Human mtDNA and Y-chromosome variation is correlated with matrilocal versus patrilocal residence.

Genetic differences among human populations are usually larger for the Y chromosome than for mtDNA. One possible explanation is the higher rate of female versus male migration due to the widespread phenomenon of patrilocality, in which the woman moves to her mate's residence after marriage. To test this hypothesis, we compare mtDNA and Y-chromosome variation in three matrilocal (in which the man moves to his mate's residence after marriage) and three patrilocal groups among the hill tribes of northern Thailand. Genetic diversity in these groups shows a striking correlation with residence pattern, supporting the role of sex-specific migration in influencing human genetic variation.

Results of single and double autografts for high-risk neuroblastoma patients.

Although intensive therapy with autologous bone marrow transplantation (ABMT) has improved the outcome of advanced neuroblastoma, nearly half the patients with this disease still relapse after a single ABMT. In our previous study, 10 of 22 patients relapsed within 16 months post-transplantation. Predictive risk-factors for relapse were the presence of bone lesions at diagnosis, and a minor response or progressive disease at transplantation. In order to improve the outcome of these high-risk patients, we tested the feasibility of double autografts. To date, eight patients have been treated, and no treatment-related deaths were observed. Six remain in CR or with stable disease for 6 to 29 months. Although more cases and longer observation are needed to draw conclusions, these results are encouraging.

Chronic graft-versus-host disease in children and adolescents after bone marrow transplantation from HLA-matched donors.

We analyzed 98 pediatric patients who underwent bone marrow transplantation (BMT) from serologically HLA-matched related donors (RD) or unrelated donors (UD) at our institute to clarify the actual status of chronic graft-versus-host disease (cGVHD). There were 36 evaluable cases of RD-BMT and 35 of UD-BMT. cGVHD was observed in 8 RD-BMT cases (22.2%) and in 23 UD-BMT cases (65.7%). In the RD-BMT cases, the limited and extensive types of cGVHD were observed in 4 cases each, whereas in the UD-BMT cases, the limited type was seen in 11 cases and the extensive type in 12. Prior acute GVHD was observed in 6 RD-BMT cases and in 18 UD-BMT cases. Two RD-BMT patients with extensive type cGVHD died of relapse and cytomegalovirus infection, and 4 UD-BMT patients died because of bronchiolitis obliterans, fungal infection, liver failure, and multiple organ failure, respectively. The incidence of cGVHD in these pediatric patients was as high as that in adult patients when UD-BMT was performed. Some UD-BMT patients required long-term immunosuppressive therapy after BMT. These findings suggest that cGVHD is a serious problem in pediatric UD-BMT. Therefore, intensive prophylaxis and treatment of GVHD must always be performed after UD-BMT.

A case of muscular hamartoma of the breast.

We describe a 74-year-old female presenting with a right breast mass. She had found the mass on self-examination. Physical examination revealed a 2.2 x 2.5 cm, firm, smooth, and mobile lump in the upper medial portion of the right breast. Mammography revealed a well marginated, oval-shaped, and isodense nodule. Calcification was not evident. On ultrasonography, the lesion was 17 x 18 x 9 mm and located 5 mm below the overlying skin. Excisional biopsy under local anesthesia was performed. The tumor was easily excised. Histopathologically, the lesion was composed of intersecting bundles of spindle-shaped smooth muscle cells, and involved peripheral ducts and fat tissue. Immunohistochemical staining showed positivity for alpha-smooth muscle actin (SMA), but was negative for S-100 protein, myoglobin, keratin, and vimentin. From these findings a muscular hamartoma of the breast, a rare subtype of hamartoma, was diagnosed.

[Medulloblastoma originating from the superior cerebellar peduncle: a case report].

A rare case of medulloblastoma originating from the superior cerebellar peduncle is reported. After tilting her neck to the right, a 4-year-old girl experienced a left-side hemiparesis for 3 months. Computed tomography (CT) scan and magnetic resonance image (MRI) showed an enhanced mass in the left tentorial incisura. The preoperative diagnosis was trochlear nerve neurinoma or tentorial meningioma, while the postoperative pathological diagnosis was medulloblastoma. Since medulloblastoma is thought to originate from the external granular layer, it is speculated that the external granular layer migrated through the superior cerebellar peduncle and changed to medulloblastoma.

Sequence variation found in the flanking region of a trimeric short tandem repeat at the PLA2 locus: its considerable effect on estimating alleles.

