Video image of genital melanosis provides strong evidence to support identification of a sexual offender.

A man in his thirties was suspected of committing a sexual offense against a young girl. A video on his mobile telephone provided the only evidence. Photographs obtained from the video showed male genitalia in two views, with the penis in both views exhibiting unique pigmentation. We appraised this case with the cooperation of dermatologists, who diagnosed the pigmentation as male genital melanosis, a relatively rare disease, which matched that on the suspected perpetrator's penis. Photographs obtained from the video were thus decisive evidence of sexual offense and identified the perpetrator.

Acrokeratosis neoplastica (Bazex syndrome): Report of two cases and literature review.

The skin often reflects the presence of internal diseases. Acrokeratosis neoplastica (Bazex syndrome) is a unique skin manifestation characterized by its erythematous hyperkeratosis with yellowish, adherent scales on the palm, sole, or other acral locations. There is a potentially high association between Bazex syndrome and malignant pathology, especially squamous cell carcinomas (SCC). To date, various skin conditions have been recognized as diagnostic indicators of insidious malignancies. The recognition of paraneoplastic dermatoses has a strong potential for prompt cancer detection and early therapeutic intervention. Here we describe clinical and forensic cases of Bazex syndrome that are associated with SCC of the glottis and lung. Bazex syndrome has been reported to be associated with a variety of cancers in addition to SCC. We review the clinical manifestations of Bazex syndrome and include updated knowledge on disease pathogenesis.

Deck-chair sign as a diagnostic clue for insidious T-cell lymphoma: An autopsy case of mycosis fungoides.

Skin reflects the presence of systemic diseases, leading to an unexpected diagnosis of insidious diseases. Deck-chair sign is a unique skin eruption characterized by widespread erythematous papules that become erythrodermic with spare skin folds. An association between the deck-chair sign and malignancies, especially hematological neoplasms, has been suggested. We report a forensic case of mycosis fungoides unexpectedly diagnosed in the presence of a deck-chair sign. Mycosis fungoides is representative of cutaneous T-cell lymphomas. Here, we successfully demonstrated the feasibility of analyzing mycosis fungoides in a forensic autopsy case using basic histopathology and serology. We emphasize that the underlying malignancy should be primarily considered in cadavers with a positive deck-chair sign and review current reports about this characteristic skin manifestation.

Fatal human herpes virus 6B myocarditis: Postmortem diagnosis of HHV-6B based on CD134+ T-cell tropism.

Human herpes virus 6 (HHV-6) is one of the most important pathogens of viral myocarditis, and is often responsible for sudden death in young adults. A 59-year-old immunocompetent man died of serious lymphocytic myocarditis, and his peripheral blood sample showed HHV-6 DNAemia. Recently, HHV-6 cell entry and reactivation have been suggested to be regulated by the expression of specific CD receptors on T lymphocytes. Here, we report a case of HHV-6 myocarditis diagnosed using an experimental method focused on this unique cell tropism. The interaction between HHV-6 and CD expression was assessed using an immunofluorescence assay. Colocalization between HHV-6B and CD134 was detected in lymphocytes infiltrating the myocardium, which was highly suggestive of an active HHV-6B infection and could be a useful criterion for postmortem diagnosis of HHV-6B myocarditis in the acute phase.

Inappropriate diet and fatal malnutrition in a 10-year-old child fed only infant formula throughout life: Novel pathological diagnostic criterion for starvation via lipophagy.

Fatal starvation is rarely seen in developed countries; when it occurs, it may be associated with medicolegal problems. Forensic pathologists are required to determine leading causes of death and provide opinions on the influence of starvation, especially in cases of suspected child abuse. Recently, starvation-induced steatosis was suggested to be regulated by lipophagy. Here, we report an extremely rare case of death by malnutrition of a 10-year-old boy, who was fed only infant formula throughout his life. The deceased presented with severe hepatic steatosis, probably related to prolonged malnutrition. Fatty liver changes, with deposition of small lipid droplets deposited in the peripheral lobules. High levels of P62 protein (overexpression of which indicates an autophagy impairment) were seen around the central vein region, whereas light-chain-3 (LC3) protein (an indicator of lipophagy activation) was unremarkable. Thus, in our case, impaired lipophagy influenced starvation-induced steatosis. To our knowledge, this article is the first to evaluate the application of lipophagy in forensic investigations as an objective diagnostic criterion.

