Diep Nguyen - Academia.edu (original) (raw)

Papers by Diep Nguyen

Research paper thumbnail of Single gene insertion drives bioalcohol production by a thermophilic archaeon

Proceedings of the National Academy of Sciences of the United States of America, Jan 9, 2014

Bioethanol production is achieved by only two metabolic pathways and only at moderate temperature... more Bioethanol production is achieved by only two metabolic pathways and only at moderate temperatures. Herein a fundamentally different synthetic pathway for bioalcohol production at 70 °C was constructed by insertion of the gene for bacterial alcohol dehydrogenase (AdhA) into the archaeon Pyrococcus furiosus. The engineered strain converted glucose to ethanol via acetate and acetaldehyde, catalyzed by the host-encoded aldehyde ferredoxin oxidoreductase (AOR) and heterologously expressed AdhA, in an energy-conserving, redox-balanced pathway. Furthermore, the AOR/AdhA pathway also converted exogenously added aliphatic and aromatic carboxylic acids to the corresponding alcohol using glucose, pyruvate, and/or hydrogen as the source of reductant. By heterologous coexpression of a membrane-bound carbon monoxide dehydrogenase, CO was used as a reductant for converting carboxylic acids to alcohols. Redirecting the fermentative metabolism of P. furiosus through strategic insertion of foreign genes creates unprecedented opportunities for thermophilic bioalcohol production. Moreover, the AOR/AdhA pathway is a potentially game-changing strategy for syngas fermentation, especially in combination with carbon chain elongation pathways.

Research paper thumbnail of MOLECULAR REGULATION OF COMPROMISED B LYMPHOPOEISIS IN AGED MICE

TheScientificWorldJOURNAL, 2001

The antibody (immunoglobulin, Ig) quality declines with age in both mice and humans. Our laborato... more The antibody (immunoglobulin, Ig) quality declines with age in both mice and humans. Our laboratory previously determined that pre-B cell numbers as well as the surrogate light (SL) chain, composed of the VpreB and lambda 5 (5) peptides, are reduced in aged mice (1-3). The SL is part of the pre-B cell receptor, critical for Ig variable heavy (VH) chain selection, cellular proliferation, and survival at the pre-B cell stage. We have also established that a human lambda 5 (hu 5) transgene is regulated in a stage-and lineage-specific fashion, similar to that of mouse lambda 5 (m 5) (4).

Research paper thumbnail of Life cycle assessment of ecological sanitation system for small-scale wastewater treatment

Science of The Total Environment, 2009

Ecological sanitation (EcoSan) concepts, relying on an environmentally sound management of water,... more Ecological sanitation (EcoSan) concepts, relying on an environmentally sound management of water, nutrient and energy fluxes, have been poorly characterized in literature and are widely ignored by public planning authorities, architects or engineers. A comparative life cycle assessment (LCA) of an EcoSan system at an office building and of conventional systems was carried out in order to provide practical data and information to (partially) fill this gap. Compared to conventional systems, EcoSan can reduce the contribution to ecosystem quality damage by more than 60%. EcoSan leads, however, to higher damages on resources and human health and higher impact on climate change. Key improvement possibilities and research needs related to these results are discussed throughout the paper.

Research paper thumbnail of The Spectrum of Central Nervous System Infections in an Adult Referral Hospital in Hanoi, Vietnam

PLoS ONE, 2012

Objectives: To determine prospectively the causative pathogens of central nervous system (CNS) in... more Objectives: To determine prospectively the causative pathogens of central nervous system (CNS) infections in patients admitted to a tertiary referral hospital in Hanoi, Vietnam. Methods: From May 2007 to December 2008, cerebrospinal fluid (CSF) samples from 352 adults with suspected meningitis or encephalitis underwent routine testing, staining (Gram, Ziehl-Nielsen, India ink), bacterial culture and polymerase chain reaction targeting Neisseria meningitidis, Streptococcus pneumoniae, S. suis, Haemophilus influenzae type b, Herpes simplex virus (HSV), Varicella Zoster virus (VZV), enterovirus, and 16S ribosomal RNA. Blood cultures and clinically indicated radiology were also performed. Patients were classified as having confirmed or suspected bacterial (BM), tuberculous (TBM), cryptococcal (CRM), eosinophilic (EOM) meningitis, aseptic encephalitis/meningitis (AEM), neurocysticercosis and others. Results: 352 (male: 66%) patients were recruited: median age 34 years (range 13-85). 95/352 (27.3%) diagnoses were laboratory confirmed and one by cranial radiology: BM (n = 62), TBM (n = 9), AEM (n = 19), CRM (n = 5), and neurocysticercosis (n = 1, cranial radiology). S. suis predominated as the cause of BM [48/62 (77.4%)]; Listeria monocytogenese (n = 1), S. pasteurianus (n = 1) and N. meningitidis (n = 2) were infrequent. AEM viruses were: HSV (n = 12), VZV (n = 5) and enterovirus (n = 2). 5 patients had EOM. Of 262/352 (74.4%) patients with full clinical data, 209 (79.8%) were hospital referrals and 186 (71%) had been on antimicrobials. 21 (8%) patients died: TBM (15.2%), AEM (10%), and BM (2.8%).

