The research conducted in our department is important in establishing more objective and accurate diagnostic techniques of death and disabilities which are in accordance with actual practices and in collecting and analysing data which contribute to evaluation and explanation of autopsy findings.

Previously, our department conducted practical research which is applicable to overall legal medicine with our main focus on two topics:

• Morphological and molecular-biological study of the central nervous system and endocrine system organs, a comprehensive examination of objective evaluation of stress diagnosis
• Physiobiochemical tests for evidence-based objective forensic-pathological diagnosis

I. Multilateral statistical analysis of forensic autopsy data

Outline: Forensic autopsies are performed to elucidate the cause and process of death and underlying diseases and/or complications associated with cases of ‘suspicious deaths’, including deaths by external causes and sudden deaths, which present potential social and legal issues. In many cases, there is limited information available on the medical history and the condition of death, yet an objective evaluation is required regardless.

Traditionally, diagnoses were heavily dependent on morphological findings; however, we, have actively applied various biomarkers used for clinical diagnosis to autopsy diagnosis. Furthermore, we have performed molecular-biological analysis of the process of death due to various causes to improve the accuracy of diagnosis.

As a result, important data on injury and illness prevention, as well as management of social crisis, are being accumulated through forensic diagnosis of individual cases. By statistically analysing and publishing these autopsy data, we can provide useful information for (1) improvement of the accuracy of forensic diagnosis, (2) prevention of injury and illness and (3) prevention of crimes and disasters. The course of data analysis is reflected in the results of appraisal for autopsies performed in our department.

II. Comprehensive analysis of selective transport mechanisms for physiologically active substances migrating from blood to cerebrospinal fluid

The purpose of this study is to clarify the physiological functions of the choroid plexus by investigating the migration of different kinds of drugs and physiologically active substances from the perspectives of forensic medicine, fine morphology, and neuroscience.

A model of the choroid plexus?capillary epithelial cell barrier will be constructed using cultured cells to elucidate the mechanisms of selective transport of various physiologically active substances from the blood to the cerebrospinal fluid.

In general, to elucidate the mechanisms by which toxins, hormones, and other physiologically active substances in the blood migrate into the cerebrospinal fluid and then into the brain, it is necessary to clarify the existence of receptors in the brain and choroid plexus, the genotypes of the different types of receptors in the brain, and the roles of such functions as the choroid plexus-capillary epithelial cell barrier (blood-cerebrospinal fluid barrier).

The blood-cerebrospinal fluid barrier is thought to have selectivity with respect to substances that migrate from the blood to the cerebrospinal fluid and then to the central nervous system, but the detailed physiological function of the choroid plexus is not understood.

We will perform a study based on cultured cells to analyze the mechanisms for the migration of substances from the cerebrospinal fluid into the brain.

III. The role of vasopressin in the progression of brain oedema and application to severity evaluation

The pathophysiology of brain oedema which occurs due to various events such as cerebrovascular disorders, head trauma, breathing disorders, various poisoning, and metabolic disorder. This information can be used to understand the role of vasopressin in the progression of brain oedema and in severity evaluation.

It is becoming clear that vasopressin, which is a hormone which controls diuresis, is involved in nerve cell protection. To clarify the significance of vasopressin in forensic diagnosis, we use immunohistological and biochemical methods to examine changes in vasopressin in the brain.

Furthermore, we examine the changes in vasopressin concentration in blood and cerebrospinal fluid while comparing with morphological changes, and examine the role of vasopressin in the progression of brain oedema and evaluation of brain oedema severity.

IV. Risk evaluation of drug poisoning deaths based on individual genetic factors

Since specific pathological findings are limited in poisoning deaths, their diagnosis is strongly dependent on toxicological test results. However, definitive toxicological findings may not be obtained for drug abusers or in cases of protracted deaths. Even within treatment doses, deaths could occur as a side effect, making the determination of cause of death difficult.

In our department, we have routinely performed pathological, toxicological, and biochemical examinations in all autopsy cases, and have referenced and analysed pathological findings and biochemical data from drug poisoning such as from alcohol, stimulants, and psychotropic drugs.

As a result, systematic biochemical examinations have clarified parts of the clinical picture of drug poisoning and related deaths. In other words, the difference between systemic failure in ‘functional deaths’ such as rhabdomyolysis, death with various external causes such as heatstroke and freezing to death, and the process of sudden deaths have become clearer.

However, pathological and biochemical examinations are insufficient in understanding internal factors of each drug addicted person. Therefore, we analysed pharmacokinetics related genes in cases of drug poisoning deaths, and examined the establishment of cause of deaths and pathophysiology in cases of drug-related deaths from the genetic perspective.