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Biomedical subjects

J Wolf

Publications and source records attributed to J Wolf.

At least 163 records · Page 9Linked to original sources
PubMed1996

Isolation of the human PC6 gene encoding the putative host protease for HIV-1 gp160 processing in CD4+ T lymphocytes.

Production of infectious HIV-1 virions is dependent on the processing of envelope glycoprotein gp160 by a host cell protease. The protease in human CD4+ T lymphocytes has not been unequivocally identified, yet members of the family of mammalian subtilisin-like protein convertases (SPCs), which are soluble or membrane-bound proteases of the secretory pathway, best fulfill the criteria. These proteases are required for proprotein maturation and cleave at paired basic amino acid motifs in numerous cellular and viral glycoprotein precursors, both in vivo and in vitro. To identify the gp160 processing protease, we have used reverse transcription-PCR and Northern blot analyses to ascertain the spectrum of SPC proteases in human CD4+ T cells. We have cloned novel members of the SPC family, known as the human PC6 genes. Two isoforms of the hPC6 protease are expressed in human T cells, hPC6A and the larger hPC6B. The patterns of SPC gene expression in human T cells has been compared with the furin-defective LoVo cell line, both of which are competent in the production of infectious HIV virions. This comparison led to the conclusion that the hPC6 gene products are the most likely candidates for the host cell protease responsible for HIV-1 gp160 processing in human CD4+ T cells.

Amino Acid Sequence↗
PubMed1996

Peripheral blood mononuclear cells of a patient with advanced Hodgkin's lymphoma give rise to permanently growing Hodgkin-Reed Sternberg cells.

A novel Hodgkin's disease (HD) derived cell line, L1236, was established from the peripheral blood of a patient with advanced Hodgkin's disease. Analysis of immunoglobulin (Ig) gene rearrangements revealed a biallelic Ig heavy chain and a monoallelic Ig kappa light chain gene rearrangement, pointing to a B-lymphoid origin of these cells. No DNA of Epstein-Barr virus was detected in L1236. The cells expressed the HD-associated surface antigens CD30 and CD15 as well as the transferrin receptor (CD71). Cytogenetic analysis of early passages of L1236 cells revealed a grossly disordered karyotype including cytogenetic aberrations described previously in other HD-derived cell lines. The Hodgkin/Reed-Sternberg (H-RS) cell origin of L1236 cells is further confirmed by Kanzler et al (Blood 87:3429, 1996), who found identical Ig gene rearrangement sequences in L1236 cells and H-RS cells of the same patient's bone marrow. L1236 cells expressed antigens necessary for efficient antigen presentation to T cells including HLA class I and II, B7.1 and B7.2, as well as adhesion molecules ICAM 1 and LFA 3. The cells secreted the interleukins (IL)-6, -8, -10, tumor necrosis factor (TNF) alpha, interferon (IFN) gamma, transforming growth factor (TGF) beta, and the granulocyte-macrophage colony stimulating factor (GM-CSF). After subcutaneous inoculation into SCID mice, a necrotic regression of initially growing tumors at the injection site was followed by disseminated intralymphatic growth. Our findings, together with the results of Kanzler et al, demonstrate that H-RS cells of B-lymphoid origin were present in the peripheral blood of a patient with advanced HD. These cells exerted a malignant phenotype with regard to their in vitro and in vivo characteristics.

Adult↗
PubMed1996

Molecular single cell analysis demonstrates the derivation of a peripheral blood-derived cell line (L1236) from the Hodgkin/Reed-Sternberg cells of a Hodgkin's lymphoma patient.

A novel cell line, L1236, was established from the peripheral blood of a patient with Hodgkin's disease (HD). Two Ig VH and one Vkappa gene rearrangements were amplified by polymerase chain reaction (PCR) from the DNA of this cell line, demonstrating its derivation from the B-cell lineage. To test the cell line for its clonal relationship to the Hodgkin/Reed-Sternberg (H-RS) cells in the patient, single H-RS cells were micromanipulated from tissue sections of a tumor-infiltrated bone marrow specimen from that patient and analyzed by PCR for Ig gene rearrangements. The same rearrangements detected in the cell line were also found repeatedly in H-RS cells of the biopsy material. Thus, L1236 is the first cell line established from a case of HD for which a derivation from the H-RS cells of the patient could be demonstrated. Furthermore, the selective isolation of identical V gene rearrangements from multiple single H-RS cells demonstrates that these cells represented a clonal population in the patient.

