Muscular Echo-Intensity of the Quadriceps by Ultrasound Is More Related to Improvement of Gait Independence than Muscle Thickness in Older Inpatients.

OBJECTIVES: This study aimed to examine whether the decrease in muscular echo-intensity of the quadriceps by ultrasound in older inpatients is related to the improvement of gait independence than the increase of muscle thickness. DESIGN: Longitudinal study. SETTING: Hospital-based study. PARTICIPANTS: This study included 171 inpatients aged ≥ 65 years (median age: 84.0 [77.0-88.0], 56.1% female). Patients who were able to walk independently at hospital admission were excluded from the study. MEASUREMENTS: Improvement of gait independence during hospital stay was assessed using the change in Functional Independence Measure (FIM) gait score (i.e., FIM gait score at hospital discharge minus FIM gait score at hospital admission) and FIM gait score at hospital discharge. Muscular echo-intensity and muscle thickness of the quadriceps were assessed at hospital admission and discharge using ultrasound images, respectively. Muscular echo-intensity has been shown to be mainly related to intramuscular adipose tissue. Multiple linear regression analysis was performed to identify the factors independently associated with the change in FIM gait score and FIM gait score at discharge. RESULTS: Change in quadriceps echo-intensity was independently and significantly associated with the change in FIM gait score (ß = -0.22, p = 0.017) and FIM gait score at hospital discharge (ß = -0.21, p = 0.017). In contrast, change in quadriceps thickness was not independently and significantly associated with the change in FIM gait score (ß = 0.16, p = 0.050) and FIM gait score at hospital discharge (ß = 0.15, p = 0.050). CONCLUSIONS: Our study indicates that a decrease in muscular echo-intensity of the quadriceps by ultrasound is more related to the improvement of gait independence than an increase of muscle thickness in older inpatients. Intervention for intramuscular adipose tissue of the quadriceps may be important for improving gait independence in older inpatients.

Higher Body Mass Index in Hospitalized Older Patients Is Related to Higher Muscle Quality.

OBJECTIVES: This study aimed to examine the relationship between muscle mass, intramuscular adipose tissue, and body mass index (BMI) in older inpatients. DESIGN: Cross-sectional study. SETTING: Hospital-based study. PARTICIPANTS: This study included 413 inpatients aged ≥ 65 years (186 men and 227 women). MEASUREMENTS: Muscle mass and intramuscular adipose tissue of the quadriceps were assessed by measuring the muscle thickness and echo intensity on ultrasound images. To examine the relationship between quadriceps thickness and echo intensity and BMI in total participants and each sex, the Kendall rank correlation coefficient was used. Multiple regression analysis was performed to examine whether BMI was independently and significantly related to the quadriceps thickness and echo intensity, even after adjusting for other variables for total participants and each sex. The independent variables in multiple regression analyses were BMI, age, disease, days from onset disease. RESULTS: The results of the correlation analyses showed that BMI was significantly related to the quadriceps thickness (total participants, τ = 0.431; men, τ = 0.491; women, τ = 0.388) and echo intensity (total participants, τ = -0.239; men, τ = -0.318; women, τ = -0.188). In the multiple regression analysis, BMI was independently and significantly associated with the quadriceps thickness (total participants, ß = 0.535; men, ß = 0.548; women, ß = 0.519) and echo intensity (total participants, ß = -0.287; men, ß = -0.398; women, ß = -0.210). CONCLUSION: This study indicated that older inpatients with a higher BMI have greater muscle mass and less intramuscular adipose tissue of the quadriceps. These results suggested that a higher BMI in older inpatients is related to higher quadriceps muscle quality.

Thinning of articular cartilage after joint unloading or immobilization. An experimental investigation of the pathogenesis in mice.

