Indium chloride bone marrow scintigraphy for hepatic myelolipoma: A case report.

BACKGROUND: As hepatic myelolipoma is rarely encountered, its radiological diagnosis using ultrasonography (US), computed tomography (CT), and magnetic resonance imaging (MRI) is challenging. Hepatic myelolipoma is similar to fat-contained hepatic lesions seen in hepatocellular carcinoma and angiomyolipoma. Therefore, further development of techniques to diagnose hepatic myelolipoma is warranted. CASE SUMMARY: A 44-year-old obese man was found to have a hepatic lesion during his medical checkup. The lesion was 50 mm × 57 mm in size and was detected in segment 8 (S8) of the liver by US. The patient was diagnosed with hepatic lesion 20 years ago, but it was left unresolved. The patient had no symptoms, liver dysfunction, hepatitis virus antibody, or tumor marker elevation. Plain CT showed a well-defined lesion in S8 of the liver. The central and peripheral areas of the lesion primarily exhibited fat density and hypodensity, respectively. MRI revealed a capsule-like structure. Biopsy was performed to address the probability of hepatocellular carcinoma. The lesion was pathologically confirmed as a myelolipoma. Bone marrow scintigraphy performed using 111InCl3 revealed accumulation of the radiopharmaceutical in the soft tissue component, except in the fat-dominant part of the tumor, as well as in the surrounding liver parenchyma due to the presence of reticuloendothelial cells in the liver. CONCLUSION: This is the first report on the diagnosis of hepatic myelolipoma using 111InCl3 scintigraphy. The effectiveness of bone marrow scintigraphy for diagnosing hepatic myelolipoma might be limited. As radiopharmaceuticals accumulate in both hematopoietic and reticuloendothelial cells, the accumulation of radiopharmaceuticals in the lesion is obscure.

Expansion and characterization of epithelial stem cells with potential for cyclical hair regeneration.

In mammals, organ induction occurs only during embryonic development except for hair follicles (HFs). However, HF-resident epithelial stem cells (HFSCs), which are responsible for repetitive HF regeneration, are not fully characterized. Here, we establish in vitro culture systems that are capable of controlling the ability of HFSCs to regenerate HFs. Based on a method that precisely controlled the number of HFs for regeneration, functional analysis revealed that CD34/CD49f/integrin ß5 (Itgß5)-triple-positive (CD34+/CD49f+/Itgß5+) cells have multipotency and functional significance for continual hair regeneration. In native HFs, these cells reside in the uppermost area of the bulge region, which is surrounded by tenascin in mice and humans. This study unveils the subpopulation of HFSCs responsible for long-term hair cycling of HFs regenerated from bioengineered HF germ, suggesting the presence of functional heterogeneity among bulge HFSCs and the utility of our culture system to achieve HF regenerative therapy.

Guidelines for the diagnosis and treatment of male-pattern and female-pattern hair loss, 2017 version.

Male-pattern hair loss (MPHL, androgenetic alopecia) is a slowly progressive form of alopecia which begins after puberty. In 2010, we published the first Japanese edition of guidelines for the diagnosis and treatment of MPHL. It achieved the original goal of providing physicians and patients in Japan with evidence-based information for choosing efficacious and safe therapy for MPHL. Subsequently, new therapeutic drugs and treatment methods have been developed, and women's perception of MPHL has undergone change and the term "female-pattern hair loss (FPHL)" is becoming more common internationally. Thus, here we report a revised version of the 2010 guidelines aimed at both MPHL and FPHL. In these guidelines, finasteride 1 mg daily, dutasteride 0.5 mg daily and topical 5% minoxidil twice daily for MPHL, and topical 1% minoxidil twice daily for FPHL, are recommended as the first-line treatments. Self-hair transplantation, irradiation by light-emitting diodes and low-level lasers, and topical application of adenosine for MPHL are recommended, whereas prosthetic hair transplantation and oral administration of minoxidil should not be performed. Oral administration of finasteride or dutasteride are contraindicated for FPHL. In addition, we have evaluated the effectiveness of topical application of carpronium chloride, t-flavanone, cytopurine, pentadecane and ketoconazole, and wearing a wig. Unapproved topical application of bimatoprost and latanoprost, and emerging hair regeneration treatments have also been addressed. We believe that the revised guidelines will improve further the diagnostic and treatment standards for MPHL add FPHL in Japan.

