[Cryotherapy combined with local spraying of isoniazid for the treatment of nasopharyngeal tuberculosis: a case report].

Nasopharyngeal tuberculosis refers to the tuberculosis in the nasopharynx, which is mainly treated with systemic chemotherapy with anti-tuberculosis drugs. Here, we reported a case of nasopharyngeal tuberculosis treated by cryosurgery combined with local spraying of isoniazid on the basis of systemic chemotherapy with anti-tuberculosis drugs. By reviewing the case data and relevant literature, we understood the clinical manifestations, diagnosis and differential diagnosis of the disease, improved everyone's understanding of the disease, and proposed a new method of cryosurgery combined with local spraying of isoniazid for the treatment of nasopharyngeal tuberculosis for clinical discussion.

[Bibliometric and visual analysis of neurological damage caused by electrical welding operations].

Objective: To analyze and summarize the trends and hot spots in the field of neurological damage caused by electric welding operations, and to provide ideas for new researches by searching the domestic and international literature. Methods: In December 2022, using Web of Science Citation Index (Web of Science), China Journal Full-Text Database (CNKI) and Wanfang Database as search databases, literature search was conducted on the Chinese and English search terms related to eletrical welding operations and neurological damage. The bibliometric analysis software VOSviewer 1.6.18 and CiteSpace 6.1.6 were used to visualize the publication year, publication quantity, country, research institution and key words of the literature. Results: A total of 309 articles (112 in Chinese and 197 in English) were included in this study. The first domestic and international papers were published in 1976 and 1994 respectively, and the number of papers reached the peak in 2006 and 2018, and then showed a downward trend to varying degrees. In China, Shandong First Medical University (including Shandong Institute of Occupational Health and Occupational Disease Prevention and Shandong Academy of Medical Sciences) and Wuhan University of Science and Technology had the largest number of publications. The 309 articles were from 52 Chinese journals and 86 English journals. The co-occurrence analysis of key words showed that the domestic research mainly focused on eletrical welding operation, welding workers, neurobehavioral function and manganese, and the nervous system damage caused by manganese in welding smoke was the field of international attention. Long term exposure, risk, and performance were key buzzwords in the field. Conclusion: The research focus in the field of nervous system damage caused by electric welding operation has an obvious trend of time evolution, gradually transiting from clinical manifestations to its toxic mechanism and early biomarkers.

[Predictive value of ultrasound-guided anesthesia injection in arthroscopy for borderline developmental dysplasia of the hip].

Objective: To evaluate the value of ultrasound-guided intra-articular anesthetic injection in predicting postoperative outcomes for borderline developmental hip dysplasia (BDDH). Methods: A follow-up study. The clinical data of 37 BDDH patients who received ultrasound-guided intra-articular anesthetic injection and arthroscopic examination in the Department of Sports Medicine, Senior Department of Orthopedics, the Fourth Medical Center of PLA General Hospital from May 2018 to February 2021 were retrospectively analyzed. Among them, there were 17 males and 20 females with a mean age of (37.9±12.8) years. All patients underwent ultrasound-guided intra-articular anesthetic injection prior to arthroscopy, and were evaluated with hip physical examination before and after injection, as well as before and after arthroscopy, in order to obtain the visual analog score (VAS) of pain for seven assessments. The total VAS score was calculated based on these evaluations. Follow-up was conducted for at least 12 months. The effective rate of injection referred to the ratio of the improvement of VAS score after anesthetic injection to the total VAS score before injection. Pearson correlation analysis and Bland-Altman analysis were used to test the correlation between modified Harris hip score (mHHS) after ultrasound-guided intra-articular anesthetic injection and mHHS score after arthroscopic surgery. A binary logistic regression model was established to analyze the substantial clinical benefit (SCB) for patients. Following the logistic regression analysis, a receiver operating characteristic (ROC) curve was constructed to evaluate the predictive power of ultrasound-guided intra-articular anesthetic injection in achieving SCB in those patients. The optimal cut-off value for injection efficacy was determined based on the ROC curve when SCB was achieved. Results: The follow-up time for all patients was (26.3±7.6) months. After anesthetic injection for 20 minutes, the total VAS score of pain [M(Q1,Q3)] decreased from 13(8,23) points before injection to 1(0,4) points; and the mHHS score [M(Q1,Q3)] increased from 60(46,70) points before arthroscopy to 90(84,96) points after, with statistically significant differences before and after injection and before and after arthroscopy (both P<0.001). Pearson correlation analysis showed that the mHHS score after intra-articular anesthetic injection was positively correlated with the mHHS score after surgery (r=0.961, P<0.001). The area under the ROC curve for predicting SCB after arthroscopy with ultrasound-guided intra-articular anesthetic injection was 0.769 (95%CI: 0.561-0.976), the Youden index was 0.663, the cut-off value was 0.569 2, the sensitivity was 96.3%, and the specificity was 70.0%. Conclusions: The results of ultrasound-guided intra-articular anesthetic injection before arthroscopy can indicate the presence of intra-articular lesions, and the degree of pain relief after injection is proportional to the functional recovery after arthroscopy. Patients with intra-articular anesthetic injection efficacy>56.92% have better results in hip arthroscopy.