Pre-administration of low-dose methamphetamine enhances movement and neural activity after high-dose methamphetamine administration in the striatum.

Methamphetamine (METH) is a powerful stimulant drug of abuse, with potent addictive and neurotoxic properties. In this study, the effects of low-dose METH administration prior to high-dose METH administration on movement and neural activity in rats were examined. Rats were administered low-dose (1 mg/kg/day) METH or saline for 5 consecutive days (m5 and s5, respectively), followed by high-dose (10 mg/kg) METH on day 6 (m5M and s5M, respectively). An accelerometer was used to evaluate the frequency of movement when rats were placed in a cage for 30 min. The expression of c-fos, a neuronal activity marker, in the striatum was analyzed using immunohistochemistry. Striatal protein expression of neuronal markers, including vesicular glutamate transporter 2 (VGLUT2), glutamate decarboxylase 67 (GAD67), tyrosine hydroxylase (TH), tryptophan hydroxylase 2 (TPH2), and the glial marker, glial fibrillary acidic protein (GFAP), was analyzed by western blot. Accelerometer counts and the numbers of c-fos-positive cells in the striatum were significantly higher in the m5M than in the s5, m5, and s5M groups. The expression levels of VGLUT2 and GAD67, but not those of TH, TPH2, or GFAP, were significantly higher in the m5M than in the s5M group. These results suggest that pre-administration of low-dose METH prior to high-dose METH administration in rats may alter excitatory and inhibitory neurons in the striatum, thereby affecting movement and neural activity in rats.

An autopsy report of accidental burial in a beach sand hole.

We present a 23-year-old married couple who died by accidental burial in a beach sand hole. The victims fell into a hole that had been covered with a plastic sheet, and were buried suddenly by sand that had been piled on the top of the sheet. At autopsy, facial congestion; petechial hemorrhages in the conjunctivae and the oral mucosa; skin petechiae at the face, neck and upper chest; congestion and hemorrhages in the cervical lymph nodes; and some minor hemorrhages in the cervical muscles were found in both victims. Little sand was evident in the airway, while sand debris was found in the oral cavity. Prior reports suggest that aspiration of sand is a major contributing factor in asphyxia after accidental burials. However, neck and chest compression and face coverage by sand masses could induce lethal asphyxia without airway obstruction caused by sand aspiration. Asphyxia was deemed to be the cause of death in both individuals and was considered to result from chest compression by sand. In addition, compression of the neck may also have contributed to asphyxia. In this instance, the sand beach hole was excavated for recreational purposes. The potentially life-threatening implications of beach sand hole excavations should be recognized and highlighted to prevent lethal accidents such as those described in this report.

Conditioned withdrawal drives heroin consumption and decreases reward sensitivity.

