Gonadotropin levels in urine during early postnatal period in small for gestational age preterm male infants with fetal growth restriction.

OBJECTIVE: The objective of this study was to estimate gonadotropin concentrations in small for gestational age (SGA) male infants with the reactivation of the hypothalamic-pituitary-gonadal axis during the first few months of life that is important for genital development. STUDY DESIGN: We prospectively examined 15 SGA and 15 appropriate for gestational age (AGA) preterm male infants between 2013 and 2014 at Kyoto University Hospital. Gonadotropin concentrations (luteinizing hormone (LH) and follicle-stimulating hormone (FSH)) were measured in serial urine samples from the postnatal days 7 to 168 and compared between SGA and AGA infants using the Mann-Whitney test. RESULTS: A longitudinal analysis showed that SGA infants had higher LH and lower FSH concentrations (P=0.004 and P=0.006, respectively) than AGA infants. CONCLUSION: Male infants who are SGA at birth because of fetal growth restriction have gonadotropin secretion abnormalities in the first few months of life.

Response to thyrotropin-releasing hormone stimulation tests in preterm infants with transient hypothyroxinemia of prematurity.

OBJECTIVE: Whether hormone supplementation is necessary for infants with transient hypothyroxinemia of prematurity (THOP) remains controversial, and further analysis of the hypothalamus-pituitary-thyroid axis of infants with THOP is necessary. STUDY DESIGN: Thyrotropin-releasing hormone (TRH) stimulation tests were performed at 2 weeks of age in 50 infants with a gestational age of 30 weeks or less, and the data were analyzed retrospectively. RESULT: Subjects were divided into three groups; group A consisted of euthyroid infants, group B consisted of infants with THOP and group C consisted of hypothyroid infants. The basal and peak thyroid-stimulating hormone level of group C in response to TRH stimulation tests was significantly higher than the others, but no differences were observed between groups A and B. CONCLUSION: The response of infants with THOP to the TRH stimulation test was not different from that of euthyroid infants, which suggested that their hypothalamic-pituitary-thyroid axis was appropriately regulated in infants with THOP.

Social support provided to caregivers of children with cerebral palsy.

OBJECTIVE: To describe the perception of caregivers of children with cerebral palsy (CP) concerning social support received and to verify how the characteristics of the children (i.e. type of CP and severity of motor impairment) and those of their caregivers (i.e. age, level of education, occupation, income and number of children) are significantly related to this perception. METHOD: A total of 50 children with CP aged between 3 and 12 years and their respective caregivers participated in this study. Children were grouped in terms of type of CP and according to the severity of motor impairment through the Gross Motor Function Classification System (GMFCS). The Social Support Questionnaire (SSQ) was used to evaluate the perception of caregivers concerning the social support they receive (number of people offering support - SSQ-N index, and level of satisfaction concerning such support - SSQ-S index). RESULTS: The caregivers reported receiving support from a mean of 1.67 people. Core and extended family members (i.e. husband, mother, siblings) and friends are the most common providers of support. In regard to level of satisfaction, caregivers considered the support they received to be positive, obtaining a mean of 5.52 out of a total of six points. Children's and caregivers' characteristics were not significantly related to the SSQ-N and SSQ-S indexes. CONCLUSION: Family members are the caregivers' primary source of social support and caregivers reported being satisfied with the support they received.

Pitfalls in the epidemiologic classification of human papillomavirus types associated with cervical cancer using polymerase chain reaction: driver and passenger.

Cervical cancer is a common malignancy in women worldwide, and it has now been established that the human papillomavirus (HPV) is both necessary and causal for these lesions. HPV itself is both ubiquitous and markedly heterogeneous but can nevertheless be classified as either a high-risk type or a low-risk type based upon its frequency of detection in cervical cancer. Given that the association between HPV and cervical cancer is causal, the classification of this virus has been strengthened by large-scale epidemiologic studies and is widely accepted across many disciplines. It is evident, however, that cervical cancer is frequently associated with multiple HPV types. Therefore, it is crucial to distinguish causal types of HPV (drivers) from noncausal types (passengers) in cervical lesions. In this review, we highlight the current pitfalls of using polymerase chain reaction methods instead of Southern blot hybridization for detecting HPV and discuss the distinction between driver and passenger HPVs with regard to the viral type, the length of the viral genome, and the levels of viral DNA associated with cervical cancer. Finally, we newly propose three categories of HPV instead of two risk groups, based on similarities between viral genes.

[Torsion of the right upper lobe due to primary lung cancer with pulmonary hypertrophic osteoarthropathy; report of a case].