OBJECTIVE: Moderate mechanical stress generated by normal joint loading and movement is essential for the maintenance of healthy articular cartilage. However, the effects of reduced loading caused by the absence of weight bearing or joint motion on articular cartilage and subchondral bone is still poorly understood. We aimed to characterize morphological and metabolic responses of articular cartilage and subchondral bone to decreased mechanical stress in vivo. METHODS: Mice were subjected to periods of hindlimb unloading by tail suspension or external fixation of the knee joints. The articular surface was observed with digital microscope and the epiphyseal bone was assessed by micro-CT analysis. Articular cartilage and subchondral bone were further evaluated by histomorphometric, histochemical, and immunohistochemical analyses. RESULTS: The joint surface was intact, but thickness of both the total and uncalcified layer of articular cartilage were decreased both after joint unloading and immobilization. Subchondral bone atrophy with concomitant marrow expansion predisposed osteoclast activity at bone surface to invade into cartilaginous layer. Uncalcified cartilage showed decreased aggrecan content and increased aggrecanase expression. Alkaline phosphatase (ALP) activity was increased at uncalcified cartilage, whereas decreased at calcified cartilage. The distributions of hypertrophic chondrocyte markers remained unchanged. CONCLUSION: Thinning of articular cartilage induced by mechanical unloading may be mediated by metabolic changes in chondrocytes, including accelerated aggrecan catabolism and exquisitely modulated matrix mineralization, and cartilage matrix degradation and resorption by subchondral osteoclasts. Cartilage degeneration without chondrocyte hypertrophy under unloading condition indicate the possible existence of mechanism which is different from osteoarthritis pathogenesis.

Interaction between gastrocnemius muscle weakness and moderate exercise deteriorates joint integrity in rat knee.

The aim of this study was to determine the effect on the knee joint of the interaction between ankle muscle weakness and moderate exercise. Gastrocnemius muscle weakness was induced by intramuscular injection of botulinum toxin type A (BTX) in rats. Low-speed treadmill running (12 m/min for 60 min) was applied for 6 weeks in rats with and without BTX. Untreated animals were used as controls. After BTX injection, the gastrocnemius muscle weakness was confirmed by 3-D motion analysis in kinematic features of the hindlimb during locomotion as an increased maximal dorsiflexion angle during the stance phase. Serum biomarker analysis by enzyme-linked immunosorbent assay revealed that low-speed running decreased the catabolic effect on type II collagen. However, the inhibition of catabolism induced by running exercise was significantly counteracted by BTX injection. In addition, thinning of the cartilage layer and a reduction in the chondrocyte density was also found in the tibial plateau of the knee in the BTX-injected rats after running for 6 weeks. These data suggest that moderate exercise have a positive effect on joint homeostasis. However, ankle muscle weakness may alter the mechanical environment of the knee and impair the integrity of joint cartilage with moderate exercise.

Inwardly rectifying potassium channel Kir4.1 is localized at the calyx endings of vestibular afferents.

Inwardly rectifying potassium (Kir) channel Kir4.1 (also called Kcnj10) is expressed in various cells such as satellite glial cells. It is suggested that these cells would absorb excess accumulated K(+) from intercellular space which is surrounded by these cell membranes expressing Kir4.1. In the vestibular system, loss of Kir4.1 results in selective degeneration of type I hair cells despite normal development of type II hair cells. The mechanisms underlying this developmental disorder have been unclear, because it was thought that Kir4.1 is only expressed in glial cells throughout the entire nervous system. Here, we show that Kir4.1 is expressed not only in glial cells but also in neurons of the mouse vestibular system. In the vestibular ganglion, Kir4.1 mRNA is transcribed in both satellite cells and neuronal somata, whereas Kir4.1 protein is expressed only in satellite cells. On the other hand, in the vestibular sensory epithelia, Kir4.1 protein is localized at the calyx endings of vestibular afferents, which surround type I hair cells. Kir4.1 protein expression in the vestibular sensory epithelia is detected beginning after birth, and its localization gradually adopts a calyceal shape until type I hair cells are mature. Kir4.1 localized at the calyx endings may play a role in the K(+)-buffering action of vestibular afferents surrounding type I hair cells.

