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Biomedical subjects

M Nasseri

Publications and source records attributed to M Nasseri.

At least 19 recordsLinked to original sources

Cultural similarities in psychological reactions to infertility.

A 74-item especially developed and validated questionnaire for Iranian culture was administered three times to 37 Iranian infertile couples and 10 fertile couples acting as control group, namely, initial consultation, during treatment, and on completion of treatment. In view of parallel data also reported for Western patients interest centered on the results of two out of the five factors measured by the questionnaire, i.e., Psychological Stress and Social Behaviour. Analysis generally showed significantly high stress and social withdrawal for the patient group, particularly at initial consultation and after an unsuccessful treatment cycle as compared to the control group. Moreover, men whose partners eventually conceived scored significantly lower on stress than men whose partners did not conceive. Similar results have also been reported for Western infertile patients. The implications of the findings are discussed.

Adaptation, Psychological↗

Human papillomavirus type 16 immortalized cervical keratinocytes contain transcripts encoding E6, E7, and E2 initiated at the P97 promoter and express high levels of E7.

Human cervical keratinocytes represent the specific host for the genital human papillomaviruses (HPV). Transfection of these cells with the DNA of a number of the oncogenic HPVs including type 16 was recently shown to result in their immortalization but not in malignant transformation. In this report we show that viral transcripts for E6 and E7 in these cells were as abundant as in cancer derived cell lines. However, in contrast to cancer derived cell lines, immortalized cervical keratinocytes contained RNA with the potential to encode a full-length E2 protein. In addition, the levels of the E7 oncoprotein were at least as high as in cancer derived cell lines, suggesting that E2 interruption, observed in cancer derived cell lines, is not causally related to the high level of E7 expression and, therefore, deregulation of the P97 promoter may not be a prerequisite for HPV-16 associated cancer development. Furthermore, we show that E6, E7, and E2 encoding transcripts all originate from the viral promoter, P97. Unlike in cancer derived cell lines, all transcripts terminated at the early poly(A) site.

Blotting, Northern↗

Genetic analysis of CRPV pathogenesis: the L1 open reading frame is dispensable for cellular transformation but is required for papilloma formation.

Genetic studies to elucidate the role of papillomaviruses in the development and progression of tumors have been severely hampered because the viruses cannot be grown in tissue culture and therefore mutants are not available. We have employed recombinant DNA for papilloma induction to identify essential sequences involved in papillomavirus pathogenesis. Here, we demonstrated that deleting most of the open reading frame (ORF) L2 did not affect the potential of viral cottontail rabbit papillomavirus (CRPV) DNA to induce papillomas. The extrachromosomally maintained DNA in the papillomas was not rearranged and the major transcripts of 1.3 and 2.0 kb encoded E7 and E6, respectively. A recombinant DNA containing a larger deletion lacking the 3' terminal half of ORF L2 and all of ORF L1 (pdlBc/l) did not induce papillomas. The results indicate that sequences in the late region not required for transformation of NIH 3T3 cells by bovine papillomavirus type-1 essential in CRPV for induction of papillomas.

Animals↗

The cleavage recognition signal is contained within sequences surrounding an a-a junction in herpes simplex virus DNA.

Herpesvirus genome maturation involves site-specific cleavage of viral DNA concatemers and encapsidation of unit-length molecules, processes that are apparently coupled. Here, applying a transfection-infection approach, we have investigated the arrangement of the DNA sequence elements involved in cleavage and shown that specific cleavage occurs independently of DNA replication. We show that the cis-acting signal for cleavage is located within a 179-bp fragment from across an a-a junction formed as part of the genome maturation process of herpes simplex virus 1. Plasmids carrying the 179-bp fragment are cleaved at the appropriate site even though they are unable to replicate in HSV-infected cells. When linked to an origin, the same 179-bp a-a fragment will replicate and package into progeny virus as a defective genome. Two highly conserved homologies, pac1 and pac2, that have been observed in all herpesviruses examined, including cytomegalovirus, Epstein-Barr virus, varicella-zoster virus, and herpes simplex virus 2 as well as the herpes simplex virus 1 genome, are contained within the 179-bp fragment. This suggests that a common mechanism is utilized for genome maturation in the herpesvirus group.

Animals↗

A variant of CRPV DNA preferentially maintained as a plasmid in NIH 3T3 cells and characterization of its transcripts in nude mouse tumors.

