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Biomedical subjects

R W Lambert

Publications and source records attributed to R W Lambert.

At least 55 records · Page 3Linked to original sources
PubMed1988

Cl(-)-HCO3- antiport in rat lacrimal gland.

With the use of analytical subcellular fractionation and tracer uptake methods we have demonstrated the presence of a Cl(-)-HCO3- antiport mechanism in the rat exorbital lacrimal gland. We find that outwardly directed gradients of HCO3- and of 35Cl- accelerated the flux of 36Cl- into isolated membrane vesicles. Because vesicle membrane potentials were clamped to 0 mV with K+-valinomycin, the observed anion gradient-dependent acceleration of Cl- influx could not be attributed to conductive fluxes. The antiporter had an apparent K0.5 for Cl- between 6 and 10 mM. It was sensitive to the stilbene derivatives 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (SITS) and 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS). It was also sensitive to the loop diuretic furosemide, which has frequently been used in tests for NaKCl2 symporter activity. Other anions inhibited anion gradient-driven Cl- influx in the sequence SCN- greater than NO3- greater than Cl- greater than HCO3- greater than SO2-4. The density distribution of Cl(-)-HCO3- antiport activity indicated that approximately 80% of the transporter was associated with intracellular membranes, suggesting the presence of cytoplasmic pools of functional antiporters. Because several studies have already shown the presence of Na+-H+ antiporter activity in lacrimal acinar cell basolateral membranes, a cellular model for lacrimal acinar electrolyte secretion is proposed in which a parallel array of Cl- -HCO3- and Na+-H+ antiporters mediates the Na+-dependent accumulation of Cl- against its electrochemical potential gradient.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1988

Pathogenesis of blepharoconjunctivitis complicating 13-cis-retinoic acid (isotretinoin) therapy in a laboratory model.

Systemic treatment of adult male New Zealand albino rabbits with 13-cis-retinoic acid (isotretinoin) resulted in a reduction in the size of the meibomian gland. Clinical signs of toxicity included weight loss, alopecia, dry skin and mild conjunctival erythema with crusting on the eyelid margin. Histopathologic findings included thickening of duct and ductule epithelium, decrease in acinar tissue, accentuation of basaloid cells and evidence of periacinar fibrosis. The model presents the first experimental data to indicate that systemic 13-cis-retinoic acid effects meibomian gland structure in a laboratory model. Future functional studies of this model may yield important insights into the relationships between meibomian gland morphology, function, the ocular surface and the pathogenesis of blepharo-conjunctivitis.

Alopecia↗
PubMed1988

Computerized tomography head scans as predictors of functional outcome of stroke patients.

Preadmission computerized tomography (CT) scans of the head were used to help develop a clinical method for the prediction of outcome of stroke patients. The functional gains and discharge outcomes of 100 stroke patients after inpatient rehabilitation were considered. Reports of preadmission (acute care hospital) CT scans of the head were analyzed and placed into six groups representing progressive anatomic involvement. Functional status was measured at admission and discharge using the patient evaluation and conference system (PECS) and placed into four functional groups. The groups ranged from normal to totally dependent in self-care activities, ambulation, and bladder and bowel functioning. Admission CT head scans reported in two categories--"normal" or "small superficial infarct"--were associated with return to independent functioning. Bihemispheric infarcts were associated with discharge to nursing home (71%), rather than to independent living. Of all patients with functional gain as measured with PECS, 79% returned home.

Adolescent↗
PubMed1987

Na+/H+ antiporter in lacrimal acinar cell basal-lateral membranes.

