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Objective The close relationship between fatty liver and metabolic syndrome suggests that individuals with fatty liver may have multiple coronary risk factors. In the present study, we investigated the relationships among fatty liver, abdominal fat distribution, and coronary risk markers. Methods and Results Eighty-seven pairs of men and 42 pairs of women who were matched for age and body mass index were enrolled in the present study. The obesity-related markers, abdominal fat distribution (examined by CT), and coronary risk markers were compared in subjects with and without fatty liver. The visceral fat area was significantly larger in the men with fatty liver than in the men without fatty liver. The plasma levels of triglyceride and low-density lipoprotein cholesterol (LDL-C), as well as the homeostasis model assessment-insulin resistance level, were higher in both males and females with fatty liver than in those without fatty liver, while the plasma levels of high-density lipoprotein cholesterol (HDL-C) and adiponectin were lower in the males and females with fatty liver. The plasma levels of apolipoprotein B, remnant-like particle cholesterol (RLP-C), and oxidized LDL were higher in men with fatty liver, but not in women with fatty liver. Conclusion Both males and females with fatty liver had lower insulin sensitivity, lower plasma levels of HDL-C and adiponectin, and higher triglyceride and LDL-C levels. However, the plasma levels of apolipoprotein B, RLP-C, and oxidized LDL were only higher and closely associated with fatty liver in men. Men with fatty liver had a higher risk of coronary disease than women with fatty liver.

Antiretroviral drugs, especially protease inhibitors (PI), are known to induce disorders of lipid and glucose metabolism. However, there are only a few reports of these side effects in patients treated with integrase strand transfer inhibitors (INSTI). We encountered the case of a 46-year-old man who had been treated for type 2 diabetes with diet and exercise. He contracted immunodeficiency virus (HIV) infection two years earlier and received highly active antiretroviral therapy (HAART). Three months before the current admission, HAART was switched from a non-nucleic acid reverse transcriptase inhibitor (NNRTI) to an INSTI (raltegravir: 800 mg/day). He developed diabetic ketoacidosis and was admitted for treatment. The state of health prior to admission was not well documented but he showed no clinical signs of acute infection. Accordingly, diabetic ketoacidosis was considered to be associated with INSTI. Diabetic ketoacidosis was treated appropriately and blood glucose level was controlled with medications before discharge from the hospital. Although the present case does not provide direct evidence for raltegravir-induced diabetic ketoacidosis, we caution physicians about the potential of such side effect associated with the use of INSTI.

The patient was a previously healthy 23-year-old woman who made an outpatient visit to our hospital's Department of General Internal Medicine after developing pain and edema of the lower legs a week earlier. The patient was diagnosed with eosinophilic cellulitis (EC) based on an increased eosinophil count of 5,418/mm

Bacterial colonization in infancy is considered crucial for the development of the immune system. Recently, there has been a drastic increase in childhood allergies in Japan. Therefore, we conducted a prospective study with 56 infants on the relationship between gut microbiota in the first year of life and the development of allergies during the first 3 years. In the lactation period, organic acid producers such as Leuconostoc, Weissella and Veillonella tended to be underrepresented in subjects who developed food allergies (FA, n = 14) within the first two years. In the weaning period, children in the FA group were highly colonized by unclassified Enterobacteriaceae and two Clostridium species closely related to Clostridium paraputrificum and C. tertium, and the whole tree phylogenetic diversity index was significantly lower in the FA group. All of these differences in the weaning period were statistically significant, even after adjusting for potential confounding factors. A higher abundance of unclassified Enterobacteriaceae was also found in the other allergic group (n = 15), whereas the two Clostridium species were highly specific to the FA group. The mode of action of these Clostridium species in childhood food allergies remains unknown, warranting further investigation.

