Transcellular Passage of Neisseria gonorrhoeae Involves Pilus Phase Variation

Piliated and nonpiliated Neisseria gonorrhoeae organisms were added on top of confluent layers of HEC-1-B cells, each maintained on a microporous Transwell-COL membrane. The bacteria released into the lower chamber were characterized with respect to the following virulence determinants: pili, which mediate adherence to target host cells; PilE, the major pilus subunit protein; and PilC, which is involved in pilus biogenesis and adherence. Even if >99% of the added bacteria of N. gonorrhoeae MS11 were piliated, bacteria recovered on the other side of the cell layer were predominantly nonpiliated. The recovered clones still expressed unassembled PilE protein, but 50% had lost PilC production. Nonpiliated gonococci, in which the 5′ end of pilE had been deleted, were released in reduced numbers, and piliated recA bacteria added to the cell layer were not released at all, at time points when piliated recA⁺ clones were found at high numbers in the lower chamber. Our data indicate that bacteria producing unassembled PilE protein are selected for during passage through an epithelial cell layer. The finding that the pilE gene sequence was altered in the transmigrants suggests that pilin sequence variation is involved in the transcellular passage of N. gonorrhoeae.     

Anterior cruciate ligament insufficiency treated by combined medial and lateral extra-articular reconstruction

Summary Thirty patients who required surgery for an unstable knee with giving way symptoms were operated during 1979-1981 with a pes anserinus transfer and an Ellison procedure at the same séance. All patients had an insufficient anterior cruciate ligament prior to surgery. Of these 24 patients had a positive pivot-shift test, and 26 patients had an anteromedial rotatory instability. Twenty-eight patients were seen at a follow-up after an average of 28 months (range 19–49). There were 12 women and 16 men, with a mean age of 28 years. Eleven patients (39%) declared that their knee function was distinctly improved, and six (21%) that it was moderately improved after surgery. Knee function was unchanged for ten patients (36%), and one patient said that the knee function had deteriorated after surgery. The functional result was not correlated with the duration of symptoms or with the followup time. Physical examination revealed that the anterior drawer had not disappeared for any of the patients. A positive pivot-shift sign was still present in 18 patients, and 23 patients displayed an increased varus instability.—All but six patients still had some instability experiences, and most of them could not completely return to active sports. However, the method could provide an alternative for patients engaged in frequent but not heavy physical activity.

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Zusammenfassung Dreißig Patienten mit Knieinstabilität wurden zwischen 1979 und 1981 mit gleichseitiger Pes anserinus- und Ellisonplastik operiert. Alle Patienten hatten vor der Operation eine Insuffizienz des vorderen Kreuzbandes mit giving way-Symptom. Bei 24 Patienten war der Pivot-shift-Test positiv, und 26 Patienten hatten eine antero-mediale Rotationsinstabilität. Es trafen keine postoperativen Komplikationen ein. 28 Patienten konnten nach 19–49 Monaten nachkontrolliert werden: 12 Frauen und 16 Männer mit einem Durchschnittsalter von 28 Jahren. 11 Patienten (39%) fanden ihre Kniefunktion deutlich verbessert, und 6 Patienten (21%) gaben an, daß ihre Kniefunktion nach der Operation etwas verbessert war. Bei 10 Patienten (36%) war die Kniefunktion unverändert, und ein Patient sagte, daß sich die Kniefunktion durch die Operation verschlechtert habe. Das funktionelle Endresultat war nicht mit der Dauer der Symptome und der Beobachtungszeit korreliert. Die klinische Untersuchung zeigte, daß alle Patienten immer noch ein positives Schubladenphänomen hatten und daß bei 18 Patienten auch der Pivot-shift-Test positiv war. Varusinstabilität wurde bei 23 Patienten festgestellt.

