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Biomedical subjects

G Gross

Publications and source records attributed to G Gross.

At least 199 records · Page 11Linked to original sources

[Epstein-Barr virus detection in oral hairy leukoplakia in AIDS patients, in leukoplakias and on normal tongue epithelia in HIV-1-negative patients].

In 3 patients seropositive for HIV 1 (2 homosexual men and 1 female drug addict), we found "oral hairy leukoplakia" on the lateral margin of their tongues. DNA of Epstein-Barr virus (EBV) and Human Papillomavirus (HPV) were identified in cellular DNA by molecular-virological means using Southern blot hybridization and/or DNA/DNA filter hybridization on epithelial cells taken by swabs from the epithelium of the tongue. The results were compared with those obtained from the identical anatomical sites of 2 HIV-1-seropositive patients without "oral hairy leukoplakia", 3 clinically healthy HIV-1-seronegative patients, and 2 HIV-1-negative patients suffering from oral leukoplakia on their lateral tongues. In all 3 cases investigated, EBV DNA was detected in cells taken from "oral hairy leukoplakia" by filter in situ hybridization. In addition, EBV DNA was found in cells taken from clinically normal epithelia of the tongue as well as in those taken from the 2 leukoplakias mentioned. EBV DNA was regularly detected on the lateral margin of the tongue, but only in one case on the pharyngeal mucosa. Electronmicroscopy on ultrathin sections revealed particles of herpes virus (EBV), particles of HPV, in one case particles of retrovirus, and in another coronavirus and diplococci.

Acquired Immunodeficiency Syndrome↗

Effect of chronic lithium administration on adrenoceptor binding and adrenoceptor regulation in rat cerebral cortex.

Lithium (Li) at a concentration, which exerts prophylactic effects in affective disorders is known to alter noradrenaline turnover and the beta-adrenoceptor-dependent cAMP accumulation. In the present study the action of chronic Li administration (at least 5 weeks) on agonist and antagonist binding to adrenoceptors and on the regulation of adrenoceptors was investigated in rat cerebral cortex. Li treatment caused a small but significant decrease in the number of beta-adrenoceptor binding sites by 10% (3H-dihydroalprenolol binding) leaving the number of alpha 1- and alpha 2-adrenoceptor binding sites (3H-prazosin and 3H-rauwolscine, respectively) unchanged. The affinity of the radioligands as well as the affinity of agonists to these binding sites were not altered. The up-regulation of beta-adrenoceptor binding sites produced by repeated reserpine injections was inhibited by 32% in rats treated concomitantly with Li, although the noradrenaline depleting effect of reserpine was not impaired. In contrast, Li treatment had no effect on the up-regulation of beta-adrenoceptor binding induced by 6-OH-dopamine, nor did it alter the beta-adrenoceptor down-regulation following chronic administration of desipramine. The up-regulation of alpha 1-adrenoceptor binding sites caused by reserpine or 6-OH-dopamine also remained unaffected by Li. It is concluded that chronic Li has limited effects on cortical adrenoceptors and their regulation. The inhibition of beta-adrenoceptor up-regulation caused by reserpine may reflect an action of Li on non-adrenergic systems rather than a general "stabilizing" effect on adrenoceptors proposed previously.

Animals↗

Alpha 1-adrenoceptors of rat myocardium: comparison of agonist binding and positive inotropic response.

Binding of agonists to alpha 1-adrenoceptors labelled by 3H-prazosin was investigated in membranes of rat myocardium and compared to the inotropic response elicited by alpha 1-adrenoceptor activation on isolated right ventricles. 1. At 30 degrees C the full agonists, adrenaline and phenylephrine, displaced 3H-prazosin with a shallow inhibition curve. The data are compatible with the assumption that 32% of the binding sites were in a state of high affinity for the agonist adrenaline (KI 85 nmol/l) and 68% in a low affinity state (KI 1738 nmol/l). GTP transformed all binding sites into the low affinity form suggesting that at least some of the cardiac alpha 1-adrenoceptors are coupled to N-proteins. 2. At 0 degree C most of the binding sites (86%) were in a state of high affinity for agonists (KI for adrenaline: 91 nmol/l). 3. For several partial agonists and antagonists (cirazoline, methoxamine, indanidine (Sgd 101-75), oxymetazoline and phentolamine) no such distinct temperature- and GTP-shifts could be demonstrated suggesting a different kind of interaction with alpha 1-binding sites. 4. When temperature was changed during incubation with adrenaline, a rise of temperature (from 0 degrees C to 30 degrees C) converted high affinity sites into the low affinity form, whereas a decrease in temperature (from 30 degrees C to 0 degrees C) failed to induce the high affinity state for agonists. Short term incubation (0.5 min) with adrenaline at 30 degrees C resulted in significantly lower IC50 values as compared to equilibrium conditions at the same temperature.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Agonists↗

Epidermodysplasia verruciformis in a patient with Hodgkin's disease: characterization of a new papillomavirus type and interferon treatment.

