[Cross-infection during scalding and plucking of broiler chickens (author's transl)]. In two poultry-processing plants, experiments were carried out to detect cross-infection during scalding and plucking of broiler chickens. These trials showed that cross-infection was only detectable when experimental infection with the indicator micro-organism Escherichia coli K12 was applied externally to the broiler chickens. When infection was applied internally, only a small degree of transmission was observed. Indicator micro-organisms applied externally to broiler chickens prior to scalding and plucking, were present on the cooled product in larger numbers than those applied internally in the intestines of broilers. The number of carcasses which were positive after cooling was found to have decreased in poultry-processing plant B compared with the situation after plucking, whereas this number was not affected to any appreciable extent in processing plant A.


Behavior of hemopoietic stem cells (CFU-S) of mice acutely poisoned with carbon tetrachloride (CC14). Behavior of Hemopoietic Stem Cells (CFU-S) of Mice Acutely Poisoned with Carbon Tetrachloride (CCL4). Tohoku J. exp. Med., 1977, 121 (4), 401-402--The femoral CFU-S of mice were reduced when CCL4 was administered in doses which produced toxic hepatitis, but it was not statistically significant.


[A preprosthetic-surgical solution for the extremely atrophic mandible]. Failures of reconstructing alveoloplasty, which are known from the literature and confirmed by the author's personal experience, are attributed to the intolerance of the load-carrying denture support. For this reason, it is suggested to perform an extra-oral intervention on the maximally atrophied mandible to reinforce its crest with autogenous bone. A second intervention is necessary in the form of a combination of floor-of-the-mouth revision and vestibuloplasty (method of Rehrmann), the load-carrying support remaining intact at the level fo the alveolar process.


[Indication and assessment of preprosthetic-surgical technics from the prosthodontist's viewpoint]. The functioning of a complete lower denture is determined by a series of clinico-anatomical characters of the edentulous mandible. These are commented upon to establish the limits of indication of preprosthetical-surgical techniques. The reflections point to the necessity for paying more attention to really reconstructing alveoloplasties.


[Functional disorders following resection of the tongue and mouth floor]. On observing 20 patients who had underwent total tongue and floor-of-the-mouth resection, the authors stated difficulties in swallowing and breathing that in certain cases called for laryngectomy. To counteract these disorders, floor-of-the-mouth and tongue reconstruction was performed with the aid of an arterialized frontal flap, which resulted in essentially undisturbed functions.


Relation of immediate post-transplant renal function to long-term function in cadaver kidney recipients. Renal function studies 12 to 41 months after transplantation have been performed on seven cadaver renal allograft recipients who demonstrated immediate primary function after transplant (group A) and seven similar recipients who had delayed primary function (group B). The groups were matched as closely as possible for major physical characteristics and their postoperative management; in particular, only one patient had a post-transplant renal biopsy. Glomerular filtration rate was determined by 24-hr creatinine clearance, endogenous creatinine clearance, and inulin clearance was usually lower in those patients having delayed primary function and they excreted more glucose per 24 hr and reabsorbed a smaller proportion of the filtered glucose load under infusion conditions. These results are discussed in relation to the effect of immediate and delayed primary function on the long-term prognosis of such patients.


Computations for a best match strategy for kidney transplantation. In some cases success or failure of a proposed innovation in transplantation may be better judged if we consider the average survival time of the graft rather than the actuarial survival at a point in time. It is suggested that HLA matching may be an example of such a case and that the possible clinical benefits of modest improvements in matching may have been underestimated. Calculations are made that show that transplanting to the best match available in a pool of 100 patients might increase the expected graft survival time by more than 1 year.


Renal transplantation and immunological abnormalities in thrombotic microangiopathy of adults: report of 5 cases. Renal transplantation was performed in five adult patients with thrombotic microangiopathy, three of whom had had a bilateral nephrectomy prior to transplantation. The graft remained functional in three patients 72, 18, and 12 months after transplantation. One patient developed a thrombosis of the renal artery and one patient died from infection. There was no clinical or histological evidence of recurrence of thrombotic microangiopathy in the five patients after transplantation. Immunological investigations were performed in four of five patients before transplantation: C3 and C1q levels were low in two patients; serum C3-splitting activity and circulating immune complexes were present in all four patients and remained unchanged on haemodialysis and/or after bilateral nephrectomy. Complement abnormalities and immune complexes were not detected in the three patients with successful renal transplantation.


The cadaver kidney transplantation programme of Milano. Immunological report. A retrospective investigation was carried out to evaluate the infuence of HLA (A, B) matching, blood transfusions, and preexistence of lymphocytotoxic antibodies on the outcome of the cadaver kidney graft: only non-NIH standard antibodies were considered, since patients with NIH standard antibodies do not undergo transplantation in the programme of Milano. It was found that (1) about one-half the patients with transplants had antibodies in their pretransplant serum. The preexistence of antibodies directed against B lymphocytes had an unfavourable effect on the graft survival; (2) the graft did particularly well in the nonimmunized patients who had been previously transfused; the graft survival was about 80% at 3 years in these patients; and (3) the HLA (A, B) match influenced the graft survival only in patients with antibodies.


A rapid method for determining the sterility of frozen-reconstituted blood. A rapid, fast, and accurate method of determining bacterial contamination in blood units is needed to provide a safe unit of frozen-reconstituted blood which can be stored at 4 C after thawing for more than the 24 hours currently allowed by law. The Bactec instrument seems to provide this method. It detects most of the organisms which have been reported in contamineted blood, and does this in a short enough period of time that any organisms introduced into the blood unit during the sampling process will not grow sufficiently to contaminate the unit while the culturing process is going on.


Changes of plasma cholinesterase activity during orthotopic liver transplantation in man. Variations of plasma cholinesterase activity were studied in eight patients with end stage liver disease having orthotopic liver transplantation and five other patients with hepatic cirrhosis undergoing surgical procedures. Serum cholinesterase activity was found to be below normal limits in every patient, even more so in those having hepatic homotransplantation, probably because of the greater severity of their disease. Blood transfusions increased pseudocholinesterase activity to normal or nearly normal levels; but only after successful transplantation did these levels remain within normality, thus suggesting that the homografts promptly assume production of the serum enzyme.


The systemic production of cytotoxic lymphoid cells in corneal allograft reaction. 1. A quantitantitative study utilizing 51chromium release assay. The purpose of the study was to determine whether the mechanism of corneal allograft rejection is systemic in nature. Utilizing a 51Cr release assay in which labelled donor and recipient corneal cells were used as targets, it was demonstrated that cytotoxic cells specific for antigens located in donor corneal cells were present in spleen and lymph nodes.


The immediate function of the kidney after 24-to 72-hr preservation. Hypothermic storage versus mechanical perfusion. Seventy-two dog kidneys were stored under hypothermia as described by Collins and Sacks between 24 and 72 hr and then transplanted. The immediate function of the kidneys was measured by p-aminohippuric acid and inulin clearances. Twenty-four hr proved to be the maximum safe preservation time with both methods. The immediate function of the kidneys stored under hypothermia could not be improved by the addition of furosemide to the flushing solution. These results were compared with those gained by mechanical perfusion of the organ. Kidney function after 72 hr of hypothermic mechanical perfusion was significantly better than after 24 hr of hypothermic storage.


Prolongation of murine skin allografts by prostaglandin E1. The effects of 16,16-dimethyl prostaglandin E2 methyl ester (di-M-PGE2) and indomethacin (an inhibitor of endogenous prostaglandin biosynthesis) on mouse skin allograft survival were studies in B10.D2 female mice receiving skin allografts from (B10.BR X B10.D2)F1 mice. Control animals with and without i.p. diluent injections had a mean allograft survival of 13.8+/-0.6 and 13.5+/-0.5 days, respectively. Daily administration of di-M-PGE2 (200 microng/kg) prolonged mean allograft survival, both when administered alone, 16.7+/-0.6 days (P less than 0.001), or with indomethacin, 4 mg/kg thrice weekly, 16.0+/0.6 days (P less than 0.005). Increasing concentrations of indomethacin (4, 6, and 8 mg/kg thrice weekly) were inversely corrleated with allograft survival ((12.7+/-0.2, 11.8+/-0.2, and 10.9+/-0.4 days, respectively), coefficient of correlation=-0.6986; P less than 0.001. Mean plasma PGE levels at the time of total allograft rejection were 879+/-80 pg/ml in control, 717+/-59 pg/ml in 100 micron g of indomethacin-treated mice, and 654+/-59 pg/ml in 200 microng of indomethacin-treated mice (P less than 0.05). Exogenous di-M-PGE2 prolonged skin allograft survival in mice. Inhibition of endogenous prostaglandin biosynthesis by indomethacin chortened allograft survival, but this effect was completely abrogated by concurrent injection of di-M-PGE2.


Transplantation of syngeneic bone marrow incubated with leucocyte antibodies. I. Suppression of lymphatic leukemia of syngeneic donor mice. "Antileukemic autotransplantation" an approach to eradicate by antibodies residual leukemia in the bone marrow taken during remission and regrafted in relapse is proposed and is the basis of investigations on the elimination of leukemic cells transferred to syngeneic mice. Rabbit antiserum against mouse T cells killed over 99% of cells when incubated with 10-5 lymphocytes of a T cell AKR/J leukemia transferred subsequently to syngeneic hosts. Seventy-five per cent of the recipients of antibody-coated and complement-treated leukemic cells survived the observation period of 80 days. Recipients conditioned with 800 R and given syngeneic bone marrow mixed with 10-5 leukemic cells died within 11 days, while 40% survived the observation period of 100 days without leukemia if the leukemic bone marrow had been preincubated with anti-T cell globulin (ATCG) and complement. A detrimental effect of ATCG on normal T cells could only be demonstrated in thymectomized, irradiated recipients of syngeneic ATCG-treated marrow. These mice did not reject H-2-incompatible skin grafts in contrast to the controls without ATCG or without thymectomy. ATCG thus inhibited leukemic lymphocytes while sparing stem cells for hemopoietic reconstitution. At the same time it did not interfere with the recovery of cellular immunity after bone marrow transplantation.


