Dominic Lam - Academia.edu (original) (raw)
Papers by Dominic Lam
Vaccines
Various types of vaccines, such as mRNA, adenovirus, and inactivated virus by injection, have bee... more Various types of vaccines, such as mRNA, adenovirus, and inactivated virus by injection, have been developed to prevent SARS-CoV-2 infection. Although some of them have already been approved under the COVID-19 pandemic, various drawbacks, including severe side effects and the requirement for sub-zero temperature storage, may hinder their applications. Bacillus subtilis (B. subtilis) is generally recognized as a safe and endotoxin-free Gram-positive bacterium that has been extensively employed as a host for the expression of recombinant proteins. Its dormant spores are extraordinarily resistant to the harsh environment in the gastrointestinal tract. This feature makes it an ideal carrier for oral administration in resisting this acidic environment and for release in the intestine. In this study, an engineered B. subtilis spore expressing the SARS-CoV-2 spike protein receptor binding domain (sRBD) on the spore surface was developed. In a pilot test, no adverse health event was observe...
Vaccines
The coronavirus diseases 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome cor... more The coronavirus diseases 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have threatened the world for more than 2 years. Multiple vaccine candidates have been developed and approved for emergency use by specific markets, but multiple doses are required to maintain the antibody level. Preliminary safety and immunogenicity data about an oral dose vaccine candidate using recombinant Bacillus subtilis in healthy adults were reported previously from an investigator-initiated trial in Hong Kong. Additional data are required in order to demonstrate the safety and efficacy of the candidate as a heterologous booster in vaccinated recipients. In an ongoing, placebo-controlled, observer-blinded, fixed dose, investigator-initiated trial conducted in the Macau, we randomly assigned healthy adults, 21 to 62 years of age to receive either placebo or a Bacillus subtilis oral dose vaccine candidate, which expressed the spike protein recepto...
The Journal of Neuroscience, 1985
Peroxidase-antiperoxidase immunocytochemistry was utilized to investigate the synaptic organizati... more Peroxidase-antiperoxidase immunocytochemistry was utilized to investigate the synaptic organization of enkephalin-like immunoreactive amacrine (Enk-amacrine) cells in the chicken retina. An initial light microscopic analysis revealed that immunostained cell bodies were situated in either the second or third tier of cells from the border of the inner nuclear and inner plexiform layers. The processes of such cells extended into the inner plexiform layer where they ramified as a fine plexus in sublaminae 1 and 3 to 5. At the ultrastructural level, enkephalin-positive somas exhibited a rather dense and evenly distributed peroxidase reaction product throughout their cytoplasm. Furthermore, the nucleus of Enk-amacrine cells was characterized by a round, unindented nuclear membrane. Immunoreactive processes of such cells were found to receive synaptic input from unstained amacrine and bipolar cells. Immunolabeled varicosities formed conventional synaptic contacts onto other vesicle-filled,...
The Journal of Neuroscience, 1981
Autoradiographic localization of high affinity [3H]glycine uptake in the retina of the goldfish h... more Autoradiographic localization of high affinity [3H]glycine uptake in the retina of the goldfish has been used to study some anatomical and physiological properties of potentially glycinergic neurons. There are two classes of retinal cells exhibiting high affinity glycine uptake: Aa amacrine cells and I2 interplexiform cells. Aa amacrine cells constitute about 20% of the somas in the amacrine cell layer and send their dendrites to the middle of the inner plexiform layer. There they are both pre- and postsynaptic primarily to other amacrine cells. Photic modulation of glycine uptake indicates that they are probably red-hyperpolarizing/green-depolarizing neurons. I2 interplexiform cells are a newly discovered type of interplexiform cell; in the outer plexiform layer, they receive direct synaptic input from the somas of red-dominated GABAergic H1 horizontal cells and are apparently presynaptic to dendrites of unidentified types of horizontal cells. The connections of I2 interplexiform c...
Human gene therapy, Feb 16, 2018
Gendicine (Recombinant Human p53 Adenovirus, AdRSV-p53), developed by Shenzhen SiBiono GeneTech C... more Gendicine (Recombinant Human p53 Adenovirus, AdRSV-p53), developed by Shenzhen SiBiono GeneTech Company, was approved by CFDA in 2003. It has been used in clinical oncology for 12 years since it entered the market in 2004. As the first-in-class product for cancer gene therapy, Gendicine met its expectation and demonstrated with ample clinical data that it is safe and effective for treating cancer. SiBiono manufactured 41 batches in compliant with CFDA QC/QA requirements. Total 169,571 vials (1.0x1012 vector particles per vial) were used in more than 50,000 patients, among them about 5,000 were international form over 50 nations outside China. Comparing with the first-line standard therapies, intratumor injection of Gendicine combined with chemotherapy and radiotherapy resulted in response rate significantly higher than chemo or radiotherapy alone. The approved indication for Gendicine is Head & Neck Cancer, including NPC. However, Gendicine has been successfully applied for various ...
