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Biomedical subjects

M Shapiro

Publications and source records attributed to M Shapiro.

At least 199 records · Page 11Linked to original sources
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

Physicians' perception of personal risk of HIV infection and AIDS through occupational exposure.

Physicians' response to acquired immune deficiency syndrome (AIDS) is poorly understood and often attributed to fear of human immunodeficiency virus (HIV) infection through occupational exposure. We surveyed 268 physicians from three geographic regions in North American with different specialties and responsibilities for HIV-positive patients. An important difference was found between the published risk and the physicians' perceived risk of infection after a single occupational exposure. Almost half of the respondents stated that they feared contracting AIDS more than other diseases. The physicians who perceived themselves to be at high physical risk were more likely than the others to report that AIDS had changed the way they interact with their patients (r = 0.26, p less than 0.001). No relation was found between the perception of physical risk and the number of HIV-infected patients (r = -0.07, p = 0.15). However, the perception of social risk showed a small inverse correlation (r = -0.15, p less than 0.02), in which the physicians with more HIV-infected patients reported less concern about negative social consequences. The physicians who perceived themselves to be at high personal risk were more likely than the others to report that surgeons have the right to refuse patients who do not wish to undergo HIV antibody testing (r = -0.16, p less than 0.01 for physical risk; r = -0.29, p less than 0.001 for social risk). Multiple regression analyses indicated that physicians' perception of physical risk was not related to age or sex but was modestly related to income source. The perception of social risk was related to sex and income source. Physicians' perception of personal risk is a crucial, yet often unacknowledged, component of the fight against AIDS. Our findings suggest that lack of attention to this issue is seriously compromising initiatives designed to facilitate physician participation in AIDS care.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Early events in hepatitis C virus infection of chimpanzees.

The cytoplasmic antigen and ultrastructural changes we described previously for chimpanzees (Pan troglodytes) infected with hepatitis C virus (HCV) or with hepatitis D virus have recently been shown to be indirect measures of viral replication and appear to represent a host response to the expression or action of interferon. The time of appearance of these changes in hepatocytes during HCV infection, when compared with similar changes in hepatitis D virus infection, suggests a very early replicative phase for HCV. To investigate the early events in HCV infection, we infected two chimpanzees with HCV and obtained blood and liver biopsy samples from them daily during the first 10 days of infection. The early stage of infection with regard to HCV replication, antigen expression, and ultrastructural changes was similar in both chimpanzees. When tested by cDNA/polymerase chain reaction, HCV sequences became detectable in the serum as early as 3 days after inoculation and remained positive through the peak of aminotransferase elevations. In one chimpanzee the peak of virus production appeared to be 7 weeks after inoculation, which was coincident with rising enzyme values. The cytoplasmic antigen, detected by immunofluorescence, and ultrastructural changes, detected by electron microscopy, became positive in hepatocytes 3 and 6 days, respectively, after HCV sequences were first detected in serum. Circulating anti-HCV appeared 13 weeks and 32 weeks after inoculation, respectively, in the chimpanzees. These data indicate a very early replicative phase for HCV and a potentially long period of infectivity before the appearance of anti-HCV.

Animals↗
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↗
PubMed1990

Selective arterial stimulation of secretin in localization of gastrinomas.

In two patients with malignant gastrinoma and the Zollinger-Ellison syndrome, we were able to use selective arterial stimulation with secretin as a technique to localize the lesions accurately, allowing resection. The technique of selected arterial secretin stimulation is one of measuring variations in gastrin levels in both the hepatic vein and a peripheral artery at specified times after injection of secretin into a specific artery. When the criteria for localization have been met, one can plot the presence of the gastrinoma within the blood supply of the injected artery and, using angiograms, thus accurately localize the lesion. This method promises to be a valuable additional tumor-localizing procedure, particularly when gastrinomas are extrapancreatic.

Adenoma, Islet Cell↗
PubMed1990

Cutaneous responses to histamine, compound 48/80 and codeine in patients with hyperthyroidism.