Antigen-reactive cell opsonization (ARCO): a mechanism of immunological enhancement. Rat renal allograft survival is markedly prolonged by passive enhancement. Radio-labelled AS-anti-HO antigen-reactive cells (*ARC) were prepared by immunizing AS rats with HO rat tissue and injecting 125IUdR over a period of 4 days. Most of the radioactivity in spleen cells from these rats were associated with antigen-reactive cells which formed rosettes specifically with HO erythrocytes. *ARC were specifically opsonized in syngeneic AS rats bearing enhanced (AS times HO)F1 kidney allografts but not in untreated, rejecting allografted rats. *ARC incubated in vitro with serum from enhanced rats and injected into normal animals were opsonized whereas serum from rats rejecting grafts was ineffective. *ARC incubated in vitro with hyperimmune AS-anti-HO serum were not opsonized, unless the antiserum was first incubated with HO tissue under conditions favouring the formation of immune complexes. These results are consistent with the hypothesis that ARC bind antigenic determinants of antigen-antibody complexes and are opsonized by virtue of the antibody Fc portion of the complexes.


The level of FC receptor leukocytes in primary and secondary skin allograft recipients. DA (Ag-B4) rats were grafted with allogeneic Lewis (Ag-B1) skin on the region of the thorax drained by the left brachial and axillary lymph nodes. A DA isograft was placed on the right side of the thorax. From 1 to 14 days after grafting the rats were either given injections of colloidal carbon, killed, and spleen and lymph nodes were assayed for noncarbon-containing Fc rosette-forming leukocytes (RFL), or allowed to complete rejection of the graft. In order to assess secondary allograft rejection within the latter animals after the grafted areas was healed, a second Lewis allograft was placed in the same region as the first and another DA isograft on the right side. Compartmental Fc RFL were enumerated 2 to 16 days thereafter by rosette formation with erythrocyte-antibody. The regional lymph nodes of animals rejecting a primary allograft exhibited a significantly (P less than 0.05) higher level of Fc RFL compared with their contralateral controls. These higher levels were evident on days 6 to 8 and disappear by day 10. However, animals undergoing a secondary allograft response exhibited significant differences by day 4. A greater density of Fc RFL were also evident in cryostat sections of the graft bed of allografts as opposed to isografts.


Coccidioidomycosis and renal transplantation. Two cases of coccidioidomycosis detected in a group of more than 750 renal transplants are presented. The first patient died from unsuspected disseminated coccidioidomycosis 4 1/2 years after primary transplantation and 6 days after retransplantation. In the second patient pulmonary coccidioidomycosis was recognized and treated by lobectomy and amphotericin B before transplantation; subsequent transplantation has provided good renal function without recurrence of infection for 5 years. Experience with six other reported cases of coccidioidomycosis illustrates the high risk of exacerbation and dissemination of preexisting coccidioidal infection in immuno-suppressed transplanted recipients. Nevertheless, this risk can be made acceptable if active coccidioidomycosis is treated vigorously before immunosuppression is started and if the possibility of exacerbation of infection after transplantation is carefully monitored.


HLA matching and cadaver kidney transplant survival in North America: influence of center variation and presensitization. In an analysis of 4,851 first cadaver kidney transplants, we found a statistically highly significant correlation between the number of HLA antigens mismatched and graft survival (P less than 0.0005 at 1 year). The difference in the survival rates of grafts with no HLA mismatch compared with grafts with four mismatches was 11 to 12%, similar to results of previous analyses. HLA-A locus antigens had a slightly stronger effect than B locus antigens. The correlation of HLA matching with graft survival was most significant at centers with poor overall transplant outcome, and there was no correlation at centers with very good overall results. Presensitization also had the strongest effect at centers with poor overall graft survival.


Kidney transplantation. Modern trends in kidney transplantation. Trends in renal transplantation stem from recognition of the virtues and drawbacks of this kind of treatment and from a better appreciation of the interrelationship between transplantation and dialysis.


Is graft irradiation of value in renal transplant rejection? Thirty-six patients who received renal transplants and who subsequently underwent rejection episodes were randomized into two groups before undergoing treatment. One group received high doses of steroid drugs, and the other group received in addition 600 rads of radiotherapy to the graft. After 3 years (minimum follow-up 12 months) the groups were compared with respect to initial response to treatment, patient and graft survivals, and level of transplant function. No benefit was obtained by the group receiving radiotherapy.


Cancer in renal allograft recipients in Australia and New Zealand. Total incidence and outcome of cancer in all renal allograft recipients in one geographic area are known: 126 (7%) of 1884 patients developed cancer during an 11-year period. Proportions with cancer 1 and 5 years following successful transplantation were 11% and 24%, respectively. Numbers, proportion of malignancies, and average time of diagnosis post transplantation were as follows: reticulum cell sarcoma (RCS) 15 (11%), 18 months; adenocarcinoma 8 (6%), 21/2 years; cancer of cervix 6 (5%), 41/2 years; leukemia 2 (2%), 5 years. All were highly malignant except cancer of the cervix, 2 localized forms of RCS, and 4 cases of cerebral RCS that responded to radiotherapy. Skin malignancy (SM) occurred in 97 patients (77% of cancers). The frequency increased with time, and after 4 years 18% of survivors had this cancer. In patients with SM 17% had multiple lesions when first diagnosed; further cancers or recurrences of the same type developed in 23%; another form of SM developed in 15%; metastases occurred 9 times (9%), 4 fatally. Six (6%) patients with SM developed other forms of malignancy, as compared to 33 (2%) of 1786 patients without SM. Ooulook for patients with SM with regard to survival and graft function was greatly improved at 5 years, as compared to that for patients without SM. Thereafter the outlook for patients with SM worsened rapidly because of additional effects of malignancy.


Related donors: costs and gains.

Related donors: costs and gains. A quantitative, sociopsychologic study of 111 donors at 1 year after a successful transplant points to long-term emotional benefits rather than costs for most donors. While no one factor is highly predictive of donors who react less well, exclusion of extremely ambivalent donors would appear advisable, as would counseling help for other relatives who wish to donate despite normal fears.


Kidney transplantation following treatment with cyclophosphamide and bone marrow grafting. Canine cyclophosphamide (CY) chimeras permanently accept kidney and skin grafts as do radiation chimeras. Three of five dogs with reversion of chimerism rejected their kidney grafts within 11-16 days, while two of them retained their kidney grafts permanently. These results suggest that the reversion of chimerism in CY chimeras may be due to different mechanisms, either immunologic rejection or a nonimmunologic substitution of the grafted marrow by the host's own hemopoiesis.


Calculations on long-term graft and patient survival in human kidney transplantation. Long-term survival rates of human kidney transplants were found to decline at constant rates following the second year after transplantation. The slopes of decline were statistically significantly different for cadaver, parent-to-child, and HLA-identifical sibling transplants, resulting in graft survival half-life times during the constant risk phase of 7.5, 11, and 34 years, respectively. The corresponding patient survival half-life times were 12, 19, and 36 years, respectively. A highly significant difference in long-term survival risk was found when seven transplant centers that had been selected on the basis of their good 1-year graft survival results were compared with seven centers known to have a poor 1-year survival rate. The cadaver graft half-life times during the constant risk phase were 3.3 years for the "poor" centers and 8.7 years for the "good" centers. Thus, although histocompatibility obviously is a main factor in determining long-term survival risk, additional factors such as clinical treatment regimen appear to be influential. Knowledge of the long-term risk constants for the different transplant categories can be applied for the projection of success rates as well as retransplant and dialysis needs.


Heart and liver transplantation. Consistent survival after prolonged donor heart preservation. Twelve dogs underwent orthotopic cardiac transplantation after donor heart preservation for 24 hr in a hypothermic hypertonic intracellular solution. Donors were divided into two groups: continuous oxygenated perfusion and nonperfusion. After 24 hr, transplantation was performed. All six perfused and four nonperfused donors hearts survived a 24-hr postoperative period. Survivors had normal cardiac output, right and left atrial pressures, and aortic pressures. After transplantation, all perfused hearts demonstrated mild left ventricular damage while nonperfused hearts had severe damage. Hypothermic hypertonic intracellular perfusion may allow improved protection for short-term myocardial preservation and survival after extended myocardial preservation.


Pancreatic transplantation. Absence of diabetes in dogs after total pancreatectomy and intrasplenic autotransplantation of pancreatic tissue. Two simple, rapid, and reproducible techniques of pancreatic tissue preparation produced favorable results after just part of the gland was autotransplanted in totally pancreatectomized animals. It is probable that the short and less traumatic treatment in vitro was responsible for the sufficient yield of viable islets. Moreover, the results show convincingly that the complete separation of endocrine from exocrine pancreas is not mandatory to insure adequate endocrine secretion. The spleen, an organ of no vital importance having a rich blood supply and belonging to the portal circulation, was a very suitable experimental implantation site, which permitted thorough evaluation of the tissue preparation techniques. These favorable results were not conditioned by the splenic tissue itself, because similar results have been obtained in dogs when the tissues were implanted into the liver via the portal vein.


Effect of HLA matching on cadaver kidney function: experience at a single large center. Whenever the results are compared within a given time period, within a given age group, within the nondiabetic population, and within groups receiving high or low doses of ALG, the advantages of well-matched kidneys continually and significantly demonstrate themselves. Tissue matching failed to improve survival and function only in diabetic patients who frequently die of problems unrelated to rejection. The results thus demonstrate an overall clear superiority in patient survival and transplant function of the better-matched kidneys.


Human endothelial cell antigens: molecular independence from HLA and expression in blood monocytes. Human alloantisera identified antigens in endothelial cells from umbilical cord veins that were not detectable in peripheral blood lymphocytes. Results of antigen redistribution experiments by the resistance to lysis induction method suggested that E-antigens were present in separate molecules of the endothelial cell surface. Monocytes from peripheral blood reacted like endothelial cells in cytotoxicity tests and were able to absorb the endothelial cytotoxic antibodies. Comparison of concordant and discordant monocyte reactions in first-degree relatives indicated that the antigens involved were inherited in linkage with HLA.


