A case of congenital retinoschisis with unexpected appearance and spontaneous regression

A case of congenital retinoschisis, with both unexpected appearance and spontaneous regression, is reported. The patient, a 22-year-old man, had been diagnosed with congenital retinoschisis when he was 11 years old. The ocular fundus showed bilateral foveal retinoschisis and peripheral retinoschisis in the right eye. Early in November 1991, he visited our hospital and complained of a visual field defect in the left eye. The ocular fundus of the left eye showed high ballooning retinoschisis. However, two weeks later, the ballooning retinoschisis had completely disappeared. Appearance and regression of peripheral retinoschisis of congenital retinoschis in an adult is a very rare occurrence.     

Immune response to rauscher virus-induced leukemia in DBA mice. I. Role of cellular and humoral immunity in spontaneous regression

DBA/1 and DBA/2 mice infected with the Rauscher leukemia virus developed a biphasic erythroleukemia. Transitory regression of the disease was closely associated with the appearance of tumor-specific antibodies and the exacerbation was preceded by the gradual decrease of antibody titer. The antibody-dependent cellular cytotoxicity could be detected earlier, than the complement-dependent cytotoxicity. Moreover, in each case the titer of antibody-dependent cellular cytotoxicity was higher than that of complement-dependent cytotoxicity. The results suggest that the antibody-dependent cellular cytotoxicity is mainly responsible for the rejection of tumor cells.     

Cytotoxic activity in a case of adult T-cell leukemia/lymphoma with spontaneous regression

Plasmid profile analysis by agarose gel electrophoresis was performed on 42 drug resistant strains of Shigella boydii serotypes 1-5, 8, 10, 12-14, collected between 1974 and 1985 from endemic cases of shigellosis in Ethiopia, and their Escherichia coli K12 transconjugants. Resistance factors (R factors) were further characterized by incompatibility testing. Patterns of small plasmids, less than 15 kb, were similar within each of the individual S. boydii serotypes. Plasmids of about 3.3-3.7 kb were found in all strains of serotypes 2 and 4. Plasmids of about 4.3-4.6 kb were found in about 86% of strains. Serotypes 1, 2 and 3 were characterized by plasmids of about 5.6-5.7 kb. The 6.4-6.7 kb plasmid was found consistently in serotypes 1, 2, 3, 5, 8, 12 and 13 which were resistant to SSu or had an SSu resistance component in their phenotypes. Large plasmids (155-186 kb) were found in most S. boydii strains. Conjugative drug resistance plasmids, most often coding for three or less drugs, were found in about 26% of drug resistant strains. R-factors, coding for AT resistance (in types 2 and 8), and ASSuT resistance (in type 4), were compatible with all reference plasmids tested. Plasmids belonging to incompatibility groups X and N were found in serotypes 5 and 10, respectively.     

Morphology and serum dependence of cloned cell lines undergoing spontaneous malignant transformation in culture

A number of morphological changes were found to correlate with the occurrence of spontaneous neoplastic transformation in sublines of five rigidly isolated clones of mouse embryo fibroblasts. These morphological changes included increased cytoplasmic basophilia, reduced spreading of cells on the substrate, increased nuclear:cytoplasmic ratio, greater heterogeneity in the size and shape of cells and nuclei, and more random orientation of cells. Because these changes were reproducible, occurring in some sublines of all five clones, they have been described and illustrated to serve as a guide for identifying spontaneous transformants among rodent fibroblasts in culture. Neoplastic transformation was determined by the growth of the cells as malignant neoplasms in syngeneic hosts. The spontaneous transformants, as compared with nonneoplastic fibroblasts derived from the same cell, showed similar saturation densities and serum dependence. Some clones had a higher transformation frequency than the parental line, which remained nonneoplastic for years. Thus, the capacity for continuous growth in vitro can be independent of malignant potential. The use of horse serum as supplement to the medium did not accelerate or increase the frequency of neoplastic transformation.     

