Identification of marker chromosomes and translocations in man using a computerized diagnostic database and fluorescent in situ hybridization

BACKGROUND: Many species of bats have two sets of submandibular glands, principal and accessory. The accessory gland may resemble the principal one but more often shows wide morphological divergence. The free-tailed bat, Tadarida thersites, is very unusual in that it has two sets of parotid glands rather than binary submandibular glands. We studied the ultrastructure of the principal parotid gland to establish a baseline for comparison with the accessory parotid. METHODS: Two specimens of adult free-tailed bats, one male and one female, were live-trapped in western Kenya. Parotid glands were fixed for electron microscopy using a protocol expressly designed for field fixation and then embedded by conventional means. RESULTS: Histologically, the principal parotid is a typical serous gland. The secretory granules of the endpiece cells have an unusual substructure in that they contain variable numbers of lucent halos and one or several spherules. Intercalated duct cells contain a significant number of dense, serous-like granules. Striated ducts have the usual basal configuration of mitochondria and folded plasma membranes, but the supranuclear cytoplasm contains many small, dense granules, so that these ducts resemble the granular convoluted tubules found in the submandibular glands of many families of rodents. The apices of the duct cells have a peculiar contour--the luminal surfaces obliquely invaginate into the apical cytoplasm, so that in thin section the luminal membranes appear to be underlaid by a layer of vacuoles. CONCLUSION: Although the principal parotid gland of the free-tailed bat shows some distinctive, species-specific ultrastructural features, it basically is similar to the parotid gland in two other molossid bats, Tadarida brasiliensis and Molossus molossus. The distinctive features in the principal parotid gland of T. thersites might relate to its feeding on hard-bodied insects and perhaps to the production of lysozyme.     

Serological properties of HIV-1 isolates from the focus of an epidemic in the Gomel region of the Belarus Republic (1996)

Immunoreactivity of sera obtained in 1996 from HIV-1-infected intravenous narcomaniacs from an epidemic focus in Gomel region, Belarus, is studied with a panel of 10-16-component synthetic peptides simulating apical epitope of surface glycoprotein gp120 V3 loop of HIV-1 variants. Comparative analysis of resultant spectra with representative immunoreactivity spectra of sera from a sampling of HIV-1-positive sera collected in 1986-1997 in different regions of the former USSR demonstrated a high homogeneity of immunoreactivity spectra of sera from Gomel region. Serotypes of HIV-1 A/C variants circulating in populations of intravenous narcomaniacs in the focus in Gomel region in 1996 and in Southern and South-Eastern Ukraine in 1995-1996 are similar. This confirms a previous conclusion about the prevalence of A/C serotype among intravenous narcomaniacs in the former USSR.     

Increased immune activation precedes the inflection point of CD4 T cells and the increased serum virus load in human immunodeficiency virus infection

In sickness-conditioned learning, animals become ill after sampling a new substance and develop an aversion that is expressed as avoidance of that substance in subsequent presentations. We examined the parameters of a one-trial, nongustatory, sickness-conditioned learning task in day-old chicks. Chicks pecked a bead and were made ill by i.p. injection of lithium chloride (LiCl). Both 0.5 and 1.0 M LiCl (0.1 ml) produced reliable avoidance at test. Chicks injected with LiCl between 15 and 45 min after training avoided the bead at test, whereas those injected within 5 or 10 min or more than 45 min after training did not. Avoidance was present until 24 h posttraining and absent after 48 h. Therefore, robust learning of the sickness-conditioned learning task occurs in one trial without the need for gustatory cues, and memory for the task lasts at least 24 h. Uses of this task to study memory formation in the day-old chick are discussed.     

Embryonic cardiomyocyte hypoplasia and craniofacial defects in G alpha q/G alpha 11-mutant mice

Heterotrimeric G proteins of the Gq class have been implicated in signaling pathways regulating cardiac growth under physiological and pathological conditions. Knockout mice carrying inactivating mutations in both of the widely expressed G alpha q class genes, G alpha q and G alpha 11, demonstrate that at least two active alleles of these genes are required for extrauterine life. Mice carrying only one intact allele [G alpha q(-/+);G alpha 11(-/-) or G alpha q(-/-);G alpha 11(-/+)] died shortly after birth. These mutants showed a high incidence of cardiac malformation. In addition, G alpha q(-/-);G alpha 11(-/+) newborns suffered from craniofacial defects. Mice lacking both G alpha q and G alpha 11 [G alpha q(-/-);G alpha 11(-/-)] died at embryonic day 11 due to cardiomyocyte hypoplasia. These data demonstrate overlap in G alpha q and G alpha 11 gene functions and indicate that the Gq class of G proteins plays a crucial role in cardiac growth and development.     

Synthesis of new bifunctional compounds which selectively alkylate guanines in DNA

The aim of this work was to develop new bifunctional alkylating agents which damage DNA in a selective manner. In order to extend our previously published work on conformationally restricted nitrogen mustards containing one piperidine ring, new bispiperidine derivatives were designed with varying lengths of carbon chain between the two rings and structure-activity relationships in these systems were studied. Thus samples of new bispiperidine salts 22-26 with chloromethyl groups at the 2-positions and a bridge between the two nitrogen atoms of 2-6 carbon atoms were synthesized. The analogous new bis(p-nitrophenylcarbamates) 17-21 were also prepared. The free bases were designed to be bifunctional alkylating agents via aziridinium ion formation with different distances between the two alkylating sites. The bispiperidines 22-24 were shown to alkylate guanines at the 7-position in the major groove of DNA more selectively than melphalan. The bispiperidine 22 with the shortest two carbon bridge was the most reactive but it was less cytotoxic than melphalan in a human colon carcinoma cell line (IC50 value approximately 30 microM) and in a human chronic myeloid leukaemia cell line (IC50 value approximately 12 microM). The most cytotoxic compound in the latter cell line was the carbamate 17, with an IC50 value of approximately 0.3 microM, and carbamates 17, 19 and 20 were most potent in a panel of human ovarian carcinoma cell lines. These compounds also showed circumvention of acquired cisplatin resistance in three paired cell lines. The carbamates 17-21, however, were less efficient at alkylating and cross-linking naked DNA than the bispiperidines 22-26.     

