Advances in stem cell and other therapies for Huntington's disease: An update.

Huntington's disease (HD) is a neurodegenerative disorder caused by an autosomal dominant mutation leading to an abnormal CAG repeat expansion. The result is the synthesis of a toxic misfolded protein, called the mutant huntingtin protein (mHTT). Most current treatments are palliative, but the latest research has expanded into multiple modalities, including stem cells, gene therapy, and even the use of 3D cell structures, called organoids. Stem cell research as a treatment for HD has included the use of various types of stem cells, such as mesenchymal stem cells, neural stem cells, embryonic stem cells, and even reprogrammed stem cells called induced pluripotent stem cells. The goal has been to develop stem cell transplant grafts that will replace the existing mutated neurons, as well as release existing trophic factors for neuronal support. Additionally, research in gene modification using CRISPR-Cas9, PRIME editing, and other forms of genetic modifications are continuing to evolve. Most recently, advancements in stem cell modeling have yielded 3D stem cell tissue models, called organoids. These organoids offer the unique opportunity to transplant a structured stem cell graft which, ideally, models normal human brain tissue more accurately. This manuscript summarizes the recent research in stem cells, genetic modifications, and organoids as a potential for treatment of HD.

Intra-individual comparison of magnesium citrate and sodium phosphate for bowel preparation at CT colonography: automated volumetric analysis of residual fluid for quality assessment.

AIM: To perform an objective, intra-individual comparison of residual colonic fluid volume and attenuation associated with the current front-line laxative magnesium citrate (MgC) versus the former front-line laxative sodium phosphate (NaP) at CT colonography (CTC). MATERIALS AND METHODS: This retrospective Health Insurance and Portability and Accountability Act-compliant study had institutional review board approval; informed consent was waived. The study cohort included 250 asymptomatic adults (mean age at index 56.1 years; 124 male/126 female) who underwent CTC screening twice over a 5 year interval. Colon catharsis at initial and follow-up screening employed single-dose NaP and double-dose MgC, respectively, allowing for intra-patient comparison. Automated volumetric analysis of residual colonic fluid volume and attenuation was performed on all 500 CTC studies. Colonic fluid volume <200 ml and mean attenuation between 300-900 HU were considered optimal. Paired t-test and McNemar's test were used to compare differences. RESULTS: Residual fluid volumes <200 ml were recorded in 192 examinations (76.8%) following MgC and in 204 examinations (81.6%) following NaP (p = 0.23). The mean total residual fluid volume was 155 ± 114 ml for MgC and 143 ± 100 ml for NaP (p = 0.01). The attenuation range of 300-900 HU was significantly more frequent for MgC (n = 220, 88%) than for NaP (n = 127, 50.8%; p < 0.001). Mean fluid attenuation was significantly lower for MgC (700 ± 165 HU) than for NaP (878 ± 155 HU; p < 0.001). Concomitant presence of both optimal fluid volume and attenuation was significantly more frequent for MgC 65.2% than for NaP (38%; p < 0.001). CONCLUSIONS: Objective intra-individual comparison using automated volumetric analysis suggests that the replacement of NaP by MgC as the front-line laxative for CTC has not compromised overall examination quality.

Subjective health complaints and psychosocial work environment among university personnel.

BACKGROUND: Questionnaires are often used to study health problems in working populations. An association between self-reported symptoms and psychosocial strain has been suggested, but results from such studies are difficult to interpret, as a gender difference might be present. The knowledge in this area is not clear. AIMS: To compare the prevalence of subjective health symptoms and their relation to psychosocial work strain among men and women in different age groups, all working as university staff. METHODS: A cross-sectional survey was carried out among university personnel. The questionnaire included a subjective health complaint inventory consisting of 29 items about subjective somatic and psychological symptoms experienced during the last 30 days and psychosocial work factors. Regression analyses were performed. RESULTS: In total, 172 (86%) of 201 eligible employees participated. Women had a higher prevalence of musculoskeletal symptoms than men. Significant differences were found between the genders for headaches, neck pain and arm pain. There was a significant relationship between musculoskeletal symptoms and work strain for both genders. This was found for both men and women below 40 years and among men above the age of 40. No significant difference was found between genders regarding pseudoneurological, gastrointestinal, allergic and flu-like symptoms. CONCLUSIONS: More female than male university personnel reported musculoskeletal symptoms. The musculoskeletal symptoms were associated with high work strain in both genders, but, for women, this was limited to employees under the age of 40. The cause of this gender difference is unknown.

