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Biomedical subjects

M May

Publications and source records attributed to M May.

At least 55 records · Page 3Linked to original sources

Nanotechnology: thinking small.

Nanotechnology--building devices on the atomic scale--may unleash some big scientific advances early in the new millennium. Last January in Arlington, Virginia, nearly 100 representatives from academia, industry, and government laid out the general goals for the next decade of nanotechnology research by U.S. government agencies. Some predict that the potentially rich opportunities in this field may trigger a nanotechnology initiative in the federal budget request for Fiscal Year 2001. In the meantime, Congress has asked the NIEHS to explore how nanotechnology might be used to address environmental heath problems.

Biotechnology↗

Identification of a gene selectively expressed in the brain, which encodes a putative transmembrane protein and a soluble cytoplasmic isoform.

Subtractive cloning procedures led to the identification of a variety of transcripts expressed in mammalian brain. However, little is known about the encoded proteins and the regulation of gene expression. Here, we describe the isolation and characterisation of a single-copy gene (83.5) of 21.7 kb which is specifically expressed in porcine brain. In situ hybridisation and immunohistochemistry experiments showed a distinct pattern of gene expression in neuronal cell types in different parts of the brain. The gene contains two mini exons, confirming neural-specific expression. cDNA cloning experiments revealed two species of mRNA differing in their 5'-regions. These transcripts are generated by two distinct transcription start sites that are under the control of different potential promoter regions as shown by primer-extension experiments. The amino acid sequences of the deduced proteins predict that one mRNA species encodes a novel type-I transmembrane protein, whereas the other transcript encodes only a part of its cytoplasmic domain. In Western-blot experiments, we detected two proteins of the predicted size and cellular localisation in porcine brain. The precise function of these proteins remains to be determined. However, our findings suggest that they may be generated by alternative promoter usage, leading to the expression of a membrane protein and its truncated cytoplasmic isoform.

Amino Acid Sequence↗

Different patterns of change in narratives of men and women during analytical group psychotherapy.

Narratives of men and women concerning their interactions with other people were evaluated before and during analytically oriented group psychotherapy using the Core-Conflictual-Relationship-Theme (CCRT) method (Luborsky & Crits-Cristoph, 1990). Relationship patterns of men and women developed differently during therapy. Some gender stereotypes persisted, others changed. During therapy the proportion of negative responses in the narratives increased in the men. Change in the narratives was not related to change in self-reported symptoms. For group treatments, the results suggest that the gender of the patients has to be taken into account. Knowledge of different developmental patterns for men and women in groups can be important in regard to the expectations of therapists and their countertransference.

Adult↗

Renpenning syndrome maps to Xp11.

Mutations in genes on the X chromosome are believed to be responsible for the excess of males among individuals with mental retardation. Such genes are numerous, certainly >100, and cause both syndromal and nonsyndromal types of mental retardation. Clinical and molecular studies have been conducted on the Mennonite family with X-linked mental retardation (XLMR) reported, in 1962, by Renpenning et al. The clinical phenotype includes severe mental retardation, microcephaly, up-slanting palpebral fissures, small testes, and stature shorter than that of nonaffected males. Major malformations, neuromuscular abnormalities, and behavioral disturbances were not seen. Longevity is not impaired. Carrier females do not show heterozygote manifestations. The syndrome maps to Xp11.2-p11.4, with a maximum LOD score of 3.21 (recombination fraction 0) for markers between DXS1039 and DXS1068. Renpenning syndrome (also known as "MRXS8"; gene RENS1, MIM 309500) shares phenotypic manifestations with several other XLMR syndromes, notably the Sutherland-Haan syndrome. In none of these entities has the responsible gene been isolated; hence, the possibility that two or more of them may be allelic cannot be excluded at present.

Abnormalities, Multiple↗

Interaction of human papillomavirus 8 regulatory proteins E2, E6 and E7 with components of the TFIID complex.

