Patients with Graves' disease who developed insulin autoimmune syndrome (Hirata disease) possess HLA-Bw62/Cw4/DR4 carrying DRB1*0406.

The insulin autoimmune syndrome (IAS) is characterized by the following diagnostic criteria: severe spontaneous hypoglycemia without evidence of exogenous insulin administration, high levels of total serum immunoreactive insulin, and the presence of a high titer of antiinsulin antibody. Just before the onset of IAS, 13 of the 35 (37%) patients with IAS examined in this study had taken methimazole for the treatment of Graves' disease. To investigate the difference between the Graves' disease patients treated with methimazole who developed IAS and other IAS patients, HLA class II genes in both groups were analyzed by serological and DNA typing methods. All 13 patients with Graves' disease who developed IAS possessed a specific allelic combination, Bw62/Cw4/DR4 carrying DRB1*0406, whereas only 1 of 50 Graves' disease patients without IAS had Bw62/Cw4/DR4 (odds ratio, 891; P < 1 x 10(-10)) and carried not DRB1*0406 (odds ratio, 2727; P < 1 x 10(-10)), but DRB1*0405. Of the 22 IAS patients without Graves' disease, 13 had the combination Bw62/Cw4/DR4 carrying DRB1*0406 (odds ratio, 19.0; P < 0.07). Thus, it is highly likely that patients with Graves' disease develop IAS via treatment with methimazole when their Bw62/Cw4/DR4 carry DRB1*0406.

[Clinicopathological study on multiple primary malignant neoplasms, related to the oral-maxillofacial region].

The present study consists of a clinical and histopathological analysis of those cases which were diagnosed as multiple primary malignant neoplasms of the oral-maxillofacial region and the other organs. 9 patients of those multiple primary malignant neoplasms out of 261 patients of malignant neoplasms in the oral-maxillofacial region, who visited in out department from 1975 to 1986, were detected. 3.4% of the incidence rate was calculated. All the cases were male, and these included each 1 case of triple and quadruple. 7 cases were detected prior in the oral-maxillofacial region to the other organs. There seemed to be a preponderance to early detection of a neoplasm in the oral-maxillofacial region. Therefore, the possibility of multiple primary malignant neoplasms should be kept in mind in the routine clinical activities. 2 cases were synchronous, 6 months or less interval between the first and the second neoplasms, the others were metachronous, averaged 5-year interval. The primary sites in the oral-maxillofacial region were tongue (3 cases), floor of the mouth (2), buccal mucosa (2), lower gingiva (1), maxillary sinus (1), all of them were diagnosed as squamous cell carcinomas, histopathologically. The other organs were esophagus (3 cases), stomach (2), colon (2), lung (2), liver (1), urinary bladder (1), hypopharynx (1). Histopathological diagnoses of them were squamous cell carcinomas (3 cases of esophagus, each 1 case of lung, urinary bladder, and hypopharynx), adenocarcinomas (2 cases of stomach and colon, and 1 case of lung), and a hepatoma. It's necessary to differentiate the multiple primary malignant neoplasms from metastases when each of them were diagnosed as squamous cell carcinomas.(ABSTRACT TRUNCATED AT 250 WORDS)

[Clinico-statistical study of medical complication in dental patients].

Eight hundred and fifty two cases, who were introduced from the Dental Hospital to Department of Internal medicine, Medical Hospital at Niigata, The Nippon Dental University, were examined for medical complications. About one hundred and fifty cases were introduced per year from the Dental Hospital, which consisted of about 15% of the total outpatients in the Department of Internal medicine. The age distribution showed a high incidence of patients in their 50's. The number of patients over 60 years old was 220 (25.8%), and the number of patients over 65 years old was 160 (18.8%). There was then a high percentage of elder patients. The reason for the initial medical examinations was the need for a pre-operative medical examination in 42.6% of the total cases. Concerning medical complications among the patients, the highest incidence was hypertension in 116 cases (13.6%); the second highest was hepato-biliary and pancreatic diseases in 114 cases (13.4%); and heart diseases in 81 cases (9.5%). Eighteen cases of HBs antigen positive (2.1%) were seen among the patients with liver diseases. Among those with blood diseases, anemia showed the highest incidence, and a small number had leukemia and hemophilia. Diabetes mellitus showed up in 39 cases (4.6%), most of them being more than 40 years of age. Mentally and physically handicapped patients accounted for 30 cases. Half of them were from the pre-operative examination area, like tooth extraction.

[Clinical significance of serum acid soluble glycoproteins (ASP) and immunosuppressive acidic protein (IAP) in inflammatory diseases and liver diseases].

