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C T Lin

Publications and source records attributed to C T Lin.

At least 145 records · Page 8Linked to original sources

Solubilization sites and acid-base forms of dibucaine-hydrochloride in neutral and charged micellar solutions.

Steady-state and time-resolved emission spectroscopic techniques have been employed to characterize the drug species of dibucaine and to identify its location in micellar Triton X-100 (neutral), hexadecyltrimethyl ammonium bromide (cationic) and lithium dodecyl sulfate (anionic) solutions at 77 K. Under physiological conditions, the dibucaine is shown to exist in the free base form (D) while solubilized in the hydrocarbon core of neutral micelles. In cationic micellar solution, dibucaine exists as the monocation species (DH+) where the anesthetic is solubilized in the extramicellar aqueous solution and D is solubilized in the hydrophobic region with close proximity to the micellar interface. In the anionic micelles, interfacial solubilization is most consistent with a site in which the tertiary amino group of the monocation dibucaine (DH+) is anchored at the micellar interface with its quinoline analog penetrating the hydrophobic region. The distinct properties observed for the drug species (i.e. D and DH+) and their solubilization sites in micelles are consistent with a balance between hydrophobic forces, surface polarity and the interfacial electrostatic potential present in the micellar solubilization sites. These observations could lend insight into the molecular basis of pharmacological action, in particular the mechanism of local anesthetic drug transport across membranes.

Dibucaine↗

High activity of low-Michaelis-Menten constant 3', 5'-cyclic adenosine monophosphate-phosphodiesterase isozymes in renal inner medulla of mice with hereditary nephrogenic diabetes insipidus.

Our previous studies on microdissected kidney tubule segments indicate that the failure of vasopressin (VP) to increase cAMP content in collecting ducts of mice with hereditary nephrogenic diabetes insipidus (NDI mice) is due to abnormally rapid cAMP catabolism via cyclic-3',5'-nucleotide phosphodiesterases (PDE). Furthermore, the VP-stimulated cAMP accumulation can be restored by addition of PDE isozyme-specific inhibitors. To elucidate the biochemical basis of the NDI syndrome, we analyzed PDE activities in extracts from inner medullary tissues of NDI mice and from control mice separated with the use of ionex fast protein liquid chromatography on a Mono-Q column. In extracts of inner medullary tissues from either control or NDI mice, the low Michaelis-Menten constant (Km) cAMP-PDE activity specific for cAMP as a substrate (cAMP-PDE) was eluted from a Mono-Q column with linear sodium acetate gradient as peak 3 at Na-acetate concentration (0.75-0.93 M) and was well separated from fractions containing the Ca(2+)-calmodulin sensitive PDE. The cAMP-PDE activity in peak 3 was significantly higher in NDI mice (greater than delta + 100%) than in controls. The sensitivity to effect of cAMP-PDE isozyme-specific inhibitors, rolipram and cilostamide, indicates that peak 3 consists predominantly (approximately 75%) of the rolipram-sensitive PDE-IV isozyme and a minor portion (approximately 25%) of cilostamide-sensitive PDE-III isozyme in both control and NDI mice. Higher activity of PDE-IV in NDI mice was due to 2.4 times higher apparent maximum velocity compared to controls, whereas the apparent Km for cAMP was not different. Our results show that low Km cAMP-PDE activities, predominantly PDE-IV, are higher in inner medulla of NDI mice. We suggest that the higher activity of PDE-IV, and to a lesser degree perhaps also PDE-III, accounts for rapid cAMP hydrolysis, which prevents the increase of cAMP generated in the response to VP in collecting ducts of NDI mice.

3',5'-Cyclic-AMP Phosphodiesterases↗

Is sick sinus syndrome an adenosine-mediated disease? Effects of intravenous aminophylline on sick sinus node function after pharmacologic autonomic blockade.