Research paper thumbnail of An essential role of Pak1 phosphorylation of SHARP in Notch signaling

Research paper thumbnail of Workshop on neutron reflection

Neutron News, 1996

The first Workshop on Neutron Reflection at Brookhaven was held May 22-23, 1996 (sponsored by Bro... more The first Workshop on Neutron Reflection at Brookhaven was held May 22-23, 1996 (sponsored by Brookhaven National Laboratory, Associated Universities and OSMIC Inc.). The workshop was organized in conjunction with the 1996 National Synchrotron Light Source (NSLS) ...

Research paper thumbnail of Differential regulation of components of the focal adhesion complex by heregulin: Role of phosphatase SHP-2

Journal of Cellular Physiology, 2002

Heregulin (HRG) has been implicated in the progression of breast cancer cells to a malignant phen... more Heregulin (HRG) has been implicated in the progression of breast cancer cells to a malignant phenotype, a process that involves changes in cell motility and adhesion. Here we demonstrate that HRG differentially regulates the site-speci®c phosphorylation of the focal adhesion components focal adhesion kinase (FAK) and paxilin in a dose-dependent manner. HRG at suboptimal doses (0.01 and 0.1 nM) increased adhesion of cells to the substratum, induced phosphorylation of FAK at Tyr-577, -925, and induced formation of well-de®ned focal points in breast cancer cell line MCF-7. HRG at a dose of 1 nM, increased migratory potential of breast cancer cells, selectively dephosphorylated FAK at Tyr-577, -925, and paxillin at Tyr-31. Tyrosine phosphorylation of FAK at Tyr-397 remained unaffected by HRG stimulation. FAK associated with HER2 only in response to 0.01 nM HRG. In contrast, 1 nM HRG induced activation and increased association of tyrosine phosphatase SHP-2 with HER2 but decreased association of HER2 with FAK. Expression of dominant-negative SHP-2 blocked HRGmediated dephosphorylation of FAK and paxillin, leading to persistent accumulation of mature focal points. Our results suggest that HRG differentially regulates signaling from focal adhesion complexes through selective phosphorylation and dephosphorylation and that tyrosine phosphatase SHP-2 has a role in the HRG signaling.

Research paper thumbnail of Cloning and functional characterization of PELP1/MNAR promoter

Gene, 2004

Proline-, glutamic acid-and leucine-rich protein 1 (PELP1)/modulator of nongenomic activity of es... more Proline-, glutamic acid-and leucine-rich protein 1 (PELP1)/modulator of nongenomic activity of estrogen receptor (MNAR), a novel coactivator of estrogen receptors (ERs; ERa and ERh), modulates the genomic and nongenomic functions of the ERs. PELP1 expression is developmentally regulated in mammary glands and overexpressed in breast tumors. However, little is known about the regulation of PELP1. In this study, we examined whether PELP1 expression is modulated by steroid hormone 17h-estradiol (E2) -ER pathway. We found that in MCF-7 breast cancer cells, E2 upregulated PELP1 expression threefold and that this upregulation was reduced by antiestrogen. We also found that E2 modulated PELP1 levels in an actinomycin-D-sensitive manner, suggesting transcriptional regulation. Cloning and analysis of the 2-kb PELP1 promoter region revealed two estrogen-responsive element (ERE) half sites in the PELP1 promoter region. In transient transfection assays, E2 upregulated PELP1 promoter activity in breast, endometrial and osteosarcoma model cancer cell lines in an ICI 182,780-sensitive manner. We demonstrated the recruitment of ER to the PELP1 promoter in vitro using EMSA assays and in vivo using a chromatin immunoprecipitation assay. The PELP1 promoter was similarly upregulated by both ERa and ERh and differentially regulated by selective estrogen receptor modulators in a cell line-dependent manner. Our results suggest that PELP1 expression is modulated by the E2-ER pathway and that PELP1 is an ER target gene. D Abbreviations: E2, 17h-estradiol; ER, estrogen receptor; ERE, estrogen response element; PELP1, proline-, glutamic acid-and leucine-rich protein; MNAR, modulator of nongenomic activity of estrogen receptor; luc, luciferase.

