Biomedical subjects

R Mah

Publications and source records attributed to R Mah.

6 recordsLinked to original sources

PubMed2001

Dual neurokinin NK(1)/NK(2) antagonists: N-[(R,R)-(E)-1-arylmethyl-3-(2-oxo-azepan-3-yl)carbamoyl]allyl-N-methyl-3,5-bis(trifluoromethyl)benzamides and 3-[N'-3,5-bis(trifluoromethyl)benzoyl-N-arylmethyl-N'-methylhydrazino]-N-[(R)-2-oxo-azepan-3-yl]propionamides.

Based on the structure of N-[(R,R)-(E)-1-(4-chlorobenzyl)-3-(2-oxoazepan-3-yl)carbamoyl]allyl-N-methyl-3,5-bis(trifluoromethyl)benzamide (1), attempts to improve the NK(2) affinity have resulted in the discovery of N-[(R,R)-(E)-1-(3,4-dichlorobenzyl)-3-(2-oxoazepan-3-yl)carbamoyl]allyl-N-methyl-3,5-bis(trifluoromethyl)benzamide (9, DNK333) exhibiting a 5-fold improved affinity to the NK(2) receptor in comparison to 1. Simplification of the structure via elimination of a chiral centre led to 3-[N'-3,5-bis(trifluoromethyl)benzoyl-N-(3,4-dichlorobenzyl)-N'-methylhydrazino]-N-[(R)-2-oxo-azepan-3-yl]propionamide (22), a potent and fairly balanced NK(1)/NK(2) antagonist.

Animals↗

PubMed2000

N-[(R,R)-(E)-1-(4-chloro-benzyl)-3-(2-oxo-azepan-3-ylcarbamoyl)-allyl]-N-methyl-3,5-bis-trifluoromethyl-benzamide: an orally active neurokinin NK1/NK2 antagonist.

The stereoselective synthesis of N-[(R,R)-(E)-1-(4-chloro-benzyl)-3-(2-oxo-azepan-3-ylcarbamoyl+ ++)-allyl]-N-methyl-3,5-bis-trifluoromethyl-benzamide (4) and its NK1 and NK2 receptor binding properties are reported. In addition the potent inhibitory effects in vivo on sar9-SP- and beta-Ala-NKA-induced airway bronchoconstriction in guinea pigs are demonstrated.

Administration, Oral↗

PubMed1999

Multimodality stereotactic brain tissue identification: the NASA smart probe project.

Real-time tissue identification can benefit procedures such as stereotactic brain biopsy, functional neurosurgery and brain tumor excision. Optical scattering spectroscopy has been shown to be effective at discriminating cancer from noncancerous conditions in the colon, bladder and breast. The NASA Smart Probe extends the concept of 'optical biopsy' by using neural network techniques to combine the output from 3 microsensors contained within a cannula 2. 7 mm in diameter (i.e. the diameter of a stereotactic brain biopsy needle). Experimental data from 5 rats show the clear differentiation between tissues such as brain, nerve, fat, artery and muscle that can be achieved with optical scattering spectroscopy alone. These data and previous findings with other modalities such as (1) analysis of the image from a fiberoptic neuroendoscope and (2) the output from a microstrain gauge suggest the Smart Probe multiple microsensor technique shows promise for real-time tissue identification in neurosurgical procedures.

Brain↗

PubMed1997

Robotic multimodality stereotactic brain tissue identification: work in progress.

Real-time identification of tissue would improve procedures such as stereotactic brain biopsy (SBX), functional and implantation neurosurgery, and brain tumor excision. To standard SBX equipment has been added: (1) computer-controlled stepper motors to drive the biopsy needle/probe precisely; (2) multiple microprobes to track tissue density, detect blood vessels and changes in blood flow, and distinguish the various tissues being penetrated; (3) neural net learning programs to allow real-time comparisons of current data with a normative data bank; (4) three-dimensional graphic displays to follow the probe as it traverses brain tissue. The probe can differentiate substances such as pig brain, differing consistencies of the 'brain-like' foodstuff tofu, and gels made to simulate brain, as well as detect blood vessels imbedded in these substances. Multimodality probes should improve the safety, efficacy, and diagnostic accuracy of SBX and other neurosurgical procedures.

Animals↗

PubMed1996

Periapical changes after orthodontic movement of root-filled ferret canines.

The effectiveness of orthodontic forces in moving root-filled teeth and the degree of apical resorption it causes have been observed in an animal model. Under general anesthesia, root canal therapy was performed on the mandibular canines on one side of 12 young male ferrets. Bilateral movement of the canines was induced with an orthodontic spring (150 to 175 g). Procion red dye was injected 1 wk presurgically to mark bone and cementum deposition. Three months later, tooth movement was assessed from pre- and posttreatment mandibular casts and by fluorescence microscopy from labeled bone deposition. Vital and nonvital teeth moved similar distances when subjected to the same forces. Root-filled teeth showed greater loss of cementum after tooth movement than vital teeth (p < 0.05), but without significant differences in radiographic root length.

Animals↗

PubMed1993

Accumulation of bldA-specified tRNA is temporally regulated in Streptomyces coelicolor A3(2).

Deletion of the bldA gene of Streptomyces coelicolor A3(2), which encodes the only tRNA for the rare UUA codon, had no obvious effects on primary growth but interfered with aerial mycelium formation and antibiotic production. To investigate the possible regulatory role of bldA, its transcription start point was identified, and time courses were determined for the appearance of its primary transcript, the processing of the primary transcript to give a mature 5' end, and the apparent efficiency of translation of ampC mRNA, which contains multiple UUA codons. The bldA promoter was active at all times, but processing of the 5' end of the primary transcript was comparatively inefficient in young cultures. This may perhaps involve an antisense RNA, evidence of which was provided by promoter probing and in vitro transcription. The presence of low levels of the processed form of the tRNA in young cultures followed by increased abundance in older cultures contrasted with the pattern observed for accumulation of a different, presumably typical tRNA which was approximately equally abundant throughout growth. The increased accumulation of the 5' processed form of bldA tRNA coincided with more-efficient translation of ampC mRNA in older cultures, supporting the hypothesis that in at least some physiological conditions, bldA may have a regulatory influence on events late in growth, such as morphological differentiation and antibiotic production.

Anti-Bacterial Agents↗