Search PubMed⌕ Search

Biomedical subjects

T M Cooper

Publications and source records attributed to T M Cooper.

At least 19 recordsLinked to original sources

The Python pit organ: imaging and immunocytochemical analysis of an extremely sensitive natural infrared detector.

The Python infrared-sensitive pit organ is a natural infrared imager that combines high sensitivity, ambient temperature function, microscopic dimensions, and self-repair. We are investigating the spectral sensitivity and signal transduction process in snake infrared-sensitive neurons, neither of which is understood. For example, it is unknown whether infrared receptor neurons function on a thermal or a photic mechanism. We imaged pit organs in living Python molurus and Python regius using infrared-sensitive digital video cameras. Pit organs were significantly more absorptive and/or emissive than surrounding tissues in both 3-5 microns and 8-12 microns wavelength ranges. Pit organs exhibited greater absorption/emissivity in the 8-12 microns range than in the 3-5 microns range. To directly test the relationship between photoreceptors and pit organ infrared-sensitive neurons, we performed immunocytochemistry using antisera directed against retinal photoreceptor opsins. Retinal photoreceptors were labeled with antisera specific for retinal opsins, but these antisera failed to label terminals of infrared-sensitive neurons in the pit organ. Infrared-receptive neurons were also distinguished from retinal photoreceptors on the basis of their calcium-binding protein content. These results indicate that the pit organ absorbs infrared radiation in two major atmospheric transmission windows, one of which (8-12 microns) matches emission of targeted prey, and that infrared receptors are biochemically distinct from retinal photoreceptors. These results also provide the first identification of prospective biochemical components of infrared signal transduction in pit organ receptor neurons.

Animals↗

Free groin flap revisited.

Reported herein are 130 consecutive cases of free groin flap transfer performed by one surgeon over a 19-year period. Transplantation was performed for soft-tissue cover or augmentation of contour defects involving the head and neck (68 cases), trunk (4 cases), upper limb (14 cases), and lower limb (44 cases). Indications for flap coverage/augmentation were classified broadly into tumor, trauma, radiation induced, and miscellaneous. Specific reconstructive problems included augmentation for Romberg's hemifacial atrophy, external ear canal reconstruction after tumor ablation, and coverage of lower limb defects. There were nine failures (total flap loss), seven cases of partial flap loss, and two cases were abandoned intraoperatively. Of 15 cases that were urgently re-explored, 9 flaps were salvaged. The failure rate for the groin flap series (130 cases) was 8.5 percent compared with the failure rate of 4.2 percent for the other 517 cases of microvascular transfer performed over the same period by the same surgeon. Donor-site complications occurred in 24 cases and included hematoma or seroma formation, hypertrophic scars, nerve paresthesiae, infection, and dehiscence. Secondary debulking procedures were performed in 26 cases. The free groin flap, contrary to some reports, is a reliable flap that provides relatively thin pliable soft-tissue cover or augmentation, with minimal donor-site morbidity. The specific indications for its use have undergone an evolution since first described in 1973.

Adolescent↗

The effect of an implantable Doppler probe on the salvage of microvascular tissue transplants.

One hundred forty-seven flaps in 135 consecutive patients undergoing microvascular transplantation were monitored using a miniature Doppler ultrasonic probe. Using a modification of a technique described previously by Swartz, the probes were secured to the outflow vein of the flap with Vicryl mesh. Twenty instances of thrombosis or spasm were detected in 16 patients, and all flaps were salvaged (100 percent). There were four false positive and no false negative results. This probe allows for safe, continuous monitoring of flap blood flow, which permits the rapid detection and hence rapid treatment of postoperative complications. Our experience suggests that a significant improvement in the salvage rate of microvascular transplants may be attainable with the use of this device.

Adolescent↗

Cross-facial nerve grafting for facial reanimation: effect on normal hemiface motion.