Objective: The Bethesda System (TBS) of uterine cervical cytology is a classification method that can improve accuracy in management and it includes descriptions on adequate specimens, human papillomavirus (HPV) involvement and estimated lesions. However, the judgment of atypical squamous cells of undetermined significance (ASC-US) using TBS features complicated diagnostic criteria and poor reproducibility due to the definition of ASC-US. Of patients diagnosed with ASC-US in the initial cytology, cervical intraepithelial neoplasia (CIN)1-2 cases positive for high-risk HPV (CIN+) and benign cases in histology negative for high-risk HPV (B-) were selected for discriminant analysis based on Mahalanobis distance, in order to improve the accuracy of the ASC-US diagnosis. Study Design: ASC-US cases featuring koilocytosis with little nuclear atypia (koilocytosis) and squamous epithelial cells with nuclear atypia (SC with atypia), morphologically diagnosed with liquid-based cytology specimens prepared using ThinPrep were included. The nuclei of koilocytosis cases (CIN+, 8 cases, and B-, 10 cases) and SC with atypia (CIN+, 19 cases, and B-, 15 cases) were three-dimensionally analyzed to conduct a discriminant analysis based on Mahalanobis distance. Results: Discrimination rates were 78.9% for CIN+ and 66.7% for B- in koilocytosis, and 50.7% for CIN+ and 72.1% for B- in SC with atypia. Conclusion: The present method allows the objective analysis of nuclear chromatin, providing effective cytology regarding CIN+ in koilocytosis and B- in SC with atypia of ASC-US cases.

Objective: It has been reported that the low level of consistency of diagnosis of atypical squamous cells cannot exclude high-grade squamous intraepithelial lesions (ASC-H) in uterine cervical cancer screening using the Bethesda System, indicating the necessity of a large-scale survey. We presented cases cytologically judged as ASC-H on our website and invited our members to give their opinions regarding the diagnosis by voting online. The Web voting results were analyzed and ASC-H was cytologically investigated. Study Design: Virtual slides of atypical cells in cytology preparations of 53 cases were prepared and presented on a website. ASC-H cases were divided into 42 cases sampled by brush scraping and 11 cases sampled by cotton swab scraping. Fifty-three cases cytologically judged as ASC-H were classified into benign and CIN2/3, and their patterns of arrangement of atypical cells and 8 cytological parameters were morphologically investigated. Results: The frequency of ASC-H diagnosis in the Web votes was low: 29.2% for brush-scraped and 26.2% for cotton swab-scraped cases. Three-dimensionality, coarse chromatin and irregular nuclei were significantly different between high-grade squamous intraepithelial lesions and benign cases. Conclusion: Web-based surveys showed the difference of cytological findings between high-grade squamous intraepithelial lesions and benign cases. To increase interobserver consistency, it may be useful to share information online, which avoids geographical and temporal limitations.

We investigated the correlation between fecal bacteria composition in early infancy and the prevalence of allergic diseases in late infancy. The fecal microbiota in the first 2 months was profiled using the 16S rRNA V6 short-tag sequences in the community and statistically compared between two groups of subjects who did and did not show allergic symptoms in the first 2 years (n = 11 vs. 11). In the allergic group, genus Bacteroides at 1 month and genera Propionibacterium and Klebsiella at 2 months were more abundant, and genera Acinetobacter and Clostridium at 1 month were less abundant than in the nonallergic group. Allergic infants who showed high colonization of Bacteroides and/or Klebsiella showed less colonization of Clostridium perfringens/butyricum, suggesting antagonism between these bacterial groups in the gastrointestinal tract. It was also remarkable that the relative abundance of total Proteobacteria, excluding genus Klebsiella, was significantly lower in the allergic than in the nonallergic group at the age of 1 month. These results indicate that pyrosequence-based 16S rRNA gene profiling is valid to find the intestinal microbiotal disorder that correlates with allergy development in later life.

Background Tubulointerstitial fibrosis (TIF) is seen as the final stage of progressive nephropathy, and the degree of TIF is reported to be a major determinant in renal outcomes. In recent years, epithelial-mesenchymal transition (EMT) and the zinc-finger transcription factor snail homolog 1 (Snai1) have each been implicated in the mechanism of TIF. The relationship between EMT and these transcription factors is unclear, however, so in this study we attempted to elucidate the correlation between the expression of Snai1 and clinical markers. Methods We performed immunohistochemical staining on human renal tissue obtained from patients with diabetic nephropathy (DN), IgA nephropathy (IgAN), minimal change disease (MCD) and minor glomerular abnormality (MGA) using anti-Snai1 and anti-vimentin antibodies. We counted Snai1-positive and Snai1/vimentin double positive tubular epithelial cells. Results Snai1 protein was mainly observed in the nuclei of flattened, damaged tubular epithelial cells, especially in IgAN and DN, and positive cell numbers were significantly higher in IgAN than in MGA, MCD or DN. Snai1/vimentin double staining showed that some vimentin-positive tubular epithelial cells also contained Snai1-positive nuclei, and double positive cell numbers were increased in IgAN and DN. Statistical analysis revealed positive correlations between Snai1/vimentin double positive cell numbers and proteinuria and creatinine in IgAN. Positive correlations were also seen between Snai1/vimentin double positive cell numbers and the severity of proteinuria in DN. Conclusions The results of this study indicate that Snai1 plays an important role in TIF in patients with progressive nephropathy.

