Expression of surfactant associated protein-A and Clara cell 10 kilodalton mRNA in neoplastic and non-neoplastic human lung tissue as detected by in situ hybridization.

Two markers for the progenitor cells of peripheral airways and their tumors are the 10 kilodalton (kd) Clara cell protein and the major surfactant associated protein-A (SP-A). We used the RNA-RNA in situ hybridization technique to study expression of the genes encoding these proteins at the cellular level in 19 pairs of non-neoplastic and neoplastic tissues from resected human lungs. Our results show that in non-neoplastic lung tissue, the Clara 10 kd protein gene was expressed in nonciliated cells of both bronchial and bronchiolar epithelium, indicating that, in contrast to previous assumptions, cells with Clara cell-like differentiation in humans may not be restricted to bronchiolar cells. The incidence of Clara 10 kd protein gene expression, as detected in lung carcinomas (1 out of 19 cases positive) was less than expected based on previous ultrastructural reports. The SP-A gene was strongly expressed in normal alveolar type II cells in non-neoplastic lung and, at higher levels, in hyperplastic cells. In addition, SP-A mRNA expression was observed in scattered bronchial and bronchiolar epithelial cells in 40% of the airways examined. Five out of 17 lung tumors, all of which were adenocarcinomas, were positive for SP-A expression, albeit generally less intense than type II cells. This expression was seen in carcinomas with papillolepidic as well as solid and glandular growth patterns. Our findings provide new insights into the peripheral airway cell differentiation.     

Multiple chromosome aberrations in an infant with acute monoblastic leukemia

A male infant was diagnosed at age 16 months with acute monoblastic leukemia. At diagnosis, studies of bone marrow revealed multiple chromosome aberrations: 48,XY,+8,+19,t(4;11). Chromosome studies have been repeated at remission and relapse over the course of his disease. To our knowledge, this combination of chromosome abnormalities has not been previously reported.     

Detection of Cattle Naturally Infected with Anaplasma marginale in a Region of Endemicity by Nested PCR and a Competitive Enzyme-Linked Immunosorbent Assay Using Recombinant Major Surface Protein 5

A competitive enzyme-linked immunosorbent assay using recombinant major surface protein 5 (rMSP5-cELISA) of Anaplasma marginale was validated in a naturally infected cattle herd in an area of eastern Oregon where A. marginale is endemic. The true positive and negative A. marginale infection status of 235 randomly selected cattle was determined by using a nested PCR (nPCR) coupled with msp5 sequence analysis and hybridization. Judgment of the reliability of the nPCR and hybridization for detection of persistent infections was based on three observations. First, the nPCR was able to detect as few as 30 infected erythrocytes per ml. Second, the nPCR was able to consistently detect low levels of rickettsemia in seven carrier cattle experimentally infected with A. marginale. Third, msp5 sequence analysis showed >95% identity among 30 nPCR amplicons from cattle naturally infected with field strains of A. marginale. The nPCR and hybridization identified 151 infected and 84 uninfected cattle among the 235 animals tested. With a cutoff point of 28%, the rMSP5-cELISA showed a sensitivity of 96% and a specificity of 95%. These results indicate that the rMSP5-cELISA can sensitively and specifically detect cattle with naturally acquired persistent A. marginale infections and suggest that it is an excellent assay for epidemiological studies, eradication programs, and regulation of international cattle movement.     

In Vivo Binding of Immunoglobulin M to the Surfaces of Babesia bigemina-Infected Erythrocytes

Babesia bigemina infection of mature bovine erythrocytes results in new proteins specifically exposed on the parasitized cell surface. Monoclonal antibody (MAb) 64/32 binds a protein, designated p94, on B. bigemina-infected erythrocytes but not on either uninfected or B. bovis-parasitized erythrocytes. However, p94 was not encoded by B. bigemina and was not a parasite-modified erythrocyte membrane protein. In contrast, we showed that p94 could be eluted from the infected erythrocyte surface and was identified as specifically bound immunoglobulin M (IgM) heavy chain for the following reasons: (i) MAb 64/32 bound a reduced molecule of 94 kDa in both infected erythrocyte lysates and normal bovine serum; (ii) MAb 64/32 bound a 94-kDa molecule in reduced preparations of purified IgM; (iii) an anti-bovine μ heavy-chain MAb, BIg73, reacted specifically with the surface of infected erythrocytes and bound the 94-kDa molecule in lysates of infected erythrocytes, normal bovine serum, and purified IgM; and (iv) immunoprecipitation of infected erythrocyte lysates with MAb 64/32 depleted the 94-kDa antigen bound by anti-μ MAb BIg73 and vice versa. Binding of IgM to the infected erythrocyte surface was detected in vivo early in acute parasitemia and occurred during both the trophozoite and merozoite stages of intraerythrocytic parasitism. The common feature of IgM binding to the parasitized erythrocyte surface among otherwise genetically and antigenically distinct B. bigemina strains is suggestive of an advantageous role in parasite survival in vivo.     

