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Biomedical subjects

H K Lau

Publications and source records attributed to H K Lau.

At least 19 recordsLinked to original sources

Neurovascular supply of the gracilis muscle: a study in the monkey and human.

A comparison of the gross anatomy, extramuscular nerve branches, and intramuscular blood supply of the gracilis muscle showed similar patterns in both monkey and human. The number and pattern of distribution of the extramuscular terminal branches to the muscle were similar. The intramuscular neural pattern demonstrated with the Sihler's staining technique was also similar in both species. In vivo electrical stimulation studies in the monkey revealed that stimulating each extramuscular terminal nerve branch produced a distinct segmental contraction of the muscle. Independent contraction with force generation was observed when the monkey muscle was split into anterior and posterior segments and stimulated through each of the two subdivisions of the main nerve trunk to the muscle. Angiograms verified that circulation was preserved in these two segments.

Animals

Modified Sihler's technique for studying the distribution of intramuscular nerve branches in mammalian skeletal muscle.

BACKGROUND: A largely forgotten technique initially designed by Sihler for staining nerve tissue has not been fully explored for staining intramuscular nerve branches in skeletal muscles. METHODS: Fresh, long heads of triceps from locally bred New Zealand white rabbits were used for this study. Immediately after their removal, the muscles with their motor nerve branches from the radial nerve were fixed in 10% unneutralized formalin, followed by maceration and depigmentation in 3% aqueous potassium hydroxide, decalcification in Sihler's solution I, micro-dissection, staining in Sihler's solution II, destaining in Sihler's solution I, neutralization in 0.05% lithium carbonate, and clearance in increasing concentrations of glycerin. RESULTS: A clear three-dimensional orientation of the distribution of the intramuscular nerve branches within the muscle belly was visualized. It was found in all specimens that the long head of triceps in the rabbit was constantly innervated by three main intramuscular nerve branches and each of them supplied different amounts of muscle fibers with some variation. CONCLUSION: The Sihler's neural staining technique can be applied to the study of the distribution of intramuscular nerve branches in limb skeletal muscles. Extension of the technique may be utilised in the identification of neuromuscular compartments in skeletal muscles. Such information may be usefully applied in free muscle transfer of segments of skeletal muscle.

Animals

Distribution of primary motor nerve branches and terminal nerve entry points to the forearm muscles.

BACKGROUND: The information available on innervation pattern of the human forearm muscles in standard anatomy texts, although adequate for routine procedures, is not detailed enough for surgical reconstruction in complex injuries of the limb and for paralytic conditions of the forearm from peripheral nerve and spinal cord injuries. METHODS: The innervation pattern in 10 cadaveric forearms was studied. The contributions of the main nerve trunks to each forearm muscle was examined. The location and number of the primary motor nerve branching points and of the terminal nerve entry points to each muscle were investigated. The location of both the primary nerve branching points and terminal nerve entry points was presented as a percentage of forearm length measured from the lateral humeral epicondyle to the radial styloid. RESULTS: Seven of 19 forearm muscles were innervated from a single branch from the main nerve trunk. The remaining 12 received more than one primary branch. Two of 19 forearm muscles had only one terminal nerve entry point. The others had two or more each. In 13 of 19 forearm muscles, the statistical median location of the primary motor nerve branching points was within the proximal one-third of the forearm length and either more proximally or distally for the remainder. The statistical median location of the terminal nerve entry points was within the proximal one-third in 9 forearm muscles and within the middle one-third of the forearm in 8 forearm muscles. In two, it was located proximal to the elbow and in the distal one-third of the forearm, respectively. CONCLUSIONS: In lacerations across the forearm, where main nerve trunks are divided, mere repair of the nerve trunks would not address the denervation of muscle or segments of muscle by the division of the primary (or secondary) nerve branches traversing the wound and which took origin proximal to the laceration either from the divided nerve trunks or from other undamaged nerve trunks. Although the main nerve trunks may be intact, segmental crush injuries will defunction muscles by direct muscle damage or by damage to the terminal nerve entry points to the muscle. Knowledge of the location of the nerve branches and the terminal nerve entry points facilitates the insertion of electrodes at the motor points of forearm muscles for functional electrical stimulation in upper motor neuron lesions. The information in this study may also be usefully applied in selective denervation procedures to balance muscles in spastic upper limbs.

