Biomedical subjects

C Berkowitz

Publications and source records attributed to C Berkowitz.

9 recordsLinked to original sources

PubMed1994

Herpes simplex virus type 1 (HSV-1) UL56 gene is involved in viral intraperitoneal pathogenicity to immunocompetent mice.

A comparison of the pathogenicity in mice of the recombinant herpes simplex virus type 1 (HSV-1) strain HSV-1-M-LacZ, in which the UL56 gene has been deleted, was made with its parental strain F, following infection in different mouse strains. The polymerase chain reaction (PCR) technique was used to study the migration of virus DNA in the mouse model. Tissues from adult mice infected intraperitoneally (IP) with one of three HSV-1 strains (F, HFEM or HSV-1-LacZ) were examined for the presence of viral DNA. DNA of the pathogenic strain F was detected in the adrenal glands, spinal cord, brain, liver and pancreas. DNA of HSV-1-M-LacZ was detected in the same tissues. However, DNA of the apathogenic strain HFEM was detected transiently (on days 2 and 3 p.i., but not days 1, 5 or 7), only in the adrenal glands and no viral DNA was detected in any of the other tissues. HSV-1 pathogenic strains injected intraperitoneally into newborn mice (7 days old) killed most of the mice. In the surviving mice viral DNA of the three virus strains was found in peritoneal exudate cells (PEC), adrenal glands, spinal cord, liver and spleen. It was found that HSV-1-M-LacZ, which lacks the UL56 gene, resembled in pathogenicity to the newborn mice the pathogenic HSV-1 strains F and KOS. The PCR technique was used to trace viral DNA in tissues of the mice which survived HSV-1 infection at 7 weeks of age. Only HSV-1 (KOS) DNA was detected in the pancreas. The brains of these mice did not contain viral DNA. It is suggested that HSV-1 DNA may reside in surviving HSV-1- infected newborn mice in a "latent" state in nonneural tissues.

Adrenal Glands↗

PubMed1994

Evaluating generalist education programs: a conceptual framework. Generalist program evaluation working group.

This paper provides and applies a conceptual framework and a list of guiding principles for evaluation of generalist education programs. Programs are systematic efforts to achieve specified objectives. Evaluations gather data in order to improve or appraise programs and have a continuum of purposes and methods. Descriptive evaluations characterize the structures, processes, and outcomes of programs; research evaluations definitively assess the effectiveness of a program in terms of outcomes. Intermediate outcomes are changes in knowledge, attitudes, and skills of program participants; conclusive outcomes reflect the quality of performance of graduates in actual clinical situations. Outcomes are affected by inputs--the qualities of students entering the program. Guiding principles of program evaluation ensure that data gathered are useful. The authors illustrate the guiding principles with an actual pilot study that determined that expert pediatricians, general internists, and family practitioners could agree on key generalist competencies and that explores evaluation design based on these competencies. Finally, they consider the implications of undertaking generalist education evaluation.

Adult↗

PubMed1993

Effect of herpes simplex virus type-1 UL41 gene on the stability of mRNA from the cellular genes: beta-actin, fibronectin, glucose transporter-1, and docking protein, and on virus intraperitoneal pathogenicity to newborn mice.

Infection with HSV-1 is accompanied by the shut-off of cellular gene expression. The virion-associated function is encoded by the viral gene UL41. An HSV-1 mutant, vhs-1, which has a genomic deletion in the UL41 gene, is incapable of inducing the shut-off of cellular gene expression. The effect of HSV-1 infection on the shut-off of the cellular genes (or mRNA degradation) was studied specifically with the cellular genes for beta-actin, fibronectin, glucose transporter-1, and the docking protein. The level of these specific mRNAs was measured in cells infected with several HSV-1 strains and was compared to that of vhs-1- and mock-infected cells. It was possible to demonstrate a marked reduction in the level of the specific mRNA from these cellular genes in cells infected with several HSV-1 strains but not with the vhs-1 mutant. The pathogenicity of the HSV-1 vhs-1 mutant to newborn mice was studied. It was found that the mutant is less pathogenic to newborn mice than its parental strain HSV-1 KOS.

Actins↗

PubMed1992

Recombinant interleukin-1 alpha, interleukin-2 and M-CSF-1 enhance the survival of newborn C57BL/6 mice inoculated intraperitoneally with a lethal dose of herpes simplex virus-1.

Recombinant Interleukin-1 alpha (IL-1 alpha), Interleukin-2 (IL-2) and recombinant macrophage colony-stimulating factor-1 (M-CSF-1) as well as combinations of IL-2 and M-CSF-1 were studied for their ability to protect seven-day-old C57BL/6 mice against HSV-1 infection. Treatment of the mice with IL-2, M-CSF-1 or combinations of IL-2 and M-CSF-1 significantly increased survival rates. Treatment with IL-1 alpha (10 U and 100 U/mouse) was most effective in protection against HSV-1, resulting in significantly increased survival rates more than four times greater than the survival rate of the infected control group.

Animals↗

PubMed1992

Mutations in the UL53 gene of HSV-1 abolish virus neurovirulence to mice by the intracerebral route of infection.