Pathways of complement activation in membranoproliferative glomerulonephritis and allograft rejection. The complement system is comprised of at least 18 plasma proteins and consists of four functional divisions: two pathways for activation (classical and alternative), a common amplification mechanism for the activating pathways, and a final common effector pathway to which the activating and amplifying sequences are directed. The classical pathway is activated by certain antigen-antibody complexes, while the alternative pathway may be initiated non-immunologically by various microbial polysaccharides. Indeed, mixtures of purified C3, B, D, and P regulated to low-grade interaction by the presence of C3bINA and beta1 H respond to zymosan with amplified C3 and B inactivation. Both pathways form enzymes termed C3 convertases that cleave C3 to generate its major fragment, C3b. C3b interacts with each C3 convertase to permit C5 cleavage in activation of the effector complement sequence, and it interacts with alternative-pathway factors B and D to generate additional C3 convertase, C3bBb, in the amplification pathway. As C3 cleavage represents the most critical step in the elaboration of the biologic effects of the complement system, modulation of this reaction by generation, stabilization, and inactivation of the amplification convertase C3bBb may well determine whether initial activation of the complement sequence eventuates in beneficial or detrimental effects for the host. Initial generation of C3bBb is dependent on prior cleavage of C3, which may occur by the classical pathway or the alternative pathway. Stabilization of C3bBb is achieved with either P or C3NeF after their binding to C3b and C3bBb, respectively. Control of this amplifying step occurs at three levels: intrinsic decay of the inherently labile C3bBb complex, extrinsic decay-dissociation of Bb from the complex by beta1H, and inactivation of C3b by C3bINA. In the presence of stabilizing factors the control proteins must function in sequence, since C3bINA cannot act on C3bBb; beta1H-mediated decay of protective Bb must precede C3b inactivation by C3bINA. C3NeF, which is found in the sera of some patients with MPGN and persistent depressions of serum C3, circumvents all three controls because of its capacity to create a stabilized convertase that is relatively resistant to decay-dissociation by beta1H. The effector complement sequence is activated by cleavage of C3 and C5, which releases vasoactive and chemotactic peptides, C3a and C5a, and generates the major fragments C3b and C5b. C3b, in addition to its function in the amplifying reaction and the C5 convertases, mediates immune adherence to cells possessing membrane-associated receptors for C3b; this in turn promotes the phagocytic and secretory functions unique to each cell type. Cell-bound C5b serves to assemble the cytolytic complex C5b6789, while fluid-phase C5d generates the hemolytically inactive chemotactic complex C567d...


Delayed cutaneous hypersensitivity and human renal allotransplantation. A group of 154 patients on chronic dialysis has been evaluated by DNCB reactivity. Viewed as a group, these patients exhibit a highly significant decrease in immunologic responsiveness in comparison to normal individuals. However, 19% of patients had an immunologic response to DNCB and 12% an irritant response. This pretransplant DNCB responsiveness correlated significantly with subsequent allograft rejection in 71 renal allotransplant recipients. For example, at 1 year after transplantation graft survival was strikingly different: DNCB- patients, 78%; DNCB+ patients, 29%; and DNCB-IR patients; 20%. Pretransplant recall-antigen testing results in 32 patients did not correlate significantly with subsequent transplant results. Serial posttransplant delayed cutaneous hypersensitivity responses in patients with a positive response to a skin test antigen in the pretransplant period suggest possible usefulness of this technique for detecting rejection in the posttransplant period. DNCB skin testing should be performed in all transplant candidates to evaluate host responsiveness and should aid in future patient management.


Anti-Ia serum blocking of macrophage function in the in vitro humoral response. Antisera directed at I-region gene products coded for by genes in the I-J subregion effectively block macrophage function in the primary in vitro response to burro erythrocytes. Pretreatment of macrophages with normal serum, nonappropriate anti-Ia antibodies, or anti-H-2 serum had no inhibitory effect. Similar antiserum pretreatment of macrophage-depleted cells did not affect their ability to function with untreated adherent splenic macrophages. The results suggest that the Ia molecule has an active role in antigen presentation by the macrophage or in macrophage-lymphocyte interaction in the primary IgM response.


Anticipation of renal transplant failure by postanastomosis biopsy and immunofluorescence. Ninety-six pre- and postanastomosis allograft biopsies from 48 transplant recipients were studied employing the direct fluorescent antibody procedure. Of the 48 transplants studied, 26 postanastomosis biopsies showed significant blood vessel wall deposits consisting predominantly of 2-4+ staining IgM and C3 deposits. The corresponding preanastomosis biopsies showed only patchy intimal surface staining. All but two of the grafts with positive biopsies had been preserved by the pulsatile perfusion method for various periods of time. Twenty-three of the twenty-six grafts with positive findings failed within 1 month while only 2 of the 19 negative postanastomosis biopsies failed within the 1-month period. Based on these findings actual graft failure occurred in 89% of the patients with postanastomosis transplant biopsies with positive findings. Although crossmatch studies were negative in all cases, further immunologic studies of eluates obtained from positive postanastomosis biopsies revealed the presence of lymphocytotoxic IgM antibodies in three of five cases studied. These findings suggest that rapid deposition of undetected preformed lymphocytotoxic antibodies accumulate in the vessel walls following anastomosis and contribute to transplant failure.


Passive enhancement of rat renal allografts by antibodies to a non-SD (Ag-B) locus analogous to Ia and demonstration of linkage to the MHC. The rat MHC contains a distinct locus for Ia-like antigens. The alleles of this locus are not always associated with like alleles of the MLR and Ag-B (SD) loci in inbred strains. This is demonstrated by the Fischer strain, which is MLR and tag-B (SD) 1 (H-11) but shares an Ia specificity with BN (Ag-B3, H-1n). The biologic significance of anti-Ia is distinctive, having in vivo graft-enhancing capability, even when it is cross-reacting (i.e., Lew anti-Fi enhances BN). In contrast, anti-AG-B (SD) does not enhance in the rat model.


Niridazole as an immunosuppressive agent. The immunosuppressive properties of niridazole, an antihelminthic drug, have been investigated in rats. When given orally at a dosage of 50 mg/kg it extended the median survival of cardiac allografts from 7 to 20 days. The immunosuppressive effect was not increased by giving either azathioprine or prednisolone concurrently, but when all three drugs were combined the immunosuppression was profound, and only 2 of 8 grafts were rejected. Drug combinations incorporating niridazole at a lower dosage or for a shorter period were less effective, and azathioprine and prednisolone on their own or together prolonged graft survival only marginally in this model.


Trial of two intermittent short-course regimens (78 doses) in the initial treatment of pulmonary tuberculosis. A controlled trial was done in Roumania to compare 2 regimens in patients with culture-positive pulmonary tuberculosis. Both regimens were of twice-weekly doses under supervision for 9 months, a total of 78 doses. Patients were followed up for 15 months after the end of treatment. The regimens were as follows: IR, isoniazid and rifampicin for 3 months followed by isoniazid and either streptomycin or ethambutol for 6 months; ISE, isoniazid, streptomycin and ethambutol for 3 months followed by isoniazid and either streptomycin or ethambutol for 6 months. Of 128 IR cases and 104 ISE cases with sensitive cultures initially all were culture-negative at 6 months. At the end of 9 months there were 1.8% of 112 in the IR group which had had 2 positive cultures in the 6-9 month period and 3.4% of 88 in the ISE group. After 15 months from the end of treatment 5.6% of 89 in the IR group had had a bacteriological relapse and 8.9% of 79 in the ISE group. Cultures from all relapsed cases were still sensitive to the drugs used. All relapses occurred during the first 12 months. In only 5.6% of 232 patients did adverse reactions necessitate change of treatment. The efficacy, cost, tolerance and suitability of the regimens for a national programme are discussed.


Fatal generalized BCG histiocytosis.

Fatal generalized BCG histiocytosis. An infant was vaccinated at the age of 3 days with BCG vaccine. At the age of 3 years 10 months he developed an infection by Salmonella typhimurium. The infection persisted with recurrent episodes of fever, peri-nephritic abscess, abscesses of lymph nodes, hepatomegaly, splenomegaly and paravertebral and retro-peritoneal abscesses, from which Salmonella were isolated. At the age of 6 years and 2 months later. At post-mortem examination there were widespread histiocytic nodules in many organs, from which Mycobacterium bovis BCG were cultured. One previous case has been reported from Czechoslovakia. The mother of that child was the sister of the father of the child reported here. It was not possible to investigate the possibility of abnormalities of humoral or cellular immunity in the family.


[Kinetics of 35S-lipoate binding in vitro by plasma proteins and formed elements of the blood]. When incubating isolated erythrocytes, leucocytes and blood plasma 35S-lipoate in rising concentrations (2.4-240 microng/ml) the intensive binding of the latter may be observed, that is 8-11% of 35S-lipoate total content in the incubation medium for proteins, 4.8-08% for erythrocytes and 1.1-0.12% for leucocytes. Calculating per 10(7) cells the binding of lipoate by leucocytes is 1-2 order higher than that by erythrocytes. In blood plasma binding of 35S-lipoate by leucocytes is 41-82% lower than in the physiological solution. The binding of lipoate by erythrocytes also drops in the presence of plasma as compared to the physiological solution, but this effect is less pronounced and significant only with the presence of 240 microng of lipoate per 1 ml of the medium. Kinetics of 35-S-lipoate binding by the blood cells is of complicated character and permits supposing the existence of the lipoate-barrier function of the plasmatic membranes which is able of regulating lipoate intake by erythrocytes up to a concentration of 24 microng/ml and by leucocytes even up to 240 microng/ml.


Immunotherapy with dinitrochlorobenzene (DNCB) for recurrent squamous cell tumor of conjunctiva. Over the course of nine years a young man sustained repeated recurrences of a squamous papillary epithelial tumor of the conjunctiva and canaliculus. Treatment had included repeated surgical excisions, fulguration, cryotherapy, and localized applications of Thiotepa. When we examined him in 1972 he had a recurrent lesion measuring about 1 cm in diameter. Because of past failures with the above-noted therapeutic modalities, we decided to treat him with immunotherapy using the immunological adjuvant DNCB (dinitrochlorobenzene). We sensitized him systemically to DNCB by applying 2,000 microng of this agent to the skin of his forearm. A spontaneous "flare" reaction, indicative of delayed hypersensitivity, developed. Delayed hypersensitivity to DNCB was confirmed by in vitro testing of his lymphocytes for their ability to produce migration inhibitory factor (MIF) in response to DNCB. Subsequent localized application of DNCB to the conjunctival tumor resulted in rapid regression of the lesion and there has been no recurrence during a follow-up period of three years. We believe this is the first time a conjunctival tumor has been successfully treated with immunotherapy.


Presumed chronic ocular histoplasmosis syndrome: a clinical-pathologic case report. An eye of a patient with clinically typical presumed ocular histoplasmosis was studied by light microscopy, electron microscopy and immuno-fluorescence techniques. There was clinical and pathological evidence of anterior segment involvement. The posterior segment showed granulomatous and nongranulomatous chorioretinal lesions with and without subretinal neovascularization. Immunohistopathological staining for histoplasma antigens revealed positive staining at sites of lymphoid inflammation. Organisms were not identified.