Adult

A cadaver study on volume and surface area of the fingertip.

The volume of the volar soft tissue, dorsal soft tissue, and bone and the area of the dorsal and volar surfaces were estimated in 35 adult cadaver fingertips. The fingertip was defined as the part of the finger distal to the plane of the palmar skin crease and the major dorsal crease at the distal interphalangeal articulation. An impression molding technique, involving silicone rubber, was used to determine the volume, while dyed imprints of the dorsal and palmar surfaces were used to determine the surface area. In all digits, the mean volume of the volar soft tissue of the fingertip was found to be about 56%, the dorsal soft tissue about 26%, and the volume of bone about 18%. The volar soft tissue includes the skin and fascia (51% of the total fingertip volume), the flexor tendon and its sheath, and the volar plate and volar joint capsule (5% of the total). Power relationships for the total fingertip volume, the volume of volar soft tissue, and the volume of bone in terms of the length of the fingertip were noted. There was also a linear relationship found between the volume of the volar soft tissue and the volar surface area. This study provides data on the ratio of soft tissue to bone in the fingertip. The maintenance of the soft tissue-to-bone ratio, so as to regain fingertip form and function, may be of particular importance when designing flaps and coverage in the reconstruction of the fingertip.

Adult

Terminal nerve branch entries (motor points) of forearm muscles: a comparative study between monkey and human.

A study of the number of muscles, the nerve branches innervating them and number and distribution of the motor points was carried out on the forearm of the monkey (Macaca fascicularis) and human. There were 8 flexor muscles and 11 extensor muscles in the human, while there were 7 flexors and 12 extensors in the monkey. The distribution of the branches of the median, ulnar and radial nerves were similar in both species. The number of motor points and their distribution in the flexor and extensor muscles also showed considerable similarity between the two species. The monkey is a suitable experimental animal model for the study of the clinical application of functional electrical stimulation of the paralyzed forearm and hand of patients with upper motor neuron lesions.

Animals

Co-administration of midazolam decreases propofol dose during anesthesia in endoscopic laryngeal microsurgery.

BACKGROUND: Propofol is commonly used in total intravenous anesthesia (TIVA) for brief surgical procedures because it offers rapid recovery and has fewer side effects. However, concomittent use of other adjuvant agents has been considered so that the same anesthetic effects can be achieved at lower doses of propofol which is more expensive without compromising rapid recovery and increasing the adverse effects. This study was therefore designed to evaluate the co-administration of midazolam and propofol during anesthesia for endoscopic microsurgery and test its influences on the consumption of propofol and the quality of anesthesia. METHODS: Forty-two patients receiving selective endoscopic microsurgery were enrolled in this study. All patients received high frequency jet ventilation (HFJV) under TIVA. The control group (n = 21) received propofol (20 mg/5 s) during induction and 10 mg/kg/h as maintenance. The study group (n = 21) received midazolam (0.06 mg/kg) and propofol (20 mg/5 s) for induction with propofol 8 mg/kg/hr for maintenance. Doses of propofol, vital signs, recovery time, post-anesthetic high cortical function, and adverse events were evaluated and compared. RESULTS: Co-administration of midazolam and propofol in TIVA could reduce the induction dose and the total dose of propofol by 51% and 26% respectively but still achieve the same anesthetic effects. Vital signs and recovery were not influenced, and incidence of adverse effects did not increase. CONCLUSIONS: Our result suggests that co-administration of midazolam and propofol in TIVA appears to be safe, effective, and economic alternative to that with propofol alone. The effects were synergic but side effects were not.