Rabbit and human papillomaviruses are strictly epitheliotropic and their DNA replicates extrachromosomally in benign lesions (warts) of their natural host. Their tissue and host specificity is thought to be genetically controlled and may account for the inefficiency in transforming heterologous cells. In our hands, CRPV DNA did not induce foci in NIH 3T3 cells and in cotransfections with a selectable marker only integrated DNA was found. The viral DNA appeared to be transcriptionally inactive since no transcripts could be detected and in cells were not tumorigenic for nude mice. In contrast to these results a spontaneously derived CRPV variant DNA was able to replicate extrachromosomally and a majority of focus-derived cell lines were tumorigenic for nude mice. In nude mouse tumors the variant DNA remained exclusively extrachromosomal and viral transcripts were detected. The sizes of the major transcripts were 2.0 and 1.3 kb and this suggested that E6 and E7 were expressed. The situation in rabbit tissue was different; both variant and wild-type DNA were maintained extrachromosomally. The extrachromosomal maintenance of the variant but not of wild-type DNA in mouse cells suggests that the variant lacks sequences which may play a role in the host and the tissue restriction of CRPV. The deletion in the variant DNA was located in the late region and included most or all of L1 and a carboxy terminal segment of L2. A second deletion eliminated some pBR322 sequences.

Animals↗

Identification of the major cottontail rabbit papillomavirus late RNA cap site and mapping and quantitation of an E2 and minor E6 coding mRNA in papillomas and carcinomas.

The capsite of the 2.6- and 4.8-kb major late transcripts of cottontail rabbit papillomavirus (CRPV) has been mapped by primer extension. A leader exon of about 300 nucleotides common to both RNAs is located in the untranslated region of the genome upstream of the capsites for early transcripts. In contrast to the early capsites which are all preceded by TATA boxes, no such sequence is present 30 nucleotides upstream of the late capsite. These data indicate that the switch from early to late transcription involves recognition of a new promoter and suppression of transcription termination at the early polyadenylation site. We have also identified a minor exon with a coding potential for a putative E2 transactivating protein. Quantitation by S1 mapping of the E2 coding exon and a minor exon coding for a full-sized E6 protein unique in size to the highly oncogenic CRPV did not reveal differences in the level of transcription between papillomas and carcinomas.

Animals↗

A human papilloma virus type 11 transcript encoding an E1--E4 protein.

The human papilloma virus (HPV) associated with a genital wart (condyloma acuminatum) was determined to be type 11. The majority of the viral DNA molecules were monomeric circles present in the cells at high copy number, as demonstrated by one- and two-dimensional agarose gell electrophoretic separation followed by Southern blot analysis. A cDNA library in phage lambda gt11 was constructed from poly(A)-selected mRNA recovered from the tissue. Recombinant clones corresponding to the most abundant 1.2-kb viral mRNA species detected by Northern blot hybridization and by electron microscopic analysis of R loops were isolated and their nucleotide sequence was determined. Comparison to the prototype HPV-11 DNA sequence revealed that this message consisted of two exons. The promotor-proximal exon spanned nucleotides 716 through 847 and the distal exon included nucleotides 3325 through 4390 or 4392. The mRNAs were alternatively polyadenylated after either of these latter two sites, in both cases following a G and preceding a U residue. Fourteen or sixteen bases upstream from the poly(A) was the hexanucleotide AGUAAA, which apparently serves as the signal for cleavage and polyadenylation of the nascent message. The splice donor and acceptor sites conformed to the usual /GU. . .AG/pattern. The exons joined open reading frame (ORF) E1, which contributed the initiation codon and four additional triplets, to ORF E4, which specified 85 amino acids to encode a protein of 10,022 Da. The cDNA also contained the ORFs E5a and E5b toward the 3' end. The complete sequence of the cDNA revealed three single-base changes from the prototype HPV-11, two resulting in altered amino acids in E4. Neither affects the coding potential of the overlapping E2 ORF. The function of the E1--E4 protein is unknown.

Base Sequence↗

Human papillomavirus types 6 and 11 mRNAs from genital condylomata acuminata.

We have identified and mapped a number of RNA species of human papillomavirus types 6 and 11 from condylomata acuminata by the electron microscopic R-loop technique. Each of the early (E)- and late (L)-region open reading frames (ORFs) deduced from the DNA sequences was represented in one or more transcripts. In addition, RNA species that could encode the modulator of DNA replication and the repressor of transcription, functions recently identified in the genetically similar bovine papillomavirus type 1, were also detected. Some ORFs were 5' proximal in one or more transcripts, whereas others were not 5' proximal in any species, suggesting that internal initiation of translation might be required to gain access to these latter ORFs. Virtually all transcripts had their 5' ends located in the E region and were polyadenylated at one of two sites, i.e., at the end of the E region or at the end of the L region. The great majority of the RNAs were derived from the E region of the genome, with one species approximately 50 to 100 times more abundant than the others. For most of the RNAs, the 5' end mapped near nucleotide 700; minor populations had 5' ends near nucleotide 100 or 1200. By correlating our mapping data with the genomic DNA sequences as well as available RNA structures and cDNA sequences of several papillomaviruses, we predict a number of mRNA splice donor and acceptor sites and suggest that the papillomaviruses have sophisticated usage of ORFs through alternative promoters, mRNA splice sites, and polyadenylation sites.