Bioengineering a 3D integumentary organ system from iPS cells using an in vivo transplantation model.

The integumentary organ system is a complex system that plays important roles in waterproofing, cushioning, protecting deeper tissues, excreting waste, and thermoregulation. We developed a novel in vivo transplantation model designated as a clustering-dependent embryoid body transplantation method and generated a bioengineered three-dimensional (3D) integumentary organ system, including appendage organs such as hair follicles and sebaceous glands, from induced pluripotent stem cells. This bioengineered 3D integumentary organ system was fully functional following transplantation into nude mice and could be properly connected to surrounding host tissues, such as the epidermis, arrector pili muscles, and nerve fibers, without tumorigenesis. The bioengineered hair follicles in the 3D integumentary organ system also showed proper hair eruption and hair cycles, including the rearrangement of follicular stem cells and their niches. Potential applications of the 3D integumentary organ system include an in vitro assay system, an animal model alternative, and a bioengineered organ replacement therapy.

Five-year efficacy of finasteride in 801 Japanese men with androgenetic alopecia.

Finasteride is standard medical treatment for androgenetic alopecia; however, no large studies with 5 years or more of follow up have been performed in Japan. The authors followed Japanese men with androgenetic alopecia treated with finasteride for 5 years to evaluate long-term treatment efficacy. Of 903 men treated with finasteride (1 mg/day), 801 patients were evaluated over 5 years by modified global photographic assessment. Although the proportion of improvement was high (99.4%), modified global photographic assessment scores after 5 years of treatment were lower in patients with more advanced disease as measured by the modified Norwood-Hamilton scale. After separating patients into "sufficient" and "insufficient" efficacy groups according to the modified global photographic assessment score after 5 years (scores ≥6 and <6, respectively), multivariate analysis showed that independent risk factors of insufficient efficacy were age at start of treatment of 40 years or more (P = 0.021) and classification on the modified Norwood-Hamilton scale (P < 0.001), whereas presence of stress at start of treatment was a negative predictor (P = 0.025). In conclusion, continuous finasteride treatment for 5 years improved androgenetic alopecia with sustained effect among Japanese. Younger age and less advanced disease at start of treatment were the key predictors of higher finasteride efficacy.

Hair organ regeneration via the bioengineered hair follicular unit transplantation.

Organ regenerative therapy aims to reproduce fully functional organs to replace organs that have been lost or damaged as a result of disease, injury, or aging. For the fully functional regeneration of ectodermal organs, a concept has been proposed in which a bioengineered organ is developed by reproducing the embryonic processes of organogenesis. Here, we show that a bioengineered hair follicle germ, which was reconstituted with embryonic skin-derived epithelial and mesenchymal cells and ectopically transplanted, was able to develop histologically correct hair follicles. The bioengineered hair follicles properly connected to the host skin epithelium by intracutaneous transplantation and reproduced the stem cell niche and hair cycles. The bioengineered hair follicles also autonomously connected with nerves and the arrector pili muscle at the permanent region and exhibited piloerection ability. Our findings indicate that the bioengineered hair follicles could restore physiological hair functions and could be applicable to surgical treatments for alopecia.

Fully functional hair follicle regeneration through the rearrangement of stem cells and their niches.

Organ replacement regenerative therapy is purported to enable the replacement of organs damaged by disease, injury or aging in the foreseeable future. Here we demonstrate fully functional hair organ regeneration via the intracutaneous transplantation of a bioengineered pelage and vibrissa follicle germ. The pelage and vibrissae are reconstituted with embryonic skin-derived cells and adult vibrissa stem cell region-derived cells, respectively. The bioengineered hair follicle develops the correct structures and forms proper connections with surrounding host tissues such as the epidermis, arrector pili muscle and nerve fibres. The bioengineered follicles also show restored hair cycles and piloerection through the rearrangement of follicular stem cells and their niches. This study thus reveals the potential applications of adult tissue-derived follicular stem cells as a bioengineered organ replacement therapy.

Single follicular unit transplantation reconstructs arrector pili muscle and nerve connections and restores functional hair follicle piloerection.