Reinnervation of the paralyzed hemiface with a cross-facial nerve graft (CFNG) required division of facial nerve branches on the normal hemiface to serve as axon donors. There is therefore concern about whether any impairment of normal hemiface motion occurs in the postoperative period. To minimize the likelihood of donor-side impairment, donor branches are chosen from the bucco-zygomatic region which was extensive cross branching, as opposed to be the single temporal or marginal mandibular branches. This study chose to determine quantitatively if this practice does, in fact, adversely affect the normal side hemiface motion governed by these branches, viz., eye closure, pucker, and smile. Since surgical procedures near the facial nerve (such as superficial parotidectomy) may leave the patient with transient facial weakness, even in the absence of nerve transection, the hypothesis was that hemiface motion would be impaired on the donor side during the early postoperative period (first month) secondary to edema and/or neuropraxia. However, based on the clinical observation that donor-side facial motion is not demonstrably impaired late after surgery, a further hypothesis was that any early facial motion is not demonstrably impaired late after surgery, a further hypothesis was that any early facial motion impairment would return to normal by 3 months postoperatively. Seven patients underwent sural CFNG as a primary or secondary component of their facial animation procedure. Their facial motion was quantified preoperatively and in serial postoperative examinations using the Maximal Static Response Assay (MSRA) of facial motion. Careful selection of redundant bucco-zygomatic branches of the facial nerve on the normal side for CFNG did not ultimately ( > or = 3 months postoperative) impair the important motions of eye closure, smile, or pucker. Early postoperative ( < or = 1 month) weakness of the smile was seen on both X and Y axes, indicating that both the risorius and zygomatic muscles were transiently weakened. The ability to elevate the lower eyelid was unaffected at any postoperative time point. Movement of the normal hemiface did not appear to be permanently affected by CFNG when a careful choice of redundant bucco-zygomatic donor branches was made.

Adult↗

Soft tissue sarcoma of the extremity.

A retrospective review of 33 cases of soft tissue sarcoma of the extremity presenting over a 10 year period was undertaken. The history, patterns of referral, diagnostic investigations, procedures undertaken and outcomes were studied. We found there was a frequent delay in diagnosis and sometimes misinterpretation of biopsy specimens. Patients were seen by a variety of specialists from disciplines such as general surgery, plastic surgery, orthopaedic surgery and rheumatology. Considerable progress has been made in the treatment of soft tissue sarcomas, often allowing local control of the tumour without amputation. We believe there should be early referral of patients having these tumours to a centre where a combined multidisciplinary approach can be undertaken.

Adolescent↗

Investigation of light-induced conformation changes in spiropyran-modified succinylated poly(L-lysine).

To determine the maximum range of coupling between side-chain photochromism and polypeptide conformation change, we modified the carboxylate side chains of succinylated poly(L-lysine) with a spiropyran to form polypeptide I. The extent of modification was determined to be 35.5%. The spacer group length between the polypeptide alpha-carbon and the dye was 12 atoms, providing minimum polypeptide-dye interaction. Conformation changes were monitored by circular dichroism as a function of light adaptation and solvent composition (hexafluoroisopropanol [HFIP] vs trifluoroethanol [TFE]). Under all solvent compositions, the dark-adapted dye was in the merocyanine form. Light adaptation by visible light converted the dye to the spiropyran form. When dissolved in TFE, I adopted a helical conformation insensitive to light adaptation. With increasing percentage HFIP, a solvent-induced helix-to-coil transition was observed around 80% (vol/vol) HFIP. At 100% HFIP, both light- and dark-adapted forms of I were in the coil state. Near the midpoint of the solvent-induced helix-to-coil transition, light adaptation caused conformation changes. Applying helix-to-coil transition theory, we measured a statistically significant difference in coil segment-HFIP binding constant for light- vs dark-adapted solutions (6.38 +/- 0.03 M-1 vs 6.56 +/- 0.03 M-1), but not for the nucleation parameter sigma (1.2 +/- 0.4 10(-3) vs 1.3 +/- 0.3 x 10(-3). The small binding constant difference translated to a light-induced binding energy difference of 17 cal/mol/monomer. Near the midpoint of the helix-to-coil transition, collective interactions between monomer units made possible the translation of a small energy difference (less than RT) into large macromolecular conformation changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Benzopyrans↗

Characterization of selective glucocorticoid-dependent responses in a glucocorticoid-resistant smooth muscle tumor cell line.

The DDT1 MF2 smooth muscle cell line was derived from an estrogen/androgen-induced leiomyosarcoma arising in the hamster ductus deferens. Growth of this cell line is arrested in G0/G1 by treatment with glucocorticoids. To facilitate the study of the mechanism of glucocorticoid-induced cell growth arrest, a glucocorticoid-resistant variant cell line, DDT1 MF2 GR1 (GR1), was developed by genetic selection. Growth of this mutant cell line is completely resistant to the inhibitory action of glucocorticoids. However, we now demonstrate that both primary and secondary glucocorticoid-induced events still exist in the GR1 cell line. By analyzing the expression and genetic pattern of glucocorticoid receptor, no detectable rearrangement of the glucocorticoid receptor gene was found although the expression of both mRNA and protein levels of the receptor were lower in the variant compared to wild-type cells. In addition, we found that the expression of two growth-associated genes, Ha-ras and transforming growth factor beta 1 (TGF-beta 1) are down-regulated by glucocorticoids in wild-type DDT1 MF2 cells but not in GR1 cells. These results indicated that the function or activity of glucocorticoid receptor in the GR1 cells is not qualitatively altered. Our data suggest that a lower glucocorticoid receptor level is not the real cause or at least not the single cause for the GR1 cell's loss of sensitivity to the inhibitory action of glucocorticoid. Instead, we postulate the existence of a defect downstream of the primary site of action of glucocorticoid receptor complexes in GR1 cells.

