Pakes Research Articles

Cocultured Schwann Cells Rescue Irradiated Pelvic Neuron Outgrowth and Increase Survival

BackgroundProstatic radiation therapy (RT) leads to erectile dysfunction by damaging peri-prostatic pro-erectile nerves of the pelvic ganglion. Schwann cells (SC) facilitate neuronal repair after mechanical injury, however, their role in repair of pelvic neurons post-radiation hasn't been explored. AimTo determine if SCs cocultured with primary pelvic neurons can rescue neuronal survival and growth after ex vivo RT. MethodsMajor pelvic ganglia (MPG) were collected from adult male Sprague-Dawley rats (n = 12) to isolate SCs. SCs received RT (0 or 8 Gy), were plated on coated coverslips and grown to confluence before the addition of neurons. Additional MPGs were irradiated (0 or 8 Gy) and digested to isolate pelvic neurons. Dissociated neurons were plated alone or atop SC-coated coverslips to create 6 experimental groups (n = 3/grp): (i) Control (CON) MPG, (ii) RT MPG, (iii) CON SC + CON MPG, (iv) CONSC + RT MPG, (v) RT SC + CON MPG, and (iv) RT SC + RT MPG. After 72 hours, coverslips were fixed and stained for beta-tubulin (neuron marker), S100 (SC marker), neuronal nitric oxide synthase (nitrergic marker), tyrosine hydroxylase (sympathetic marker), and terminal deoxynucleotidyl transferase dUTP nick-end labeling. OutcomesWe measured neurite length, branching, specific neuron populations and apoptosis. ResultsEx vivo RT decreased MPG neuron length, increased apoptosis and decreased nitrergic neurons in monoculture. Compared to all other groups, CON SC + RT MPG cocultures demonstrated increased neurite outgrowth (P < .001). Neurite branching was decreased in the RT MPG + RT SC coculture, but unchanged in other cocultures. Groups containing RT MPG neurons exhibited increased apoptosis, but coculture with CON SC reduced the degree of RT-induced apoptosis (P < .01). The number of tyrosine hydroxylase positive neurons was unchanged while nitrergic neurons were significantly lower in RT neurons and coculture with CON SCs was unable to prevent nitrergic loss. Clinical TranslationThese findings suggest that SCs may be an important target in prostate cancer patients with radiation-induced pelvic neuropathy to promote MPG neuron survival and neuronal repair after RT. Strengths and LimitationsThis is the first study to characterize the ex vivo ability of SCs to rescue pelvic nerve growth and survival. The study is limited by little supporting mechanistic molecular data and the need to confirm the ability of healthy SCs to promote pelvic neuron survival and repair following prostatic RT in vivo. ConclusionUnirradiated SCs partially mitigated RT-induced MPG apoptosis but did not affect the loss of nitrergic neuron populations suggesting that SCs promote irradiated MPG neuron survival and facilitate intrinsic repair functions.Randolph JT, Pak ES, McMains JC, et al. Cocultured Schwann Cells Rescue Irradiated Pelvic Neuron Outgrowth and Increase Survival. J Sex Med 2022;19:1333–1342.

Ex Vivo Radiation Leads to Opposing Neurite Growth in Whole Ganglia vs Dissociated Cultured Pelvic Neurons