Somatic diversification and affinity maturation of IgM and IgG anti-DNA antibodies in murine lupus

Molecular events occurring during the process of generation of pathogenic immunoglobulin (Ig)G anti-DNA antibodies in systemic lupus erythematosus (SLE) were studied using a newly established method. We analyzed the Ig variable (V) region gene sequence and DNA-binding activity of IgM and IgG anti-DNA monoclonal antibodies (mAb) from individual SLE-prone (NZB x NZW) F1 mice. The first event appeared to be clonal selection and expansion of IgM anti-DNA clones, in which several clones had intraclonal V gene mutations. Although the number of mutations was small, the mutated IgM clones were associated with an increase in DNA-binding activity. The somatic mutations located in complementarity-determining regions (CDR) and in framework regions (FR) of V genes were apparently related to changes in DNA-binding activity. IgG anti-DNA clones that progressively increased in number with aging had numerous somatic mutations in the V region genes and there was a pair of clones which showed an intraclonal accumulation of mutations, in association with increase in the DNA-binding activity. All these findings show that somatic mutations associated with affinity maturation of the V region begin immediately before isotype-switching from IgM to IgG of the clones that have been selected and expanded, in an antigen-driven manner and/or by other forces. We propose that further accumulations of intraclonal somatic hypermutation, in association with selection and expansion of high affinity IgG clones, may lead to formation of highly pathogenic anti-DNA antibodies.     

Ear canal reflectance in the presence of spontaneous otoacoustic emissions. I. Limit-cycle oscillator model

Allen et al. [Abstract in Eighteenth Midwinter Research Meeting of the Association for Research in Otolaryngology, Des Moines, IA (1995)] have found that the ear canal reflectance passes through a minimum around the frequency of a spontaneous otoacoustic emission (SOAE). They considered this result to constitute evidence against active nonlinear cochlear function as the basis for SOAEs. In order to investigate theoretically the expected behavior of ear canal reflectance in the neighborhood of a SOAE associated with an active-nonlinear cochlea, we use a simplified model in which the ear drum end of the ear canal is effectively terminated by a nonlinear-active element. Under the influence of a sinusoidal driver at the entrance of the ear canal, this element will, to a good approximation, either (1) oscillate at both the frequency of the driver (at which the reflectance is determined) and the SOAE (at a suppressed level, corresponding to nonentrainment), or (2) be entrained and only oscillate at the driving frequency. The magnitude of the nonlinear ear canal reflectance is found to exceed unity only at sufficiently low stimulus levels, and occurs under conditions of entrainment and nonentrainment of the spontaneous emission. Otherwise, the reflectance is less than unity and, as a function of frequency, has a minimum around the SOAE frequency.     

Evaluation of cell-mediated immunity and circulating immune complexes as prognostic indicators in cancer patients

Cell-mediated immunity (CMI) and circulating immune complexes (CIC) were estimated in 55 cancer patients and 25 control volunteers to evaluate their prognostic significance. Cancer patients comprised head and neck cancer (11), breast cancer (13), gastrointestinal cancer (10), genitourinary cancer (11), and lymphomas and sarcomas (10). CMI was tested in vitro by early rosette-forming cells (ARFC) and total rosette-forming cell (TRFC) counts. ARFC count in control group was 758.1 +/- 78.09 cells/cumm. In advancing clinical stages of cancer (I-IV), ARFC counts were decreased (i.e., 601.12 +/- 74.96 [p < 0.01]; 494.8 +/- 71.83 [p < 0.001]; 432.44 +/- 36.05 [p < 0.001], and 438.55 +/- 69.99 [p < 0.001] cells/cumm, respectively). TRFC count in control group was 1029 +/- 88.39 cells/cumm. In cancer stages I through IV, these counts decreased significantly (i.e., 699.63 +/- 66.24; 597.55 +/- 82.9; 505.11 +/- 52.56; and 501.55 +/- 69.99 cells/cumm, respectively [p < 0.001]. Dinitrochlorobenzene cutaneous reactivity in vivo was 100% positive in control group, 62.5% positive in cancer stage I, 5% positive in stage II, and negative in stages III and IV. CIC of intermediate size were estimated by polyethylene glycol precipitation (PEG pptn) technique, which detects CIC in the ratio of 2:1 (Ag2Ab). Mean PEG index in control group was 39.5 +/- 4.65; sequential increase in CIC was observed in advancing clinical stages of cancer (I-IV)(i.e., 49 +/- 7.03 [p < 0.01]; 75.38 +/- 44.01 [p < 0.001]; 93.38 +/- 44.57 [p < 0.001]; and 216.00 +/- 147.05 [p < 0.001], respectively). Latex agglutination inhibition (LAI) titer was done to detect CIC as small as 8s, which constitute the opposite polar end of CIC spectrum. LAI titers in control group were nil. However, LAI titers in cancer stages I through IV were 1 +/- 2.64; 8.6 +/- 5.6 (p < 0.001); 12.00 +/- 8.11 (p < 0.001); and 25.77 +/- 9.06 (p < 0.001), respectively. Decrease in CMI and subsequent increase in CIC indicate unfavorable prognosis in cancer patients, and also precede clinical manifestation of increased tumor mass in vivo.     