Aspects of drug withdrawal may become conditioned to previously neutral environmental stimuli via classical conditioning processes. Nevertheless, the significance of conditioned withdrawal effects in motivating drug intake remains largely unexplored. Here, we investigated the effects of conditioned withdrawal in modulating heroin consumption and brain reward sensitivity in rats. Rats intravenously self-administered heroin (20 microg/infusion) during 0 h (control), 1 h (nondependent), or 23 h (dependent) sessions and had daily intracranial self-stimulation (ICSS) thresholds assessed. ICSS thresholds remained stable and unaltered in control rats. In nondependent rats, heroin self-administration induced a transient activation of reward systems, reflected in lowering of ICSS thresholds. In dependent rats, heroin intake escalated across sessions and was associated with a gradual decrease in reward sensitivity, reflected in progressively elevated ICSS thresholds. Thus, as dependence develops, heroin may be consumed not only for its acute reward-facilitating effects, but also to counter persistent deficits in reward sensitivity. In nondependent rats, the opioid receptor antagonist naloxone (30 microg/kg) increased heroin consumption and reversed heroin-induced lowering of ICSS thresholds, effects resistant to classical conditioning. In contrast, in dependent rats naloxone (30 microg/kg) increased heroin consumption and also elevated ICSS thresholds above their already elevated baseline levels (i.e., precipitated withdrawal). Most importantly, stimuli repeatedly paired with naloxone-precipitated withdrawal provoked heroin consumption and elevated ICSS thresholds in dependent rats. Thus, conditioned stimuli predicting the onset of heroin withdrawal, and hence the reward deficits coupled with this state, may play a critical role in provoking craving and relapse in human opiate addicts.

Toluene inhalation induced neuronal damage in the spinal cord and changes of neurotrophic factors in rat.

We investigated the effects of toluene inhalation on neurons and neurotrophic factors in the spinal cord and the relationship between them. Male Wistar rats were exposed to toluene (1500ppm for 4h per day) for 7 days. To observe damage of the neurons in spinal cord with the toluene, expression of microtubule associated protein 2 (MAP2) and 70kDa heat shock protein (HSP70) in spinal cord were performed by immunohistochemistry. MAP2 was degraded and HSP70-immunoreactivity was enhanced in nerve cell bodies of the gray matter in toluene inhalation group. Immunoreactivity of glial fibrillary acidic protein (GFAP), a marker of astrocytes, was enhanced in the toluene-treated group. Furthermore, glial cell line-derived neurotrophic factor (GDNF)- and brain-derived neurotrophic factor (BDNF)-immunoreactivity in spinal cord were slightly decreased in the treated group. In addition, the concentrations of GDNF and BDNF in the spinal cord were determined using enzyme linked immunosorbent assay (ELISA). Concentration of GDNF was reduced significantly by toluene exposure. BDNF also reduced, but not significantly. The toluene inhalation caused the damage of the neuron in the spinal cord, which was accompanied by the decrease in the neurotrophic factors, such as BDNF and GDNF.

Altered expression of cytokeratin 7 and CD117 in transitional mucosa adjacent to human colorectal cancer.

The multi-step progression of colorectal cancer through precancerous lesions (adenoma and dysplasia) is associated with cumulative molecular alterations, a number of which have also been demonstrated to be present in morphologically normal transitional mucosa adjacent to colorectal cancer. The cytoskeletal protein cytokeratin 7 (CK7) and the receptor tyrosine kinase, KIT proto-oncogene receptor tyrosine kinase (CD117), encoded by the proto-oncogene c-Kit, are lacking in normal colorectal crypt epithelium and are aberrantly expressed in a subset of colorectal cancer. The aim of the present study was to evaluate the expression of CK7 and CD117 in morphologically normal transitional mucosa adjacent to colorectal cancer. Immunohistochemical staining for CK7 and CD117 was performed in the mucosa adjacent to five groups of surgically resected colorectal tumors [low-grade adenoma, high-grade adenoma, mucosal adenocarcinoma, small-sized invasive adenocarcinoma (≤2 cm) and large-sized invasive adenocarcinoma (>2 cm)]. CK7 was expressed in the mucosa adjacent to a subset of colorectal tumors, and the positivity ratio increased according to tumor grade from low-grade adenoma up to small-sized invasive adenocarcinoma (61.2%). However, the positivity ratio of CK7 in the mucosa adjacent to the large-sized invasive adenocarcinoma (25.0%) was significantly lower compared with that of the next lower grade. CD117 was also expressed in the mucosa adjacent to a subset of colorectal tumors. In contrast to CK7, the positivity ratio of CD117 increased according to tumor grade from low-grade adenoma all the way through to the large-sized invasive adenocarcinoma (45.0%). Based on these results, the mechanism of CK7 and CD117 expression in the transitional mucosa adjacent to colorectal cancer may be different, and analysis of their individual expression may provide novel insights into the development and progression of colorectal cancer.

