Impact of diagnostic immunohistochemistry on the recognition and management of two cases of thyroid cancer with protracted courses

This report presents two cancer cases with protracted courses in which diagnostic immunohistochemistry for thyroglobulin and/or calcitonin was performed several years after the original light microscopic interpretation. In both cases, diagnostic immunohistochemistry suggested significant changes in tumor classification. In light of current controversies and interpretive problems in this area, confirmatory tests for serum calcitonin and serum thyroglobulin and scans for iodine 131 uptake were performed. These confirmed the immunohistochemical evidence, and led to major changes in patient management. Several similar cases were found in the literature. In cancer cases with a protracted course, but with atypical or discordant clinical and/or pathologic features, diagnostic immunohistochemistry for thyroid markers may merit consideration because of the potential for meaningful changes in clinical management.     

Identification of a gene disrupted by a microdeletion in a patient with X-linked retinitis pigmentosa (XLRP)

The gene for the most frequent from of X-linked retinitis pigmentosa (XLRP), RP3, has been assigned by genetic and physical mapping to a segment of less than 1000 kbp, which is flanked by the marker DXS1110 and the ornithine transcarbamylase (OTC) gene. In search of microdeletions, we have screened the DNA of 30 unrelated patients with XLRP by employing a representative set of YAC-derived DNA fragments that were generated by restriction enzyme digestion and PCR amplification. In one of these patients, a 6.4 kbp microdeletion was detected which was not present in the DNA of 444 male controls. A cosmid contig spanning the deletion was constructed and used to isolate cDNAs from retina-specific libraries. Exons corresponding to these expressed sequences as well as other putative exons were identified by sequencing more than 30 kbp of the critical region. So far, no point mutations in these putative exon sequences have been identified.      

Trisomy of the short arm of chromosome 8: Association with translocation between chromosomes 8 and 22 46,XY,22−,t(8p22q)+

The case of a retarded child with trisomy of the short arm of chromosome 8 associated with translocation between the short arm of chromosome 8 and the long arm of chromosome 22 is reported. Balanced translocation involving the same chromosomes was present in the mother and brother of the propositus. The specific chromosomes involved in the abnormality in this family were identified by use of fluorescence microscopy with quinacrine mustard staining, autoradiography and Giemsa banding. This appears to be the first case report of this anomaly, although trisomy of the short arm of chromosome 9 has been reported previously.     

The effect of Levamisole on peripheral blood lymphocyte subpopulations in patients with rheumatoid arthritis and ankylosing spondylitis.

Although Levamisole, an antihelmintic drug, has shown to have some modulatory effect on the immune response in clinical trials and experimental models, its mode of action remains obscure. In a group of fifteen patients with rheumatoid arthritis and ankylosing spondylitis receiving Levamisole on an intermittant regime, simultaneous determinations of the lymphocyte subpopulations were made prior to Levamisole administration and 3 months thereafter. No significant changes were observed either in the absolute or in the relative number of T- and B-cell populations, while a statistically significant reduction was found in the "null" cells. These findings suggest that the immune potentiating effect of Levamisole may at least partially be due to a maturation process of the "null" cells.     

Psychosis as a predictor of response to lithium maintenance treatment in bipolar affective disorder

Sixty-six bipolar I lithium clinic patients were studied for a history of psychotic symptoms at some time during the course of their illness. Agreement between different sources of information was calculated, and the patient population was divided into psychotic and non-psychotic subgroups. Probability of remaining well on lithium for the different subgroups was analyzed by the life table method. Psychosis during mania appeared to be associated with especially good early lithium prophylaxis.     

Initial organ localisation of blood-borne Candida albicans in a rat model of disseminated candidosis.

The rat was evaluated as an experimental model for disseminated candidosis by quantitating blood clearance and initial organ localisation of 3H-leucine-labelled Candida albicans after intravenous injection into the tail or portal vein. Viable or formalin-killed blastoconidia or viable blastoconidia with germ tubes were injected into experimental animals. Blood and tissue samples were obtained up to 24 h after injection and processed for liquid scintillation counting (to determine the distribution of labelled yeasts) and quantitation of viable organisms. Yeasts were cleared rapidly after intravenous (i.v.) injection by either route, i.e., < 5% of the radioactivity was detected in the blood after 5 min. The liver and lung were the major organs that sequestered blood-borne yeasts 1 h after tail vein injection (42.5 SD 15% and 41.4 SD 6.4% of labelled yeasts injected, respectively). However, injections via the portal vein resulted in trapping of the yeasts predominantly by the liver. Recovery of radioactivity and viable yeasts from all organs except the kidneys decreased with time. Overall, the results indicated that the rat might serve as a reliable model for short-term studies on organ distribution and thus contribute to our understanding of tissue trophism in candidosis.     

