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The retrotransverse foramen of the human atlas vertebra. A distinctive variant within primates.

The occurrence of a retrotransverse foramen of the atlas has been investigated in a series of 409 nonhuman primates representative of 40 genera, and in a series of 500 human atlases (dried bones). In nonhuman primates, no retrotransverse foramen was found in any of the individuals studied. In humans, the retrotransverse foramen was observed in 71 cases (14.2%). It was present bilaterally in 21 cases (29.6% of the 71 foramina), and unilaterally in 50 cases (70.4%). The foramen was present in 44 cases on the right side, and 48 on the left side. The character was noted as present only if it was complete; partial forms were not recorded. Various aspects of the retrotransverse foramen were observed. The present observations suggest that the retrotransverse foramen is a uniquely derived trait (autapomorphy) within primates which is restricted to some individuals in Homo sapiens. Appearance of this foramen in human evolution can be related to the acquisition of the erect posture and bipedal locomotion, and consecutive modifications of the regional venous circulation.

Animals↗

[Augustin Belloste (1654-1730), aspects of the surgery in military hospitals during the Piemont-Savoie War (1686-96)].

The surgical practice in military hospitals during the XVIIth century remains poorly known. An original statement is provided by A. Belloste (1654-1730) who enlisted as military surgeon in 1686. In 1690 began the Piemont-Savoie War during which he was in position in the military hospitals of Briançon, Pignerol, and Oulx. In 1696, after the end of the war, A. Belloste published a treatise, the hospital surgeon, written according to the experience he gained and the observations he consigned during his ten years of practice, particularly in the military hospital of Briançon. Interesting information is given concerning the military hospitals recruitment and the patients origins. The transfer to a military hospital seemed to be considered as the last resort, with sometimes wounded persons waiting during long months in dreadful conditions. The pathologies observed and treated consisted principally in war traumatisms by sword or firearms, but also came victims of traumatisms happened during great defensive works as those of Vauban, or presenting pathologies related to the specificites of the alpine environment as falls, altitude or cold... The lodging conditions in hospital were summary, and were often unfavourable to a good evolution of the injuries. A. Belloste particularly developed and defended the interest of a soft, measured, and rational treatment of the wounds.

General Surgery↗

Evolution of dentition in prehistoric Ohio Valley Native Americans III. Metrics of deciduous dentition.

Deciduous tooth size in Native Americans of the Ohio Valley area is fairly stable from the terminal Late Archaic (3200 BP) through the Late Prehistoric (350 BP) periods. Some fluctuation in average size did occur during this time. These fluctuations most likely reflect random changes due to gene drift. However, no difference in the pattern of interactions among the sizes of teeth (covariance structures) can be demonstrated during this period. Principal components analysis of the buccolingual and mesiodistal dimensions in the total sample indicate that the major axis of deciduous tooth size in the Ohio Valley population shows an allometric relationship, with the dimensions of the anterior teeth increasing (or decreasing) as the 1.33 power of the dimension of m1(1) and as the 2.0 power of the dimension of m2(2). Comparison of the Ohio Valley samples with other samples from the Eastern Woodlands suggests that geography may have played a minor role in structuring deciduous tooth size variation. For the most part, however, widely separated Eastern Woodlands populations appear to have been evolving independently with respect to deciduous tooth size.

Anthropology, Physical↗

Abberant cytogenetic evolution pattern of Philadelphia-positive chronic myeloid leukemia treated with interferon-alpha.

The cytogenetic evolution of 32 Philadelphia (Ph)-positive chronic myeloid leukemias (CML) receiving interferon-alpha (IFN-alpha) therapy was compared to the patterns in untreated CML and cases treated with busulfan (Bu), hydroxyurea (Hy), and allogeneic bone marrow transplantation (BMT). Half of the CML receiving IFN-alpha had at least one of the well-known major or minor route aberrations whereas 16 cases displayed unusual secondary abnormalities, of which only del(7p) and del(13q) were recurrent; a frequency significantly higher than in CML without therapy or after Bu and Hy treatment (P < 0.001) but similar to the one found post-BMT. The incidence of cases with cytogenetically divergent subclones, ie cell populations with unrelated aberrations in addition to the t(9;22), was also higher in the IFN-alpha group compared to the untreated, Bu and Hy groups (P < 0.01) but similar to the post-BMT group. Finally, 14 of the 32 IFN-alpha-treated CML displayed cytogenetic evolution already during the chronic phase; again a higher incidence than in the untreated, Bu and Hy groups (P < 0.001) but not different from the post-BMT group. These findings strongly indicate that IFN-alpha, directly or indirectly, can induce clones with aberrant chromosomal evolution patterns to evolve and proliferate, but the mechanisms underlying these cytogenetic peculiarities remain to be elucidated.