The first step in the formation of lacrimal gland fluid is believed to depend on transport systems which couple a flux of Cl- ions to the passive influx of Na+ ions across the acinar cell basal-lateral plasma membrane. The transport systems which mediate these fluxes have not yet been characterized, but a review of previous studies (Parod and Putney, Am J Physiol 239:G106, 1980) raises the possibility that Na+/H+ antiporters might represent a major pathway for Na+ influx. This conclusion is of interest, because antiporter mediated Na+ fluxes can, potentially, drive net Cl- fluxes. We have now examined a sample of basal-lateral membrane vesicles from rat exorbital lacrimal gland to verify the presence of a Na+/H+ antiporter activity. Imposition of an outward H+ gradient caused a 4.4-fold increase in the 22Na influx rate, while imposition of an outward Na+ gradient accelerated H+ uptake as determined by changes in acridine orange absorbance. All transport experiments were done in the presence of valinomycin and symmetrical K+ concentrations, eliminating the possibility of conductive Na+ or H+ fluxes driven by diffusion potentials. The pH gradient dependent Na+ influx was completely inhibited by 1 mM amiloride, indicating that it was mediated by a Na+/H+ antiporter similar to those described in other tissues. Comparison of the density distributions of Na+/H+ antiport and standard membrane marker enzyme activities confirmed that the antiporter was primarily localized to the basal-lateral membranes.

Animals↗
PubMed1986

Synthesis and structure-activity relationships of antibacterial phosphonopeptides incorporating (1-aminoethyl)phosphonic acid and (aminomethyl)phosphonic acid.

Phosphonodipeptides and phosphonooligopeptides based on L- and D-(1-aminoethyl)phosphonic acids L-Ala(P) and D-Ala(P) and (aminomethyl)phosphonic acid Gly(P) at the acid terminus have been synthesized and investigated as antibacterial agents, which owe their activity to the inhibition of bacterial cell-wall biosynthesis. A method for large-scale synthesis of the potent antibacterial agent L-Ala-L-Ala(P) (1, Alafosfalin) is described. Structure-activity relationships in the dipeptide series have been studied by systematic variation of structure 1. L stereochemistry is generally required for both components. Changes in the L-Ala(P) moiety mostly lead to loss of antibacterial activity, but the phosphonate analogues of L-phenylalanine, L-Phe(P), and L-serine, L-Ser(P), give rise to weakly active L-Ala-L-Phe(P) and L-Ala-L-Ser(P). Replacement of L-Ala in 1 by common and rare amino acids can give rise to more potent in vitro antibacterials such as L-Nva-L-Ala(P) (45). Synthetic variation of these more potent dipeptides leads to decreased activity. Phosphonooligopeptides such as (L-Ala)2-L-Ala(P) have a broader in vitro antibacterial spectrum than their phosphonodipeptide precursor, but this is not expressed in vivo, presumably due to rapid metabolism to 1. Stabilized compounds such as Sar-L-Nva-L-Nva-L-Ala(P) (46) have been developed that are more potent in vivo and have a broader in vivo antibacterial spectrum than the parent phosphonodipeptide.

Alanine↗
PubMed1986

Antiviral activity of 5'-PAA and 5'-PFA phosphate esters of 2'-deoxyuridines.

The 5'-PAA and 5'-PFA phosphate esters of 5-bromo-2'-deoxyuridine (BUdR) were synthesized and their antiherpes virus activity was evaluated in vitro. Both compounds showed activity of the same order as the parent nucleoside, BUdR, against HSV-2 but were 4 to 12 times less potent against HSV-1. The 5'-PAA phosphate ester of BUdR (Ro 21-9875) was also active against varicella-zoster virus (VZV) and human cytomegalovirus (HCMV). The 5'-PAA phosphate ester of 5-bromovinyl-2'-deoxyuridine (BVdU) was also synthesized and showed good antiviral activity against HSV-1 only (ID50 = 1.3 mg/l). Further evaluation against selected mutants (TK- or PAAr) indicated a requirement for the expression of the virus-coded thymidine kinase (TK) for the antiviral activity of Ro 21-9875. Kinetic studies revealed non-competitive mixed inhibition of the viral enzyme by this compound. This suggests that it may have some intrinsic TK mediated activity though breakdown to its component parts is undoubtedly a significant contributing factor.

Animals↗
PubMed1986

Comparison of mandibular movement trajectories and associated patterns of oral muscle electromyographic activity during spontaneous and apomorphine-induced rhythmic jaw movements in the guinea pig.