Can air pollution affect tear film stability? A cross-sectional study in the aftermath of an explosion accident.

BACKGROUND: After an explosion and fire in two tanks containing contaminated oil and sulphur products in a Norwegian industrial harbour in 2007, the surrounding area was polluted. This caused an intense smell, lasting until the waste was removed two years later. The present study reports examinations of tear film break up time among the population. The examinations were carried out because many of the people in the area complained of sore eyes. The purpose of the study was to assess the relationship between living or working close to the polluted area and tear film stability one and a half years after the explosion. METHODS: All persons working or living in an area less than six kilometres from the explosion site were invited to take part in the study together with a similar number of persons matched for age and gender living more than 20 kilometres away. Three groups were established: workers in the explosion area and inhabitants near the explosion area (but not working there) were considered to have been exposed, and inhabitants far away (who did not work in the explosion area) were considered to be unexposed. A total of 734 people were examined, and the response rate was 76 percent. Tear film stability was studied by assessing non-invasive break-up time (NIBUT) using ocular microscopy. In addition Self-reported Break Up Time (SBUT) was assessed by recording the time the subject could keep his or hers eyes open without blinking when watching a fixed point on a wall. Background information was obtained using a questionnaire. Non-parametric Wilcoxon-Mann-Whitney-tests with exact p-values and multiple logistic regression analyses were performed. RESULTS: Both NIBUT and SBUT were shorter among the male exposed workers than among the inhabitants both near and far away from the explosion area. This was also found for SBUT among males in a multiple logistic regression analysis, adjusting for age and smoking. CONCLUSIONS: Reduced tear film stability was found among workers in an area where an explosion accident had occurred.

Biological impact of low dose-rate simulated solar particle event radiation in vivo.

C57Bl6-lacZ animals were exposed to a range of low dose-rate simulated solar particle event (sSPE) radiation at the NASA-sponsored Research Laboratory (NSRL) at Brookhaven National Laboratory (BNL). Peripheral blood was harvested from animals from 1 to 12 days after total body irradiation (TBI) to quantify the level of circulating reticulocytes (RET) and micronucleated reticulocytes (MN-RET) as an early indicator of radiation-induced genotoxicity. Bone marrow lymphocytes and hippocampal tissues from each animal were collected at 12 days and up to two months, to evaluate dose-dependent late effects after sSPE exposure. Early hematopoietic changes show that the % RET was reduced up to 3 days in response to radiation exposure but recovered at 12 days postirradiation. The % MN-RET in peripheral blood was temporally regulated and dependant on the total accumulated dose. Total chromosome aberrations in lymphocytes increased linearly with dose within a week after radiation and remained significantly higher than the control values at 4 weeks after exposure. The level of aberrations in the irradiated animals returned to control levels by 8 weeks postirradiation. Measurements of chromosome 2 and 8 specific aberrations indicate that, consistent with conventional giemsa-staining methods, the level of aberrations is also not significantly higher than in control animals at 8 weeks postirradiation. The hippocampus was surveyed for differential transcriptional regulation of genes known to be associated with neurogenesis. Our results showed differential expression of neurotrophin and their associated receptor genes within 1 week after sSPE exposure. Progressive changes in the profile of expressed genes known to be involved in neurogenic signaling pathways were dependent on the sSPE dose. Our results to date suggest that radiation-induced changes in the hematopoietic system, i.e., chromosome aberrations in lymphocytes, are transient and do not persist past 4 weeks after radiation. On the other hand, alteration in the profile of genes known to be involved in neurotrophic functions in the hippocampal tissue appears to persist for up to 8 weeks after radiation exposure. Such temporal changes confirm that, although cytogenetic changes after a single dose of low-dose and low-dose-rate protons appear to be transient, the impact of this exposure is sufficient to lead to persistent dynamic changes in neuronal tissues long after the initial radiation exposure.

Symptoms, complaints, ocular and nasal physiological signs in university staff in relation to indoor environment - temperature and gender interactions.