The Journal of Cell Biology, 1978
A method has been developed for the preparation of large numbers of glial (Muller) cells from the... more A method has been developed for the preparation of large numbers of glial (Muller) cells from the turtle retina. After proteolytic dissociation of the retina, Muller cells were separated from retinal neurons by velocity sedimentation at unit gravity. Fractions containing >90 percent morphologically identifiable Muller cells were prepared by this procedure. Fractions containing only Muller cells were obtained by drawing selected cells individually into a micropipette under visual observation. Biochemical analyses of isolated Muller cells showed that (a) these cells did not synthesize and accumulate acetylcholine, γ-aminobutyric acid, or catecholamines when incubated with appropriate radioactive precursors; (b) the specific activities of choline acetyltransferase (EC 2.3.1.6), glutamate decarboxylase (EC 4.1.1.15), and tyrosine hydroxylase (EC 1.14.16.2) in these cells were less than 2 percent of those found in the retina; (c) Muller cells, however, contained high activities of tra...
Proceedings of the National Academy of Sciences, 1983
We have combined immunocytochemical localization of L-aspartate aminotransferase (L-aspartate:2-o... more We have combined immunocytochemical localization of L-aspartate aminotransferase (L-aspartate:2-oxoglutarate aminotransferase, EC 2.6.1.1; glutamic-oxaloacetic transaminase) with autoradiographic localization of high-affinity uptake sites for L-glutamate or L-aspartate to identify the neurotransmitters of mammalian photoreceptors. In both human and rat retinas, high aspartate aminotransferase immunoreactivity is found in cones but not in rods; certain putative bipolar and amacrine cells are also heavily stained. In the human retina, and perhaps also in the rat retina, cones possess a high-affinity uptake mechanism for L-glutamate but not L-aspartate, whereas rods and Müller (glial) cells take up both L-glutamate and L-aspartate. Taken together, our results indicate that (i) L-glutamate is much more likely than L-aspartate to be the transmitter for human cones, and possibly for cones of other mammalian species as well, and (ii) major differences exist between mammalian cones and rods...
Proceedings of the National Academy of Sciences, 1989
By transfecting mouse fibroblast L-M cells with human genomic DNA, we have established and identi... more By transfecting mouse fibroblast L-M cells with human genomic DNA, we have established and identified several clonal cell lines that stably express a high-affinity serotonin (5-HT)-uptake mechanism absent in untransfected host cells. One such cell line, L-S1, possesses features of 5-[3H]HT uptake similar to those previously characterized in the central nervous system and blood platelets: (i) specificity for 5-HT; (ii) antagonism by imipramine, a known inhibitor of high-affinity 5-HT uptake; (iii) both Na+ and temperature dependences; (iv) kinetic saturability; and (v) high affinity for 5-HT (Km = 0.39 +/- 0.10 microM; Vmax = 2.14 +/- 0.55 pmol/min per mg of protein). This cell line can be used to compare the relative efficacies of known blockers of 5-HT uptake and thereby offers a rapid and reliable assay system for testing novel inhibitors of this system. Since L-S1 contains stably integrated human DNA in its genome, we postulate that the observed 5-HT-uptake system resulted from t...
![Research paper thumbnail of The Uptake of [γ- 3 H] Aminobutyric Acid in the Goldfish Retina](https://attachments.academia-assets.com/88321493/thumbnails/1.jpg)
](Proceedings of the National Academy of Sciences, 1971
After goldfish retinas had been incubated for 1 hr with [γ- 3 H]aminobutyric acid, we found by au... more After goldfish retinas had been incubated for 1 hr with [γ- 3 H]aminobutyric acid, we found by autoradiography that the label was localized to a few restricted types of retinal cells. In particular, external and internal horizontal cells from light-stimulated retinas were more heavily labeled than corresponding cells from retinas kept in darkness. Some other cells and tissues in the retina also incorporated the labeled acid. Light stimulation, however, did not cause a pronounced change in the amount of label associated with these cells. Among these were some heavily labeled cells on the vitreal side of the inner nuclear layer, and scattered grains associated with the ganglion cell and optic nerve layers. Electrophoresis of retinal extracts after incubation with the labeled acid also showed that light-stimulated retinas contained about 40-100% more radioactivity than retinas kept in darkness, and that 90% of this activity remained as [γ- 3 H]aminobutyric acid. The role of the acid in...