Vertical and horizontal movements of the lower jaw (mandible) of ketamine-anesthetized guinea pigs were recorded in association with electromyographic (EMG) activity in the anterior digastric, lateral pterygoid, medial pterygoid, and deep masseter muscles during spontaneously occurring rhythmic jaw movements (SRJMs) and during rhythmical jaw movements induced by the intravenous administration of apomorphine (ARJMs). Both ARJMs and SRJMs were near periodic and occurred at frequencies in the 2- to 5-Hz range. However, the profiles of the mandibular movements and associated patterns of jaw muscle EMG activity differed dramatically for SRJMs versus ARJMs. SRJMs were characterized by prominent lateral excursions of the mandible that occurred in association with both the jaw opening and closing movements. The lateral excursions were directed to the left side on some SRJM cycles and to the right side on others. The direction of the lateral component alternated irregularly, but no more than three consecutive cycles with horizontal movements to the same side were observed at any time. Each SRJM cycle was generated by the occurrence of one of two coordinated sequences of EMG activity. One sequence produced right-sided cycles, the other produced left-sided cycles. Each sequence was initiated by an EMG burst in the digastric muscle ipsilateral to the direction of the horizontal excursion of the mandible, followed by EMG bursts in the contralateral digastric, lateral pterygoid, and medial pterygoid muscles. The EMG bursts in the digastrics and contralateral lateral pterygoid muscles were associated with jaw opening and the initial stage of lateral movement. EMG activity in the contralateral medial pterygoid muscle was associated with the onset of closing and a second stage of lateral movement. Masseter muscle activity was also observed during SRJMs, but only in a subset of the animals tested (3 of 12). When present, the masseter activity began well after the onset of jaw closing. No significant horizontal mandibular movements were observed during ARJMs. The mandibular trajectories during opening and closing always remained close to the midline. The opening phase of ARJM cycles was associated with bilaterally synchronized activity in the digastric and lateral pterygoid muscles. The closing phase was associated with bilaterally symmetric activity in the masseter muscles. The medial pterygoid muscles displayed little or no EMG activity during ARJMs. The durations of the EMG bursts recorded in the masseter muscle were correlated with cycle time during SRJMs, as were the burst durations of the digastric and lateral pterygoid muscles during ARJMs.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1986

Glomerular permeability in the isolated perfused rat kidney.

Increased glomerular permeability to protein occurs during isolated rat kidney perfusion in the absence of ultrastructural changes in the glomerular capillary wall. The increase is greater with age, varies with strain and is reduced by amino acid supplementation of the perfusate. Glomerular permeability to protein is thus perceptibly influenced by non-pathogenic stimuli. Such phenomena, in turn, may influence glomerular function in disease or after experimental damage.

Amino Acids↗
PubMed1985

The relationship between cortically induced mandibular movements and lateral pterygoid and digastric muscle EMG activity in the anesthetized guinea pig.

Vertical and horizontal jaw movements along with lateral pterygoid (PT) and anterior digastric (DIG) muscle electromyogram (EMG) activity were recorded in anesthetized guinea pigs during electrical stimulation of the masticatory area of cortex. Both repetitive stimulation at 25 Hz and short pulse-train stimulation (3 pulse, 500 Hz) delivered 2/s produced jaw opening with a horizontal component contralateral to the side of cortex stimulated in addition to short latency (7-12 ms) evoked EMG bursts in the ipsilateral PT muscle and in the DIG muscles bilaterally. Evidence was also obtained which indicated that both types of cortical stimulation resulted in time-locked inhibition of the contralateral PT muscle. Unlike each short train of stimulus pulses, however, each pulse in the repetitive train did not evoke jaw movement and EMG bursts of a consistent amplitude. Rather, repetitive stimulation produced rhythmical movements of the jaw associated with recurrent periods of activity and inactivity in the EMG records. These results demonstrate the presence of a corticotrigeminal pathway between masticatory cortex and PT motoneurons in addition to a similar pathway to DIG motoneurons, and suggest that both pathways are similarly modulated by a central pattern generator to produce rhythmical jaw movements.

Anesthesia, General↗
PubMed1985

The effects of orofacial sensory input on spontaneously occurring and apomorphine-induced rhythmical jaw movements in the anesthetized guinea pig.