Adult↗
PubMed1996

Seasonal alteration in taste detection and recognition threshold in seasonal affective disorder: the proximate source of carbohydrate craving.

Increased appetite with associated carbohydrate craving are core symptoms of seasonal affective disorder (SAD) and have been attributed to decreased central serotonergic function. The proximate mechanisms for centrally mediated selective macronutrient consumption are unknown. We questioned whether seasonal alterations in taste sensation could serve as a mediator of dietary intake, as implied by the term 'craving'. Specifically, individuals who were seasonally depressed and reported carbohydrate craving would be more sensitive to gustatory cues associated with the presence of carbohydrate than nondepressed subjects. Taste detection and recognition thresholds for the four primary gustatory sensations--sweet, sour, salty, and bitter--were obtained in a group of 25 SAD patients and 23 non-psychiatric subjects during the winter, after 2 weeks of 10 000 lux morning and evening light treatment, and during the summer. Relative to the comparison group, the SAD group was less sensitive to sweet taste during the winter. Sweet taste threshold in the SAD group normalized during the summer; however, 2 weeks of light treatment failed to alter sweet detection thresholds in the SAD group. Moreover, within the SAD group, season exerted significant effects on sweet, sour, and bitter detection, but it did not influence salt-detection thresholds. The findings represent the first demonstration of specific changes in taste perception associated with the self-report of carbohydrate craving in SAD and are discussed in terms of the development of sweet craving and the serotonin hypothesis of SAD.

Adult↗
PubMed1996

Localization of pleiotrophin and its mRNA in subpopulations of neurons and their corresponding axonal tracts suggests important roles in neural-glial interactions during development and in maturity.

Trophic factors are being increasingly recognized as important contributors to growth, differentiation, and maintenance of viability within the mammalian nervous system during development. Pleiotrophin (PTN) is a secreted 18-kDa heparin binding protein that stimulates mitogenesis and angiogenesis and neurite and glial process outgrowth guidance activities in vitro. We localized the sites and time course of expression of the Ptn gene and its protein product in developing and adult mouse nervous system. Expression of the Ptn gene was first observed at embryo day 8.5 (E8.5). At E12.5, transcripts of the Ptn gene were localized in developing neuroepithelium at sites of active cell division in the spinal cord and brain. At E15.5, transcripts were found in the somata of some but not all neurons and glia whereas in the adult its pattern of expression was nearly exclusively restricted to the brain. The PTN protein was found almost entirely in association with the axonal tracts during development and in adults. Furthermore, as opposed to the finding of PTN in both central and peripheral nervous systems during development, PTN was not expressed beyond the exit where axonal tracts become the peripheral nervous system in adults. At all sites and times examined, the somata that contained Ptn transcripts corresponded with the axonal tracts that contained the PTN protein. The results establish that Ptn is expressed in early development at sites of active mitogenesis in developing neuroepithelium and later in both glial cells and neurons at sites of neuronal and glial process formation in developing axonal tracts. The findings establish a correspondence in the localization of PTN within the nervous system at sites of normal developmental processes that correlate with the functional activities of PTN previously described in vitro.

Aging↗
PubMed1996

Growth inhibition of human cervical cancer cells with the recombinant adenovirus p53 in vitro.

Human papillomavirus (HPV) has been identified in the majority of invasive cancers of the uterine cervix sampled and has been found to contribute in a significant way to the genesis of human cervical cancer. HPV has two transforming genes that encode the oncoproteins E6 and E7. E6 can form complexes with p53 and promote p53 degradation. We introduced wild-type p53 into a cervical cancer cell line via a recombinant adenoviral vector, Ad5CMV-p53. Human cervical cancer cell line HeLa, which has HPV type 18 and wild-type p53, was used in this study. Cells were grown in RPMI medium supplemented with 10% heat-inactivated fetal bovine serum. Ad5CMV-p53 was created by inserting the cytomegalovirus promoter, wild-type p53 cDNA, and SV40 polyadenylation signal in a minigene cassette into the E1-deleted region of the modified Ad5 adenovirus. The transduction efficiency was 100% when a dose ensuring a multiplicity of infection of 100 or greater was used. The p53 protein was detected in Ad5CMV-p53-infected cells by immunohistochemical and Western blot analyses. The growth of the Ad5CMV-p53-infected cells was greatly suppressed as detected by both cell count and [3H]thymidine incorporation assay. These data suggest that transfection of HPV-positive cervical cancer cells with a wild-type p53 gene in a form such as Ad5CMV-p53 is a potential novel therapy for cervical cancer.