Animals↗

Kinetic study of the helix to coil dark reaction of poly(spiropyran-L-glutamate).

An investigation of kinetics of the helix to coil dark reaction of light adapted poly(spiropyran-L-glutamic acid) (PSLG) dissolved in hexafluoroisopropanol was performed. The reaction was associated with the spiropyran (SP) to merocyanine (MC) ring opening. The ring opening reaction monitored with UV/VIS spectroscopy showed first order kinetics. Chromophore and polypeptide backbone circular dichroism data fit to an expression consistent with a single intermediate series mechanism. By FTIR, we monitored the polypeptide alpha-helix amide I, the MC chromophore--C = C--stretch and the protonated unmodified carboxylate C = O stretch bands. During the first step of the series mechanism, changes in the hydrogen bonding of the unmodified carboxylate groups occurred, suggesting breakup of polypeptide aggregates. The second step of the proposed series mechanism was dominated by the helix to coil transition and the ring opening of SP to MC. The CD spectrum of MC in the dark adapted PSLG was red shifted and had a narrower bandwidth than the UV/VIS spectrum. The kinetic and spectroscopic data suggested that a fraction (population I) of the MC chromophores experienced optical activity induced by the chiral polypeptide environment, while the remainder of the MC chromophores (population II) were solvated and enantiomeric.

Benzopyrans↗

Platelet function in the peri-operative period.

Although platelets have an important role in haemostasis and in thrombosis, what happens to platelet function postoperatively is not well understood. We investigated platelet function in the peri-operative period by measuring total platelet count and several products released by activated platelets, thromboxane, betathromboglobulin and lyso-platelet activating factor (lyso-PAF). The only changes detected were a significant rise in total platelet count between 48 h and 5 days post-operation, and a progressive fall in lyso-PAF up to 48 h post-operation. It is possible that other changes may have occurred, but were an immediate effect and were not apparent at time of the first blood sample 2-3 h post-operation.

Adult↗

Cloning of a mu-class glutathione S-transferase complementary DNA and characterization of its glucocorticoid inducibility in a smooth muscle tumor cell line.

A cDNA (designated hGSTYBX) encompassing the complete coding sequence of a hamster mu-class glutathione S-transferase (GST) subunit was cloned from a lambda ZAP library constructed with mRNA isolated from triamcinolone acetonide-treated smooth muscle tumor cells (DDT1 MF-2). Analysis of its nucleotide and deduced amino acid sequences demonstrated highest homology to the rat mu-class GST YB2 subunit. In proliferating subconfluent cells, in which constitutive expression of hGSTYBX mRNA was undetectable, glucocorticoid treatment induced hGSTYBX expression after a time lag of 3 h, and maximal induction occurred at 10 h. Nuclear run-on analysis showed that glucocorticoid induction resulted at least in part from an increased rate of transcription. Simultaneous treatment with glucocorticoid and cycloheximide prevented glucocorticoid induction, but had little effect on basal expression in confluent cells. In contrast, cycloheximide treatment 3 h after glucocorticoid treatment resulted in nearly full induction. These results taken together suggest that hGSTYBX induction may be a secondary glucocorticoid response.

Amino Acid Sequence↗

Drinking coffee and carbonated beverages blocks absorption of nicotine from nicotine polacrilex gum.

Patients failing to obtain benefit from nicotine polacrilex gum in their efforts to quit smoking may be inadvertently blocking nicotine absorption. Effective nicotine absorption depends on the mildly alkaline saliva that is produced when buffering agents in the polacrilex are released along with nicotine as the polacrilex is chewed. We found that intermittent mouth rinsing with coffee or cola, but not distilled water, substantially reduced salivary pH and nicotine absorption. Because many commonly consumed substances were also found to be highly acidic, we recommend that patients do not ingest any substance during or immediately before nicotine polacrilex use.

Absorption↗

The effect of conformation on the CD of interacting helices: a theoretical study of tropomyosin.