To assess the effects of intravenous aminophylline on the sinus node, 12 patients with clinical and Holter monitor-documented sick sinus syndrome were studied (1) during the control state, (2) after pharmacologic autonomic blockade and (3) 5 min after intravenous administration of aminophylline. The effects of aminophylline on sinus node function were compared with those after pharmacologic autonomic blockade. No significant improvement of sinus node function was found after intravenous aminophylline administration with a mean sinus cycle length and a mean maximum CSRT of 968 +/- 218 and 1832 +/- 1036 ms, respectively. The mean serum theophylline level was 10.9 +/- 1.7 micrograms/ml. Since aminophylline is an adenosine receptor antagonist, these findings suggest that intrinsic adenosine may not play an important role in pathogenesis in patients with chronic and advanced sick sinus syndrome.

Adenosine↗

Open-lung biopsy in patients with pulmonary infiltrate.

The application of open-lung biopsy to a patient with diffuse pulmonary infiltrate is dependent on whether it affords to a specific information and leads to a change in therapy. To evaluate the impact of open-lung biopsy on diagnosis and treatment of diffuse pulmonary infiltrates, we conducted a retrospective review of 37 patients undergoing this procedure during a 8-year period. There were 26 males and 11 females, at an average age of 53 years (ranging from 3 months to 79 years). Diagnostic yield was 97.2%, and biopsy yielded a specific diagnosis in 25(67.6%) patients and a change in therapy in 19 (51.4%) patients. Complications developed in 4 (11%) patients and the rate was higher under local anesthesia (3/4). Seven patients died, but no one was related to biopsy procedure. A specific diagnosis was obtained in 4 (50%) of the 8 immunocompromised patients, and a change in therapy occurred in 2 (25%) of these patients after biopsy, but these findings could not affect the survival rates. A specific diagnosis was obtained in 21 (72.4%) of the 29 nonimmunocompromised patients and a change in therapy occurred in 17 (58.6%) patients in this group. Five (83%) of 6 patients, who lacked definite tissue diagnosis by transbronchial biopsy, achieved confirmed diagnosis by open-lung biopsy. Open-lung biopsy in patients with a diffuse pulmonary infiltrate is an accurate diagnostic tool and frequently leads to a change in treatment. The procedure can be performed with acceptable morbidity and mortality in nonimmunocompromised patients, but should be used conservatively in immunocompromised patients.

Adult↗

[Patterns of recurrence in resected non-small-cell lung cancer--emphasis on its relation to cell type and staging].

Pulmonary resection remains the most effective treatment for patients with non-small-cell lung cancer. The purpose of this study is to determine the incidence, pattern, and site of lung cancer recurrence in patients surviving resection for non-small-cell lung cancer. One hundred ninety-eight patients with post-surgical non-small-cell lung cancer were followed up from 6.5 to 0.5 years (median: 2.0 years). Recurrent cancer developed in 103 patients (52.0%). Nineteen cases had local recurrence (9.6%) and 84 (42.4%) were distant metastasis. The incidence of recurrence increased with TN status, but there was no significant difference (P = 0.451) in the overall rate of recurrent lung cancer among the various TN staging. The overall recurrent rate of non-squamous cell lung cancer was 57.4%, which was higher than 47.7% in squamous cell lung cancer. Still, it made no significant difference among the various cell types (P = 0.058). Distant metastasis occurred most commonly to the bone (22.7%), then the contralateral lung (12.6%). Curative resection with accurate staging, appropriate adjuvant therapeutic modality and continued periodic surveillance are necessary in all patients who overcome the initial carcinoma.

Adenocarcinoma↗

Primary adenocarcinoma of the esophagus.

From Oct. 1982 to Sep. 1990, 450 cases of tissue proven carcinoma of the esophagus were treated at Taichung Veterans General Hospital, seven of these were primary adenocarcinoma of the esophagus, but only two had been diagnosed pre-operatively (by endoscopy). Most primary lesions may have originated from the submucosal gland of esophagus. The pathological characteristics included submucosal tumor infiltration without dysplasia of epithelium around the tumor margin and absence of Barrentt's epithelium. Five of the seven patients received surgical resection and four patients showed negative lymph node metastasis. Three of the node negative patients are still alive 23, 29 and 58 months after the operation. Thus long term survival may be expected after surgical resection in node negative primary adenocarcinoma of the esophagus.