The cell fusion protein, the product of the UL53 gene, is responsible for intracerebral (IC) pathogenicity of HSV-1. Recombinant HSV-1 R15 is apathogenic to mice by the IC route of inoculation, while intratypic recombinants, in which the UL53 gene in R15 was replaced by an analogous sequence from the pathogenic strain R19, regained IC pathogenicity. The nucleotide sequence of the UL53 gene of HSV-1 strains R15 (apathogenic) and R19 (pathogenic) was determined and compared to that of other pathogenic strains. Four mutations were found which are thought to be responsible for the apathogenic phenotype of HSV-1 strain R15. Northern blot hybridization of RNA extracted from BSC-1 cells infected with several HSV-1 strains indicated that all of the virus strains tested expressed equal amounts of UL53 mRNA in infected cell cultures. Demonstration of the expression of UL53 mRNA in brains of mice infected with HSV-1 strains was made possible by the combined use of a rapid method for mRNA extraction (Oligo dT-linked magnetic beads) and a highly sensitive technique for detection of the existence of the UL53-specific mRNA (cDNA synthesis followed by PCR). It was shown that both pathogenic (KOS and P42) and apathogenic (R15) HSV-1 strains expressed the UL53 gene in brains of IC infected mice.

Amino Acid Sequence↗

PubMed1991

Elimination of UL56 gene by insertion of LacZ cassette between nucleotide position 116030 to 121753 of the herpes simplex virus type 1 genome abrogates intraperitoneal pathogenicity in tree shrews and mice.

In order to investigate whether or not the UL56 gene is involved in those processes determining the viral pathogenicity and latency, a recombinant virus HSV-1-M-LacZ was constructed in which the DNA sequences between nucleotide position (np) 116030 and 121753 were replaced by the E. coli beta-galactosidase (LacZ) gene. This deletion spans from the carboxyterminus of UL55 (np 116030) to the second exon of IE110 (np 121753) eliminating UL56 and the variable region of the BamHI DNA fragment B which were implicated in intraperitoneal pathogenicity and latency. The host range and growth kinetics of the recombinant virus HSV-1 M-LacZ were comparable to the parental strain HSV-1 F. As expected it was found that HSV-1-M-LacZ lost its virulent phenotype and was not able to develop acute infection in animals. The state of the UL56 gene was investigated by determining the cDNA sequence of the UL56 gene transcript of HSV-1 F using PCR products obtained after amplification of the cDNA with oligonucleotide primers corresponding to the translational start and stop codons of this gene. This analysis revealed that the DNA sequence of the UL56 gene of HSV-1 F differed from those DNA sequences determined for the genomic DNA of HSV-1 strain 17. Between nucleotide position 116343 and 116344 two nucleotides -AG- are inserted which prolong the ORF of the UL56 gene to 233 amino acids with a predicted molecular weight of 30 kDa.

Adrenal Glands↗

PubMed1977

Comparative responses to dobutamine and nitroprusside in patients with chronic low output cardiac failure.

The acute hemodynamic effects of dobutamine and nitroprusside were compared in 19 patients with low output cardiac failure. At dosage levels yielding similar increases in cardiac index (12 patients), nitroprusside resulted in significantly lower arterial systolic and wedge pressures and did not increase heart rate suggesting advantages over dobutamine when reduction in myocardial oxygen requirement or pulmonary congestion is a major goal. Systemic arterial mean and diastolic pressures were minimally changed with dobutamine, but fell significantly with nitroprusside suggesting advantages of dobutamine over nitroprusside in patients where hypotension could limit coronary blood flow or perfusion of other vital organs. Reduction in pulmonary arteriolar resistance occurred only with nitroprusside. Arterial hypoxemia developed in three patients during nitroprusside infusion suggesting the possibility of increased right-to-left intrapulmonary shunting resulting from a direct vasodilating effect of nitroprusside on pulmonary arteriole smooth muscle. Although both inotropic and vasodilator drugs can result in hemodynamic improvement when administered to patients with chronic low output cardiac failure, significant differences of potential clinical importance exist between these two modes of therapy.

Adult↗

PubMed1975

Hazards of overconcentrated milk formula. Hyperosmolality, disseminated intravascular coagulation and gangrene.

Severe hypertonic dehydration with hyperglycemia developed in a 7-week-old infant girl after she was fed an overconcentrated milk formula for five days. Renal failure,disseminated intravascular coagulation, gangrene of the legs, and coma were added complications. Intravenous rehydration, peritoneal dialysis, and heparin administration corrected the metabolic and coagulation derangements, and renal function returned to normal. Bilateral below-the-knee amputations were performed and the child subsequently learned to walk with artificial limbs. The dangers of overconcentrated formulas in infant feeding should be widely publicized through warnings printed on all commercial milk preparations.

Age Factors↗

PubMedDate not supplied

Bone marrow-derived dendritic cells and the protection against X-ray-induced thymic leukemia in mice. A new interpretation.

About forty years ago, Henry Kaplan and collaborators reported that four weekly X-ray doses of 160 rads each were highly leukemogenic in C57BL mice. A single dose of 350 Rads had a week leukemogenic effect. These authors also demonstrated that lead shielding of the thigh during irradiation prevented the development of leukemia. They reported that intravenous injection of syngeneic bone marrow cells into irradiated mice facilitated the regeneration of the thymus and prevented the development of X-ray-induced tumors. We characterized the thymic Ia+ dendritic cells (DC) with the aid of a fluorescence-activated cell-sorter (FACS). It was found that exposure of mice to a leukemogenic regimen of fractionated X-irradiation treatment led to a gradual decrease in the number of thymic DC. The disappearance of thymic DC and the development of leukemia were prevented by intravenous injection of syngeneic bone marrow or by lead shielding of the femur during irradiation. These results indicated that the fractionated irradiation caused a decline in the number of DC and, as a result, diminution of the natural defense against the developing tumor. Homing of the injected bone marrow DC into the thymus can be connected to the prevention of tumor development. Since leukemogenic T cells produce interleukin-4(IL-4), we tested the effect of the conditioned medium in which YAB-3 cells (tumorigenic Th cells: CD4+, CD8-, Thy-1+) were cultivated. Following injection of the conditioned medium into the mouse footpads, the number of skin Langerhans cells (LC) decreased.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