The regulatory effects of various endocrine factors on allergic processes have been widely studied. The clinical importance of hyperthyroidism in asthma and in chronic urticaria has been demonstrated in several cases. These observations may be attributed to modulatory effects of thyroid hormones on mast cell releasability and/or on other target organs as blood vessels. To evaluate the effects of thyroid hormones on mast cell releasability and on the cutaneous vasculature, we analyzed the wheal and flare response to compound 48/80, to codeine, and to histamine in patients with hyperthyroidism and in a control group. No significant difference was found between the two groups. We could not demonstrate any in vivo effect of the thyrotoxic state on the cutaneous response to these substances.

Adolescent↗
PubMed1989

Human IgG Fc receptor (hFcRII; CD32) exists as multiple isoforms in macrophages, lymphocytes and IgG-transporting placental epithelium.

We previously isolated cDNA clones from a human monocyte library that encoded one member of a family of low-affinity surface receptors for the Fc domain of IgG (hFcRII-A). To investigate possible structural and functional heterogeneity among these receptors, we have now isolated two additional cDNAs (hFcRII-B and hFcRII-C) from a human placental library, placenta being a good source of FcR-bearing macrophages and epithelial cells. Three cDNAs encoded related but distinct transmembrane glycoproteins containing two immunoglobulin-like domains; however, transfected cells produced receptors that were indistinguishable on the basis of ligand binding or reactivity with anti-hFcRII monoclonal antibodies. The sequences of hFcRII-A and -B were most closely related and were identical except for several amino acid substitutions and one small internal deletion. While the ectodomain of hFcRII-C was identical to hFcRII-B, its cytoplasmic tail was unrelated but highly homologous to the corresponding domain of the receptor isoform (mFcRII-B2) found in murine macrophages. Thus, human FcRII may be derived from at least two alternatively spliced genes. Northern blots revealed little difference in the pattern of expression of hFcRII isoforms among various myeloid and lymphoid cells or cell lines. However, the blots--as well as in situ hybridization and immunohistochemistry--demonstrated that hFcRII-C (along with a second monocyte marker, the c-fms encoded CSF-1 receptor) was expressed in placental syncytiotrophoblasts. Since syncytiotrophoblasts comprise the IgG-transporting epithelium of the placental villus, these findings suggest that FcR found in the immune system and in certain epithelia may be structurally or functionally related.

Amino Acid Sequence↗
PubMed1989

Screening antenatal blood samples for anti-human immunodeficiency virus antibodies by a large-pool enzyme-linked immunosorbent assay system. Results of an 18-month investigation.

Blood samples submitted for routine antenatal testing from 104,683 pregnant women resident in the southern Transvaal were screened for antibodies to the human immunodeficiency virus (HIV) during an 18-month period--1 May 1987 - 31 October 1988. All blood samples were initially screened by a modified enzyme-linked immunosorbent assay whereby 48 samples are tested simultaneously in one microtitre well. Each positive 48-pool was subdivided and retested in a 12-pool system. The individual positively reacting sample, having been identified, was submitted to a reference laboratory for confirmatory testing which included Western blotting. In the cohort of 84,527 black women tested, the incidence of confirmed anti-HIV positivity was 1:2753 (0.036%) in the first 3 months of the study and increased to 1:461 (0.217%) in the last 3-month period.

Black or African American↗
PubMed1989

Randomised study of myringotomy, amoxycillin/clavulanate, or both for acute otitis media in infants.

In a prospective study, 105 infants aged 3-12 months with acute otitis media were randomly assigned to one of three treatment groups: amoxycillin/clavulanate ('Augmentin') alone (36 patients), myringotomy plus placebo (35 patients), or augmentin plus myringotomy (34 patients). The last two groups were double-blinded. Bacterial pathogens, mainly Haemophilus influenzae (of which 20% were beta-lactamase producers) and Streptococcus pneumoniae, were isolated from 60% of the ear exudates and all isolates were sensitive to augmentin. Most of the infants improved clinically within 3-6 days irrespective of the treatment protocol. As judged by otoscopy, 60% of the patients receiving augmentin, with or without myringotomy, recovered completely compared with 23% of patients treated with myringotomy plus placebo. Treatment with augmentin was also more effective than myringotomy with regard to persistence of ear infection. In the myringotomy plus augmentin group closure of the incision and resolution of the discharge from the incision site was faster than in the myringotomy plus placebo group. The addition of myringotomy to augmentin did not seem to affect either the persistence of the infection after treatment or the residual middle ear effusion.

