Retinoic Acid Deficiency Underlies the Etiology of Midfacial Defects.

Embryonic craniofacial development depends on the coordinated outgrowth and fusion of multiple facial primordia, which are populated with cranial neural crest cells and covered by the facial ectoderm. Any disturbance in these developmental events, their progenitor tissues, or signaling pathways can result in craniofacial deformities such as orofacial clefts, which are among the most common birth defects in humans. In the present study, we show that Rdh10 loss of function leads to a substantial reduction in retinoic acid (RA) signaling in the developing frontonasal process during early embryogenesis, which results in a variety of craniofacial anomalies, including midfacial cleft and ectopic chondrogenic nodules. Elevated apoptosis and perturbed cell proliferation in postmigratory cranial neural crest cells and a substantial reduction in Alx1 and Alx3 transcription in the developing frontonasal process were associated with midfacial cleft in Rdh10-deficient mice. More important, expanded Shh signaling in the ventral forebrain, as well as partial abrogation of midfacial defects in Rdh10 mutants via inhibition of Hh signaling, indicates that misregulation of Shh signaling underlies the pathogenesis of reduced RA signaling-associated midfacial defects. Taken together, these data illustrate the precise spatiotemporal function of Rdh10 and RA signaling during early embryogenesis and their importance in orchestrating molecular and cellular events essential for normal midfacial development.

Effects of a combined exercise plus diet program on cardiorespiratory fitness of breast cancer patients.

BACKGROUND: Decreases in cardiorespiratory fitness among breast cancer patients have often been reported in previous studies, affecting patients' health and survival. Peak oxygen uptake ([Formula: see text]) is the gold standard for assessing cardiorespiratory fitness and is inversely correlated with cardiovascular disease among women with breast cancer. Some previous studies have reported that aerobic exercise and proper diet positively influence [Formula: see text]. However, almost all studies have been conducted in the Western countries, and few studies are investigating on Asian women who have lower BMI compared with Western ones. PURPOSE: Investigating the effects of a combined exercise and diet program among Japanese cancer patients undergoing therapy on [Formula: see text]. METHODS: Thirty-two Japanese women with breast cancer undergoing endocrine therapy (age; 50 ± 6 years, body weight; 59 ± 10 kg) were voluntarily assigned to either intervention group (n = 21) or control group (n = 11). The intervention group completed a 12-week combined exercise plus diet program, consisting of weekly aerobic exercise and maintaining a nutritionally well-balanced 1200 kcal/day diet. The control group was instructed to continue with their usual activities. Anthropometric indices and [Formula: see text] were measured at baseline and after the 12-week program. RESULTS: All 21 women completed the 12-week program. The [Formula: see text] significantly increased from 26.7 to 30.4 mL/kg/min (1.57-1.62 L/min) in the intervention group, while it remained unchanged (26.9-26.9 mL/kg/min) in the control group. Mean reduction of body mass index was - 2.1 in the intervention group (P < .001) and + 0.1 in the control group. CONCLUSIONS: Our combined exercise plus diet program may contribute to improvement in cardiorespiratory fitness and body weight compared with control group.

Correction to: Effects of a combined exercise plus diet program on cardiorespiratory fitness of breast cancer patients.

In the original publication of this article, Table 1 was published incorrectly. The correct Table 1 is given in the following page.

Association of arch height with ankle muscle strength and physical performance in adult men.

Differences in arch height may have a certain impact on lower extremity muscle strength and physical performance. However, there is little evidence from investigation of the possible correlation of arch height with ankle muscle strength and physical performance measures. Sixty-seven participants took part in this study. Arch height index (AHI) was assessed and categorized using a 3-dimension foot scanner. Ankle muscle strength was measured employing a dynamometer. Physical performance measures including agility, force and proprioception were randomly tested. Compared to the medium AHI, the high AHI had lower plantarflexion and inversion peak torque. The high AHI also had lower peak torque per body weight value for plantarflexion and inversion at 120°/s (P = 0.026 and 0.006, respectively), and dorsiflexion at 30°/s (P = 0.042). No significant ankle muscle strength difference was observed between the low and medium AHI. Additionally, AHI was negatively correlated with eversion and inversion peak torque at 120°/s, and negatively associated with plantarflexion, eversion and inversion peak torque per body weight at both 30°/s and 120°/s (r ranged from -0.26 to -0.36, P values < 0.050). However, no significant relationship was found between arch height and physical performance measures. The results showed that high arches had lower ankle muscle strength while low arches exhibited greater ankle muscle strength. Arch height was negatively associated with ankle muscle strength but not related to physical performance. We suggest that the lower arch with greater ankle muscle strength may be an adaptation to weight support and shock absorption.

