American Society for Blood and Marrow Transplantation guidelines for training.
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Bone Marrow Transplantation↗
Biomedical subjects
J Wolf
Publications and source records attributed to J Wolf.
Successful treatment of disseminated human Hodgkin's disease in SCID mice with deglycosylated ricin A-chain immunotoxins.
To evaluate the effects of deglycosylated ricin A-chain (dgA) immunotoxins against disseminated Hodgkin's lymphoma, we used RFT5.dgA (CD25) and IRac.dgA (70 kD) to treat L540Cy Hodgkin cells in severely immunodeficient SCID mice. In this model, more than 90% of the animals developed multiple lymphomas in various organs such as the lymph nodes, liver, bone marrow, and extranodal sites that killed untreated animals after a mean survival time (MST) of 36.3 days. A single intraperitoneal injection of 8 micrograms of either immunotoxin rendered 95% (RFT5.dgA) and 93% (IRac.dgA), respectively, of mice tumor-free when applied 1 day after tumor challenge. The MST of the RFT5.dgA-treated group was extended by more than 80 days (P < .00001). SCID mice treated 12 days after tumor challenge had lower remission rates (46%), suggesting that the antitumor effect of the immunotoxins depends on the number of tumor cells present. We conclude that ricin A-chain immunotoxins have potent antitumor effects against disseminated Hodgkin's tumors in SCID mice and that this model is ideally suited for the evaluation of different immunotoxin treatment modalities.
Animals↗
Evaluation of a training program for improving adherence-promotion skills of dietetic interns.
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Adult↗
Comparison of cognitive-behavior therapy and desipramine in the treatment of bulimia nervosa.
A comparison of cognitive-behavior therapy alone, desipramine alone, and cognitive-behavior therapy combined with desipramine was made in the treatment of bulimia nervosa. The study was terminated early with an N of only 7 subjects per condition because of a high drop-out rate and lack of positive response in the desipramine alone group compared to the other two groups. By this time it was also apparent that at posttreatment and at 6 months follow-up no benefit was being realized from combining cognitive-behavior therapy with desipramine.
Adolescent↗
Human milk secretory IgA antibody to nontypeable Haemophilus influenzae: possible protective effects against nasopharyngeal colonization.
Sixty-eight children fed human milk were followed prospectively from birth to 12 months of age to assess the effect of milk antibody on nasopharyngeal colonization. Human milk secretory IgA antibody to P6, a highly conserved outer membrane protein of nontypeable Haemophilus influenzae, was measured with the use of an enzyme-linked immunosorbent assay. Nasopharyngeal colonization with nontypeable H. influenzae and the occurrence of otitis media were determined. Nasopharyngeal colonization was found in 22 children (32%), and 39 children (57%) had otitis media. Frequency of isolation of nontypeable H. influenzae was directly related to episodes of otitis media (r = 0.35; p = 0.001). The level of human milk anti-P6 secretory IgA antibody was inversely related to frequency of isolation of the organism (r = -0.27; p = 0.026). The average antibody level, expressed as nanograms per 0.1 mg total secretory IgA, in human milk fed to children with no colonization of nontypeable H. influenzae was significantly higher than in milk fed to children in whom colonization occurred on multiple occasions (156 +/- 120 vs 69 +/- 50; p = 0.013). Prevention of colonization was most evident during breast-feeding. These data suggest that the protective effects of human milk against otitis media may be due in part to inhibition of nasopharyngeal colonization with nontypeable H. influenzae by specific secretory IgA antibody.
Acute Disease↗
Crossbreeding effects for body weight and carcase traits in Pekin duck.
1. Three sire lines of Pekin duck, three dam lines and 9 crosses between these two groups were tested in replicated tests from 1987 to 1991. Body weight at the age of 7 weeks (n = 5189), carcase percentage, percentage of abdominal fat and thickness of breast muscles were recorded (n = 1432 for carcase traits). 2. The data were analysed by linear models. All models contained the factors test and sex. When analysing only crosses, general and specific combining abilities (GCA and SCA respectively) were included as well as their interactions with the test. Using the complete data set (lines and crosses), direct genetic and heterotic effects were considered. 3. The factors test and sex were significant in both data sets for all traits. 4. For body weight, all genetic factors were significant. The average heterosis was 65 g +/- 9 g (2.2%); the highest observed heterosis was 7.7%. 5. For carcase percentage, the heterosis was always negative (up to -2.1%), whereas in abdominal fat, a desirable negative heterosis was observed only in one cross. No significant heterotic or combining ability effects were observed in the thickness of breast muscles. 6. Significant interactions between at least one genetic factor and test were found in all traits. 7. The relative importance of GCA and SCA, possible sources of confounding estimates of genetic effects, the importance of heterotic effects and genotype x environment interactions are discussed.