A new human papillomavirus (HPV) was discovered in disseminated, macular, pityriasis versicolor-like lesions on the skin of the neck, face, scalp, and pubic region of a 42-year-old male suffering from Hodgkin's disease. Histopathology revealed features characteristic of epidermodysplasia verruciformis (ev). In contrast to classical ev, the lesions were almost exclusively seen in previously irradiated and UV-exposed skin areas. Papillomavirus capsid antigen was demonstrated with the genus-specific antiserum and the patient's serum, which had IgM and IgG antibody titers. HPV DNA was isolated from biopsies and cloned into the vector pIC20H. It proved to be related to ev-associated viruses, showing 23% cross-hybridization with DNA of the closest relative HPV14. The new HPV type was named HPV46. The genome was physically mapped and colinearly aligned with HPV8 DNA to establish its gene organization. Interferon treatment of the patient did not significantly change the clinical picture nor was the concentration of viral DNA per lesion affected. However, no virus capsid antigen was detectable after starting treatment.

Adult↗

[Postoperative interferon hydrogel treatment. A method for the successful therapy of chronic persistent giant condylomas in an immunologically deficient patient with Hodgkin's disease].

The local application of recombinant interferon alpha 2c hydrogel (1.10(6) I.U. recombinant interferon alpha 2c/g hydrogel) given as an adjuvant therapy after electrosurgery led to a complete cure, without relapse, of previously recalcitrant giant condylomata acuminata similar in appearance to Buschke-Löwenstein's tumors in a 19-year-old female patient suffering from Hodgkin's disease (stage II/III). Recombinant interferon alpha 2c hydrogel given as an adjuvant therapy to surgery may have more antiviral and antiproliferative effects than immunomodulating activities. This combined topical application form of interferon alpha is a safe and effective treatment, which is recommended especially in immunocompromised individuals suffering from genital HPV infection unresponsive to systemic interferon treatment or conventional therapy modalities.

Adult↗

Structure of secondary cleavage sites of E. coli RNAaseIII in A3t RNA from bacteriophage T7.

Five 'secondary' cleavage sites of E. coli RNAaseIII within the initiator RNA A3t (141 nucleotides) from bacteriophage T7 are described. Cleavage takes place apparEntly within or at the bottom of a short double-stranded stretch of RNA. Three secondary sites are efficiently cleaved in the presence of magnesium 2+ ions, two additional sites are cleaved in the presence of manganese 2+ ions at low monovalent salt concentrations (less than 0.05 M).

Base Sequence↗

Promoter and enhancer elements in the rearranged alpha chain gene of the human T cell receptor.

We cloned and compared the sequence of a rearranged human T cell receptor (TCR) V alpha J alpha gene and its germline counterparts. The only difference in the coding region sequence was confined to the joining region where three nucleotides, TTG, unaccountable by either V alpha or J alpha sequence, were present. By nuclease S1 mapping we identified the mRNA start of the alpha chain 70 nucleotides upstream from the initiator ATG. A 600 bp fragment containing the sequences upstream to the ATG drives the expression of the bacterial chloramphenicol acetyltransferase (CAT) gene. This promoter activity is T cell specific since it can be demonstrated in human T cells but not in B cells or HeLa cells. A 1.1 kb BamHI- HindIII fragment located 5' to the first exon of the C alpha gene was found to enhance transcription from either the heterologous SV40 promoter or the homologous TCR alpha chain promoter. This enhancement activity was independent of the location of the fragment with respect to CAT and was specific to lymphoid cells (either T or B cells) but cannot be demonstrated in HeLa cells.

Amino Acid Sequence↗

Urapidil and some analogues with hypotensive properties show high affinities for 5-hydroxytryptamine (5-HT) binding sites of the 5-HT1A subtype and for alpha 1-adrenoceptor binding sites.

