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Biomedical subjects

M Martin

Publications and source records attributed to M Martin.

At least 541 records · Page 30Linked to original sources

Identification and localization of a nucleolin homologue in onion nucleoli.

A protein homologous to nucleolin, a major nucleolar protein with multifunctional features involved in pre-rRNA synthesis and early processing, has been identified and localized in situ in onion root meristematic cells by different techniques, which have included the use of an antibody raised against hamster nucleolin. The protein was identified on Western blots of nucleolar proteins as a 64-kDa band, by means of the anti-nucleolin antibody, bismuth staining, and the silver staining-nucleolar organizer (Ag-NOR) method. The experiments also suggested that nucleolin could be a target of these two cytochemical stainings. Although the 64-kDa band corresponds to a major nucleolar protein, it is a minor one among total nuclear proteins. The same techniques were used in situ at the ultrastructural level, and the immunogold detection of the nucleolin homologue was quantitatively evaluated. The protein accumulates in the transition area from nucleolar fibrillar centers to the dense fibrillar component, which is considered to be the structural result of ribosomal gene transcription. Out of this transition area, the dense fibrillar component may be divided into two regions, proximal and distal with respect to fibrillar centers, which show, respectively, the significant and unsignificant presence of nucleolin; we interpret this fact as the expression of the topological arrangement of pre-rRNA processing. Fibrillar centers themselves showed a weak but significant labeling with the anti-nucleolin antibody. However, bismuth staining was absent from the interior of fibrillar centers, indicating that the nucleolin in them is not phosphorylated. Ag-NOR staining uniformly covered fibrillar centers and the dense fibrillar component (at least in its proximal region), but it did not stain condensed chromatin inclusions in heterogeneous fibrillar centers, showing that the binding of nucleolin to chromatin is associated with its decondensation. This work provides additional evidence of the high phylogenetic conservation of molecular motifs which take part in ribosome biogenesis.

Allium↗

Invasive maxillary aspergillosis after dental extraction. Case report and review of the literature.

Paranasal sinus aspergillosis has usually been considered a rare disease, but it is seen more frequently in both immunocompromised and immunocompetent persons. Invasion may reach the sinuses via the nose or from the mouth after dental procedures. Even though the infection is usually limited to one or more sinuses, it may in certain cases extend to vascular or intracranial structures with a fatal outcome. In these cases, aggressive treatment is justified. We report a case of maxillary sinus aspergillosis that developed after dental extraction. Attention should be given to this possibility even after an apparently uncomplicated dental extraction.

Adult↗

Cell-to-cell spread of HIV-1 occurs within minutes and may not involve the participation of virus particles.

Although virus infections have been classically studied with "cell-free" virion preparations, many animal viruses are able to spread both in vitro and in vivo by inducing cell-cell fusion. An efficient system to monitor the cell-to-cell spread of HIV-1 has been developed employing chronically infected H9 donor cells. Under appropriate conditions of cocultivation with uninfected cells, the synthesis of unintegrated viral DNA, monitored by Southern blot hybridization, occurred between 2 and 4 hr following infection; viral proteins were detected 8 to 12 hr following cocultivation and progeny virions were released into the medium by 16 hr. The use of metabolic inhibitors or specific envelope/receptor antibodies revealed that the cell-to-cell spread of HIV required: (1) gp120-CD4 interaction and (2) reverse transcription. Light and electron microscopy, fluorescent dye redistribution, and soluble CD4 competition experiments all demonstrated that the HIV-induced cell-cell fusion began within 10 to 30 min of cocultivation. Surprisingly, the electron microscopic analyses also suggested that budding or mature virus particles did not participate in this process. Thus the virus-induced cell-cell fusion observed is very likely the result of gp120/gp41 proteins, on the surface of infected cells, interacting with CD4 molecules on uninfected cells. These findings are of immediate importance in understanding the mechanism(s) of HIV-1 transmission in vivo and for the design of effective vaccines and antiviral agents.

Blotting, Western↗

A method for using serum or plasma as a source of DNA for HLA typing.