Adenoviridae↗
PubMed1996

Report on the workshop biology of the Third International Symposium on Hodgkin's Lymphoma in Cologne 1995.

Micromanipulation of single Hodgkin-Reed/Sternberg cells and subsequent nucleic acid amplification (H-RS single cell PCR) has now been established as a new and powerful method for specific genetic analysis of the tumor cells in Hodgkin's disease (HD). Although there are still some discrepancies in the results presented by different groups, most probably due to methodological problems, H-RS cells, at least in a substantial proportion of cases, seem to be B-lymphoid cells of monoclonal origin. In addition, new data were presented on the cytokine/cytokine receptor interaction in HD, on transcription factors in HD-derived cell lines and on a promising approach for identification of tumor associated antigens in HD.

Hodgkin Disease↗
PubMed1996

Effect of head positioning in panoramic radiography on vertical measurements: an in vitro study.

OBJECTIVE: To assess whether it is possible to make accurate vertical measurements of the jaws from panoramic radiographs. METHODS: Five dry skulls were shifted 5 mm forwards and backwards and tilted 5 degrees up and down in the sagittal plane. Panoramic radiographs of each skull were obtained in nine different positions. In the maxilla, three reference lines were used and vertical measurements were made at the distal surfaces of the first premolar and first molar and in the midline. In the mandible, measurements were made at the distal surfaces of the first premolar and first molar, and at the mental foramen on both sides, and in the midline. The points and lines were marked manually and the radiographs were digitized, magnified and measured. RESULTS: Sagittal shifting and tilting had only a slight effect on measurements in the mandible. Sagittal tilting of the head had the greatest effect on all the measurements made from the line between the articular eminences to the alveolar crest, as well as measurements in the maxillary midline. CONCLUSIONS: The line between the articular eminences is unsuitable as a reference line for measurements of the tooth-bearing areas. A slight misalignment of the head does not significantly affect the vertical measurements in the mandible or of the posterior maxilla if the reference lines are in the same vertical plane as the teeth.

Analysis of Variance↗
PubMed1996

Dental health in 14- to 17-year-old Estonian schoolchildren in Tartu and Tallinn.

The dental health of 392 Estonian schoolchildren aged 14-17 years (197 in Tartu and 195 in Tallinn) was studied. In Tartu only 1 child had lost teeth because of caries, as against 30 in Tallinn. Clinically caries-free dentitions were found in 15% of the children in Tartu and in 3% in Tallinn. The mean DMFT value was 3.7 in Tartu and 7.0 in Tallinn, being higher among girls in both cities. The mean DT value was 1.0 in Tartu and 2.6 in Tallinn. All subjects examined had a gingival bleeding index (GBI) higher than zero. The mean GBI was 20% in Tartu and 18% in Tallinn.

Adolescent↗
PubMed1996

Height of mandibular basal bone in dentate and edentulous subjects.

Age-related differences in the height of the mandibular basal bone were compared between young and old dentate subjects and between dentate and old edentulous subjects by means of panoramic radiographs. The distances of the mental foramen and mandibular canal from the lower border of the mandible, when measured, showed the mandibular basal bones in old dentate and in old edentulous men to be higher than those of young dentate men in the molar region (P < 0.05). The height of the basal bone below the mental foramen was smaller in old edentulous women than in young and old dentate women (P < 0.05). A slight bone deposition along the lower border of the mandible in the molar region seems to take place with increasing age. The mental foramina of edentulous women move toward the lower border of the mandible as a result of alveolar bone resorption.

Adolescent↗
PubMed1996

[Hodgkin disease--pathogenesis and therapy].