Acute Disease↗
PubMed1989

Understanding physicians' response to AIDS.

Attempts to comprehend physicians' extreme reaction to AIDS (acquired immune deficiency syndrome) have met with great difficulty since the disease brings into question traditional norms and assumptions. As the medical profession struggles to develop guidelines and policies to help it deal with this disease, it can draw on very little systematic research on the effect of AIDS on physicians' attitudes and practices. We suggest a framework developed from the literature on physicians' and society's response to other disorders that would provide a basis for organizing the ever-increasing amount of information on physicians and AIDS and would guide systematic research aimed at understanding and predicting physicians' participation in the prevention and management of AIDS. Within this framework we consider how characteristics of the disease, elements of the health care system and physicians' attitudes interact to influence clinical and personal practices. AIDS had led to new delineations of physicians' responsibility, modification of prevailing beliefs about physician autonomy and thus a redefinition of the role of the physician in North America.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Reappearance of hepatitis D virus (HDV) replication in chronic hepatitis B virus carrier chimpanzees rechallenged with HDV.

Four chronic hepatitis B virus (HBV) carrier chimpanzees, which had apparently cleared hepatitis D virus (HDV) after a first experimental challenge with HDV, were reinoculated with a homologous strain of HDV. All animals had reappearance of low levels of serum HDV RNA and transient, mild alanine aminotransferase (ALT) elevations, which in two cases correlated with HDV RNA positivity. Plasmas obtained from two chimpanzees after rechallenge were inoculated into two other chronic HBV carrier animals that had recovered from a previous HDV infection. A similar reappearance of HDV RNA in serum (without ALT elevation) was noticed. These same plasmas, however, when inoculated into a chronic HBV carrier chimpanzee never exposed to HDV caused a severe acute hepatitis D. Rechallenge with HDV in chimpanzees apparently recovered from a first HDV infection resulted in the reappearance of HDV replication, sometimes associated with hepatitis. This can be interpreted as reinfection with HDV, but other explanations are possible. Although the serum level of HDV RNA observed after rechallenge with HDV is low, its transmission to individuals susceptible to HDV infection can result in severe acute hepatitis D.

Alanine Transaminase↗
PubMed1989

In vitro production of infectious woodchuck hepatitis virus by lipopolysaccharide-stimulated peripheral blood lymphocytes.

Peripheral blood lymphocytes (PBLs) from a wild-caught woodchuck (WC192) chronically infected with woodchuck hepatitis virus (WHV) carried low levels of nonreplicating WHV genomes. In a previous study, these WHV genomes were induced to replicate and intact WHV particles were released when these PBLs were cultured in the presence of the generalized mitogen, lipopolysaccharide (LPS). To determine whether the culture-derived WHV particles were infectious, adult woodchucks were inoculated with cell-free culture medium from either LPS-stimulated or unstimulated WC192 PBLs. None of three animals inoculated with medium from the unstimulated PBL cultures developed positive WHV serologic markers or elevated liver enzyme levels during a 42-w observation period. In contrast, all three animals that received medium from the LPS-stimulated cultures displayed serologic markers of acute WHV infections 8-10 w after inoculation at up to a 100-fold dilution of the original culture medium. One of the three infected animals developed an acute hepatitis coincident with the appearance of the WHV markers. These results demonstrate that the WHV particles released from LPS-stimulated WC192 PBLs in culture are mature, infectious virions that also cause liver disease. Thus the LPS-induced replication of WHV in these cell cultures represents a transition from a latent to productive viral infection.

Animals↗