UNLABELLED: Symptoms, signs, perceptions, and objective measures were studied in university buildings. Two problem buildings with a history of dampness and complaints were compared with two control buildings. Health investigations among university staff were performed at the workplace (n = 173) including tear film stability [non-invasive break-up time (NIBUT) and self-reported break-up time (SBUT)], nasal patency (acoustic rhinometry), nasal lavage fluid analysis [NAL: eosinophil cationic protein (ECP), myeloperoxidase (MPO), lysozyme and albumin] and atopy by total serum IgE and IgE antibodies (Phadiatop). Exposure assessment included inspections, thermal and atmospheric climate at 56 points modelled for all work sites. Multiple regressions were applied, controlling for age and gender. Exposure differences between problem buildings and controls were small, and variations between rooms were greater. Workers in the problem buildings had more general and dermal symptoms, but not more objective signs than the others. Adjusted day NIBUT and SBUT increased at higher night air temperatures, with B (95% CI) 0.6 (0.04-1.2) and 1.3 (-0.02 to 2.5), respectively. Higher relative humidity at mean day air temperature <22.1 degrees C was associated with adjusted NIBUT and SBUT, with B (95% CI) 0.16 (0.03-0.29) and 0.37 (-0.01 to 0.75), respectively. Air velocity below recommended winter values and reduced relative humidity in the range of 15-30% were associated with dry air and too low temperature. PRACTICAL IMPLICATIONS: Thermal climate in university buildings may be associated with both perceptions and physiological signs. Reduced night time air temperature, increased difference in air temperature between day and night, and fast changes in air temperature might impair indoor environment. This may have implication for energy-saving policies. It might be difficult to identify the exposure behind, and find the reason why, some buildings are defined as 'problem buildings'.

Pet keeping and dampness in the dwelling: associations with airway infections, symptoms, and physiological signs from the ocular and nasal mucosa.

UNLABELLED: The aim was to utilize data from a study of occupational indoor environments to analyze symptoms and physiological signs in relation to the home environment. A medical investigation was performed at the workplace among university staff (n = 173) from four university buildings in Bergen, in March 2004. Tear film break up time (BUT) was measured by two methods. Nasal patency was measured by acoustic rhinometry. Nasal lavage fluid analysis (NAL) included eosinophilic cationic protein (ECP); myeloperoxidase (MPO), lysozyme and albumin. Atopy was assessed by total serum IgE and specific IgE (Phadiatop). Totally 21%, 21%, 18%, 11%, and 27% had weekly ocular, nasal, facial dermal symptoms, headache and tiredness, respectively, 15% had a damp dwelling, and 20% had a cat or dog. Multiple linear or logistic regressions were applied, controlling for age gender, smoking, and environmental factors. Building dampness was associated with increased NAL-lysozyme (P = 0.02) and an increase of airway infections [odd ratio (OR) = 3.14, P = 0.04]. Pet keeping was associated with difficulties to concentrate (OR = 5.10, P = 0.001), heavy headedness (OR = 4.35, P = 0.004), four more days with tiredness per month (P = 0.04), and less airway infections (OR = 0.32; P = 0.02). In conclusion, pet keeping was associated with more central nervous system (CNS)-symptoms but less airway infections. Dampness in the dwelling may have inflammatory effects on the airway mucosa, possibly mediated via increased infection proneness. PRACTICAL IMPLICATIONS: The main health focus on pet keeping has been allergen exposure. Our study indicates that effects on airway infections and other types of symptoms should also be considered. The findings support the view that measures should be taken to reduce building dampness in dwellings.

Evaluation of the impact of shielding materials in radiation protection in transgenic animals.