BackgroundProstatic radiation therapy (RT) often causes erectile dysfunction (ED) and the mechanisms governing RT-induced ED are unclear with a lack of therapeutic strategies. AimTo determine the effects of ex vivo RT on major pelvic ganglion (MPG) neuron survival, and neurite growth in whole vs dissociated culture. MethodsMPGs were removed and irradiated (0 or 8 Gy) from male Sprague Dawley rats. For dissociated culture, MPG neurons were digested in collagenase/dispase and cultured on coverslips. Immunofluorescent staining for beta-tubulin III (TUBB3; neuron marker), neuronal nitric oxide synthase (nNOS; nitrergic marker), tyrosine hydroxylase (TH; sympathetic marker), and terminal deoxynucleotidyl transferase dUTP nick end labeling assessed neurite length, branching, autonomic neuron density, and apoptosis. For whole organ culture, MPGs were grown in Matrigel. Gene expression of apoptotic markers (caspase 1, 3), TUBB3, nNOS, TH, and Schwann cells (Sox10, Krox20, glial fibrillary acid protein) was measured in whole organ cultured MPGs by quantitative polymerase chain reaction. OutcomesAfter 72 hours, neurite length, branching, autonomic neuron density, and apoptosis were assessed, and gene expression was measured. ResultsRT increased apoptosis in dissociated neurons measured by terminal deoxynucleotidyl transferase dUTP nick end labeling (P < .001) and whole MPG culture via upregulation of caspase 3 gene expression (P < .05). Nitrergic neurons were markedly decreased in irradiated dissociated culture (P < .05), while nNOS gene expression was upregulated in irradiated whole organ culture (P < .05). The proportion of dissociated sympathetic neurons and whole organ TH gene expression remained unchanged after RT. Interestingly, RT dissociated neurites were 22% shorter than controls, while RT whole organ neurites were 15% longer than controls (P < .01). MPG Schwann cells markers (Sox10, Krox20) were elevated after RT in whole organ culture. Clinical TranslationProstatic RT leads to increased neuronal cell death and less erectogenic nitrergic neurons contributing to ED. Strengths & LimitationsThe advantages of dissociated neuron culture include distinct neurites which are easily measured for apoptosis, length/branching, and specific neuron types. In contrast, whole MPG culture is advantageous as it contains all the supporting cells present in vivo. ConclusionThe 2 different culture methods demonstrated opposing neurite growth after RT indicating the importance of supporting cell network to promote pelvic neuron neuritogenesis and survival following RT.Randolph JT, Pak ES, Koontz BF, et al. Ex Vivo Radiation Leads to Opposing Neurite Growth in Whole Ganglia vs Dissociated Cultured Pelvic Neurons. J Sex Med 2020;17:1423–1433.

Prostate-Confined Radiation Decreased Pelvic Ganglia Neuronal Survival and Outgrowth

BackgroundErectile dysfunction (ED) is common following radiation therapy (RT) for prostate cancer. Although the cause of RT-induced ED is unknown, damage to both the neuronal and vascular components supporting erections are often implicated. AimTo determine the effects of prostatic RT on erections, penile vascular physiology, and major pelvic ganglia (MPG) neuron growth and survival in a rat model. MethodsMale rats underwent 0 Gy or 22 Gy single fraction of prostate-confined, conformal RT. At 2 weeks or 10 weeks post-RT (n = 10/group), cavernous nerve stimulation was performed and erections were assessed. Tissue bath experiments were performed to assess both penile artery and internal pudendal artery (IPA) function. MPGs were dissociated and neurons grown in culture for 72 hours. Immunofluorescence staining was done to quantify neuron survival (terminal deoxynucleotidyl transferase nick-end labeling), outgrowth (beta-tubulin III), type (nitric oxide synthase [nNOS] and tyrosine hydroxylase [TH]), and nerve injury markers (small GTPase Rac1 and ninjurin-1 [Ninj-1]). Whole MPG real-time quantitative polymerase chain reaction (qPCR) was performed to measure expression of genes related to nerve type, neuron injury, repair, and myelination, such as Ninj-1, Rac1, ATF3, GAP43, GFAP, SOX10, and KROX20. OutcomesIntracavernosal pressure (ICP) to mean arterial pressure (MAP) ratio, smooth muscle contractility and relaxation, gene expression, neuritogenesis, and apoptosis. ResultsFollowing RT, ICP/MAP was unchanged at 2 weeks or 10 weeks. Nerve-mediated penile contraction was increased at 2 weeks, whereas adrenergic contraction was reduced at 10 weeks. Penile relaxation and IPA vasoreactivity were unchanged. Neuronal apoptosis was more than doubled both early and late post-RT. RT caused a progressive decrease in neurite branching but an early increase and then late decrease in neurite lengthening. RT reduced the numbers of nNOS-positive neurons both early and late and also decreased MPG nitrergic gene expression. TH neurons and gene expression were unchanged at 2 weeks; however, both were decreased after 10 weeks. Although most markers of gene injury and repair were unaffected early post-RT, MPG expression of Ninj1 and GFAP increased. After 10 weeks, Ninj1 and GFAP remained elevated while markers of neuron injury (ATF3), outgrowth (GAP43 and Rac1), and myelin regulation (SOX10) were decreased. Clinical TranslationRT-induced ED may result from damage to the ganglia controlling erections. Strengths & LimitationsThis study used a clinically relevant, prostate-confined model to examine neurovascular structures not accessible in human studies. Unfortunately, rats did not exhibit ED at this time point. ConclusionThis is the first study to demonstrate impaired health and regeneration potential of dissociated MPG neurons following RT. Neuronal injury was apparent early post-RT and persisted or increased over time but was insufficient to cause ED at the time points examined.Powers SA, Odom MR, Pak ES, et al. Prostate-Confined Radiation Decreased Pelvic Ganglia Neuronal Survival and Outgrowth. J Sex Med 2019;16:27–41.