     

Anterior cruciate ligament insufficiency treated by combined medial and lateral extra-articular reconstruction

Thirty patients who required surgery for an unstable knee with "giving way" symptoms were operated during 1979-1981 with a pes anserinus transfer and an Ellison procedure at the same séance. All patients had an insufficient anterior cruciate ligament prior to surgery. Of these 24 patients had a positive pivot-shift test, and 26 patients had an anteromedial rotatory instability. Twenty-eight patients were seen at a follow-up after an average of 28 months (range 19-49). There were 12 women and 16 men, with a mean age of 28 years. Eleven patients (39%) declared that their knee function was distinctly improved, and six (21%) that it was moderately improved after surgery. Knee function was unchanged for ten patients (36%), and one patient said that the knee function had deteriorated after surgery. The functional result was not correlated with the duration of symptoms or with the follow-up time. Physical examination revealed that the anterior drawer had not disappeared for any of the patients. A positive pivot-shift sign was still present in 18 patients, and 23 patients displayed an increased varus instability.--All but six patients still had some instability experiences, and most of them could not completely return to active sports. However, the method could provide an alternative for patients engaged in frequent but not heavy physical activity.     

Effects of acute and chronic treatment with imipramine on 5-hydroxytryptamine nerve cell groups and on bulbospinal 5-hydroxytryptamine/substance P/thyrotropin releasing hormone immunoreactive neurons in the rat. A morphometric and microdensitometric analysis

Summary Groups of male rats were treated for a period of 14 days with imipramine (10mol/kg) given twice daily. Separate groups of rats received a single dose treatment using the same dose and experimental design as for the repeated treatment. Employing the avidin-biotin immunoperoxidase technique for immunohistochemistry 5-hydroxytryptamine (5-HT)-, substance P (SP)- and thyrotropin releasing hormone (TRH)-like immunoreactivities (IRs) were visualized in consecutive coronal sections of the brain stem and of the spinal cord. The IRs were studied by means of morphometric and microdensitometric procedures using automatic image analysis on profiles representing nerve terminal networks of the ventral horn of the cervical and lumbar enlargements of the spinal cord as well as their coexistence (5-HT/SP and 5-HT/TRH). With the same technique 5-HT IR was measured in the 5-HT nerve cell groups of the medulla oblongata (B 1, B 2, B 3) and of the nucleus raphe dorsalis (B 7) of the midbrain. In addition 5-HT and 5-hydroxyindolacetic acid (5-HIAA) levels were measured in the ventral and dorsal horns of the cervical and lumbar enlargements of the spinal cord using high performance liquid chromatography (HPLC). In the same parts of the spinal cord SP IR was studied by means of radioimmunoassay (RIA).The microdensitometric studies showed that chronic, but not acute, imipramine treatment selectively increased SP IR in the 5-HT/SP/TRH costoring nerve terminals of the medial part of the ventral horn in both the cervical and the lumbar enlargements. Furthermore, quantitative analysis of the entity of coexistence in the 5-HT nerve terminal networks of these areas showed that all the 5-HT nerve terminals contained SP and TRH IRs and that this phenomenon remained after acute and chronic imipramine treatment. The microdensitometric studies on the 5-HT nerve cell groups of the medulla oblongata and of the nucleus raphe dorsalis demonstrated that chronic, but not acute, imipramine treatment selectively increased 5-HT IR in the nerve cell bodies of the lateral part of group B 3 as evaluated from the median grey values. Acute, but not chronic, imipramine treatment significantly increased the field area of 5-HT IR of nerve cell bodies in group B 7, reflecting an increase in the mean profile area of the 5-HT IR nerve cell body profiles. Instead, the mean profile area of 5-HT IR cell bodies of group B 1 was acutely reduced by imipramine.The biochemical studies demonstrated that chronic imipramine treatment selectively reduced 5-HT utilization in the ventral horn of the spinal cord and selectively increased SP IR in the dorsal horn of the lumbar enlargement.In view of these observations it is suggested that chronic imipramine treatment specifically increases SP IR in the 5-HT/SP/TRH costoring nerve terminals of the ventral horn probably related to reduced SP release and reduced 5-HT utilization in these terminals. The results obtained in group B 7 may be explained by a regulation by the³H-imipramine raphe binding sites of fast axonal transport, an influence which may have therapeutic consequences. This mechanism may also be responsible for the increase in 5-HT IR seen upon chronic imipramine treatment in the lateral part of the 5-HT nerve cell body group B 3. Such an effect may lead to a metabolic down-regulation of group B 7, having a possible role for the antidepressant activity of imipramine. The reduction of the mean profile area of 5-HT IR cell bodies of group B 1 seen in the acute treatment can possibly be caused by, noradrenaline (NA) uptake inhibition in inhibitory NA terminals innervating the B 1 group. These results also illustrate the heterogeneities in the responses of the 5-HT nerve cell groups to antidepressant treatment. The ability of chronic imipramine treatment to increase SP IR in the dorsal horn of the lumbar enlargement may reflect the existence of a monoamine-SP interaction in the substantia gelatinosa due to the NA and/or 5-HT uptake blocking activity of imipramine. The existence of such an interaction may help to explain the antinociceptive effect of chronic imipramine treatment.Part of the paper was presented at the 17th International Congress of the International Society of Psychoneuroendocrinology, Bergen, June 29–July 4, 1986.     