We are using a plasmid-based transgenic mouse mutation model system to evaluate the effectiveness of aluminum or low-density polyethylene (LDPE) shielding after 250 MeV/u protons or 1 GeV/u iron ion irradiation. Transgenic mice, with multiple copies of the plasmid pUR288 lacZ transgene integrated into the genome of every cell of the animal, were either irradiated or sham-treated. Multiple endpoints, including early cytogenetic damage in erythrocytes at 48 h after exposure, chromosome aberrations in bone marrow lymphocytes, and lacZ mutant frequencies (MF) in brain and spleen tissues were measured in the same animals. The frequency of total circulating reticulocytes (fRET) dropped precipitously at 48 h after 2 Gy of proton irradiation. The average level of micronucleated reticulocytes (fMN-RET) was fivefold higher in the irradiated samples relative to the controls at the same time point. There was an increase in total chromosome aberrations in bone marrow lymphocytes at 8 weeks after proton irradiation but this increase was not statistically significant relative to the controls. Evaluation of the lacZ MF in the brain and spleen tissues showed that proton irradiation induced a twofold increase in MF in each tissue. Similar samples were collected from animals that were shielded from the proton beam by aluminum. Compared to the unshielded treatment group, we noted no difference in fRET, fMN-RET, chromosome aberrations in lymphocytes and lacZ MF in brain and spleen tissues obtained from these animals. In a separate study, animals were exposed to high-energy iron ions with or without 10 or 15 cm LDPE. Using the same approach, we noted a precipitous drop in fRET, and an elevation in fMN-RET within 48 h after 1 Gy of iron ions. Total chromosome aberrations in bone marrow lymphocytes were slightly elevated but not significant at 8 weeks after iron ion exposure. Shielding animals with 10 or 15 cm of polyethylene appeared to have no effect on the level of RET, MN-RET or chromosome aberrations in these animals. LacZ MF in brain and spleen tissues increased 1.5-2-fold above control levels after 1 Gy iron ions at 8 weeks after treatment. On the other hand, MF in tissues harvested from shielded animals appeared to be lower than their unshielded litermates, suggesting the polyethylene shielding was effective in reducing the iron-induced genomic damage in tissues. Although shielding may be effective, in some cases, in reducing the physical dose of particle radiation, our cytogenetic results showed that the biological impact of the particle beam remain unchanged. On the other hand, reduction in transgene MF in tissues from LDPE-shielded animals but not in the aluminum-shielded animals strongly suggests that careful consideration of the biological endpoints used is necessary in the evaluation of the efficacy of the selected shielding material.

Assessment of the genotoxic potential of ISIS 2302: a phosphorothioate oligodeoxynucleotide.

ISIS 2302, a phosphorothioate oligodeoxynucleotide with antisense activity against human ICAM-1 mRNA, was evaluated in a battery of tests to assess genotoxic potential. There was no evidence of genotoxicity in three in vitro studies performed: (i) a bacterial reverse mutation test; (ii) a chromosomal aberration test in Chinese hamster ovary cells; (iii) a mammalian cell gene mutation assay in L5187Y cells. Additionally, there was no in vivo evidence of genetic toxicity in a bone marrow micronucleus study in male and female mice. For all tests, top concentrations or doses assessed met harmonized regulatory guidelines. The cellular uptake of ISIS 2302 into target cells was confirmed using capillary gel electrophoresis and immunohistochemistry. Intracellular uptake into CHO cells, L5187Y cells, Salmonella typhimurium TA98 and bone marrow was concentration- and time-dependent. Consistent with what is known about the physical and chemical properties of phosphorothioate oligodeoxynucleotides, there was no evidence of genotoxicity in any of the assessed end-points. Furthermore, the absence of genotoxicity could not be ascribed to test system insensitivity or to an absence of exposure of the test system to ISIS 2302.

Metabolism of N-isopropylacetanilide in rat.

1. Radioactivity from oral doses of N-isopropyl[1-14C]acetanilide was excreted in urine (53.5%), faeces (8.1%) and expired air (17.0%) of rat. 2. Enterohepatic circulation occurred during formation of approximately 34% of the metabolites. N-isopropylacetanilide was metabolized by oxidation in all moieties of the molecule with subsequent conjugation with glucuronic and sulphuric acids. 3. The sulphate ester of 4'-hydroxyacetanilide (acetaminophen) was the major metabolite (28 % of the dose).

Identification of the major urinary and fecal metabolites of 3,5-dinitrobenzamide in chickens and rats.

Colostomized chickens given oral doses of 3,5-dinitrobenzamide (nitromide) cleared nitromide predominantly through the urine (58% of dose) and feces (21% of dose). Rats cleared 52% of nitromide via urinary excretion and 44% via feces. Major urinary metabolites for both chickens and rats include: 3-amino-5-nitrobenzamide, 3-acetamido-5-nitrobenzamide, 3-acetamide-5-aminobenzamide, and 3,5-diacetamidobenzamide. The major fecal metabolite in chickens was 3-acetamido-5-nitrobenzamide (67% of fecal 14C) and 3-acetamido-5-aminobenzamide in rats (approximately 50%).

Intermediary metabolism of pentachloronitrobenzene in the control and germ-free rat and rat with cannulated bile ducts.