Anus Neoplasms↗

Cottontail rabbit papillomavirus-specific transcripts in transplantable tumors with integrated DNA.

The viral DNA and viral transcripts of a VX2 and a VX7 transplantable carcinoma lines were analyzed. Both tumor lines contain equivalent numbers of gene copies per cell of exclusively integrated viral DNA. Integration is in head-to-tail tandem repeats, in probably three sites and at least two integration sites are common. In both tumors, about half of the viral genomes share a 90-bp deletion. Common integration sites and deletions suggest that the two tumor lines were derived from the same parent tumor. The tumors contain the same major viral transcripts of 1.3 and 2.0 kb also found in both papillomas and primary carcinomas of domestic rabbits [M. Nasseri, F. O. Wettstein, and J. G. Stevens, J. Virol. 44, 263-268 (1982)]. However, the carcinoma lines differ in their minor transcripts. VX7 has four minor transcripts of 5.2, 3.8, 3.6, and 3.0 kb and VX2 has two of 4.8 and 3.0 kb. The 4.8-kb transcript is relatively major and appears to be identical to a major transcript present in virus-producing tumors of cottontail rabbits [M. Nasseri and F. O. Wettstein, J. Virol. 51, 706-712 (1984)].

Animals↗

Differences exist between viral transcripts in cottontail rabbit papillomavirus-induced benign and malignant tumors as well as non-virus-producing and virus-producing tumors.

Five major cottontail rabbit papillomavirus-specific polyadenylated RNA species with sizes of 4.8, 2.6, 2.0, 1.3, and 0.9 kilobases (kb) were found in virus-producing tumors of cottontail rabbits (the natural host for the virus). Two of the RNA species (sizes, 2.0 and 1.3 kb) are indistinguishable with respect to size and map position from the RNA species detected previously in non-virus-producing benign and malignant tumors (Nasseri et al., J. Virol. 44:263-268, 1982). The 2.0-kb RNA in virus-producing benign tumors is more abundant than the 1.3-kb RNA. This, together with similar observations of benign non-virus-producing tumors, suggests that the predominance of the 2.0-kb RNA is a general feature of benign tumors. The change to a preferential synthesis of the 1.3-kb RNA appears to be a phenomenon of tumor progression from papillomas to carcinomas. Three transcripts of 4.8, 2.6, and 0.9 kb are unique to virus-producing tumors. The RNA molecules were mapped in two steps. First, hybridization of Northern blots with subgenomic probes revealed the approximate map position of the transcripts. Second, with nuclease S1 and exonuclease VII mapping procedures and end-labeled probes, the major exons of the 4.8-, 2.6-, 2.0-, and 1.3-kb RNAs were mapped precisely, and it is shown that all RNAs are transcribed from the same DNA strand. Both 1.3- and 2.0- kb RNAs consist of two exons which are separated by an identical 2.45-kb intron. The 5' ends of the 5'-proximal exons of the 2.0- and 1.3-kb RNAs map to positions 0.07 and 0.16, respectively. Some of the 2.0-kb RNA molecules, especially in the carcinoma, have an alternative 5' end at position 0.06. The 3' ends of both exons map to position 0.22, where two ends were found about seven nucleotides apart. The sizes of the 5'-proximal exons of the 2.0- and 1.3-kb RNAs are 1.23 and 0.48 kb, respectively. The 1.3- and 2.0-kb RNAs share a common 3'-proximal exon of 0.66 (0.61) kb. This exon has two 5' ends 50 nucleotides apart at map position 0.53 and a 3' end at map position 0.61. Only the 3'-proximal part of the 4.8- and 2.6-kb RNAs have been mapped precisely. Both RNAs share a common 3' end at position 0.99. The 2.6-kb RNA part consists of a single 1.59-kb exon which extends to map position 0.79.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Two colinear and spliced viral transcripts are present in non-virus-producing benign and malignant neoplasms induced by the shope (rabbit) papilloma virus.

