Recommendations for eligibility criteria concerning bariatric and metabolic surgical and endoscopic procedures for obese Hong Kong adults 2024: Hong Kong Society for Metabolic and Bariatric Surgery Position Statement.

The surgical management of obesity in Hong Kong has rapidly evolved over the past 20 years. Despite increasing public awareness and demand concerning bariatric and metabolic surgery, service models generally are not standardised across bariatric practitioners. Therefore, a working group was commissioned by the Hong Kong Society for Metabolic and Bariatric Surgery to review relevant literature and provide recommendations concerning eligibility criteria for bariatric and metabolic interventions within the local population in Hong Kong. The current position statement aims to provide updated guidance regarding the indications and contraindications for bariatric surgery, metabolic surgery, and bariatric endoscopic procedures.

[A comparative study on quality of life of pneumoconiosis patients between from rural migrant workers and from a state-owned enterprise in Zhaotong City Yunnan Province].

Objective: To compare the quality of life of pneumoconiosis patients between from rural migrant workers and from a state-owned enterprises in Zhaotong City Yunnan Province, and to explore the factors influencing quality of life of pneumoconiosis patients. Methods: In August 2017, 83 patients from rural migrant workers in Zhaotong City Yunnan Province and 126 pneumoconiosis patients from a state-owned coal mining enterprises were selected as target population. World Health Organization on Quality of Life Brief Scale (WHOQOL-BREF) and self-designed questionnaires were used to collect information from two groups. The demographic information, health status and quality of life of two groups were compared. The factors influencing quality of life were analyzed by multi-liner regression analyses. Results: Average annual household income of rural migrant workers group was lower than that of state-owned enterprises group, and the average annual household expenditure for health of rural migrant workers group was higher than that of state-owned enterprises group (P<0.01) . Overall score of WHOQOL-BREF and scores for four domains including physiology, psychology, social relationship and environment of rural migrant workers group were lower than the scores of patients from state-owned enterprises group (P<0.01) . The result of multi-liner regression analysis showed that average annual household income (b=0.00015, 95%CI: 0.00010-0.00020) , being rural migrant workers (b=-5.904, 95%CI: -8.436--3.372) , better action ability (b=2.595, 95%CI: 0.706-4.483) and have complication (b=-2.542, 95%CI: -4.698--0.387) were factors influencing overall score of WHOQOL-BREF of pneumoconiosis patients (P<0.05) . Conclusion: The quality of life of pneumoconiosis patients from rural migrant workers is lower than that from state-owned enterprises. And the average annual household income, action ability and having complication or not are factors influencing the quality of life of pneumoconiosis patients.

[Association of sleep quality with hypertension in the elderly of Jino nationality: a multilevel model analysis].

Objective: To evaluate the association of sleep quality with hypertension in the elderly population aged 60 years and older of Jino nationality. Methods: In August 2015, a cross-sectional population-based survey was conducted to investigate the prevalence of hypertension in 805 subjects sampled by multistage stratified and cluster sampling from the elderly population of Jino nationality, the sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI, a poor sleep group was defined as having a global PSQI score>7, a good sleep group was with a score of 7 or less), and the multilevel Logistic regression model was applied to analyze the association of sleep quality with hypertension. Results: A total of 793 eligible participants were available for analysis. Overall, 118 participants (14.9%) were in the poor sleep group, and 675 participants (85.1%) were in the good sleep group. The prevalence of hypertension, prevalence of isolated systolic hypertension, average systolic blood pressure (SBP) and diastolic blood pressure (DBP) of the poor sleep group were significantly high than those of the good sleep group[73.7%, 22.0%, (139.2±17.7) and (82.5±10.6) mmHg (1 mmHg=0.133 kPa) vs 33.0%, 9.0%, (131.2±15.0) and (78.5±8.9) mmHg, all P<0.05]. The results of covariate-adjusted multilevel Logistic regression model indicated that subjective sleep quality (OR=2.64, 95% CI: 1.08-6.44), sleep latency (OR=2.98, 95% CI: 1.52-5.86), sleep disturbance (OR=2.93, 95% CI: 1.06-8.10), daytime dysfunction (OR=3.86, 95% CI: 1.74-8.58) and poor sleep (OR=3.98, 95% CI: 2.05-7.73) had the positive correlation with hypertension. Conclusions: The elderly population of Jino nationality with poor sleep have high SBP and DBP. There are positive associations of PSQI and its components with hypertension in the elderly population of Jino nationality.

