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Biomedical subjects

A D Hoffman

Publications and source records attributed to A D Hoffman.

At least 37 records · Page 2Linked to original sources

Replication of HIV-1 in a wide variety of animal cells following phenotypic mixing with murine retroviruses.

Human T cells co-infected with the human immunodeficiency virus type 1 (HIV-1) and the xenotropic or dual-tropic mouse type C virus (MuLV) give rise, by phenotypic mixing, to progeny virus that can transfer HIV-1 into a wide variety of mammalian and avian cells. Differences in the extent of HIV-1 replication in these animal cells can be observed. Replication is best in human cells, but occurs substantially in cells from many animal species including mink, horse, and bush wallaby. Virus production in murine and avian cells is very limited. These results confirm that the major block to HIV-1 infection of animal cells is at the cellular surface but that intracellular regulation of viral replication is also involved. Moreover, an enhancement of HIV-1 cytopathic effects can be seen in human cells co-infected by MuLV. All these data suggest phenotypically mixed viruses might be useful for developing an animal model system for studying AIDS, and that the pathological expression of HIV-1 could be modified by the presence in cells of other retroviruses. They also indicate a potential mechanism by which HIV strains can be generated with an increased ability to spread in nature.

Acquired Immunodeficiency Syndrome↗

Craniofrontonasal dysostosis with deafness and axillary pterygia.

Craniofrontonasal dysostosis (CFND) is an inherited disorder previously referred to as craniofrontonasal dysplasia. However, there is no evidence of tissue dysplasia and, therefore, the term dysostosis has been substituted. The disorder is characterized by frontonasal dysostosis, coronal craniostenosis, and the variable presence of other skeletal defects, including short webbed neck, sloping shoulders, polydactyly, syndactyly, and broad first toes. Here we report an affected mother and daughter who also have limited hip abduction. In addition, the mother had an axillary pterygia, congenital footplate fixation of the left ear, and right sensorineural hearing loss; these manifestations have not been reported previously in CFND and expand the phenotype of this syndrome. Both patients had marked restriction of shoulder abduction, and the mother had limited forearm pronation; these manifestations have been reported in only one other patient with CFND. Awareness of the possibility of these abnormalities may allow for early intervention by physical therapy and hearing aides in infants and young children with these manifestations as a component of CFND.

Abnormalities, Multiple↗

Factors associated with infantile hypertrophic pyloric stenosis.

We examined perinatal factors in relation to the rise in incidence of infantile hypertrophic pyloric stenosis among children in Olmsted County, Minnesota, during the period from 1950 through 1984. Primogeniture was associated with male infants but not female infants; some factor related to primogeniture, such as breast-feeding, may be etiologically important. Our data did not support a role for maternal disease, use of doxylamine succinate-pyridoxide hydrochloride (Bendectin), or an infectious process. Further study should be directed toward environmental factors associated with primogeniture.

Birth Order↗

Trends in infantile hypertrophic pyloric stenosis in Olmsted County, Minnesota, 1950-1984.

In the 35-year period, 1950-1984, 154 Olmsted County, Minnesota, infants were diagnosed with definite infantile hypertrophic pyloric stenosis (IHPS). Patients were identified using outpatient and inpatient records of all providers of care to the circumscribed population, and ascertainment was complete insofar as diagnosed cases are concerned. The overall incidence of IHPS was 2.6 per 1000 person-years (95% confidence interval: 2.2-3.0), with a male:female ratio of 4.1:1. A dramatic rise in incidence was seen among male infants over the study period, but not for females, so that by 1980-1984 the rates for the two sexes were 6.2 and 0.9 per 1000 person-years, respectively. Improvements in diagnostic capabilities and case identification may have occurred but seem unlikely to entirely account for these changes. Aetiologic hypotheses should reflect the different trends for male and female infants.

Cohort Studies↗

Mouse xenotropic viruses can inhibit cell transformation.

Mammalian type C retroviruses can be detected by their induction of foci of cell transformation in S+I - cells. We have noted that certain subtypes of the mouse xenotropic type C retrovirus (MuLV) inhibit this cell alteration. This inhibition, associated with intact virions, is irreversible and gives the infected cells a phenotype of uninfected cells. In comparison to the transformed cells, the inhibited cultures showed primarily a decrease in murine sarcoma virus (MSV) progeny production concomitant with a reduction in the MSV mos RNA expression. No difference in beta-actin RNA production was observed between the inhibited and transformed cultures. This selective effect of mouse xenotropic MuLV on MSV and mos RNA production in these cells focuses attention on the mechanism of transformation in this system.

Actins↗

Enhanced AKR leukemogenesis by the dual tropic viruses. I. The time and site of origin of potential leukemic cells.

The occurrence of potential leukemia cells (PLC) among bone marrow, spleen, and thymus of AKR mice during the preleukemic period was tested by an in vivo transplantation bioassay. The presence of PLC in 30- and 75-day-old AKR mice was demonstrated mostly among bone marrow cells, less in spleen, and was lacking in thymus. Occurrence of PLC in young AKR mice was shown to be thymus independent. However, progression of PLC from young donors (14-80 days old) into overt leukemia following transplantation into F1 recipients was shown to be dependent on specific host conditions including an intact thymus and an Fv-1nn allele. In contrast, PLC from 7-9-month-old AKR mice or frank leukemic cells when transplanted grew in any intact or thymectomized histocompatible host, thereby indicating their autonomous growth state. Infection of 2-week-old AKR mice with the dual-tropic virus DTV-70 induced characteristic changes in the thymus and accelerated leukemia development. DTV-70 inoculation into 14-day-old AKR mice did not change the spontaneous PLC distribution pattern in the tested host organs within 30 days postinfection, nor did it change PLC-specific host requirements for further progression into leukemic cells; however, it enhanced PLC transition to autonomous leukemic cells. The preferential cell tropism of DTV-70 for target cells (prothymocytes) among bone marrow and young spleen cells rather than for thymocytes was also demonstrated in an in vitro-in vivo test. The dual tropic virus may act as a promoter on preexisting PLC (present mostly among bone marrow cells) by enhancing their ability to progress into autonomous leukemic cells.