Development of fulminant Type 1 diabetes with thrombocytopenia after influenza vaccination: a case report.

BACKGROUND: Fulminant Type 1 diabetes was originally reported as idiopathic Type 1 diabetes. Involvement of viral infections in the pathogenesis of fulminant T1D has been suggested, but the development of fulminant Type 1 diabetes after influenza vaccination has not been reported. CASE REPORT: We report a case of fulminant Type 1 diabetes with thrombocytopenia following influenza vaccination. A 54-year-old man was admitted to hospital with hyperglycaemia and diabetic ketosis. Seven days before admission, he received a seasonal influenza vaccine for the prevention of influenza infection. On admission, blood glucose was 29 mmol/L and HbA1c 40 mmol/mol (5.9%). Fasting and 2-h C-peptide immunoreactivity were <0.0333 nmol/L and 0.0999 nmol/L, respectively. Anti-GAD and anti-IA-2 antibodies were negative, so no autoimmunity seemed to participate in the etiology. ELISPOT assay also showed no association with T cell-mediated autoimmunity. HLA genotypes were consistent with susceptibility to fulminant Type 1 diabetes. After the abrupt onset of diabetes, he showed mild thrombocytopenia, which has been observed for approximately 5 years after diabetes development. CONCLUSION: This is the first description of fulminant Type 1 diabetes after influenza vaccination. Our observation raises the possibility that influenza vaccination might trigger this condition via the TLR7 pathway.

Mucosal eosinophilia and recurrence of nasal polyps - new classification of chronic rhinosinusitis.

BACKGROUND: Eosinophils and nasal polyps are believed to affect the surgical outcome of chronic rhinosinusitis (CRS). CRS is classified based on the presence of nasal polyps in western countries. The majority of patients with CRS with nasal polyps (CRS with NP) are characterized by predominantly eosinophilic inflammation. However, Asian patients with CRS with NP show characteristics indicative of neutrophilic inflammation. Therefore, are eosinophils or nasal polyps more important for the classification of CRS? METHODS: A prospective cohort study conducted from April 2007 to March 2008 classified patients with CRS based on the presence of nasal polyps and mucosal eosinophilia. The recurrence rate of nasal polyps was compared between the groups. Recurrence rate was analysed as a time-dependent variable by the Kaplan-Meier method. RESULTS: Eosinophilic inflammation was found in 59.6% of patients with CRS with NP. Patients with mucosal eosinophilia had higher polyp recurrence rate than patients without mucosal eosinophilia, whereas patients with nasal polyps did not have higher polyp recurrence rate than patients without nasal polyps. CONCLUSIONS: Presence of mucosal eosinophilia is a more important factor than nasal polyps for classifying CRS in terms of the surgical outcome.

Breast tumor progression induced by loss of BTG2 expression is inhibited by targeted therapy with the ErbB/HER inhibitor lapatinib.

The B-cell translocation gene-2 (BTG2), a p53-inducible gene, is suppressed in mammary epithelial cells during gestation and lactation. In human breast cancer, decreased BTG2 expression correlates with high tumor grade and size, p53 status, blood and lymph vessel invasion, local and metastatic recurrence and decrease in overall survival, suggesting that suppression of BTG2 has a critical role in disease progression. To analyze the role of BTG2 in breast cancer progression, BTG2 expression was knocked down in mammary epithelial cells. Suppression of BTG2 enhances the motility of cells in vitro and tumor growth and metastasis in vivo. The effects of BTG2 knockdown are mediated through stabilization of the human epidermal growth factor receptor (HER) ligands neuregulin and epiregulin and activation of the HER2 and HER3 receptors, leading to elevated AKT phosphorylation. Suppression of HER activation using the tyrosine kinase inhibitor lapatinib abrogates the effects of BTG2 knockdown, including the increased cell migration observed in vitro and the enhancement of tumorigenesis and metastasis in vivo. These results link BTG2-dependent effects on tumor progression to ErbB receptor signaling, and raise the possibility that targeted inhibition of this pathway may be relevant in the treatment of breast cancers that have reduced BTG2 expression.