[Preparation of antilymphocytic globulin by means of repeatedly-used immunoadsorbents (author's tranl)]. A method is described for the purification of horse anti-human lymphocyte serum, whereby absorption of haemagglutinating antibodies was performed with human RBC ghosts. These ghosts were repeatedly used after desorption. Desorption was carried out in glycine-HCl buffer solution pH = 3,0. The advantages of this method consist of a reduction in the amount of RBC needed for absorption and the relatively low loss of lymphocytotoxic antibodies. The final product is effective in an in vitro test system and complies with the requirements for human use.


Parietal cell (highly selective or proximal gastric) vagotomy for peptic ulcer disease. Parietal cell vagotomy has been in clinical use for 7 years in elective treatment of nonobstructive duodenal ulcer, and for even a shorter period for complicated cases and for gastric ulcer The evolution of the surgical technique has not yet come to an end and the ability to perform the procedure is still improving. It can therefore be questioned, if this operation is yet ripe for a realistic clinical trial, and the great variation in recurrence rate reported in pilot series as well as in prospective randomized clinical trials points to the possibility that we will have to wait several years before the anticipated mean recurrence rate is known. At present it can be stated that even if gastric emptying is not quite undisturbed, the addition of a drainage procedure in nonobstructive cases is unnecessary. The same may be true in some patients with pyloric obstruction. Furthermore, the mortality rate is very low and the incidence of moderate-to-severe dumping and diarrhea is virtually nil.


Isolation of viable human pancreatic islets. This article reports a method for the isolation of viable pancreatic islets from the human pancreas. Isolated islets were obtained from human pancreata of cadavers, patients undergoing surgical operations, and fetuses, using a freehand microdissection procedure. Viability was assessed by light microscopy of sections stained with aldehyde fuchsin and by measuring the insulin output of islets in response to a glucose stimulus in vitro using a perifusion system. Ten pieces of cadaver pancreas were studied. Islets were isolated from 6 specimens and in 5 of these were shown to respond to a glucose stimulus in vitro. Histologically the islets showed minimal damage with slight degranulation of the beta cells. Five pieces of pancreas removed at operation were studied as well. Islets were isolated in all cases, but only 2 showed a response to a glucose stimulus. Pancreata from a 26-week and 34-week human fetus were also studied. It was not possible to microdissect islets from either case, but small pieces of pancreas from the 26-week fetus were shown to respond to a glucose stimulus by producing a significant increase in insulin output.


The effect of stored blood on mesenteric oxygen extraction during exdotoxin shock. Storage of blood in acid-citrate-dextrose (ACD) solution gradually depletes red cell 2,3-diphosphoglycerate (DPG) and increases the affinity of hemoglobin for oxygen. We examined the effect of exchange transfusion of DPG-depleted blood on mesenteric blood flow and oxygen consumption in dogs subjected to endotoxin shock. Two groups of 6 dogs each were anesthetized and subjected to exchange transfusion with either fresh ACD blood or 21-day-old ACD blood prior to administration of Escherichia coli endotoxin (2 mg/kg). Mesenteric blood flow, arteriovenous oxygen content difference and systemic arterial blood pressure were monitored continuously before and for 60 min after endotoxin. Mesenteric blood flow was reduced from 250 +/- 21 ml/min before endotoxin to 114 +/- 15 ml/min at 5 min, 157 +/- 29 ml/min at 30 min, and 112 +/- 17 ml/min at 60 min after endotoxin in the dogs exchanged with fresh blood. Corresponding values for intestinal oxygen consumption were 10.4 +/- 1.0, 7.5 +/- 0.8, 8.4 +/- 1.0, and 6.8 +/- 0.7 ml/min. In dogs transfused with 21-day-old blood, pre-endotoxin blood flow was 208 +/- 2ml/min and declined to 115 +/- 12, 93 +/- 5, and 80 +/- 8 ml/min at 5, 30, and 60 min post-endotoxin. Corresponding values for intestinal oxygen consumption were 8.1 +/- 0.9, 6.6 +/- 0.7, 6.2 +/-0.5, and 5.5 +/- 0.7 ml/min. There was no significant difference (p greater than 0.1) in responses of blood flow or oxygen consumption to endotoxin shock between the two groups of dogs. These findings indicate that exchange transfusion with DPG-depleted blood does not impair oxygen extraction by the ischemic intestine.


Review of elective surgical treatment of chronic duodenal ulcer. This article is a review of 20 clinical trials of various forms of elective surgical treatment of chronic duodenal ulcer conducted between 1964 and 1975, some of them prospective and others retrospective in nature. Comparisons have been made of the results following truncal vagotomy with drainage, truncal vagotomy with antrectomy, and partial gastrectomy. Additionally, selective vagotomy and truncal vagotomy have been compared in some studies and various forms of drainage, such as pyloroplasty and gastrojejunostomy, have been compared in others. In general, the results of all current forms of elective surgery for chronic duodenal ulcer have been very good, and the differences among the effects of the various procedures have been small. There have been no significant differences in the mortality rates associated with the several operations when they have been performed electively. The rate of ulcer recurrence and incidence of diarrhea have been somewhat higher after truncal vagotomy with drainage, whereas the frequency of dumping and amount of weight loss have been somewhat greater after all forms of gastric resection. Selective vagotomy appears to be associated with less frequent and severe diarrhea than does truncal vagotomy. There have been no apparent differences in the results of the various drainage procedure that have been combined with vagotomy. Highly selective vagotomy without drainage, the most recent operation for duodenal ulcer, has resulted in the lowest incidence of post-operative side effects of any surgical procedure in current use. However, the frequency of ulcer recurrence after this therapeutic measure remains to be determined by long-term studies.


[Transient behavior of the ammonium-limited chemostatic cultures of Escherichia coli ML 30]. In connection with the bistability of pyruvate formation in ammonium limited continuous cultures of E. coli ML 30 (Bergter u. Roth 1977) the transient behaviour of cell density and pyruvate concentration were studied. Immediately after a shift up in the dilution rate from D = 0.15 h-1 to D = 0.6 h-1 the bacteria excreted pyruvate into the medium, followed by a resumption of pyruvate. The specific pyruvate formation rate as well as the specific growth rate reached the new steady state with damped oscillations. Possibly the excretion of pyruvate after the shift is caused by the higher non limiting concentrations of ammonium during the first of the transition. This hypothesis is supported by the transient behaviour of an ammonium limited continuous culture after a pulse of ammonium to the culture. The relations between ammonium metabolism and pyruvate formation are discussed.


Low temperature inhibition on binding, trasport, and incorporation of leucine, arginine, methionine, and histidine in Escherichia coli). A multiple amino acid auxotroph and a wild type of Escherichia coli K12 were used to study the effects of near minimum growth temperatures on the binding, transport, and cellular incorporation of selected amino acids. Both strains of the bacterium showed the same minimum growth temperature (8 degrees C) when previously grown at 15 degrees C. At 8 degrees C and above, the auxotroph exhibited an overall greater ability to bind and transport amino acids than did the wild type. Below the minimum growth temperature, transport and cellular incorporation including respiration ((uptake) were significantly lower for either organism. The NEU and HEPPEL osmotic shock treatment indicated the removal of the specific histidine-binding protein and the ability to bind histidine was not recovered by further incubation below 8 degrees C. At 8 degrees C and above, the cells recovered their ability to bind histidine within one hour. The evidence presented indicates a direct relationship between the auxotroph's minimum growth temperature and its ability to bind amino acids, specifically methionine.


[Hypo- and hyperparathyroidism in pregnancy]. During pregnancy the maternal calcium metabolism is submitted to special loads. Overchallenging of the functional capacity of the parathyroid gland may evoke an insufficiency of the parathyroid gland which on its part induces a fetal secondary hyperparathyroidism. Therefore, the early diagnostic recognition of the insufficiency of the parathyroid gland is of importance, since (also in basic diseases known before pregnancy) now special therapeutic conditions are given. Maternal hyperparathyroidism leads to fetal hypoprarthyroidism with resulting developmental disturbances; it furthers the tendency to abortions and perinatal mortality. Epidemiological prospective investigations have shown that among the identified cases of oligo- or asymptomatic functional disturbances of the parathyroid glands there are very often women at an age, when they are capable of bearing children. This statement confirms the postule regularly to control serum calcium content during pregnancy. Objectifying the disturbed integrity of the calcium metabolism, therapeutic measures are necessary, the details of which are demonstrated according to own experiences. In such cases the cooperation between the gynaecologist being in charge of the pregnant woman and the internist working in the field of endocrinology is to be wished.


Induction of lymphocyte proliferation and membrane changes by lipopeptide derivatives of the lipoprotein from the outer membrane of Escherichia coli. Lipoprotein from the outer membrane of E. coli, a potent novel mitogen, was digested by pronase treatment resulting in lipopeptide fragments containing 2-5 amino acids bound to diacylglyceryl-N-acylcysteinthioether. The lipopeptides were characterized by amino acid analysis and gas chromatography and were checked for mitogenicity. We found that all lipopeptide fragments were able to stimulate the uptake of 3H-uridine into RNA and 3H-thymidine into DNA in mouse spleen cells of several strains. The response of splenocytes of congenitally athymic mice was comparable to that of normal animals. A weak stimulation of DNA synthesis was also observed in thymocytes. The mitogenicity of the products was abolished by mild alkali hydrolysis which removes the ester-bound fatty acids. We conclude that the N-terminal lipopeptide region of lipoprotein is responsible for the mitogenic activity of the molecule. Lipopeptide as well as lipoprotein were found to cause early membrane changes in lymphocyte plasma membranes. After 4 hours we found an increased incorporation of 14C-oleate and 14C-acetate into lecithin. The membrane changes observed are similar to those brought about by mitogenic lectins, which suggests a similar mechanism for the induction of lymphocyte activation for both types of mitogens.


[Treatment of urethral stricture in man using one-stage urethroplasty with subcutaneous pedicle graft]. It is reported on a new one stage urethroplasty which, using a subcutaneous pedicle graft, is based on the spontaneous formation of a tube of a urethra-skin-strip submerged into the depth. The procedure was tested on a clinical material of 140 cases and is recommended as method of choice in strictures of the urethra.


[History and technical development of hip joint replacement operations (author's transl]. The development of hip replacement operations is closely connected with the failures in operations to save the head of the femur. After many materially determined set-backs and errors due to false biomechanical ideas, there was renewed progress in allo-arthroplasty of the hip in the, 50's. But even newer models--like the Weber-Huggler-prosthesis-show that the technical development does not yet fully take into account the actual biological demands.