Psychological aspects of breast reconstruction following mastectomy

In order to analyse the experiences of women after breast reconstruction and to find variables influencing these experiences, 45 women were studied with quantitative methods and 14 with deep interviews, one to four years after breast reconstruction. By factor analysis, five dimensions of experiences were identified. With a more or less common background of variables evaluating the satisfaction with and the subjective importance of the reconstruction, these dimensions emphasized experiences of restoration, freedom from depression, changes in public body image, freedom from tenderness of the reconstruction site, and changes in life patterns, respectively. The dimensions were basically not correlated with each other. The "influence" of other variables on these dimensions was studied using multiple regression methods. Social and physical variables (the consistency of the reconstruction included), the incidence of significant life events, and the availability of social support could not be shown to influence the adjustment factors. Some personality traits were of importance, suggesting that the psychological coping style of the patients is influential. The saliency of personality variables is seen against the background that the technical results of the reconstructions on the whole are satisfactory and their variance restricted. In the deep interview, similar patterns of experiences as those identified by the quantitative methods, were found. The relative satisfaction with the reconstruction was for all interviewed patients the result of a process of adjustment that took varying lengths of time.     

Feasibility and delivery of patient-reported outcomes in clinical practice among racially diverse bladder and prostate cancer patients

ObjectiveTo assess the feasibility of enrollment and collecting patient-reported outcome (PRO) data as part of routine clinical urologic care for bladder and prostate cancer patients and examine overall patterns and racial variations in PRO use and symptom reports over time.Subjects/Patients and MethodsWe recruited 76 patients (n = 29 Black and n = 47 White) with prostate or bladder cancer at a single, comprehensive cancer center. The majority of prostate cancer patients had intermediate risk (57%) disease and underwent either radiation or prostatectomy. Over half (58%) of bladder cancer patients had muscle invasive disease and underwent cystectomy.Patients were asked to complete PRO symptom surveys using their preferred mode [web- or phone-based interactive voice response (IVR)]. Symptom summary reports were shared with providers during visits. Surveys were completed at 3 time points and assessed urinary, sexual, gastrointestinal, anxiety/depression, and sleep symptoms. Feasibility of enrollment and survey completion were calculated, and linear mixed effects models estimated differences in outcomes by race and time.ResultsSixty three percent of study participants completed all PRO measures at all 3 time points. Black patients were more likely to select IVR as their survey mode (40% vs. 13%, P < 0.05), and less likely to complete all surveys (55% vs. 74%, P = 0.13). Patients using IVR were also less likely to complete all surveys (41% vs. 69%, P = 0.046).ConclusionsReported preferences for survey mode and completion rates differ by race, which may influence survey completion rates and highlight potential obstacles for equitable implementation of PROs into clinical care.     