The mechanism responsible for the antihypertensive effect of urapidil is not yet completely understood. Its vasodilator action has been attributed to an antagonism at vascular alpha 1-adrenoceptors. However, it has been suggested that a central action contributes to the hypotensive effect. Recently, three potent analogues of urapidil have been described which also lower blood pressure by a central mechanism. 5-Hydroxytryptamine (5-HT) receptors of the 5-HT1A subtype have been implicated with the central control of cardiovascular function. In the present study, the affinities of these urapidil derivatives (5-acetyl, 5-formyl- and 5-methyl-urapidil) for 5-HT receptors were investigated using 3H-8-hydroxy-2-(di-n-propyl-amino)tetralin (3H-8-OH-DPAT), 125I-iodocyanopindolol (125I-ICYP) and 3H-ketanserin for labelling 5-HT1A, 5-HT1B and 5-HT2 binding sites, respectively. 3H-Prazosin and 3H-clonidine were used as selective alpha 1- and alpha 2-adrenoceptor radioligands, respectively. Urapidil and its analogues produced half-maximum inhibition of 3H-8-OH-DPAT binding at concentrations of 4 x 10(-9) mol/l to 4 x 10(-7) mol/l with the following order of potency: urapidil less than 5-acetyl- less than or equal to 5-formyl- less than 5-methyl-urapidil. Thus, 5-methyl-urapidil is one of the most potent ligands at 5-HT1A recognition sites known to date. The IC50 values of urapidil and its derivatives for 3H-prazosin binding were in the range of 5 x 10(-8) mol/l to 8 x 10(-7) mol/l (order of potency: urapidil less than 5-formyl- less than 5-acetyl- less than 5-methyl-urapidil).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effect of antidepressant and neuroleptic drugs on the electrically evoked release of serotonin from rat cerebral cortex.

The effect of antidepressant and neuroleptic drugs on the electrically evoked release of serotonin (5-HT) was investigated in rat brain cortical slices preincubated with 0.1 mumol/l 3H-5-HT. Zimelidine, trazodone, clomipramine, doxepin, and viloxazine (1 mumol/l each) enhanced the electrically-induced 3H overflow by 20-44%. Six other antidepressants and five neuroleptics did not increase the evoked transmitter release. Only trazodone and viloxazine also increased the 3H overflow in experiments in which neuronal 5-HT reuptake was already blocked by 6-nitroquipazine. 5-HT and clonidine inhibited the electrically-induced 3H-5-HT release by stimulation of presynaptic 5-HT autoreceptors and alpha 2-adrenoceptors, respectively; trazodone and viloxazine had no effect on the concentration-response curves of 5-HT and clonidine. Other psychotropic agents with well known antiserotonergic activities also failed to block presynaptic 5-HT autoreceptors. It is concluded that zimelidine, clomipramine, and doxepin enhanced the 3H-5-HT overflow by inhibition of neuronal 5-HT uptake, whereas the increase produced by trazodone and viloxazine cannot be explained by reuptake inhibition or interaction with presynaptic receptors.

Animals↗

Vascular access options for outpatient cancer therapy.

Knowledge of the abilities and limitations of various access devices can help the surgeon decide which is best matched to an individual cancer patient receiving outpatient therapy. Implanted ports have become the mainstay of long-term treatment. Hickman catheters are useful for long-term nutritional support and pain control when parenteral narcotics are required. Long-arm catheters and central venous catheters can be utilized for short-term therapy. Proper utilization of the various vascular access devices can optimize patient care in a cost-effective manner.

Ambulatory Care↗

HDL clearance and receptor-mediated catabolism of LDL are reduced in hypothyroid rats.

Hypercholesterolemia associated with hypothyroidism is due partly to increased plasma LDL and partly to increased HDL cholesterol concentrations. The increase in LDL cholesterol has been shown to be secondary to reduced plasma clearance of LDL. To determine which catabolic route was thyroid dependent, the present study examined the effects of hypothyroidism on the receptor-mediated pathway and the 'receptor-independent' pathway of LDL metabolism. Wistar rats (327 +/- 22 g; mean +/- SD) were made hypothyroid by feeding propylthiouracil (0.1%, w/w) and rat 131I-LDL (rLDL; d = 1.019-1.050) and 125I-methylated-LDL (rLDL-CH3) were simultaneously injected i.v. after which the rates of clearance of labelled LDL in plasma were determined over 0-54 h. Total LDL and 'receptor-independent' clearances were represented by clearance of 131I-rLDL and 125I-rLDL-CH3 respectively and the difference between the two represented high affinity receptor-mediated clearance. The data were analyzed using Matthews' model and the fractional catabolic rates (FCR) were calculated. The FCR of rLDL clearance via the receptor-mediated pathway was 0.1042 +/- 0.0112 pools/h (n = 6) in controls vs. 0.0613 +/- 0.0079 pools/h (n = 6) in hypothyroid animals (P less than 0.01). The FCR via the 'receptor-independent' pathway was 0.0642 +/- 0.0040 pools/h (n = 6) in controls vs. 0.0561 +/- 0.0036 pools/h (n = 6) in hypothyroid animals (not significant). The plasma HDL cholesterol concentration was also increased in hypothyroid rats (70.4 +/- 6.7 mg/dl) compared to control (53.3 +/- 3.1 mg/dl) (P less than 0.025).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Alpha interferon in condylomata acuminata and juvenile diabetes mellitus].