Animals↗
Is Hodgkin's disease an infectious disease?
Several lines of evidence question the concept of Hodgkin's disease (HD) starting as a true malignant disorder of the lymphatic system: (i) In early stages HD exerts pronounced clinical and biological features of an atypic immune response. (ii) Despite extensive investigations, the Hodgkin/Reed-Sternberg (H/RS) cells have not been unequivocally determined as the definite malignant cell population in HD. (iii) The epidemiological pattern of HD strongly resembles that of an infectious disease. (iv) About 50% of HD cases can be linked to infection with Epstein-Barr virus. Hodgkin's disease in early stages might thus be understood as the unsuccessful attempt of the organism to eliminate a cell expressing a putative (cellular or viral) target antigen. A stepwise transformation of this antigen-carrying cell, possibly triggered by an inherent genetic instability, might then lead to outgrowth of a malignant cell clone in late stages of the disease.
Antibody Formation↗
Nasopharyngeal colonization with nontypeable Haemophilus influenzae and recurrent otitis media. Tonawanda/Williamsville Pediatrics.
The relationship between nasopharyngeal colonization with nontypeable H. influenzae and recurrent otitis media was assessed in 157 children followed prospectively from birth through 12 months of age. Forty-nine (31%) became colonized. Nasopharyngeal secretory IgA (sIgA) reactive with the P6 outer membrane protein was detected in all colonized children. Reduction or elimination of the organism was associated with a better mucosal immune response (560 +/- 864 units/ng/mL of sIgA) than was persistence in the nasopharynx (121 +/- 81; P = .04). Forty colonized children (82%) and 61 noncolonized children (56%) developed otitis media (P = .004); colonized children were four times more likely to be classified as otitis prone (P = .003). The frequency of otitis media episodes was directly related to the frequency of colonization (r = .42, P < .01). These results demonstrate a strong relationship between nasopharyngeal colonization patterns and otitis media. The mucosal immune response may be important in elimination of potential pathogens from the respiratory tract.
Age Factors↗
CD30: cytokine-receptor, differentiation marker or a target molecule for specific immune response?
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Antibody Formation↗
Antimicrobial susceptibility of nasopharyngeal isolates of potential pathogens recovered from infants before antibiotic therapy: implications for the management of otitis media.
Antimicrobial susceptibility was determined for strains of Streptococcus pneumoniae, nontypable Haemophilus influenzae and Moraxella catarrhalis recovered from the nasopharynxes of children followed from birth. The bacteria tested were the first potential pathogens isolated from each child before any treatment with antibiotics. Minimal inhibitory concentrations of commonly used oral antibiotics demonstrated the following overall rates of resistance for (1) S. pneumoniae: penicillin 1.2% (intermediate susceptibility 4.8%), trimethoprim-sulfamethoxazole 20%; (2) nontypable H. influenzae: ampicillin 32%, cefaclor 17%; (3) M. catarrhalis: ampicillin 90%, trimethoprim-sulfamethoxazole 19%. Antibiotic regimens used for treatment of otitis media may have to be evaluated in light of changing antibiotic susceptibilities.
Anti-Bacterial Agents↗
Radiographic findings in the jaws of clinically edentulous old people living at home in Helsinki, Finland.
In the present survey the radiographic findings in the jaws of 124 clinically edentulous old people living at home in Helsinki, Finland, were studied, using panoramic radiography supplemented by intraoral radiographs. Only 9% of the subjects had root remains. Impacted teeth were found in 4%, radiolucent lesions in 3%, and radiopaque findings in 13%. Deviations from normal condylar structure were found in 17% and mucosal thickenings in the maxillary sinuses in 7%. The mental foramen was situated at the top of the residual ridge in 42% of the subjects. Topically situated mental foramen and condylar changes were commoner in women. The radiographic oral health status of the population studied was good.
Aged↗
Dental radiographic findings in the elderly in Helsinki, Finland.