Comparison of the T2 relaxation time of the temporomandibular joint articular disk between patients with temporomandibular disorders and asymptomatic volunteers.

BACKGROUND AND PURPOSE: T2 relaxation time is a quantitative MR imaging parameter used to detect degenerated cartilage in the knee and lumbar intervertebral disks. We measured the T2 relaxation time of the articular disk of the temporomandibular joint in patients with temporomandibular disorders and asymptomatic volunteers to demonstrate an association between T2 relaxation time and temporomandibular disorder MR imaging findings. MATERIALS AND METHODS: One hundred forty-four patients with temporomandibular disorders and 17 volunteers were enrolled in this study. An 8-echo spin-echo sequence for measuring the T2 relaxation times was performed in the closed mouth position, and the T2 relaxation time of the entire articular disk was measured. Patients were classified according to the articular disk location and function, articular disk configuration, presence of joint effusion, osteoarthritis, and bone marrow abnormalities. RESULTS: The T2 relaxation time of the entire articular disk was 29.3 ± 3.8 ms in the volunteer group and 30.7 ± 5.1 ms in the patient group (P = .177). When subgroups were analyzed, however, the T2 relaxation times of the entire articular disk in the anterior disk displacement without reduction group, the marked or extensive joint effusion group, the osteoarthritis-positive group, and the bone marrow abnormality-positive group were significantly longer than those in the volunteer group (P < .05). CONCLUSIONS: The T2 relaxation times of the articular disk of the temporomandibular joint in patients with progressive temporomandibular disorders were longer than those of healthy volunteers.

Multiple-slice magnetic resonance imaging can detect visceral adipose tissue reduction more accurately than single-slice imaging.

BACKGROUND/OBJECTIVE: Imaging methods by magnetic resonance imaging are being increasingly used to quantify visceral adipose tissue (VAT), but there is no clear consensus as to a standardized protocol. We compared the ability of two commonly used imaging protocols (multiple slice versus single slice) to detect changes in VAT with diet or exercise. SUBJECTS/METHODS: We utilized data from the participants who completed our diet (n=22) or exercise (n=35) based weight-loss interventions. The intervention mainly comprised of weekly dietary modification sessions or aerobic exercise sessions over 12 weeks. Multiple-slice images obtained from T9 to S1 and a single-slice image at L4-L5 were compared using the effect size of the VAT change. In addition, we calculated the sample size needed to compare the two imaging protocols' ability to detect significant changes in VAT. RESULTS: VAT and subcutaneous adipose tissue volumes and areas, and other anthropometry decreased significantly after both the diet and exercise interventions. For VAT, a single-slice image had a lower effect size (diet: 1.23; exercise: 0.49) than the multiple-slice images (diet: 1.81; exercise: 0.90). The sample size required for multiple slice was substantially lower than for the single-slice with both weight-loss interventions. CONCLUSIONS: The different image protocols may lead to different results in relative VAT changes. Furthermore, single-slice imaging required a substantially larger sample size than multiple-slice imaging, and for researchers to detect smaller changes in VAT with single-slice imaging, a larger sample size would be needed. Thus, multiple-slice imaging has advantages for assessing VAT change in future clinical research.

Effects of structural anisotropy of cancellous bone on speed of ultrasonic fast waves in the bovine femur.