Adult

Increase of a urokinase receptor-related low-molecular-weight molecule in colorectal adenocarcinomas.

Proteolytic activity is important for tumor growth and metastasis. Plasminogen and urokinase-type plasminogen activator (u-PA) constitute one of the most extensively studied proteolytic systems believed to participate in these processes. u-PA cleaves plasminogen to plasmin, which in turn degrades surrounding extracellular matrix and allows tumor cells to migrate to other areas. The specific receptor for u-PA (u-PAR) has also been implicated as an essential modulator in this pathway. Eleven paired samples of colorectal cancers and normal mucosal tissues from the same patients were removed at surgery. The tissues were homogenized and the supernatants assayed for u-PAR immunoreactivity, u-PAR antigen concentration, u-PAR binding activity and u-PA activity. Immunoblot analysis showed that a major u-PAR species of approximately 55 kDa was present in all tissues. In addition, a protein band of approximately 41 kDa, which crossreacted with anti-u-PAR antibodies, was also found in the tumors. This protein band was either absent, or present in relatively small amounts in the normal colorectal tissues. Cross-linking experiments showed that the approximately 55 kDa band only, and not the approximately 41 kDa band, was able to bind either single chain urokinase-type plasminogen activator (scu-PA) or the amino terminal fragment of urokinase (ATF). The tumor samples also exhibited highly elevated u-PA activity and u-PAR antigen relative to the corresponding normal tissues. Elevated u-PA activity appeared to correlate with elevated u-PAR antigen in colorectal cancers, but not in the normal tissues. These increases were also associated with increase of the u-PAR-related, low-molecular-weight protein in the tumor samples. The measurement of u-PAR and the u-PAR-related protein, in addition to u-PA activity, could have diagnostic or prognostic value in this type of cancer.

Adenocarcinoma

Fatigue reduction by sequential stimulation of multiple motor points in a muscle.

The purpose of this study was to determine the optimal method of stimulating multiple motor points in a muscle in an attempt to improve fatigue resistance. The long head of triceps, which has 2 to 3 motor points, in an adult New Zealand white rabbit was used as the muscle model. The fatigue index, defined as the percentage of maximum force at time t, was compared during the fatigue tests. Five test groups were defined based on the stimulation pattern of the muscle: (1) Group A1: The proximal motor point was stimulated at 20 Hz; (2) Group A2: The distal motor point was stimulated at 20 Hz; (3) Group B: Both motor points were stimulated simultaneously at 20 Hz; (4) Group C: Both proximal and distal motor points were stimulated at alternate intervals of 10 seconds at 20 Hz; and (5) Group D: Both motor points were stimulated sequentially at 10 Hz. Each test was conducted for 6 minutes. In sequential stimulation (Group D), the fatigue index was significantly higher when compared with the other test groups at Minutes 4, 5, and 6. In groups A1, A2, B, and C, there were no significant differences in the fatigue indices. For optimal control of muscle contraction in functional electrical stimulation, electrodes should be inserted into all motor points for a given muscle. Sequential stimulation of these points can improve fatigue resistance.

Animals

Clinical applications of functional electrical stimulation.

Functional Electrical Stimulation (FES) allows the restoration of controlled muscle contractions, and hence limb function via computer control, in patients with irrecoverable upper motor neuron lesions. Wide experience has been recorded in spinal cord injured paraplegics and tetraplegics and to a lesser extent in cerebrovascular accident victims. The electrodes, either surface or implanted, stimulate muscles electrically through a stimulator activated by a control source which is in turn activated by the remaining functions of the user. Future advances in electrode technology and control and command sources activation systems as well as development of "close-loop" systems need to be made if wide patient acceptance of this modality is to be ensured.

Cerebrovascular Disorders

Contractile characteristics on electrical stimulation of muscle with multiple motor points. An in vivo study in rabbits.