A simple method for obtaining DNA from serum and plasma is described. Using appropriate primer pairs the polymorphic segments of HLA class II genes were amplified by the polymerase chain reaction (PCR) from this DNA, and typed using allele-specific oligonucleotide hybridization. When compared with DNA obtained from peripheral blood lymphocytes, the efficiency of the PCR was only minimally compromised and could be augmented by increasing the number of amplification cycles and/or by the addition of glycerol to the reaction mixture. This method serves as a reasonable alternative when no other source of DNA is available.

Base Sequence↗

Second head and neck cancers following radiation therapy of T1 and T2 cancers of the oral cavity and oropharynx.

The risk of second cancer in the head and neck region following definitive radiation therapy was evaluated among 600 patients who were treated for T1 and T2 cancers of the oral cavity and oropharynx at the Henri Mondor hospital between January 1970 and March 1987. Seventy-five patients (12.5%) were managed with external irradiation only, 243 (40.5%) with RT and Iridium 192, and 282 (47%) with Iridium 192 alone. One hundred fifteen patients (19%) developed a second cancer from 3 to 183 months after initial therapy (median: 32 months), including 69 patients (11.5%) in whom the second malignancy was diagnosed in the head and neck region. An increased and constant actuarial risk of development of second head and neck cancer was found (2.7%/year of observation). Univariate analysis showed that age, sex, stage, and modality of the initial treatment did not influence the risk of second head and neck cancer; there was a greater risk of second head and neck malignancy for those patients with soft palate carcinoma (p less than 0.05). Multivariate analysis revealed that the only group of patients who developed a second head and neck cancer more frequently were those who were irradiated with Iridium 192 only (p = 0.0076). There was a trend toward a greater risk of second head and neck malignancy for those with soft palate carcinoma (p = 0.059). Radical treatment of the second head and neck malignancy by surgery and/or re-irradiation was performed for 67% of patients. Patients initially treated by Iridium 192 only could undergo salvage treatment more often than those who previously received external beam radiotherapy (79% vs 53%, p = 0.02). The overall 2-year and 5-year survivals after the diagnosis of the second head and neck cancer were 32% and 10%, respectively.

Adult↗

Gender influences the in vitro renin release responses to dopamine and adrenergic receptor blockade in the summer-active ground squirrel Spermophilus lateralis.

1. 10(-4) M Dopamine stimulated and 10(-7) M inhibited in vitro resting renin release (RR) only in the female animals. 2. Alpha- or beta-adrenergic blockade prevented the stimulation but not the inhibition of RR by dopamine in the female animals. 3. Membrane receptor mechanisms mediating these changes do not involve alterations in tissue cyclic AMP content. 4. The sensitivity of the juxtaglomerular cells to dopamine challenge is gender dependent during summer activity.

Adrenergic Antagonists↗

Progressive loss of antiemetic efficacy during subsequent courses of chemotherapy.

The maintenance of the antiemetic efficacy of a combined protocol (intravenous methylprednisolone, oral thiethylperazine and oral amitriptyline) during six consecutive courses of adjuvant FAC chemotherapy (5-fluorouracil, doxorubicin, cyclophosphamide) was analysed in 107 female breast cancer patients who completed the six planned courses of treatment. A continuous decrease in complete (no vomiting episodes) and major protection rate (0-2 vomiting episodes) was evident during chemotherapy. Complete protection rate decreased from 62.6% in the first course to 48.6% in the sixth (P less than 0.05, chi 2 test). The respective figures for major protection rate were 76.6% and 58% (P less than 0.01, chi 2 test). These data, together with other from the literature, should be taken into consideration when reviewing the overall results of current antiemetic trials, which usually only mention the results obtained in the first course of chemotherapy.

Adult↗

Adrenocorticotropin hormone, beta-endorphin and cortisol responses to oCRF in melancholic patients.