Autologous platelet collection and storage to support thrombocytopenia in patients undergoing high-dose chemotherapy and circulating progenitor cell transplantation for high-risk breast cancer

The differential diagnosis of recurrent hepatitis C following orthotopic liver transplantation (OLT) may be difficult. We evaluated the diagnostic significance of IgM anti-hepatitis C virus (anti-HCV) core antibodies in 27 patients undergoing OLT because of HCV-associated cirrhosis. Serial serum samples collected before and after OLT were tested for the presence of IgM anti-HCV core antibodies. Results were compared with the histological evidence of liver damage, the presence, level, and genotype of serum HCV RNA and the degree of immunosuppression. All patients underwent recurrent HCV infection. Recurrent hepatitis was diagnosed histologically in 21 patients an average of 48 weeks after OLT (range 2-209 weeks): 18 had persistence or (re-)appearance of the IgM anti-HCV core after OLT, one lost the IgM anti-HCV core after OLT, and two never secreted IgM anti-HCV core either before or after OLT. The remaining six patients did not develop recurrent hepatitis after a follow-up of 44-241 weeks from OLT; in these patients, IgM anti-HCV core either disappeared (1 case) or decreased (1 case) after OLT or were persistently negative throughout the study (4 cases). Thus, 18/21 patients with recurrent hepatitis, but only one of six without recurrent hepatitis, secreted IgM anti-HCV core after OLT (P < 0.05). The IgM anti-HCV core levels were not correlated with the level or genotype of serum HCV RNA or the degree of immunosuppression. In conclusion, secretion of IgM anti-HCV core antibodies after OLT seems associated with recurrence of HCV-associated liver disease and may have diagnostic significance.     

Spindle and epithelioid cell nevi in children and adults. A review of 211 cases of the Spitz nevus

A large series of 211 Spitz nevi is reviewed. 30% of the lesions were from patients 20 years of age and over. The trunk and lower extremity were most commonly involved. There were no significant histologic differences between cases from adults and children. Features which may help in differentiating atypical Spitz nevi from malignant melanoma include the presence of some nevus cell maturity at the base, an absence of atypical mitoses, no significant upward epidermal spread and the nuclear chromatin pattern.     

Enhanced lymphoid cell recovery after bone marrow transplantation: correlation with the presence of costimulatory antibodies in serum