The purpose of this study was to investigate the significance of motor points in muscle and to determine their role in functional electrical stimulation. The long head of the triceps in adult female rabbits was used as the muscle model to study the contractile response to electrical stimulation of 1 motor point as opposed to simultaneous stimulation of multiple motor points in the muscle belly. The contractile response was studied with gradually increasing voltage amplitude and with or without added loads. Simultaneous stimulation of multiple motor points gave a consistently greater range of elbow extension when compared with stimulation of individual motor points. At low-voltage values, simultaneous stimulation of multiple motor points gave excursions obtainable only with high voltages on a single motor point. This pattern was observed with and without loads. These findings indicate that for optimal control of muscle contraction in functional electrical stimulation, electrodes may need to be inserted into multiple motor points for a given muscle. Stimulation for maximal muscle function then may be possible in the optimal low-voltage range without relying on spillover effect of high voltages. Nerve, muscle, and electrode damage also may be avoided.

Animals

Soluble urokinase receptor from fibrosarcoma HT-1080 cells.

A soluble form of urokinase-binding protein has been isolated from the human fibrosarcoma cell line HT-1080 and cell lines derived from it. Conditioned media of these cells were collected after overnight incubation under serum-free conditions, and were concentrated and passed through a column of Sepharose 4B to which high-molecular-weight urokinase had been attached. After thorough washing, a polypeptide could be eluted from the column with 1 M acetic acid. This material appeared to be a single band of approximately 60 kDa on SDS polyacrylamide gel. It cross-reacted with commercial antibodies made against urokinase receptor, and could be chemically cross-linked to the amino terminal fragment of urokinase. This material was similar to the urokinase receptor that was cleaved from HT-1080 cells by means of phosphatidylinositol-specific phospholipase C.

Chromatography, Affinity

Anticoagulant function of a 24-Kd fragment isolated from human fibrinogen A alpha chains.

A fibrinogen fragment obtained by limited-plasmin proteolysis has been isolated and purified to apparent homogeneity by gel filtrations. This fragment, denoted as 24-Kd fragment, has an apparent M(r) approximately 24,000 and contains an N-terminal sequence of met-glu-leu-glu-arg-pro-gly-gly-asn-glu-ile. The fragment contains a large number of acidic amino acid residues, and its amino acid composition is similar to several fibrinogen A alpha chains degradation fragments isolated previously. It corresponds to a peptide of the fibrinogen A alpha chains, the N-terminal of which starts at alpha Met-240. This peptide delays thrombin plasma clotting time. It does not bind calcium ions and does not inhibit thrombin's amidolytic activity. It binds to immobilized fibrin but not fibrinogen. It also inhibits the polymerization of desAA and desAABB fibrin monomers by simultaneously decreasing the maximum rate and the maximum level of the polymerization reaction. However, the initial lag period of this reaction is not affected by the fragment.

Amino Acid Sequence

Modulation of the plasminogen activation system in murine macrophages.

We have dissected the state of fibrinolytic balance in the C57/BL mouse macrophages, by means of immunotrap assays and zymography. We have monitored the individual changes of plasminogen activator (PA) and plasminogen activator inhibitor (PAI) activities of cellular lysates and secretions of these macrophages, after they were stimulated by various exogenous agents. The resident peritoneal macrophages were found to have very little PA but high level of PAI, and are therefore highly anti-fibrinolytic in nature. Upon stimulation by thioglycollate, PA activity increased and PAI activity decreased, thus raising the fibrinolytic balance in these macrophages. Upon incubation of resident or thioglycollate-activated macrophages by lipopolysaccharide (LPS), the PA level was depressed while the PAI level was increased, resulting in a large drop in the total fibrinolytic balance of the activated cells. When resident or thioglycollate-activated macrophages were incubated with the anti-inflammatory agent dexamethasone, the drug depressed both the expressions of PA and PAI, in the lysate and conditioned medium of both cell types. Thus cell-bound or secreted forms of macrophage PA and PAI activities were either increased or decreased in response to thioglycollate, LPS or dexamethasone challenge. The changes in PA and PAI resulted in different state of fibrinolytic balance in macrophages, and could be related to the different functions of these macrophages at different stages of their development.