Several authors have reported attenuated adrenocorticotropin hormone (ACTH) responses to corticotropin releasing factor (CRF) administration in melancholic patients as compared with healthy controls. In order to explore the integrity of the hypothalamic-pituitary-adrenal (HPA)-axis in melancholics, we examined the following parameters in 98 subjects: the ACTH; beta-endorphin; and cortisol responses to ovine CRF (oCRF) (100 micrograms/i.v.); and the postdexamethasone cortisol values. We found significant lower CRF-induced ACTH responses in melancholic patients as opposed to healthy controls and minor depressives, while major depressives occupied an intermediate position. The psychopathological correlates of the blunted CRF-induced ACTH responses were feelings of worthlessness, self-reproach, or excessive guilt. The CRF-stimulated beta-endorphin and cortisol response did not differ between the study samples. Higher baseline plasma cortisol was associated with attenuated CRF-induced ACTH responses, but these effects were not pertinent to melancholia. There were no relationships between the disordered oCRF test results, and postdexamethasone cortisol values, age, body size, sex and severity of illness. The diagnostic power of the oCRF and the dexamethasone suppression test for melancholia is enhanced when both test results are combined.

Adrenocorticotropic Hormone↗

A novel class of cardiotonic agents: synthesis and biological evaluation of 5-substituted 3,6-dihydrothiadiazin-2-ones with cyclic AMP phosphodiesterase inhibiting and myofibrillar calcium sensitizing properties.

As part of a search for new cardiotonic agents significantly sensitising the myocardial contractile proteins to calcium, together with cardiac cyclic AMP-PDE inhibitory activity, we have discovered that novel 5-substituted 3,6-dihydrothiadiazin-2-ones may fulfill both properties. The sensitising effect of the contractile proteins to calcium, assessed by the shift in the calcium sensitivity of canine cardiac myofibrillar magnesium-dependent ATPase, is determined by steric and electronic requirements. The requirements for phosphodiesterase inhibition, especially that of a near-planar arrangement for the phenyl and thiadiazin-2-one ring are consistent with those already described for analogous pyridazinones. The synthesis and structure-activity relationships are discussed.

3',5'-Cyclic-AMP Phosphodiesterases↗

Influence of contextual features on the activation of ambiguous word meanings.

Three studies examined whether initial meaning activation is sensitive to context. Experiment 1 demonstrated that contextually appropriate targets were activated more than inappropriate targets. Experiment 2 evaluated activation across intervals of 0, 300, and 600 ms. Constraining sentences activated contextually appropriate meanings over inappropriate meanings. This was maintained across the intervals for highly salient targets. Less-salient targets, although initially activated, were no longer activated 300 ms following the homograph. Experiment 3 converged on context-sensitive activation following a 50-ms exposure of the sentence-final homograph. Conclusions are (a) initial meaning activation can be sensitive to context, (b) when a homograph is instantiated, it is congruent with a broad scope of targets, and (c) less-salient targets receive less activation over the time course.

Adult↗

TSH responses to TRH as a function of basal serum TSH: relevance for unipolar depression in females--a multivariate study.

Baseline thyroid-secreting-hormone (TSH)-assessed by means of ultrasensitive assays (IRMA)-and free-thyroid-hormone (FT4) levels were determined in 84 depressed females, and the TSH responses to 200 micrograms thyrotropin-releasing hormone (TRH) (IV) measured. It was found that TRH-induced TSH responses were linearly and positively related to basal TSH-IRMA; lower TRH-stimulated TSH secretion in melancholic patients was attributable to lowered basal TSH-IRMA values. A progression was found-within the euthyroid range-of basal TSH-IRMA values towards lower levels along the diagnostic spectrum: the highest basal TSH-IRMA levels were witnessed in minor depressives and the lowest in melancholics, while simple major-depressed females occupied an intermediate position. This shift appears to be indicative of severity of illness. Basal TSH-IRMA data can roughly be used as a clinical tool separating melancholia from minor depression: at a threshold value of less than or equal to 1 microUI/ml, sensitivity was 56% and specificity 92%. It is concluded that basal TSH-IRMA provides a more accurate representation of melancholia than peak TSH responses, which appear to constitute little more than a magnified, but biased signal of basal TSH-IRMA. In future, the assay of basal TSH-IRMA could replace TRH testing.