The mediating role of Internet addiction in depression, social anxiety, and psychosocial well-being among adolescents in six Asian countries: a structural equation modelling approach.

OBJECTIVES: This study examines the associations of Internet addiction with social anxiety, depression, and psychosocial well-being among Asian adolescents. A self-medication model conceptualizing Internet addiction as a mediating role in relating depression and social anxiety to negative psychosocial well-being was tested. STUDY DESIGN: A cross-sectional survey. METHODS: In the Asian Adolescent Risk Behavior Survey (AARBS), 5366 adolescents aged 12-18 years from six Asian countries (China, Hong Kong, Japan, South Korea, Malaysia, and Philippines) completed a questionnaire with items of the Internet Addiction Test (IAT), Social Anxiety Scale for Adolescents (SAS-A), Center for Epidemiological Studies Depression Scale (CESD), Self-Rated Health of the Nation Outcome Scales for Children and Adolescents (HoNOSCA-SR) in the 2012-2013 school year. Structural equation modelling was used to examine the mediating role of Internet addiction in depression, social anxiety, and subjective psychosocial well-being. RESULTS: Significant differences on the scores of IAT, SAS-A, CESD, and HoNOSCA-SR across the six countries were found. The proposed self-medication model of Internet addiction received satisfactory goodness-of-fit with data of all countries. After the path from social anxiety to Internet addiction had been discarded in the revised model, there was a significant improvement of the goodness-of-fit in the models for Japan, South Korea, and the Philippines. CONCLUSIONS: Depression and social anxiety reciprocally influenced, whereas depression associated with poorer psychosocial well-being directly and indirectly through Internet addiction in all six countries. Internet addiction mediated the association between social anxiety and poor psychosocial well-being in China, Hong Kong, and Malaysia.

Preclinical safety evaluation of subretinal AAV2.sFlt-1 in non-human primates.

We report on the long-term safety of AAV2.sFlt-1 (a recombinant adeno-associated virus serotype 2 carrying the soluble form of the Flt-1 receptor) injection into the subretinal space of non-human primates. Levels of sFlt-1 protein were significantly higher (P<0.05) in the vitreous of four out of five AAV2.sFlt-1-injected eyes. There was no evidence of damage to the eyes of animals that received subretinal injections of AAV2.sFlt-1; ocular examination showed no anterior chamber flare, normal fundus and electroretinography responses equivalent to those observed before treatment. Notably, immunological analysis demonstrated that gene therapy involving subretinal injection of AAV2.sFlt-1 does not elicit cell-mediated immunity. Biodistribution analysis showed that AAV2.sFlt-1 could be detected only in the eye and not in the other organs tested. These data indicate that gene therapy with subretinal AAV2.sFlt-1 is safe and well tolerated, and therefore promising for the long-term treatment of neovascular diseases of the eye.

The risks of disordered eating in Hong Kong adolescents.

OBJECTIVE: This study examines the risks of disordered eating among Hong Kong adolescents. SUBJECTS: A total of 893 students (12-18 years old) participated in a cross-sectional study in 2007. METHODS: Students' height and weight were measured and the Eating Attitudes Test (EAT-26) was completed. The risks of disordered eating were assessed by EAT-26 results and weight status. Sex differences in the risks of disordered eating were examined by logistic regression models with adjustment for age. RESULTS: Based on the EAT-26 results, 18.5% of boys and 26.6% of girls were at risk of disordered eating with a significant adjusted odds ratio (OR) of 1.58 [95% confidence interval (CI) 1.15-2.18] for sex. A significant OR of 1.60 (95%CI 1.21-2.13) for sex was also obtained when both EAT-26 results and weight status were used for the screening. CONCLUSIONS: Hong Kong adolescent girls have a higher risk of disordered eating than boys. EAT-26 results together with measured weight status are useful criteria for screening disordered eating attitudes and behaviors in adolescents.

Upconversion blue laser by intracavity frequency self-doubling of periodically poled lithium tantalate parametric oscillator.

