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Biomedical subjects

R Freund

Publications and source records attributed to R Freund.

At least 55 records · Page 3Linked to original sources
PubMed1991

A single-amino-acid substitution in polyomavirus VP1 correlates with plaque size and hemagglutination behavior.

The plaque size and hemagglutination characteristics of five cloned wild-type strains of polyomavirus were determined. The strains fell into two groups, those with large or small plaques, each with distinctive hemagglutination behavior at different temperatures and pHs. The nucleotide sequence of VP1, the major capsid protein of the virus, was determined for each of the viral strains. The PTA (large-plaque) and RA (small-plaque) strains differed only at residue 92 of VP1, where there is a glutamic acid or glycine, respectively (R. Freund, A. Calderone, C. J. Dawe, and T. L. Benjamin, J. Virol. 65:335-341, 1991). The same amino acid difference in VP1 correlated with plaque size and hemagglutination properties of the other sequenced viruses. Mutagenesis converting amino acid 92 from glutamic acid to glycine converted the plaque size and hemagglutination behavior of the large-plaque PTA strain to that of a small-plaque strain. Furthermore, PTA and RA VP1 proteins produced in Escherichia coli behaved as their parental viruses did in hemagglutination assays. These results demonstrate that amino acid residue 92 of VP1 is involved in determining the plaque size and hemagglutination behavior of polyomavirus and strongly suggest that this region of the VP1 polypeptide interacts directly with cell receptors.

Amino Acid Sequence↗
PubMed1990

T-cell lymphomas emerging as epineoplasms in mice bearing transplanted polyoma virus-induced salivary gland tumors.

A subset of salivary epithelial tumors induced by mouse polyoma virus (PyV) has been designated lymphoepithelioma on the basis of a prominent lymphocytic component. Serial transplantation of this variant has previously been observed to result in lymphoma development. A recent repetition of this phenomenon allowed us to characterize the lymphoma cell populations with regard to phenotypic markers and PyV content. Lymphomas emerged in recipients of the third, fifth, sixth, and seventh transplant generations of the lymphoepithelioma. Most lymphomas were widely disseminated in hematopoietic and lymphoreticular tissues, and other sites as well. Flow cytometric analysis of lymphocyte populations from lymphomas in six recipients revealed that, while all lymphomas expressed phenotypic markers of immature cortical thymocytes, i.e., Thy-1, Pgp-1, Jlld, and CD5, they were not uniform with regard to other T-cell markers, notably CD4 and CD8. Varying levels of T-cell receptor markers CD3 and alpha/beta, as well as interleukin 2 receptor, were also noted. DNA blot analysis failed to detect PyV in lymphoma cells at a sensitivity level capable of detecting less than one intact copy per cell. It appears improbable the lymphoma was directly induced by PyV. Hypotheses invoking other mechanisms of lymphoma development are outlined.

Animals↗
PubMed1990

Control of immediate postoperative pain with topical bupivacaine hydrochloride for laparoscopic Falope ring tubal ligation.

Conflicting reports exist in the literature on the effectiveness of topical local anesthetic applied to the serosal surface of the fallopian tubes for the control of immediate postoperative pain after mechanical (band or clip) tubal ligation. Sixty-four patients were studied prospectively during outpatient laparoscopic Falope ring tubal ligation using the modified McGill Present Pain Intensity Scale. Patients randomly assigned to four groups received topical bupivacaine hydrochloride on both fallopian tubes, the right tube only, or the left tube only, or received none (controls). A unique study design was incorporated which allowed the untreated fallopian tube to serve as a within-subject control for each patient receiving unilateral treatment. Statistical analysis confirmed significant benefit when both fallopian tubes were treated as compared with no treatment (P less than .05). There was also consistent evidence of decreased immediate postoperative pain perception on the treated side for patients receiving unilateral treatment. The value of topical bupivacaine was demonstrated by both subjective patient response (McGill Pain Scale) and reduced need for pain medication before outpatient discharge. Our data support the value of topical bupivacaine applied to the serosal surface of the fallopian tubes for the reduction of postoperative pain after outpatient laparoscopic mechanical (band or clip) tubal ligation.

Adult↗
PubMed1990

[Effects of health reform law on the handicapped from the viewpoint of social assistance].