Amplified alleles at the PLA2 short tandem repeat locus were sequenced and analyzed using different combinations of the PCR primer. When changing one side of the primers from the previous design to our original one, additional alleles, which had been previously hidden, could be newly detected in two out of 60 DNA samples of unrelated Japanese individuals. The sequence data revealed both 'hidden alleles' to be accompanied by a 3-bp deletion in the 5'-flanking region of the trimeric short tandem repeat. The position of the deletion corresponded to the exact 3' end of the primer, which had been formerly used. In the present case, both of the base numbers, which constituted the core repeat unit and which were deleted in the 'hidden alleles', were equal. Therefore, it was impossible to distinguish an allele from that with not only an additional trimeric repeat but a 3-bp deletion without the sequence analysis. This result indicates that the estimated allele size does not always reflect the difference in the repeat number even if the alleles regularly differ in size by one repeat unit. Moreover, this study suggests the presence of apparent homozygotes, of which the fellow of the heterozygous alleles is hidden by an unsuccessful amplification due to the sequence variation.

Combined polymorphism associated with a 3-bp deletion in the 5'-flanking region of a tetrameric short tandem repeat at the CYP19 locus.

Allele frequencies for a tetrameric short tandem repeat locus, CYP19, were determined in 220 unrelated Japanese individuals. The frequency distribution was similar to that of a previous report. However, PCR amplification using two sets of primers suggested that one allele consisting of 7 TTTA repeats (the allele 7) was divided into two separate ones, 7P (standard) and 7(-3), which differed in length for 3 bp. Sequence analysis of the two alleles revealed that the smaller 7(-3) had a 3-bp deletion in the 5'-flanking region of the tetrameric repeat. The deletion was also observed as the allele 7(-3) in non-Japanese such as Caucasians and Africans; it was only found in a part of the allele 7 [7(-3)], but not in the other alleles, in all examined populations. In the Japanese population, the deletion was observed in 39.6% of the allele 7, or 24.8% of all of the alleles. When the STR polymorphism at the CYP19 locus was combined with the polymorphic deletion adjacent to the repeat region, the numerical indices of genetic polymorphisms (heterozygosity, polymorphism information content and the power of discrimination) in Japanese rose from 0.541, 0.46 and 0.723 to 0.723, 0.66 and 0.864, respectively. Accordingly, the combined polymorphism at the CYP19 locus can be considered appropriate for hereditary analysis in the field of forensic science.

[A case of common bile duct cancer responding to MMC leucovorin, 5-FU, and UFT combination chemotherapy and radiation].

A case of unresectable common bile duct cancer involving the portal vein and with Virchow lymph node metastasis was treated with MMC, Leucovorin, 5-FU and UFT combination chemotherapy as well as radiation. The case was a 71-year-old female who was admitted to the hospital with vomiting and anorexia. Abdominal US study showed obstructive jaundice. The PTCD tube was pierced to dilate the intrahepatic bile duct. Bile juice cytology was class V. Abdominal CT showed paraaortic lymph node metastasis. Angiography revealed portal vein invasion, and the diagnosis was unresectable common bile duct cancer. We started anticancer therapy and radiation. The anticancer therapy selected was MMC, LEUCOVORIN, 5-FU and UFT combination chemotherapy. After 2 cycles of the treatment, Virchow lymph node completely disappeared and the symptoms diminished. These combination therapies were effective for common bile duct cancer.

Size separation of sodium dodecyl sulfate complexes of human plasma proteins by capillary electrophoresis employing linear polyacrylamide as a sieving polymer.

Electrophoretic conditions to separate sodium dodecyl sulfate (SDS) complexes of human plasma proteins according to their size differences, by capillary electrophoresis employing linear polyacrylamide as a sieving matrix (LPA-CE), have been examined. Using the optimized separation conditions, SDS complexes of human plasma proteins not treated with reducing agents were separated into about 40 peaks and shoulders within 60 min. The molecular mass values of major peaks in a separation pattern were estimated from a plot of molecular mass and migration time for standard proteins and some of the major plasma proteins have been identified on the pattern. The electrophoretic conditions were successfully applied for the analysis of proteins in immunoglobulin G (IgG) myeloma sera.

[Informing advanced cancer patients of the terminal nature of their disease and how this influenced their mental state].