Aging↗

[The magnesium and calcium content of pre- and postmenopausal myometrium].

Magnesium and calcium, as well as sodium and potassium, have an important influence on the physiology of contraction of the uterus. The ionic concentrations in the pre- and postmenopausal myometrium were examined. We assumed, that there are differences in the electrolytic contents because of the different functions of the corpus, isthmic part and cervix uteri during pregnancy and throughout labour. Small tissue samples from 37 premenopausal and 20 postmenopausal patients, who underwent an operation with different indications, were dissected after hysterectomy. Magnesium and calcium levels were determined by atomic absorption spectrophotometry and potassium and sodium by emission spectrometry in the wet tissue. In both groups, we found significant differences of the electrolytic contents of the myometrium. In the premenopausal uteri, the magnesium levels decrease significantly (p < 0.001) from the corpus (mean = 4.14 mmol/kg) to the cervix (mean = 2.14 mmol/kg). The same scenario can be observed for the potassium levels (Corpus mean = 56.2 mmol/kg and cervix mean = 25.4 mmol/kg). In contrary, the calcium levels (Corpus mean = 1.60 mmol/kg and cervix mean = 2.26 mmol/kg) and sodium levels (Corpus mean = 69.3 mmol/kg and cervix mean = 93.0 mmol/kg) increase significantly (p < 0.001). In the postmenopausal group, we found slightly elevated concentrations of magnesium, sodium and potassium. Only the calcium content of the corpus uteri rises up to three times about 20 years after the menopause (from mean = 1.60 mmol/kg) (p < 0.001). The electrolytic contents in the myometrium were shown to be different in the corpus, isthmus and cervix uteri.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Neoadjuvant combination of carboplatin and 5-FU in head and neck cancer: a randomized study.

A prospective, randomized, multicenter study of patients with oropharyngeal and pharyngolaryngeal tumors compared locoregional treatment alone with neoadjuvant chemotherapy with carboplatin/5-fluorouracil (5-FU) followed by locoregional treatment. The aim of the study was to evaluate the role of chemotherapy on survival and on the need for mutilating surgery. Since 1988, 219 patients (105 with oropharyngeal and 114 with pharyngolaryngeal tumors) have entered the study. All patients randomized to neoadjuvant chemotherapy received three cycles of carboplatin 400 mg/m2 day 1 and 5-FU 1 g/m2/d as a continuous infusion days 1 through 5 every 3 weeks. Neoadjuvant chemotherapy was given to 108 patients. The 268 evaluable courses induced a low rate of grade 3 or 4 toxicity. Four patients (3.6%) died of major complications. The complete response (CR) rate was 31%, which represented a decrease in mutilating surgery of 30%. (Patients with CRs had radiotherapy alone instead of radiosurgical treatment as originally planned.) The objective response rate was 61%. Survival curves for the chemotherapy and chemotherapy-naive groups were not significantly different. The rate of nodal recurrence was significantly higher in the chemotherapy group, however, and chemotherapy did not decrease the rate of second primary tumors or distant metastases. Thus, the justification for neoadjuvant chemotherapy may be a decreased rate of mutilating surgery. These preliminary results are encouraging, but follow-up is as yet too short to allow definite conclusions.

Adult↗

Factors associated with invasive lung aspergillosis and the significance of positive Aspergillus culture after liver transplantation.

From January 1981 to December 1990, 2180 patients underwent orthotopic liver transplantation at the University of Pittsburgh. Thirty-two patients (1.5%) were identified with invasive aspergillosis (29 lung, 2 intraabdominal, 1 meningitis). Of 29 patients with invasive lung disease, only 23 (79%) had positive culture (Aspergillus fumigatus, 20; Aspergillus flavus, 3). Forty-eight variables were analyzed and compared in 23 patients with invasive disease with positive cultures and 9 patients with colonization only. The variables associated with pulmonary invasive disease, by univariate analysis, were surgical time (P = .03), presence of laparotomies (P = .02), higher creatinine level at time of Aspergillus isolation (P = .01), and use of OKT3 (P = .02). However, in a multivariate analysis, only the last two (creatinine, OKT3) were associated with invasive lung aspergillosis. Of 4 patients with positive abdominal wound culture, 2 had local invasive aspergillosis. Therefore, positive cultures of Aspergillus organisms from respiratory secretions and wound drainage may represent invasive disease and should not be ignored.