Effect of position of electrodes relative to the innervation zone onsurface EMG.

We investigated the effect of the position of electrodes relative to the innervation zone (IZ) of the biceps brachii muscle during isometric elbow flexion using eight-channel surface array electrodes. We estimated the location of the IZ near the centre of the muscle in 20 male subjects. The pulse peaks from electromyogram (EMG) waveforms were detected for each channel and averaged, the triphasic pulse was determined, and the peak values of the first and third phases were compared. The results showed significantly greater pulse values for the first phase when the electrode placement was proximal to the estimated IZ, and for the third phase when the electrode placement was distal to the estimated IZ. Using this method, the positional relationship between electrodes and IZ can be determined using a surface EMG waveform recorded with a pair of bipolar electrodes. This method may be clinically useful in confirming the reliability of a recorded surface EMG.

Vasorelaxant effects of forsythide isolated from the leaves of Forsythia viridissima on NE-induced aortal contraction.

Forsythide (F1) isolated from the leaves of Forsythia viridissima (Oleaceae) showed vasorelaxant effects on norepinephrine (NE)-induced contraction of rat aorta with or without endothelium. This compound did not affect contraction induced by high concentration potassium (60 mM K(+)) and phorbol 12,13-diacetate, but inhibited NE-induced contraction in the presence of nicardipine. These results demonstrated the inhibitory effects of F1 on NE-induced vasocontraction presumably due to decrease of calcium influx from extracellular area, which was induced by NE.

Contrasting alteration patterns of different cartilage plates in knee articular cartilage after spinal cord injury in rats.

STUDY DESIGN: Experimental, controlled trial, animal study. OBJECTIVE: To assess morphologic changes in different cartilage plates after spinal cord injury and identify the localization of these alterations. SETTING: Saitama, Japan. METHODS: A total of 16 Wistar rats were used. Eight rats underwent a spinal cord injury and eight rats had no intervention as control. The cartilage alterations of the knee joint were evaluated with radiography and histomorphometric analysis. To quantify cartilage alterations, we selected the histologic characteristics: thickness of the articular cartilage, number of chondrocytes, matrix staining to toluidine blue as a reflection of proteoglycan content and surface irregularity. RESULTS: No differences in knee joints were found between the groups by radiography. In the medial knee joint, cartilage thickness of spinal-cord-injured knees increased at the anterior femoral region and decreased at the tibial and posterior femoral regions; however, in the lateral knee, that of spinal cord injuries did not change compared with control knees. Spinal cord injuries decreased the number of chondrocytes, especially at the anterior femoral regions. Matrix staining increased partially at the tibial regions. Surface irregularity of spinal-cord-injured knees was comparable to that of control knees in all cartilage plates. CONCLUSION: The present findings exhibit characteristics of the cartilage after spinal cord injury. These alterations were different in nature between the medial and lateral regions. Future studies should assess separately different cartilage plates, to overestimate these severities when the changes at the medial knee were examined and to underestimate when the changes at the lateral knee were examined.

Structure of thymic cysts in congenital lymph nodes-lacking mice.

The ALY (aly/aly) mouse, a mutant of the C57BL/6j strain, has a severe immunodeficiency because of immature development of the immune organs. Both lymph nodes and Peyer's patches are lacking and both the thymus and spleen are small. Previous microscopical observation of their thymus glands revealed the presence of an indistinct border between the cortex and medulla, the absence of Hassal's corpuscles and the reduction of the medullary epithelial cell population. However, other microscopical findings for these glands have not yet been reported. In the present study, we performed light and electron microscopical observation of the thymus and found the consistent presence of extremely irregular shaped cystic cavities lined by microvilli-bearing epithelium in the medulla. The cysts comprised ceca and did not open into adjacent capillaries, although they contained some lymphocytes and macrophages in their lumens. In the thymus glands of normal C57BL/6j mice, only some small cysts oval in shape could be inconspicuously found in the medulla. Therefore, the thymic cysts may normally regress during thymic development, however, in ALY mice, the cysts may remain because of the organ immaturity.

