CONTRIBUTION OF BONE MARROW CELLS AND LACK OF EXPRESSION OF THYMOCYTES IN GENETIC CONTROLS OF IMMUNE RESPONSES FOR TWO IMMUNOPOTENT REGIONS WITHIN POLY-(PHE,GLU)-POLY-PRO--POLY-LYS IN INBRED MOUSE STRAINS

Previous cellular studies on the genetic regulation of immunological responsiveness for two immunopotent regions within the branched chain synthetic polypeptide (Phe, G)-Pro--L demonstrated a direct correlation between the number of detectable immunocompetent splenic precursor cells and the response patterns of SJL, DBA/1, and F1 mice (21). In order to establish the cellular origin(s) of the genetic defect, the present study first demonstrated that thymus and bone marrow cell cooperation was required for (Phe, G)- and Pro--L-specific immune responses. Secondly, limiting dilution experiments, in which several graded and limiting inocula of marrow cells were mixed with a non-limiting number of 108 thymocytes and injected into irradiated, syngeneic recipients, indicated that the low responsiveness of the SJL and DBA/1 strains to the (Phe, G) and Pro--L specificities, respectively, could be attributed to a reduced number of precursor cells found in bone marrow. About five times more marrow precursors were detected in SJL mice for Pro--L than for (Phe, G), whereas about five times as many precursor cells were estimated for (Phe, G) as for Pro--L in the DBA/1 strain. These differences are similar to those obtained using spleen cells from unimmunized SJL and DBA/1 donors (21), and indicate that these genetically determined variations in responsiveness can be accounted for by differences in the frequencies of monospecific populations of immunocompetent cells present in bone marrow. In contrast, limiting dilution transfers of thymocytes or thymus-derived cells with an excess of syngeneic marrow cells resulted in equally frequent (Phe, G) and Pro--L responses for both SJL ad DBA/1 strains. This finding in conjunction with the observation that the generation of (Phe, G)- and Pro--L-specific responses were associated in individual recipients injected with limiting inocula of thymocytes indicated that a single population of thymocytes was stimulated by (Phe,G)-Pro--L. Therefore, it is improbable that the thymic population of immunocompetent cells contributes to expression of these genetically controlled defects

CELLULAR BASIS OF THE GENETIC CONTROL OF IMMUNE RESPONSES TO SYNTHETIC POLYPEPTIDES : I. DIFFERENCES IN FREQUENCY OF SPLENIC PRECURSOR CELLS SPECIFIC FOR A SYNTHETIC POLYPEPTIDE DERIVED FROM MULTICHAIN POLYPROLINE ([T, G]-PRO--L) IN HIGH AND LOW RESPONDER INBRED MOUSE STRAINS

SJL mice are high responders to the synthetic multichain polypeptide antigen (T,G)-Pro--L, whereas DBA/1 mice are low responders (10, 11). In order to determine whether the genetic control of immune response can be correlated with the number of antigen-sensitive precursor cells, spleen cell suspensions from normal and immunized SJL and DBA/1 donor mice were transplanted into lethally X-irradiated syngeneic recipients (incapable of immune response) along with (T, G)-Pro--L. Anti-(T, G)-Pro--L responses (donor-derived) were assayed in the sera of the hosts 12–16 days later. By transplanting graded and limiting numbers of spleen cells, inocula were found which contained one or a few antigen-sensitive precursors reactive with the immunogen. Using this method to estimate the relative numbers of such cells for the high responder SJL strain, one precursor was detected in ∼1.3 x 106 and ∼7.2 x 106 spleen cells from immunized and normal donors, respectively. In contrast, one precursor was detected in about 30 x 106 spleen cells from low responder DBA/1 mice, irrespective of whether the donors had been immunized. These results indicate that the genetic control of immunity to the synthetic polypeptide antigen investigated is directly correlated to the relative number of precursor cells reactive with the immunogen in high and low responder strains

CONTRIBUTION OF DIFFERENT CELL TYPES TO THE GENETIC CONTROL OF IMMUNE RESPONSES AS A FUNCTION OF THE CHEMICAL NATURE OF THE POLYMERIC SIDE CHAINS (POLY-L-PROLYL AND POLY-DL-ALANYL) OF SYNTHETIC IMMUNOGENS