We report a design for upconversion 435 nm blue lasers based on simultaneously fulfilling the nonlinear processes of optical parametric oscillation (OPO) and second-harmonic generation (SHG) in a 7.9 mum periodically poled lithium tantalate (PPLT). The uncoated 15-mm-long PPLT device exhibits a low threshold of 150 mW and a differential slope efficiency of 22.6%, rendering 56 mW blue generation when pumped by a pulsed 532 nm green laser with an average power rating of 400 mW. These observations were attributed to a quasi-phase-matching (QPM) structural design with a 75% domain duty cycle to ensure the concurrence of frequency doubling with the first-order QPM-OPO PPLT device via the second-order QPM-SHG process.

A rapid method for the simultaneous determination of 11 saponins in Panax notoginseng using ultra performance liquid chromatography.

A rapid ultra performance liquid chromatography coupled with photo diode array detection method (UPLC-PDA) was developed for the simultaneous determination of 11 saponins, namely notoginsenoside R1, ginsenoside Rg1, Re, Rf, Rb1, Rg2, Rc, Rb2, Rb3, Rd and Rg3 in Panax notoginseng. The analysis was performed on Acquity UPLC system with Acquity UPLC BEH C(18) column and gradient elution of water and acetonitrile in 12 min. The high correlation coefficient (r(2)>0.9968) values indicated good correlations between the investigated compounds' concentrations and their peak areas within the test ranges. The LOQ and LOD were lower to 0.2-2.4 and 0.1-1.8 ng on column, respectively. The overall intra- and inter-day variations (R.S.D.) of 11 saponins were lower than 3.1%. The developed method was successfully used for the analysis of saponins in P. notoginseng with overall recovery of 93.0-101.6% for the analytes. The results show that UPLC is a powerful tool for analysis of components in Chinese medicines.

Qualitative and quantitative analyses of nucleosides and nucleobases in Ganoderma spp. by HPLC-DAD-MS.

A high-performance liquid chromatography-diode array detector-mass spectrometry (HPLC-DAD-MS) analytical method was developed for detection of the nucleosides and nucleobases in two species of Lingzhi, the dried sporophore of Ganoderma lucidum and G. sinense. The method, combining advantages of both DAD and MS, was successfully used to qualitatively identify for six nucleosides namely, adenosine, cytidine, guanosine, inosine, thymidine, uridine and five nucleobases namely, adenine, guanine, hypoxanthine, thymine and uracil in Lingzhi samples. Quantitative analyses showed that uridine was the most abundant nucleoside in these Lingzhi samples and the contents of nine target analytes were found to be different in pileus and stipes of the fruiting bodies and among the different species of G. spp. The established method might apply as an alternative approach for the quality assessment of Lingzhi.

A rapid HPLC-ESI-MS/MS for qualitative and quantitative analysis of saponins in "XUESETONG" injection.

'XUESETONG' injection, one of the most widely used proprietary medicines in traditional Chinese medicine, consists of total saponins made from Panax notoginseng, which is a highly valued and important Chinese medicinal herb. It is used to treat cardiovascular diseases. In order to control the quality of XUESETONG injection, a rapid HPLC-ESI-MS/MS method was developed for qualitative and quantitative determination of the saponins. The analyses were performed on SB-C18 column using gradient elution in 25 min. Full scan and time programmed selected reaction monitoring (SRM) were used for qualitative and quantitative analysis of saponins, respectively. Twenty-seven saponins were identified and nine of them including notoginsenoside R1, ginsenoside Rb1, Rb2, Rb3, Rc, Rd, Re, Rf and Rg1 were quantified. Ten XUESETONG injections were analyzed and compared. The results showed that there is a great variation among different samples. In conclusion, the developed method is rapid, accurate and sensitive for qualitative and quantitative analysis of saponins in XUESETONG injection. Moreover, it also can be used for the quality control of P. notoginseng raw material and its preparations.

Simultaneous determination of nine saponins from Panax notoginseng using HPLC and pressurized liquid extraction.

A HPLC and pressurized liquid extraction (PLE) method was developed for simultaneous determination of nine saponins, including notoginsenoside R1, ginsenoside Rg1, Re, Rf, Rb1, Rc, Rb2, Rb3 and Rd in Panax notoginseng. The analysis was performed on C18 column with water-acetonitrile gradient elution and the investigated saponins were authenticated by comparing retention time and mass spectra with their reference compounds. Several methods including PLE, ultrasonication, soxhlet extraction and immersion were used for sample preparation and their extraction efficiency was compared. The results showed that PLE has the highest extraction efficiency and repeatability, which would be valuable on standardization of sample preparation for quality control of Chinese medicines. The developed HPLC and PLE is an effective approach for simultaneously quantitative determination of sapoinins in P. notoginseng, which could be used for quality control of P. notoginseng and its preparations.