[Management of delivery in twin abnormalities--a case report]. Report of the leading of delivery of an Ileothoracopagus per vias naturalis. There are described the importance of X-ray-examination prior to delivery, the progress of delivery, and the leading of delivery. It is pointed to the stiching up of skin over the prominent parts of bones after dividing the newborns sub partu to avoid a laceration of the mother womb and vagina.


Immunoferritin studies on the multiplication of Sindbis virus in chick embryo fibroblasts. Replication of Sindbis virus chick embryo fibroblasts was studied by means of the immunoferritin technique. Virus specific antigens, diffusely distributed in the cytoplasm, were observed at first 3 hours p.i. At the same time in ohter cells ferritin particles in linear arrangement occured at the surface of vesicles. At these places heavily labelled nucleocapsids were observed later on. This means, that the surface of vesicles is a site of assembly of nucleocapsids. Maturation of virus takes place at the cell surface as well as at the vesicles by budding. In early stages of replication maturation at the membrane prevalis.


A contemporary review of incidence and detection of enterotoxigenic E. coli strains in human diarrheal diseases. Methodical possibilities for detection of enterotoxic strains of E. coli and the frequency of appearence of these strains in infants and adults suffering from diarrheal diseases are reviewed. Our own study, using the ligated rabbit intestinal loop, revealed 6.8% incidence of enterotoxin producing strains among the classical enteropathogenic serotypes of E. coli, isolated from stools of infants with mild diarrhoea. The model of mice intestinal loop was not found to be suitable for detection of enterotoxin of E. coli strains. The most sensitive model seems to be the intestine of precolostral piglet; however this model is not suitable for routine tests.


"R"-living vaccine against colibacillosis. Communication I. After our estimation of the LD100 of enteropathogenic E. coli 0149 and 0138 (and their toxins) in rabbits and mice (intravenously and subcutaneously or intraperitoneally, respectively), rabbits and mice were vaccinated subcutaneously by the living "R" 0149 vaccine. All animals showed resistance against the LD100 of both E. coli serotypes; this state of resistance lasted 1-5 months in rabbits, and 1-3 months in mice. Sera of vaccinated rabbits showed bactericidal activity against both E. coli serotypes. The R-E-system of rabbits which were immunized by the endotoxin of "R" 0149 living vaccine, showed mobilization of immunocytes. The vaccine seems to be harmless to newborn piglets after oral vaccination; 2 colostrum deprived piglets, despite vaccination at once after birth, did not survive the big chalenge with 100 ml of broth culture of E. coli 0149 "S" (anapylactic shock). But in comparison to 1 not vaccinated control piglet, the two piglests showed only few E. coli colonies in the intestines, while the intestine of the control animal was very massively colonized by the virulent strain. As the immunizing potency of the "R" 0149 living vaccine was clearly shown in rabbits and mice, further investigations on piglets (newborns, weaning epriod, and after weaning) are needed, to state whether the value of this vaccine corresponds with the immunizing potency shown in our preliminary experiments. The "R"-vaccine seems to open some perspective in colibacillosis prevention of children and animals, and therefore it deserves our attention.


Parallel study of two techniques for identification of gram negative anaerobic bacilli. The authors have used two different methods for the identification of 45 strains of stric anaerobic gram negative rods: a study of biochemical characters by the API 20 anaerobic kit, and system proposed by SUTTER and FINEGOLD (susceptibility to discs loaded with antibiotics associated with some simple biochemical characters). A good correlation has been observed between those two techniques. However, a precise diagnostic can be given only by a whole study of biochemical characters, as proposed by the system API 20 Anaerobic.


[Newer antimycotics. III. Halogen- and nitro-substituted anilines and phenols (author's transl)]. The author produced a number of halogeno- and nitro-derivatives of anilines and phenols, investigated their antimicrobial efficiency in vitro, further the toxicity on mice of their most effective representatives. From the author's results it can be concluded that trihalogenoanilines and tetrachloroaniline exerted a relatively strong fungistatic activity with a broad spectrum of efficiency (Tab. 2) likewise to the polyhalogenophenols and halogenonitrophenols (Tab. 3). The acute toxicity of the most effective halogenoanilines was relatively small; they were found to be significantly less toxic than halogenophenols and tetramethyl-thiuramdisulfide (Tab. 5). On the basis of the intensive fungistatic activity and small toxicity of the tri- and tetrahalogenoanilines, it seems that a number of representatives of these types of chemical compounds could be given a role in the chemotherapy of superficial human and animal dermatomycoses, and also in the chemoprophylaxis of certain phytomycoses.


Purulent conjunctivitis caused by group B streptococci. To the already known pathological pictures caused by group B streptococci, mucopurulent conjunctivitis is added. Clinical pictures in adult and children are described shortly. Bacteriological findings are added. Pharyngeal streptococci of the same group found in some cases in people nearby, may be incriminated as the source of infection of conjunctiva.


[Growth of non-sporing anaerobes in an oxygen-free blood culture system (author's transl)]. The efficacy of the commercially available Vacutainer blood culture system to support the growth of non-sporing anaerobes was compared with two laboratory-prepared blood culture media (supplemented thioglycollate medium and brain heart infusion). The media were inoculated with 10, 100 and 1000 organisms of the species tested, and the number of colony-forming units was determined at intervals of 8-10 hrs. Analogous experiments were performed with batches of the media to which 10% vol/vol of human blood had been added. From the results obtained with strains of Bacteroides fragilis, Bacteroides thetaiotaomicron, Bacteroides splanchnicus, Sphaerophorus necrophorus, Peptostreptococcus anaerobius and Propionibacterium acnes it became obvious that growth of non-sporing anaerobes was significantly enhanced in the Vacutainer culture tubes, whereas Enterobacteriaceae and Streptococcus spp. grew equally well in all the media tested.


[Detection of a factor suppressing leukocyte migration in the sera of allergy patients following antigen administration]. The effect on donor leukocyte migration of serum obtained from the patients with tuberculosis of the lungs, chronic pneumonia and healthy persons was studied after subcutaneous or intradermal injection of the microbial antigen (PPD, streptococcus and staphylococcus antigen). A factor inhibiting donor leukocyte migration appeared in the blood serum of sensitized individuals after the antigen injection. This factor proved to be localized in the serum fraction III obtained after the gel-filtration of sephadex G-200, and is sorbed by leukocytes.


[Patterns in the formation of proteolytic enzymes by different strains of C1. botulinum type F]. The authors studied regularities attending the accumulation of proteolytic enzyme and toxin by C1. botulinum, type F, strains in the medium. Strains No. 470, 200, 76, 55 proved to possess caseinolytic capacity, whereas strains Eklund and Craig were "nonproteolytic". C1. botulinum strain, type F, medium and growing conditions providing a high yield of proteolytic enzymes were selected. Some properties of proteolytic enzyme of strain No. 470 were studied.


[Biological activity of extracts isolated from a virulent strain of Sh. flexneri grown in the presence of calcium ions]. The authors carried out a comparative study of the genetically connected Sh. flexneri cultures (3 virulent strains, 3 clones of an avirulent mutant selected in the flux of an oblique light from the virulent strain, and lac+ Kcp A-hybrids obtained by crossing the initial virulent cultures with the E. coli K12 Hfr strains). The absence of any correlation between the virulence of the strains under study and the lipopolysaccharide (by rhamnose) content in the extracts from them in growing the cultures in the presence of calcium ions was noted. Toxicity of the extracts from the virulent cultures was demonstrated on a model of developing chick embryos. No such property was possessed by the extracts from avirulent strains. The extracts from the virulent cultures in nontoxic doses possessed the capacity to decrease LD50 of shigella strains used for the infection. The biologically active factor determined in the extracts from the virulent cultures apparently was not lipopolysaccharide.


[Checking the reliability of the PathoTec biochemical test system for bacterial identification]. Tests of the PathoTec system intended for express bacteriological diagnosis were checked in comparative experiments with the common biochemical methods. Cultures of the following microbes were used: Schigella, Salmonella, Escherichia, Citrobacter, Klebsiella, Enterobacter, Proteus, Providencia, Pseudomonas, Bordetella, Staphylococcus, Streptococcus. In a number of tests, such as determination of cytochromoxidase, nitrate reduciase, phenylalaninedeaminase, indol, acetoin (for the differentiation of enterobacteria), detection of plasmocoagulation and mannite fermentation (for staphylococci) there was revealed a complete coincidence of the results. However, discrepancies were revealed with three of the reagents tested (for lysine decarboxylase, urease, citrate utilization) with regard to some groups of enterobacteria. The advantages of the PathoTec system consisted in more rapid results, simplicity of procedures, economy of media and ware.


[Morphologic mutant of Escherichia coli K12 having disorders in morphology, division and cell wall biosynthesis]. A study was made of the properties of a spherical mutant obtained from the E. coli K12 HfrC strain under the effect of N-nitroso-N-methyl-urea. The growth of the mutant of full value media was characterized by a marked reduction of the cell division at the rest phase, but exponential growth phase failed to differ from the growth of the parental strain. Electron microscopic study of surface structures of the mutant cells which grew under physiological conditions permitted to distinguish two types: the first type had a typical structure of the cell wall characteristic of Gram negative microbes; the second type was framed by a bicontour membrane without any distinct structure. The presence of these two types of cells was also confirmed by their different sensitivity to the ionic detergents. On the basis of chemical analysis of peptidoglycan of the cell wall (which was markedly decreased in amount in the mutant cells), and also of the unsually high accumlation of the UDP-precursors of peptidoglycan under conditions of penicillin action it is supposed that normal regulation of metabolism of the cell walls was deranged. Mutation designated by 11rA symbol was plotted by phase PI transduction alongside of strA gene.


[Conditions for S. typhimurium transfection by isolated DNA from bacteriophage P22 H5]. Transfection of spontaneous S. typhimurium LT2 WTR mutant, sensitive to bacteriophages FO, Ffm, 6SR, and resistant to bacteriophages P22 H5, C-21 and P1 vir, by DNA of P22 H5 bacteriophage in the presence of Ca2+ ions was demonstrated. The following were conditions of infection providing maximal and reproducible results: concentration of the recipient cells of 6--7x 109 cells/ml, DNA concentration of 30 microng/ml, CaC12 concentration of 0,25 M. The efficacy of transfection was 5 x 10-8.