In the legislator's intention, the recent health reform legislation is aimed at strengthening solidarity and self-responsibility, so that our statutory insurance-based health care system may continue to be efficient and financially viable. The essential steering mechanism introduced is a system of fixed amount benefits in the various benefit areas, among them medicaments, technical aids such as wheelchairs, hearing aids, glasses, and various orthopaedic aids. Only part of the guidelines, tables and regulations needed for implementation have however been made available so far. It is therefore impossible as yet to undertake appropriate, objective evaluation of the advantages and disadvantages of the reform for patients and health funds. It may however already be said that, in respect of dentures, transport, as well as burial costs, health fund insurants have to raise considerable extra means, partly touching on the financial substance of many insurants. A hardship/overcharge clause is intended to keep the additional burdens socially compatible. This device however is absolutely insufficient in the case of chronically ill and very severely disabled people, paying no regard to the considerable additional expenses these populations have to incur for participating in general community life. The inclusion of benefits for domiciliary nursing and care is viewed as only a first step. The financial resources for protection against the risk of nursing and care dependency, however, should not come from the statutory health insurance scheme, but be based on a common pool of funds to be financed by the various social protection branches.(ABSTRACT TRUNCATED AT 250 WORDS)

Cost Control↗
PubMed1989

Phosphorylation of middle T by pp60c-src: a switch for binding of phosphatidylinositol 3-kinase and optimal tumorigenesis.

Substitution of phenylalanine for tyrosine 315 of the polyoma virus middle T (mT) protein lowers the incidence and limits the spectrum of tumors induced following inoculation of the virus into newborn mice. This substitution removes the major site of phosphorylation by pp60c-src without altering the ability of mT to associate with or to activate pp60c-src. The mutant mT fails to show binding of a phosphatidylinositol 3-kinase (Ptdlns 3-kinase) activity that is normally present in wild-type mT complexes. Furthermore, an anti-peptide antiserum that specifically recognizes mT lacking phosphate at tyrosine 315 precipitates binary (mT-pp60c-src) but not ternary (mT-pp60c-src-Ptdlns 3-kinase) complexes from wild-type infected cell extracts. Reprecipitation with either anti-pp60c-src or anti-mT serum brings down ternary complexes containing mT phosphorylated on tyrosine 315. Phosphorylation of mT by pp60c-src in vivo is therefore a critical event for binding of Ptdlns 3-kinase and for expression of the full tumorigenic potential of the virus.

Amino Acid Sequence↗
PubMed1989

Separation of host range from transformation functions of the hr-t gene of polyomavirus.

hr-t mutants of polyomavirus are defective in virus growth as well as in cell transformation, and have genetic alterations that invariably affect both the middle and small T proteins. We have examined the growth properties of three site-directed mutants that either eliminate or alter the middle T without affecting the small T protein. Mutant 808A encodes large and small T proteins but no middle T; it grew poorly in NIH 3T3 cells. In contrast, mutants 1387T and 1178T which express altered middle T along with normal large and small T proteins grew nearly as well as wild-type virus. Thus, although the altered middle T proteins encoded by 1387T and 1178T are defective for cell transformation, they retained the ability to induce expression of a cellular permissivity factor(s) required for virus production. At the biochemical level, the induction of permissivity by middle T was manifested primarily in terms of phosphorylation of VP1 on threonine and in efficient encapsidation of viral DNA to form infectious virus. The natural role of middle T involves regulation of phosphorylation events, and can be enacted, at least in part, independently of interactions with pp60c-src.

Animals↗
PubMed1988

Duplication of noncoding sequences in polyomavirus specifically augments the development of thymic tumors in mice.

A 40-base-pair duplication of noncoding sequences in polyomavirus specifically augmented the development of thymic epitheliomas following inoculation of virus into newborn mice. Virus strains carrying only one copy of this sequence induced a full spectrum of tumors except for overt thymic tumors. This 40-base-pair repeat, on the early side of the replication origin, constituted a tissue-specific regulatory determinant for tumor induction.

Animals↗
PubMed1988

The middle T proteins of high and low tumor strains of polyomavirus function equivalently in tumor induction.

The PTA strain of polyomavirus induces a variety of epithelial as well as mesenchymal tumors at high frequencies, while the RA strain induces only rare mesenchymal tumors following inoculation into newborn mice. DNA sequence analysis has revealed one amino acid difference between the middle T (mT) proteins encoded by these two virus strains. To test for possible biological differences between the mT proteins we constructed a recombinant virus carrying mT-coding sequences of RA on a PTA background. The tumor profile induced by this recombinant is like that of PTA, demonstrating that the transforming protein of the low tumor strain is competent to induce a high tumor profile. We conclude that a structural determinant(s) outside of mT in the PTA virus strain is important in induction of a broad spectrum of tumors and particularly those of epithelial origin.