Research paper thumbnail of Bloch electron dynamics

Foundations of Physics, 1995

, zone number n, charge -el: dvj mj --~-= -e(E + v • B)/ are proposed, where v =ae,,(p)/ap is the... more , zone number n, charge -el: dvj mj --~-= -e(E + v • B)/ are proposed, where v =ae,,(p)/ap is the velocity, and {mj} are the principal masses m 71 = a2t./ap} along the normal and the two principal axes of curvatures at each point of the constant-energy surface represented by e=s,,(p). Their advantages over the prevalent equations of motion where the left-hand-side is replaced by hfcj are demonstrated by examining de Haas-van Alphen oscillations and orientation-dependent cyclotron resonance peaks. (1) J where E is the electric field; v -i-= ae,,(p) (2) OP is the velocity of the electron with charge q = -e, and e = e,,(p)= e,,(h k) are

Research paper thumbnail of Thyroid Dysfunction During Interferon Alpha Therapy for Chronic Hepatitis C

Clinical Nuclear Medicine, 2005

Interferon-alpha therapy is well known to induce a wide range of thyroid dysfunction. A 22-year-o... more Interferon-alpha therapy is well known to induce a wide range of thyroid dysfunction. A 22-year-old woman with chronic hepatitis C developed overt hyperthyroidism while on interferon-alpha and ribavirin therapy. Tc-99m thyroid scintigraphy demonstrated virtually absent tracer uptake consistent with subacute thyroiditis. Ten months after starting antiviral therapy, overt hyperthyroidism recurred. Repeat thyroid scintigraphy revealed diffusely increased tracer uptake throughout the thyroid gland consistent with Graves disease. This is an unusual case of 2 forms of hyperthyroidism-confirmed scintigraphically and occurring in the same patient over time while on interferon-alpha therapy.

Research paper thumbnail of Occult Bony Metastatic Disease Demonstrated on Labeled Leukocyte Scintigraphy

Clinical Nuclear Medicine, 2005

Abstract Labeled leukocyte scintigraphy is well established in confirming the presence of infecti... more Abstract Labeled leukocyte scintigraphy is well established in confirming the presence of infection and/or inflammation. There are various methods of labeling leukocytes with either indium-111 or technetium-99m. Although the procedure is sensitive, it is not specific. As a ...

Research paper thumbnail of Increased Activity on In-111 Octreotide Imaging Due to Radiation Fibrosis

Clinical Nuclear Medicine, 2008

Indium-111 octreotide scintigraphy is a useful investigation in the diagnosis and staging neuroen... more Indium-111 octreotide scintigraphy is a useful investigation in the diagnosis and staging neuroendocrine or nonendocrine malignancies such as carcinoid, granulomas, small cell lung cancer, medullary thyroid carcinoma, and others. Tumors with large numbers of somatostatin receptors can be accurately imaged and this can be useful in guiding treatment. Although uncommon, false-positives studies have been reported and often the cause is unexplained but assumed to be a high number of somatostatin receptors in other pathology. We present a case with increased uptake resulting in a scan due to pulmonary fibrosis.

Research paper thumbnail of Demonstration of Peritoneo-Scrotal Communication by Tc-99m MAA Scintigraphy Following False-Negative Contrast CT

Clinical Nuclear Medicine, 2010

Abstract A 69-year-old man with end stage renal failure was on peritoneal dialysis for 5 months. ... more Abstract A 69-year-old man with end stage renal failure was on peritoneal dialysis for 5 months. He developed sudden onset of scrotal swelling after lifting and presented for investigation. Clinically he had bilateral scrotal swelling with findings suggestive of ...