Ultrasonic waves in cancellous bone change dramatically depending on its structural complexity. One good example is the separation of an ultrasonic longitudinal wave into fast and slow waves during propagation. In this study, we examined fast wave propagation in cancellous bone obtained from the head of the bovine femur, taking the bone structure into consideration. We investigated the wave propagation perpendicular to the bone axis and found the two-wave phenomenon. By rotating the cylindrical cancellous bone specimen, changes in the fast wave speed due to the rotation angle then were observed. In addition to the ultrasonic evaluation, the structural anisotropy of each specimen was measured by X-ray micro-computed tomography (CT). From the CT images, we obtained the mean intercept length (MIL), degree of anisotropy (DA), and angle of insonification relative to the trabecular orientation. The ultrasonic and CT results showed that the fast wave speed was dependent on the structural anisotropy, especially on the trabecular orientation and length. The fast wave speeds always were higher for propagation parallel to the trabecular orientation. In addition, there was a strong correlation between the DA and the ratio between maximum and minimum speeds (V(max)/V(min)) (R(2) = 0.63).

The transport mechanisms of (222)Rn in soil at Tateishi as an anomaly spot in Japan.

The (222)Rn concentration profiles in soil have been measured at an anomaly spot in Tateishi, Japan. In winter, the concentrations were low and showed a negative gradient with depth, but in other seasons, the concentration had both positive and negative gradients with depth, and dramatically changed by time. On the assumption that there was ventilation in deep layers and with driving forces of wind and temperatures, these phenomena were successfully explained. This finding would contribute to a numerical model for (222)Rn transport in soil.

Repeated adenoviral administration into the biliary tract can induce repeated expression of the original gene construct in rat livers without immunosuppressive strategies.

BACKGROUND: Systemic adenoviral readministration appears to be limited by immunogenicity. AIMS: We examined the feasibility of repeated adenovirus mediated gene transfer into the liver via the biliary tract. METHODS: Recombinant adenoviruses carrying a reporter lacZ gene were infused retrogradely into the common bile duct of rats. Transduction efficiency of the lacZ gene was estimated histochemically and quantitatively. RESULTS: Retrograde administration of recombinant adenoviruses into the common bile duct of rats resulted in efficient transgene expression in the liver, specifically in hepatocytes, but not in biliary epithelia. Transduction efficiency induced by intrabiliary adenoviral administration was not substantially different from that induced by intraportal adenoviral infusion. Transgene expression in the liver was however transient, and development of neutralising antibodies against adenovirus was observed in serum but not in bile. When adenoviruses were readministered into the common bile duct, successful re-expression of the transgene in the liver was achieved despite the existence of neutralising antibodies in serum. Interestingly, although proliferation of adenovirus specific T cells in response to adenoviral readministration was suppressed significantly by immunosuppressive FK506 treatment, levels of transgene expression in the liver achieved by intrabiliary adenoviral readministration were not significantly different between animals treated with and without FK506. Furthermore, third adenoviral administration into the common bile duct also induced successful transgene expression in the liver. CONCLUSIONS: These results suggest that adenovirus mediated gene transfer into the liver may be repeatable without immunosuppressive strategies in clinical settings by means of endoscopic retrograde cholangiography.

Two cases of colonic tuberculosis presenting with massive melena.

The clinical symptoms of colonic tuberculosis are variable, among which massive melena is extremely rare. Herein, we report two cases of colonic tuberculosis representing with massive melena, both of whom never had active pulmonary tuberculosis. The first case was a 55-year-old woman. Although her emergency colonoscopic setting suggested colonic tuberculosis, no evidence of tuberculosis could be found at that time. We performed a therapeutic trial and observed a drastic regression of the initial changes with 4-week treatment using antituberculous agents. The second case was a 37-year-old man. His emergency colonoscopy showed lesions mimicking colon carcinoma. However, the histological examinations did not indicate malignancy. The polymerase chain reaction of colonic biopsy specimen was positive for Mycobacterium tuberculosis. Similar to the first case, a significant improvement of the initial lesions was observed after 4-week treatment using antituberculous agents. Collectively, although the massive melena is a rare manifestation, tuberculosis of the colon should be suspected in the patients with such symptom.

Enzymatic synthesis of cross-linkable polyesters from renewable resources.

Enzymatic synthesis of a new class of cross-linkable polyesters has been achieved. Polymerization of divinyl sebacate and glycerol using Candida antarctica lipase as catalyst in the presence of unsaturated higher fatty acids produced the polyesters having an unsaturated group in the side chain. The polyester was subjected to hardening by cobalt naphthenate catalyst or thermal treatment, yielding cross-linked transparent film.

[Pneumatosis intestinalis after allogeneic bone marrow transplantation for acute lymphocytic leukemia].