[Association between polymorphism of CASP and NOX3 with risk of noise-induced hearing loss].

Objective: To explore the effect of gene polymorphism on workers suffering from noise induced hearing loss (NIHL) . Methods: In May 2019, a case-control study was conducted to select noise exposed workers in five factories in Zhejiang Province from 2017 to 2018. The average hearing threshold of binaural high frequency (3, 4, 6 kHz) was >25 dB (A) as the NIHL group, and the hearing threshold of any language frequency (0.5, 1, 2 kHz) was ≤25 dB (A) as the non NIHL group, with 307 people in each group. The general demographic data, occupational history, pure tone audiometry results and oral swab mucosal samples of noise exposed workers were collected, and the DNA of oral mucosal cells was extracted. The relationship between genetic risk score (GRS) and NIHL was analyzed, single nucleotide polymorphisms (SNP) were genotyped, the relationship between genotype and NIHL was analyzed by logistic regression, and the relationship between haplotype and NIHL was analyzed by R language. Results: After adjusting for gender, age, education and working years, the risk of NIHL among workers carrying cysteine-aspartic acid protease 3 gene (CASP3) rs1049216 recessive model GG genotype, rs6948 recessive model TT genotype, NADPH oxidase 3 gene (NOX3) rs12195525 additive model GT genotype and dominant model TT+GT genotype decreased (P<0.05) , the risk of disease was higher in workers with AA genotype carrying cysteine-aspartic acid protease 7 gene (CASP7) rs12415607 additive model (P<0.05) . There was a strong linkage disequilibrium (LD) relationship between rs1049216 and rs6948 (D'>0.8) . Haplotype AT and GG composed of rs1049216-rs6948 increased the risk of NIHL (P<0.05) . The risk of NIHL increased with the increase of GRS (OR=2.69, P<0.05) . Conclusion: Genotype polymorphisms at rs1049216 and rs6948 (CASP3) , rs12195525 (NOX3) , rs12415607 (CASP7) may be associated with susceptibility to NIHL.

[Evaluation of kurtosis on hearing loss caused by non-steady state noise in general equipment manufacturing industry].