We describe a patient with T cell deficiency who underwent bone marrow transplantation (BMT) from an HLA-identical brother. The patient's white blood cell count recovered with exceptional rapidity post-BMT: after 7 to 9 days it rose sharply to 98x10(9) cells/L, 76% of which were mononuclear leukocytes. It then decreased, and a second peak was observed 250 days post-BMT. Lymphocytes from both peaks displayed a phenotype of mature T cells together with characteristics of a constitutively activated state; that is, they 1) exhibited high levels of tyrosine-phosphorylated T cell receptor (TCR) zeta chain, 2) spontaneously secreted IL-2, 3) expressed activation specific cell surface markers, and 4) were unresponsive to in vitro stimuli. The increased cell counts in both peaks correlated with the presence of anti-lymphocytic antibodies in the patient's serum, which reacted with peripheral blood lymphocytes (PBLs) both from the donor and from unrelated individuals. These antibodies were present before BMT and reappeared post-BMT. Variable number tandem repeats analysis revealed that the patient's PBLs were chimeras for up to 2 years post-BMT. This finding could explain the newly synthesized post-BMT anti-lymphocytic antibodies and the appearance of the second WBC peak during that period. The patient's anti-lymphocytic antibodies displayed costimulatory activity, enhancing the in vitro proliferation of normal T cells suboptimally activated via the TCR. The unique characteristics of these antibodies could explain the enhanced T cell recovery observed post-BMT as well as the constitutive activation state of these cells. Furthermore, such antibodies may eventually facilitate development of a therapeutic method for inducing enhanced post-BMT recovery.     

Cellular immunity in pregnancy: subpopulations of T lymphocytes bearing Fc receptors for IgG and IgM in pregnant women

Studies on the change of peripheral T and B lymphocytes and T cells bearing Fc receptors for IgG and IgM in pregnant women were performed by using rosette-formation tests. There was no significant difference in the proportion of T and B lymphocytes between pregnant and non-pregnant women. The percentage of T cells bearing Fc receptors for IgG in the T lymphocytes which are considered to have suppressive activity increased in the various stages of pregnancy and post-partum as compared with that in non-pregnant women. On the contrary, the percentage of T cells bearing Fc receptors for IgM in the T lymphocytes which have a helper function decreased in pregnant and post-partum women. The results of this investigation suggest that the depression of cell-mediated immunity during pregnancy depends on the qualitative change of T lymphocytes, i.e. increased suppressor and decreased helper T lymphocyte subpopulations.     

Candiduria in non-neutropenic critically-ill surgical patients. Detection of IgA, IgG and IgM antibodies to Candida albicans by germ tube immunofluorescence

The significance of indirect immunofluorescence using Candida albicans germ tube as well as blastospore antigens in the diagnosis of isolated candiduria in non-neutropenic, critically-ill surgical patients was assessed. Ten patients with isolated candiduria, 12 with systemic candidosis and 10 with multifocal muco-cutaneous candidosis were included in the study. The sera of another 10 critically-ill patients with no signs of candidosis served as controls. The patients' sera were tested for IgG, IgA and IgM antibodies. The results obtained confirmed that indirect germ tube immunofluorescence is a useful procedure for differentiating systemic candidosis from colonisation of the urinary tract. Indirect immunofluorescence with blastospores, although more sensitive than germ tube immunofluorescence, cannot distinguish muco-cutaneous candidosis from systemic candidosis. Therefore, indirect germ tube immunofluorescence is regarded a useful complementary test to evaluate candiduria in non-neutropenic, HIV-negative, critically ill patients.     

Quantitative analysis of cellular proliferative activity in 35 T-cell non-Hodgkin's lymphomas. Use of proliferating cell nuclear antigen and Ki-67 (MIB-1) antibodies and nucleolar organizer regions

OBJECTIVE: To analyze-cellular proliferation in non-Hodgkin's lymphoma (NHL) of T-cell origin using three variables available on histologic paraffin, dewaxed sections. STUDY DESIGN: The study group consisted of 35 T NHLs (22 low and 13 high grade). Two immunohistochemical methods established the percentage of cells expressing proliferating cellular nuclear antigen (PCNA), or PCNA index, and the Ki-67 antigen, or MIB-1 index. The third method quantified nucleolar organizer regions (NORs) with an image analyzer, giving the NOR area and number of NORs; an internal reference on lymphocytes was used. RESULTS: For the PCNA index, each subtype of low grade NHL demonstrated a difference as compared with high grade NHL except for angioimmunoblastic type NHL (AILD). The difference between the two grades became significant after including AILD-type NHL within high grade NHL (P = .02). The MIB-1 index gave similar results. The PCNA index and MIB-1 correlated (r = .55, P = .008). The relative NOR area and number of NORs differed significantly between the two grades (P < 10(-4) and P < 10(-2); the absolute NOR area differed to a lesser degree (P = .02), and no difference was observed for the absolute number of NORs (P = .07), stressing the importance of an internal reference. NOR areas and numbers correlated highly (r = .90 for relative and .78 for absolute variables, P < 10(-4)). No relation was found between PCNA and MIB-1 indexes. CONCLUSION: Correlations between these variables and grades of malignancy, between the two indices with each other and between the AgNOR variables with each other, including referring to internal lymphocytes, were reported for these T NHL-like tumors in studies on B NHL. The proliferative character of the AILD-type T NHL was in accordance with their worse prognosis. The absence of a correlation between PCNA or MIB-1 indices and NOR variables may reflect a biologic difference between B and T NHLs in a shorter cell cycle or more important functional activity in T NHL.     