1. Nearly 70% of single oral doses of 14C-labelled pentachloronitrobenzene (PCNB) was excreted in bile within 24 h. 2. The characterized biliary metabolites of PCNB were either mercapturic acid pathway metabolites or catabolites thereof (thiols, methylthiols, S-glucuronides). 3. A major biliary metabolite was S-(aminotetrachlorophenyl)glutathione. 4. Conjugation with glutathione with subsequent catabolism to bis-methylthiotetrachlorobenzene was the major pathway in the control rat. 5. Germ-free experiments showed that only nitro- group displacement occurred, and no nitro- group reduction was detected.

Detection of cardiac transplant rejection with 111In-labeled lymphocytes and gamma scintigraphy.

BACKGROUND: Cardiac transplantation is an increasingly important treatment for patients with end-stage heart failure. Rejection is one of the major limitations, and currently, serial endomyocardial biopsies are required to diagnose rejection. In the year after transplantation, patients routinely undergo 12, 14, or more biopsies. Infiltration of lymphocytes into the graft is a central feature of rejection. Previous studies from our laboratory have demonstrated the feasibility of detecting early rejection noninvasively with gamma scintigraphy after administration of autologous lymphocytes labeled with 111In. METHODS AND RESULTS: Eight patients were studied at the time of routine biopsy an average of 4.5 months after cardiac transplantation. Autologous lymphocytes were isolated and labeled with 111In. Forty-eight to 72 hours later, patients underwent planar scintigraphic imaging. Myocardial accumulation of labeled lymphocytes was quantified (indium excess, IE) with a previously described and validated technique. Animal studies have shown that an IE > or = 0.07 is associated with rejection. Two of four patients with biopsy grade 0 or 1A rejection had no excess accumulation of labeled lymphocytes. The other two patients with biopsy grade 0 or 1A had an average IE of 0.13 +/- 0.04 (SD), which may actually represent the higher sensitivity of the scintigraphic approach, since the whole myocardium is interrograted. All four patients with biopsy grade 1B rejection had increased accumulation of labeled lymphocytes (IE = 0.18 +/- 0.06, P = .06 compared with all patients with grade 0 or 1A biopsies). CONCLUSIONS: The development of a sensitive, specific, and noninvasive method of diagnosing cardiac allograft rejection in humans might obviate the need for endomyocardial biopsy as well as improve the accuracy of diagnosis. The results suggest that scintigraphic detection of labeled lymphocytes is a promising approach for the noninvasive detection of cardiac transplant rejection. In addition, the approach should permit the assessment of the efficacy of antirejection therapy.

Haemodynamic classification of symptomatic obstructive carotid artery disease.

63 subjects with symptomatic obstructive carotid artery disease were investigated with transcranial Doppler ultrasonography. Their blood velocities at rest (V) in the middle and posterior cerebral artery (MCA and PCA) and in the extracranial internal carotid artery were measured and the pulsatility index (PI) and Uhem index (VMCA.PIMCA/VPCA.PIPCA) calculated. The vasomotor responses in both MCAs were also tested. The subjects were divided into groups based on the findings on physical examination and cerebral computed tomography. In the patient group with lacunar/territorial infarction we found in the stroke hemisphere: VMCA > VPCA, PIMCA = PIPCA and normal values for the Uhem index and total vasomotor reactivity. In the patient group with watershed infarction this hemisphere was characterized by: VMCA < VPCA, PIMCA < PIPCA and subnormal scores for the Uhem index and total vasomotor reactivity. Displaying features from both stroke groups, we obtained in the hemisphere of interest in patients with transient ischaemic attacks: VMCA = VPCA, PIMCA < PIPCA and normal values for the Uhem index and total vasomotor reactivity. Five patients with clinical evidence of stroke but with negative cerebral computed tomography findings had scores similar to those of the watershed group of patients. For the stroke patients, individual measurements of V, PI and total vasomotor reactivity failed to clearly identify to which stroke group a subject might belong. However, such an identification was achieved in all subjects when using the Uhem index. The Uhem index data in patients with transient ischaemic attacks suggest two subgroups with different pathogenesis underlying, the ischaemic events.

Rate of glycolysis during ischemia determines extent of ischemic injury and functional recovery after reperfusion.