Objective: To study the effect of occupational exposure to non-steady state noise on hearing loss in the general equipment manufacturing industry, and to explore the feasibility of applying kurtosis index to evaluate hearing loss caused by non-steady state noise. Methods: A total of 233 workers exposed to non-steady state noise in 6 general equipment manufacturing enterprises were selected as the observation group, and 237 workers exposed to steady noise in 4 textile enterprises were selected as the control group between 2012 and 2018. Personal normalized continuous A-weighted sound pressure level equivalent to an 8 h-working-day (L(Aeq, 8 h)) was determined by a noise dosimeter. Cumulation noise exposure (CNE) was calculated from L(Aeq, 8 h) and related working age, and the CNE was adjusted by using noise kurtosis (CNE' after adjustment) . Meanwhile, questionnaires and hearing loss tests were performed for all subjects. The changes in the threshold of high-frequency hearing and the incidence of high-frequency hearing loss caused by noise in the two groups were compared before and after the adjustment of the kurtosis of CNE. The correlation between CNE and the incidence of high-frequency hearing loss before and after kurtosis adjustment was analyzed. Results: There was an difference between the 3000-8000 Hz hearing threshold of workers in different CNE groups (P<0.05) . logistic regression analysis showed that CNE was a risk factor of high-frequency hearing loss for workers in the observation group (OR=1.189, P<0.05) , and trend Chi-square test showed that the incidence of high-frequency hearing loss increased with CNE levels (χ(2)(trend)=34.415, P<0.05) .Before the kurtosis adjustment, in the CNE 95~<110 dB (A) ·year level group, the incidence of high-frequency hearing loss and the high-frequency hearing threshold in the observation group were significantly higher than those in the control group (P<0.05) . After kurtosis adjustment, there was no significant difference in the incidence of high-frequency hearing loss between the observation group and the control group in each level group (P>0.05) . The correlation between CNE after kurtosis adjustment and the incidence of high-frequency hearing loss was better than that before adjustment (after R(2) adjustment >before R(2) adjustment) . Conclusion: The effect of non-steady state noise on high-frequency hearing loss of workers in general equipment industry increases with the increase of CNE, and the effect of non-steady state noise on high-frequency hearing loss of workers is greater than that of steady noise. CNE' can be used to evaluate the hearing loss caused by non-steady state noise.

[Dose-response relationship between noise kurtosis and noise-induced hearing loss].

Objective: To analyse the dose-response relationships between the kurtosis metric of noise and noise-induced hearing loss (NIHL) and study the role of kurtosis in the evaluation of NIHL associated with non-Gaussian noise. Methods: From January 2012 to December 2017, a total of 1869 workers in seven manufacturing industries were selected as the study subjects. The basic data of the workers were investigated by questionnaire, personal noise waveform was collected for a long time, and pure tone hearing threshold was tested. The 8-hour continuous equivalent A sound level (L(Aeq, 8 h)) , cumulative noise exposure (CNE) and kurtosis structure indexes were calculated. The dose-response relationships between kurtosis and NIHL were analyzed by stratification analysis method, which controlled the influence of CNE, L(Aeq, 8 h), exposure duration, age and sex on hearing loss using high-frequency noise-induced permanent threshold shift (NIPTS(346)) and high-frequency noise-induced hearing loss (HFNIHL) as outcome indicators. Results: When CNE was <90 dB (A) ·year and ≥100 dB (A) ·year, NIPTS(346) in the extremely high kurtosis group was significantly greater than that in the Gaussian kurtosis, low kurtosis and medium kurtosis group (P<0.05) . In the workers exposed to L(Aeq, 8 h)<85 dB (A) and ≥94 dB (A) , NIPTS(346) in the extremely high kurtosis group was significantly greater than that in the Gaussian kurtosis group (P<0.05) . Among workers under the age of 50 or male workers, NIPTS(346) in the extremely high kurtosis group was significantly greater than that in the Gaussian kurtosis, low kurtosis and medium kurtosis group (P<0.05) . Kurtosis was positively correlated with NIPTS(346) (r=0.121, P<0.05) . When CNE was <100 dB (A) ·year, the detection rate of HFNIHL increased with the increase of kurtosis level (P<0.01) . Logistic regression analysis showed that kurtosis was an important influencing factor for HFNIHL (OR=1.321) . Conclusion: Kurtosis has a dose-response relationship with the detection rate of HFNIHL in noise exposed workers, and noise kurtosis is an influencing factor of NIHL.

[Investigation on noise exposure characteristics of workers in wooden furniture manufacturing industry and textile industry].