A recent report [M. E. Holtzer, et al. (1988) Biophysics Journal, 53, 96a] of the anomalous CD spectrum of the tropomyosin (TM) fragment 11TM127 motivated us to model the system as two 21-residue alpha-helices distorted to a coiled-coil conformation. We used strong-coupling exciton theory to model the optical properties of the system. Two backbone amide excited states (n pi* and pi pi*) were considered, as well as four excited states (Lb, La, Bb, Ba) for the phenolic side chain. We calculated the effect of superhelix formation on the backbone CD spectrum. The decrease in molar ellipticity of the alpha-helix parallel-polarized transition at 208 nm was found to be a simple function of superhelix tilt angle. We then modeled a coiled coil (radius = 5.5 A, pitch = -140 A) with one aromatic ring per superhelix. Steric interactions between aromatic side chains in a coiled coil were calculated as a function of side-chain conformation and heptet position. Steric interactions between phenolic rings will be significant for heptet positions a and d, but not for positions b, c, e, f, or g. We calculated the phenolic Lb transition rotational strength as a function of position within the heptet repeats, and of all possible side-chain dihedral angles, chi 1 and chi 2. When tyrosines were placed at heptet positions b, c, e, f, or g, the rotational-strength surface was nearly identical to that of a single tyrosine in an undistorted helix. In contrast, the rotational-strength surface for tyrosines in heptet positions a or d showed substantial intertyrosine coupling components. The rotational-strength surfaces for the three types of heptet positions (position a, position d, and the others) allowed an interpretation of the aromatic CD spectra of TM and its fragments. It was predicted that the three types of heptet positions will be spectroscopically distinguishable.

Circular Dichroism↗

The relationships of concentrations of insulin, intact proinsulin and 32-33 split proinsulin with cardiovascular risk factors in type 2 (non-insulin-dependent) diabetic subjects.

Standard radioimmunoassay for insulin may substantially overestimate levels of insulin because of cross-reaction with other insulin-like molecules. We have measured concentrations of insulin, intact proinsulin and 32-33 split proinsulin using two-site monoclonal antibody based immunoradiometric assays, and of insulin by a standard radioimmunoassay ("immunoreactive insulin") in 51 Type 2 (non-insulin-dependent) diabetic subjects in the fasting state. The relationships of these concentrations were sought with those of total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, triglyceride, plasminogen activator inhibitor, blood pressure, and indices of body fat distribution. Significant relationships were apparent between concentrations of "immunoreactive insulin" as measured by standard radioimmunoassay and triglyceride (rs = 0.42, p less than 0.001), total cholesterol (rs = 0.25, p = 0.038), high density lipoprotein cholesterol (rs = -0.30, p = 0.018) and body mass index (rs = 0.30, p = 0.017), but only the relationships with triglyceride (rs = 0.36, p = 0.006) and body mass index (rs = 0.26, p = 0.34) remained significant when concentrations of immunoradiometrically measured insulin were employed. Concentrations of 32-33 split proinsulin, which comprises the major insulin-like molecule in these subjects, correlated positively with triglyceride (rs = 0.33, p = 0.009), total cholesterol (rs = 0.23, p = 0.050), and plasminogen activator inhibitor (rs = 0.26, p = 0.049), and negatively with high density lipoprotein cholesterol (rs = -0.29, p = 0.021).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Influence of energy and nitrogen contents of enteral diets on nitrogen balance: a double blind prospective controlled clinical trial.

Results of recent controlled studies show that because of difficulties in administering adequate quantities of enteral diet, positive nitrogen balance is not consistently achieved during enteral feeding. In order to determine whether nitrogen balance can be improved in routine clinical practice by prescribing enteral diets containing higher concentrations of nutrients, 118 patients with normal gastrointestinal function needing enteral nutrition were randomised to receive daily 21 of one of three polymeric diets: Standard diet (1.0 kcal/ml; 6.3 gN/l), Energy Dense diet (1.5 kcal/ml; 7.8 gN/l), and Energy-Nitrogen Dense diet (1.5 kcal/ml; 9.4 gN/l. The three diets, administered by continuous nasogastric infusion, were equally well tolerated. Results were analysed only for patients fed five or more days and who received at least 60% of prescribed enteral diet (n = 42). Positive nitrogen balance was achieved only in the patients receiving the Energy-Nitrogen Dense diet (n = 16; + 1.6 (SE) 0.6 gN/d, compared with the Standard diet (n = 12; -3.8 (1.1) gN/d; p less than 0.001), and the Energy Dense diet (m = 14; -1.9 (0.8) gN/d; p less than 0.005). As the findings of this prospective controlled trial show that positive nitrogen balance was not consistently achieved by administering 21 enteral diet containing up to 15.6 gN, consideration could, therefore, be given to routinely using enteral diets containing up to 9.4 gN/l.

Adolescent↗