Adult↗

A prospective randomized trial of continuous infusion 5-fluorouracil (5-FU) versus 5-FU plus cisplatin in patients with advanced colorectal cancer. A trial of the Spanish Cooperative Group for Digestive Tract Tumor Therapy (T.T.D.).

One hundred sixty consecutive patients with histologically confirmed colorectal cancer (advanced disease) without prior chemotherapy were entered in a randomized trial comparing 5-fluorouracil (5-FU) 1,000 mg/m2 intravenously per day for 5 consecutive days in continuous infusion versus cisplatin (CP) 100 mg/m2 on day 1 plus 5-FU as described on days 2 to 6. In both arms, treatment was recycled every 4 weeks. Both groups were well balanced for age, sex, colon or rectal origin, median time between diagnosis to advanced disease, performance status at entry, and visceral involvement. The overall response rate in the combination and in the single arm were 18 and 23%, respectively. There were no differences in time to progression (a median of 17.8 and 14.9 weeks for CP-5-FU and 5-FU, respectively) and in overall survival (a median of 71.2 and 59.6 weeks, respectively). The incidence of grade 3-4 emesis was significantly higher in the CP-containing chemotherapy (p = .00001). Our study has failed to demonstrate any clinical benefit from adding cisplatin to 5-FU in patients with cancer of the colon and rectum.

Adenocarcinoma↗

Intravenous and oral magnesium supplementations in the prophylaxis of cisplatin-induced hypomagnesemia. Results of a controlled trial.

The effects of oral and intravenous magnesium supplementation on cisplatin (CDDP)-induced hypomagnesemia were investigated in 41 patients treated with 100 mg/m2 CDDP. Patients were randomly allocated to receive no magnesium supplementation, intravenous magnesium supplementation (magnesium sulphate, 3 g before each CDDD administration) or oral magnesium supplementation (magnesium pidolate, 2 g orally every 8 hours on days 2 to 21 of each CDDP course) during the first 4 courses of CDDP treatment. Patients in both supplementation arms showed significantly higher magnesium levels than control patients from the second course on (oral magnesium arm) or from the third course on (intravenous magnesium arm). Three of the 9 patients (33%) in the intravenous magnesium arm and 4 of the 9 (44%) in the oral magnesium arm developed hypomagnesemia after the fourth course of CDDP, compared with 9 of the 10 (90%) unsupplemented patients. There were no magnesium-related side effects in patients on intravenous magnesium supplementation. Two patients treated with oral magnesium developed mild gastrointestinal symptoms (emesis and diarrhea), probably from magnesium therapy. Our study showed that both intravenous and oral magnesium supplementations appear to be safe and efficacious in the prevention of CDDP-induced hypomagnesemia. Since patients were not completely protected, and since the analysis was limited to the first four courses of chemotherapy, additional studies are needed to determine the best schedule of magnesium supplementation, especially in patients who receive more than four courses of CDDP chemotherapy.

Administration, Oral↗

Breast pain associated with mammographic compression.

Firm breast compression during film-screen mammography is necessary to achieve optimum image quality while minimizing radiation dose. Of 374 women who fully completed a questionnaire following mammography, 225 (60%) reported no pain, 115 (31%) moderate pain and only 3 (1%) reported severe pain. Only one patient stated that the pain from the procedure would prevent her from having a further mammogram. Underlying breast disease (usually fibrocystic disease) is associated with a greater incidence and severity of breast pain, but, no relationship has been demonstrated with regards to the patient's age, hormonal status, menstruation or caffeine intake. The high level of acceptance of firm compression by women in our study indicates that undue concern regarding patient discomfort should not deter people from referral for mammography or from the application of firm compression.

Breast↗