A 61-year-old woman was admitted due to severe coughing. Chest X-ray revealed a mass in the right lower lung field at standing position and in the right upper lung field at supine position. A position of the mass changed with change in her posture because of lobar torsion. Bronchoscopic biopsy of the polypoid tumor obstructing the right upper bronchus revealed adenocarcinoma. She had hypertrophic osteoarthropathy simultaneously. Right pneumonectomy was performed. Postoperative course has been uneventful for 3 years.

Detection of human papillomavirus type 34 in Bowen's disease on the pubic area.

We describe an 86-year-old man with Bowen's disease on the pubic area. The lesion was clinically a black-brownish keratotic nodule resembling seborrheic keratosis. Histopathological findings showed those of Bowen's disease and harboured human papillomavirus type 34 DNA. Genital, but not skin, human papillomaviruses are responsible for Bowen's disease on the skin.

Bowen's carcinoma of the scrotal skin associated with human papillomavirus type 82.

We have previously cloned human papillomavirus type 82 (HPV-82) from a vaginal intraepithelial neoplasia, but it is not known whether HPV-82 can induce a cutaneous lesion. A large erosive nodule developed on the scrotum of a 50-year-old Japanese patient. Histopathologically, the lesion was composed of two distinct parts; one part showing changes characteristic of Bowen's disease in the epidermis, and the other showing elongated rete ridges and proliferation of atypical basaloid cells in the dermis. These parts were partially connected, giving the diagnosis of Bowen's carcinoma. Immunohistochemically, HPV capsid antigen was detected only in the nuclei of a few cells on the upper part of the epidermis. HPV-82 was identified in the lesion by blot hybridization and viral DNA was demonstrated in the lesion by in situ hybridization. HPV-82 has tropism for both the skin and the genital regions.

The characteristics of bone turnover in the second decade in relation to age and puberty development in healthy Japanese male and female subjects--Japanese Population-based Osteoporosis Study.

BACKGROUND: There are few studies that clarify the characteristics of bone turnover in children and adolescents. Furthermore, little has been published on changes in urinary CrossLaps(TM) (CTx) in Japanese subjects. AIM: To investigate biochemical markers of bone turnover in subjects, in relation to age and puberty development. SUBJECTS AND METHODS: We measured serum bone specific alkaline phosphatase (B-Alp) and CTx in 1207 Japanese subjects aged 9-18 years. As an indicator of puberty development, the age that pubic hair appeared in males and menstruation started in females was obtained from questionnaires. RESULTS: B-Alp and CTx/Cr (creatinine) had high values before and just after the indicators and was lower thereafter, reaching a plateau in both genders. There was no significant difference in these values in males 5-6 years, or 7 years and more after the appearance of pubic hair. B-Alp and CTx/Cr values 7 years and more after menarche were significantly lower than those 5-6 years after menarche, however the differences were relatively small. CONCLUSIONS: Subjects in the second decade can be divided into three groups: 'before the appearance of pubic hair for males and menarche for females', 'up to and including 3-4 years after them' and '5-6 years and more after them'.

Relationship between partition of heavy metals in sewage sludge and elution of heavy metals.

Heavy metals in sewage sludge were classified into three partitions associated with extracellular and intracellular organic matters and the residue before and after different elution processes of heavy metals from the sludge. Alkalization of the sludge to pH 11 decreased the content of Cu in the three partitions and that of Ni in extracellular organic and residual ones. Acidification of the sludge to pH 3 decreased the content of Cd, Mn, Ni and Zn in all of the partitions and that of Cu in the intracellular organic one. A further decrease in the pH to 2 caused a decrease in the content of Cu in extracellular organic and residual partitions and that of Ni in the inorganic one. The addition of ferric sulfate to the sludge effectively lowered the content of Cd and Cu in extracellular organic and inorganic partitions under acidic conditions. These results would give information on a selection of the method for removing heavy metals from the sludge.

Lung herniation as an anatomic consequence of pneumonectomy.