Research paper thumbnail of Single gene insertion drives bioalcohol production by a thermophilic archaeon

Proceedings of the National Academy of Sciences of the United States of America, Jan 9, 2014

Bioethanol production is achieved by only two metabolic pathways and only at moderate temperature... more Bioethanol production is achieved by only two metabolic pathways and only at moderate temperatures. Herein a fundamentally different synthetic pathway for bioalcohol production at 70 °C was constructed by insertion of the gene for bacterial alcohol dehydrogenase (AdhA) into the archaeon Pyrococcus furiosus. The engineered strain converted glucose to ethanol via acetate and acetaldehyde, catalyzed by the host-encoded aldehyde ferredoxin oxidoreductase (AOR) and heterologously expressed AdhA, in an energy-conserving, redox-balanced pathway. Furthermore, the AOR/AdhA pathway also converted exogenously added aliphatic and aromatic carboxylic acids to the corresponding alcohol using glucose, pyruvate, and/or hydrogen as the source of reductant. By heterologous coexpression of a membrane-bound carbon monoxide dehydrogenase, CO was used as a reductant for converting carboxylic acids to alcohols. Redirecting the fermentative metabolism of P. furiosus through strategic insertion of foreign genes creates unprecedented opportunities for thermophilic bioalcohol production. Moreover, the AOR/AdhA pathway is a potentially game-changing strategy for syngas fermentation, especially in combination with carbon chain elongation pathways.

Research paper thumbnail of MOLECULAR REGULATION OF COMPROMISED B LYMPHOPOEISIS IN AGED MICE

TheScientificWorldJOURNAL, 2001

The antibody (immunoglobulin, Ig) quality declines with age in both mice and humans. Our laborato... more The antibody (immunoglobulin, Ig) quality declines with age in both mice and humans. Our laboratory previously determined that pre-B cell numbers as well as the surrogate light (SL) chain, composed of the VpreB and lambda 5 (5) peptides, are reduced in aged mice (1-3). The SL is part of the pre-B cell receptor, critical for Ig variable heavy (VH) chain selection, cellular proliferation, and survival at the pre-B cell stage. We have also established that a human lambda 5 (hu 5) transgene is regulated in a stage-and lineage-specific fashion, similar to that of mouse lambda 5 (m 5) (4).

Research paper thumbnail of Life cycle assessment of ecological sanitation system for small-scale wastewater treatment

Science of The Total Environment, 2009

Ecological sanitation (EcoSan) concepts, relying on an environmentally sound management of water,... more Ecological sanitation (EcoSan) concepts, relying on an environmentally sound management of water, nutrient and energy fluxes, have been poorly characterized in literature and are widely ignored by public planning authorities, architects or engineers. A comparative life cycle assessment (LCA) of an EcoSan system at an office building and of conventional systems was carried out in order to provide practical data and information to (partially) fill this gap. Compared to conventional systems, EcoSan can reduce the contribution to ecosystem quality damage by more than 60%. EcoSan leads, however, to higher damages on resources and human health and higher impact on climate change. Key improvement possibilities and research needs related to these results are discussed throughout the paper.

Research paper thumbnail of The Spectrum of Central Nervous System Infections in an Adult Referral Hospital in Hanoi, Vietnam

PLoS ONE, 2012

Objectives: To determine prospectively the causative pathogens of central nervous system (CNS) in... more Objectives: To determine prospectively the causative pathogens of central nervous system (CNS) infections in patients admitted to a tertiary referral hospital in Hanoi, Vietnam. Methods: From May 2007 to December 2008, cerebrospinal fluid (CSF) samples from 352 adults with suspected meningitis or encephalitis underwent routine testing, staining (Gram, Ziehl-Nielsen, India ink), bacterial culture and polymerase chain reaction targeting Neisseria meningitidis, Streptococcus pneumoniae, S. suis, Haemophilus influenzae type b, Herpes simplex virus (HSV), Varicella Zoster virus (VZV), enterovirus, and 16S ribosomal RNA. Blood cultures and clinically indicated radiology were also performed. Patients were classified as having confirmed or suspected bacterial (BM), tuberculous (TBM), cryptococcal (CRM), eosinophilic (EOM) meningitis, aseptic encephalitis/meningitis (AEM), neurocysticercosis and others. Results: 352 (male: 66%) patients were recruited: median age 34 years (range 13-85). 95/352 (27.3%) diagnoses were laboratory confirmed and one by cranial radiology: BM (n = 62), TBM (n = 9), AEM (n = 19), CRM (n = 5), and neurocysticercosis (n = 1, cranial radiology). S. suis predominated as the cause of BM [48/62 (77.4%)]; Listeria monocytogenese (n = 1), S. pasteurianus (n = 1) and N. meningitidis (n = 2) were infrequent. AEM viruses were: HSV (n = 12), VZV (n = 5) and enterovirus (n = 2). 5 patients had EOM. Of 262/352 (74.4%) patients with full clinical data, 209 (79.8%) were hospital referrals and 186 (71%) had been on antimicrobials. 21 (8%) patients died: TBM (15.2%), AEM (10%), and BM (2.8%).