Escalation of methamphetamine self-administration in rats: a dose-effect function.

RATIONALE: The transition from stable to escalated drug intake has been demonstrated in rats self-administrating cocaine and heroin using a single dose of drug. OBJECTIVES: To investigate the prolonged exposure to methamphetamine self-administration and the effect of various training doses of methamphetamine on the changes of methamphetamine intake over a 21-day period. METHODS: Two groups of rats were trained in 1-h daily sessions of methamphetamine self-administration [0.033 mg/infusion (inf); approximately 0.066 mg/kg/inf]. Methamphetamine access was increased to 6 h in one group [Long Access (LgA)] or maintained at 1 h in another [Short Access (ShA)]. The same procedure was repeated in rats exposed to different training doses of methamphetamine (0.05, 0.1, and 0.2 mg/kg/inf). RESULTS: In LgA rats, total and first hour intake of methamphetamine significantly increased compared to ShA rats at various methamphetamine doses. LgA animals, at all doses in the second study, escalated intake to 8-9 mg/kg per 6-h session, with the most rapid escalation occurring at 3-5 days at a methamphetamine dose of 0.1 mg/kg/inf. CONCLUSIONS: The escalation of drug intake observed with extended access is produced at multiple doses of methamphetamine. The rapidity of escalation depends on the dose. Ultimately, all doses in the dose-response study engendered self-administration of the same amount of total drug in a 6-h session in the extended-access group. Results suggest that the rapidity of escalation is dependent on dose and has an upper limit of intake over a period of 21 days.

An autopsy case of adrenal insufficiency 20 years after hypophysectomy: relation between stress and cause of death.

A 63-years-old man was found dead with the body soaking in water lying face up on a riverbank. Autopsy and diatom examination demonstrated that the cause of death was drowning. He had undergone hypophysectomy 20 years earlier. Autopsy, pathological and endocrinological findings demonstrated secondary and chronic hypothyroidism, hypogonadism, and adrenal insufficiency. The cadaver had fallen into the river, and received numerous wounds such as abrasions and subcutaneous hemorrhage. Moreover, it was suspected that he had developed hypothermia before death. Cortisol in the blood and 17- OHCS in urine were within the reference range. We suspect that the adrenocortical hormone was secreted into the blood as a result of various stresses due to wounds and hypothermia. However, it was suspected that sufficient hormone might not be secreted due to chronic adrenal insufficiency. This insufficient cortisol causes the decrease in the stress resistance, and might influence his cause of death. Moreover, as hypothyroidism decreases thermogenesis, he might have fallen into hypothermia easily. In addition, because both adrenocortical insufficiency and hypothyroidism caused the hypoglycemia, he might have fallen into the loss of consciousness. Therefore, it was considered that he had died by drowning, in relation to the adrenocortical insufficiency and panhypopituitarism.

Changes in renal function and oxidative damage in methamphetamine-treated rat.

In this study, we observed renal damage and peroxidative injury as the acute or sub-acute effect of methamphetamine (MA) to determine whether MA intoxication can be diagnosed from immunohistochemical changes in the kidney. In addition, renal function was investigated in relation to the immunohistochemical changes. A single administration of MA (group I) (50mg/kg/ (i.p.)) and repeated administration (group II) (10mg/kg/day (i.p.) for 5 days) were designed as an acute model and a sub-acute or chronic model. Immunohistochemically, cell damage markers were observed. Then, renal function markers and minerals in blood were measured. Myoglobin and creatinine phosphokinase (CPK) in blood were also analyzed. In group I, ubiquitin immunoreactivity was enhanced only in the renal tubules. Creatinine increased, while K, Ca, and P decreased (P<0.01). CPK increased significantly (P<0.01). Therefore, it was suspected that MA might induce renal dysfunction with renal tubule damage. This damage might be related to leakage of CPK from muscle. In group II, 8-hydroxy-2'-deoxyguanosine (8-OH-dG) increased immunohistochemically and quantitatively (P<0.01). It was considered that oxidative DNA damage might be induced by repeated administration. It was considered that this study offers basic information for the evaluation of pathological changes in the kidney in MA-related autopsy cases.