The autologous transplantation of hair follicles that have been separated into single follicular units is an accepted treatment for androgenetic alopecia. Recent studies demonstrate that the multiple stem cell populations and surrounding cutaneous tissues coordinately regulate the hair follicle functions and skin homeostasis. Therefore, the critical issues for consideration regarding functional hair restoration therapy are reproduction the correct connectivity and cooperation with host cutaneous tissues, including the arrector pili muscle (APM) and nerve system. We report successful establishment of mouse single follicular transplantation model and autonomous restoration of transplanted hair follicle piloerection in mouse skin. Transplanted hair follicles were responsive to the neurotransmitter acetylcholine and formed proper connections with surrounding host tissues such as APM and nerve fibers, which in turn connect with not only the hair follicle bulge region but also the APM. These results demonstrate that the piloerection ability of transplanted hair follicles can be estimated quantitatively. This study makes a substantial contribution towards the development of transplantation therapy that will facilitate future functional regeneration therapy for skin and skin appendages.

Evaluation of efficacy and safety of finasteride 1 mg in 3177 Japanese men with androgenetic alopecia.

Before now, there has been no study of finasteride use exceeding 1 year in Japanese men with androgenetic alopecia (AGA) except the study subsequently conducted from the development phase. Since the launch of finasteride, no study in a larger population had been reported. Ethnic variation of the onset age, progressive nature and degree of hair loss of androgenetic alopecia are known. The therapeutic effect of oral finasteride (Propecia) was examined on androgenetic alopecia of Japanese men. The efficacy and safety of finasteride (1 mg tablet) was evaluated in Japanese men with AGA in the long term. The study enrolled 3177 men given finasteride 1 mg/day from January 2006 to June 2009 at our clinic. Efficacy was evaluated in 2561 men by the modified global photographic assessment; the photographs were assessed using the standardized 7-point rating scale. Safety data were assessed by interviews and laboratory tests in all men enrolled in the study. The overall effect of hair growth was seen in 2230 of 2561 men (87.1%), in whom hair greatly (11.1%), moderately (36.5%) and slightly (39.5%) increased. The response rate improved with increasing duration of treatment. Adverse reactions occurred in 0.7% (23/3177) of men; seven men discontinued treatment based on risk-benefit considerations. No specific safety problems associated with long-term use were observed. This study represents data collected at a single institution. Many patients did not receive follow-up examination. In Japanese men with AGA, oral finasteride used in the long-term study maintained progressive hair regrowth without recognized side-effect.

Polymorphic CAG repeat numbers in the androgen receptor gene of female pattern hair loss patients.

Female pattern hair loss (FPHL) is frequently referred to as female androgenetic alopecia (FAGA). However, the role of androgen in this type of hair loss remains uncertain. We previously reported greater therapeutic efficacy of finasteride in Japanese male androgenetic alopecia (MAGA) patients in cases where the CAG repeats of the androgen receptor (AR) gene were short. To examine the correlation between CAG repeat numbers and the therapeutic efficacy of finasteride in FPHL patients, the efficacy of finasteride (1 mg/day) was evaluated macroscopically. Because women have two X-chromosomes, the shorter and longer CAG repeat numbers were analyzed in 37 Japanese FPHL patients, then the correlation of these factors was statistically analyzed by anova. No statistical significance in terms of the differences in CAG repeat numbers was detected among the four groups classified on the basis of the efficacy of finasteride. From these results, it may be concluded that the efficacy of this medicine in each FPHL patient cannot be predicted by the CAG repeat numbers in the AR gene.

Intralesional laser treatment of voluminous vascular lesions in the oral cavity.

OBJECTIVE: In laser treatment of voluminous vascular lesions, there are many cases in which submucosally located angioma remnants cannot be reached by noncontact superficial laser application. To diminish these remnants we used intralesional photocoagulation (ILP) in treatment of oral vascular lesions, because this approach is effective in treatment of voluminous vascular lesions of the skin. STUDY DESIGN: Four cases of voluminous vascular malformation in the oral cavity were treated by ILP using a potassium-titanyl-phosphate (KTP) laser. In 1 case, treatment was carried out under ultrasound and manual control. RESULTS: All lesions showed more than 70% regression after the first ILP session, and the treatment outcome was satisfactory. There were no serious complications, such as bleeding or invasive infection. Ultrasonography was useful for guiding laser treatment in the oral cavity. CONCLUSION: Intralesional photocoagulation treatment with a KTP laser is effective and safe for treatment of a vascular lesion in the oral cavity.