A 45-year-old man was diagnosed as having acute lymphocytic leukemia (ALL) in February 1997. Complete remission was achieved by chemotherapy, and allogeneic BMT from his HLA-identical sister was performed on November 13, 1997. He developed acute GVHD (grade II), but quickly recovered after methyl-PSL pulse therapy. On June 5, 1998--day 202 after BMT--abdominal pain developed. X-ray and CT examinations showed pneumatosis intestinalis, pneumoperitoneum, pneumomediastinum and abdominal free air. We performed oxygen administration and methyl-PSL pulse therapy, and this quickly improved the symptoms. Corticosteroid and chronic GVHD were thought to be the causative factors of pneumatosis intestinalis in this case. Although pneumatosis intestinalis is relatively rare, it is one of the important potential complications that can occur after allogeneic BMT.

A potential approach for electrochemotherapy against colorectal carcinoma using a clinically available alternating current system with bipolar snare in a mouse model.

BACKGROUND: Although electrochemotherapy appears promising for the treatment of superficial tumors, its usefulness against internal tumors, such as colorectal carcinoma (CRC), has not been well examined. Furthermore, since direct current electric pulses have been used for electropermeabilization of tumors in all in vivo electrochemotherapy studies, including clinical trials, the usefulness of alternating current systems has not been examined at all. In a mouse model it was examined whether the alternating current system with a bipolar snare, which has been employed already as a clinical endoscopic treatment modality, was useful for electrochemotherapy against CRC. METHODS: Murine CRC colon 26 cells were implanted subcutaneously into syngeneic BALB/c mice and electrochemotherapy with bleomycin (BLM) using the alternating current system was performed against established CRC tumors. RESULTS: Electrochemotherapy significantly suppressed the growth of established CRC tumors, resulting in significantly prolonged survival of animals with CRC. Histological examination revealed that electrochemotherapy caused massive necrosis of CRC tumors. Subsequent analysis revealed that the delivery of alternating current electric pulses to CRC tumors profoundly increased intratumoral amounts of BLM. CONCLUSIONS: Because the alternating current system using a bipolar snare has been used widely as an endoscopic treatment modality in clinical settings, these results indicate that electrochemotherapy using the alternating current system may be a promising approach for the treatment of CRC.

A novel type II cytokeratin, mK6irs, is expressed in the Huxley and Henle layers of the mouse inner root sheath.

Hair follicle differentiation involves the expression of both epithelial-type keratins or cytokeratins and hair keratins as well as hair keratin-associated proteins. In this study, a cDNA clone encoding a cytokeratin family member was isolated using RNA differential display techniques. The predicted amino acid sequence derived from this clone, revealed a homology with a number of cytokeratins, not only in the central alpha-helical regions but also in the conserved portions of the amino and carboxy terminal domains, indicating that this protein represents a new member of the mouse type II cytokeratin family. Northern blot analysis showed expression in mouse skin, but not in other tissues, including tongue, esophagus, and forestomach. One- and two-dimensional western blot analysis showed that this new cytokeratin was 57 kDa in size and ran slightly below the area of cytokeratin 5, which corresponded to that of the cytokeratin 6 family members. Both RNA in situ hybridization and immunohistochemical studies of mouse anagen hair follicles demonstrated expression of this cytokeratin in the inner root sheath hair cone during anagen III and in the Henle and Huxley layers of the inner root sheath during anagen VI. The expression of the new cytokeratin began in the hair bulb and progressed up to the height of the keratogenous zone. Taken together the sum of the data analyzed, we have termed this novel cytokeratin mK6irs (mouse gene nomenclature k2-6g) to indicate both its similar mobility with K6 in two-dimensional gels and its specific expression in the inner root sheath of the hair follicle.

Intravenous readministration of an adenoviral vector performed long after the initial administration failed to induce re-expression of the original transgene in rats.

Although most humans have been exposed to wild-type adenoviruses in their childhood, titers of neutralizing antibodies against viruses decrease with the passage of time. In the present study, we infused adenoviruses carrying the lacZ gene into the tail vein of rats, and re-infused the same adenoviruses long after the initial administration. However, development of neutralizing antibodies against adenovirus and proliferation of adenovirus-specific T cells were elicited profoundly by adenoviral readministration, and transgene expression was not induced in rats. Our results may have important implications for efficacy considerations when adenoviral vectors are employed in clinical settings for the treatment of cancer.