Preoperative irradiation therapy and radical hysterectomy: prognostic value of tumor regression after initial irradiation of squamous cell carcinoma of the cervix

OBJECTIVE: To investigate the role of tumor persistence in patients submitted to irradiation therapy and radical hysterectomy. DESIGN: A retrospective analysis of prognostic factors. LOCATION: Hospital A.C. Camargo, S?o Paulo, Brazil, a private non-profitmaking foundation and tertiary referral centre. PATIENTS: A total of 629 cases of invasive squamous cell carcinoma of the cervix were studied. Criteria for inclusion in the study were: confirmed histological diagnosis of squamous cell carcinoma and no previous treatment (except for preoperative radiotherapy carried out at the Hospital A.C. Camargo itself). At the end of the follow-up period, 410 patients (65%) had no evidence of disease and 219 (34.8%) had died because of the tumor. INTERVENTION: The patients were submitted to radical surgery and radiation therapy, separately or in combination between 1953 and 1982. MAIN OUTCOMES MEASURES: Multivariate analysis of the different variables was performed according to the Cox regression method. RESULTS: The variables of prognostic value were, in decreasing order of importance: the decade of patient admission (p = 0.0001), the modality of therapy employed (p = 0.0005), the presence of residual tumor in the surgical specimens (p = 0.0055) and the clinical stage of the disease (p = 0.0575). CONCLUSION: Radiation therapy controlled a considerable number of local tumors and pelvic lymph nodes but not all of them in every patient. There is a specific group of patients for whom radical surgery is necessary to achieve control of the disease.     

Prenatal cocaine alters social competition of infant, adolescent, and adult rats

This series of experiments examined whether gestational cocaine exposure alters later social behavior exhibited during competition for biologically relevant stimuli. Rat offspring were derived from dams that received subcutaneous injections of 40 mg/kg/3cc cocaine HCl daily on gestational Days 8-20, pair-fed dams injected with saline, or nontreated control dams. Offspring competed with peers for access to a nipple in infancy, and to water in adolescence or adulthood. Prenatal cocaine exposure resulted in a decreased ability of cocaine-exposed infant rats to compete successfully for a nipple. Although adolescent and adult cocaine-exposed rats were no less successful than controls when competing for water, they exhibited a notable increase in aggression toward competitors during testing. Data provide evidence of alterations in social behavior and social competition as a result of prenatal cocaine exposure.     

Molecular beacon sequence analysis for detecting drug resistance in Mycobacterium tuberculosis

Strictureplasty for treatment of symptomatic intestinal strictures secondary to Crohn's disease is being performed with increasing frequency. To determine the overall clinical results after strictureplasty for Crohn's disease, all patients undergoing this procedure were prospectively studied. Between 6/1/89 and 2/1/97, 57 Crohn's disease patients underwent 60 operations utilizing strictureplasties. A total of 109 strictureplasties were performed (90 Heineke-Mikulicz, 6 Finney, and 13 side-to-side isoperistaltic). The 30-day perioperative morbidity was 12%, with complications being less common for patients undergoing elective versus unscheduled operations (p < 0.002). Recurrence of Crohn's disease requiring operation was seen in seven patients after a mean follow-up of 38 months. The estimated cumulative recurrence rate after 2 years was 15 +/- 6% (+/- standard error) and 22 +/- 10% at 5 years. A recurrence developed at the site of the previous strictureplasty in only five cases. Strictureplasty is a safe, effective means of providing long-term surgical palliation to selected patients with Crohn's disease. Perioperative complication rates are comparable to those seen with standard surgical treatment, and recurrences are not excessive.     

p53 and thymidylate synthase expression in untreated stage II colon cancer: associations with recurrence, survival, and site

We initiated a retrospective study to determine whether p53 status and thymidylate synthase (TS) protein expression in primary colon tumors influence recurrence and survival for patients with stage II colon cancer. Tumor specimens from 45 consecutive untreated patients with stage II colon cancer were examined for p53 and TS protein expression using immunohistochemistry. The median follow-up was 5.1 years. Eighteen patients had left-sided tumors, and 27 had right-sided tumors. Fourteen of 45 patients (31%) developed recurrence. p53 overexpression was detected in the tumors of 18 patients (40%); 10 patients (55%) with p53 overexpression recurred; and 4 of 27 (15%) without evidence of p53 overexpression recurred (P = 0.002). High TS expression was detected in the tumors of 16 patients (36%): 8 patients (50%) with high TS expression recurred, and 6 patients (21%) with low TS expression recurred (P = 0.027). Patients with p53 overexpression had a significantly poorer survival than did those patients without p53 overexpression (P < 0.001). High TS expression was associated with poor survival (P = 0.004). p53 overexpression and high TS expression were significantly associated with left-sided tumors (P = 0.003 and P = 0.022). Thirteen of 16 patients (81%) with high TS expression also overexpressed p53, and 24 of 29 patients (81%) with low TS expression did not manifest p53 overexpression (P < 0.001). p53 and TS expression in primary stage II colon cancer are associated and appear to influence recurrence and survival. In this pilot study, left-sided tumors demonstrate significantly more p53 overexpression and significantly higher TS expression than do right-sided tumors, which may explain the significantly poorer survival for patients with left-sided tumors.