The influence of antibiotic exposure in the early postnatal period on the development of intestinal microbiota was monitored in 26 infants including five antibiotic-treated (AT) subjects orally administered a broad-spectrum antibiotic for the first 4 days of life and three caesarean-delivered (CD) subjects whose mothers were intravenously injected by the similar type of antibiotics in the same period. The faecal bacterial composition was analysed daily for the first 5 days and monthly for the first 2 months. Terminal restriction fragment length polymorphisms in the AT subjects showed less diversity with the attenuation of the colonization of some bacterial groups, especially in Bifidobacterium and unusual colonization of Enterococcus in the first week than the control antibiotic-free infants (AF, n=18). Quantitative real-time PCR showed overgrowth of enterococci (day 3, P=0.01; day 5, P=0.003; month 1, P=0.01) and arrested growth of Bifidobacterium (day 3, P=0.03) in the AT group. Furthermore, after 1 month, the Enterobacteriaceae population was markedly higher in the AT group than in the AF group (month 1, P=0.02; month 2, P=0.02). CD infants sustained similar, although relatively weaker, alteration in the developing microbiota. These results indicate that antibiotic exposure at the beginning of life greatly influences the development of neonatal intestinal microbiota.

Objective Diabetic nephropathy (DN) is a common cause of end-stage renal disease. However, the precise mechanism of DN, which involves the role of lipid, is still not fully understood. Lectin-like oxidized LDL receptor-1 (LOX-1) is a type II single-transmembrane protein that binds oxidized low density lipoprotein (Ox-LDL). This study examined the expression of LOX-1 mRNA in renal tissues from type 2 diabetes patients with DN using in situ hybridization (ISH). Patients and Methods Renal tissues were obtained from 15 type 2 patients with DN and 5 minimal change nephrotic syndrome (MCNS), membranous nephropathy (MN) and normal human kidney (NHK). Glomerular and tubulointerstitial LOX-1 mRNA expression was evaluated by ISH. Results The cells positive for LOX-1 mRNA were identified in the glomeruli of DN, MCNS, MN and NHK, however, there was no positive signal in the tubulointerstitial area in MCNS and NHK. Some cells positive for LOX-1 mRNA were detectable in the tubulointerstitial area in DN and MN. In the results of glomerular staining, there was no significant difference between them. There was a significant correlation between the tubulointerstitial LOX-1 expression and the degree of the tubulointerstitial damage and urinary protein in DN. Conclusion Increased expression of LOX-1 mRNA in the tubulointerstitial area may be closely linked to the development and progression of human DN, and in particular the tubulointerstitial damage.

Objective The loss of podocytes has been reported to have a role in the onset and progression of diabetic nephropathy (DN). Although structural changes such as podocyte hypertrophy are considered to be associated with podocyte loss, the relationship has not been thoroughly investigated using human DN renal tissues. Methods The subjects were 17 patients with DN diagnosed histopathologically by renal biopsy. Immunostaining was performed with antibodies for Wilm's tumor 1 (WT1) and synaptopodin (SPD), which are markers of podocytes, to determine the number of podocytes and assess podocyte hypertrophy. Results The number of podocytes was decreased in DN patients compared with the controls. An inverse correlation was observed between the number of podocytes and both the urinary protein excretion and the extent of mesangial expansion. Podocyte hypertrophy was also more marked in DN patients compared with controls. Conclusion Based on these results, podocyte loss and hypertrophy were suggested to be involved in the development and progression of human DN.

We have sequenced the insulin gene in 72 unrelated Japanese subjects (52 with type 2 diabetes mellitus and 20 with normal glucose tolerance). We identified 6 mutations and all were found at a low frequency (1% to 4%). Three mutations were new. These included a C-to-G substitution in the promoter region, a G-to-A substitution in codon-2 resulting in an Ala-to-Thr replacement in amino acid -2 of the signal peptide, and a G-to-A substitution in intron 2. We have no evidence that any of the mutations that we found are the cause of diabetes. Thus, mutations in the insulin gene do not appear to be an important genetic factor contributing to the development of diabetes in this population.