Generation of transgenic mice with mild and severe retinal neovascularisation.

AIM: To generate a mouse model for slow progressive retinal neovascularisation through vascular endothelial growth factor (VEGF) upregulation. METHODS: Transgenic mice were generated via microinjection of a DNA construct containing the human VEGF165 (hVEGF) gene driven by a truncated mouse rhodopsin promoter. Mouse eyes were characterised clinically and histologically and ocular hVEGF levels assayed by ELISA. RESULTS: One transgenic line expressing low hVEGF levels showed mild clinical changes such as focal fluorescein leakage, microaneurysms, venous tortuosity, capillary non-perfusion and minor neovascularisation, which remained stable up to 3 months postnatal. Histologically, there were some disturbance and thinning of inner and outer nuclear layers, with occasional focal areas of neovascularisation. By contrast, three other lines expressing high hVEGF levels presented with concomitantly severe phenotypes. In addition to the above, clinical features included extensive neovascularisation, haemorrhage, and retinal detachment; histologically, focal to extensive areas of neovascularisation associated with retinal folds, cell loss in the inner and outer nuclear layers, and partial retinal detachment were common. CONCLUSIONS: The authors generated four hVEGF overexpressing transgenic mouse lines with phenotypes ranging from mild to severe neovascularisation. These models are a valuable research tool to study excess VEGF related molecular and cellular changes and provide additional opportunities to test anti-angiogenic therapies.

A rapid fatal erythroleukemia caused by J2E cells can be treated ex vivo with erythropoietin.

The J2E cell line is an immature erythroid line which terminally differentiates in response to erythropoietin (epo), producing mature, hemoglobin-synthesizing red blood cells. We have shown that when these cells were injected into mice a rapid and fatal erythroleukemia developed with symptoms of severe anemia and hepatosplenomegaly. Southern blotting demonstrated that the leukemic cells were the introduced J2E cells. In addition to spleen and liver, the bone marrow was a major site of leukemic cell infiltration, and when grown in vitro leukemic cells from bone marrow remained responsive to erythropoietin. We reasoned, therefore, that treatment of mice with this hormone should alleviate the erythroleukemia, but regular injections of epo in vivo failed to arrest the progress of the disease. However, when bone marrow from leukemic mice was exposed continuously to the hormone ex vivo, before reinfusion into naive recipients, a marked extension in life span was observed. It was concluded that ex vivo epo treatment could be used therapeutically for J2E cell erythroleukemias.

Inhibition of angiogenesis by adenovirus-mediated sFlt-1 expression in a rat model of corneal neovascularization.

Pathological angiogenesis, or the production of new capillary vessels from preexisting vasculature, within the eye is a serious event that often leads to blindness. Upregulation of vascular endothelial growth factor (VEGF) has been linked to neovascularization in the eye, suggesting that it could be a suitable target to inhibit angiogenic changes. This work investigated whether the presence of a proven antiangiogenic factor, the soluble variant of the VEGF receptor, sFlt-1, in the anterior chamber is sufficient to inhibit new vessel formation in the cornea in an animal model of corneal neovascularization. A recombinant adenovirus vector that can mediate efficient in vivo gene transfer and expression in ocular cells was selected as a delivery agent. We have shown that after the injection of Ad.betagal into the anterior chamber of normal and cauterized rat eyes, corneal endothelial cells and cells of the trabecular meshwork were efficiently transduced and that beta-galactosidase (beta-Gal) expression was maintained up to 10 days postinjection. Cauterization significantly increased the amount of immunoreactive VEGF in vehicle- or Ad.null-injected animals (t test, p < 0.001 and p < 0.001, respectively). However, when cauterization was combined with Ad.sflt injection there was no statistically significant increase in the amount of immunoreactive VEGF (p = 0.12). The injection of Ad.sflt into the anterior chamber slowed or inhibited VEGF-induced angiogenic changes. After cauterization, 100% of uninjected and vehicle-injected and 82% of Ad.null-injected animals developed moderate to severe corneal angiogenesis in contrast to 18% of Ad.sflt-injected animals. These in vivo results suggest that the transient presence of antiangiogenic agents in the anterior chamber can be successfully used to inhibit the development of corneal angiogenesis.