Alteration in articular cartilage of rat knee joints after spinal cord injury.

OBJECTIVE: Mechanical forces are crucial for the maintenance of the morphologic and functional integrity of articular cartilage. The alteration of the articular cartilage after spinal cord injury (SCI) has been described in relation to a suppression of mechanical forces, since the joint is unloaded and restricted in movement. However, the morphological and biochemical characteristics of the cartilage after SCI are still poorly understood. We identified the localization of cartilage alterations after SCI and verified the influence of mechanical forces on the articular cartilage. METHOD: A total of 32 Wistar rats were used. Sixteen animals underwent an SCI and 16 animals served as control. The articular cartilage of the knee joint was assessed, respectively, at 4, 8, 10, and 12 weeks after intervention by histochemical, histomorphometric, immunohistochemical, and biochemical analyses. RESULTS: Cartilage thickness of spinal cord-injured knees decreased at the tibial and posterior femoral (FP) regions and increased at the anterior femoral (FA) region. Spinal cord injuries decreased the number of chondrocytes at the anterior regions and decreased the cartilage matrix staining only at the tibial regions. Immunolabeling to collagen type II was noted comparably in the superficial layer but noted weakly from the middle to deep layer. Collagen type I existed excessively at the cartilage surface and the pericellular regions. CONCLUSION: Cartilage alterations after SCI would not be explained by only a suppression of mechanical forces by unloading and immobilization, but there may be influences on the cartilage in addition to the change in mechanical forces.

Primary extramedullary plasmacytoma of the small intestine. A case report and review of the literature.

A case of primary extramedullary plasmacytoma of the small intestine in a 73-year-old Japanese woman was reported. The patient underwent local resection of the tumor, and showed no signs of local recurrence or dissemination of the disease after 28 months follow-up. The tumor cells had relatively large nuclei with distinct nucleoli and wide and slightly basophilic cytoplasm with a high N/C ratio which showed the morphology of atypical plasma cells. Immunohistochemical examination revealed that the tumor cells contained IgG gamma-type immunoglobulin in their cytoplasm but they did not contain IgA, IgM, IgD, and kappa-light chains. The tumor cells were also positive for CD79a and CD138 and negative for LCA, CD20 and CD45RO. These findings clearly indicated this case to be plasmacytoma.

Retroperitoneoscopic radical nephrectomy in obese patients: outcomes and considerations.

OBJECTIVE: To determine whether obesity is associated with surgical outcome in Japanese patients undergoing retroperitoneoscopic radical nephrectomy (RRN). PATIENTS AND METHODS: Between November 1999 and March 2005, we performed 98 RRN procedures for patients with renal cell carcinoma. Patients with a body mass index (BMI) of 25.0 or more were defined as obese (group A, n=33) and those with a BMI of <25.0 were defined as non-obese (group B, n=65), in accordance with the criteria of the Japan Society for the Study of Obesity. Patient background, degree of surgical invasiveness, and period of convalescence were compared between groups A and B. RESULTS: No statistically significant differences were observed between the groups in terms of age, gender, tumor laterality, tumor size, and time until resumption of oral intake and ambulation. However group A had a significantly longer insufflation time (172.1 vs. 137.4 min), greater blood loss (195.3 vs. 48.4 ml) and higher renal specimen weight (440.0 vs. 306.0 g) than group B. CONCLUSION: Obesity is not a factor that affects patient eligibility for RRN, but is a risk factor for longer insufflation time and greater blood loss.