Objective: To investigate the occupational noise exposure characteristics and distribution of workers in wood furniture manufacturing industry and textile industry, so as to provide the basis for the establishment of noise source database and the prevention and control of noise hazards in China. Methods: In March 2020, a total of 653 workers in wood furniture manufacturing industry and textile industry were selected by cluster sampling method. A general questionnaire survey was conducted to measure the characteristics of noise exposure and analyze the changes of 8 h equivalent A-level (L(Aeq, 8 h)) and kurtosis of different industries and types of work. Results: The noise exposure L(Aeq, 8 h) of workers was (91.2±6.9) dB (A) , the median kurtosis and mean kurtosis were 37.0 and 105.0, respectively. 84.1% (549/653) of the workers had L(Aeq, 8 h)≥85 dB (A) , 49.0% (320/653) and 68.5% (447/653) of the workers had median kurtosis and mean kurtosis >10. The L(Aeq, 8 h) level of the textile industry was higher than that of the wooden furniture manufacturing industry, while the median and mean of kurtosis levels of the textile industry was lower than the wooden furniture manufacturing industry (P<0.01) . The L(Aeq, 8 h) levels of spinners and weavers were higher, and the median and mean of kurtosis of nailers were higher (P<0.05) . The mean and median of kurtosis were highly correlated among workers of two industries (r=0.80, P<0.01) . The L(Aeq, 8 h) was positively correlated with mean and median of kurtosis among workers of wooden furniture manufacturing industry (r=0.33 and 0.35, P<0.01) , while it was negatively correlated with mean and median of kurtosis among workers of textile industry (r=-0.45 and -0.40, P<0.01) . Conclusion: Indicators for noise exposure characteristics, such as L(Aeq, 8 h) and kurtosis vary greatly by industries and type of works. Multi-indicator joint measurement is conducive to comprehensive assessment of noise exposure and its health effects.

[Survey on present status of noise exposure of workers in metal processing industry].

Objective: To investigate the distribution of noise exposure between non-steady state noise and steady-state noise for metal processing workers, which will provide scientific basis for the prevention and treatment of noise hazards in metal processing industry. Methods: The cross-section method was used to investigate the noise exposure of 737 workers from three metal processing industries in Zhejiang Province from October to December 2017. The general demographic information and occupational history were collected by questionnaire. The noise was recorded by individual noise meters, and the noise exposure intensity (equivalent continuous A-weighted noise exposure level normalized to an 8 h-working-day, L(Aeq, 8 h)) and kurtosis were calculated. Results: Workers exposed to noise in the metal processing industry were mainly 18-40 years old (527 workers, 71.51%) , men (570 workers, 77.34%) , and junior high school education background (416 workers, 56.45%) . There were 572 workers (77.61%) with noise exposure intensity (L(Aeq, 8 h)) greater than 85 dB (A) , 558 workers (75.71%) exposed to non-steady state noise (kurtosis ≥4) , and 634 workers (86.02%) with exposure duration less than 8 years. Among the 30 work types investigated, the work types with noise intensity reaching 100% were the stamping, welding and others from a children's car manufacturing factory in Ningbo, operating, chamfering, tapping, and thread rolling from an automobile parts manufacturing factory in Ningbo; The work types with a rate of 100% exposed to non-steady state noise were the grinding from a children's car manufacturing factory in Ningbo, assembling, assembly operating and others from an automobile brake manufacturing factory in Wenzhou, and polishing from an automobile parts manufacturing factory in Ningbo. Conclusion: Metal processing workers have a high rate of over-standard exposed to high noise intensity and a high proportion exposed to non-steady state noise. It is necessary to take sound insulation and noise reduction engineering control, and strengthen personal protection and occupational health management measures to prevent and control the noise hazards.

[Research progress on non-steady state noise-induced hearing loss].

Non-steady state noise has become the main type of workplace noise. Compared with steady state noise, non-steady state noise may cause more serious hearing loss. This paper reviews the new situation of occupational hearing loss caused by non-steady state noise exposure, the overview of international noise exposure assessment standards and new challenges, and the new evidence of non-steady state noise induced hearing loss, so as to provide the basis for the future research of non-steady state noise induced hearing loss.

[Applied study of Singapore occupational semi-quantitative risk assessment technique in occupational health risk assessment in a chair furniture manufacturing enterprise].