A total of 169 dentate persons, aged 76, 81, and 86 years, living at home in Helsinki, Finland, were examined by means of panoramic radiography supplemented by intraoral radiographs. The older the age group, the fewer teeth remained. Altogether 75% of the subjects had radiographically detectable caries. A high proportion of the carious teeth (62%) was found in a relatively small number (24%) of subjects. The number of carious teeth and their percentage of the total number of teeth were greater in the older age groups. The proportion of endodontically treated teeth was 19% in the 76-year-olds and 26% in the 86-year-olds. Of the subjects 41% had periapical periodontitis, which was commoner in root-filled teeth (18%) than in other teeth (4%). Caries and periapical radiolucent and radiopaque findings were commoner in men. Vertical bone pockets (3 mm or deeper) were found in 51% and furcation lesions in 28% of the subjects. Compared with earlier Finnish studies, the results indicate an improving oral health status among elderly Finns.
Age Factors↗
Expression of a developmentally regulated epitope on fibronectins from the synovial fluid of patients with rheumatic disease.
OBJECTIVE: To determine if differential glycosylation of fibronectin (Fn) in inflammatory synovial fluid (SF) included expression of an oncofetal epitope (Onf Fn) heretofore detected only on Fn derived from embryonal or neoplastic tissue. METHODS: Fn were purified from plasma, SF and synoviocyte conditioned medium by affinity chromatography and were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting utilizing a monoclonal antibody (FDC-6) specifically recognizing the Onf Fn. RESULTS: The Onf Fn was not expressed on Fn isolated from normal or RA plasma but was strongly expressed on Fn from rheumatoid arthritis (RA) SF and to a lesser extent osteoarthritis SF. Onf Fn was also detected on Fn secreted by cultured RA synoviocytes. CONCLUSION: Fn present in the SF but not plasma of patients with rheumatic disease contains an epitope previously thought to be restricted to Fn produced by embryonal or malignant tissue.
Antibodies, Monoclonal↗
[The Freiburg Group Intervention Program for children of separated and divorced families].
Group sessions for children from separated and divorced families are currently experiencing a boom with those responsible for private and public youth relief organizations. The aim of these sessions is to normalize separation and divorce for children, to encourage solidarity amongst them and to teach them strategies to cope with their situation early on. The authors present a group intervention program which consists of 17 group meetings, 2 evenings with parents and a prediagnostic session. Based on American curricula, it has been specially developed for educational counseling centers. Experiences regarding indication, implementation, choice of material and work with parents are presented and discussed.
Adaptation, Psychological↗
[Possibilities for preoperative determination of transplant quality using an osteoporosis index].
Preprosthetic procedures and reconstructive measurements are typically performed in elder patients. In this age group osteoporotic changes of the skeleton are common. The facial bones are persistently envolved within this process. Preoperative assessment of bone height and width are nowadays routine procedures in preprosthetic surgery, little attention is paid towards the bone quality at the recipient site of dental implants and the donor and recipient sites of bone-grafts. This study is performed to investigate the possibility to evaluate the bone quality prior to preprosthetic and reconstructive operations. The amount of the mineralization of the skeleton was determined in 17 patients which were scheduled for preprosthetic and reconstructive surgery with the help of Dual Energy X-Ray Absorptiometry (DEXA). The amount of mineralization of the skeleton and the osteoporosis-index, which were determined with the help of DPX-scans, are representative also for the facial skeleton. In our preliminary study patients with a low skeletal mineralization have a tendency towards increased complications after preprosthetic and bone-graft surgery. In addition the preoperative assessment of bone quality serves the basis for a accompanying osteoporosis therapy.
Adult↗
A CD16/CD30 bispecific monoclonal antibody induces lysis of Hodgkin's cells by unstimulated natural killer cells in vitro and in vivo.
In order to target NK cells against the Hodgkin's-derived cell line L540, we developed bispecific monoclonal antibodies (Bi-MAbs) by somatic hybridization of the 2 mouse hybridoma cell line HRS-3 and A9 which produce monoclonal antibodies (MAbs) with reactivity against the Hodgkin and Reed-Sternberg cell-associated CD30 antigen and the CD16 antigen (Fc gamma III receptor), respectively. The CD16 MAb-producing cell line A9 was selected as a partner for HRS-3 because of its efficiency in inducing lysis of the A9 hybridoma cells by resting NK cells. The hybrid hybridoma cell line HRS-3/A9 produced the supernatant with the strongest bispecific reactivity and was repeatedly subcloned and used for ascites production. Crude supernatant and purified HRS-3/A9 Bi-MAb triggered specific lysis of the CD30+ Hodgkin's-derived cell line L540, but not of the CD30- cell line HPB-ALL by unstimulated peripheral-blood lymphocytes and NK-cell-enriched populations. Moreover, treatment of SCID mice bearing heterotransplanted human Hodgkin's tumors with HRS-3/A9 and human peripheral blood lymphocytes induced specific complete tumor regression in 10/10 animals. We thus report successful tumor treatment in an in vivo model using NK-cell-associated Bi-MAbs and show that the Bi-MAb HRS-3/A9 is an efficient promoter of the anti-tumor effects of NK cells in vitro and in vivo.