Consumption of commercial whole and non-fat milk increases the incidence of 7,12-dimethylbenz(a)anthracene-induced mammary tumors in rats.

BACKGROUND: Breast cancer has become the most common cancer among women worldwide. Although the consumptions of milk and dairy products were considered to be a risk factor for breast cancer in some epidemiological studies, the results were inconsistent. METHODS: In the present study, female Sprague-Dawley rats received a single oral dose of 5mg 7,12-dimethylbenz(a)anthracene (DMBA). One week later, the animals were divided into four groups: whole milk (WM), artificial whole milk (A-WM), non-fat milk (NFM) or artificial non-fat milk (A-NFM) mixed with commercial powder chow. Rats were palpated weekly to monitor tumor development. At week 20 after DMBA administration, rats were decapitated and the volume and weight of mammary tumor were recorded. RESULTS: Tumor incidence, the cumulative number of tumors and the sums of tumor volume were higher in the WM and NFM groups than in the A-WM and A-NFM groups both at palpation and at autopsy. CONCLUSION: Combining our previous studies, we found the consumption of milk promoted the development of DMBA-induced mammary tumors in rats independent of the fat level.

One-day dietary restriction changes hepatic metabolism and potentiates the hepatotoxicity of carbon tetrachloride and chloroform in rats.

Although dietary restriction (DR) is common in modern society, research about hepatic metabolism and the hepatotoxicity induced by DR has been conducted less intensively than that induced by fasting. In the present study, we fed male Wistar rats at five levels of food intake for one day, including conventional feeding (60 kcal), three of DR (45, 30, and 15 kcal), and fasting (0 kcal), and observed the metabolic changes of hepatic cytochrome P450 2E1(CYP2E1) and the hepatotoxicity of chloroform (CHCl(3)) and carbon tetrachloride (CCl(4)). The CYP2E1 content was significantly increased in 15 kcal-food and fasting groups. The hepatic glutathione (GSH) content, which protects the liver from hepatotoxic agents, was depleted in 15 kcal-food and fasting groups. After the challenge by CHCl(3) and CCl(4), the activities of aspartate aminotransferase and alanine aminotransferase, marker enzymes for liver damage, were elevated remarkably at all food groups. Moreover, their activities increased significantly in DR groups, in comparison to the corresponding 60 kcal-food group. After the challenge, the hepatic GSH content was also depleted significantly in 15 kcal-food and fasting groups. CHCl(3) was cleared by hepatic metabolism about 8-10 times faster than that of CCl(4). Similarly, the areas under the blood concentration-time curve of CCl(4) was as much as twice that of the corresponding CHCl(3). In conclusion, when food was restricted to less than half of conventional amount, hepatic metabolism was affected and the hepatotoxicity induced by CCl(4) or CHCl(3) was augmented by, at least in part, CYP2E1 induction and GSH depletion.

Commercial cows' milk has uterotrophic activity on the uteri of young ovariectomized rats and immature rats.

Cows' milk contains considerable quantities of estrogens, mainly in the form of estrone sulfate (ES). To determine whether the commercial milk has any biologically significant hormonal effects, 2 series of uterotrophic tests were performed, 1 with young ovariectomized rats and the other with sexually immature rats. Thirty-six rats were used for each test. They were divided into 3 groups of 12 animals each, and were kept for 7 days on powdered chow with 1 of 3 drinking solutions: low-fat milk (LFM), artificial milk (AM, negative control), or AM containing ES at 100 ng/ml (positive control). At autopsy, both the wet and blotted uterine weights were measured. The cell heights of uterine epithelia in ovariectomized rats were also determined. The significance of differences among groups was tested by Dunnett's multiple comparisons test. In each test, the weights of the uteri in the LFM group were significantly greater than those of the respective weights in the AM group (p < 0.01). Furthermore, in ovariectomized rats, the uterine epithelial-cell height in the LFM group was significantly greater than that observed in the AM group (p < 0.01). The uterotrophic effect of 100 ng/ml ES solution was greater than that of LFM in immature rats (p < 0.01), whereas the effect of the solution was almost comparable to that of LFM in young ovariectomized rats (p > 0.05). In conclusion, commercially available milk has uterotrophic effects in both young ovariectomized rats and sexually immature rats.