A block in glycoprotein processing correlates with small plaque morphology and virion targetting to cell-cell junctions for an oral and an anal strain of herpes simplex virus type-1

Summary The characteristics of two clinical isolates of HSV-1 obtained from an oral (424) and an anal (490) lesion were compared with the highly passaged KOS strain. In contrast to KOS, the clinical isolates produced small plaques, were more cell-associated and the predominant viral glycoprotein species for gC and gD in infected cell lysates was the precursor, high mannose glycoform. Total virus production in Vero cells was equivalent for the three virus strains in one-step growths. Pulse-chase studies of glycoprotein C processing showed a reduction in rate at 7.5h post infection and a significant block in processing at 10.5h post infection for 424 and 490 but not KOS. Similar results were obtained for gD. The significant reduction in glycoprotein processing for 424 and 490 suggests a block in transport of viral glycoproteins or virions to and through the Golgi apparatus. Extracellular virions and the cell surface, prior to cell lysis, contained the processed gC glycoform suggesting a competent cellular glycan processing system. Upon co-infection of 424 or 490 with KOS or a gC^– KOS strain, gC was processed to levels equivalent to KOS indicating that 424 and 490 are not inhibitory but that an activity(s) encoded by KOS facilitates maturation of gC from 424 and 490. Unlike KOS infected Vero cells, virion-containing vacuoles were observed in the cytoplasm at 12h p.i. and extracellular virions were concentrated at cell-cell junctions of 424 or 490 infected cells but not in the perinuclear region. These results suggest that intracellular transport of viral glycoproteins and virions in 424 and 490 infected cells is different from KOS infected cells. The reduced level of viral glycoprotein maturation, virus release, cell surface presence and presence of virions at cell-cell junctions are consistent with small plaque production in tissue culture cells.Portions of this work were presented in the 17th International Herpesvirus Workshop, Pittsburgh, PA, 1993.     

Neonatal social isolation alters both maternal and pup behaviors in rats

The development of emotional behavior is dependent on the early experiences of the infant and the quality of maternal care. In these experiments, the effects of social isolation during the preweaning period on both pup behavior and maternal responsivity were examined. In the first study, the number of ultrasonic vocalizations (USVs) emitted after brief maternal separation was measured in neonatal rats with differing histories of social isolation. The social isolation procedure consisted of 5 days of daily separation from the dam and littermates for either 3 or 6 hr. At both ages tested, socially isolated pups vocalized significantly less than control pups. In the second study, the effects of prior isolation either daily for 5 previous days (Chronic Isolation) or for 4 hr prior to testing (Acute Isolation) were examined in a T-maze choice test. Pup vocalizations in the presence of the dam and dams' maternal behavior were assessed. When the dam was confined to the start box or during the maternal free access period, both Chronic and Acute Isolates vocalized less than pups that had never left the home nest. Dams spent more time with and licked and groomed more frequently and for a longer time both Chronic and Acute Isolates compared to pups that had always been with dams in the home nest. These results suggest that early isolation experience can alter subsequent responses to separation stress in neonatal rats and that maternal behavior is sensitive to the prior experiences of offspring.     

Cardiac isoenzyme methodology and the diagnosis of acute myocardial infarction

In view of rapidly evolving technology, a thorough appreciation of the subtle nuances of isoenzyme analysis is mandatory in the selection of appropriate methods. The effectiveness of a given laboratory in diagnosing and monitoring ischemic heart disease is related to the sensitivity and specificity of the methods employed. The occurrence of variants of creatine kinase will decrease the specificity of some isoenzyme methods. This study compares the sensitivity and efficiency of four methods for CK-MB and two methods for LD isoenzymes currently available to the laboratory community. The significance of isoenzyme patterns in confirming myocardial infarction was compared with other cardiac diagnostic parameters to determine the most effective laboratory methods. The selection of methods for measurement of cardiac isoenzymes will determine the effectiveness of the laboratory in the diagnosis of myocardial infarction.     

Nutzung von Gen5 und Gen6 ts-Mutanten des Phagen T3 für die Anzeige von Hemmstoffen der DNS-Synthese

In an enzyme-specific drug screening system nalidixic acid and 3'FTdR, inhibitors of DNA synthesis, both reduce the growth of wild type and temperature-sensitive point mutants of phage T3 with different efficiencies. The wild type shows the strongest sensitivity against the drugs, while an exonuclease mutant is the most insensitive variant. The DNA polymerase mutants exhibit an intermediate degree of inhibition. The anthracycline antibiotics violamycin BI and adriblastin which preferentially inhibit RNA synthesis show the same degree of inhibition for all mutants. This is true also for the RNA synthesis inhibitor lambdamycin, which is identical with chartreusin. The protein synthesis inhibitors chloramphenicol and o-phenanthroline, a chelating agent, impair all mutants to the same extent. Our data confirm the hypothesis that structural variants of essential viral enzymes, when compared with the wild type should sensitivities against specific inhibitors and show that this T3 system could be used for the indication of specific inhibitors of DNA synthesis.