Human papillomavirus 8 (HPV8) is one of the oncogenic HPV types specifically associated with skin cancers of epidermodysplasia verruciformis patients. The early gene products of this virus exert functions in transformation (E2, E6, E7), replication (E1, E2) and in the control of viral transcription (E2, E7). Many viral and cellular transactivators of transcription have been shown to interact selectively and directly with a number of TATA-box-binding protein (TBP)-associated factors (TAFIIs), which then play a role as coactivators. Using glutathione-S-transferase (GST) pull-down experiments, we tested in vitro interactions between GST-HPV8-E1, -E2, -E6 and -E7 and 7 in-vitro-translated TAFIIs in the human (h) system (hTAFII18, hTAFII20, hTAFII28, hTAFII30, hTAFII55, hTAFII100, hTAFIIDeltaN135) or TBP. We could show that GST-HPV8-E2 interacts directly at least with hTAFII55 and TBP. Deletion analysis indicated that a domain overlapping with the C-terminal moiety of HPV8-E2 is required for binding to TBP, whereas determinants for interactions with hTAFII55 are in the central and C-terminal part of the E2 protein. In similar binding studies, GST-HPV8-E6 interacted with hTAFII28, hTAFIIDeltaN135 and TBP, and more weakly with hTAFII20, whereas GST- HPV8-E7 bound to hTAFII20, hTAFII28, hTAFII55, hTAFIIDeltaN135 and TBP. Deletion analysis revealed that the C-terminal part of HPV8-E7 is required for the interaction with these hTAFIIs. In contrast, no interactions were observed between GST-HPV8-E1 and in-vitro-translated hTAFIIs.

Binding Sites↗

Human TAF(II)135 potentiates transcriptional activation by the AF-2s of the retinoic acid, vitamin D3, and thyroid hormone receptors in mammalian cells.

We report for the first time the cloning of a complete cDNA encoding the human TFIID subunit hTAF(II)135 (hTAF(II)130). Full-length hTAF(II)135 comprises 1083 amino acids and contains two conserved domains present also in dTAF(II)110 and hTAF(II)105. We show that expression of hTAF(II)135 in mammalian cells strongly and selectively potentiates transcriptional stimulation by the activation function-2 (AF-2) of the retinoic acid, thyroid hormone, and vitamin D3 receptors (RAR, TR, and VDR), but does not affect the AF-2s of the estrogen (ER) or retinoid X (RXR) receptors. The coactivator activity requires an hTAF(II)135 region that is located between the conserved domains but is itself not conserved in dTAF(II)110 and hTAF(II)105. Expression of hTAF(II)135 also stimulates RAR AF-2 activity when a promoter with a low-affinity TATA element (TGTA) is used, indicating that hTAF(II)135 overexpression compensates for the low-affinity of TBP for this promoter and may facilitate the recruitment of TFIID by the RAR AF-2.

Amino Acid Sequence↗

Linkage analysis in a family with the Opitz GBBB syndrome refines the location of the gene in Xp22 to a 4 cM region.

The Opitz GBBB syndrome (OS) is characterized in part by widely spaced inner ocular canthi and hypospadias. Recently, linkage analysis showed that the gene for the X-linked form to be located in an 18 cM region spanning Xp22. We have now conducted linkage analysis in a family previously published as having the BBB syndrome and found tight linkage to DXS7104 (Z = 3.3, theta = 0.0). Our data narrows the candidate region to 4 cM and should facilitate the identification and characterization of one of the genes involved in midline development.

DNA↗

Do intact viral particles survive excimer laser ablation?

OBJECTIVE: To determine if intact and potentially infectious viral particles can withstand excimer laser ablation and possibly pose a health hazard to medical personnel. METHODS: Excimer laser ablation of fibroblasts infected with attenuated varicella-zoster virus was performed. The laser plume was collected for polymerase chain reaction analysis and viral culture. RESULTS: While viral DNA was detected in the material trapped from the laser plume, live virus could not be demonstrated to have survived ablation. CONCLUSIONS: Attenuated varicella-zoster virus does not seem to survive excimer laser ablation. However, we recommend the use of safety precautions such as wearing a mask during the procedure. Further research is necessary to determine if other viruses could possibly remain infectious despite exposure to excimer laser radiation.

DNA, Viral↗

Role of MRI in the diagnosis of insufficiency fractures of the sacrum and acetabular roof.