PAKE PROTOCOL WITH OTSP AND IMAGE BASED PASSWORD AUTHENTICATION

To diminish the harm of different assault in banks, governments, and other security touchy regions are conveying one time secret key frameworks, after utilized that watchword will consequently devastate. In past a few years concocted numerous secret word verification key trade conventions like DH-PAKE, J-PAKE and so on, however they all experienced some basic security issues. We give a formal way to deal with beat these different issues in secret key confirmation key trade conventions. We utilize one time session secret word (OTSP) with regards to watchword validation key trade (PAKE), which takes into consideration common check, session key assention, and restriction to different basic assaults. Improve greater security in our convention we have utilized solid session keys which is produced by imaged based key process.

Enhanced Electrical Field Stimulated Nitrergic and Purinergic Vasoreactivity in Distal vs Proximal Internal Pudendal Arteries

BackgroundThe internal pudendal arteries (IPAs) supply blood to the penis and are highly susceptible to vascular remodeling in rodent models of diabetes, hypertension, aging, and chronic kidney disease, thus contributing to erectile dysfunction. Interestingly, vascular remodeling primarily occurs in the distal and not in the proximal IPA, suggesting distinct local physiologic signaling differences within the IPA. AimTo examine the role of purinergic signaling and neurotransmitter release by electrical field stimulation (EFS) in the regulation of proximal and distal IPA vascular tone. MethodsProximal and distal IPAs were mounted in wire myographs and vascular responses to phenylephrine, acetylcholine, and 2-(N,N-diethylamino)-diazenolate-2-oxide, diethyl-ammonium salt (DEA NONOate) were measured. EFS-mediated contraction and non-adrenergic non-cholinergic (NANC) relaxation were evaluated in the absence and presence of a nitric oxide synthase antagonist. Purinergic agonist and NANC relaxation responses were assessed in the presence and absence of P2X1 and P2Y1 antagonists. Protein expression of P2X1 and P2Y1 receptors was measured by western blot. Main Outcome MeasuresProximal and distal IPA contraction and relaxation were measured during increasing agonist administration and EFS in the presence and absence of antagonists. ResultsProximal and distal IPA concentration response curves to phenylephrine, acetylcholine, and DEA NONOate did no differ. Interestingly, distal IPA exhibited greater EFS-mediated contraction and NANC relaxation compared with proximal IPA. Nitric oxide synthase inhibition completely inhibited distal IPA NANC relaxation but did not affect proximal IPA relaxation. P2X1 or P2Y1 receptor antagonism during NANC relaxation increased distal IPA relaxation but decreased proximal IPA relaxation. Combined P2X1 and P2Y1 receptor antagonism had no effect on proximal IPA relaxation but significantly increased distal IPA NANC relaxation. Clinical TranslationUnderstanding neurovascular regulation of IPA vascular tone through nitrergic and purinergic mechanisms could yield new therapeutic targets to improve IPA blood flow and treat vasculogenic erectile dysfunction. Strengths and LimitationsThis study is the first to illustrate the differences in mechanisms responsible for regulating vascular tone in the proximal and distal IPAs. All presented findings are currently limited to ex vivo vascular function. ConclusionThe regulation of vascular tone differs regionally in the IPA. The distal IPA is controlled through neurotransmitter-mediated NO-dependent mechanisms and increased sensitivity to purinergic P2X1 and P2Y1 receptor inhibition.Odom MR, Pak ES, Brown DA, Hannan JL. Enhanced Electrical Field Stimulated Nitrergic and Purinergic Vasoreactivity in Distal vs Proximal Internal Pudendal Arteries. J Sex Med 2017;14:1285–1296.