From January, 1983 to July, 1987, advanced cancer patients, who have since died, were analysed as to the influence of their mental state after being told of the terminal nature of their disease. After obtaining family consent, 27 out of total of 65 patients were told the true nature of their disease, in contrast to the remaining 38 terminal patients who were kept unaware that they had cancer on the insistence of their families. The depression observed just before death was the marker used to determine the patients' mental distress during the terminal period, and it was noted that the incidence of this terminal depression was higher in the uniformed patients, and highest in those with pain who had not been told. Thus it was concluded that informing a patient that he or she has terminal cancer does not always induce mental distress, even in patients in an advanced cancer stage. Further, the pain that cancer causes must be effectively fought, since this was the major cause of mental distress during the terminal stage of the disease.

A genetic study of 2,000-year-old human remains from Japan using mitochondrial DNA sequences.

We present nucleotide sequence data for mitochondrial DNA extracted from ancient human skeletons of the Yayoi era (ca. 2,000 BP) excavated from the Takuta-Nishibun site in northern Kyushu of Japan. Nucleotide sequence diversity showed that the Yayoi people of the Takuta-Nishibun site were not a genetically homegeneous population. This site shows a diversity in the burial style. Phylogenetic analysis indicated a statistically significant correlation between burial style and the genetic background of the Takuta-Nishibun individuals, and revealed no discrete clusterig patterns for the Yayoi individuals, for early modern Ainu, or for the Jomon people.

Correlation of plasma protein separation patterns obtained by two-dimensional polyacrylamide gel electrophoresis and by capillary electrophoresis.

We used three different electrophoretic techniques for the analysis of human plasma proteins: (i) two-dimensional polyacrylamide gel electrophoresis (2-D PAGE), with sodium dodecyl sulfate (SDS) used only in slab gel electrophoresis; (ii) capillary isoelectric focusing (CIEF) with no denaturants; (iii) linear polyacrylamide (LPA)-filled capillary electrophoresis with SDS (SDS-CE). With technique (i), data on isoelectric point and molecular size of plasma proteins can be obtained. Techniques (ii) and (iii) are suited to obtain quantitative information on proteins. The separation principle used in technique (ii) is closely related to that used in the first dimension of technique (i), and that used in technique (iii) related to that in the second dimension of technique (i). Therefore, we could successfully correlate protein separation patterns obtained by 2-D PAGE and those obtained by capillary electrophoresis. The advantages of correlating data obtained by various electrophoretic techniques in the course of constructing a comprehensive database on human plasma proteins are discussed.

Molecular genetic analysis of remains of a 2,000-year-old human population in China-and its relevance for the origin of the modern Japanese population.

We extracted DNA from the human remains excavated from the Yixi site ( approximately 2,000 years before the present) in the Shandong peninsula of China and, through PCR amplification, determined nucleotide sequences of their mitochondrial D-loop regions. Nucleotide diversity of the ancient Yixi people was similar to those of modern populations. Modern humans in Asia and the circum-Pacific region are divided into six radiation groups, on the basis of the phylogenetic network constructed by means of 414 mtDNA types from 1, 298 individuals. We compared the ancient Yixi people with the modern Asian and the circum-Pacific populations, using two indices: frequency distribution of the radiation groups and genetic distances among populations. Both revealed that the closest genetic relatedness is between the ancient Yixi people and the modern Taiwan Han Chinese. The Yixi people show closer genetic affinity with Mongolians, mainland Japanese, and Koreans than with Ainu and Ryukyu Japanese and less genetic resemblance with Jomon people and Yayoi people, their predecessors and contemporaries, respectively, in ancient Japan.

[A case of bilateral metastatic breast carcinoma from gastric carcinoma].

The patient was a 48-year-old woman who had undergone radical surgery for gastric carcinoma in 1981. Seventeen months after the operation, recurrence of gastric carcinoma at the anastomotic stoma was found, and total gastrectomy was performed. Fourteen months after the second operation, she was revealed to have bilateral breast tumors and underwent exploratory excision. Histological examination suggested primary malignant tumor of the breast. Bilateral standard radical mastectomy was done seven days after the excision. Final histological examination revealed metastatic breast cancer originating from the stomach. She died from general metastasis seven months after the radical mastectomy in spite of adjuvant immunochemotherapy.

[The importance of the mesocolon in the occurrence of liver metastasis from primary colorectal carcinomas].

The frequency of liver metastasis was analyzed in 1,558 patients with primary colorectal carcinomas. The highest frequency of liver metastasis occurred in carcinomas of the transverse colon (17%) and the sigmoid colon (15%), when compared to the other segments, such as the cecum (10%), ascending colon (9%), descending colon (6%), rectum (9%) and anal canal (0%). It would appear that carcinoma located in those segments of the human colorectum containing any portion of the mesocolon are more prone to metastasize into the liver.