Interactions of cardiovascular drugs with the cytotoxicity induced by epirubicin and irradiation in-vitro

Vasoactive drugs have been suggested to modulate the cytotoxicity of chemotherapy and radiotherapy. In this study, we have tested whether a number of commonly used vasoactive drugs interact with epirubicin- and radiation-induced toxicity on Chinese hamster fibroblast cell line V-79. The adrenoceptor agonist epinephrine, enchanced die effects of irradiation as measured by cloning capacity. In contrast, epineprine and terbutaline decreased epirubicin cytotoxicity. The beta-adrenoceptor antagonist propranolol and the alpha-antagonist phentolamine, at 100 mumol/l, caused a significant enhancement of epirubicin cytotoxicity. None of the vasoactive drugs showed intrinsic cytotoxic effects. Radiation-induced cytotoxicity was unaffected by propranolol or phentolamine. The calcium channel blocker, verapamil, enhanced the toxicity induced by epirubicin and radiation. These results indicate that vasoactive drugs such as epinephrine, propranolol and phentolamine can interfere with radiotherapy and with anthracycline cytotoxicity. Further studies are warranted before conclusions on the mechanisms of action can be drawn.     

Analysis of T-cell receptor expressing lymphocytes infiltrating squamous cell carcinomas of the upper aerodigestive tract

T-lymphocytes expressing T -cell receptors (TCRs) of the / type have been suggested to play an important role in mucosal defense against infection and neoplastic transformation. In this study, an immunohistochemical investigation was performed on the distribution of / and / TCRs among tumor-infiltrating lymphocytes. Thirteen patients with squamous cell carcinomas of the upper aerodigestive tract were studied, using monoclonal antibodies and an avidin-biotin-peroxidase technique. Most of the T-cells had an / TCR. Only 1.6% of the T-cells within the cancer tissue and 1.2% of the T-cells in the parenchyma adjacent to the cancer tissue expressed /gd TCRs. These results are consistent with the results of similar studies in bronchial and breast carcinomas. Biopsies from normal oral mucosa in nine healthy individuals showed that 1.3% of the T -cells within the epithelium and 1.0% of those in the lamina propria adjacent to the epithelium expressed / TCRs. Quantitatively the results do not support the theory that / T-cells play an important role in the immunological response against cancer tissue in the mucosa of the upper aerodigestive tract. The functional role of these cells in the mucosa and in response to carcinomas is, however, still uncertain.     

Within-day variability of magnetic fields among electric utility workers: consequences for measurement strategies

Occupational exposure to 50-Hz magnetic fields was surveyed among electric utility workers to investigate (1) components of exposure variability, (2) patterns of autocorrelation between short-term measurements, and (3) imprecision and misclassification due to short-term measurements. Spot measurements every 10 seconds during 81 working days were analyzed for 42 electric utility workers from 10 occupational subgroups and during 8 working days for 4 office workers from the same company. For the 8-hour time-weighted average (TWA) magnetic fields, the variability was partitioned into its components: within workers, between workers, and between groups. For spot measurements of magnetic fields, the within-day variance component also was examined. Autocorrelation functions were determined and numbers of short-term measurements necessary for reliable estimates of 8-hour TWA magnetic fields were assessed. Spot measurements of magnetic fields, as well as 8-hour TWA magnetic fields, were approximately log normally distributed among workers. The mean exposure to magnetic fields was 0.47 microT (n = 81 days) in electric utility workers and 0.12 microT (n = 8 days) in office workers. A large fraction, 76% of the spot measurements total variance, could be attributed to variability within days. For the 8-hour TWA magnetic fields, between-group variability was small and of the same magnitude as between-worker variability. Significant autocorrelations between short-term averages of 7.5, 15, and 30 minutes were present, when taken within periods of 30 minutes. One-hour averages showed no autocorrelation. Simulations showed that, due to high within-day variability and autocorrelation, a limited number of short-term measurements of magnetic fields in electric utility workers are likely to result in imprecise estimates of 8-hour TWA magnetic fields. Measurement strategies relying on short-term (spot) measurements are therefore likely to result in misclassification of exposure and consequently absent or spurious exposure-response relations.