Animals

Hypofibrinolysis in patients with hypercoagulability: the roles of urokinase and of plasminogen activator inhibitor.

The prevalence of abnormalities of fibrinolysis in patients with venous thromboembolism is as yet unknown. Defined abnormalities include congenital dysfunction and deficiency of plasminogen, and probably impaired plasminogen activation secondary to elevated levels of plasminogen activator inhibitor type 1 (PAI-1) or to impaired release of tissue plasminogen activator (tPA). In this preliminary study, we analyzed plasma samples from 21 patients for whom an investigation for possible thrombophilia was requested. Twenty of the patients had venous thromboembolism, and one had arterial thrombosis at an early age. Two patients had deficiency of protein C or protein S, but no other recognized biochemical disturbances related to thrombophilia were identified. Patient samples and plasma from 25 normal controls were assayed for tPA activity, PAI-1 activity, and urokinase (uPA) activity and antigen. tPA activity and antigen were not significantly different in patients than in controls. PAI-1 activity was significantly greater in patients (P < 0.0001). uPA activity was not different in the two groups. However, uPA antigen was significantly reduced in patients compared to controls (P = 0.001). These data suggest that hypofibrinolysis leading to a risk of thrombosis may be caused not only by elevated PAI-1 activity but also by reduced total uPA concentration.

Adult

Characterization of immunotrap assays for urokinase plasminogen activator and its inhibitors and measurements of these molecules in human plasma and mouse macrophage in culture.

1. Immunotrap assays that can measure the activities of urokinase-type plasminogen activator (uPA) and its inhibitors (PAIs) were characterized. 2. Both human plasma and mouse macrophages in culture were found to contain much higher inhibitor activity than uPA-like activity. 3. The balance between pro- and anti-fibrinolytic activities was quantitatively changed in the murine macrophages after the injection of thioglycollate. uPA-like materials were synthesized by the macrophages and secreted to the conditioned medium continuously, while PAI activity was unchanged during the same time period.

Animals

Characterization of radioimmunoassays for high- and low-molecular weight urokinases and estimation of different molecular forms of urokinase in urine and plasma.

Antibody populations against high- and low-molecular weight urokinases (HUK and LUK) were purified by passage of rabbit antiserum immunoglobulin fractions made against HUK and LUK through HUK- or LUK-bound Sepharose 4B (Pharmacia AB, Uppsala, Sweden) gels, respectively. Radioimmunoassays were then set up with these antibody populations. The characteristics of these radioimmunoassays were studied by competition of different antigens against radiolabeled HUK or LUK for these antibodies. We found that the anti-HUK antibody population recognizes epitopes on the light chain of HUK, most of which are situated outside of the urokinase-receptor binding sequence of amino acids. The anti-LUK antibody population probably recognizes a region on LUK distinct from its catalytic site. This region is also present in HUK but is altered in single-chain urokinase, suggesting that a conformation change takes place when single-chain urokinase is converted to HUK. The complexes of HUK and LUK with plasminogen activator inhibitor 1 or 2 could compete in either radioimmunoassay, with different and diminished efficiencies. Taking advantage of this result, we devised a procedure to measure the concentrations of various urokinase species in human urine. We found that freshly voided urine contained substantial amounts of free HUK, some HUK- and LUK-plasminogen activator inhibitor complexes, and a small amount of single-chain urokinase. By using a combination of radioimmunoassay and zymography, we found that human plasma contains mostly HUK-plasminogen activator inhibitor 1 complexes, a small amount of single-chain urokinase or HUK, and no LUK or LUK-inhibitor complexes.

Antibodies