[Change in phagocytic activity toward the agent of tularemia in highly sensitive animals with mixed infections]. An increase of the ingestive and digestive capacity of neutrophils to the homologous causative agent and tularemia microbe was revealed by the opsonophagocytic test in Microtus arvalis, albino mice and guinea pigs infected with sublethal Yersinia pseudotuberculosis and Salmonella typhimurium doses. In subsequent tularemia infection some of the animals displayed a reduction of the septicemia intensity, prolongation of the disease and elevation of the susceptibility threshold. Period of manifestation of the inhibitory action on tularemia coincided with that of the increase in phagocytic activity


[Detection of the localization of C1. botulinum antigens in regional lymph node cells by the immunofluorescence technic]. As a result of the study of lacalization of the C1. botulinum toxoids of the A, B, and E types in cells of the regional lymph nodes of rabbits by the indirect Coons' method and by the smear-print method it was revealed that different types of lymphoid tissue cells took part in the ingestion and digestion of these antigens; the antigens of the A and B types were at first revealed in the cytoplasm of pseudoeosinophils, and then in the macrophages. The antigen of the E type was revealed in the course of the whole experiment in the macro phages of the regional lymph node, although the number of pseudoeosinophils also increased. Apparently there was a different activity of pseudoeosinophils against the C1. botulinum toxoids, the types A, B and E.


[Role of several physico-chemical surface properties of bacteria in the machanism of the initial phases of phagocytosis]. An attempt was made on E. coli pattern to reveal the role played by the surface charge and the extent of the surface hydration in the mechanism of the initial phagocytosis phases (attraction and submersion). Phagocytosis experiments with washed bacteria and washed rabbit leukocytes demonstrated a marked direct dependence of the electrophoretic velocities of escherichia and the intensity of their phagocytic ingestion, and a strong reverse relationship between the extent of hydration and the phagocytic activity. Treatment of bacteria with rabbit plasma with subsequent washing led to a significant reduction of hydration and to an insignificant reduction of the electrophoretic velocities with parallel increase of the phagocyte activity. Correlation between the phagocytosis intensity and the acquired physico-chemical properties of bacteria became weak.


[Methods of treating the Itsenko-Cushing hypothalamo-hypophyseal syndrome]. Studies of a group of patients with the Icenko-Cushing syndrome during the period of 6 months to 6 years permitted to establish that the treatment of the disease, irrespective of the etiology, is most effective when using preparations of gamma-amino-butyric acid, vegetotropic preparations and antidepressive drugs in combination with electrosleep. The adovementioned treatment methods permit to significantly and steadily improve the condition of the patients and preserve, in most of the cases, their working capacity.


Proteolysis of procollagen I.

Proteolysis of procollagen I. 1. Digestion of procollagen I which trypsin, pepsin or pronase performed at 20 degrees C causes the release of acidic non-collagenous fragments and hydroxyproline-rich fraction. Enzymatic proteolysis performed at 41 degrees C (above the temperature of denaturation) results in degradation of procollagen I to low-molecular peptides. 2. The hydroxyproline-rich fraction obtained by limited proteolysis of procollagen I with pepsin (at 20 degrees C) contains a material corresponding to alpha and beta subunits of tropocollagen. Reduction of the hydroxyproline-rich fraction released by trypsin or pronase (at 20 degrees C) causes the appearance of polypeptides similar to pro-alpha subunits.


Effect of prolactin inhibitory agents on the ectopic anterior pituitary and the mammary gland in rats. The purpose of the present study was to investigate the biological effectiveness of two highly potent prolactin (PRL) inhibitors, lisuride hydrogen maleate (LMH) and 2-Br-alpha-ergocryptine (CB-154), in the absence of hypothalamic factors acting directly at the level of the anterior pituitary. Hypophysectomized female rats bearing 4 transplanted pituitaries beneath the kidney capsules were treated with oestradiol benzoate (OeB) and progesterone (P) with or without simultaneous administration of LHM or CB-154 for 22 days in order stimulate or inhibit lobula-alveolar growth of the mammary glands. In addition to the investigation of the mammary glands by DNA determination and assessment of the histological pictures, the aim of this study was directed towards the influence of the substances tested at the level of the anterior pituitary remote from the hypothalmus. In this connection the changes in the different cells within the ectopic pituitaries as revealed by immunoenzyme-cytochemical studies were investigated. The results obtained support the classical view of a neuroendocrine regulation of mammary gland growth and the importance of oestrogens, P and PRL within this system. Both ergot derivatives LHM and CB-154 were able to antagonize the stimulatory effect of OeB combined with P on the mammary gland. With regard to the mechanism of action of LHM and CB-154 it is concluded that both substances act via a direct action on dopaminergic receptors within the ectopic anterior pituitary.


Ovarian steroid effects on gonadotrophin output, and on the incorporation of 35S from methionine into protein of discrete brain areas and the anterior pituitary. The effects of various ovarian hormones administered on the morning of pro-oestrus on gonadotrophin levels and the incorporation of 35S from methionine into protein of discrete areas of the brain and the anterior pituitary were investigated at 15.00 h of the same day in female rats. The hormones which were investigated in this study could be divided in general into two groups according to their actions. The first group, consisting of oestradiol-17 beta and progesterone, tended to advance the pre-ovulatory surge of luteinizing hormone (LH) by 3-6 h from 18.00-21.00 h, together with the peaks of [35S]incorporation in the median eminence area and the anterior pituitary which normally accompany the LH surge. The second group, consisting of the LH-stimulated reduced progesterone metabolites, 5 alpha-pregnane-3,20-dione (pregnanedione) and 20 alpha-hydroxy-pregn-4-en-3-one (dihydroprogesterone), tended to inhibit serum gonadotrophin levels as well as inhibiting the pro-oestrous increase of [35S]incorporation in the median eminence area and in the amygdala, but not in the preoptic area and the anterior pituitary. On the afternoon of pro-oestrus in intact animals, luteinizing hormone-releasing hormone or LH administration had the same effect on [35Si1incorporation in the brain as did the progesterone metabolites, though this effect was not observed if the animals had been ovariectomized a few hours beforehand. It is suggested that certain ovarian hormones are involved in the neural events which induce the pre-ovulatory LH surge, while others are associated with neural events which terminate the stimulus for the LH surge.


Temporal changes in the hypothalamic and serum luteinizing hormone-releasing hormone (LH-RH) levels and the circulating ovarian steroids during the rat oestrous cycle. Cycling female rats were sacrificed at various times during the 4-day oestrous cycle. LH-RH in the medial basal hypothalamus (MBH) and serum LH-RH, LH, oestradiol (Oe2), and progesterone were analyzed by radioimmunoassays. The MBH LH-RH content was lowest at 19.55-20.15 h during pro-oestrus but increased gradually  through oestrus and dioestrus I to significantly higher values at noon of dioestrus II, and then decreased precipitously at 18.00 h. Although serum LH levels remained basal from midnight of pro-oestrus through dioestrus II, serum LH-RH levels were significantly elevated at 12.00 and 21.00 h on oestrus (vs. the midnight pro-oestrus levels) and declined between 15.00 and 22.00 h of dioestrus I. In conjunction with high Oe2 titres, LH-RH in the MBH and serum declined initially during pro-oestrus between 14.07-14.45 h and then increased abruptly between 14.55-15.55 h; the pre-ovulatory rise in serum LH was observed from 16.05 h onwards. LH-RH activity in the MBH and serum receded gradually to the early afternoon levels by 19.55-24.00 h while the peak in serum LH was observed at 17.05-18.05 h. These studies suggested that the hypersecretion of the MBH LH-RH (synthesis + release) may be responsible for the pre-ovulatory discharge of LH.


Plasma LH and FSH response to LRH and plasma testosterone levels in boys with irregular puberty. Nineteen boys with irregular puberty (IP), defined as a discrepancy of two or more pubertal stages between the criteria for genitalia and that for pubic hair, were subjected to a standard LRH test (50 microng/m2, iv) and the response of gonadotrophins as well as the basal levels of plasma testosterone, LH and FSH were compared to those of boys with normal, regular puberty. When the results were plotted against the pubertal stage for genitalia (Pg), it was found that in the boys with IP the basal plasma testosterone levels were lower and the response of plasma LH to LRH stimulation lesser than in the controls. However, when these parameters were plotted against the pubertal stage for pubic hair (Ph) it was found, that in the boys with IP the plasma testosterone levels were significantly higher and the response of both LH and FSH stimulation greater than in the control group. It was concluded that irregular puberty in boys may be regarded as a normal variation. The delayed development of sexual hair and penile length, and retarded pubertal growth spurt and bone age maturation seen in these boys, with normal testicular development, may be explained by a temporary reduced peripheral sensitivity to androgens and a compensatory effort by the pituitary, manifested in increased secretion of LH and testosterone, relatively to their pubertal stage for pubic hair.


Sex hormone binding globulin binding capacity, testosterone, 5alpha-dihydrotestosterone, oestradiol and prolactin in plasma of patients with prostatic carcinoma under various types of hormonal treatment. Sex hormone binding globulin (SHBG) binding capacity, the concentrations of testosterone (T), of 5alpha-dihydrotestosterone (DHT), of oestradiol-17beta (Oe2), of oestrone (Oe1), of prolactin (hPr) and the percentual specific binding of T to SHBG (%TB) were measured in plasma of patients suffering from prostatic carcinoma and of a control group of similar age. No significant differences in any of the investigated parameters were found between the control group and the carcinoma patients before treatment although 15% of the latter showed distinctly elevated hPr values. Treatment of carcinoma patients with 1) Antiandrogen (cyproterone acetate, Androcur) resulted in a significant decrease of T, Oe2 and SHBG. The DHT/T-ratio increased. n=5. 2) Orchidectomy caused an even more pronounced fall in T, DHT, Oe1 and Oe2 blood levels. SHBG was not altered. DHT/T-ratio increased. n=32. 3) Cyproterone acetate after orchidectomy led to elevated hPr values. n=5. 4) Oestrogen (diethylstiboestrol-diphosphate, Honvan) after orchidectomy increased SHBG and hPr. n=6. 5) Corticosteroid (Prednisone, Decortin) after orchidectomy decreased T and SHBG below the levels found after orchidectomy alone. n=5. 6) Diureticum (Mefruside, Baycaron) (n=5) or 7) a placebo (n=7) did not alter any of the parameters measured. 8) Treatment with HCG (Primogonyl) of patients suffering from oligozoospermia resulted in a significant increase of T, DHT and Oe2. SHBG was not altered. DHT/T-ratio decreased. n=7.