Adenocarcinoma↗

Cytogenetic characterization of a nasopharyngeal carcinoma cell line and its subline.

Cytogenetic results of a nasopharyngeal carcinoma (NPC) cell line NPC-TW039 and its subline NPC-TW039-N1, established from the nude mouse transplant, were reported. This is the third case of NPC presented with banded karyotype, to date, in the literature. A 3q + marker chromosome, with involvement of band q25 similar to that present in the two previously reported cases, was detected in most tumor cells from both cell lines. The structural chromosome abnormalities of NPC-TW039-N1 were similar to its original cell line, NPC-TW039, except that the subline lost one marker chromosome and gained a new one.

Chromosome Aberrations↗

Statistical descriptors for the size and shape of globular proteins.

The atomic structures of proteins epitomize the ideas of complexity and irregularity in three-dimensional objects. For such objects, size and shape are difficult to quantify, and therefore the development of unbiased parameters for these properties could facilitate their description. Statistical analysis of the frequency distribution of interatomic distances in protein structures of different classes has revealed two numerical descriptors that correlate with physicochemical properties of these macromolecules. The median (mu) of the distribution correlates (r greater than .98, n = 45) with variables indicative of size (e.g., molecular weight and radius of gyration). The exponent of the Box-Cox transformation lambda, used for converting this distribution into a symmetrical one, correlated (r = .75, n = 43) with a general dimensionless shape parameter defined as the combination of the shape-related accessible surface (A0s), molecular volume (V), and radius of gyration (Rg) in the form s = (A0sRg/V). It is suggested that for globular proteins lambda is a function of both the shape parameter s and the fractal dimension D of the protein surface. These objective descriptors of size and shape could be useful to describe other complex objects.

Chemical Phenomena↗

Photophysical studies of local anesthetics, tetracaine and procaine: drug aggregations.

The effects of solvent and concentration on the photophysical properties of tertiary amine local anesthetics, tetracaine and procaine were studied experimentally using low temperature (77 K) emission spectroscopy and confirmed theoretically using a HAM/3 method. For tetracaine free base in methylcyclohexane, a broad fluorescence band observed at approximately 375 nm for concentrations greater than 1 x 10(-3) M is assigned to the molecular self-associated species. The disappearance of this band in ethanol (i.e. a model hydrophobic environment) indicates a greater tendency of neutral tetracaine towards molecular hetero-association. In an aqueous solution of procaine.HCl, a broad emission band centered at approximately 400 nm is detected even at a concentration as low as 1 x 10(-4) M and is attributed to the charged aggregates of procaine.HCl. Two general observations for procaine, tetracaine and dibucaine are noted: (1) the monocation and free base local anesthetics in ethanol solutions give identical photophysical properties, suggesting that the monocation drug species in ethanol is H+ dissociative, and (2) the lowest singlet excited state of neutral local anesthetics is calculated to have a charge-transfer character originating from a non-bonding electron in the N of tertiary amine group to the pi orbital of aromatic ring. The possible pharmacological implications of the deprotonation, the drug aggregations and the charge-transfer excitations of local anesthetics on the molecular basis of anesthesia are discussed.

Photochemistry↗

Establishment and characterization of two nasopharyngeal carcinoma cell lines.