Significant postoperative refractive errors in vivo with the Mentor Memorylens intraocular lens

PURPOSE: To determine the difference between the predicted and postoperative refraction in eyes after implantation of the Mentor MemoryLens intraocular lens (IOL) and compare these results with those of 2 other types of foldable IOLs implanted by the same surgeons. SETTING: Community-based group practice ophthalmology clinic. METHODS: All operated eyes (341) of all patients who had routine phacoemulsification with implantation of a MemoryLens IOL performed by 1 of 2 surgeons were evaluated retrospectively. The predicted refractive error and actual postoperative refractive error were compared in each eye in the MemoryLens group and in 2 smaller control groups with an AcrySof acrylic (Alcon) or SI-40 silicone (Allergan Medical Optics) IOL implanted by the same surgeons using identical technique and IOL calculation parameters. Patients in whom the difference between the predicted and actual postoperative refraction fell significantly outside expected parameters were rechecked with repeat axial length and keratometric readings, and these measurements were used to back-calculate the effective in vivo IOL power. RESULTS: The MemoryLens group had significantly greater variability in postoperative refractive results from those predicted by the Hoffer program than the 2 control groups. The postoperative refractive error in the MemoryLens group differed from +1.50 to -5.50 diopters (D) from that predicted by the IOL calculation formulas. When the outlier groups (ie, greater than +0.50 D or less than -1.00 D from predicted refractive error) were evaluated and compared to the rest of the MemoryLens group and the 2 control groups, no significant difference in axial length, keratometric measurements, operative surgeon, surgical technique, or patient age was found. Repeat axial length and keratometric measurements in the outlier group were not significantly different from those in the same eyes preoperatively. Back-calculation using postoperative axial length and keratometric measurements in the highly myopic outlier group showed that the mean difference between the labeled IOL power and actual in vivo IOL power in the outlier group was -3.08 D (range -1.98 to -7.54 D). The best corrected visual acuity was not affected in patients in the outlier groups despite the refractive variability. CONCLUSION: The variation in postoperative refractive results in the MemoryLens group was significantly greater than in the 2 other foldable IOL groups.     

Tuberculosis of the larynx.

Tuberculosis of the larynx, once a common disease, has become quite rare with the advent of anti-tuberculous chemotherapy. In the pre-antibiotic era two modes of laryngeal infection were recognized; bronchogenic and hematogenous. The literature is briefly reviewed. Thirteen patients in the past 15 years in whom tuberculous laryngitis was diagnosed upon indirect laryngoscopy by members of the University of Michigan Department of Otorhinolaryngology are presented. Bronchogenic infection was present in 11, and in two patients the disease was consistent with hematogenous spread. Tissue biopsy from a case of bronchogenic contamination demonstrated epithelioid tubercles, while numerous subepithelial acid-fast bacilli without typical tuberculous histological change were present in a case of hematogenous laryngeal infection. A case of cicatricial laryngeal stenosis was successfully treated surgically by laryngofissure, excision of fibrosis with arytenoidectomy, and free mucous membrane grafting. Finally, the initial subtle presentation of many of our patients emphasizes the importance of a consideration of tuberculosis in the differential diagnosis of chronic laryngitis.     

Age, sex, and season of onset of juvenile diabetes in different geographic areas.

Age, sex, and estimated time of onset of insulin-dependent diabetes were determined for children in Pittsburgh (N = 673), Gainesville (N = 976), Galveston (n = 741), and Melbourne (N = 851). The US cities had a decrease in new cases during the summer and peak incidence in January through April. In Melbourne, monthly trends were reversed: there were more cases during May through August. In US cities, but not in Melbourne, children less than 6 years old showed a greater variation by season than children 6 years old and older. Observations of the same fall and winter onset (in different calendar months) of insulin-dependent diabetes in Australia and the United States, and exaggeration of seasonal differences in young US children, suggest that onset of insulin-dependent diabetes is associated with seasonally varying viral diseases. Mumps and rubella infections do not seem to be responsible for much of the seasonal variation. Seasonal peaks of mumps and rubella are later than those observed for insulin-dependent diabetes, and immunization with live mumps and rubella viruses has not been associated with changes in incidence of insulin-dependent diabetes. An increase in disease incidence in boys over girls below age 6 years and in girls over boys at ages 6 through 11 years was consistently observed but not explained.