OBJECTIVE: To review the risk factors and the radiological appearance of insufficiency fractures of the sacrum and acetabular roof. DESIGN AND PATIENTS: Twenty patients with sacral and acetabular roof insufficiency fractures were reviewed retrospectively. There were 16 women (80%) and 4 males (age range 48-86 years, excluding an 8-year-old boy). Thirteen patients had a known tumour, and nine had received pelvic irradiation. All patients, except one who was asymptomatic, presented with low back or hip pain. In patients with a known tumor, metastases were suspected. Plain radiography (20), bone scintigrams (16), MR examinations (20), and bone densitometry (14) were performed. Nine patients also each had a CT scan. RESULTS AND CONCLUSIONS: In three cases the CT scan performed 10-25 days after onset of symptoms was interpreted as normal. MR examination performed a few days after the CT scan showed in each of these three patients a fracture line with a band of edema. Scintigraphy was very sensitive, but the H-shaped pattern of sacral uptake, specific for an insufficiency fracture, was detected in only three of 16 cases. The earliest MR sign was medullary edema, seen as early as 18 days after the onset of symptoms. On spin echo (SE) T1-weighted images (T1WI), the hypointense signal of edema could mask a fracture line. On SE T2WI the fracture line could be detected within the hyperintense edema (10 of 17 patients with examinations including SE T2WI). However, in four patients a fracture of the sacrum was not seen on T2WI, these having been obtained in the axial plane. For this reason, intravenous gadolinium was injected, revealing a fracture line in 12 of 14 examinations, or fat suppression sequences were performed, revealing a fracture line in five of five cases. The total number of fractures detected was 17 [15 fractures of the sacrum (bilateral in 10 cases) and two of the acetabular roof]. At a later stage, the edema resolved and the fracture was clearly seen. The two cases of fracture of the acetabular roof were easily recognized at MRI, particularly in the sagittal plane.

Acetabulum↗

Inoculating the urban poor in the late eighteenth century.

Historical accounts of the practice of smallpox inoculation in the late eighteenth century invariably made a distinction between the widespread general inoculations carried out within small rural parishes and the partial inoculations in urban centres such as London, Manchester, Newcastle and Leeds. This distinction, moreover, is generally reinforced by concluding that the rural inoculation programmes were 'highly effective' or 'successful' in contrast with the urban inoculation schemes, which are often seen as 'marginally effective' or indeed 'failing'. Success or failure tends to be judged by the impact which inoculation had upon reducing mortality from smallpox, but as a result of this demographic focus the motives behind the implementation of urban inoculation have been overlooked. My paper readjusts this balance by looking more closely at motives and by judging success in relation to aims. To achieve this I have taken a new approach towards the history of smallpox inoculation as a whole, and portray the basic idea of giving a person smallpox in order to confer subsequent immunity as being modified in the hands of different people throughout the course of the century. Hence it is possible to trace the development of inoculation from a folk practice carried out within the home with the aim of protecting individuals, to large-scale general inoculation of an entire community, which aimed to eradicate the disease altogether.

History, 18th Century↗

Infant and child mortality determinants in Bangladesh: are they changing?

From the data of the 1989 Bangladesh Fertility Survey, aggregate deaths reported at ages 0-12 and 13-60 months are used to estimate infant and child mortality. Multivariate analysis shows that preceding birth interval length, followed by survival status of the immediately preceding child, are the most important factors associated with differential infant and child mortality risks; sex of the index child and mother's and father's education are also significant. Demographic factors are influential during infancy as well as childhood, but social factors, particularly mother's and father's education, now emerge as significant predictors of infant mortality risks. This indicates a change in the role of socioeconomic factors, since the earlier Bangladesh Fertility Survey in 1975.

Adult↗

Homing in virtual environments: effects of field of view and path layout.