In order to study the clinical significance of ASP and IAP, we have measured serum concentration of ASP and IAP in 259 patients with inflammatory diseases, non-inflammatory diseases, autoimmune diseases and liver diseases. Significantly higher correlation (coefficient of correlation = 0.922) was found between ASP and IAP. There were good correlation between ASP, IAP levels and erythrocyte sedimentation rate (ESR), C-reactive protein (CRP). Coefficient of correlation were 0.705 and 0.673 between ESR and ASP, IAP; 0.621 and 0.623 between CRP and ASP,IAP, respectively. There were food correlations between ASP levels and thrombo test (TT) and hepaplastin test (HPT). The positive rate and mean concentration of ASP, IAP in patients with inflammatory diseases were significantly higher than noninflammatory diseases. It is suggested that serum ASP, IAP could be one of the useful indicator for evaluating the clinical course of patients with inflammatory diseases. Serum concentration of ASP, IAP in patients with chronic liver diseases were lower than normal subjects, especially serum levels in patients with decompensated liver cirrhosis and chronic hepatitis (active) were significantly lower than normal subjects. In patients with hepatoma with cirrhosis, serum levels of ASP, IAP were significantly lower than the hepatoma patients without cirrhosis. The determination of ASP, IAP in liver diseases seems to be useful for evaluating the severity of diseases, the effects of therapy and the forecast of prognosis.

[Study on renal osteodystrophy using 2-compartment model analysis of bone scintigraphy. 1. Clinical significance of K Index].

The dynamic analyses of bone scintigraphy were performed in 30 cases of hemodialysed patients. The regression analyses between biochemical data or duration and K indexes obtained from the 2-compartment model analysis in the maxillofacial region were carried out. The obtained results were as follows. 1) The duration and K indexes were significantly correlated with 1 or 2% of significance level in the parietal bone and the zygomatic bone. 2) Serum Ca and K indexes were highly correlated in every settled ROI. The correlation coefficients were distributed from 0.58 to 0.79. In the cranial bone the correlation were more higher than in maxilla and mandibular bone. 3) Serum ALP and K indexes have more higher significant level of correlation than the results of Ca. The correlation coefficients were distributed from 0.48 to 0.83. The level of significance were changed by location. The highest correlation coefficient was 0.83 in the parietal bone. 4) Serum c-PTH and K indexes have significant correlation in every settled ROI with the correlation coefficient from 0.59 to 0.69. The significance level were nearly equal in every location. 5) In the case of subtotal parathyroidoectomy the K indexes which were abnormally high in preoperation showed the tendancy to decrease toward normal range in postoperation. These results indicated that K indexes reflected the bone change caused by renal osteodystrophy. And the K indexes considered to be usefull to estimate the bone improvement.

[Clinical evaluation of serum immunosuppressive acidic protein (IAP) and acid soluble glycoproteins (ASP) in patients with malignant tumors].

In order to study the clinical significance of IAP and ASP, we have measured serum concentration of IAP and ASP in patients with different cancer types including digestive organs, head and neck. Significantly higher correlation (coefficient of correlation = 0.924) was found between IAP and ASP. IAP and ASP levels were elevated in about 60-80% of cancer from digestive organs except hepatocellular carcinoma, and in about 56-100% of head and neck tumor. There was no correlation between IAP, ASP and various tumor markers (CEA, CA19-9, AFP) in all malignancies except pancreatic cancer. There was positive correlation between CEA and IAP, ASP in pancreatic cancer. IAP and ASP levels were significantly higher in patients with cancer having evidence of disease than the patients with cancer who had no evidence of disease, and so the determination of IAP and ASP was clinically useful for the diagnosis of tumor existence. At the time of diagnosis of recurrence, the levels of IAP and ASP were elevated in about 70% of patients with cancer recurrence. There was a definite relation between IAP, ASP and the gastric cancer stage. In later state (stage III and IV), serum IAP and ASP levels were significantly higher than the levels of stage I and II. In hepatocellular carcinoma without liver cirrhosis, the levels of IAP and ASP were higher than the patients with cirrhosis. The determination of IAP and ASP seems to be useful for monitoring clinical course, judgement of therapeutic effects.

[Clinico-statistical study of inpatients and autopsied cases in our clinic].

The statistics of clinical observation at Department of Internal Medicine, Nippon Dental University at Niigata from July 1981 to December 1987 (duration 6.5 years) were as follows: Total number of inpatients: 1,238, Total number of death cases: 106. Findings include: 1) Ratio of male patients to female patients 1.34:1.00. Male deceased patients to female deceased patients 1.52:1.00. 2) Average patients number hospitalized per year was 200. The high percentaged of certain advanced aged groups was reflected by the recent demographic changes in the society in general.; in their 60's 46.0%, in their 70's 24.3%, in their 80's 6.7%. In these age groups, female number is tendency to increase the number of male. 3) The diseases of inpatients were mostly due to the digestive tract, which accounted for 60.4% of the total. Of this percentage, 65% was due to hepato-biliary diseases. 4) The death statistics of malignant tumor was 68.9%; Benign diseases being 31.1%. Male patients died from hepatocellar carcinoma, lung cancer, colon cancer and stomach cancer, in descending order. Females died from cancer of the biliary tract, stomach cancer and hepatocellular carcinoma, again, in descending order. 5) 71.7% of all deaths were caused by the digestive tract, in particular, hepatocellular carcinoma, cancer of the biliary tract, liver cirrhosis and primary biliary cirrhosis, all belonging primarily to the hepato-biliary disease group. 6) As a result of 58 autopsies performed for 106 death cases, 32 cases had complete autopsies and 26 cases had partial organ punctures.