A new model of insulin-deficient diabetes: male NOD mice with a single copy of Ins1 and no Ins2.

AIMS/HYPOTHESIS: We describe a novel model of insulin-deficient diabetes with a single copy of the gene encoding insulin 1 (Ins1) and no gene encoding insulin 2 (Ins2). MATERIALS AND METHODS: We constructed five lines of mice: mice with two copies of Ins1 (NOD( Ins1+/+,Ins2-/-)), mice with a single copy of Ins1 (NOD( Ins1+/-,Ins2-/-)), mice with two copies of Ins2 (NOD( Ins1-/-,Ins2+/+)), mice with a single copy of Ins2 (NOD( Ins1-/-,Ins2+/-)) and NOD( Ins1+/-,Ins2-/-) mice with a transgene encoding B16:Ala proinsulin. RESULTS: By 10 weeks of age, all male NOD( Ins1+/-,Ins2-/-) mice were diabetic, whereas all female NOD( Ins1+/-,Ins2-/-) were not diabetic (p < 0.0001). In contrast, neither male nor female NOD( Ins1-/-,Ins2+/-) with a single copy of Ins2 (rather than single copy of Ins1) developed early diabetes and no mice with two copies of either gene developed early diabetes. Islets of the diabetic male NOD( Ins1+/-,Ins2-/-) at this early age had no lymphocyte infiltration. Instead there was heterogeneous (between islet cells) weak staining for insulin. Although only male NOD( Ins1+/-,Ins2-/-) mice developed diabetes, both male and female NOD( Ins1+/-,Ins2-/-) mice had markedly decreased insulin content. In NOD( Ins1+/+,Ins2-/-), there was also a significant decrease in insulin content, whereas NOD( Ins1-/-,Ins2+/+) mice, and even NOD( Ins1-/-,Ins2+/-) mice, were normal. Male NOD( Ins1+/-,Ins2-/-) mice were completely rescued from diabetes by introduction of a transgene encoding proinsulin. On i.p. insulin tolerance testing, male mice had insulin resistance compared with female mice. CONCLUSIONS/INTERPRETATION: These results suggest that Ins1 is a 'defective gene' relative to Ins2, and that the mouse lines created provide a novel model of sex-dimorphic insulin-deficient diabetes.

The wide distribution of endornaviruses, large double-stranded RNA replicons with plasmid-like properties.

The International Committee on Taxonomy of Viruses (ICTV) recently accepted Endornavirus as a new genus of plant dsRNA virus. We have determined the partial nucleotide sequences of the RNA-dependent RNA polymerase regions from the large dsRNAs (about 14 kbp) isolated from barley (Hordeum vulgare), kidney bean (Phaseolus vulgaris), melon (Cucumis melo), bottle gourd (Lagenaria siceraria), Malabar spinach (Basella alba), seagrass (Zostera marina), and the fungus Helicobasidium mompa. Phylogenetic analyses of these seven dsRNAs indicate that these dsRNAs are new members of the genus Endornavirus that are widely distributed over the plant and fungal kingdoms.

Comparison of muscular and articular factors in the progression of contractures after spinal cord injury in rats.

STUDY DESIGN: Experimental, controlled trial. OBJECTIVES: To identify the relationship between the muscular and articular factors in the progression of contractures after spinal cord injury (SCI). SETTING: Hiroshima University, Hiroshima, Japan. METHODS: In total, 48 female Wistar rats were used. The 24 experimental rats that underwent a spinal cord transection and the other 24 control rats that underwent a sham-operation were assessed at 2, 4, 8, 12, 16, or 24 weeks postsurgery. Knee joint motion was measured for flexion and extension. Myotomy of the transarticular muscles was then performed and range of motion was measured again. The degree of contractures was assessed by goniometry measuring the femorotibial angle before and after the myotomies. RESULTS: The spinal cord-injured rats demonstrated flaccid paralysis during the first few days postsurgery and thereafter spastic paralysis. Intra- and inter-rater reliabilities for all measurements were >0.814. Knee flexion contractures developed in the all experimental rats, and progressed for the first 12 weeks and plateaued thereafter. Both the muscular (48+/-5%) and articular (52+/-5%) factors contributed almost equally to the overall progression of the contracture. CONCLUSION: The present findings may shed light on the underlying pathophysiology of contractures and should help guide research towards finding the elucidation of contracture development after SCI.