Hodgkin's lymphoma exerts characteristics of a true hematopoietic neoplasia as well as of an atypic immune response. In affected lymphatic tissue a minority of malignant Hodgkin-Reed Sternberg [H-RS] cells is surrounded by a majority of reactive, nonmalignant cells. Clinical features and biological studies suggest a pronounced, but inefficient, T-cell response against a yet undefined [viralS/B] target antigen expressed on H-RS cells. The role of the Epstein-Barr virus [EBV] which can be detected in the H-RS cells in about 50% of cases remains to be defined. By micromanipulation of single H-RS cells from frozen sections and subsequent enzymatic amplification of nucleic acids [single cell PCR] for the first time a monoclonal B-cell origin of H-RS cells could be demonstrated in several cases of Hodgkin's disease. Therapeutic strategies in Hodgkin's disease, in contrast to non-Hodgkin's lymphoma, are not based on the histological subtype, but rather on precise determination of the stage of disease. Treatment of choice in limited disease stages without risk factors is radiation therapy. Intermediate stages are treated with combined chemo- and radiation therapy, advanced stages with intensive chemotherapy [subsequent radiation only on bulk tumors]. Thus, about 85% of all patients suffering from Hodgkin's disease, can be cured definitely. High-dose chemotherapy followed by autologous stem cell transplantation in relapsed Hodgkin's lymphoma is currently proofed in clinical studies.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

Amphotericin B lipid complex compared with amphotericin B in the treatment of cryptococcal meningitis in patients with AIDS.

The study objective was to obtain preliminary information regarding the safety and efficacy of amphotericin B (AmB) lipid complex (ABLC) in the treatment of AIDS-associated cryptococcal meningitis. Of 55 patients randomly assigned to 6 weeks of therapy with ABLC (1.2-5.0 mg/[kg.d], with ascending doses for three sequential cohorts) or AmB (0.7-1.2 mg/[kg.d]), 46 received > or = 12 doses. Transfusion requirements, mean decreases in hemoglobin level, and mean increases in creatinine level were significantly greater with AmB than with ABLC. The total number of adverse events, infusion-related events, and occurrences of hypomagnesemia and hypokalemia associated with each form of therapy were similar. Among 21 recipients of ABLC at a dosage of 5 mg/kg (daily for 2 weeks and then thrice weekly for 4 weeks), symptoms and signs resolved for 18 (86%). Of those receiving > or = 12 doses of ABLC, cultures converted to negative for 8 (42%), were undeterminable for 3 (16%), and remained positive for 8 (42%) despite resolution of symptoms. Although preliminary, these data suggest ABLC has significant activity in patients with AIDS-associated cryptococcal meningitis. Because this formulation has less hematologic and renal toxicity than does AmB, further evaluation of ABLC is warranted.

AIDS-Related Opportunistic Infections↗
PubMed1996

Epidemiology of nasopharyngeal colonization with nontypeable Haemophilus influenzae in the first two years of life.

A total of 200 children were followed from birth through 2 years of age with nasopharyngeal (NP) cultures to determine the normal colonization pattern of nontypeable H. influenzae (NTHI) in young children. NP cultures were obtained routinely at 13 scheduled visits. 44% of children became colonized by 2 years; acquisition was greatest in the first year. Colonization with the initial strain, as determined by outer membrane proteins, persisted from 1-5 months, median 2 months. Children carried one predominant strain at a time but became colonized with up to 7 different strains, mean 2.2, over 2 years. Three patterns of colonization were observed: i) rapid elimination of the initial strain, ii) prolonged colonization with the initial strain, and iii) colonization with different strains. Reacquisition of a previously carried strain was rare. Changes in outer membrane protein patterns reflected acquisition of new strains rather than phenotypic changes of old strains. Children colonized with 1 strain for < or = 2 months generated a greater mucosal antibody response, log 2.35, U/ng/ml SIgA, than children colonized with different strains, log 1.89, U/ng/ml SIgA, p <0.01. These data suggest that duration of colonization with one strain and the acquisition of a new strain is regulated by the local specific SIgA.

Bacterial Outer Membrane Proteins↗
PubMed1995

Selective loss of integrated Epstein-Barr virus genomes after long-term cultivation of Burkitt's lymphoma x B-lymphoblastoid cell hybrids due to chromatin instability at the integration site.