Adult↗

Pre-malignant and malignant lymphoproliferations in an HCV-infected type II mixed cryoglobulinemic patient are sequential phases of an antigen-driven pathological process.

Type II mixed cryoglobulinemia (MC) is a systemic vasculitis characterized by the presence in the serum of a monoclonal cryoprecipitable IgM with rheumatoid factor (RF) activity. Hepatitis C virus (HCV) has been recognized as its major etiologic factor. Because MC frequently evolves into overt B-cell non-Hodgkin's lymphoma (NHL), chronic HCV infection is hypothesized to lead to both benign and malignant lymphoproliferative disease. In this study, we investigated mutations in the V(H) and V(K) genes of the B-cell clone originating the overt B-cell lymphoma in a subject with MC. Mutational patterns were analyzed longitudinally in two bone marrow biopsies obtained at the stage of MC, as well as in multiple involved tissues (bone marrow, liver, and peripheral blood cells) at the stage of overt NHL. Hybridization of variable-diversity-joining (VDJ) PCR products with a probe specific for the neoplastic clone indicated that the lymphoma originated from one of the clones over-stimulated during MC. This clone producing an IgM highly homologous to a protein with RF specificity may explain the MC syndrome in the patient. Moreover, the presence of an IgH ongoing mutation process and the expression of an Ig antigen receptor significantly homologous to an anti-HCV protein support the hypothesis that the MC syndrome and the subsequent evolution to NHL are antigen-driven lymphoproliferative processes possibly sustained by HCV. Furthermore, the marked reduction in intra-clonal diversity in the last bone marrow biopsy obtained at the stage of overt NHL points out a minor dependence of the cells on the antigen-driven mechanism, although an intrinsic propensity of the neoplastic cell to undergo replacement mutations cannot be excluded.

Amino Acid Sequence↗

Genetic variation in yellow fever virus: duplication in the 3' noncoding region of strains from Africa.

The nucleotide sequences of three regions of the genomes of 13 yellow fever (YF) virus isolates were determined to define genetic variation and evolution of the virus. Phylogenetic trees generated from sequences of either the 5' terminal 1320 nucleotides of the genome, 754 nucleotides from the NS4A and NS4B genes, or the 3' terminal 511 nucleotides were very similar and contained minor differences. Overall, these results suggested that there were at least four major genotypes of YF virus, including one in Central/East Africa, one in West Africa, and two in South America. Examination of the 3' noncoding region (3'NCR) showed that only West African strains had a 3'NCR of 511 nucleotides while strains from Central/East Africa and South America had shorter 3'NCRs (443-469 nucleotides) due to the absence of YF specific repeat sequences (RYFs). Central/East African strains have two RYFs and West African strains have three RYFs while South American strains only have one copy of the RYF. It is speculated that duplication of the RYF took place in West Africa subsequent to the presumed introduction of YF virus into South America. Thus, both tick-borne (Mandl et al., J. Virol. 65, 4070-4077, 1991 and Wallner et al., Virology 213, 169-178, 1995) and mosquito-borne flaviviruses have variable 3'NCRs.

Africa↗

Characterization of a tandemly repeated DNA sequence family originally derived by retroposition of tRNA(Glu) in the newt.

A previous report from this laboratory showed that in vitro transcription of total genomic DNA of the newt Cynopus pyrrhogaster resulted in a discrete sized 8 S RNA, which represented highly repetitive and transcribable sequences with a glutamic acid tRNA-like structure in the newt genome. We isolated four independent clones from a newt genomic library and determined the complete sequences of three 2000 to 2400 base-pair PstI fragments spanning the 8 S RNA gene. The glutamic acid tRNA-related segment in the 8 S RNA gene contains the CCA sequence expected as the 3' terminus of a tRNA molecule. Further, the 11 nucleotides located 13 nucleotides upstream from one of the two transcription initiation sites of the 8 S RNA were found to be repeated in the region upstream from the termination site, suggesting that the original unit, which is shorter than the 8 S RNA, was retrotransposed via cDNA intermediates from the PolIII transcript. In the upstream region of the 8 S RNA gene, a 360 nucleotide unit containing the glutamic acid tRNA-related segment was found to be duplicated (clones NE1 and NE10) or triplicated (clone NE3). Except for the difference in the number of the 360 nucleotide unit, the three sequences of the 2000 to 2400 base-pair PstI fragment were essentially the same with only a few mutations and minor deletions. Inverse polymerase chain reaction and sequence determination of the products, together with a Southern hybridization experiment, demonstrated that the family consists of a tandemly repeated unit of 3300, 3700 or 4100 base-pairs. Thus during evolution, this family in the newt was created by retroposition via cDNA intermediates, followed by duplication or triplication of the 360 nucleotide unit and multiplication of the 3300 to 4100 base-pair region at the DNA level.

