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Abstract: Background: Complex I (CI) deficiency is the most frequent cause of OXPHOS disorders. Recent studies have shown increases in reactive oxygen species (ROS) production and mitochondrial network disturbances in patients'' fibroblasts harbouring mutations in CI subunits. Objectives: The present work evaluates the impact of mutations in the NDUFA1 and NDUFV1 genes of CI on mitochondrial bioenergetics and dynamics, in fibroblasts from patients suffering isolated CI deficiency. Results: Decreased oxygen consumption rate and slow growth rate were found in patients with severe CI deficiency. Mitochondrial diameter was slightly increased in patients'' cells cultured in galactose or treated with 2′-deoxyglucose without evidence of mitochondrial fragmentation. Expression levels of the main proteins involved in mitochondrial dynamics, OPA1, MFN2, and DRP1, were slightly augmented in all patients'' cells lines. The study of mitochondrial dynamics showed delayed recovery of the mitochondrial network after treatment with the uncoupler carbonyl cyanide m-chlorophenyl hydrazone (cccp) in patients with severe CI deficiency. Intracellular ROS levels were not increased neither in glucose nor galactose medium in patients'' fibroblasts. Conclusion: Our main finding was that severe CI deficiency in patients harbouring mutations in the NDUFA1 and NDUFV1 genes is linked to a delayed mitochondrial network recovery after cccp treatment. However, the CI deficiency is neither associated with massive mitochondrial fragmentation nor with increased ROS levels. The different genetic backgrounds of patients with OXPHOS disorders would explain, at least partially, differences in the pathophysiological manifestations of CI deficiency. [Copyright &y& Elsevier]

The article discusses the disruption of CDKL5 gene in a 2-year-old girl with X-linked infantile spasm syndrome. It mentions that she experienced myoclonic seizures with cyanosis at the age of 1 month while she presents generalized hypotonia, lack of eye contact, and poor pupilar reflex at her present age. It also states that the patient has undergone several diagnostic examinations such as cranial computed tomography scan, electroencephalogram, and human androgen receptor assay (HUMARA).

At present, radiation-attenuated plasmodia sporozoites ( gamma -spz) is the only vaccine that induces sterile and lasting protection in malaria-naive humans and laboratory rodents. However, gamma -spz are not without risks. For example, the heterogeneity of the gamma -spz could explain occasional breakthrough infections. To avoid this possibility, we constructed a double-knockout P. berghei parasite by removing 2 genes, UIS3 and UIS4, that are up-regulated in infective spz. We evaluated the double-knockout Pbuis3(-)/4(-) parasites for protective efficacy and the contribution of CD8(+) T cells to protection. Pbuis3(-)/4(-) spz induced sterile and protracted protection in C57BL/6 mice. Protection was linked to CD8(+) T cells, given that mice deficient in beta (2)m were not protected. Pbuis3(-)/4(-) spz-immune CD8(+) T cells consisted of effector/memory phenotypes and produced interferon- gamma . On the basis of these observations, we propose that the development of genetically attenuated P. falciparum parasites is warranted for tests in clinical trials as a pre-erythrocytic stage vaccine candidate. [ABSTRACT FROM AUTHOR]

Holstein dairy heifers were randomly assigned to 1 of 2 treatments to determine whether a presynchronization strategy using GnRH would improve reproductive performance after synchronization of ovulation and timed artificial insemination (TAI!. Heifers (n = 82) in the first treatment (GPG) received a hormonal protocol for synchronization of ovulation and TAI (100 µg of GnRH, d 0; 25 mg of PGF2α d 6; 100 Ixg of GnRH + TAI, d 8); whereas heifers (n = 84) in the second treatment (GGPG) received GPG, but with the addition ofa GnRH injection ( 100 µg) 7 d before initiation of the GPG protocol. The proportion of heifers receiving AI before d 8 was similar for GPG (4.9%) and GGPG (9.5%), and the proportion of heifers diagnosed pregnant 30 d after AI did not differ between treatments (45 vs. 51%, respectively). Treatment did not affect the proportion of heifers ovulating after the second GnRH injection or the proportion in which a corpus luteum regressed after treatment with PGF2α. In conclusion, presynchronization with GnRH 7 d before initiation of synchronization of ovulation using GnRH and PGF2α did not affect the proportion of heifers expressing estrus before TAI or improve synchronization response or fertility to the synchronization protocol. [ABSTRACT FROM AUTHOR]

This article discusses findings of a study which compared the trends in cesarean delivery among Puerto Rican women who delivered in Puerto Rico and on the U.S. mainland during 1992-2002. Between 1996 and 2002, total and primary cesarean rates increased for Puerto Rican women in both countries. The findings of the study suggested that measures to reduce the number of cesarean deliveries in Puerto Rico should focus on decreasing the rate of primary cesarean deliveries, particularly on women who are at low risk for a cesarean delivery.