Animals↗
PubMed1987

Polyomavirus tumor induction in mice: influences of viral coding and noncoding sequences on tumor profiles.

We determined the DNA sequences of the noncoding regions of two polyomavirus strains that differ profoundly in their abilities to induce tumors in mice. Differences between strains were found, both on the late side of the replication origin in the region containing known enhancer elements and on the early side of the origin, affecting the number and location of large-T-antigen-binding sites. By constructing and analyzing recombinant viruses between these high- and low-tumor strains, we attempted to localize determinants which affect the frequency and histotype of tumors. Seven recombinants were constructed and propagated in vitro, and the tumor profile of each was established by inoculation into newborn C3H mice. Recombinants containing noncoding sequences from the high-tumor strain and coding sequences from the low-tumor strain behaved like the latter, inducing tumors at a low frequency and strictly of mesenchymal origin. Reciprocal recombinants with noncoding sequences of the low-tumor strain linked to structural determinants from the high-tumor strain induced several types of epithelial tumors typical of the high-tumor strain but at reduced frequency, in addition to mesenchymal tumors. A high frequency and full diversity of epithelial tumors required, in addition to structural regions from the high-tumor strain, noncoding sequences on the early side of the origin also present in this strain. A high-tumor profile thus resulted from the combined effects of structural and regulatory determinants in the high-tumor strain, with the former affecting primarily the tissue tropism and the latter affecting the frequency of tumors. No differential effects of the enhancer regions from the late side of the origin in the two virus strains were seen in this study.

Animals↗
PubMed1987

Variations in polyoma virus genotype in relation to tumor induction in mice. Characterization of wild type strains with widely differing tumor profiles.

The authors have explored the effects of variations in mouse polyoma virus genotype on patterns of tumor formation in the mouse. Four "wild type" virus strains were surveyed. Two were highly oncogenic, inducing multiple tumors of epithelial and mesenchymal origin, at high frequency and with short latency. The other two strains were weakly oncogenic, inducing fewer tumors, solely of mesenchymal origin, and after a long latency. These sharply contrasting tumor profiles were reproduced with virus stocks derived from molecularly cloned viral genomes. Though vastly different in their oncogenic properties, these cloned viruses proved equally effective in transforming established rat fibroblasts in culture and showed the same patterns of tumor antigen expression in cultured mouse cells. Complexes of polyoma middle T antigen and pp60c-src were demonstrated in extracts of epithelial tumors induced by a highly oncogenic virus strain. It is concluded that polyoma viral genetic determinants for tumor induction in the mouse are more complex than those previously defined by the use of cell transformation systems.

Animals↗
PubMed1987

Necrotizing arterial lesions in mice-bearing tumors induced by polyoma virus.

In the course of determining tumor profiles for wild-type and recombinant mouse polyoma viruses (MPyV's), we fortuitously discovered two types of necrotizing arterial disease in polyoma tumor-bearing C3H/BiDa mice. One type, designated BLAND, consisted of foci of necrosis unaccompanied by inflammatory reaction, in the muscular coat of aorta, pulmonary arterial trunk, and primary or occasionally secondary branches of these vessels. BLAND lesions contained MPyV capsid antigen VP1 as shown by immunocytochemistry, and appeared to be the result of viral cytolytic infection within artery walls. Lesions of the second type are designated PANoid in view of their resemblance to polyarteritis nodosa in humans. PANoid lesions had much the same distribution in the arterial tree as BLAND lesions and were also focal, but had the histologic properties of highly destructive acute inflammatory reactions. Specifically, there were dense infiltrations of polymorphonuclear leukocytes in any and often all coats of the arterial wall, acute fibrinoid necrosis, endothelial proliferations, intravascular thrombosis, and in one example, rupture of the intimal and medial coats with microaneurysm formation. In the acute phase, PANoid lesions exhibited attenuation, fragmentation, and loss of elastic laminae, and in the healing phase, intimal and medial fibrosis with varying degrees of lumenal occlusion. PANoid lesions gave negative immunocytochemical reactions for MPyV capsid antigen VP1, indicating either that the antigen was not present, or that it was masked in complexes with antibody and C3. BLAND lesions were found in 51% of 459 MPyV-infected mice, while PANoid lesions were found in 11%. There was no sex predilection for either type lesion, and practically all mice with lesions fell within ages 60-200 days. We suspect the PANoid lesions are examples of immune-complex arteritis related to persistent MPyV infection, but support for this hypothesis is presently tenuous, resting entirely on the coexistence of BLAND and PANoid lesions in MPyV-infected mice and the histological resemblance of PANoid lesions to naturally occurring and experimentally induced immune complex arteritis.