Animals↗
Hodgkin's lymphoma-derived tissue serially transplanted into severe combined immunodeficient mice.
Hodgkin (H) and Reed-Sternberg (RS) cells are considered to be the malignant cell population in Hodgkin's disease (HD). To date, their analysis has been hampered by their scarcity in primary tumors, poor growth in vitro, and lack of an animal model. To establish an in vivo system for the characterization of the malignant cells in HD, tumor biopsy samples from 13 HD patients were transplanted beneath the renal capsule or into the liver of severe combined immunodeficient (SCID) mice. HD-derived tissue from three patients gave rise to human tumors in SCID mice. Three different histologic patterns were observed: (1) lymphoproliferative disease (LPD), (2) anaplastic large cell lymphoma (ALCL), (3) Hodgkin-like lesions (HDLL). Immunohistochemical analysis showed that the tumors consisted of activated B cells (CD30+, CD20+). Epstein-Barr virus (EBV)-encoded transcripts were found in 80% to 100% of the tumor cells, although H and RS cells in the primary tumors of two patients were EBV-. All tumors examined (3 of 3) and the majority (6 of 10) of cell lines recultured in vitro had an abnormal karyotype. Southern blot analysis of the human Ig heavy chain gene showed that monoclonal or oligoclonal tumors of different B-cell origin grew in the SCID mice from the same germ line-configurated primary biopsy specimen. Our data suggest that the human cells in the SCID mice have either been derived from EBV superinfected H and RS cells or from EBV-infected bystander cells. If the latter is true, then these bystander cells must be genetically abnormal. The genetic defect would be either aneuploidy or instable euploidy. In either case, the cells might proliferate into malignant aneuploid HDLL or ALCL under the influence of EBV and the special environment encountered in the SCID mice.
Adult↗
CD30-specific AB1-AB2-AB3 internal image antibody network: potential use as anti-idiotype vaccine against Hodgkin's lymphoma.
The tumor-associated CD30 antigen is presently under study as a target for active specific immunotherapy of Hodgkin's lymphoma with anti-idiotypic antibodies. Internal image antibodies (Ab2 beta) 9G10 and 14G9 against the CD30-specific antibody HRS-4 (Ab1) have been described, which induce a CD30-specific T- and B-cell response in BALB/c mice and New Zealand white rabbits. In extension of this work, murine monoclonal anti-idiotypic Ab2 beta 9G10, mimicking structures of the nominal CD30 antigen, was used to generate monoclonal Ab3 in mice and polyclonal Ab3 in rabbits with specificity for CD30. The Ab2 beta 9G10-specific murine monoclonal Ab3 4A4 bound specifically to the 120-kDa band of CD30 present on Hodgkin cell lines and Hodgkin tumor tissue, and effectively inhibited binding of Ab1 HRS-4 to Ab2 9G10 as well as to CD30+ cells. Monoclonal Ab3 4A4 was cytotoxic for CD30+ cell lines in vitro and effectively prevented the s.c. growth of L540 cell tumors after passive i.v. administration in a SCID mouse tumor model. While this cytotoxic effect of the IgM subclass monoclonal Ab3 4A4 was due to complement activation, the murine monoclonal Ab1 HRS-4 and a polyclonal Ab3 preparation of IgG-subclass from New Zealand white rabbits were cytotoxic by an antibody-dependent cell-mediated mechanism in vitro. In conclusion, Ab2 beta 9G10 is able to induce a CD30-specific cytotoxic IgG and IgM response. Cytotoxicity was shown to be mediated by complement activation and antibody-dependent cell-mediated cytotoxicity in vitro and in vivo and across species barriers. Thus, the CD30-like Ab2 beta 9G10 may hold promise for effective active specific immunotherapy of human Hodgkin's lymphoma.
Animals↗