Prevalence of IgG and IgM anti-Toxoplasma antibodies in patients with HIV and acquired immunodeficiency syndrome (AIDS)

OBJECTIVE/STUDY DESIGN: After blood loss, production of erythropoietin in adults increases, which accelerates erythropoiesis and restores the erythroid mass. It is unclear whether preterm infants with large phlebotomy losses have a similar response. We therefore measured serum erythropoietin concentrations in 11 ill preterm infants (1057 +/- 167 gm) as their phlebotomy losses accumulated. RESULTS: Before the first transfusion, erythropoietin concentrations were 68.9 +/- 36.2 mU/ml (range 0 to 205 mU/ml) at 5 ml/kg blood out, 17.4 +/- 8.9 mU/ml at 10 ml/kg, and 4.8 +/- 2.6 mU/ml at 15 ml/kg. Erythropoietin concentrations did not increase in any patients despite increasing phlebotomy losses. CONCLUSION: Serum erythropoietin concentrations in ill preterm infants do not increase in the face of significant blood loss. Although the mechanistic explanation for this failure is unclear, it likely contributes to the transfusion requirements of this population.     

Evidence for the presence of immunoglobulin E antibodies specific to the cell wall phosphomannoproteins of Candida albicans in patients with allergies

To determine the major antigenic component of Candida albicans against immunoglobulin E (IgE) antibodies in the sera of patients with allergies who were positive for IgE antibodies to C. albicans crude antigen in a CAP system, phosphomannoproteins (CAMP/A or CAMP/B for serotype A or B strain, respectively) and their acid-stable portions (CAMP-S/A or CAMP-S/B) were isolated from beta-mercaptoethanol (2-ME) extracts of C. albicans cells of serotypes A and B, and IgE antibodies against these components were compared with those against protein complex and enolase (CAE) fractions isolated from C. albicans cells. The dot blot test, which was used to detect IgE antibodies to the C. albicans antigens, showed that IgE antibodies to the 2-ME extract and phosphomannoprotein fractions were present in the sera of 98.0% (2-ME extract), 96.8% (CAMP/A), 93.2% (CAMP-S/A), 97.2% (CAMP/B), and 81.5% (CAMP-S/B) of the patients, whereas IgE antibodies to the protein complex and CAE fractions were found in the sera of 73.6 and 48.8% of the patients, respectively. The extent of IgE binding to the 2-ME extract and phosphomannoproteins was well correlated with the fluorescence intensities estimated with the CAP system. Furthermore, the results obtained from the inhibition experiment with the CAP system indicated that the binding of IgE antibodies to Candida antigens is strongly inhibited by the phosphomannoprotein fraction and is an indication that the serum of the patients contained IgE antibodies specific to the cell wall phosphomannoproteins of C. albicans. Finally, an initial chemical analysis indicated that the epitopes for IgE antibodies on the phosphomannoproteins is a carbohydrate portion, since the ability of CAMP/A to inhibit the binding of IgE antibodies to the homologous CAMP/A was destroyed after oxidation by sodium periodate but not after digestion with proteinase K.     