Persistent condylomata acuminata in a 21-year-old patient with diabetes mellitus were treated with highly purified interferon-alpha (IFN-alpha) obtained by recombinant DNA technology. Daily dose was 1.5 X 10(6) IU, given subcutaneously. Already during treatment the condylomata regressed. Two weeks after the end of therapy, i.e. after a total dose of 10.5 X 10(6) IU IFN-alpha, all condylomata had completely receded. Blood glucose levels remained constant with concomitant insulin therapy. Toxic side-effects or antibodies to IFN-alpha were not observed.

Adult↗

Molecular cloning of two new HPV types (HPV 37 and HPV 38) from a keratoacanthoma and a malignant melanoma.

Several benign and malignant skin tumors were analyzed for the presence of human papillomavirus (HPV) DNA. By hybridization with different HPV DNA probes under non-stringent conditions (Tm -40 degrees C), two tumors were found to contain HPV-specific DNA sequences in high copy numbers: (1) a keratoacanthoma from a patient who also suffered from a basalioma; (2) a superficial spreading malignant melanoma of an immunosuppressed patient. For further analysis of these DNA sequences genomic libraries from both tumor DNAs were constructed and, out of these, 4 different HPV DNA types have been cloned. By cross-hybridization experiments and restriction map analysis HPV 9 DNA was identified in the keratoacanthoma whereas HPV 17a DNA could be cloned from the malignant melanoma. From each tumor one additional HPV-type not identical to other known HPV-types was cloned. These isolates are closely related to HPV 9, 15, 17, 22 and 23. A physical map of both HPV DNAs was constructed. Size (7.8 kbp), co-linear alignment to HPV 16, cross-hybridization with other HPV-types under conditions of low stringency and monomeric episomal state of the HPV molecules indicate that these two DNA probes represent new HPV types that have been tentatively designated as HPV 37 (keratoacanthoma) and HPV 38 (malignant melanoma). None of these two HPV types could be found in any other of 231 tumor DNAs originating from different tissues.

Cloning, Molecular↗

[Lymphomatoid papulosis--pseudolymphoma with uncertain prognosis].

On account of its distinct clinical and histological picture, lymphomatoid papulosis (l.p.) is mostly considered an entity. A 70-year-old patient with l.p. is described. Histologically, there were similarities to the granulomatous type of pseudolymphoma. The oral treatment with penicillin for 4 weeks was successful, but we cannot exclude a spontaneous remission.

Aged↗

Spin-lattice relaxation (T1) times of cerebral white matter in multiple sclerosis.

Magnetic resonance imaging was used to evaluate the cerebral white matter of three subject groups: (1) 22 patients with known multiple sclerosis (MS) (11 with disease of shorter duration (0-5 years) and 11 with disease of longer duration (greater than 5 years]; (2) 9 patients with suspected MS; and (3) 12 normal volunteers. Transverse spin-echo (SE) 30/500 and 120/1000 radiofrequency pulse sequences were used for anatomic localization and plaque identification, respectively, while combined spin echo-inversion recovery was used for T1 determination. T1 values were calculated for grossly normal cerebral white matter in the frontal, parietal, and occipital lobes of normal volunteers and MS patients, and for plaques in MS patients. When compared with normals, the T1 values of plaque-free areas from definite MS patients (shorter and longer duration disease groups combined) were significantly longer in the frontal lobe (MS = 374 +/- 34 ms, Normal = 352 +/- 39 ms, P less than 0.05) and in the occipital lobe (MS = 414 +/- 37, Normal = 378 +/- 40, P less than 0.02). Although the T1 values of the shorter duration MS group were longer than those of normals, the difference was not statistically significant. Thus, the significant difference between the definite MS group (both shorter and longer duration) is more heavily weighted by the longer duration MS group. T1 values in patients with suspected MS without plaques were not significantly different from those of normals. In diagnosed MS patients, T1 values of plaques were significantly longer than T1 values of corresponding normal areas (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Analysis of benign and malignant urogenital tumors for human papillomavirus infection by labelling cellular DNA.

A total of 268 biopsies from the genital region was screened for the presence of human papillomavirus DNA. The specimens included carcinoma of the vulva, vagina, cervix, corpus uteri, ovaries and penis, and Bowen's carcinomas, Bowenoid papuloses, Bowen's disease, cervical intraepithelial neoplasias (CIN I to III), Buschke-Löwenstein tumors, a cervical polyp, decidua, endometrium and histologically normal biopsies. Of 45 carcinomas, 18 contained either HPV 16 and/or 18 and 3 HPV 6-related sequences. In a few individual biopsies double or even triple infections were noted. Unusual was the presence of HPV 2-related DNA in one biopsy from Bowen's disease, whereas 2 condylomata acuminata contained HPV 3-related DNA and one contained HPV DNA related to a group of epidermal HPV's found in epidermodysplasia verruciformis lesions.

Biopsy↗