Cognitive Therapy for Bipolar Disorder
Cognitive Therapy for Bipolar Disorder
Comparative Immunology, Microbiology and Infectious Diseases, 1998
Vaccines
Various types of vaccines, such as mRNA, adenovirus, and inactivated virus by injection, have bee... more Various types of vaccines, such as mRNA, adenovirus, and inactivated virus by injection, have been developed to prevent SARS-CoV-2 infection. Although some of them have already been approved under the COVID-19 pandemic, various drawbacks, including severe side effects and the requirement for sub-zero temperature storage, may hinder their applications. Bacillus subtilis (B. subtilis) is generally recognized as a safe and endotoxin-free Gram-positive bacterium that has been extensively employed as a host for the expression of recombinant proteins. Its dormant spores are extraordinarily resistant to the harsh environment in the gastrointestinal tract. This feature makes it an ideal carrier for oral administration in resisting this acidic environment and for release in the intestine. In this study, an engineered B. subtilis spore expressing the SARS-CoV-2 spike protein receptor binding domain (sRBD) on the spore surface was developed. In a pilot test, no adverse health event was observe...
Vaccines
The coronavirus diseases 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome cor... more The coronavirus diseases 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have threatened the world for more than 2 years. Multiple vaccine candidates have been developed and approved for emergency use by specific markets, but multiple doses are required to maintain the antibody level. Preliminary safety and immunogenicity data about an oral dose vaccine candidate using recombinant Bacillus subtilis in healthy adults were reported previously from an investigator-initiated trial in Hong Kong. Additional data are required in order to demonstrate the safety and efficacy of the candidate as a heterologous booster in vaccinated recipients. In an ongoing, placebo-controlled, observer-blinded, fixed dose, investigator-initiated trial conducted in the Macau, we randomly assigned healthy adults, 21 to 62 years of age to receive either placebo or a Bacillus subtilis oral dose vaccine candidate, which expressed the spike protein recepto...
The Journal of Neuroscience, 1985
Peroxidase-antiperoxidase immunocytochemistry was utilized to investigate the synaptic organizati... more Peroxidase-antiperoxidase immunocytochemistry was utilized to investigate the synaptic organization of enkephalin-like immunoreactive amacrine (Enk-amacrine) cells in the chicken retina. An initial light microscopic analysis revealed that immunostained cell bodies were situated in either the second or third tier of cells from the border of the inner nuclear and inner plexiform layers. The processes of such cells extended into the inner plexiform layer where they ramified as a fine plexus in sublaminae 1 and 3 to 5. At the ultrastructural level, enkephalin-positive somas exhibited a rather dense and evenly distributed peroxidase reaction product throughout their cytoplasm. Furthermore, the nucleus of Enk-amacrine cells was characterized by a round, unindented nuclear membrane. Immunoreactive processes of such cells were found to receive synaptic input from unstained amacrine and bipolar cells. Immunolabeled varicosities formed conventional synaptic contacts onto other vesicle-filled,...
The Journal of Neuroscience, 1981
Autoradiographic localization of high affinity [3H]glycine uptake in the retina of the goldfish h... more Autoradiographic localization of high affinity [3H]glycine uptake in the retina of the goldfish has been used to study some anatomical and physiological properties of potentially glycinergic neurons. There are two classes of retinal cells exhibiting high affinity glycine uptake: Aa amacrine cells and I2 interplexiform cells. Aa amacrine cells constitute about 20% of the somas in the amacrine cell layer and send their dendrites to the middle of the inner plexiform layer. There they are both pre- and postsynaptic primarily to other amacrine cells. Photic modulation of glycine uptake indicates that they are probably red-hyperpolarizing/green-depolarizing neurons. I2 interplexiform cells are a newly discovered type of interplexiform cell; in the outer plexiform layer, they receive direct synaptic input from the somas of red-dominated GABAergic H1 horizontal cells and are apparently presynaptic to dendrites of unidentified types of horizontal cells. The connections of I2 interplexiform c...
Human gene therapy, Feb 16, 2018
Gendicine (Recombinant Human p53 Adenovirus, AdRSV-p53), developed by Shenzhen SiBiono GeneTech C... more Gendicine (Recombinant Human p53 Adenovirus, AdRSV-p53), developed by Shenzhen SiBiono GeneTech Company, was approved by CFDA in 2003. It has been used in clinical oncology for 12 years since it entered the market in 2004. As the first-in-class product for cancer gene therapy, Gendicine met its expectation and demonstrated with ample clinical data that it is safe and effective for treating cancer. SiBiono manufactured 41 batches in compliant with CFDA QC/QA requirements. Total 169,571 vials (1.0x1012 vector particles per vial) were used in more than 50,000 patients, among them about 5,000 were international form over 50 nations outside China. Comparing with the first-line standard therapies, intratumor injection of Gendicine combined with chemotherapy and radiotherapy resulted in response rate significantly higher than chemo or radiotherapy alone. The approved indication for Gendicine is Head & Neck Cancer, including NPC. However, Gendicine has been successfully applied for various ...