We investigated the effect of T cell-dependent B cell activation on the production of IL-10 and IL-12 by peripheral blood mononuclear cells (PBMCs) obtained from patients with Graves' disease vs Hashimoto's thyroiditis, type 1 diabetes or normal controls. Incubation of PBMCs, from each of the subject groups, with a combination of anti-CD40 monoclonal antibodies and interleukin 4 (IL-4)-activated B cells, as shown by an increased level of soluble CD23. There was also a notable increase in the number of CD23(+)cells in PBMCs from patients with Graves' disease as compared to the other subject groups. This combination of B cell stimulants increased production of IL-10 in PBMCs obtained from patients with Graves' disease relative to those patients with Hashimoto's thyroiditis, type 1 diabetes, or the control subjects. The production of IL-12 showed wide variation that depended on the basal IL-12 level. In subjects with a low basal IL-12 level there was a positive correlation between the production of IL-12 and that of IL-10 from PBMCs stimulated with anti-CD40 antibodies plus IL-4. On the contrary, in the patients with a high basal IL-12 level, no change or a decrease of IL-12 production was observed after the stimulation. Thus, T cell-dependent B cell activation via a CD40 pathway triggers the overproduction of IL-10 and overcome the effect of IL-12 to shift the Th(1)/Th(2)balance to Th(2)dominance in patients with Graves' disease but not in Hashimoto's thyroiditis or type 1 diabetes.

To investigate whether the two free-radical scavengers, Cu, Zn- and Mn-superoxide dismutase (SOD), are changed in leukocytes of diabetic patients, and the alteration of these enzymes correlates with the diabetic state, we measured the activity and concentration of these enzymes in leukocytes from diabetic patients. Both Cu, Zn-SOD and Mn-SOD activities in neutrophils and lymphocytes were significantly lower in patients with non–insulin-dependent diabetes mellitus than in healthy controls. The concentrations of these enzymes in leukocytes from diabetic patients, however, did not differ from those in controls. Cu, Zn-SOD and Mn-SOD activities in neutrophils inversely correlated with HbA 1c concentrations. Myeloperoxidase activity in leukocytes was significantly reduced in NIDDM patients. These findings suggest that changes in these enzymes may affect the susceptibility to infection and immunocompetence of patients with diabetes.

Objective: To increase the accuracy of the diagnosis of atypical squamous cells of undetermined significance (ASC-US), ASC-US were divided into high-risk human papillomavirus (HPV HR+) and non-high-risk HPV (HPV HR-) cases to analyze the significance of binucleated cells with compression. Study Design: ThinPrep specimens of ASC-US were examined. This study included 21 CIN and HPV HR+ (CIN+), 19 benign and HPV HR- (B-) and 10 benign and HPV HR+ (B+) cases. The number of cells were examined by defining binucleated cells with their nuclei pressing against each other as positive compression, and their relation to the relative light units (RLUs) of the DNA Hybrid capture 2 (HC2) was determined. Results: 95.2% of CIN+ and 15.8% of B- cases were compression positive, while 4.8% of CIN+ and 84.2% of B- cases were compression negative, which was significantly different. The average number of cells with positive compression was 5.7 ± 5.3 in CIN+, 2.0 ± 0.7 in B- and 5.5 ± 1.5 in B+ cases, with significant differences between CIN+ and B- and between B- and B+ cases. The number of compression-positive cells increased as HPV HC2 RLUs became higher. Conclusion: Positive compression is useful in determining ASC-US with HPV HR+. The identification of positive compression is highly practical because it can be observed morphologically.

Objective To determine the clinical usefulness of long-term intensive insulin therapy in Japanese patients with type 2 diabetes. Patients and methods Various clinical indicators and potential of withdrawal from insulin therapy were investigated in 20 type 2 diabetic patients receiving treatment in the outpatient clinic over a period of 8 years after starting intensive insulin therapy between April 1997 and March 1999. Results The mean glycated hemoglobin (HbA1c) was approximately 6.5%, and there was no significant increase in insulin dose over a period of 8 years after commencement of intensive insulin therapy. Withdrawal from insulin therapy could be sustained in previously untreated patients. Conclusion Our results indicated the clinical usefulness of intensive insulin therapy over the long term in Japanese patients with type 2 diabetes and that such therapy could be especially useful for previously untreated patients.