MR perfusion imaging study of the hepatic hemodynamics in pigs

Objective To evaluate the MR perfusion imaging in measuring the hemodynamics of liver.Methods CT and MR perfusion imaging were performed in livers of 13 pigs.The hepatic artery perfusion(HAP),portal vein perfusion(PVP),total hepatic blood flow(THBF),portal vein perfusion index(PVI),distribution volume(DV)and mean transit time(MTT)were calculated and compared respectively.Hemodynamics of the liver from two kinds of imaging was compared by paked t-test,and the relativity was analyzed by Pearson correlation analysis.Results In CT and MR perfusion imaging of the 13 pigs:the hepatic artery perfusion(HAP)were(37.7±7.38)and(35.80±7.31)ml-min-1·100ml-1.the portal vein perfusion(PVP)were(123.16 35.89)and(121.40±36.81)ml·min-1·100 ml-1.the total hepatic blood flow(THBF)were(160.88±37.05)and(157.21±38.71)ml·min-1·100 ml-1.the portal vein perfusion index(PVI)were(75.95±5.21)%and(76.63±5.24)%,the distilbution volume(DV)were(35.10±11.17)%and(41.03±10.06)%。The mean transit time(MTT)were(14.08±1.40)and(14.94±1.32)s.There were no statistical differences for HAP,PVP,THBF and PVI between CT and MR perfusion imaging(t=1.263,0.926,1.225,-1.115,P＞0.05).There were no statistical differences for DV and MTT(t=-3.345,-3.200,P＜0.01).Analysis of these two kinds of imaging showed the correlation coefficient of PVP,THBF and PVI were hishly related(r＞0.85,P＜0.01).Correlation coefficient of HAP,DV and M1T were moderately related(r＞0.70,P＜0.01).Conclusions MR perfusion Call quantify the blood flow parameters of liver accurately.It is close to that of the CT perfusion imaging. Key words: Magnetic resonance imaging; Tomography,X-ray computed; Liver

Smoking and Colorectal Cancer: Different Effects by Type of Cigarettes?

Although smoking is suggested to be a risk factor for colorectal cancer, the evidence to date is conflicting and may be confounded. Moreover, the effect of tobacco smoke may vary by time since initiation, type of tobacco product, anatomic subsites, and among ethnic groups. Data were derived from two consecutive population-based case-control studies conducted among Caucasians, Japanese, Native Hawaiians, Filipinos, and Chinese in Hawaii, including 1,959 ethnicity-, sex-, and age-matched case-control pairs. A lifetime history of smoking for different tobacco products and information on other risk factors were obtained by in-person interviews. Odds ratios (OR) and corresponding 95% confidence intervals (95% CI) were estimated using conditional logistic regression models with adjustment for potential confounders. Subjects who ever smoked were at an increased risk of colorectal cancer compared with never smokers (OR, 1.23; 95% CI, 0.99-1.52 for men and OR, 1.27; 95% CI, 1.01-1.59 for women). Increasing quartiles of pack-years over all tobacco products showed a clear dose-dependent association in men [for the highest quartile, Q4 (>40 pack-years) versus never smokers: OR, 1.48; 95% CI, 1.12-1.96; P(trend) = 0.002]. The dose-response trend was also present in women [for the highest quartile, Q4 (>30 pack-years) versus never smokers: OR, 1.38; 95% CI, 0.91-1.95; P(trend) = 0.04] and each ethnic group. There was a suggestion of a difference in risk with type of tobacco product. Non-filtered cigarettes increased risk of both colon and rectal cancer [for Q4 versus never smokers: OR, 1.59; 95% CI, 1.15-2.21; P(trend) = 0.001 and OR, 1.84; 95% CI, 1.18-2.86; P(trend) = 0.02, respectively], whereas filtered cigarettes seemed to increase risk of rectal but not colon cancer (OR, 1.37; 95% CI, 0.88-2.13; P(trend) = 0.06 and OR, 1.05; 95% CI, 0.79-1.39; P(trend) = 0.98, respectively). The effect of smoking was not limited to the distant past, and accumulated pack-years of smoking seemed to be more important than the time in which smoking occurred. The data from this large study corroborate previous reports of a positive association between smoking and colorectal cancer and suggest that the association may vary by type of cigarette.

Total hip replacement rates are higher among Caucasians than Asians in Hawaii.