BACKGROUND: Pneumonectomy causes an overdistention of the remaining lung as an adaptive response. Excessive lung herniation occasionally causes serious lung dysfunction. METHODS: Twenty-seven patients were selected from 152 patients who underwent pneumonectomy for lung cancer between 1990 and 1998. Complete resections were accomplished; no recurrence was observed for 3 years in these 27 patients. To evaluate the extent of herniation, the Lung Herniation Index (LHI) was developed and defined as the sum of proportions of the maximal transverse length of the remaining lung divided by the transverse length of the thoracic cavity, measured at the level of the aortic arch and the inferior pulmonary vein on chest computed tomography. Sequential changes in LHI were compared between groups. RESULTS: Changes in LHI did not differ between groups delineated on the basis of an FEV1 of 70 % (p = 0.45) and RV/TLC of 40 % (p = 0.99). Patients with a low body mass index (BMI) (< 20 kg/m(2)), however, showed a significantly greater degree of lung herniation than those with a high BMI (> or = 20 kg/m(2)) (p < 0.05). CONCLUSIONS: Concomitant COPD has no effect on lung herniation. Some preventive procedure should be considered for patients with low BMI.

Protean manifestations of human papillomavirus type 60 infection on the extremities.

BACKGROUND: Human papillomavirus type 60 (HPV-60) induces a ridged wart or an epidermal cyst on the sole of the foot, exhibiting identical pathological changes, with a single refractile eosinophilic intracytoplasmic inclusion body in infected cells. However, there is no information on the role of HPV-60 in the development of cutaneous lesions on other anatomical sites. OBJECTIVES: To perform the clinicopathological analysis of various cutaneous lesions of a patient in relation to HPV genotype. PATIENT: A 50-year-old male patient developed multiple papules, plaques and nodules on his hand, arm and legs. RESULTS: Clinicopathologically, the lesions were classified into three categories. A common wart on the finger showed papillomatosis and acanthosis characterized by numerous keratohyalin granules. Plane warts on the arm showed perinuclear vacuolization of the cells in the upper Malpighian layer. On the other hand, a pigmented papillomatous nodule on the finger, and the other lesions on the hands and legs exhibited similar histological features with a unique cytoplasmic eosinophilic inclusion body. All the three categorized lesions were equally positive for HPV capsid antigen by immunohistochemistry. By blot hybridization analysis for HPV sequences, it was revealed that a common wart on the finger and plane warts on the arm harboured HPV-27 and HPV-3, respectively, while all the other lesions harboured HPV-60. The histological localization of each viral DNA was confirmed in the corresponding lesions by in situ hybridization. CONCLUSIONS: HPV-60 is able to induce papular and nodular lesions on the extremities.

Optimal alveolar oxygen concentration for cold storage of the lung.

BACKGROUND: Ischemia of the lung is different from that of solid organs because the lung contains gas in the alveoli. However, the optimal gas composition in the alveoli during cold storage remains uncertain. We investigated the relationship between the alveolar oxygen concentration and reperfusion injury. METHODS: The lungs inflated with 0% O2, 5% O2, room air, 50% O2, or 100% O2 were reperfused after 8 hR storage at 4 degrees C and pulmonary functions were measured for 120 min using an ex vivo rat lung model. The levels of high-energy phosphate and lipid peroxidation of the lung were analyzed after a PA flush, preservation, and reperfusion. Additionally, respiration of the mitochondria in the lungs was measured after preservation. RESULTS: The pulmonary functions were significantly superior in the 5% O2 group than those in the 0% O2, 50% O2, and 100% O2 groups. Pulmonary edema developed in the 0% O2, 50% O2, and 100% O2 groups, but not in the 5% O2 group. After preservation, the energy level in the lungs decreased only in the 0% O2 group. Although lipid peroxidation of the lungs did not increase in any group after preservation, significant increases were observed in the room air, 50% O2 and 100% O2 groups after reperfusion. State 3 and 4 ratios of the mitochondrial respiration significantly decreased in the lungs of the room air, 50% O2 and 100% O2 groups. CONCLUSIONS: Although the cold-preserved lungs require oxygen, hyperoxygenation induced mitochondrial dysfunction and increased lipid peroxidation and led to deleterious lung function after reperfusion. Therefore, hypoxic conditions that can maintain the energy level of the lung during cold storage would be optimal.

Relationships between 80 human papillomavirus genotypes and different grades of cervical intraepithelial neoplasia: association and causality.

To clarify the causal relationship between human papillomavirus (HPV) and cervical intraepithelial neoplasia (CIN), we analyzed 386 unfixed biopsy specimens by blot hybridization at Tm -40 degrees C, targeting 38 skin and 42 genital HPVs. By the recognition of PstI, BanI, and MspI cleavage patterns, single genital, but no skin's HPVs were identified with more than 10 copies per cell in 354 CIN (88 CIN I, 94 CIN II, and 172 CIN III). HPVs 40, 42, 43, 54, 62, or 71 was found in 10 CIN I, while HPVs 18, 30, 39, 51, 56, 59, 66, 68, 69, or 82 was found in 35 CIN I, 20 CIN II, or 8 CIN III. On the other hand, HPVs 16, 31, 33, 35, 52, 58, or 67 was identified in 43 CIN I, 74 CIN II, or 164 CIN III. The results are strongly indicative that most genital HPVs have potency to induce CIN I; however, HPV 16 and its closely related types are able to efficiently induce CIN III. We discuss the definition of causal HPV for CIN with regard to viral prevalence and viral load.