[Clinical analysis on the temporomandibular joints of the fifteen patients of rheumatoid arthritis].

It is seemed to be really important, when making a selection on the treatment for rheumatoid arthritis, to gain an insight into progress and activity of the disease. This analysis was taken in order to look upon the clinical symptoms and the radiographic abnormalities of the temporomandibular joints, obtained from fifteen rheumatoid arthritis patients who has visited on our department, since 1974. Ten patients (66.7%) had clinical evidences of temporomandibular joint. The most frequent symptom was pain on movement, followed by disturbances on mouth opening and crepitation. Patients who had been suffering from the disease for a long period offered more frequent clinical evidences. The acute phase symptoms, such as disturbances on mouth opening, swelling and oppressive pain in the preauricular area, was found in one patients. All of the patients showed some radiographic abnormalities. We've devised a criteria on the degree of condylar absorption on the purpose of comparison to the other abnormalities. The degree 1 was found in 3 joints, the degree 2 in 12 joints, the degree 3 in 14 joints, and the degree 4 in 7 joints. An absorption on the articular fossae and the tubercles were well along with this degrees. The higher degree the more frequent of clinical evidences in each joints was disclosed. And the period of the disease was related on the degrees, too. We can expect the bone scintigraphy by using 99mTc-MDP to be a good way for expression of the activity of the disease.

A study of intracytoplasmic inclusions in myeloma cells from two patients with multiple myeloma.

Two cases of multiple myeloma which showed inclusions within the cytoplasma of myeloma cells were reported. One contained crystalline inclusions which were not stained by May-Grünwald and Giemsa, and the other contained Auer rod-like spindle shaped inclusions which were stained by May-Grünwald and Giemsa and PAS. Both cases were stained intensively by acid phosphatase but they were not stained by Congo red or by thioflavine-T. Moreover, they reacted only with anti-kappa sera in the immunofluorescent study and showed the same structure on electron microscopic observation. Although they showed different staining behaviors according to their compositions, they were considered to be essentially the same. It appears that light chains produced in excess are concentrated and form inclusions through the addition of sugar or digestion by lysosomal enzymes.

A case of chronic lymphocytic leukemia with properties characteristic of natural killer cells.

A case of chronic lymphocytic leukemia that consisted of a homogeneous population of cells that had properties similar to those described for natural killer (NK) cells is presented. These leukemic cells had a morphology of large granular lymphocytes (LGL) and receptors for sheep erythrocytes (ER) and for the Fc portion of IgG (Fc gamma-R). They expressed pan-T antigens OKT3 and Leu-4, but neither helper/inducer T-cell differentiation antigens OKT4 and Leu-3a nor cytotoxic/suppressor T-antigens OKT8 and Leu-2a. HNK 1 antigen, which can be expressed on human NK cells, could be detected on almost all leukemic cells (LGL), whereas a myeloid differentiation antigen, OKM1, which can be expressed on macrophages, granulocytes, and NK cells, was not detected. Thus, it was concluded that the leukemia cells had a characteristic profile of the surface markers: ER+, Fc gamma-R+, HNK-1+, OKT3+, Leu-4+, OKT4-, OKT8-, Leu-3a, Leu-2a, and OKM1-. Although freshly isolated leukemic cells showed no cytotoxicity on NK targets, after incubation at 37 degrees C, the cells did show a potent cytotoxicity on targets of erythroleukemic cell, T cell, and monocyte (but not B cell) origins. When the cells were incubated at 37 degrees C, interferon (IFN gamma) was spontaneously produced in the culture fluids. Treatment with anti-HNK-1 and complement completely abrogated expression of NK activity and interferon production of the patient's lymphocytes in culture. These characteristic features of surface markers and functions strongly suggest the possibility that the leukemia cells of this case are of NK cell origin. The relationship between this case and chronic lymphocytic leukemia of T-cell origin is discussed.

Teratogenic potential of di- and mono-(2-ethylhexyl)phthalate in mice.

Fetotoxicity of di-(2-ethylhexyl)phthalate (DEHP) and its metabolite, mono-(2-ethyhexyl)phthalate (MEHP) was studied in pregnant mice (ddY-Slc female X CBA male). With the oral administration of DEHP 5.0 or 10.0 ml/kg representing 1/6 or 1/3 of the acute LD50 dose on day 7 of gestation there were no live fetuses. When DEHP 10.0 ml/kg was given on days 9 or 10 of gestation, however, the rates of live fetuses were 91.7% and 95.4% respectively. Gross and skeletal abnormalities in the live fetuses occurred with 2.5 or 7.5 ml/kg of DEHP given orally on days 7 or 8 of gestation respectively. Similar toxic effects were observed with the administration of MEHP. The oral administration of 0.5 or 1.0 mg/kg on day 8 of gestation resulted in 11-19% and 100% of gross and skeltal abnormalities, respectively. The gross abnormalities included exencephaly, open eyelid and club foot. Skeltal abnormalities occurred in the skull, cervical and/or thoracic bones. Thus both DEHP and MEHP exert similar effects on the mouse fetus and the lethal and/or teratogenic effects of DEHP are probably due to its metabolite, MEHP.