Animals↗

The chromosome complement of Sorex granarius--the ancestral karyotype of the common shrew (Sorex araneus)?

We present the G-band karyotype of Sorex granarius (Miller, 1910). With minor exceptions, each of the acrocentric autosomes in this karyotype is completely homologous to one of the chromosome arms in the karyotype of the common shrew (Sorex araneus L., 1758). If, as is the simplest interpretation, the karyotypic evolution in S. araneus is by repeated Robertsonian fusion, the karyotype in S. granarius represents the ancestral condition. We urge breeding studies to establish whether the designation of S. granarius as a full species is justified.

Animals↗

Insecticide use and organophosphate resistance in the coffee leaf miner Leucoptera coffeella (Lepidoptera: Lyonetiidae).

Increasing rates of insecticide use against the coffee leaf minerLeucoptera coffeella(Guérin-Méneville) and field reports on insecticide resistance led to an investigation of the possible occurrence of resistance of this species to some of the oldest insecticides used against it in Brazil: chlorpyrifos, disulfoton, ethion and methyl parathion. Insect populations were collected from ten sites in the state of Minas Gerais, Brazil and these populations were subjected to discriminating concentrations established from insecticide LC99s estimated for a susceptible standard population. Eight of the field-collected populations showed resistance to disulfoton, five showed resistance to ethion, four showed resistance to methyl parathion, and one showed resistance to chlorpyrifos. The frequency of resistant individuals in each population ranged from 10 to 93% for disulfoton, 53 to 75% for ethion, 23 to 76% for methyl parathion, and the frequency of resistant individuals in the chlorpyrifos resistant population was 35%. A higher frequency of individuals resistant to chlorpyrifos, disulfoton and ethion was associated with greater use of insecticides, especially other organophosphates. This finding suggests that cross-selection, mainly between organophosphates, played a major role in the evolution of insecticide resistance in Brazilian populations of L. coffeella. Results from insecticide bioassays with synergists (diethyl maleate, piperonyl butoxide and triphenyl phosphate) suggested that cytochrome P450-dependent monooxygenases may play a major role in resistance with minor involvement of esterases and glutathione S-transferases.

Animals↗

Coordination of Chloroplastic Metabolism in N-Limited Chlamydomonas reinhardtii by Redox Modulation (II. Redox Modulation Activates the Oxidative Pentose Phosphate Pathway during Photosynthetic Nitrate Assimilation).

The onset of photosynthetic NO3- assimilation in N-limited Chlamydomonas reinhardtii increased the initial extractable activity of the glucose-6-phosphate dehydrogenase (G6PDH), the key regulatory step of the oxidative pentose phosphate pathway. The total activated enzyme activity did not change upon NO3- resupply. The higher activity, therefore, represents activation of existing enzyme. No activation occurred during NH4+ assimilation. Incubation of extracts with DTT reversed the NO3- stimulation of G6PDH activity, indicating that the activation involved redox modulation of G6PDH. Phosphoribulosekinase, an enzyme activated by thioredoxin reduction, was inhibited at the onset of NO3- assimilation. A 2-fold stimulation of O2 evolution and a 70% decrease in the rate of photosynthetic CO2 assimilation accompanied the enzyme activity changes. There was an immediate drop in the NADPH and an increase in NADP upon addition of NO3-, whereas NH4+ caused only minor fluctuations in these pools. The response of C. reinhardtii to NO3- indicates that the oxidative pentose phosphate pathway was activated to oxidize carbon upon the onset of NO3- assimilation, whereas reduction of carbon via the reductive pentose phosphate pathway was inhibited. This demonstrates a possible role for the Fd-thioredoxin system in coordinating enzyme activity in response to the metabolic demands for reducing power and carbon during NO3- assimilation.

Journal Article↗

A 7 year survey of acute hepatitis type B.