Studies of immunoglobulins, bentonite flocculation and IgE, IgG and IgM antibodies in serum from patients with trichinosis

Serial serum samples were obtained from two patients from a family of four who ingested raw pork at a known time and in whom trichinosis developed. Single and occasionally two serum samples were obtained from other patients with proved trichinosis. Studies of these serum samples showed that elevations of serum immunoglobulin E (IgE) levels do occur but not in all serum samples and that even when these levels are elevated, they are not high enough to be of diagnostic value. This is also true for serum immunoglobulin M (IgM). Using a solid phase radioimmunoadsorbent test, IgE, IgG and IgM antibodies were detected in the serums. The IgE antibody activity appeared early but was not present in all samples. The IgM antibody activity appeared later than the IgE and IgG antibody activity, and there was a statistically significant correlation between IgM antibodies as determined by radioimmunoassay and the bentonite flocculation titers suggesting that the bentonite flocculation is due to IgM antibody. IgM antibodies detected by radioimmunoassay were positive in all serum samples from patients with trichinosis except for a sample obtained 3 days after the onset of symptoms. The early increase in IgG antibodies and the occurrence of these antibodies in all serum samples obtained more than 3 days after onset of symptoms suggest a potential diagnostic use if serial samples are available early in the course of the disease.     

Alterations in the number of circulating leucocytes, phenotype of monocyte and cytokine production in patients undergoing cardiothoracic surgery

Organogenesis in plants occurs at the shoot apical meristem, a group of indeterminate stem cells that are organized during embryogenesis. Regulated initiation of leaves or flowers from the shoot meristem gives rise to the familiar geometric patterns observed throughout the plant kingdom. The mechanism by which these patterns, termed phyllotaxies, are generated, remains unclear. Maize plants initiate leaves singly, alternating from one side to the other in a regular pattern. Here we describe a recessive maize mutant, abphyl1, that initiates leaves in opposite pairs, in a pattern termed decussate phyllotaxy. The decussate shoot meristems are larger than normal throughout development, though the general structure and organization of the meristem is not altered. abph1 mutants are first distinguished during embryogenesis, prior to true leaf initiation, by a larger shoot meristem and coincident larger expression domain of the homeobox gene knotted1. Therefore, the abph1 gene regulates morphogenesis in the embryo, and plays a role in determining the phyllotaxy of the shoot.     

Prevalence of specific anti-Cryptosporidium IgG, IgM and IgA antibodies in cat sera using an indirect immunofluorescence antibody test

Sera from 258 healthy and sick domestic and feral cats were screened for specific anti-Cryptosporidium antibodies using an indirect immunofluorescence antibody test (IFA). Sera were positive for IgG, IgM and IgA antibodies in 192 (74%), 84 (32%) and 67 (26%) samples, respectively. Antibody was not detected at dilutions of 1:10 and 1:20 or greater in any of eight specific pathogen-free kittens. IgM and IgA antibody classes were more prevalent in sick than in healthy domestic cats. The presence of IgM and/or IgA antibodies indicated early infection. However, these antibody classes were present in sera from cats either positive or negative for Cryptosporidium infection by faecal examination. Pronounced polar fluorescence was observed in the sporozoites in positive samples under fluorescence microscopy. The higher prevalence of specific anti-Cryptosporidium antibodies and the absence of Cryptosporidium oocysts in faecal samples from some IFA-positive animals suggests that detection of these antibodies in sera from cats could be helpful for the diagnosis of feline cryptosporidiosis.     

Cell interaction in tumor allograft immunity. Suppressor cell in the spleen of allogeneic tumor-sensitized mice

It is known that the myocardial necrosis of potassium depletion heals by reconstitution and not by scarring, when animals are replenished with potassium. In the course of studies on DOCA-induced myofibrillar degeneration, we found that a membrane-like structure persisted in the area where the disintegrating myofiber was being removed by macrophages. This structure resembled the basal lamina, and enclosed a space in which macrophages with phagosomes containing disintegrating myofibral constituents were seen in association with undifferentiated cells. We postulate that this basal lamina-like structure along with the undifferentiated cells, play a role in the reconstitution of the myocardium during the stage of potassium repletion, and that the scaffolding by basal lamina may be effective in myocardial reconstitution.