Research paper thumbnail of An essential role of Pak1 phosphorylation of SHARP in Notch signaling

Research paper thumbnail of Workshop on neutron reflection

Neutron News, 1996

The first Workshop on Neutron Reflection at Brookhaven was held May 22-23, 1996 (sponsored by Bro... more The first Workshop on Neutron Reflection at Brookhaven was held May 22-23, 1996 (sponsored by Brookhaven National Laboratory, Associated Universities and OSMIC Inc.). The workshop was organized in conjunction with the 1996 National Synchrotron Light Source (NSLS) ...

Research paper thumbnail of Differential regulation of components of the focal adhesion complex by heregulin: Role of phosphatase SHP-2

Journal of Cellular Physiology, 2002

Heregulin (HRG) has been implicated in the progression of breast cancer cells to a malignant phen... more Heregulin (HRG) has been implicated in the progression of breast cancer cells to a malignant phenotype, a process that involves changes in cell motility and adhesion. Here we demonstrate that HRG differentially regulates the site-speci®c phosphorylation of the focal adhesion components focal adhesion kinase (FAK) and paxilin in a dose-dependent manner. HRG at suboptimal doses (0.01 and 0.1 nM) increased adhesion of cells to the substratum, induced phosphorylation of FAK at Tyr-577, -925, and induced formation of well-de®ned focal points in breast cancer cell line MCF-7. HRG at a dose of 1 nM, increased migratory potential of breast cancer cells, selectively dephosphorylated FAK at Tyr-577, -925, and paxillin at Tyr-31. Tyrosine phosphorylation of FAK at Tyr-397 remained unaffected by HRG stimulation. FAK associated with HER2 only in response to 0.01 nM HRG. In contrast, 1 nM HRG induced activation and increased association of tyrosine phosphatase SHP-2 with HER2 but decreased association of HER2 with FAK. Expression of dominant-negative SHP-2 blocked HRGmediated dephosphorylation of FAK and paxillin, leading to persistent accumulation of mature focal points. Our results suggest that HRG differentially regulates signaling from focal adhesion complexes through selective phosphorylation and dephosphorylation and that tyrosine phosphatase SHP-2 has a role in the HRG signaling.

Research paper thumbnail of Cloning and functional characterization of PELP1/MNAR promoter

Gene, 2004

Proline-, glutamic acid-and leucine-rich protein 1 (PELP1)/modulator of nongenomic activity of es... more Proline-, glutamic acid-and leucine-rich protein 1 (PELP1)/modulator of nongenomic activity of estrogen receptor (MNAR), a novel coactivator of estrogen receptors (ERs; ERa and ERh), modulates the genomic and nongenomic functions of the ERs. PELP1 expression is developmentally regulated in mammary glands and overexpressed in breast tumors. However, little is known about the regulation of PELP1. In this study, we examined whether PELP1 expression is modulated by steroid hormone 17h-estradiol (E2) -ER pathway. We found that in MCF-7 breast cancer cells, E2 upregulated PELP1 expression threefold and that this upregulation was reduced by antiestrogen. We also found that E2 modulated PELP1 levels in an actinomycin-D-sensitive manner, suggesting transcriptional regulation. Cloning and analysis of the 2-kb PELP1 promoter region revealed two estrogen-responsive element (ERE) half sites in the PELP1 promoter region. In transient transfection assays, E2 upregulated PELP1 promoter activity in breast, endometrial and osteosarcoma model cancer cell lines in an ICI 182,780-sensitive manner. We demonstrated the recruitment of ER to the PELP1 promoter in vitro using EMSA assays and in vivo using a chromatin immunoprecipitation assay. The PELP1 promoter was similarly upregulated by both ERa and ERh and differentially regulated by selective estrogen receptor modulators in a cell line-dependent manner. Our results suggest that PELP1 expression is modulated by the E2-ER pathway and that PELP1 is an ER target gene. D Abbreviations: E2, 17h-estradiol; ER, estrogen receptor; ERE, estrogen response element; PELP1, proline-, glutamic acid-and leucine-rich protein; MNAR, modulator of nongenomic activity of estrogen receptor; luc, luciferase.