Objective: To assess the occupational health risk level of a small-scale furniture manufacturer, and to explore the applicability of the Singapore-developed semi-quantitative occupational risk assessment model for chemical exposure (Singapore model) in small-scale furniture manufacturers, and to provide a basis for the continuous occupational health management of manufacturers. Methods: A small-scale furniture manufacturer was selected as the study subject; an on-site occupational hygiene investigation was performed on the above manufacturer during April to June in 2017, and a risk assessment was carried out using the Singapore model. Results: The assessment results of the Singapore model indicated that risk levels of occupational exposure to harmful chemicals for the key positions in the workplace were inconsistent between the actual exposure level method and the exposure index method except for the following: high risk for formaldehyde exposure (risk level: 3.5 and 4.1, respectively) during woodworking process, high risk for dimethyl benzene exposure (risk level: 3.5 and 3.5, respectively) during burnishing process, medium risk for methyl benzene and dimethyl benzene exposure (risk level: 3.0 and 3.4, respectively) as well as for dimethyl benzene exposure (risk level: 3.0 and 3.3, respectively) during primer coating process, medium risk for methyl benzene exposure (risk level: 3.0 and 3.4, respectively) during gel painting process, and medium risk for cyclohexanone exposure (risk level: 2.8 and 2.8, respectively) during oil polishing process. The exposure index method yielded a higher risk level than the actual exposure level method, especially in the risk level of benzene exposure, which was rated as "high" and "very high" by the former but "low" by the latter. Conclusion: The Singapore model is suitable for risk assessment of occupational exposure to harmful chemicals in small-scale furniture manufacturers, which can provide a basis for further prevention and control measures taken by manufacturers.

[Analysis on the quality of life and its influencing factors of visual display terminal operators in Internet enterprises].

Objective: To investigate the quality of life of the visual display terminal (VDT) operators in Hangzhou Internet enterprises and to analyze its influencing factors. Methods: Through cluster sampling,, 944 employees were investigated by demographic and general health questions and the MOS 36-Item Short Form Health Survey Questionnaire from October to November in 2016 and carried out statistical analysis. Results: VDT operators' physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, mental health, physical component summary and mental component summary scores were (86.3±17.0) , (82.5±30.3) , (80.6±16.1) , (56.8±18.6) , (53.7±15.6) , (78.5±17.8) , (81.2±31.9) , (48.8±19.3) , (51.1±8.9) , (43.8±9.1) . Except physical functioning, role-physical and physical component summary scores, the scores of other scales and mental component summary were lower than the norm (P<0.05) . Multivariable logistic regression showed that vegetable intake, sleeping and physical exercise had an impact on the physical component summary score. The influential factors of mental component summary score included marital status, education, neck pain and health concerns. Conclusion: We should pay attention to the quality of life of VDT operators in Internet enterprises, especially their mental health.

[Effects of p-phenylenediamine on lung function and health-related quality of life of workers].

Objective: To study the effects p-phenylenediamine (PPD) on lung function and health-related quality of life of occupational exposed workers. Methods: This study was based on data from a company that produce hair dye containing PPD in China. Workers who exposed to PPD were selected as the study group, and workers un-exposed to PPD were selected as the control group. Questionnaires on health-related quality of life of workers using the 36-item Short Form Health Survey (SF-36) . Occupational health examination assessment results were tested in Taizhou Cancer Hospital. The lung function test includes forced vital capacity (FVC) , forced expiratory volume in one second (FEV(1.0)) , and ratio of FEV(1.0) to FVC (FEV(1.0)/FVC) . Results: The difference in systolic blood pressure between the PPD exposed group and the control group was statistically significant (P<0.05) . FVC, FEV(1.0), and FEV(1.0)/FVC of the lung function indexes in the exposed group were lower than those in the control group (P<0.05) . In the health-related quality of life, body pain (P=0.002) , general health (P=0.029) , vitality (P=0.038) , and mental health (P=0.003) were lower in the exposed group than in the control group. Conclusion: Occupational exposed to PPD may induce hazard to the workers'lung function and may cause detrimental effect on workers' health-related quality of life.

[Effects of p-Phenylene diamine on liver and kidney functions of occupational exposed workers].