Animals↗
PubMed1986

[Blood pressure-dependent, process-controlled hemostasis to minimize tourniquet syndrome].

The usual limitation of the pneumatic blood arrest period to 1.5 hours is a protective measure in order to prevent permanent injuries due to tissular hypoxia and local pressure. The generally applied cuff pressure of 300 mm Hg for the upper and 500 mm Hg for the lower extremity is an arbitrary value which has been obtained by empiric research and is completely lacking in scientific foundation. The risk of damaging tissues lying under the cuff which are sensitive to pressure would be considerably reduced by decreasing this pressure to a value just beyond the systolic blood pressure. The differences between systolic pressure and cuff pressure leading to a safe blood arrest in the extremity operated upon have been determined in narcotized patients. It was shown that the cuff pressure only has to be a little higher than the systolic blood pressure in order to produce a constant blood arrest. This difference, however, is also dependent on the circumference of the extremity as well as on the age and sex of the patient and the tissue turgor. It was therefore necessary to construct a unit providing a permanent pressure control in the pneumatic blood arrest cuff depending on the variations of blood pressure during surgical intervention. This was obtained by the use of rapidly working minicomputers and new monitoring devices.

Arm↗
PubMed1984

Long terminal repeat nucleotide sequence and specific insertion of the gypsy transposon.

We have determined the nucleotide sequences of the long terminal repeats of the transposable element gypsy from the cloned mutant alleles sc1, bx3, and bx34e. These mutations are suppressible by the suppressor of Hairy-wing, su(Hw). The long terminal repeats are 482 base pairs long and are highly conserved. In each case, gypsy is inserted into the sequence T-A-C-A-T-A and generates a duplication of the sequence T-A-C-A. This was verified by sequencing an empty site in the wild-type bx gene. Consideration of the sequence of the long terminal repeats and their surroundings limits the possible explanations for the mechanism of mutation by these gypsy insertions and for their suppression by su(Hw).

Animals↗
PubMed1983

Progestagenic and antigonadotrophic activities of STS 557.

STS 557 (17 alpha-cyanomethyl-17 beta-hydroxy-estra-4, 9-dien-3-one) was tested for progestagenic activity in rabbits and for ovulation-inhibiting activities in rabbits and rats in comparison with levonorgestrel and, in some cases, with norethisterone acetate or chlormadinone acetate. In the immature rabbit, the endometrium transformation-inducing activity of STS 557 was about 5 times higher than levonorgestrel for both oral and subcutaneous administration. The ovulation-inhibiting effect of STS 557 was 3.5 times higher than that of levonorgestrel in the rabbit after oral administration, and about 7 times higher in the rat. After subcutaneous injection, however, the antiovulatory activity of STS 557 in rats was only about 4% of that of levonorgestrel when the ED 50 were compared.

Administration, Oral↗
PubMed1982

Splenic abscess-clinical symptoms and diagnostic possibilities.

A 71-yr-old female patient was admitted for investigation of a massive leukocytosis and loss of weight. Physical examination revealed a reduction in the respiratory excursion of the left lung, a left pleural friction rub located ventrobasally and tension of the upper abdominal wall. Additional diagnostic procedure excluded extrasplenic disease. Ultrasound-guided puncture demonstrated the presence of pus in the splenic bed, and splenic abscess was diagnosed. Subsequent surgery confirmed this diagnosis. Histological findings revealed extensive splenic infarction. Since bacteriological investigation revealed the identical pathogens in the pus obtained with the puncture needle, in the intraoperative swab and in the midstream urine, the splenic abscess was most likely caused by hematogenous spread of a urinary tract infection into the splenic infarction. The postoperative course was uneventful, and the patient was discharged on the 11th postoperative day, free of symptoms. The clinical picture, radiological diagnosis, origin, therapy and course of splenic abscess are discussed with reference to the literature.

Abscess↗