Incontinentia pigmenti (IP) is a genodermatosis with an X-linked dominant mode of inheritance, characterized by ectodermal, mesodermal, neurological, ocular, and dental manifestations. The purpose of this case study was to report the oral and dental manifestations of an IP case in a Venezuelan pediatric patient. A 9 year-old Venezuelan girl was evaluated. She showed macular pigmented lesions in her face, trunk, back, legs, and fingers as well as abnormal hair distribution, alopecia on the vertex, and hypoplasia of eyebrows. During the dental examination, conical shaped-teeth and delayed dental eruption was evidenced. The microanalytical examination showed dentin without significant alterations in the mineralization except for hypermineralization in focal areas. In addition, a decrease in the enamel mineralization was observed. [ABSTRACT FROM AUTHOR]

Holstein heifers (n = 189) were submitted to a 42-d artificial insemination (AI) period in which they underwent AI after once-daily evaluation of rubbed tail chalk. At the onset of the AI period (d 0), heifers were assigned randomly to receive synchronization of ovulation and timed AI (TAI; d 0:100 µg of GnRH; d 6: 25 mg of PGF2α; d 8: 100 µg of GnRH + TAI) either without (GPG; n = 95), or with inclusion of a CIDR insert (CIDR; n = 94) from d 0 to 6. No CIDR heifers received AI before d 8 compared with 24% of GPG heifers, and pregnancy rate per AI (PR/AI) at 30 d after TAI did not differ between treatments. To synchronize return to estrus for heifers failing to conceive after TAI, heifers (n = 166) receiving TAI to first service were randomly assigned to receive no further treatment (control; n = 85) or receive a new CIDR insert between 14 and 20 d after TAI (Resynch; n = 81). No Resynch heifers received AI during CIDR treatment compared with 35% of control heifers, and the proportion of heifers receiving AI within 72 h after the day of CIDR removal was 78 vs. 50% for Resynch vs. control heifers, respectively. No treatment x inseminator interaction was detected at first or second AI; however, overall PR/AI was modest for heifers throughout the experiment due to poor performance of 2 of the 3 herd inseminators (14, 6, and 58% PR/AI, respectively). Inclusion of CIDR inserts suppressed estrus during the TAI protocol with no reduction in PR/ AI. Resynchronization of estrus using CIDR inserts resulted in tighter synchrony of estrus among nonpregnant heifers compared with untreated controls. [ABSTRACT FROM AUTHOR]

Nonlactating Holstein dairy heifers (n = 352) 13 mo of age were managed using a 42-d artificial insemination (AI) breeding period in which they received AI after removed tail chalk evaluated once daily. At AI breeding period onset (d 0), heifers were randomly assigned to receive synchronization of ovulation (100 µg of GnRH, d 0; 25 mg of PGF2α d 6; 100 µg of GnRH, d 8) and timed AI (TAI; d 8) and AI after removed tail chalk for the entire AI breeding period (GPG; n = 175), or AI after removed tail chalk for the entire AI breeding period (TC; n = 177). As expected, 17.7% (31/175) of GPG heifers received AI after removed tail chalk before scheduled TAI. Pregnancy rate per artificial insemination (PR/AI) at ∼30 d after first AI tended to be greater for TC (46.5%) than for GPG (38.3%) heifers. No treatment x inseminator interaction was detected; however, overall PR/AI was low for heifers in both treatments due to variation among the 3 inseminators (24.8, 30.0, and 58.0%). Pregnancy loss from ∼30 to ∼75 d after first AI was 10% and did not differ between treatments. Based on survival analysis, days to first AI was greater for TC than for GPG heifers, whereas days to pregnancy across the 42d AI breeding period did not differ between treatments. Overall, 81.2% of GPG heifers receiving TAI synchronized luteal regression and ovulated within 48 h after the second GnRH injection. We conclude that this synchronization protocol can yield acceptable fertility in dairy heifers if AI to estrus is conducted between treatment with GnRH and PGF2α and AI efficiency is optimized. [ABSTRACT FROM AUTHOR]