Two human nasopharyngeal carcinoma (NPC) cell lines have been established. One derived from a 64-year-old male, and the other from a 36-year-old female Chinese patient living in Taiwan. Both were keratinizing squamous cell carcinoma in nature and designated as NPC-TW039 and NPC-TW076. Both have been grown in culture system for more than 100 passages. Single cells from both cell lines could form colonies in 0.3% soft agar. In the nude mouse transplantation experiment, both cell lines could produce tumor mass with metastasis. The karyotypic analysis showed multiple chromosomal abnormality. The number of chromosomes ranged between 76 to 109 and 80 to 105 with an average of 98 and 95, respectively. The doubling time was 10.5 hours and 10.8 hours, respectively. The NPC-TW039 cell line has been subcloned and three subclones have been obtained. Ultrastructural studies from those two cell line, three subcloned cell lines and two transplanted tumor masses, all showed two types of morphology: the dark and light cells. This morphologic difference is probably derived from the different metabolic state, but not due to an artifact. Three oncogene probes have been used to check the oncogene expression; none of those five cell lines is positive. Similarly, six Epstein-Barr virus fragments have been labeled to hybridize with NPC cellular DNA preparations, results from the Southern blotting showed no detectable Epstein-Barr virus DNA sequence.

Animals↗

Surgical management of spontaneous pneumothorax.

From 1982 to 1989, 293 patients with spontaneous pneumothorax were treated at VGHTC. There were 251 males and 42 females, aged 1-85 years, mean 49.3 years. The location of pneumothorax included right side 148 cases, left side 129 cases and bilateral 16 cases. The treatment included tube thoracostomy in 282 cases, thoracotomy abrasive pleurodesis in 39 cases, median sternotomy bilateral abrasive pleurodesis in 31 cases and chemical pleurodesis in 18 cases. Indications for pleurodesis included (1) recurrent pneumothorax (2) bilateral pneumothorax (3) persistent air leakage more than 7 days (4) massive air leakage (5) complications of pneumothorax. From our study, we concluded that: (1) The simplest management for spontaneous pneumothorax is tube thoracostomy. (2) In young adults or suspicious bilateral lesions, median sternotomy with bilateral abrasive pleurodesis is first choice of management for some special indications. (3) In aged patients or patients needing concomitant procedure for other pulmonary disease, thoracotomy abrasive pleurodesis is better choice. (4) When poor lung function and contraindicated to have an operation, chemical pleurodesis can also get some advantages.

Adult↗

Immunocytochemical investigation of L-glutamic acid decarboxylase in the rat hippocampal formation: the influence of transient cerebral ischemia.

The hippocampus is especially vulnerable to ischemic damage. Neurons in the CA3c region and dentate hilus demonstrate fast progressive damage while CA1 pyramidal cells demonstrate delayed neuronal damage. The delayed CA1 pyramidal cell loss could be caused by postischemic neuronal hyperactivity if hippocampal interneurons are lost after ischemia. Therefore we have counted the L-glutamic acid decarboxylase (GAD)-immunoreactive neurons in the hippocampus from control rats and rats surviving 4 or 11 days after 20 minutes of cerebral ischemia. All rats were injected intraventricularly with colchicine before they were killed. The hippocampal cell counts showed an increase in GAD-immunoreactive somata visualized on the fourth postischemic day. Eleven days after ischemia, the number of GAD-immunoreactive neurons visualized in the hippocampus CA1 and CA3c region decreased. GAD-immunoreactive baskets were visualized in the pyramidal cell layer and the granule cell layer in controls and 4 days after ischemia, but not in the CA1 and CA3c pyramidal cell layer 11 days after ischemia. We suggest the number of GAD-immunoreactive neurons visualized on the fourth postischemic day increases because somatal GAD accumulation increases and, therefore, ischemia may enhance GAD production. Our previous counts of CA1 interneurons 21 days after ischemia in toluidine-stained semithin sections demonstrated no interneuron loss. Therefore we suggest that the decreased number of CA1 and CA3c GAD-immunoreactive neurons visualized 11 days after ischemia is related to a decreased GAD production. It is possible at this stage after ischemia that the interneurons have decreased their GAD production because they have lost their input and/or target cells. We conclude that our counts of GAD-immunoreactive neurons visualized after ischemia express changes in the content of somatal GAD rather than the actual number of GAD-immunoreactive somata. Finally, we conclude that the delayed loss of CA1 pyramidal cells seen 4 days after ischemia is not preceded by loss of hippocampal GAD-immunoreactive neurons.