Objective: To study the effect of p-phenylenediamine (PPD) on liver and kidney function in occupational exposed workers. Methods: Workers in a hair dye production enterprise which used p-phenylenediamine as a raw material for production were selected as the main research population. Then we conducted a questionnaire survey on the basic conditions of workers and conducted occupational health checkups on general health status, liver and kidney function. Occupational health examination assessment results were tested in Taizhou Cancer Hospital. All data was built using EpiData 3.1 software, and statistical analysis was performed using software SPSS 20.0. Results: The liver function indicators including direct bilirubin, prealbumin, total protein, and white protein, globulin, aspartate aminotransferase, glutamyl transpeptidase, and total bilirubin in the workers exposed to high concentration of PPD were at high normal values, and these indicators were significantly different from low PPD concentration group (P<0.05) . The serum creatinine and serum uric acid in the renal function index were significantly higher in workers exposed to PPD than in workers exposed to low concentrations and in the control group (P<0.05) . Conclusion: Occupational exposed to PPD may have a hazard to the workers' liver and kidney function. Long-term occupational exposure to PPD may lead to increased cumulative exposure of workers, which may cause potential chronic liver and kidney damage in occupationally exposed populations.

The intrapapillary capillary loop (IPCL) changes in superficial esophageal lesions.

The aims of this study were to investigate intrapapillary capillary loops (IPCLs) of superficial esophageal lesions changes in different types classified by the Japan Esophageal Society classification. The calibers, areas, and densities of IPCLs were detected in 34 cases of esophageal lesions using immunohistochemical analysis. Statistically significant differences in calibers, areas, and densities of IPCLs were observed between type A, type B1/B2, and type B3 area (P < 0.001). In conclusion, the results of this observation showed the Japan Esophageal Society classification of IPCL would help endoscopists to diagnose the type and the invasion depth of lesion in esophagus, and decide the treatment strategy.

[The application of two occupation health risk assessment models in a wooden furniture manufacturing industry].

Objective: To explore the applicability of 2 different models of occupational health risk assessment in wooden furniture manufacturing industry. Methods: American EPA inhalation risk model and ICMM model of occupational health risk assessment were conducted to assess occupational health risk in a small wooden furniture enterprises, respectively. Results: There was poor protective measure and equipment of occupational disease in the plant. The concentration of wood dust in the air of two workshops was over occupational exposure limit (OEL) , and the CTWA was 8.9 mg/m3 and 3.6 mg/m3, respectively. According to EPA model, the workers who exposed to benzene in this plant had high risk (9.7×10-6 ~34.3×10-6) of leukemia, and who exposed to formaldehyde had high risk (11.4 × 10-6) of squamous cell carcinoma. There were inconsistent evaluation results using the ICMM tools of standard-based matrix and calculated risk rating. There were very high risks to be attacked by rhinocarcinoma of the workers who exposed to wood dust for the tool of calculated risk rating, while high risk for the tool of standard-based matrix. For the workers who exposed to noise, risk of noise-induced deafness was unacceptable and medium risk using two tools, respectively. Conclusion: Both EPA model and ICMM model can appropriately predict and assessthe occupational health risk in wooden furniture manufactory, ICMM due to the relatively simple operation, easy evaluation parameters, assessment of occupational- disease-inductive factors comprehensively, and more suitable for wooden furniture production enterprise.

Laboratory transmission of Jamestown Canyon and snowshoe hare viruses (Bunyaviridae: California serogroup) by several species of mosquitoes.

The ability of 14 species of mosquitoes to biologically transmit Jamestown Canyon virus was tested. Four species not previously described as vectors of that virus transmitted to suckling mice. Among membrane-fed mosquitoes with disseminated infections, field-collected Aedes canadensis (1/3), Anopheles punctipennis (1/12), Coquillettidia perturbans (2/14) and a laboratory strain of Ae. epactius (19/67) transmitted virus. Two species were tested for their ability to transmit snowshoe hare virus: field-collected Ae. provocans (4/20) and Ae. abserratus-punctor (2/20) successfully transmitted to suckling mice. Evidence regarding the role of these species as field vectors is summarized.