The Journal of Cell Biology, 1978
A method has been developed for the preparation of large numbers of glial (Muller) cells from the... more A method has been developed for the preparation of large numbers of glial (Muller) cells from the turtle retina. After proteolytic dissociation of the retina, Muller cells were separated from retinal neurons by velocity sedimentation at unit gravity. Fractions containing >90 percent morphologically identifiable Muller cells were prepared by this procedure. Fractions containing only Muller cells were obtained by drawing selected cells individually into a micropipette under visual observation. Biochemical analyses of isolated Muller cells showed that (a) these cells did not synthesize and accumulate acetylcholine, γ-aminobutyric acid, or catecholamines when incubated with appropriate radioactive precursors; (b) the specific activities of choline acetyltransferase (EC 2.3.1.6), glutamate decarboxylase (EC 4.1.1.15), and tyrosine hydroxylase (EC 1.14.16.2) in these cells were less than 2 percent of those found in the retina; (c) Muller cells, however, contained high activities of tra...
Proceedings of the National Academy of Sciences, 1983
We have combined immunocytochemical localization of L-aspartate aminotransferase (L-aspartate:2-o... more We have combined immunocytochemical localization of L-aspartate aminotransferase (L-aspartate:2-oxoglutarate aminotransferase, EC 2.6.1.1; glutamic-oxaloacetic transaminase) with autoradiographic localization of high-affinity uptake sites for L-glutamate or L-aspartate to identify the neurotransmitters of mammalian photoreceptors. In both human and rat retinas, high aspartate aminotransferase immunoreactivity is found in cones but not in rods; certain putative bipolar and amacrine cells are also heavily stained. In the human retina, and perhaps also in the rat retina, cones possess a high-affinity uptake mechanism for L-glutamate but not L-aspartate, whereas rods and Müller (glial) cells take up both L-glutamate and L-aspartate. Taken together, our results indicate that (i) L-glutamate is much more likely than L-aspartate to be the transmitter for human cones, and possibly for cones of other mammalian species as well, and (ii) major differences exist between mammalian cones and rods...
Proceedings of the National Academy of Sciences, 1989
By transfecting mouse fibroblast L-M cells with human genomic DNA, we have established and identi... more By transfecting mouse fibroblast L-M cells with human genomic DNA, we have established and identified several clonal cell lines that stably express a high-affinity serotonin (5-HT)-uptake mechanism absent in untransfected host cells. One such cell line, L-S1, possesses features of 5-[3H]HT uptake similar to those previously characterized in the central nervous system and blood platelets: (i) specificity for 5-HT; (ii) antagonism by imipramine, a known inhibitor of high-affinity 5-HT uptake; (iii) both Na+ and temperature dependences; (iv) kinetic saturability; and (v) high affinity for 5-HT (Km = 0.39 +/- 0.10 microM; Vmax = 2.14 +/- 0.55 pmol/min per mg of protein). This cell line can be used to compare the relative efficacies of known blockers of 5-HT uptake and thereby offers a rapid and reliable assay system for testing novel inhibitors of this system. Since L-S1 contains stably integrated human DNA in its genome, we postulate that the observed 5-HT-uptake system resulted from t...
Proceedings of the National Academy of Sciences, 1971
After goldfish retinas had been incubated for 1 hr with [γ- 3 H]aminobutyric acid, we found by au... more After goldfish retinas had been incubated for 1 hr with [γ- 3 H]aminobutyric acid, we found by autoradiography that the label was localized to a few restricted types of retinal cells. In particular, external and internal horizontal cells from light-stimulated retinas were more heavily labeled than corresponding cells from retinas kept in darkness. Some other cells and tissues in the retina also incorporated the labeled acid. Light stimulation, however, did not cause a pronounced change in the amount of label associated with these cells. Among these were some heavily labeled cells on the vitreal side of the inner nuclear layer, and scattered grains associated with the ganglion cell and optic nerve layers. Electrophoresis of retinal extracts after incubation with the labeled acid also showed that light-stimulated retinas contained about 40-100% more radioactivity than retinas kept in darkness, and that 90% of this activity remained as [γ- 3 H]aminobutyric acid. The role of the acid in...
Cognitive Therapy for Bipolar Disorder
Cognitive Therapy for Bipolar Disorder
Comparative Immunology, Microbiology and Infectious Diseases, 1998