Effect of hypothermia on postmortem alterations in MAP2 immunostaining in the human hippocampus.

Ischemic neuronal injury induce degradation of microtubule-associated protein 2 (MAP2). In addition to ischemia, postmortem brains show alterations in MAP2 immunoreactivity in the hippocampus, suggesting that the factors inducing cytoskeletal disruption in postmortem brain are similar to those in ischemic brains. Hypothermia reduces the severity of ischemic injury including disruption of MAP2 in the hippocampus. However, whether hypothermia reduces postmortem changes of MAP2 was not clear. In this study, we evaluated the effect of hypothermia on postmortem degradation of MAP2 in the human hippocampus at various postmortem intervals using immunohistochemistry. In postmortem brains without hypothermia (the normothermic group), the locus of MAP2 immunoreactivity moved from the dendrites to the cell bodies prior to becoming undetectable with increasing postmortem interval, particularly in the CA1-subiculum region. On the other hand, the change in MAP2 immunoreactivity was remarkably attenuated in brains of death from cold (the hypothermic group). The present study demonstrated that MAP2 disruption is remarkable in the CA1-subiculum region of autopsied brains and that hypothermia reduces the postmortem change of MAP2, as observed in ischemic brain. Therefore, immunostaining of MAP2 in the hippocampus could be used to diagnose hypothermia.

Effect of hypothermia on postmortem alterations in MAP2 immunostaining in the human hippocampus.

Ischemic neuronal injury induce degradation of microtubule-associated protein 2 (MAP2). In addition to ischemia, postmortem brains show alterations in MAP2 immunoreactivity in the hippocampus, suggesting that the factors inducing cytoskeletal disruption in postmortem brain are similar to those in ischemic brains. Hypothermia reduces the severity of ischemic injury including disruption of MAP2 in the hippocampus. However, whether hypothermia reduces postmortem changes of MAP2 was not clear. In this study, we evaluated the effect of hypothermia on postmortem degradation of MAP2 in the human hippocampus at various postmortem intervals using immunohistochemistry. In postmortem brains without hypothermia (the normothermic group), the locus of MAP2 immunoreactivity moved from the dendrites to the cell bodies prior to becoming undetectable with increasing postmortem interval, particularly in the CA1-subiculum region. On the other hand, the change in MAP2 immunoreactivity was remarkably attenuated in brains of death from cold (the hypothermic group). The present study demonstrated that MAP2 disruption is remarkable in the CA1-subiculum region of autopsied brains and that hypothermia reduces the postmortem change of MAP2, as observed in ischemic brain. Therefore, immunostaining of MAP2 in the hippocampus could be used to diagnose hypothermia.

Toluene inhalation induces glial cell line-derived neurotrophic factor, transforming growth factor and tumor necrosis factor in rat cerebellum.