The efficacy of increasing glycolysis during ischemia for enhancing the salutary effects of reperfusion was evaluated in isolated perfused rabbit hearts subjected to low-flow ischemia followed by reperfusion. Control hearts were perfused with buffer containing 0.4 mM palmitate, 5 mM glucose, and 70 mU/l insulin. Additional groups of hearts were perfused with double glucose/insulin and 1 mM dichloroacetate or were subjected to substrate priming to increase preischemic glycogen content. Ischemic contracture was completely prevented in hearts perfused with high glucose/insulin and was delayed markedly by either dichloroacetate or enhanced preischemic glycogen [45 +/- 14 and 31 +/- 20 min, respectively; P < 0.01 each vs. control (11 +/- 10 min)] and inversely related to the rate of lactate production. With reperfusion, recovery of developed pressure was 56 +/- 23% of baseline in control hearts, 90 +/- 8% in hearts receiving high glucose/insulin, 92 +/- 5% in hearts receiving dichloroacetate, and 79 +/- 19% in hearts with increased glycogen (P < 0.05 each vs. control hearts). Creatine kinase release was reduced by > 55% in treated hearts. Thus enhancement of glycolysis by diverse mechanisms during ischemia decreased ischemic damage and improved the recovery of contractile function with reperfusion.

Effect of AT-125 on the metabolism of propachlor and the glutathione conjugates of propachlor and bromobenzene in rat.

1. Dosing rats with the gamma-glutamyl-transpeptidase inhibitor AT-125 results in the excretion of free glutathione in the urine of rat: this treatment did not lead to the excretion of glutathione conjugates of orally dosed xenobiotics, neither did AT-125 increase the biliary excretion of glutathione conjugates. 2. Dosing rat with AT-125 prior to dosing with 2-chloro-N-isopropylacetanilide decreased the excretion of 2-methylsulphonylacetanilide metabolites from 23% of the dose to < 0.5%. 3. We conclude that glutathione and glutathione-xenobiotic conjugates are probably not processed in vivo by the same pathway, and that AT-125 can alter the in vivo transport of mercapturic acid pathway metabolites.

Glutathione-mediated methylthio-turnover and sex differences in the metabolism of pentachlorothioanisole by rat.

1. Sex differences observed in the metabolism of pentachlorothioanisole in rat were due to: (1) greater excretion in urine by females, and greater biliary excretion by males; (2) formation of pentachlorophenyl mercapturic acid pathway metabolites by females; and (3) redox-cycling between methylthio and methylsulphoxyl oxidation congeners in intermediary metabolites by females. 2. Three methylthio-turnover processes are proposed in the intermediary metabolism of pentachlorothioanisole.

Comparative metabolism of the cysteine and homocysteine conjugates of propachlor by in situ perfused kidneys of rats.

1. 14C-Cysteinyl- and homocysteinylpropachlor were metabolized to their respective mercapturic acids by rat kidneys in situ. First-pass elimination of 14C in urine was 47.5% for the cysteine conjugate and 36% for the homocysteine conjugate. 2. About half of the perfused 14C-labelled material isolated from urine from kidneys perfused with homocysteinylpropachlor was unchanged homocysteinylpropachlor and about half was the corresponding mercapturic acid. However, only the corresponding mercapturic acid and the S-oxide of this mercapturic acid (31.4% and 1.7% of the dose) were found in urine from kidneys perfused with cysteinylpropachlor, indicating that rat kidneys more efficiently acetylated the natural substrate, the cysteine conjugate.

Conjugation of polychlorinated agrochemical sulphoxides and sulphones by glutathione.

1. Pentachlorophenyl methyl sulphoxide and pentachlorophenyl methyl sulphone were found to be substrates for microsomal and cytosolic glutathione-S-transferase of rabbit, monkey, chicken and human liver, covalently immobilized on beaded sepharose. 2. Protein was immobilized with greater than 95% transferase activity, measured by dinitrochlorobenzene. Immobilized rabbit liver microsomal transferase activity was more stable than immobilized cytosolic activity. 3. The sulphoxide moiety was displayed by glutathione in the presence of chicken liver microsomal protein. The sulphone moiety was displayed by glutathione in the formation of a diglutathione under catalysis by rhesus monkey liver cytosolic and microsomal protein. 4. Chlorine was displaced by transferases from all species to form regioisomeric monoglutathiones. 5. Qualitative and quantitative differences were observed in product distributions between species and between microsomal and cytosolic protein.