Triangle completion (ie homing to the starting point after completing two legs of a triangle) is a widely used method for examining path-integration abilities in animals and humans. Two experiments are reported in which homing was used to examine the efficiency of purely visual mechanisms (eg optical flow) for spatial-information coding and integration. Adult observers had to complete triangles in an interactively simulated three-dimensional environment which consisted of two critical objects and a homogeneous set of white cylinders serving as background. Each participant completed twenty-seven triangles corresponding to a factorial combination of three geometrical fields of view (40 degrees, 60 degrees, or 80 degrees) and nine triangle layouts (with variations of the first turning angle and the second leg). Homing performances revealed strong effects of triangle layout, but no effect of geometrical fields of view: variations in the amount of simultaneous visible spatial information did not influence the acquisition of spatial knowledge in the environments used. Applying the encoding-error model to the data revealed severe systematic errors of picking up directional information while moving through visually simulated environments. These results are discussed with respect to informational differences between situations of purely visual and nonvisual navigations in space.

Adult↗

Arch fingerprints, hypotonia, and areflexia associated with X linked mental retardation.

A syndrome with distinctive facies, poor muscle tone, absent deep tendon reflexes, tapered fingers, excessive fingerprint arches, genu valgum and mild-moderate mental retardation has occurred in four males in two generations of a white family of European ancestry. The facies are characterised by square configuration, tented upper lip, and thickening of the helices, upper eyelids, and alae nasi. At birth and at maturity, growth (head circumference, height, weight) of affected males is comparable to or greater than unaffected male sibs. Moderate impairment of cognitive function was documented (IQ scores between 40-51). Carriers show no heterozygote manifestations. This X linked condition appears to be different from other syndromes with mental retardation, although there are certain similarities with the alpha thalassaemia-mental retardation syndrome (ATR-X). Linkage analysis found tight linkage to DXS1166 and DXS995 in Xq13 and Xq21 respectively.

Abnormalities, Multiple↗

Multiple interactions between hTAFII55 and other TFIID subunits. Requirements for the formation of stable ternary complexes between hTAFII55 and the TATA-binding protein.

We have cloned and characterized the human TATA-binding protein (TBP)-associated factor hTAFII55. hTAFII55, which has no known Drosophila counterpart, is present in both of the previously described TFIIDalpha and TFIIDbeta subpopulations. We describe the interactions of hTAFII55 with other subunits of the transcription factor TFIID. By cotransfection in COS cells, we show that hTAFII55 interacts with hTAFII250, hTAFII100, hTAFII28, hTAFII20, and hTAFII18, but not with hTAFII30 or TBP. Analysis of the binding of hTAFII55 and TBP to hTAFII28 deletion mutants indicates that distinct regions of hTAFII28 are required for these interactions. Although hTAFII55 does not interact by itself with TBP, stable ternary complexes containing hTAFII55 and TBP can be formed in the presence of hTAFII250, hTAFII100, or hTAFII28. These results not only show that hTAFII100 and hTAFII28 interact with TBP, but also that they can nucleate the formation of partial TFIID complexes.

Amino Acid Sequence↗

Environmental and developmental signals modulate proline homeostasis: evidence for a negative transcriptional regulator.

In many plants, osmotic stress induces a rapid accumulation of proline through de novo synthesis from glutamate. This response is thought to play a pivotal role in osmotic stress tolerance [Kishor, P. B. K., Hong, Z., Miao, G.-H., Hu, C.-A. A. and Verma, D. P. S. (1995) Plant Physiol. 108, 1387-1394]. During recovery from osmotic stress, accumulated proline is rapidly oxidized to glutamate and the first step of this process is catalyzed by proline oxidase. We have isolated a full-length cDNA from Arabidopsis thaliana, At-POX, which maps to a single locus on chromosome 3 and that encodes a predicted polypeptide of 499 amino acids showing significant similarity with proline oxidase sequences from Drosophila and Saccharomyces cerevisiae (55.5% and 45.1%, respectively). The predicted location of the encoded polypeptide is the inner mitochondrial membrane. RNA gel blot analysis revealed that At-POX mRNA levels declined rapidly upon osmotic stress and this decline preceded proline accumulation. On the other hand, At-POX mRNA levels rapidly increased during recovery. Free proline, exogenously added to plants, was found to be an effective inducer of At-POX expression; indeed, At-POX was highly expressed in flowers and mature seeds where the proline level is higher relative to other organs of Arabidopsis. Our results indicate that stress- and developmentally derived signals interact to determine proline homeostasis in Arabidopsis.

Amino Acid Sequence↗