Rats were exposed to toluene (1500 ppm for 4 h per day) for 7 days. After toluene inhalation, only granule cells in the dentate gyrus of the hippocampus were slightly shrunken. In the cerebellum, several Purkinje cells were shrunken and lost, and the white matter was thinner than in controls. Microtubule-associated protein 2 (MAP2)-immunopositive filaments of neuronal processes were slightly disarrayed in the radial layer of the hippocampus, and were fragmented in the molecular layer of the cerebellum. It was considered that toluene induced neuronal changes both in the cerebellum and the hippocampus. To elucidate the effect of neurotrophic factors on those neuronal changes, glial cell line-derived neurotrophic factor (GDNF), transforming growth factor (TGF) and tumor necrosis factor (TNF) in rat brain were examined immunohistochemically. In control rats, TNF-alpha was not stained in either the hippocampus or the cerebellum, while TGF-beta1 was scarcely expressed in the cerebellum. GDNF was minimally expressed in the Purkinje cells in the cerebellum. After toluene-treatment, TGF-beta1 was over-expressed in the endothelium of the capillary vessel walls in both regions. In the cerebellum, TNF-alpha was induced only in the granule cells, while GDNF expression was enhanced in the Purkinje cells. These data suggest that toluene induces astrocyte activation through TGF-beta1 upregulation, which then induces GDNF in the Purkinje cells and TNF-alpha in the granule cells of the cerebellum. The differences in the expression of the neurotrophic factors may account for neurobehavioral changes after toluene exposure.

Toluene inhalation induced 8-hydroxy-2'-deoxyguanosine formation as the peroxidative degeneration in rat organs.

The effect of toluene inhalation on oxidative damage in rat organs was examined. Male Wistar rats was inhaled toluene (1500 ppm for 4 h a day) for 7 days. Quantitatively and immunohistochemically, oxidative DNA damage, lipid peroxide (LPO) and superoxide dismutase (SOD) were examined. As a marker of the oxidative DNA damage, 8-hydroxy-2'-deoxyguanosine (8-OH-dG) immunoreactivity increased in the lung, liver and kidney. The amount of 8-OH-dG also increased in liver and kidney significantly. In the testis, the amount of 8-H-dG did not increase, however 8-OH-dG immunoreactivity enhanced in the spermatogonia. SOD immunoreactivity increased in the lung, liver and kidney. However, 4-hydroxy-nonenal immunoreactivity and the amount of LPO did not change in each organ. Thus, oxidative damage by toluene is mainly DNA damage, especially, the oxidative DNA damage observed in the lung, liver and kidney for the increase of the immunoreactivity and amount of 8-OH-dG.

An adult autopsy case of acute encephalopathy associated with influenza A virus.

On a cold winter morning, a 35-year-old male was unexpectedly found dead and therefore autopsied. Macro- and microscopically, the lungs were demonstrated bronchopneumonia. On the surface of brain, small blood vessels were slightly congested. Microscopically, brain edema was also observed, and proliferation of lymphocytes was observed around the capillary vessels of the hippocampus. These findings suggested a viral infection of the cerebrum. We conducted an immunohistochemical study with antibody against influenza virus. Influenza A virus antigen was detected in both the lungs and brain. Therefore, findings were compatible with influenza A encephalopathy. Even when serological inspection is not performed, it is useful to inspect localization of the virus antigen immunohistochemically. We considered that it is necessary to perform pathological examination for influenza encephalopathy in sudden death cases when influenza is epidemic.

Influence of post-mortem changes on DNA typing (D1S80, TH01, HLA DQA 1, and PM typing system): case studies for personal identification.

Between 1996 and 2002, we tested a total of 20 unidentified bodies for DNA typing. We describe here the relationships among detection rates achieved by four DNA typing systems (D1S80 typing, TH01 typing, HLA DQA1 typing, and PM typings), the post-mortem interval, types of specimens (bone, nail, and blood), post-mortem changes, and the site at which the corpse was found (indoors, outdoor, or in the sea). Detection rates for PM typings, HLA DQA1 typing, TH01 typing, and D1S80 typing in all cases were 94.7, 90.0, 73.7, and 50.0%, respectively. The success of the typings was highly influenced by the post-mortem interval. Using blood, almost all DNA types were detected, while the nail showed comparatively higher detection rates than bone. The detection rate decreased in order with indoor, outdoor, sea, and soil as the site at which the corpse was found. It is important to consider the specimen, the site at which the corpse was found, and the post-mortem interval to successfully achieve DNA typing.