Epidemiological and clinical features of acute symptomatic hepatitis type B were evaluated in 51 otherwise healthy children and in 13 children receiving immunosuppressive treatment for leukaemia and malignancy, who were admitted to hospital with acute hepatitis B surface antigen (HBsAg) positive hepatitis during a period of 7 years. Blood transfusions, or intimate contacts with asymptomatic HBsAg carriers or with contaminated material during repeated admission to hospital were the possible sources of infection in the immunosuppressed patients, whereas percutaneous exposure was identified as the source in a minority of non-immunosuppressed patients. Features of the acute phase of the illness differed little between the two groups of patients (acute liver failure developed in one patient with leukaemia and in two untreated children). Conversely, chronic evolution was observed in 69% of immunosuppressed patients but in only 9% of untreated children and affected only patients born to HBsAg positive mothers (two of four patients) or patients presenting with papular acrodermatitis (both patients).

Age Factors↗

Targetoid hemosiderotic nevus. A trauma-induced simulator of malignant melanoma.

BACKGROUND: Simulators of malignant melanoma comprise a heterogenous group of melanocytic and nonmelanocytic lesions of the skin. Among frequent clinical mimickers of melanoma are injured melanocytic nevi. Any change in the clinical appearance of a pre-existing nevus should alert the clinician to exclude the possibility of malignant transformation in order to early identify a lesion at a stage when complete cure can still be achieved. OBJECTIVE: The purpose of this study was to present the clinical, dermoscopic and histopathologic findings of a series of acquired melanocytic nevi which abruptly developed a pigmented peripheral halo, presumably following minor trauma. METHODS: A series of 6 cases of acquired melanocytic nevi which suddenly developed a targetoid halo were included in the study. All lesions were evaluated by dermoscopy. Three cases were surgically removed at different stages of evolution and submitted to histopathologic examination. In all cases, follow-up was obtained. RESULTS: All the lesions arose on trauma-prone skin sites of young women. The sudden development of an asymptomatic, targetoid halo on a long-lasting, acquired exophytic nevus was the main presentation. Whereas the central nevus persisted, the ecchymotic halo ultimately disappeared. Histopathologic examination disclosed changes of the traumatized nevus in the central part, whereas the ring showed hemorrhage and hemosiderin deposits. Increased numbers of small vessels with hobnail characteristics were associated features. CONCLUSIONS: Targetoid hemosiderotic nevus is a distinctive clinicopathologic variant of traumatized acquired melanocytic nevus which should be included in the list of clinical simulators of melanoma.

Adolescent↗

Emerging treatments for ovarian cancer.

The survival at 5 years, of patients with ovarian cancer, has steadily improved since 1960, when surgery and alkylating agents were the only initial modalities employed to cope with the usual late presentation of the disease. In the 1980s, cisplatin and then carboplatin became established as the most active drugs, alone or in combination with other drugs. In the last decade, the antimicrotubulin drug paclitaxel, and the topoisomerase I inhibitor topotecan were noted to be active after failure of platinum drugs. These drugs, as well as others with known activity in the second-line setting, such as the pegylated liposomal doxorubicin, gemcitabine and oral etoposide, all play a role in the treatment of these patients and likely prolong survival without eradicating the disease. The plight of these patients has stimulated new areas of drug development. Here, the evolution of the current therapeutic strategy, the scientific rationale for cytotoxic and non-cytotoxic agents and their status at present are reviewed. 'Targeted' drug trials, in contrast to trials studying cytotoxic drug analogues, currently represent only a minor portion of clinical trials in ovarian cancer.

Animals↗

Lectin characterization of cystogenesis in the SBM transgenic model of polycystic kidney disease.

The generation of a novel transgenic mouse model of polycystic kidney disease with a construct (SBM) that links the coding region of the c-myc proto-oncogene to the simian virus 40 enhancer and beta-globin promoter was previously reported (see reference 1). In order to determine the site of origin and histogenesis of renal cysts in this model, lectin/immunohistochemical and electron microscopic studies on mice of varying ages (from birth to adulthood) are described here. Cysts are detectable at birth and increase in number and diameter with age. Cysts predominantly involve the collecting tubules of young transgenic mice but progressively affect the proximal tubules with advancing age. A minority of cysts are of distal tubular origin in all age groups studied. Tubular hyperplasias are primarily reactive with proximal tubular markers and appear to precede the development of proximal tubular cysts in adult mice. This particular phenotypic evolution of polycystic kidney disease with advancing age suggests that the cystogenic potential of the transgene is modulated by yet unidentified tubular segment-specific responses.

Animals↗

[Skin aplasia of the vertex. Report of a familial form].