[Dynamic tests with GnRH, L-dopa, clomiphene, cyclophenyl, HCG and HMG in 98 cases of dysspermia due to a variety of causes]. Radioimmunological methods have been used to assay the plasma concentrations of gonadotropins, androgens (expressed as the sum of testosterone and dihydrotestosterone) and 17beta-oestradiol in 98 patients suffering from dysspermia of variable etiology, after stimulation with GnRH, Clomiphene, L-Dopa, Cyclophenyl, HCG in various dosage schemes, and HMG. Results show L-Dopa and HMG tests to be of little value in assessing the endocrine function in infertile men. They also confirm, in keeping with data found in the literature the usefulness of dynamic stimulation with GnRH, Clomiphene, and HCG for purposes of andrologic diagnosis. The GnRH proved useful for the distinction between primary and secondary hypogonadotropism as well as for assessing the therapeutic efficacy of releasing factors. The functional efficacy of the endocrine axis which is often impaired in patients with dysspermia can be evaluated by the Clomiphene test. In the small number of cases in which it was applied, Cyclophenyl brought about changes in gonadotropin concentration which require further study. The HCG tests, to be performed in patients with lower than normal testosterone plasma lavels, permits the discrimination between primary and secondary Leydig cell deficiencies as well as the assessment of interstitial tissue sensitivity to chorionic gonadotropin stimulation. Of the three dosage schemes (5000 IU, 7500 IU "step up", 10.000 IU) the last one is most suitable for clinical use.


Choroidal absorption angiography with patent blue V. The vital dye patent blue V is used as a negative contrast dye in order to obtain information about the vascular filling events of the choroid in relation to the retinal circulation and the papilla employing intravenous injection and serial photography. Patent blue is bound to plasma proteins to a limited degree and the angiograms therefore do not only picture the choroidal vessels but also reveal the filling of the choriocapillaris and the transcapillary exchange. It is demonstrated by microdensitometry that the patent blue leakage and subsequent reabsorption is rapid, and that the choroidal dilution curve almost parallels that of the retinal vessels. Our measurements might indicate a diffusion of patent blue from the choroid to the papillary tissue.


Osteogenesis after bone and bone-marrow transplantation. I. Studies with combined myelo-osseous grafts in the guinea pig. There has been conflicting evidence in the past regarding the contribution made to new bone formation by various components of a bone graft. This study in guinea pigs has compared cortical and cancellous bone allografts, both non-decalcified and hydrochloric acid decalcified, inserted into a muscular site for up to thirteen days, both alone and combined with autologous bone marrow. New bone formation was seen only if the implant contained fresh autologous marrow and it was not seen before the ninth day of implantation. There were no differences in the cell populations about cortical and cancellous grafts. Undecalcified bone evoked giant cell formation as well as new bone.


Airborne contamination and postoperative infection after total hip replacement. The results of 163 hip replacements at the Uppsala University Hospital are presented. Deep infection occurred in ten cases and was caused by Staphylococcus aureus in four early or intermediate infections and by anaerobes in four late infections. The remaining two infections (both of which were late) were probably associated with Staphylococcus albus--in one case possibly also with alpha streptococci. Two superficial infections not affecting the operative result were caused by Staphylococcus aureus and betahaemolytic streptococci. The results of environmental analyses of staphylococci and the total number of bacteria in the air during 77 operations did not indicate that airborne infection is a major cause of postoperative infections--there was no difference between the number of bacteria found in the air during operations after which infection occurred and uninfected operations, and the use of special zonal ventilation with high rates of air exchange in the operating area had no effect on the infection frequency.


Effect of obesity on the hypothalamo-pituitary-gonadal function in childhood. In 22 normal and 35 obese boys a gonadal function test (2000 IU of hCG i.m. daily for three days and assays of plasma testosterone before and after the hCG administration) was carried out. All the "short normal" children and 31 obese subjects underwent the LH-RH test (50 microng i.v.). While basal testosterone was similar in the two groups of children, after hCG testosterone was significantly (p less than 0.001) lower in the obese boys, In the normal children a significant positive correlation between bone age and basal and after hCG testosterone was demonstrated; this correlation was not found in the obese boys. The pituitary reserve of gonadotrophins did not show significant differences between the two groups of children. Finally a significant positive correlation (p less than 0.01) between the LH curve area during the LH-RH test and bone age was found only in the normal boys.


Asymptomatic bacteriuria in schoolgirls. VI. The correlation between urinary and faecal Escherichia coli. Relation to the duration of the bacteriuria and the sampling technique. The occurrence of the urinary strain in the anus, rectum and faeces was investigated in 27 girls with asymptomatic bacteriuria (ABU). In patients with bacteriuria of relatively short duration 46% of the faecal isolates were of the urinary strain as compared to only 18% in patients with bacteriuria of relatively long duration. In general the correlation between the urinary and faecal flora is striking at the time of establishment of ABU but diminishes with time. The diminished correlation may be due to two factors: firstly, the composition of the faecal flora changes with time. Secondly, the correlation may be obscured by complex changes in the properties of bacterial strains established in the urinary tract. Contamination by the infected urine did not seem to be a serious problem when the rectal mucosa was swabbed proximal to the anal canal.


Gonadotropin-releasing hormone (LH-RH) and human chorionic gonadotropin in the treatment of two boys with hypogonadotrophic hypogonadism. Two brothers, 16 and 14 years of age, with hypogonadotrophic hypogonadism and anosmia were treated with subcutaneous injections of 200 microng gonadotropin-releasing hormone at 8-hour intervals for 4 weeks. Serum FSH increased to the range of normal adult men, but serum LH and serum testosterone showed little change and no clinical signs of pubertal development occurred. Thereafter the 2 patients were given HCG for 11 months and a combination of HCG and HMG for a further 3 months. In response to this treatment, the serum testosterone levels increased to the range of normal adult men and marked development of the secondary sex characteristics was seen.


The elasticity in the presence of diluents. A review is given of the thermoelastic measurements performed om different materials. Basically, all materials can be divided into two groups. Fro crystalline and glassy materials the enthalpy component of the retractive force is large and the entropy component is small. On the other hand, for amorphous, crosslinked polymers the opposite is true. After corrections are made for volume changes, the energy component is generally small and the entropy component is large. Only rubber-like polymers, whether diluted or not, are known to display the latter behavior. Moreover, these materials generally undergo glass transitions upon cooling. In these physical properties elastin behaves like the latter class. Therefore in the absence of evidence to the contrary, elastin must be considered to be an amorphous, crosslinked polymer displaying rubberlike elasticity.


Prevention of arterial thromboembolism with acetylsalicylic acid. A controlled clinical study in patients with aortic ball valves. Prevention of arterial thromboembolism with acetylsalicylic acid (ASA) was studied in 148 patients with single Starr-Edwards aortic ball-valve prostheses. These patients are suitable for such a study because they have a high incidence of arterial emboli derived mainly from thrombi formed on the valves. They were given either 1 Gm. of ASA daily or placebo in combination with anticoagulants, and were observed for 2 years. Only two emboli occurred in patients receiving ASA, none of them severe. In the placebo group 12 thromboembolic episodes were diagnosed in 10 patients, and three with cerebral emboli died; in one a subdural hematoma unrelated to the embolus was found. In addition, one fatal and the one nonfatal intracranial bleeding occurred in each group, whereas gastrointestinal complications were seen more frequently in patients taking ASA. It is concluded that ASA combined with anticoagulants offered a significantly better protection against arterial thromboembolism than did anticoagulant therapy alone.


Efficacy of disopyramide phosphate in the treatment of refractory ventricular tachycardia. The effects of intravenously administered disopyramide phosphate were evaluated in seven patients with refractory ventricular tachycardia. All patients had organic heart disease, including acute infarction (three patients), chronic coronary artery disease (two patients) and cardiomyopathy (two patients). The severity of the heart disease was reflected in the advanced patient age (average 64 years) and the occurrence before disopyramide therapy of cardiac arrest in five patients and congestive heart failure in all seven patients. In five patients, disopyramide was given as a bolus injection, 2 mg/kg body weight, followed by an infusion of 20 to 40 mg/hour. The final two patients received 4 mg/kg divided as a bolus injection and an infusion over 1 hour followed by a 0.4 mg/kg infusion during the next hour. Intravenous administration of disopyramide resulted in more effective electrical stability in all patients and completely eliminated ventricular tachycardia in six. Recurrence of ventricular tachycardia was prevented in six patients with subsequent long-term oral administration of disopyramide. Possible dose-related cardiac pump depression occurred in two patients, but disopyramide was otherwise well tolerated. Therefore, these data document the therapeutic efficacy of disopyramide in the treatment of refractory life-threatening ventricular tachyarrhythmias.


An electron microscopic study of absorption of peroxidase-conjugated immunoglobulin G by guinea pig visceral yolk sac in vitro. In the guinea pig and some other animals, passive immunity is conferred on the developing fetus by passage of immunoglobulin from mother to fetus across the yolk sac. In order to examine the cytological pathway involved in immunoglobulin transport, guinea pig visceral yolk sacs from late in gestation were exposed in vitro to peroxidase-conjugated guinea pig immunoglobulin G (IgG-HRP). Tissue was then fixed, incubated to show the site of localization of peroxidase reaction product and prepared for electron microscopy. The results suggested that the first step in the uptake of IgG-HRP by yolk sac is attachment of the protein to the surface coats of endocytic invaginations at the apical surfaces of the endodermal cells. The endocytic vesicles then appear to pinch off from the surface and move deeper into the cytoplasm. Some of the small endocytic vesicles fuse with large apical vacuoles, which often contain large amounts of reaction product. Other small endocytic vesicles pinch off from the surface, move deeper into the cytoplasm and fuse with the lateral plasmalemma; their protein content is emptied into the intercellular space by exocytosis. From the intercellular spaces the protein presumably diffuses across the basement membrane and connective tissue spaces and enters the vitelline capillary bed. It is postulated that the latter cellular pathway, involving small vesicles and the intercellular spaces, is utilized by those immunoglobulins which are transferred intact across the yolk sac endoderm.


Minerals in human teeth: differences between preindustrial and contemporary Hopi Indians. Mineral elements in dentin from 17th century Hopis were compared with samples from contemporary Hopis living in the same geographic area. Less lead, zinc, and copper, and more strontium were found in the preindustrial teeth. Trace element levels in the contemporary Hopi teeth were similar to those in suburban Californian teeth.