Isolation of Jamestown Canyon virus (California serogroup) from Aedes mosquitoes in an enzootic focus in Michigan.

Twenty isolates of Jamestown Canyon virus were obtained from adult females of 5 Aedes species collected at the Houghton Lake Wildlife Research Area, Missaukee County, in north-central Michigan between 1985 and 1989. Fourteen were from Aedes provocans, and 6 were from 4 other snowmelt Aedes species. One isolate of trivittatus virus and one Cache Valley-like virus were also obtained. Seasonal succession patterns for numerous mosquito species were recorded over 4 years. The temporal association of adult mosquito emergence, virus isolations, and infection and seroconversion of sentinel deer suggest that Ae. provocans is a primary enzootic vector of Jamestown Canyon virus in that focus. We hypothesize that Ae. provocans provides an overwintering reservoir for Jamestown Canyon virus at the study site. A large dry ice-baited "tent trap" was the most productive method for collecting numerous aedine and other mosquito species.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-resistant, flat-cell PC12 variants having a partial loss of transformed phenotype.

We have cloned and characterized two variants of PC12 cells. MPT1 cells were selected by their resistance to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), and variant 2068 was isolated nonselectively as a large, flat-cell variant commonly occurring in PC12 cultures. Variant 2068 cells also exhibit resistance to MPTP. Karyotype analysis revealed that these variants are true derivatives of wild-type PC12 cells; however, each variant is tetraploid, whereas the wild-type parent is diploid. The two variants contain an altered level and composition of lactate dehydrogenase isoenzymes, which could account for a previously described difference in lactate metabolism. Both variants exhibit a partial loss of transformed phenotype in culture in that they are nonrefractile, grow in monolayers, and fail to multiply in soft agar. We suggest that this alteration in transformed phenotype may result in altered mitochondria and lactate dehydrogenase and thus account for their resistance to MPTP. Compared with wild-type PC12 cells, MPT1 cells have a decreased level of fos mRNA and an increased level of myc mRNA; the latter results from an increased level of transcription of exon 1 of the myc gene. Studies with hybrid cells obtained by fusing MPT1 cells with wild-type-like cells show that most, but not all, of the parameters of the MPT1 phenotype predominate.

Transforming growth factor alpha and a PC12-derived growth factor induce neurites in PC12 cells and enhance the survival of embryonic brain neurons.

We have identified and characterized a 5000-Da protein that induces neurite outgrowth from PC12 pheochromocytoma cells, enhances the survival of embryonic rat brain neurons in primary culture, and induces the multiplication of embryonic rat brain astrocytes in primary culture. The factor is produced by a flat cell PC12 variant that expresses the activated ras oncogene after transfection of the gene. The factor resembles transforming growth factor alpha (TGF alpha) and epidermal growth factor (EGF) in that it induces anchorage-independent colony formation of normal rat kidney cells in soft agar and competes with EGF for binding to the EGF receptor. Rat TGF alpha and human TGF alpha also induce neurite outgrowth from PC12 and enhance the survival of embryonic brain neurons. The PC12 variant-derived factor can be distinguished from TGF alpha and EGF immunologically and by migration rates on reversed-phase high-performance liquid chromatography.

Covalent labeling of the cocaine-sensitive catecholamine transporter.

Xylamine is an alkylating agent that is a substrate for and specific irreversible inhibitor of the cocaine-sensitive catecholamine transporter that functions in catecholamine reuptake into neurons and PC12 cells. [3H]xylamine prominently labels nine PC12 proteins; the relative xylamine-alkylation of a Mr 54,000 protein was decreased by cocaine and increased in the case of a PC12 variant, B9, which is deficient in catecholamine transport. [3H]xylamine labels no such protein in another transport variant, MPT1. We propose that this Mr 54,000 protein 1) is a component of the catecholamine transporter, 2) is present in B9 cells but in a conformation that reduces transporter activity and makes alkylation by xylamine more likely, and 3) is absent in MPT1 cells. Nerve growth factor treatment restores transporter activity in B9 cells but not in other transporter-deficient variants.