The authors report about a familial case of skin aplasia of the vertex cranii, of which they present a form that required emergent surgical repair with a favorable outcome. The investigation allowed tracing two relatives with minor forms expressed as alopecia of the vertex. Skin aplasia of the vertex cranii is an exceptional condition, which consists in the congenital absence of cutaneous, bony and/or dural tissue in the cranium. The various etiopathogenetic, clinical, diagnostic, evolutive and therapeutic aspects are reviewed.

Congenital Abnormalities↗

Virological effects of ISIS 14803, an antisense oligonucleotide inhibitor of hepatitis C virus (HCV) internal ribosome entry site (IRES), on HCV IRES in chronic hepatitis C patients and examination of the potential role of primary and secondary HCV resistance in the outcome of treatment.

Antisense oligonucleotides represent a promising class of antiviral agents. ISIS 14803 is a 20-unit phosphorothioate oligodeoxynucleotide that inhibited hepatitis C virus (HCV) replication and protein expression in cell culture and mouse models. A Phase I dose-escalation clinical study of ISIS 14803 was performed in 24 patients with HCV genotype 1 chronic hepatitis C. The patients received 0.5, 1.0, 2.0 or 3.0 mg/kg of ISIS 14803 for 4 weeks. Two of them receiving 2.0 mg/kg, experienced a significant (>1.0 log10) viral load reduction and nine other patients experienced minor (<1.0 log10) viral load reductions that were difficult to definitively distinguish from assay or patient variations. The aims of this study were to examine the effect of ISIS 14803 on its target site and neighbouring region quasispecies evolution, and to determine whether primary and secondary HCV resistance contributed to the observed virological response rate. The HCV internal ribosome entry site (IRES), including the ISIS 14803 target site in virus specimens collected from patients at baseline and end-of-treatment, was sequenced. An extensive IRES quasispecies analysis was performed in 10 of the patients at various time points before, during and after ISIS 14803 treatment. A significant IRES genetic evolution was found in three out of 10 patients through quasispecies analysis suggesting that treatment with ISIS 14803, a drug designed to bind to HCV RNA, exerted a selective pressure on HCV IRES. However, no mutations in the ISIS 14803 target site, which would inhibit binding of the oligonucleotide to HCV RNA, were detected before (primary resistance) or after treatment (secondary resistance) with the oligonucleotide. Furthermore, no obvious nucleotide changes in the surrounding IRES region that might possibly affect oligonucleotide binding were detected.

5' Untranslated Regions↗

[Role of computed tomography in splenic blunt trauma].

The CT scans of 18 patients (12 males and 6 females; mean age: 43.6 years) with splenic blunt trauma were reviewed. CT examinations had been made at different times after trauma. The CT images were grouped according to the time of examination and both structure and densitometry were evaluated in all lesions. In all cases CT findings were correlated with surgical and pathologic data. The patients were divided into two groups: group I included 11 subjects in whom CT had been performed within 48 hours following trauma and group II included 7 patients who had undergone CT at different times after trauma (3-13 days; mean: 6.5 days). All the lesions in group I exhibited blurred outlines, while the lesions in group II had clear-cut margins. The lesions in group I were always hyperdense while those in group II were hypodense. CT diagnosis was always in agreement with surgical findings. In conclusion, we confirm the value of CT in the examination of splenic lesions by blunt abdominal trauma. The evolution of splenic lesions is usually typical: CT yields useful information for injury evaluation and is therefore very important to plan treatment. We believe that CT should be performed as soon as possible, even on the basis of minor clinical and laboratory data.

Adolescent↗

Reconstruction of microsatellite mutation history reveals a strong and consistent deletion bias in invasive clonal snails, Potamopyrgus antipodarum.

Direct observations of mutations and comparative analyses suggest that nuclear microsatellites show a tendency to expand, with reports of deletion biases limited to very long alleles or a few loci in multilocus studies. Here we investigate microsatellite evolution in clonal snails, Potamopyrgus antipodarum, since their introduction to Britain in the 19th century, using an analysis based on minimum spanning networks of multilocus microsatellite genotypes. British populations consist of a small number of highly distinct genotype groups with very few outlying genotypes, suggesting clonal lineages containing minor variation generated by mutation. Network patterns suggest that a single introduced genotype was the ancestor of all extant variation and also provide support for wholly apomictic reproduction within the most common clonal lineage (group A). Microsatellites within group A showed a strong tendency to delete repeats, with an overall bias exceeding 88%, irrespective of the exact method used to infer mutations. This highly unusual pattern of deletion bias is consistent across populations and loci and is unrelated to allele size. We suggest that for persistence of microsatellites in this clone, some change in the mutation mechanism must have occurred in relatively recent evolutionary time. Possible causes of such a change in mechanism are discussed.

Animals↗