Desaturation of bile and cholesterol gallstone dissolution with chenodeoxycholic acid. The feeding of one of the major biliary bile acids, chenodeoxycholic acid, at a dose of 10 to 15 mg/kg per day causes the circulating bile acid pool to become greatly enriched in this bile acid. When chenodeoxycholic acid composes more than 70% of the biliary bile acids, the amount of cholesterol secreted in bile falls, and bile becomes unsaturated in cholesterol. If cholesterol gallstones are present and are exposed to this unsaturated bile, they will dissolve in 4 to 24 months in the majority of patients. Extensive clinical experience indicates that such medical therapy is safe, despite unequivocal toxicity of chenodeoxycholic acid in several nonhuman primates. When therapy is stopped, bile resaturates, and stones may recur. Since cholecystecomy is a rapid, safe, effective, and usually permanent treatment for all gallstones, the value of medical therapy remains uncertain at present, except for patients in whom surgery is inadvisable. Nonetheless, the demonstration that chenodeoxycholic acid ingestion will desaturate bile and induce gallstone dissolution would appear to be an important pharmacological advance.


Mutagenicity of benzidine and related compounds employed in the detection of hemoglobin. Seven compounds commonly used as chromagens for the detection of hemoglobin and its derivatives have been assayed for mutagenicity employing the Salmonella/mammalian microsome test. Three of these compounds, benzidine, o-dianisidine, and o-tolidine, were shown to be mutagenic. Since benzidine and o-tolidine are already known to be carcinogens, there is a high probability that o-dianisidine will also prove to be a carcinogen. Four compounds tested with this system, o-anisidine, diphenylamine, guaicol, and o-toluidine, were not mutagenic.


Amyloid AA protein. Cellular distribution and appearance. To investigate the cellular distribution and possibly the cellular origin of the AA protein associated primarily with the fibrils of secondary amyloid deposits, a variety of human tissues was studied by indirect immunofluorescence using a specific anti-AA immunoglobulin and FITC-goat anti-rabbit IgG. Positive cells were most frequently identified in reactive lymphoid tissues. They were most numerous in tonsils and, to a lesser extent, frequent in spleens. Both cellular appearance and distribution of the positive cells suggested a plasmacytic nature. Double staining with rhodamine-labeled anti-IgG demonstrated IgG within some of these cells. The data suggest that the AA protein may be an immunoprotein. In the absence of kinetic data, however, it is not possible definitively to assign the origin of the AA protein to the plasma cell.


Immunodiagnosis of melanoma using chimpanzee antihuman melanoma antiserum. Three cases of metastatic malignant lesions are presented. By conventional pathologic examination these lesions were diagnosed as undifferentiated carcinomas. They were studied using a chimpanzee antiserum specific for human melanoma-associated antigens. In each case, cells from the tumor were reactive with the anti-melanoma antiserum. The tumors were also studied using the DOPA test. All three tumors were positive in the DOPA test, suggesting the presence of tyrosinase within the tumor cells. The results suggest that serologic identification of melanoma may provide a rapid, inexpensive means for tumor diagnosis.


Differentiation of renal tubular epithelium in renal transplantation cytology. Increased numbers of renal tubular epithelial cells are present in the urinary sediments of renal transplant recipients during acute rejection. Few investigators have described characteristics of renal tubular epithelial cells in cytologic preparations. This study compiles morphologic characteristics of various tubular epithelial cells and determines the type of the tubular cells present during acute allograft rejection. The results demonstrate that cuboidal forms from the small collecting ducts are the predominent tubular epithelial cells exfoliated in voided urine during acute allograft rejection.


Hemagglutination as an alternate technic for the detection of melanoma-specific cytoplasmic antigens. The extensive use of the single technic of immunofluorescence has resulted in the detection of an array of melanoma-specific antigens. Those antigens residing in the cytoplasm of the melanoma cell have been shown to cross-react across various melanoma cell lines in tissue culture, as well as across all fresh tumor cells isolated directly from patients. The ubiquitous nature of this antigenic activity, as defined by immunofluorescence, suggests that the presence of this activity may be important diagnostically. Isolation of one or more antigens from the cytoplasm, however, requires the development of an assay for antigenic activity in cell fractions. Data presented here indicate that passive hemagglutination provides as effective a means of visualizing antigenic activity as does immunofluorescence. Evidence showing that melanoma-specific antigenic activity is present as a soluble component in the cytosol and as a membrane-associated component of the endoplasmic reticulum is also presented.


Detection of cryptococcal polysaccharide using counterimmunoelectrophoresis. Counterimmunoelectrophoresis was used to detect Cryptococcus neoformans capsular polysaccharide in the body fluids of infected patients. Using rabbit anti-C. neoformans A15 globulin, counterimmunoelectrophoresis detected 1.25 microgram of purified cryptococcal polysaccharide per ml of cerebrospinal fluid (CSF) or urine and 2.5 microgram per ml of serum. When the body fluids were subjected to a hundredfold concentration prior to testing, as little as 25 ng of purified cryptococcal polysaccharide/ml CSF or urine and 80 ng/ml serum was detected. Among patients with cryptococcal meningitis, counterimmunoelectrophoresis detected polysaccharide in the CSF when the India-ink examination was negative. Using counterimmunoelectrophoresis, the concentrations of polysaccharide antigen in the body fluids of these patients could be estimated. Specificity of the rabbit anti-C. neoformans A15 globulin was evaluated. There was no crossreaction that detracted from its diagnostic usefulness. Rheumatoid factor was not a source of false-positive tests. Counterimmunoelectrophoresis is a useful technic for establishing a rapid, specific serologic diagnosis of cryptococcosis.


Corynebacterium equi infection complicating neoplastic disease. Corynebacterium equi, a soil-residing diphtheroid pathogenic in horses, swine and cows, caused pulmonary infection with bacteremia in two patients with lymphomas. Both patients were being treated with immunosuppressive therapy, as were the patients in three previously reported human cases. Unless certain characteristics of these organisms are recognized, they may be regarded as normal flora or contaminating diphtheroids. They could also be mistaken for other gram-positive rods, such as Bacillus species, Listeria monocytogenes, or Erysipelothrix insidiosa. C. equi isolates have usually been sensitive to erythromycin, tetracycline, gentamicin, and carbenicillin. One of the patients reported here was successfully treated with erythromycin, tetracycline, and surgery.


Adrenocorticosteroid therapy in alcoholic hepatitis. A prospective, double-blind randomized study. In a prospective, randomized, double-blind study of prednisolone therapy of acute alcoholic hepatitis, 39% of the total group of 28 patients died. Mortality and cumulative survival were similar in steroid- and placebo-treated patients. After 14 days of therapy, the serum albumin concentration and white blood count were significantly higher in the steroid group, but all other parameters were similar. An increased risk of fungal infection appeared to be associated with steroid therapy.


Multicentric colonic lymphoma complicating ulcerative colitis. A 72-year-old female with ulcerative colitis of 30 years duration underwent total proctocolectomy for a cecal mass thought to be an adenocarcinoma. Pathologic examination of the colon revealed 22 tumors, all of which proved to be malignant lymphoma, histiocytic type. Thirteen cases of non-Hodgkins malignant lymphoma and 2 cases of Hodgkins disease of the colon arising in ulcerative colitis are reviewed and discussed.


Epidemiologic differences among serotypes of Cryptococcus neoformans. In the USA, the most prevalent serotype of the fungus, Cryptococcus neoformans, was serotype A. The serotype constituted 203 of 272 isolates from infections and 85 of 89 isolates from the environment. Serotype B or C isolates were infrequent causes of infection, except in Southern California, and were infrequent causes of infecand were not isolated at all from environmental sources. In Southern California, the absence of serotypes B and C in 67 soil and pigeon dropping isolates was striking, considering that 25 of 49 isolates from infections were serotypes B or C. The site in nature where serotypes B and C exist is currently unknown but differs from that of serotypes A and D. Serotype D may be unusually prevalent in both environmental and patient isolates from Denmark and Italy. Of 24 isolates from those countries, 21 were serotype D.


Preventing, detecting and managing adverse reactions of antihypertensive agents in the ambulant patient with essential hypertension. The adverse reactions of antihypertensive agents are reviewed, including their clinical implications and suggested methods of preventing, detecting and managing them. The drugs discussed are: (1) diuretics--thiazides, furosemide, ethacrynic acid and spironolactone; (2) sympatholytics--reserpine, methyldopa, guanethidine, propranolol and clonidine; (3) vasodilators--hydralazine, prazosin and minoxidil. It is suggested that cooperative multi-disciplinary efforts should be undertaken to counteract the factors which contribute to improper use of antihypertensive agents.


Toxic reactions and side effects of glucocorticoids in man. The toxic reactions and side effects of glucocorticoids in humans are discussed. The effects reviewed include metabolic (muscle and skin, carbohydrates and lipids), cardiovascular, cellular, immunologic, skeletal and growth, gastrointestinal, nervous system, ocular, and hypothalmic-pituitary-adrenal.


Effect of unit dose packaging of respiratory therapy medications on incidence of pulmonary infections. The effect on pulmonary infection rate of using respiratory therapy medications packaged in unit dose syringes versus multiple-dose vials was studied. Study data were collected on 141 patients during a three-month period; 78 patients were treated with respiratory medications packaged exclusively in unit dose syringes, and the balance received medications from multiple-dose vials. Based on information collected from patient charts, the presence of definite or probable pulmonary infections was determined. Of the 83 patients who did not have pulmonary infections prior to therapy, 23% developed one; there was no significant difference in the incidence of infection according to type of medication packaging. Nor did packaging have a significant effect on the incidence of infection among the 39 patients who were predisposed to infection. Finally, method of packaging had no significant effect among the 58 patients who had an infection before therapy started. It is suggested that the decision to employ unit dose packaging for respiratory therapy medications must be based on factors other than the incidence of infection.


Terminal half-lives of drugs studied in patients with hepatic diseases. Published evidence of the effects of liver diseases on the terminal half-lives of drugs in man is presented. Formulas are given to aid the reader in determining the hepatic clearance of drugs. The effect of various liver diseases on hepatic function is reviewed. Data on 38 drugs are tabulated.


Hypokalemic, metabolic alkalosis induced by high-dose ampicillin sodium. A case of hypokalemic metabolic alkalosis precipitated by high-dose intravenous ampicillin sodium is discussed. Cases of hypokalemic metabolic alkalosis attributable to ampicillin sodium have not been reported previously. There have been reports of this phenomenon associated with high doses of penicillin sodium and carbenicillin disodium. The possible mechanism of antibiotic-induced hypokalemic metabolic alkalosis is discussed. It is suggested that most cases of antibiotic-induced hypokalemia respond to oral or intravenous potassium chloride.