Testing potential effect of environmental endocrine disruptors in cow milk on reproductive index in female rats.

OBJECTIVE: To study the effect of endocrine disruptor chemicals in cow milk on female reproductive system. METHODS: A two-generation reproduction was conducted according to U. S. FDA standard. Milk was fed in special bottle to Wistar rats of both sexes through two successive generations (F0 and F1) in the milk group while artificial milk was fed to rats in the control group. Twenty-four rats of each sex were mated in each group. Measurements were made according to this guideline. RESULTS: Reproductive parameters in the milk group such as fertility index, gestation index, weights of uterus and ovary, days of vaginal opening, estrous cycles, histological morphological changes were comparable to those in the control group. However, the means of body weight had some differences. The body weight gains increased significantly in the milk-treated group in F1 and F2 generation compared with those in the control group. The concentration of insulin-like growth factor-1 (IGF-1) in blood in the milk group was comparable to that in the control group, but the standard deviation changed greatly in the milk-treated rats. CONCLUSION: Endocrine disruptor chemicals in milk have no severe effects on the female reproductive system.

Voglibose potentiates the hepatotoxicity of carbon tetrachloride and acetaminophen by inducing CYP2E1 in rats.

BACKGROUND: : Voglibose is an alpha-glucosidase inhibitor used to decrease postprandial hyperglycemia in diabetic patients. Although clinical concern has not yet been raised, hepatic dysfunction has been reported in a few patients taking this drug. METHOD: : In the present study, we studied the effects of voglibose on the hepatotoxicity of carbon tetrachloride (CCl(4)) and acetaminophen (APAP) in rats, since both of these agents exert their effects through isoforms of cytochrome P450. Male Sprague-Dawley rats were given a daily ration (20g) of powdered chow diet containing 0, 2.5, 5.0 or 10.0mg/100g of voglibose. Three weeks later, the rats were challenged with either 0.50g/kg CCl(4) orally or 0.75g/kg APAP intraperitoneally for biochemical examinations or killed for an in vivo metabolism study. RESULTS: : Voglibose at these three experimental doses potentiated CCl(4) and APAP hepatotoxicity, as evidenced by significantly increased levels of both plasma asparate transaminase (AST) and alanine transaminae (ALT). The glutathione (GSH) content was decreased while malondialdehyde (MDA) increased in the liver after CCl(4) or APAP administration. Hepatic cytochrome P450 2E1 (CYP2E1) concentration was increased at doses of 5.0 and 10.0mg/100g of voglibose and its activity increased in the three voglibose dosage groups, while hepatic cytochrome P450 3A (CYP3A) and cytochrome P450 1A2 (CYP1A2) were only slightly changed at any dose. CONCLUSION: : Our study demonstrated that voglibose can potentiate CCl(4) and APAP hepatotoxicity in rats by inducing hepatic CYP2E1.

Cerebral regional cortical blood flow response during joint stimulation in cats.

Noxious stimulation of an elbow joint in the anesthetized cat increases cerebral blood flow over broad, bilateral areas of the cerebral cortex and increases systemic blood pressure. In order to eliminate the confounding effects of elevated blood pressure on cerebral blood flow, we re-examined this phenomenon in cats with a transected spinal cord at the T1 level. Noxious stimulation of an elbow joint resulted in a significant increase in blood flow in the forelimb area of the contralateral primary somatosensory cortex; the blood pressure remained unchanged. These data in cats suggest that the previously described bilateral increase in cerebral blood flow following noxious joint stimulation was due, in part, to the increased blood pressure.

The possible role of female sex hormones in milk from pregnant cows in the development of breast, ovarian and corpus uteri cancers.