Human papillomavirus type 58 in Bowen's disease of the elbow.

Human papillomavirus (HPV) can be detected in skin lesions of Bowen's disease, particularly on the fingers, and its genotype is associated with mucosal/genital types of HPV. We report herein an 85-year-old woman who had HPV-associated Bowen's disease on her elbow. HPV-58 DNA was detected in the lesion by polymerase chain reaction with restriction fragment length polymorphism and by Southern blot hybridization. In situ hybridization revealed numerous hybrid cells in the nuclei of the upper epidermis and stratum corneum of Bowen's disease. A high-risk type of mucosal HPV-58 DNA is associated with Bowen's disease in this case, suggesting that HPV-related Bowen's disease is not always restricted to genital or finger lesions.

Preferential pharmacological inhibition of macrophage ACAT increases plaque formation in mouse and rabbit models of atherogenesis.

The cholesteryl ester, foam cell-enriched vulnerable plaque is a principle pharmacological target for reducing athero-thrombosis. Acyl CoA:cholesterol Acyl Transferase (ACAT) catalyzes the esterification of free cholesterol in intestine, liver, adrenal and macrophages, leading in the latter cells to intracellular cholesteryl ester accumulation and foam cell formation in the arterial intima. Previous studies suggested the existence of several isoforms of ACAT with different tissue distribution and this has largely been confirmed by molecular cloning of ACAT-1 and ACAT-2. We developed a series of ACAT inhibitors that preferentially inhibited macrophage ACAT relative to hepatic or intestinal ACAT based on in vitro assays and ex vivo bioavailability studies. Four of these compounds were tested in three models of atherosclerosis at oral doses shown to give sufficient bioavailable monocyte/macrophage ACAT inhibitory activity. In fat-fed C57BL/6 mice, chow fed apo E-/- mice and KHC rabbits, the various ACAT inhibitors had either no effect or increased indices of atherosclerotic foam cell formation. Direct and indirect measurements suggest that the increase in plaque formation may have been related to inhibition of macrophage ACAT possibly leading to cytotoxic effects due to augmented free cholesterol. These results suggest that pharmacological inhibition of macrophage ACAT may not reduce, but actually aggravate, foam cell formation and progression.

Distinctive distribution of human papillomavirus type 16 and type 20 DNA in the tonsillar and the skin carcinomas of a patient with epidermodysplasia verruciformis.

BACKGROUND: Epidermodysplasia verruciformis (EV) is a rare skin disease characterized by disseminated pityriasis versicolor-like or flat wart-like lesions and by the development of skin carcinomas. It is well established that specific cutaneous human papillomaviruses (EV-HPVs) are associated with both benign and malignant skin lesions in EV patients. However, little is known of the relationship between HPV and the mucosal lesions of EV patients. OBJECTIVES: To detect and identify HPV types associated with skin and mucosal lesions of an EV patient. PATIENT/METHODS: We investigated the skin carcinoma and the coexisting tonsillar carcinoma of a 41-year-old man with EV. Histopathologically, both lesions were squamous cell carcinomas. We analysed these two lesions by immunohistochemistry, in situ hybridization, and by molecular virology. RESULTS: Neither skin nor tonsillar lesions exhibited positivity for HPV capsid antigen by immunohistochemistry. By Southern blot hybridization, however, the skin carcinoma harboured 'EV-specific' HPV20 DNA, while the tonsillar carcinoma harboured 'genital' HPV16 DNA. In addition, in situ hybridization localized the respective viral DNA in the corresponding lesion. CONCLUSIONS: The results indicate that EV-HPV could be responsible for the development of the skin carcinoma, but not the mucosal carcinoma in this patient.

Antinociceptive effect of the combination of pentazocine with morphine in the tail-immersion and scald-pain tests in rats.