The in vitro expression patterns of individual type I interferon genes in Newcastle disease virus infected murine splenocytes and fibroblasts.

Murine type I interferon levels present in mice sera following Newcastle disease virus infections are influenced by the If-1 locus. Sera interferon levels in C57BL/6 mice (If-1h allele) are 10- to 15-fold higher than in BALB/c mice (If-1(1) allele). The B6.C-H-28c strain, which carries BALB/c If-1(1) allele on C57BL/6 genomic background, has low interferon levels in sera. This study examined the expression of interferon alpha 1, alpha 4, alpha 5, alpha 6, alpha 9 and beta mRNAs at 7 hr after Newcastle disease virus infection of primary cells (splenocytes and mouse embryo fibroblasts) from C57BL/6, B6.C-H-28c and BALB/c mouse genotypes. Total RNA from these cells was reverse transcribed and all known type I interferon subtypes were amplified. The products were identified by differential hybridization to a panel of subtype specific oligonucleotides. The results show that the pattern of interferon subtypes examined in splenocytes did not differ between If-1h and If-1(1) allele carrying C57BL mice. However, when the genotype was different (BALB/c splenocytes) the pattern of type I interferon mRNAs seen was altered. This genotype-dependent expression was also seen in newcastle disease virus infected fibroblasts. Within a given mouse strain, there were also differences in the subtype response patterns detected in fibroblasts compared with those seen in splenocytes. In conclusion, the present study indicates that mouse genotype appears to be a major determinant of the subtype response pattern seen and tissue specific pattern differences are present within a given mouse genotype.

Kinetics of esmolol, an ultra-short-acting beta blocker, and of its major metabolite.

Esmolol is an ultra-short-acting beta blocker. Its kinetics was studied in eight healthy subjects after continuous intravenous infusion of 400 micrograms/kg/min over 2 hr. The concentrations of esmolol and its major metabolite, 3-[4-(2-hydroxy-3-[isopropylamino]propoxy)phenyl]propionic acid, in blood and urine were determined by gas chromatographic-mass spectrometric assay and HPLC. The distribution and elimination t1/2s of esmolol averaged 2.03 and 9.19 min. The apparent volume of distribution of esmolol averaged 3.43 l/kg and was four times the volume of the central compartment. The total clearance of esmolol averaged 285 ml/min/kg, indicating that nonhepatic routes play a predominant role in its clearance. The t1/2s of formation and elimination of the metabolite averaged 2.82 min and 3.72 hr. The ratio of the metabolite formation and elimination rate constants of the parent drug (kf/k10) averaged 0.829, suggesting that 82.9% of esmolol was converted to the metabolite (which is consistent with the urinary recovery of 71% of the dose as unconjugated metabolite). The volume of distribution and total clearance of the metabolite averaged 0.411 l/kg and 1.28 ml/min/kg. Esmolol was followed by a significant reduction of isoproterenol-induced increase in heart rate and systolic blood pressure at doses of 50, 150, and 400 micrograms/kg/min.(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacokinetics, pharmacodynamics, and minimum effective clinical dose of intravenous nicardipine.

Nicardipine hydrochloride was administered intravenously to two groups of hypertensive patients: one group of 37 patients with mild to moderate hypertension and one group of 20 patients with severe hypertension. In the first group, doses of 0.5, 1, 2, and 4 mg/hr, as well as placebo, were infused for 48 hours in a double-blind fashion. Blood pressure and heart rate were monitored for this period and for the 24 hours after the infusion was discontinued. Significant decrements in blood pressure were noted with all doses; 4 mg/hr produced lowering that was greater than all other doses; 1 and 2 mg/hr produced lowering that was greater than 0.5 mg/hr but that were not different from each other. Excellent correlation of blood pressure reduction and plasma level was observed and linear kinetics existed. In the severe hypertensive patients, 1, 2, 4, 5, and 8 mg/hr were infused to established minimal and ineffective doses. One milligram per hour was an ineffective dose; 4, 5, and 8 mg/hr all produced significant reductions over the course of the study that were undistinguishable from each other. Two milligrams per hour produced modest reductions in blood pressure. Blood pressure reduction also correlated with plasma levels in the severe hypertensive group.