Animals↗

Is there an excitonic interaction or antenna system in bacteriorhodopsin?

The presence of a biphasic circular dichroism (CD) observed in the visible absorption spectrum of retinal in bacteriorhodopsin (bR) has been believed for many years to be due to excitonic-type interaction within the trimeric structure of the retinal in the protein membrane. In the present work, we present data and discuss previous observations that strongly suggest the absence of such an excitonic interaction. The magnetic CD spectrum of the trimer is found to be similar to that of the monomer and shows no sign of absorption to the doubly degenerate state predicted to be present from the exciton theory. This, together with the previous observations on the CD spectra of the photocycle intermediates of bR as well as the linear polarization studies of the fluorescence and the daughter absorption, sheds doubt on the presence of exciton interaction and thus suggests the presence of neither an antenna system nor a viable special reaction center in bR. Possible explanation for the observed biphasic nature of the CD spectrum is given in terms of having more than one type of bR with different protein conformations around the retinals in the trimer giving each similar absorption maximum but opposite signs for its rotary dispersion power.

Journal Article↗

Uterine malignancy developing after long term use of IUCD additional report of 2 cases: endometrial stromal sarcoma and leiomyosarcoma.

In our 2 previous papers published in this Journal, we had 5 cases of uterine malignancies developing after long term use of IUCD's. In the present paper 2 cases of such association are to be added. One case ATH with right adnexectomy was performed for persisting vaginal bleeding after 22 years of Lippes Loop application and recurrence 8 years after the first operation. Pathological diagnosis is endometrial stromal sarcoma. The other case is a leiomyosarcoma developing after 25 years of Lippes Loop application. Although no cause and effect relationship between IUCD use and uterine malignancy in human beings has been proved, the increase in such cases suggests to us that long term application should be avoided, particularly in view of the positive animal experiments. The successive detection of such cases in a relatively short period of time prompts us to make further studies to gain a deeper insight into such associations.

Female↗

Interaction of dibucaine.HCl local anesthetics with bacteriorhodopsin in purple membrane: a spectroscopic study.

Several spectroscopic techniques (absorption, emission, transient absorption and differential scanning calorimetry--DSC) were used to investigate the deprotonation of dibucaine.HCl in a hydrophobic environment, and the interaction sites and mechanisms of the local anesthetic dibucaine.HCl on bacteriorhodopsin (bR) in purple membrane. The important results are summarized as follows: (1) the visible absorption features of native (lambda max = 568 nm) and deionized (lambda max = 608 nm) bR are sensitive to the amount of dibucaine.HCl added; (2) the emission spectrum of dibucaine.HCl embedded in the retinal-free mutant bR is similar to that of dibucaine free base in Triton X-100 micellar solutions; (3) the phosphorescence emission of dibucaine at 77 K is completely quenched by bR and the fluorescence quenching rate for the incorporated dibucaine.HCl in bR was determined as kq = 4.09 x 10(13) M-1 s-1; (4) the incorporation of dibucaine.HCl in bR inhibits the slow component rate of formation of M412 and decreases the amount of M412 formation in the photochemical cycle of bR; and (5) the thermal stability of native bR was measured by DSC in the presence and absence of dibucaine and yielded an endothermic transition at 95.9 +/- 1.0 degrees C with 13.6 J/g (3.25 +/- 0.12 cal/g) of enthalpy changes. All observations suggest that the action site of the local anesthetic, dibucaine.HCl, is near or at the chromophore, i.e. the retinal Schiff base of bR. The anesthetic action on bR purple membrane is probably via a specific site binding, but not a conformational mechanism.

Bacteriorhodopsins↗