The continued increase in incidence of some hormone-related cancers worldwide is of great concern. Although estrogen-like substances in the environment were blamed for this increase, the possible role of endogenous estrogens from food has not been widely discussed. We are particularly concerned about cows' milk, which contains a considerable quantity of estrogens. When we name cows' milk as one of the important routes of human exposure to estrogens, the general response of Western people is that "man has been drinking cows' milk for around 2000 years without apparent harm." However, the milk that we are now consuming is quite different from that consumed 100 years ago. Unlike their pasture-fed counterparts of 100 years ago, modern dairy cows are usually pregnant and continue to lactate during the latter half of pregnancy, when the concentration of estrogens in blood, and hence in milk, increases. The correlation of incidence and mortality rates with environmental variables in worldwide countries provides useful clues to the etiology of cancer. In this study, we correlated incidence rates for breast, ovarian, and corpus uteri cancers (1993-97 from Cancer Incidence in Five Continents) with food intake (1961-97 from FAOSTAT) in 40 countries. Meat was most closely correlated with the breast cancer incidence (r=0.827), followed by milk (0.817) and cheese (0.751). Stepwise multiple-regression analysis (SMRA) identified meat as the factor contributing most greatly to the incidence of breast cancer ([R]=0.862). Milk was most closely correlated with the incidence of ovarian cancer (r=0.779), followed by animal fats (0.717) and cheese (0.697). SMRA revealed that milk plus cheese make the greatest contribution to the incidence of ovarian cancer ([R]=0.767). Milk was most closely correlated with corpus uteri cancer (r=0.814), followed by cheese (0.787). SMRA revealed that milk plus cheese make the most significant contribution to the incidence of corpus uteri cancer ([R]=0.861). In conclusion, increased consumption of animal-derived food may have adverse effects on the development of hormone-dependent cancers. Among dietary risk factors, we are most concerned with milk and dairy products, because the milk we drink today is produced from pregnant cows, in which estrogen and progesterone levels are markedly elevated.

Effects of fiber intake on the blood pressure, lipids, and heart rate in Goto Kakizaki rats.

OBJECTIVE: The prevalence of hypertension in individuals with diabetes mellitus is higher than that in individuals without diabetes mellitus. High fiber intake decreases blood glucose and lipids levels. This study investigated the effects of cereal fiber intake on systolic and diastolic blood pressures in a rat model of type 2 diabetes mellitus. METHODS: Thirty male Goto Kakizaki rats were randomly assigned to one of three groups. Each group was fed a barley diet, a white rice diet, or cornstarch diet. The rats were pair fed for 16 wk. Systolic and diastolic blood pressures were measured once every 4 wk by the photoelectric oscillometric tail-cuff method without anesthesia. RESULTS: The barley diet significantly decreased systolic blood pressure from week 12 and decreased the plasma levels of total cholesterol, triacylglycerol, and low-density lipoprotein cholesterol. There were significant positive correlations between plasma lipids levels and systolic blood pressure. CONCLUSIONS: High fiber intake has beneficial effects on systolic blood pressure and blood lipids levels and suggests that fiber intake should be increased in individuals who have diabetes mellitus to prevent complications.

A two-generation reproduction study to assess the effects of cows' milk on reproductive development in male and female rats.

OBJECTIVE: To examine whether the considerable quantities of increased female sex hormone levels found in modern milk as a result of modern dairy farming practices are safe for human consumption. DESIGN: Males and females of the P generation were maintained on a diet containing milk for 10 weeks before mating. Exposure to milk was continued up to the end of weaning of the F2b offspring. SETTING: Two-generation reproduction study. ANIMAL(S): Male and female Wistar Galas rats. INTERVENTION(S): P- and F1-generation rats were mated. MAIN OUTCOME MEASURE(S): Fertility, fecundity, and morphology and function of reproductive organs. RESULT(S): Although milk had growth-promoting effects in both parents and offspring, it caused no impairments in fertility, fecundity, or reproductive organ development in either generation. However, a whole litter from a dam of the P generation was born dead, three litters in total had a pup with skeletal abnormalities, and the AGD of F2a female pups was reduced. These events occurred only in the milk-treated rats. It is unknown whether these issues had any relevance to milk or only happened by chance. CONCLUSION(S): Further study is required to determine whether milk from pregnant cows is completely free from adverse effects on reproductive health.