The effects of tonic mandibular loading (jaw depression) on spontaneously occurring and apomorphine (APO)-induced rhythmical jaw movements (RJMs) were examined in the anesthetized guinea pig. It was found that this type of perturbation significantly increased only the amplitude and burst duration of the masseter (jaw closer) EMG activity, whereas the frequency of RJMs was not changed. The data suggest that jaw closer muscle spindle or temporomandibular joint feedback does not strongly influence the activity of the neural networks responsible for determining the frequency of RJMs in the anesthetized guinea pig.

Anesthesia, General↗
PubMed1985

An instrument to measure the activity level of the blind.

A questionnaire to measure the activity level of people with visual handicaps was developed in which separate components of activity are measured: "independence" and "difficulty" in performing various activities, "felt loss" in not performing the activities, and "motivation to learn" the activities. The responses of 129 veterans who completed this questionnaire were analyzed. Attempts were made to determine the reliability and validity of the scales. The questionnaire can be regarded as useful to evaluate both what patients are specifically taught and how that training effects activities not specifically taught.

Activities of Daily Living↗
PubMed1983

Anterior thalamic lesions and neuronal activity in the cingulate and retrosplenial cortices during discriminative avoidance behavior in rabbits.

Bilateral electrolytic lesions of the anteroventral (AV) nucleus of the thalamus given after training impaired retention performance (extinction and reacquisition) of rabbits in a differential avoidance conditioning task. In addition, the lesions abolished the excitatory, discriminative multiple-unit discharges that had developed in the cingulate and retrosplenial cortices to the auditory conditional stimuli (CSs) during the course of behavioral acquisition, prior to the induction of the lesions. The excitatory discharges were supplanted in the subjects with lesions by CS-elicited reduction of neuronal firing to levels below the prestimulus baseline. Lesions given before training did not disrupt behavioral acquisition, but they did eliminate the excitatory tone-elicited neuronal discharges that normally occur in the cortex before and during training. The CS-elicited reduction of neuronal firing did not occur at the beginning of training in the subjects given lesions before training, but it developed during the course of training. The lesions did not eliminate the excitatory and discriminative neuronal activity of the prefrontal cortex. These results demonstrate that excitatory and discriminative neuronal discharges in the cingulate and retrosplenial cortices are critically dependent on the connections of these areas with the anterior thalamic nuclei. Also the lesion-induced disruption of performance during extinction and reacquisition but not during original learning confirms a prediction from past electrophysiological studies, that the AV thalamic nucleus is involved in the mediation of the maintenance and retention of the conditioned avoidance behavior, but not in its original acquisition.

Animals↗
PubMed1983

Phosphonopeptides as substrates for peptide transport systems and peptidases of Escherichia coli.

Peptide transport and peptidase susceptibility of the antibacterial agent alafosfalin and other phosphonopeptides have been characterized in Escherichia coli. Phosphonodipeptides were accumulated by a process which appeared to involve multiple permeases; saturation was not achieved even at concentrations of 128 microM. Competition studies showed that these compounds had only a low affinity for the system transporting phosphonooligopeptides and were rapidly taken up by and were inhibitory to E. coli mutants unable to transport the toxic peptide triornithine. Phosphonodipeptides containing D-residues were not appreciably transported. By contrast, phosphonooligopeptides were generally transported by a distinct saturable permease system for which they had a high affinity. This system was identical to that utilized by triornithine. Phosphonooligopeptides with simple monoalkyl substituents at the amino terminus were also transported except in the case of a t-butyl substituent. The oligopeptide permease was also able to transport certain derivatives which contained some residues having D rather than L stereochemistry. Intracellular metabolism of phosphonooligopeptides was initiated almost exclusively by hydrolysis from the N terminus by an L-specific peptidase. This initial hydrolytic activity was unaffected by the aminopeptidase inhibitor bestatin, unlike the final hydrolysis step which yields L-1-aminoethylphosphonic acid from the phosphonodipeptide intermediate.

Biological Transport↗
PubMed1983

Technical note: a new method for preparing renal tissue for microdissection.

The rat kidney has been prepared for microdissection by in vivo perfusion with hyaluronidase and collagenase and subsequent fixation with glutaraldehyde. The procedure ensures preservation of cytoplasmic detail, and the principle of fixation after maceration should provide a foundation for developing a variety of staining and histochemical studies.

Animals↗
PubMed1982

Cingulate cortical and anterior thalamic neuronal correlates of the overtraining reversal effect in rabbits.