Genetic regulation of immunological responsiveness was studied at the cellular level by comparing the limiting dilutions of immunocompetent cells from spleen, thymus, and bone marrow of high and low responders as a function of the poly-L-prolyl and poly-DL-alanyl side chains of two synthetic polypeptide immunogens. The spleens of immunized and unimmunized high responder DBA/1 mice were found to contain respectively, 18- and 7-fold more limiting precursor cells specific for (Phe, G)-A--L than the spleens of SJL low responder donors. These results, using a synthetic polypeptide built on multichain poly-DL-alanine, confirm the findings reported for polypeptides built on multichain poly-L-proline (1, 2), that there is a direct correlation between immune response potential and the relative number of immunocompetent precursors stimulated. Cell cooperation between thymocytes and bone marrow cells was demonstrated for both (T, G)-Pro--L and (Phe, G)-A--L. Limiting dilutions of thymus and bone marrow cells in the presence of an excess amount of the complementary cell type indicated an eightfold lower number of detected (T, G)-Pro--L-specific precursors in DBA/1 (low responder) marrow when compared with SJL (high responder) marrow. No differences were observed in the frequency of relevant high and low responder thymocytes for the (T, G)-Pro--L immunogen. These results are similar to those reported for the (Phe, G)-Pro--L (3). In contrast to the cellular studies reported for the Pro--L series of immunogens, the marrow and thymus cell dilution experiments for (Phe, G)-A--L revealed genetically associated differences in both the marrow and thymus populations of immunocytes from high (DBA/1) and low (SJL) responders. In addition to a fivefold difference in limiting marrow cell precursors (similar to that seen in the Pro--L studies), a striking difference was observed between the helper cell activity of high responder DBA/1 and low responder SJL thymocytes. This difference was indicated by the observation that low responder thymocyte dilutions followed the predictions of the Poisson model, whereas dilutions of high responder thymocytes did not conform to Poisson statistics. Transfers of allogeneic thymus and marrow cell mixtures from DBA/1 and SJL donors confirmed the syngeneic dilution studies showing that the genetic defect of immune responsiveness to (Phe, G)-A--L is expressed at both the thymus and marrow immunocompetent cell level. The parameters presently known for genetic control of immune responses specific for (Phe, G) (Ir-1 gene) and for Pro--L (Ir-3 gene) have been compared. The Ir-1 and Ir-3 genes are not only distinct by genetic linkage tests (to H-2) (5, 6, 9), but they are also seen to be different by cellular studies. Furthermore, expression of low responsiveness within a given cell population was shown to depend on the chemical structure of the whole immunogenic macromolecule

THE ROLE OF THYMOCYTES AND BONE MARROW CELLS IN DEFINING THE RESPONSE TO THE DINITROPHENYL HAPTEN ATTACHED TO POSITIVELY AND NEGATIVELY CHARGED SYNTHETIC POLYPEPTIDE CARRIERS : CELL FRACTIONATION OVER CHARGED COLUMNS

An inverse relationship exists between the net electrical charge of immunogens and the antibodies they elicit (1). Results of an earlier study have demonstrated that the net charge phenomenon has a cellular basis, since the immune response potential of murine spleen cells to 2,4-dinitrophenyl (DNP) on a negatively charged synthetic polypeptide carrier was reduced by cell fractionation over negatively charged glass beads, whereas the response to the same hapten on a positively charged carrier was unaffected (14). To verify that the net charge correlation is expressed at the cellular level, spleen cells were fractionated over positively charged poly-L-lysine-coated glass bead columns, and their immunocompetence to DNP on positively and negatively charged carriers was tested by cell transfers in irradiated recipient mice. In this case, the fractionated cells showed reduced response potential to DNP on the positively charged carrier only. Thus, the cellular basis of the net charge phenomenon has been demonstrated for both positively and negatively charged immunogens (for the same specificity) by cell separation techniques over columns of opposite charge. In order to establish whether the cell population relevant for the charge properties of immunogens was of thymus or marrow origin, thymocytes and bone marrow cells were selectively passed over positively or negatively charged columns and mixed with unfractionated cells of the complementary type. Transfers of the filtered and unfiltered cell mixtures in irradiated recipient mice immunized with DNP on either a positive or a negative synthetic polypeptide carrier indicated that fractionation of thymocytes, but not of marrow cells, correlated with the spleen population. Thus, thymocytes fractionated over negatively charged columns and mixed with unfractionated marrow cells exhibited reduced response to DNP on the negative carrier, but normal responses to DNP on the positive carrier. The opposite result was obtained when thymocytes were passed over positively charged columns. No effect on the anti-DNP response was detected by filtration of bone marrow cells over columns of either charge. These findings indicate that it is possible to distinguish between thymocytes on the basis of their capacity to react with more acidic or more basic surfaces and that a population of thymus-derived cells may recognize immunogens on the basis of their overall electrical charge. No evidence was found by these techniques that marrow-derived cells contribute to the net charge phenomenon

The Use of Alphabet Flash Cards Learning Media in the Process of Learning While Playing at the Community Learning Activity Center in North Sulawesi Province