Research paper thumbnail of Bloch electron dynamics

Foundations of Physics, 1995

, zone number n, charge -el: dvj mj --~-= -e(E + v • B)/ are proposed, where v =ae,,(p)/ap is the... more , zone number n, charge -el: dvj mj --~-= -e(E + v • B)/ are proposed, where v =ae,,(p)/ap is the velocity, and {mj} are the principal masses m 71 = a2t./ap} along the normal and the two principal axes of curvatures at each point of the constant-energy surface represented by e=s,,(p). Their advantages over the prevalent equations of motion where the left-hand-side is replaced by hfcj are demonstrated by examining de Haas-van Alphen oscillations and orientation-dependent cyclotron resonance peaks. (1) J where E is the electric field; v -i-= ae,,(p) (2) OP is the velocity of the electron with charge q = -e, and e = e,,(p)= e,,(h k) are

Research paper thumbnail of Thyroid Dysfunction During Interferon Alpha Therapy for Chronic Hepatitis C

Clinical Nuclear Medicine, 2005

Interferon-alpha therapy is well known to induce a wide range of thyroid dysfunction. A 22-year-o... more Interferon-alpha therapy is well known to induce a wide range of thyroid dysfunction. A 22-year-old woman with chronic hepatitis C developed overt hyperthyroidism while on interferon-alpha and ribavirin therapy. Tc-99m thyroid scintigraphy demonstrated virtually absent tracer uptake consistent with subacute thyroiditis. Ten months after starting antiviral therapy, overt hyperthyroidism recurred. Repeat thyroid scintigraphy revealed diffusely increased tracer uptake throughout the thyroid gland consistent with Graves disease. This is an unusual case of 2 forms of hyperthyroidism-confirmed scintigraphically and occurring in the same patient over time while on interferon-alpha therapy.

Research paper thumbnail of Occult Bony Metastatic Disease Demonstrated on Labeled Leukocyte Scintigraphy

Clinical Nuclear Medicine, 2005

Abstract Labeled leukocyte scintigraphy is well established in confirming the presence of infecti... more Abstract Labeled leukocyte scintigraphy is well established in confirming the presence of infection and/or inflammation. There are various methods of labeling leukocytes with either indium-111 or technetium-99m. Although the procedure is sensitive, it is not specific. As a ...

Research paper thumbnail of Increased Activity on In-111 Octreotide Imaging Due to Radiation Fibrosis

Clinical Nuclear Medicine, 2008

Indium-111 octreotide scintigraphy is a useful investigation in the diagnosis and staging neuroen... more Indium-111 octreotide scintigraphy is a useful investigation in the diagnosis and staging neuroendocrine or nonendocrine malignancies such as carcinoid, granulomas, small cell lung cancer, medullary thyroid carcinoma, and others. Tumors with large numbers of somatostatin receptors can be accurately imaged and this can be useful in guiding treatment. Although uncommon, false-positives studies have been reported and often the cause is unexplained but assumed to be a high number of somatostatin receptors in other pathology. We present a case with increased uptake resulting in a scan due to pulmonary fibrosis.

Research paper thumbnail of Demonstration of Peritoneo-Scrotal Communication by Tc-99m MAA Scintigraphy Following False-Negative Contrast CT

Clinical Nuclear Medicine, 2010

Abstract A 69-year-old man with end stage renal failure was on peritoneal dialysis for 5 months. ... more Abstract A 69-year-old man with end stage renal failure was on peritoneal dialysis for 5 months. He developed sudden onset of scrotal swelling after lifting and presented for investigation. Clinically he had bilateral scrotal swelling with findings suggestive of ...