Interferon-alpha inhibits erythropoietin-induced proliferation, but not differentiation, and restricts erythroleukemia development.

The immature erythroid cell line J2E responds to erythropoietin (Epo) by proliferating and terminally differentiating into hemoglobin-synthesizing red blood cells. These cells produce a rapid, fatal erythroleukemia in mice characterized by hepatosplenomegaly and severe anemia. The aim of this study was to investigate the effects of murine interferons-alpha (MuIFN-alpha) on J2E cells in vitro and in vivo. Here we show that in culture MuIFN-alpha inhibited the Epo-induced proliferation of J2E cells but did not interfere with differentiation. When mice with J2E erythroleukemias were treated with MuIFNs in vivo, an extension of their life span was observed. Moreover, numerous necrotic lesions of infiltrating leukemic cells were detected in the spleens of these mice. Finally, ex vivo treatment of leukemic bone marrow cells with Epo and MuIFNs delayed mortality even further. It was concluded that MuIFNs (1) suppressed the proliferation of J2E cells in vitro but did not affect Epo-induced differentiation, and (2) inhibited the progress of erythroleukemias, especially in combination with Epo.

The use of adenovirus-mediated gene transfer to develop a rat model for photoreceptor degeneration.

PURPOSE: To investigate the effects of recombinant adenovirus-mediated downregulation of cathepsin S (CatS) on the retinal pigment epithelium and/or neural retina in vivo. METHODS: The expression of green fluorescent protein (gfp) after subretinal injection of a recombinant adenovirus, Ad.gfp, into rat eyes was first established by in vivo fundus fluorescence photography and fluorescence microscopy. The autofluorescent debris accumulation in Ad.CatSAS (recombinant adenovirus carrying the antisense CatS gene)injected rat eyes was monitored by fluorescence microscopy, and the antisense CatS RNA expression was demonstrated by in situ hybridization. Changes in the retinal morphology were assessed by light microscopy. ResuLTS. The gfp expression was present in 30% to 90% of the injection area at 3 days and was absent 9 days after Ad.gfp injection. In Ad.CatSAS-injected eyes, the expression of antisense CatS RNA was demonstrated by in situ hybridization. Autofluorescent debris accumulation was significantly higher in Ad.CatSAS-injected eyes than in control eyes. The shortening of photoreceptor outer segments in Ad.CatSAS-injected eyes coincided with intense autofluorescent debris accumulation. The number of layers of photoreceptor cells decreased with time and were 11, 9, and 8 at 7, 14, and 28 days after Ad.CatSAS injection, respectively. In control eyes, the number of layers of photoreceptor cells (14) remained unchanged. CONCLUSIONS: These results demonstrate that recombinant adenovirus-mediated transient modulation of gene expression in retinal pigment epithelial (RPE) cells could induce changes in the retina, and, in spite of the low expression of endogenous CatS in RPE cells, this enzyme plays an important role in maintenance of normal retinal function.

The in vivo expression patterns of individual type I interferon genes in murine cytomegalovirus infections.

Type I interferon (IFN) family has more than 10 structurally related subtypes of alpha IFN (IFNA) genes and a single beta IFN (IFNB) gene. This study examined the expression of MuIFNA1, A4, A5, A6, A9 and MuIFNB mRNAs in the livers and spleens of MCMV-infected mice at 2, 4 and 6 h post infection. The three strains of inbred mice studied were C57BL/6, B6.C-H-28c and BALB/c. B6.C-H-28c strain is a congenic strain of C57BL/6 genomic background. Detection of the specific mRNAs was by an established semiquantitative procedure based on reverse transcription and PCR amplification followed by differential hybridization to specific oligonucleotides. Similar expression patterns of the type I IFN mRNAs were found in C57BL/6 and B6.C-H-28c strains of mice. However, when the genotype was significantly different (BALB/c), a different expression pattern of IFN mRNAs was seen. Differences in the expression patterns of the type I IFN mRNAs was also seen between the livers and spleens of a given mouse strain. Thus, the present study indicates that mouse genotype appears to be a major determinant of the subtype response pattern seen in vivo and that tissue-type can influence the subtype response pattern seen within a given mouse genotype.