The development of the out-of-school education sector has a strategic role in improving the quality of human resources. In order to increase motivation and learning achievement of citizens learning to read, learning media is needed in the form of alphabet cards that are used by learning resources to develop learning models while playing for learning citizens. The purpose of this research is to: 1) design alphabet card learning media in the application of the development of the learning process, 2) applying the development of the learning process, and 3) finding the effectiveness of the implementation of the development of the learning process of reading while playing through the learning media of alphabet cards for citizens learning literacy in PKBM, North Sulawesi Province. This study has used the ”research and development” method, following the stages of ADDIE model development research (analyze, design, develop, implement, and evaluate) in 4 districts: 1) South Bolaang Mongondow, 2) East Bolaang Mongondow, 3) Talaud Islands, and 4) North Minahasa. This research is designed for 2 years and the first year, 2022, has been carried out in 3 stages, namely: 1) analyze stage, 2) design stage, and 3) development stage. Meanwhile, for the second year, there will be 2 stages, the implementation stage and the evaluation stage. It was concluded that: 1) prototype product design of Alphabet Card Learning Media can be understood and mastered by learning citizens; 2) the application of the development of the learning process is carried out through stages: (1) Recruitment of tutors, learning residents, and forming study groups; (2) Conducting training of trainers (TOT) for tutors; and (3) trials development; 3. The learning process is effective because: (1) The learning residents who were formerly literate but forgot their letters have re-learned them. (2) An improvement in the cognitive abilities of learning citizens; (3) A better ability to put letters together to form meaningful words; (4). Citizens who are learning become more involved. It is suggested that: 1) The teacher must develop an adaptable lesson plan; 2) The following aspects require revision: (1) the physical card alphabet’s size in both height and width; (2). For the sake of IPR and patent rights, a unique logo is required. 3). At the implementation and evaluation stage, this study must be continued. Keywords: learning to read, while playing, alphabet card

Legal Certainty in the Pawn Guarantee System in Indonesia in Anticipation of Opportunities and Challenges of Global Economic Competition

The Credit system with guarantee pledge long has its roots in public life in Indonesia based on settings in the KUH Perdata article 1150. Advantages of the credit system with the pawn lies in a simple procedure and based on the principle of inbezet stelling who controlled goods are considered as owner. In the development system pawn shops especially with modern business, trends start in doubt because of suspicions about pawn shops as holding “barang tada” (stolen). This weakness appears due to legal certainty in the pawn guarantee system in Indonesia is related to the responsibility of PT Pegadaian Indonesia, against the pawn shops and the dispute resolution system. It became the focused of the problem in this research by using the methods of normative legal research found that interest in system pawn shops quite high in Indonesia. The fundamental weakness of the system has not been applied to pawn shops customer recognition system it must be addressed in improving public confidence towards the pawn shops to be able to compete with other financial institutions in globalization. Keywords: pawn, guarantee, legal certaint

Inguinal hernia – epidemiology, risk factors, treatment methods (literature review)

Inguinal hernias (IH) are widespread in the human population and occur in 27–43 % of men and 3–6 % of women. Many risk factors for IH have been overestimated in the last decade: male gender is considered the leading factor (the ratio between men and women is approximately 1:7), less significant factors are heredity (most significant for women), physical activity (more significant for men), age (peak prevalence of IH occurs at 5 years and 70–80 years), congenital or acquired connective tissue dysplasia, history of prostatectomy, low body mass index.Hernioplasty with the use of synthetic mesh prostheses remains the most popular technique for surgical correction of IH. Performing non-prosthetic hernioplasty is only recommended if mesh prostheses are not available, for example in poor countries. In open hernioplasty using mesh prostheses, different methods are used today: Plug & Patch, Prolene Hernia System, Parietene Progrip, sutureless plastic according to Trabucco, Stoppa, preperitoneal techniques TIPP (trans-inguinal pre-peritoneal), TREPP (transrectus pre-peritoneal), TEP (total extraperitoneal), however, none of them showed significant advantages over the gold standard of open hernioplasty – tensionfree repair according to Liechtenstein.Laparoscopic IH correction is represented by the TAPP (transabdominal preperitoneal) technique, performed through the abdominal cavity, and TEP (total extraperitoneal) – extraperitoneal prosthetic hernioplasty. None of them has a significant advantage in the treatment of IH; therefore, when choosing a treatment method, the surgeon should be guided by the cost of the operation and the level of proficiency in one or another hernioplasty technique

Allogeneic Whole Pancreas Transplantation in Insulin-Dependent Diabetes Mellitus

A clinical whole organ pancreas transplantation program for patients with insulin-dependent diabetes mellitus complicated by end-stage renal disease was initiated at Henry Ford Hospital in 1987. Five patients have received pancreatic allografts after a previous kidney transplant (phase 1), and six patients had simultaneous pancreas-kidney transplants (phase 2). Ten patients had functioning pancreatic grafts after surgery, and all of them had normal carbohydrate tolerance with appropriate plasma free insulin responses to an oral glucose tolerance test three months after transplantation. As long as 28 months postsurgery six patients remained free of insulin requirements; however, one patient rejected the pancreatic allograft, and three patients died because of cytomegalovirus pneumonia. Two of the latter patients had functioning pancreatic allografts at the time of their demise. These results compare favorably with those of the International Pancreas Transplant Registry which reflects the world experience. Pancreas transplantation is a unique experimental treatment with the potential of restoring euglycemia and improving the prognosis of insulin-dependent diabetic patients