The aim of this work was to detect and typify human papillomaviruses (HPV) in oral squamous cell carcinoma (OSCC) in a Venezuelan population. Eighteen tissue samples were obtained from biopsies, formalin-fixed, and paraffin-embedded; 16 were diagnosed as SCC. We isolated DNA from paraffin-embedded tissue; two to three sections of 5 μm were obtained and resuspended in digestion buffer and proteinase K. Five microliters of the aqueous phase was used for polymerase chain reaction (PCR). The PCR for HPV amplification was carried out with consensus primers for L1 region (MY09 and MY11) and β-globin gene was used as internal control. The viral types were determined by molecular hybridization with a mix of probes for high/intermediate and low HPV oncogenic risk types. The HPV-DNA was detected in 50% (eight of 16) of the SCC cases. Of these HPV-DNA-positive samples, 68% were histopathologically diagnosed as moderately differentiated SCC. The most common anatomical location was the alveolar ridge mucosa. All positive biopsies contained high oncogenic HPV types. We observed a high prevalence of HPV infection of high oncogenic potential types in patients with SCC in our studied group. The moderately differentiated SCCs were more associated to HPV infection. These differences could be influenced by nutritional, environmental and genetical factors in our population but further studies should be carried out to determine these aspects. [ABSTRACT FROM AUTHOR]

Bulk milk from 60 herds of dairy cattle in a rural region in the central highlands of Peru was tested for antibodies to bovine viral-diarrhoea virus (BVDV) and bovine herpesvirus type 1 (BHV-1). None of the herds had been vaccinated against BVDV or BHV-1. Commercially available indirect ELISA-kits were used for antibody detection. True prevalences of BVDV and BHV-1 antibody-positive herds were 96 and 51%, respectively. A relatively low proportion of strongly positive herds suggests, however, a low prevalence of active BVDV infection. BVDV optical densities (ODs) in bulk milk increased with herd size—indicating a higher within-herd prevalence in the larger herds (probably, in part a consequence of a higher rate of animal movement into these herds). For BHV-1, this pattern was not found; a relatively high proportion of the herds was free from BHV-1 infection in each size category. This could indicate a low rate of reactivation of latent BHV-1 infection. [Copyright &y& Elsevier]

A 30-month-old boy with mental retardation, hypotonia, joint hyperlaxity, Brushfield spots, open mouth, distal axial triradius t′′, and ulnar loops on both forefingers was found to have a 47,XY,+psu idic(21)(q22.1).ish psu idic(21)(q22.1)(D13Z1/D21Z1++,ETS2-) karyotype. The patient’s phenotype, with only some Down’s syndrome (DS) features, is probably related to his disomy for most or all of the critical region 21q22.2→q22.3 and agrees with the current notion that certain DS features may also result from 21q proximal duplications. The phenotypical comparison with 2 other patients with a similar extra idic(21) reveals some discrepancies, which may be related to the inherent clinical variability of similar imbalances; yet, a real difference between the tetrasomic segments cannot be excluded. Noticeably, all 3 patients with 21q proximal tetrasomy did not have cardiac defect and exhibited none or just one out of the five other DS phenotypic features attributed to a single gene or cluster on distal 21q22. [ABSTRACT FROM AUTHOR]

Low density lipoprotein receptors (LDLR), capable of internalizing LDL, are expressed in polymorphonuclear neutrophils (PMN). The expression was assessed using anti-LDLR antibody by flow cytometry. The internalization of LDL was assessed by: (i) quantification of the uptake of labelled LDL with 1,1′-dioctadecyl-3,3,3′,3′ tetramethyl-indocarboxycyanine perchlorate (DiI) by flow cytometry; and (ii) the binding of LDL-125I. In fresh purified cells, Lineweaver-Burk analysis of LDL binding (LDL-DiI) revealed that the calculated Kd (internalized LDL) for PMN (15.0 × 10-9 ) is lower than the Kd for monocytes (1.1 × 10-7 ) and the Kd for lymphocytes (3.2 × 10-7 ). Scatchard analysis (LDL-125I) revealed 25000 binding sites and a Kd of 9.6 × 10-9  for PMN. The interaction of LDL with its receptor caused a two-fold fast (peak at 1 min) and transient increase in the oxidative burst, measured by the formation of 2′,7′ dicholoflurescein (DCF) by flow cytometry. This effect was not observed in monocytes or lymphocytes, and it was blocked by anti-LDLR antibody. The stimulation of LDL was optimal at 10 μg of protein/ml. LDL was able to suppress DCF formation induced by phorbol myristate acetate (PMA) and PMA was unable to further stimulate LDL-treated cells, suggesting protein kinase-C (PKC) involvement in LDL effects. Using a PKC assay, LDL was shown to induce a two-fold increase in PKC translocation to the membrane. Thus, LDL increases PMN oxidative burst through a PKC-dependent pathway. [ABSTRACT FROM AUTHOR]