Independently established somatic cell hybrid clones between the Burkitt's lymphoma (BL) cell line BL 60 and the autologous Epstein-Barr virus (EBV)-immortalized lymphoblastoid cell line (LCL) IARC 277 were analyzed with regard to physical state of EBV and karyotype changes in long-term culture. Early after fusion these hybrids carry EBV genomes of the parental BL cell line integrated near the breakpoint of a translocation chromosome der(19) t(11;19) as well as episomal viral DNA molecules of the parental LCL. During long-term culture, however, all hybrid cell lines lost the integrated EBV sequences and retained exclusively episomal EBV, whereas in parental BL cells the EBV genomes remained stably integrated. Loss of integrated EBV in all cases resulted from a break proximal to the EBV integration site. Fluorescence in situ hybridization revealed that this integration site had become a gap-like chromatin area. We thus conclude that the integration of the EBV genomes constitutes a chromosomal region prone to break events akin to the phenomenon of fragile sites. This instability might have led directly to the loss of the EBV DNA itself and of the chromosome 11 region distal to it.

B-Lymphocytes↗
PubMed1995

Suppression of Burkitt's lymphoma tumorigenicity in nude mice by co-inoculation of EBV-immortalized lymphoblastoid cells.

EBV-immortalized B-lymphoblastoid cell lines (LCL) inoculated s.c. into T-cell-deficient nude mice regress completely after a short initial growth period. We tested whether the putative host response underlying this phenomenon might also be directed against progressively growing Burkitt's lymphoma (BL) tumors in nude mice. Outgrowth of BL tumors was suppressed when cells of the highly tumorigenic BL cell line BL 60 were mixed with cells of the autologous LCL IARC 277 before s.c. inoculation into nude mice. Even when the cells were inoculated separately and simultaneously into contralateral flanks of the mice, regression of initially growing BL tumors could be observed, albeit with reduced frequency and dependent on the dose of LCL cells. Tumor growth of BL 60 cells could also be suppressed by co-inoculation with the non-autologous LCL IARC 174 and IARC 277 cells could suppress growth of the non-autologous BL cell line Eli. Pronounced infiltration with murine (m)CD-11b-positive mouse macrophages and mCD-8a-positive mouse lymphoid cells, most probably natural killer cells, was seen in histological tissue sections of regressing BL 60 tumors when LCL cells were inoculated contralaterally. In regressing BL tumors, these mouse cells were present not only in necrotic areas but also in vital BL tissue, indicating that infiltration of mouse cells had taken place before the development of necrosis. Since tumor-infiltrating mouse cells can be activated at least by some human cytokines, we measured cytokine production of BL 60 and IARC 277. High amounts of IL 6 and IL 10 were produced by the LCL cells, whereas IL-6 and IL-10 production by the BL 60 cells was beyond or close to the detection threshold. In addition, IL 8 was secreted up to 5-fold more by the LCL than by the BL cells. The results presented here thus suggest a host response of the nude mouse, which is triggered by cytokines released from the LCL but, once induced, is directed also against BL cells.

Animals↗
PubMed1995

The in vivo expression of the FGF receptor FREK mRNA in avian myoblasts suggests a role in muscle growth and differentiation.

Muscle growth during embryogenesis is the result of a balance between the proliferation of myoblasts and their differentiation into mature, contractile fibers. Fibroblast growth factors (FGFs) are potent stimulators of myoblast proliferation and inhibitors of myoblast differentiation in vitro. However, it is not clear at present if FGFs and their receptors regulate this process in vivo, partially because no FGF receptor was known to be expressed by myoblasts during embryogenesis. In this study, we have used quail/chick grafting and BrdU labeling techniques to demonstrate that a recently cloned avian FGF receptor, FREK, is expressed by replicating skeletal muscle myoblasts, while differentiated muscle cells no longer express this receptor. In the limb, muscle progenitors originating from the somite start expressing FREK at 3 days of development (E3). FREK expression in the limb myoblasts follows that of Pax-3 and Pax-7, but precedes that of MyoD. Since MyoD expression signals the onset of terminal differentiation, this demonstrates that FREK is expressed in muscle progenitors prior to overt muscle differentiation. A more complex situation is observed in the trunk region, where a first wave of MyoD-positive myocytes, which are postmitotic and never express FREK, appear in the early myotomal compartment of the somite. Slightly later, at E2.5, FREK-positive myoblasts migrate into the myotome as a second wave of muscle progenitors, 15 hr after the first MyoD-positive cells. FREK's expression by myoblasts arising at all stages of myogenesis indicates that this growth factor receptor represents one of the earliest molecular markers for this cell population. FREK's prominent expression during muscle differentiation sets it apart from other FGF receptors and suggests that this molecule plays an important role during muscle growth and differentiation.

Animals↗