The etiology of hip osteoarthritis remains unknown but may involve genetic or lifestyle factors. Most cases of total hip replacement are performed because of osteoarthritis. To examine possible ethnic differences, hospital records in Hawaii from 1985 to 1989 were reviewed. Preoperative radiographs were reviewed for a subset of patients to ascertain the reason for total hip replacement. Osteoarthritis accounted for a greater percentage of total hip replacements among whites (59% for women and 66% for men) than among Japanese (36% of women and 30% of men). The incidence of total hip replacement for whites was three to 25 times greater than that of other ethnic groups (Japanese, Chinese, Filipino, and Hawaiians). For example, the risk of total hip replacement for white women 40 years to 84 years of age was 4.4%, compared with 1.1% for Japanese women and 1.7% for Chinese women of the same age group. Compared with published data, the incidence was similar for Chinese in Hawaii and San Francisco; however; whites in Hawaii had a total hip replacement incidence less than half that of whites in San Francisco. Lifestyle differences might account for the lower incidence of total hip replacement for whites in Hawaii, compared with those in San Francisco. The lower incidence among Asians suggests a possible genetic basis for osteoarthritis.

Relative Income, Race, and Fertility

If a white husband's income is higher than expected for men of his age, race, education, job characteristics, and region, economic theory predicts higher complete fertility for his wife. In the present study one per cent public use samples from the 1970 Census for California and Hawaii were used to examine the effect of relative income on Japanese, Chinese, and black fertility. Relative income was defined in two ways: (1) with regard to earnings of husbands of the same race, education, employment, and state; (2) with regard to earnings of white husbands of the same education, employment, and state. High relative incomes defined in each way were associated with increased completed fertility of Japanese and Chinese in Hawaii, where Orientals form a majority. Neither definition of high relative income was associated with the completed fertility of Japanese, Chinese, or blacks in California, where non-whites form a minority. The results suggest that the effect of relative income on fertility for a racial grou...

Minority-Group Status and Fertility: A Study of Japanese and Chinese in Hawaii and California

Since there is a racial majority in California but not in Hawaii, these two states provide a natural experiment for testing the minority-status theory of fertility. The following propositions were deduced from the theory: (1) no net differences in Japanese, Chinese, and white fertility in Hawaii; (2) lower Japanese, and Chinese than white fertility in California; (3) lower Japanese and Chinese fertility in California than in Hawaii. Support for the first and third propositions and partial support for the second proposition in 1970 census public-use samples suggest that minority status may have depressed the fertility of currently married Japanese and Chinese women in California. The implications are explored.

The Sandalwood Mountains: Readings and Stories of the Early Chinese in Hawaii

The Sandalwood Mountains: Readings and Stories of the Early Chinese in Hawaii

The Sandalwood Mountains: Readings and Stories of the Early Chinese in Hawaii.

The Sandalwood Mountains: Readings and Stories of the Early Chinese in Hawaii.

The Relation Between Position and Status in the Assimilation of Chinese in Hawaii

The functional correspondence between position in the ecological order and status in the social order is disrupted by migration. The sequence of changes in the relationship between the position and status of migrants may be viewed as phases of the assimilative process. Among Chinese in Hawaii the main stages in this sequence have been: a plantation period, with social isolation and residential and occupational segregation; a period of urbanization, with residential segregation but expanding occupational distribution; a third period,still in process, with residential dispersion within the city, continued infiltration into all parts of the occupational structure, and increased social contacts with other groups in the interracial society. In the latest phase of the process status of the person again tends to coincide with position but in a larger, more impersonal society.

Transition from Familism to Nationalism Among Chinese in Hawaii

Shifts in group loyalties and identifications among immigrants and their descendents, particularly with reference to the institutions of political and social control in which they participate, constitute an index of their progressive assimilation into the new society. Early institutions established by Chinese migrants in Hawaii, although based on traditional familial sentiments, represent an expansion of Old World local identifications. Development of nationalistic societies, taking forms corresponding to movements in China, indicate further enlargement of the migrants' social world. Another shift in the area of group loyalties is revealed in the establishment of institutions designed to deal with problems confronting the Chinese community in Hawaii as a whole. Increased identification with the envolving Hawaiian society is represented by individual migrants who became citizens and functionaries of the Hawaiian government. The assimilation of the Hawaiian-born Chinese must be analyzed in terms of this changing configuration of identifications and loyalties of the immigrants.

Growth of Kwangtung Chinese in Hawaii

American Journal of Physical AnthropologyVolume 11, Issue 3 p. 473-500 Article Growth of Kwangtung Chinese in Hawaii V. B. Appleton, V. B. Appleton Honolulu, HawaiiSearch for more papers by this author V. B. Appleton, V. B. Appleton Honolulu, HawaiiSearch for more papers by this author First published: April/June 1928 https://doi.org/10.1002/ajpa.1330110304Citations: 5AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume11, Issue3April/June 1928Pages 473-500 RelatedInformation