A possible association of Pro12Ala polymorphism in peroxisome proliferator-activated receptor gamma2 gene with obesity in native Javanese in Indonesia.

BACKGROUND: Peroxisome proliferators-activated receptor gamma (PPAR gamma) is a nuclear hormone receptor that serves as a master regulator of adipocytes-specific genes contributing to adipocytes differentiation, susceptibility to obesity, and insulin sensitivity. The substitution of proline to alanine at codon 12 of the PPAR gamma2 gene (Pro12Ala polymorphism) is most frequently identified and the associations with diabetes, obesity, and other clinical parameters have been reported and discussed in several ethnic groups. Among native Javanese ethnicity, however, there is no report about this polymorphism. AIMS AND METHODS: Aims of this study were to estimate the allele frequency of the Pro12Ala polymorphism of PPAR gamma2 gene among native Javanese in Indonesia and to investigate the relationship between this polymorphism and obesity or diabetes. This study included 540 native Javanese subjects consisting of 337 diabetic patients and 203 normal glucose tolerance subjects. Both groups included totally 160 obese subjects (body mass index > or = 25 kg/m(2)). PCR-restriction fragment length polymorphism was used for the genotype determination. RESULTS: The allele frequency of Pro12Ala polymorphism in PPAR gamma2 gene among native Javanese is lower than that in other ethnic groups. No association is seen between the Pro12Ala and diabetes (0.01 vs 0.017%, p = 0.404), a trend of the higher BMI was observed in Pro12Ala carriers in nondiabetic subjects, although this association is limited by small numbers. CONCLUSION: In this study, no association is seen between the Pro12Ala polymorphism in PPAR gamma2 gene and diabetes; a weak association with obesity is seen.

Differential immune response to B:9-23 insulin 1 and insulin 2 peptides in animal models of type 1 diabetes.

Mice have two insulin genes that differ in the insulin sequence by two amino acids, including the B9 position. Given prior studies of the B:9-23 insulin peptide in NOD mice, a fundamental question is whether the immune response to the B:9-23 peptide of the two insulins is identical. We investigate responses to the immunization with B:9-23 insulin 1 and 2 peptides in NOD and RIP-B7.1 Balb/c mice. NOD and F1 (Balb/c x C57/Bl6) B7.1 transgenic mice were given either B:9-23 insulin 1, B:9-23 insulin 2 or tetanus toxoid (TT) control peptide. Insulin autoantibodies (IAA), and anti-B:9-23 antibodies (IgG1 and IgG2c) were measured. Subcutaneous injection of the insulin 2 but not the insulin 1 peptide significantly protected NOD mice from diabetes. Conceptually similar, insulin 1 peptide immunization accelerated diabetes in the B7.1 mice compared with insulin 2 peptide. Insulin 1 and 2 peptides induced similar levels of IAA in the NOD mice except at week 26, where insulin 2 induced higher levels of IAA. Anti-IgG1 B:9-23 peptide antibodies were higher in the insulin 2 immunized group of NOD mice, while IgG2c anti-B:9-23 peptide antibodies were higher in the insulin 1 group. Adoptive transfer of splenocytes from insulin 1 immunized mice to NOD.scid mice demonstrated accelerated diabetogenicity. The protection afforded by insulin 2 peptide but not insulin 1 peptide in the NOD mouse is reflected by its predominant Th2 humoral response. This may relate to the protection conferred by the insulin 1 knockout when bred onto NOD mice in contrast to acceleration of disease with an insulin 2 knockout.