Animals↗

Enhanced AKR leukemogenesis by the dual tropic viruses. II. Effect on cell-mediated immune responses.

We examined the relationship of the leukemia-accelerating properties of a dual-tropic virus (DTV-70) (when injected into the thymus of 14-day-old AKR mice) to its ability to impair T cell functions. Splenic lymphocytes from virus-infected AKR mice were found to have reduced T cell mitogenic responses; moreover, these cells suppressed phytohemagglutinin stimulation of cells from normal, uninfected AKR mice. The response to the B cell mitogen lipopolysaccharide was slightly enhanced at 15 days following DTV-70 infection and was unaffected at later ages. AKR mice infected with DTV-70 showed reduced ability to develop delayed-type hypersensitivity reaction and interleukin 2 production. In contrast, spleen cells from the virus-infected mice responded normally to allogeneic stimulation in mixed lymphocyte culture and mounted an almost normal graft versus host reaction. The data suggest that DTV-70 impairs certain T cell functions that could interfere with immune surveillance and thus permit progression of preleukemic cells into overt leukemia. These T cell functions are suppressed normally by 6 months of age, perhaps by spontaneously arising DTV.

Age Factors↗

Characterization of the AIDS-associated retrovirus reverse transcriptase and optimal conditions for its detection in virions.

The RNA-dependent DNA polymerase of the AIDS-associated retrovirus (ARV) gives highest activity with the synthetic template, poly(rA)oligo(dT) and prefers Mg2+ over Mn2+ as a divalent cation. It can use other template-primer combinations but with poly(rCm)oligo(dG), it prefers Mn2+ over Mg2+. Detection of ARV reverse transcriptase in culture fluids is substantially increased with an optimal KCl concentration and a special combination of EGTA and reducing agents. Our results indicate some distinguishing characteristics of the ARV reverse transcriptase and optimal conditions for its detection.

Cell Line↗

Computed tomography in stage III neuroblastoma.

This multicenter study was designed to determine if CT can assess operability in stage III neuroblastoma. Nineteen children (11 boys, eight girls), aged 2-51 months, considered to have, by conventional clinical and radiographic examinations, localized neuroblastoma that crossed the midline were examined by CT. After intravenous and oral contrast media enhancements, CT was able to show the relation of the tumor to the adjacent vital vessels: aorta, celiac axis, and superior mesenteric artery. In all 15 patients, tumors that encased the aorta or its major branches were unresectable. However, three of four tumors crossing the midline but not coming into contact with the aorta or adherent only to one side of the vessel could be resected. Because surgery currently plays the major role in the treatment of neuroblastoma, the relation of the tumor to the aorta and great vessels is a more reliable and important factor in predicting the outcome of these children than the extension and location of the tumor with reference to the midline. CT after intravenous contrast enhancement can establish this relation and assess resectability.

Abdominal Neoplasms↗

Isolation of lymphocytopathic retroviruses from San Francisco patients with AIDS.

Infectious retroviruses have been detected in 22 of 45 randomly selected patients with acquired immune deficiency syndrome (AIDS) and in other individuals from San Francisco. The AIDS-associated retroviruses (ARV) studied in detail had a type D morphology, Mg2+-dependent reverse transcriptase, and cytopathic effects on lymphocytes. The viruses can be propagated in an established adult human T cell line, HUT-78. They cross-react with antiserum to the lymphadenopathy-associated retrovirus isolated from AIDS patients in France. Antibodies to ARV were found in all 86 AIDS patients and in a high percentage of 88 other homosexual men in San Francisco. This observation indicates the widespread presence of these lymphocytopathic retroviruses and their close association with AIDS.

Acquired Immunodeficiency Syndrome↗

Murine xenotropic type C viruses. V. Biologic and structural differences among three cloned retroviruses isolated from kidney cells from one NZB mouse.

Three xenotropic retroviruses have been biologically cloned from cells cultured from the kidney of a 3-month-old NZB female mouse. They were obtained by first cocultivating the kidney cells for several weeks with mink, dog, and human cells and then cloning them by endpoint dilution. The cloned viruses differ in their infectivity and replicative ability in a variety of heterologous cell lines. The mink cell line-derived virus (X-NZB/K-Mlc) reaches titers in culture of over 10(8) infectious viruses/ml, and is produced in high titer within 24 hr after infection of mink lung cells. The human and dog cell-derived NZB viruses (X-NZB/K-Huc and X-NZB/K-Dgc) grow to lower titers and are similar in many respects. They differ in their relative ability to replicate in dog and human cells and to transform mink S+L- cells. Peptide mapping studies indicate that the X-NZB/K-Mlc virus has a unique p15(E) protein which distinguishes it from the other two cloned NZB viruses. These results lend further support to the observation that several types of xenotropic virus are present in a mouse strain and that more than one virus can be expressed by one organ of a particular mouse.

Animals↗

Problems in the clinical and roentgenographic diagnosis of pneumonia in young children.

The difficulty of diagnosing pneumonia by chest x-ray in children less than 4 years of age was studied by comparing the chest roentgenograms of 34 healthy children with the chest roentgenograms of 34 children previously diagnosed as having pneumonia. Review of these films without knowledge of the previous interpretation and without clinical information disclosed variations regarding the roentgenographic confirmation of pneumonia in 24 percent of the cases and variations regarding the location of the lesion in about 50 percent of the cases.

Child, Preschool↗