Background Alpha-actinin-4 is an actin filament crosslinking protein that interacts with intercellular adhesion molecules. Recent animal studies suggested that alpha-actinin-4 is an essential component of the glomerular filtration barrier. However, little is known about its expression in human diabetic nephropathy (DN). Methods Renal biopsy tissues were obtained from 17 patients with DN. We determined the mRNA and protein expression levels of alpha-actinin-4 by in situ hybridization and immunohistochemistry. The histopathological severity of DN was classified into two groups: mild and moderate mesangial expansion groups. We also measured urinary protein excretion and creatinine clearance. Results Podocytes were positively stained for alpha-actinin-4 mRNA and protein. In the glomeruli, the percentage of cells positive for alpha-actinin-4 mRNA was significantly lower in moderate mesangial expansion group than in mild mesangial expansion group and control. The percentage of immunohistochemically positive area for alpha-actinin-4 protein in moderate mesangial expansion group was significantly lower than in mild mesangial expansion group and control. The percentage of cells positive for alpha-actinin-4 mRNA and area positive for the protein correlated inversely with severity of proteinuria. Conclusion Our results suggest that low expression levels of alpha-actinin-4 mRNA and protein are linked to the progression of glomerulopathy and proteinuria in human DN.

We investigated the clinical characteristics of intensive insulin therapy in Japanese type 2 diabetes patients who commenced intensive insulin therapy during the in-hospital diabetes education program at Tokai university hospital.81 type 2 diabetes patients who received intensive insulin therapy and in-hospital diabetes education program were examined their clinical features.Intensive insulin therapy maintained HbA(1C) below 7% at all time points during the 2-year follow-up, though it was not necessary to increase the insulin dose, thus highlighting the clinical utility of the therapy in preventing diabetic complications. Insulin therapy could be withdrawn from more than 25% of patients. The diabetic morbid period was shorter and urinary C-peptide level at admission was higher in patients of the withdrawal group than those of the non-withdrawal group, suggesting that patients with well maintained pancreatic β cell reserve could be withdrawn from insulin therapy.Based on our results of the efficacy of strict glycemic control for preventing the development and progression of diabetic complications, we recommend early introduction of intensive insulin therapy to achieve better glycemic control.

Objective Membranous nephropathy (MN) is the most common cause of adult-onset nephrotic syndrome and its management is still controversial. The aim of this study was to determine the effectiveness of corticosteroid-alone therapy for controlling proteinuria in MN. Methods Twenty-three patients, which had moderate proteinuria (admission 24-hour urinary protein excretion 1.0 to 3.5 g/day) with primary MN were studied retrospectively. Results Thirteen patients received corticosteroid-alone therapy combined with rest and dietary therapy (steroid group), while the other 10 patients were treated with rest and diet alone (non-steroid group). These two groups did not differ with respect to their laboratory features at the time of admission. After discharge, 5 of 13 patients of the steroid group dropped out . Therefore, only 8 patients could be followed up. As the result, 5 of 8 patients (62.5%) achieved complete remission (CR) and 3 of 8 patients (37.5%) had incomplete remission (ICR), so none of the patients failed to improve. On the other hand, 3 of 10 patients of the non-steroid group dropped out. Then, 7 patients were followed up. None of the 7 patients showed improvement during follow-up and 5 of these 7 patients were started on corticosteroids. Finally, as this result, 4 of 5 patients (80%) could achieve CR by 2 years after hospital discharge. Moreover, in the remaining 2 patients from the non-steroid group, no remission could be achieved even 2 years after discharge. Conclusion These results suggest that long-term corticosteroid-alone therapy is beneficial for controlling proteinuria in patients with MN.

The amounts of sorbitol (SOR) excreted in 24-h urine were determined on two groups, i.e., diabetic and nondiabetic patients, using an improved method in which ion exchange resin column processing was applied, and these levels were compared with SOR levels in whole blood. Urinary SOR concentration was also determined in diabetic and normal rats in the same manner and its relationship to aldose reductase (AR) activity in whole blood was investigated. Changes in SOR levels in urine and whole blood were compared in diabetic rats after administration of an AR inhibitor (ARI). Whole blood SOR levels and urinary SOR excretion were significantly higher in diabetic patients than in nondiabetic patients. The same results were obtained in the animal models. In diabetic rats, the urinary SOR excretion was about five times higher than that in control rats, and the AR activity in whole blood was also significantly higher. The increase in urinary SOR excretion and whole blood SOR levels, as well as AR activity, in blood in the diabetic state was inhibited by ARI administration. The influence of the diabetic state and the efficacy of the ARI were more marked in urinary SOR excretion than in whole blood SOR levels. These data indicate that determinations of urinary SOR excretion and AR activity are easily measurable and of benefit to assessing the diabetic condition.