The nature of Shope virus-specific RNA was investigated in non-virus-producing Shope (rabbit) papilloma virus-induced benign and malignant domestic rabbit tumors and in a cell line derived from the VX-7 transplantable carcinoma. RNA transfer (Northern) blot analysis of polyadenylated RNA isolated from whole cell extracts of all three sources was resolved into two major bands of 1.3 and 2.0 kilobases. Two additional minor bands of 3.5 and 4.8 kilobases could be seen in some analyses. RNA of the VX-7 cell line was further separated into nuclear, cytoplasmic, and polysomal fractions. The cytoplasmic fraction only contained the 1.3- and 2.0-kilobase species, and virus-specific RNA was found to be associated with polysomes. The two major transcripts present in VX-7 cells were mapped by hybridization of RNA transfer blots with subgenomic probes, and the results indicated that both transcripts are spliced and are most likely colinear. Our results are consistent with the suggestion that the two viral transcripts are necessary for induction and maintenance of the neoplasms.

Animals↗

Generalized infection and lack of delayed hypersensitivity in BALB/c mice infected with Leishmania tropica major.

The susceptibility of a few strains of mice to a subcutaneous injection of Leishmania tropica major, the causative agent of cutaneous leishmaniasis in humans, was studied. The infection in six strains (CBA, AKR/J, AKR/cu, C57BL/6, A/J, and C3H) remained cutaneous, and the animals recovered within 3 to 4 months. In contast, the infection in BALB/c became generalized and killed 1005 of infected animals. Intraperitoneal injection of infected liver of BALB/c to A/J and syngeneic mice produced a lethal disease in BALB/c but no infection in A/J mice. Lower doses of the parasite produced a lethal infection in BALB/c but no apparent disease in A/J. Hence, the host rather than the parasite is responsible for the outcome of the disease. The peak antibody titer of BALB/c mice was not significantly higher than that of A/J mice. However, BALB/c failed to show any delayed hypersensitivity to leishmania tested by footpad reaction, whereas A/J mice showed a strong response.

Animals↗

[Effects of bacterial peritonitis on the low-pressure system in man].

The effective compliance (C) of the "low-pressure system" has been measured in ten patients with bacterial peritonitis by means of plotting pressure and volume on the first postoperative day (deltaV = 500 ml/10 min). The value of C is decreased in one group of patients, while it increases to as much as five times that of "normal patients" in the other. The cause might be a summation effect of hypovolemia, blood volume shift from intra- to extrathoracic space, and endotoxin reaction on the tone of vascular smooth muscle. The augmentation of the intravascular volume results in an increase of portal venous pressure, which is less than central venous pressure. Splanchnic pooling through increased vascular resistance does not appear.

Bacterial Infections↗

[Varied circulatory effects after rapid infusion of hydroxyethyl starch, dextran 60 and blood in the postoperative patient].

The acute hemodynamic effects which occur after a quick infusion (500 ml per 10 minutes) of hydroxyethyl starch, dextran 60 or autologous blood with identical hematocrit were studied in three groups of 10 patients each on the first day after laparotomy. If blood is infused there is only a moderate increase of the total perfusion (+18%) observed, however hydroxyethyl starch or dextran 60 infusions result in a striking increase of the cardiac output (+34%, +44%, respectively). There is no significant difference among the latter two groups. Thus, hydroxyethyl starch as well as dextran 60 can be considered as a potent volume substitute, if an acute effectiveness is wanted.

Blood Transfusion, Autologous↗

[Postoperative peritonitis. A contribution on diagnosis].

Symptoms and signs of 18 patients with postoperative bacterial peritonitis were compared with the findings in uncomplicated postoperative cases. Their diagnostic values were examined: 1. Elevated temperature, hyperventilation, and somnolence are relevant, being indicative of bacterial peritonitis and already occurring before the typical findings on abdominal examination. 2. In those patients with peritonitis, hemodynamics, and metabolism are characterized by hyperdynamic circulation, premature arterial hypotension with dry warm skin, and lactate accumulation. 3. Laboratory data often reveal thrombocytemia, leucocytosis with shift to the left, and a relative and absolute hypophosphatemia.

Blood Circulation↗

[Aortic arch syndrome (author's transl)].

This report demonstrates a case of a fully developed aortic arch syndrome with an unusual lack of symptoms. A sufficient collateralisation and nearly free cerebral vessels were hiding the clinical manifestations of arteriosclerosis for a long time. Besides the diagnostic maneuvers the operative therapy is shown during which a short, acute circulatory failure occurred caused by a reflex reaction of the carotic sinus due to the improved blood supply.

Aortic Arch Syndromes↗