Multiple-unit activity of the cingulate cortex and the anteroventral (AV) nucleus of the thalamus in rabbits was recorded during reversal training, following differential conditioning of a locomotory (wheel rotation) avoidance response. The CS+ and CS- were pure tones (1 or 8 kHz) and the UCS was a footshock delivered through the grid floor of the wheel. One group of the rabbits received original training to a criterion followed immediately by reversal training. A second group received training to criterion followed by additional training sessions (overtraining), prior to reversal training. The results indicated that the overtraining reversal effect (ORE) occurred. That is, the overtrained subjects acquired the reverse discrimination in significantly fewer sessions than the non-overtrained subjects. The overall (non-discriminative) neuronal reactivity in all cingulate cortical laminae was reduced by overtraining, whereas the overall reactivity of the AV thalamus was enhanced. In addition, the non-overtrained subjects manifested a discriminative neuronal response appropriate to the original task (i.e. a greater response to the CS- than to the CS+ for reversal training), throughout the precriterial sessions of reversal training. This persistent 'original habit effect' occurred only at brief latencies (20-30 msec) after CS onset, and only in the deep cortical laminae (V-VI). The neuronal activity of the superficial laminae (I-IV) in non-overtrained subjects underwent a transition, in parallel with the behavior, from a discriminative response appropriate to the original task to one appropriate to the reversal task. No significant training-related changes were seen at any cortical depth in the overtrained subjects. Presentation of non-contingent footshocks during two sessions of reversal training following criterion re-enhanced the overall reactivity and the brief-latency discriminative neuronal response appropriate to the original task, which had undergone decline during reversal training, in the deep cortical laminae of the non-overtrained subjects. The enhanced overall reactivity and the discriminative activity in the superficial laminae of non-overtrained subjects had not declined during reversal training and were not altered by the non-contingent footshocks. The implications of these data are discussed in regard to the neural causation of the ORE.

Animals↗
PubMed1982

Antibacterial activity and mechanism of action of phosphonopeptides based on aminomethylphosphonic acid.

Phosphonopeptides based on aminomethylphosphonic acid as the C-terminal residue linked to L-amino acids possessed antibacterial activity in vitro and in vivo. Analogs in this series were generally less potent than corresponding compounds based on L-1-aminoethylphosphonic acid such as alafosfalin (L-alanyl-L-1-aminoethylphosphonic acid). Significant differences in antibacterial spectra were observed. The mechanism of action involved active transport of the peptide mimetics into the bacterial cells, followed by intracellular release of high concentrations of aminomethylphosphonic acid which inhibited bacterial cell wall biosynthesis. Aminomethylphosphonic acid behaved as a mimetic of both D- and L-alanine and inhibited D-Ala-D-Ala synthetase (EC 6.3.2.4.), alanine racemase (EC 5.1.1.1.), and UDP-N-acetylmuramyl-L-alanine synthetase (EC 6.3.2.8.). The minimal inhibitory concentration of L-norvalyl-aminomethylphosphonic acid was essentially unaffected by the presence of D-alanine, whereas the activity of the corresponding L-norvalyl derivative of L-1-aminoethylphosphonic acid was markedly decreased. Substantial differences in the inhibitory and lytic activity of the L-norvalyl derivatives of aminomethylphosphonic and L-1-aminoethylphosphonic acids were also observed when these agents were combined with other inhibitors of bacterial cell wall biosynthesis.

Animals↗
PubMed1982

Evaluating the rehabilitation process: an example with the blind.

The research methods presented here were developed for the evaluation of the CBRC (Central Blind Rehabilitation Center) at Hines. These methods are applicable to the evaluation of other blind rehabilitation programs. In addition, most of the strategies are applicable to other kinds of rehabilitation programs. The process of defining goals and of determining outcome variables is a necessary step in effective evaluation regardless of the population and program in question. It is essential to measure the influence of patient variables on treatment outcomes for all populations undergoing rehabilitation. The measures to evaluate these out-come and patient variables must be demonstrably reliable and valid. The methods used to identify and define variables, the research design and methods to produce reliable measures all can be used to evaluate a variety of programs as well as individual treatments and devices.

Blindness↗