ErbB family members, such as epidermal growth factor receptor 1 (erbB1), erbB2, erbB3 and erbB4, are widely distributed in organ tissues, and these receptors are suspected tumorigenesis factors. We measured erbB mRNA in thyroid tissues of benign and malignant thyroid tumors or Graves' disease using Genescan. ErbB2 is associated with aggressive cancers and is used as a biological marker for the disease; Northern blot and reverse transcription-polymerase chain reaction (RT-PCR) analyses have shown it to be increased in Graves' disease. Additional studies indicated a similar result in papillary carcinoma cells; mRNAs of erbB2 and erbB3 were increased but erbB4 mRNA was decreased, suggesting distorted erbB expression may be associated with tumorigenesis. However, only erbB2 overexpression is associated with Graves' disease. These data further implicate transmembrane-type receptors in tumorigenesis in the thyroid.

The possible role of abnormal T cell-dependent B-cell activation in Graves' disease was investigated by comparing lymphocyte subset distribution and the production of soluble CD8 (sCD8), sCD23, IL-10 and IL-12 by peripheral blood cells (PBMC) and thyroid-infiltrating lymphocytes (TL) in vitro. In TL, the percentage of CD8(+) cells was slightly higher and the sCD8 concentration was significantly higher than in PBMC. The ratio CD23(+) cells to CD20(+) cells (activated B/pan B cells) was increased in TL compared to PBMC from Graves' or normal controls, although the percentage of CD20(+) cells was decreased. Compared to PBMC in Graves' disease, the relative ratio of IL-10 to IL-12 release (IL-10/IL-12) by unstimulated TL was increased, despite a lack of significant difference between PBMC and TL in mean values for either IL-10 or IL-12 secretion. Incubating PBMC with a combination of anti-CD40 monoclonal antibodies and interleukin-4 (IL-4) resulted in B cell activation, reflected in an increase in the sCD23 level in both controls and Graves' patients, but especially prominent in the latter. Stimulation with anti-CD40 antibody and IL-4 also decreased the percentage of CD8(+) cells in PBMC but not TL from both Graves' disease and normal controls, and the percentage of CD8(+) cells in TL was higher than PBMC after the stimulation. The sCD23 concentration in TL was decreased compared to PBMC both in patients with Graves' disease and normal controls. However, in contrast to the increased responses observed in Graves' PBMC or normal controls after stimulation, sCD23 levels remained the same in stimulated TL from Graves' patients. This combination of B cell stimulants increased production of IL-10 in PBMC but not in TL obtained from patients with Graves' disease, and the increased IL-10/IL-12 ratio declined to a value no different from that in PBMC group after stimulation. Thus, T cell-dependent B-cell activation via a CD40 pathway may cause a shift in the Th(1)/Th(2) balance to Th(2) dominance in Graves' disease, while increased CD8(+) cells in TL may suppress sCD23 production and IL-10-producing Th(2) cells.

In general, many cases of malignancy-associated hypercalcemia are due to HHM. In patients with humoral hypercalcemia of malignancy (HHM), it has been reported that plasma parathyroid hormone-related protein (PTHrP) and cyclic adenosine monophosphate (cAMP) levels were elevated, while plasma PTH and active vitamin D(3) levels were suppressed. Our patient showed hypercalcemia with a concurrent increase in plasma and tumor tissue PTHrP and PTH concentrations and also high cAMP and low 1-25(OH)(2)VD(3) levels in the plasma. These data suggest that the hypercalcemia exhibited by our patient was consistent with HHM due to lung cancer and its liver metastasis. Moreover, diagnostic imaging and autopsy findings showed no appreciable lesions of the parathyroid gland. In addition, histopathologic examination of the primary and metastatic tumors revealed the existence of PTH immunohistochemically stained with anti-PTH antibodies, suggesting an ectopic-PTH-producing lung tumor. From these data, our patient was diagnosed with a rare case of lung cancer, which produced both ectopic PTH and PTHrP.