Hepatic adenomas treated with percutaneous ethanol injection in a patient with glycogen storage disease type Ia.

We report a 20-year-old man with glycogen storage disease type Ia (GSD Ia) who presented multiple hepatocellular adenomas (HCAs) in 1993 and in whom percutaneous ethanol injection (PEI) was conducted as treatment for some enlarging tumors beneath the liver surface. In a 6-year follow-up period, we observed gradual enlargement of some of the HCAs, and the rapid growth of a newly developed tumor. In August 1996, one slow-growth HCA was 52 mm in diameter and was located beneath the surface of the liver. We conducted PEI therapy to prevent its spontaneous rupture. During the following year, another tumor developed beneath the liver surface, but showed extremely rapid growth, reaching 51 mm in diameter, from being undetectable, within 12 months. PEI therapy was again conducted for this newly developed tumor. Although additional PEI therapy was required for each tumor, because of suspected recurrence, no findings of discrete recurrence have been detected by computed tomography and magnetic resonance imaging for more than 2 years, up to the time of this study. We consider PEI to be a useful and effective therapeutic modality for individual HCAs in patients with GSD Ia.

Endotoxin clearance and its relation to hepatic and renal disturbances in rats with liver cirrhosis.

BACKGROUND/AIMS: Little is known about endotoxin clearance and secretion of cytokines from macrophages in liver cirrhosis. The aims of this study were to investigate the relationship of endotoxin clearance and release of tumor necrosis factor alpha by various macrophages to hepatic and renal disturbances in liver cirrhosis. METHODS: Male Sprague-Dawley rats were given 0.04% thioacetamide orally for 6 or 12 months. The organ distribution of infused [3H]-endotoxin (10 microg/kg b.w.) was analyzed at 30 min or at 24 h. Uptake of [3H]-endotoxin and secretion of tumor necrosis factor alpha by Kupffer cells, splenic macrophages and peripheral blood monocytes (1 x 10(4) cells/ml) from cirrhotic and control rats were determined. RESULTS: In cirrhotic rats, more endotoxin was left in the body and more endotoxin accumulated in the spleen and kidney, and thus was related to elevation of serum total bilirubin, aspartate aminotransferase, alanine aminotransferase, blood urea nitrogen, creatinine and tumor necrosis factor alpha. Endotoxin uptake and tumor necrosis factor alpha release by the Kupffer cells were decreased and those by the splenic macrophages and peripheral blood monocytes were increased in cirrhotic rats. CONCLUSIONS: In liver cirrhosis, impaired clearance of endotoxin together with increased secretion of tumor necrosis factor alpha by extrahepatic macrophages may play an important role in the progression of hepatic and renal disturbances.

Augmented hepatocellular carcinoma progression and depressed Kupffer cell activity in rat cirrhotic livers.

To examine the property of hepatocellular carcinoma (HCC), rat HCC cells were implanted into normal and cirrhotic rat livers. Implanted HCC grew much more progressively in cirrhotic livers than in normal livers. Kupffer cells were decreased profoundly in cirrhotic livers, resulting in markedly impaired phagocytic activity. Furthermore, production of Kupffer cell-related cytokines, such as interleukin-1 beta and tumor necrosis factor-alpha, was decreased profoundly in cirrhotic livers. Our results indicate that liver cirrhosis is a prominent promoting factor in HCC progression, and that markedly depressed Kupffer cell activity may play a role in augmented HCC progression in cirrhotic livers.

High-frequency SEP components generated in the somatosensory cortex of the monkey.

To investigate the origin of high-frequency somatosensory evoked potential (SEP) components, we recorded median nerve SEPs from the scalp and the depth in six monkeys. Laminar field potentials were analyzed in area 3b (N10; corresponding to human N20) and area 1 (P12; corresponding to human P25). After digital filtering (300-900 Hz), 4-6 components were identified, and the 1st to 4th peaks in area 3b (7-11 ms in latency) and the 3rd to 5th in area 1 (9-13 ms) showed clear polarity reversals between the surface and the depth of the cortex. These results provide direct evidence for intracortical origin of early high-frequency components in area 3b and of late ones in area 1.