We investigated the antinociceptive effect of pentazocine hydrochloride (pentazocine) in combination with morphine hydrochloride (morphine) using two antinociceptive tests; i.e., the tail-immersion and scald-pain tests, in rats. In the tail-immersion test, the rat's tail was immersed in warm water at 47 degrees C, and the latency to a nociceptive response was measured. In the scald-pain test, the right hind foot was scalded by immersion into hot water at 57 degrees C. Two hours later, additional thermal stimulus was applied to the same foot, and the latency to a nociceptive response was measured. Subcutaneous treatment with either pentazocine (6, 12, 24 mg/kg) or morphine (1.5, 3, 6 mg/kg) alone dose-dependently showed antinociceptive effects in both tests. The ED50 values (95% confidence limit) of pentazocine and morphine were 13.0 (5.4-31.5) and 2.4 (1.6-3.7) mg/kg in the tail-immersion test and 11.0 (4.5-26.6) and 3.8 (1.8-7.2) mg/kg in the scald-pain test, respectively. Simultaneous treatment with pentazocine at the similar dose augmented the morphine (1.5 mg/kg)-induced antinociception, but did not diminish the morphine (6 mg/kg)-induced antinociception in both tests. These results suggest that the simultaneous administration of pentazocine at the antinociceptive dose and morphine exerts additional antinociceptive activity against thermal and scald-induced inflammatory pain.

Applicability of zinc complex of L-carnosine for medical use.

Zinc complex of L-carnosine (L-CAZ; generic name Polaprezinc) is the first drug for oral administration in which zinc plays an essential role. L-CAZ was approved as an anti-ulcer drug of membrane protection type. Characterization of L-CAZ was achieved by various spectroscopic methods along with elemental analysis. Zinc ion coordinates with L-carnosine to form a quadridentate 1:1 complex of polymeric nature in order to maintain low strain of chelate rings. L-CAZ can remain in stomach juice without rapid dissociation and adhere to ulcerous lesion specifically, after which L-carnosine and zinc are released to heal the ulcer. L-CAZ exhibited high efficacy in clinical use without any serious side effect. L-CAZ exhibited an inhibitory effect on Helicobacter pylori. Physicochemical aspects on carnosine, zinc, and zinc complex can explain favorable features of L-CAZ as a drug.

Molecular cloning and nucleotide sequence analysis of a novel human papillomavirus (Type 82) associated with vaginal intraepithelial neoplasia.

The genome of a novel human papillomavirus (HPV-82) was cloned from a vaginal intraepithelial neoplasia grade I. In our series of 291 biopsy specimens, HPV-82 was identified in one case each of cervical intraepithelial neoplasia grade II and grade III by blot hybridization. The histological localization of HPV-82 DNA in the three lesions was confirmed by in situ hybridization. The results indicated that HPV-82 is an etiologic agent for vaginal and cervical intraepithelial neoplasia. By nucleotide sequence similarity of L1 open reading frame (ORF), HPV-82 was closely related to HPV-26, -51, and -69. To know the precise relationship between the HPVs, we determined the complete sequence of HPV-82, as well as that of HPV-69. Sequencing revealed that the four HPVs had no initiation codon in the E5 ORF and had extensive nucleotide sequence similarities in all ORFs. In addition, they exhibited unique frame position patterns for ORFs, different from those of the other genital HPVs.

Reference data of forearm bone mineral density in healthy Japanese male and female subjects in the second decade based on calendar age and puberty onset: Japanese Population Based Osteoporosis (JPOS) study.

Osteoporosis is a major public health problem in Japan. The second decade is an important period in which to attain a high peak bone mass. However, normal values of forearm bone mineral density (BMD) are not well known in children and adolescents. BMD at one-third of forearm length proximal to the ulnar end plate (BMD1/3) and the ultradistal forearm (BMDud) was measured using dual-energy X-ray absorptiometry (DXA) in 1207 (631 males, 576 females) Japanese subjects aged 9-18 years. Puberty onset was assessed by questionnaire, by obtaining the time that pubic hair appeared in males and the time that menstruation started in females. BMD1/3 and BMDud increased steadily with age in males. In relation to puberty development, these parameters also increased after puberty onset although the increase in BMD1/3 was not statistically significant after the fifth year from puberty onset and that of BMDud was not significant after the sixth year from puberty onset. BMD1/3 and BMDud increased with age and then plateaued in females. The increase in BMD1/3 was not statistically significant after 15-16 years of age and that of BMDud was not significant after 13-14 years of age. In relation to puberty development, the increase in BMD1/3 leveled out after the fourth year from puberty onset and that of BMDud also plateaued after the third year from puberty onset. We provide reference values of forearm BMD in Japanese children and adolescents by DXA according to calendar age and puberty development. Peak bone mass of the forearm may be in the late second decade in Japanese females.