A 13 year old male with a severe progressive neurological disorder was found to have a pseudodicentric chromosome resulting from a telomeric fusion 15p;20p. In lymphocytes, the centromeric constriction of the abnormal chromosome was always that of the chromosome 20, while in fibroblasts both centromeres were alternately constricted. Cd staining was positive only at the active centromere, but a weak anticentromere immunofluorescence was present at the inactive one. We suggest that centromere inactivation results from a modified conformation of the functional DNA sequences preventing normal binding to centromere specific proteins. We also postulate that the patient's disorder, reminiscent of a spongy glioneuronal dystrophy as seen in Alper's and Creutzfeldt-Jakob diseases, may be secondary to the presence of the pathogenic isoform of the prion protein encoded by a gene mapped to 20p12----pter. [ABSTRACT FROM PUBLISHER]

A Mexican mestizo family is reported in which two opposite sexed sibs, born to consanguineous parents, had a skeletal dysplasia. The salient features were a bell shaped thorax owing to short ribs, short limbed dwarfism, pelvic hypoplasia, dislocatable radial heads, elongated distal fibulae, and improvement with age. It is concluded that the present observation probably represents a distinct autosomal recessive thoraco-limb dysplasia identifiable at birth. [ABSTRACT FROM PUBLISHER]

Two unrelated patients with monosomy 13q32.3----qter are reported. Comparison with six similar cases previously published indicates that the craniofacial dysmorphism of the 13qter monosomy syndrome is related to band 13q34, the thumb hypoplasia to band 13q32, and an apparently different phenotype to band 13q33. Coagulation deficiency appears to be non-specific in monosomy 13qter. [ABSTRACT FROM PUBLISHER]

The presence of the small ac electric fields produced by living cells is shown by the gentle dielectrophoretic force on tiny dielectric particles. The beauty of the field patterns is made evident as the cell and particles settle in a hanging drop. Patterns characteristic of repulsion and of attraction, as well as of a dipolar and quadripolar nature, are observable. [ABSTRACT FROM AUTHOR]

An inv ins(7;2)(q21.2;q3105q24.2) was found to segregate through four generations of a family. Adjacent-1 segregation aneusomies were ascertained in five patients: three monosomics and two trisomics; and the corresponding syndromes were delineated. The comparative analysis between these and other previously described 2q aneusomic individuals led to the conclusion that a large cleft between first and second toes is a constant feature in monosomy 2q24→q31. No other trait could plausible be mapped. Risks of 7.9 to 31.9% for aneusomic children and of 26.3% for abortion were estimated in the present family. [ABSTRACT FROM AUTHOR]

A 12 month-old male patient with a karyotype 46, XY,-15,+der(15),t(13;15)(q22;q26)pat is presented. His stillborn sib showed malformations compatible with the 13q deletion syndrome, probably due to a 46,XY, der(13) karyotype. Phenotypic analysis of 41 cases from the literature with partial distal 13q (D13q) trisomies indicate that the segment 13q22 → qter in trisomy with or without another concomitant aneusomy is sufficient to produce the majority of the trisomy 13 syndrome features, some of which (cleft palate, increased HbF and projections in PMN) are present in different non-overlapping partial 13q trisomies. About 82% of the D13q trisomies are inherited, more frequently from the mother. [ABSTRACT FROM AUTHOR]

A family with a distinct form of congenital generalized hypertrichosis was studied. Males were more severely affected than females, who exhibited asymmetric hair distribution. This finding was attributed to lyonization, since genealogical studies indicated an X-linked pattern of inheritance. A back mutation is postulated as the origin of this new phenotype. [ABSTRACT FROM AUTHOR]

Two patients with typical Langer-Giedion or trichorhino-phalangeal type II syndrome are reported. One had an apparently normal karyotype. The second had an intercalary del 8q23. Attention is drawn to the severe bone defects seen in the latter and observations from the literature are discussed. The critical segment is assigned to band 8q23. The syndrome may result in a number of cases from a visible deletion, and in other instances from a more conventional gene mutation, although the molecular mechanism is uncertain. [ABSTRACT FROM AUTHOR]

Secondary hyperparathyroidism (SHPT) is a serious complication in dialysis patients and is routinely managed with medical therapy. Refractory disease is usually treated either surgically or by local ethanol injection into the parathyroid glands. Total parathyroidectomy with deltoid implant can be successful; however, recurrent, resistant disease is not uncommon. Local ethanol injection was applied to the deltoid autoimplant of a patient with recurrent, resistant SHPT, which had not been resolved with surgical treatment. Serum intact parathyroid hormone (iPTH) levels subsequently decreased from 1,400 to 219 pg/dl and remained stable for the next 6 months. To our knowledge, this procedure has not been previously described in the literature. Local injection of ethanol may represent an interesting alternative to surgery for the treatment of deltoid parathyroid cell hyperplasia in patients in which surgical treatment is not an option. [ABSTRACT FROM AUTHOR]

