleton by preventing depolymerization, an event necessary for dynamic reordering of actin microfilaments. NBD-phallicidin loading is not cytotoxic as assessed by lactic dehydrogenase release, protein synthesis, transepithelial resistance, and the ability of the loaded cells to pump Na+ in an absorptive direction in response to the apical addition of a Na+ ionophore. However, cAMP-elicited redistribution of F-actin and the cAMP-elicited Cl- secretory response are both markedly impaired in NBD-phallicidin preloaded T84 cells. In contrast, the carbachol-elicited Cl- secretory response (Ca++ mediated) is not attenuated by NBD-phallicidin preloading nor is it accompanied by redistribution of F-actin. These findings suggest that the cAMP-elicited cytoskeletal redistribution we describe is an integral part of cAMP-elicited Cl- secretion in T84 cells.

Actins↗
PubMed1991

Legionellosis at Hadassah University Hospital: a 1-year survey.

During 1985 in the Hadassah University Hospital we studied all hospitalized patients whose serum had been submitted for Legionella antibodies. Of 133 patients, 12 (9%) had legionellosis as diagnosed by serology, direct fluorescence, or culture. All Legionella cases appeared to be sporadic, nonseasonal, community-acquired pneumonia. There were no specific environmental co-factors or clustering. A significant predilection of the disease for immunosuppressed individuals was observed; the in-hospital mortality was high (5/12), especially if erythromycin therapy was delayed. L. pneumophila and L. bozemanii were the dominant etiological species. In Jerusalem, Legionella is not infrequently the etiological agent in community-acquired pneumonia in immunosuppressed patients.

Adult↗
PubMed1991

The sequences of the human and mouse c-cbl proto-oncogenes show v-cbl was generated by a large truncation encompassing a proline-rich domain and a leucine zipper-like motif.

The murine Cas NS-1 retrovirus carries the v-cbl oncogene and induces pre-B cell lymphomas and myeloid leukemias. The cellular homolog of v-cbl has been identified in mouse and human DNA, and was recently mapped to mouse chromosome 9 and human chromosome 11q23. To determine the coding sequences of the human and mouse c-cbl proto-oncogenes cDNA clones were isolated from libraries prepared from the human T cell leukemia lines CCRF-CEM and HUT 78, and the mouse pre-B cell line 70Z/3. DNA sequencing revealed an open reading frame encoding 906 amino acids in the human cDNAs and 896 amino acids in 70Z/3. The sequence showed that v-cbl is a markedly truncated form of murine c-cbl containing 355 N-terminal amino acids. The nucleotide sequence of v-cbl is identical to murine c-cbl in this region, and the human sequence has only five amino acid changes in the v-cbl portion. The most notable features of the sequence which was lost in the generation of v-cbl is a C-terminal leucine zipper and a stretch of 208 amino acids containing 23% proline and 19% serine/threonine residues. This proline-rich sequence has similarities to the transcriptional activation domains of some transcription factors, and v-cbl's transforming potential may be due to the loss of this region and the leucine zipper.

Amino Acid Sequence↗
PubMed1990

Failure of prolonged treatment with ciprofloxacin in acute infections due to Brucella melitensis.

A randomized prospective, pilot study was performed to compare the efficacy of oral ciprofloxacin (750 mg or 1000 mg bd) with standard oral antimicrobial therapy (rifampicin plus doxycycline) in the treatment of acute infection with Brucella melitensis. All antimicrobial drugs were administered for 42 days. Although all patients responded rapidly, five of the six patients receiving ciprofloxacin relapsed following cessation of therapy. There were no relapses among the patients who received doxycycline/rifampicin. Despite its in-vitro activity against B. melitensis (MIC 0.5 mg/l), ciprofloxacin, administered twice daily, does not appear to constitute adequate therapy for acute brucellosis.

Acute Disease↗
PubMed1979

Use of antimicrobial drugs in general hospitals: patterns of prophylaxis.

The patterns of prophylactic use of antimicrobial drugs were reviewed in 5288 charts drawn by a random method from 20 randomly selected short-stay general hospitals in Pennsylvania. About 10 per cent of hospitalized patients received antimicrobial drugs for prophylaxis in operations or nonsurgical procedures, and prophylaxis accounted for about 30 per cent of all antimicrobial drugs administered in hospitals. The drugs used most often for prophylaxis were cephalosporins, followed by benzyl penicillins, ampicillin and tetracyclines, in that order. Despite indications that prophylaxis, when useful at all, is effective only when given concurrently with and for 24 to 48 hours after operation, it was usually continued throughout hospitalization. Almost 80 per cent of prophylactic antimicrobial drugs were administered at least 48 hours after an operation or procedure -- suggesting that limiting prophylaxis to the first 24 to 48 hours, as currently recommended, would substantially reduce expenditures for antimicrobial drugs in hospitals.

Ampicillin↗