We present a case of primary oral tuberculosis, affecting the maxillary gingiva and causing alveolar bone loss in a 34-year-old Colombian female patient. Definitive diagnosis was facilitated by polymerase chain reaction analysis, a useful modern tool for the diagnosis of infectious diseases. The location and clinical presentation of this lesion is unusual and underlines the importance of considering tuberculosis in the differential diagnosis of oral lesions that affect the gingiva and alveolar bone. [ABSTRACT FROM AUTHOR]

A female infant who died at 2 years of age with growth and psychomotor retardation, wide anterior fontanelle, downward slanting palpebral fissures, large, simple ears, joint dislocation/contractures, recurrent infections, and severe pulmonary hypertension was found to have a de novo 7p+ chromosome. The G banding pattern was suggestive of a triplication of 7p21.3 and 7p22; results of fluorescence in situ hybridisation studies using a chromosome 7 specific library, a subtelomeric 7p repeat (109A6), and yeast artificial chromosome clones 786g1 and 850a1, which are respectively associated with the (CA)n repeat markers D7S517 and D7S513, supported the cytogenetic interpretation and showed that the middle repeat was inverted. The patient's phenotype was consistent with the 7p duplication syndrome, allowing for the effects of the extra burden introduced by the partial tetrasomy. The present rearrangement may have resulted from several meiotic events occurring at the four chromatid stage, namely an unequal crossover or interhomologue translocation with points of exchange at 7p22 and 7p15 followed by the inverted insertion of 7p21.3-->p21.2 at the former breakpoint junction; moreover, a further duplication including D7S517 within the terminal 7p22 band is also required. [ABSTRACT FROM PUBLISHER]

We report on a 16 month old girl with hypomelanosis of Ito and a balanced de novo (X;13)(q10;q10) translocation in which the der(Xp13q) had the X centromere (as assessed by FISH with the DXZ3 probe). A functional Xp disomy was shown in a small proportion of cultured lymphocytes by means of a BrdU terminal pulse. This observation supports the notion of a distinct form of hypomelanosis of Ito resulting from a functional Xp disomy. [ABSTRACT FROM PUBLISHER]

A maternally transmitted Xp+ chromosome was associated with an abnormal phenotype, including developmental delay and short stature, in two male cousins and their 12 year old aunt. The respective mothers were not mentally impaired but had short stature. The G banding pattern identified the extra chromosome segment as a repeat of Xq26.3-->qter attached to an apparently intact Xp22.3 sub-band, so the Xp+ chromosome may be described as rea(X)(Xqter-->p22.3::Xq26.3-->Xqter). The rearranged chromosome was late replicating in 97 to 100% of the metaphases in the mothers but it was early replicating in 43% of the lymphocytes in the mentally defective female (n = 100 cells/subject). Fluorescence in situ hybridisation using X and Y chromosome paints, as well as cosmids A and 1A1 specific for loci within Xq28, confirmed both the identity of the extra segment and the entirety of the Xp pseudoautosomal region. Therefore, the phenotypic consequences in this family can be related to the Xq26.3-->qter functional disomy allowing for the effects of X inactivation in the female carriers. [ABSTRACT FROM PUBLISHER]

A 12-year-old patient with Turner syndrome was found to have a complex mosaicism for a microchromosome (MC) and a psu dic(Y)(q11). The MC was smaller than Yp, appeared pale in G, C and late replicating bands, had a pair of small centromeric dots, was associated with other chromosomes in most metaphases, and was rather stable both in size and during mitosis. The psu dic(Y) was Cd-positive only at the active centromere, had two pericentromeric heterochromatic regions, and lacked the Yq12 band. No cells with both abnormal chromosomes were found. To evaluate the association of the MC with all ordinary chromosomes, 857 G-banded cells with the marker were screened. The MC was considered as 'associated' whenever the distance between it and other chromosome(s) was equal to, or smaller than, 18p. Out of 848 associations registered, 489 (57.7%) were centromeric, 202 (23.8%) telomeric, and 157 (18.5%) interstitial; i.e., centromeric associations were overrepresented ( P < 0.001) and showed a random distribution, except for an excessive involvement of chromosome 8. This association pattern, also exhibited by two similar MCs in human beings, the minute Y of a marsupial and certain B chromosomes in plants, probably reflects the Rabl orientation of chromosomes in interphase. [ABSTRACT FROM AUTHOR]