To determine whether young patients with IDDM already have atherosclerosis and what factors would relate to atherosclerosis, we examined the intimal-medial thickness (IMT) of the common carotid artery by ultrasonography. Subjects were 29 young patients with IDDM (aged 17-39 years, duration 4-31 years) without manifest macroangiopathy and 13 healthy controls of comparable age (22-29 years). The carotid artery IMT of young patients with IDDM were significantly higher than those of controls (0.60 +/- 0.09 vs. 0.46 +/- 0.02 mm, P < 0.0001). The levels of IMT significantly correlated to diastolic blood pressure (r = 0.45, P < 0.02), and were higher in those with proliferative retinopathy than those without retinopathy (0.66 +/- 0.09 vs. 0.55 +/- 0.08 mm, P < 0.02). The levels of IMT showed no significant correlation to the attained age, duration of IDDM, HbA1c, systolic blood pressure, and cholesterol level. These findings suggest the usefulness of this examination for the early detection of diabetic macroangiopathy, and point to a close relationship between microangiopathy and macroangiopathy in IDDM.

Adolescent↗

PubMedDate not supplied

Changes of albumin concentrations in the first morning urine according to age and sex in 2990 healthy children and adults.

This study was performed to clarify the changes in urinary albumin excretion according to age and sex in healthy subjects, for the appropriate judgment of microalbuminuria in insulin-dependent diabetes mellitus (IDDM). Concentrations of albumin in the first morning urine from 2990 healthy individuals (1713 males, 1277 females) aged from 6 to 39 years were measured by turbidimetry immunoassay. Reference values of the concentrations for each age group were obtained from the 95% confidence limits from the distribution simulated by the chi 2-test (k = 1). Reference values were 1.3-2.2 mg/dl in children aged 6-11 years. Values for females increased significantly from 22 mg/dl at age 11 years to 3.9 mg/dl at age 12 years (P < 0.0001) and those of males increased gradually from 1.7 mg/dl at age 11 years to 3.9 mg/dl at age 16 years. There were significant differences between males and females at the ages of 12 (P < 0.0001), 13 (P < 0.0001), and 14 (P < 0.0007). After 17 years, the values decreased from 3.9 mg/dl to 3.3 mg/dl in females, and to 2.9 mg/dl in males. We conclude that reference values of urinary albumin excretion change according to age and sex, which should be taken into consideration in the assessment of diabetic nephropathy in IDDM.

Adolescent↗

PubMedDate not supplied

Development of diabetic nephropathy in Japanese patients with insulin-dependent diabetes mellitus: Tokyo Women's Medical College epidemiologic study.

To clarify the development of diabetic nephropathy in Japanese insulin-dependent diabetes mellitus (IDDM), 373 patients with IDDM who had no proteinuria at the first visit to our Diabetes Center were evaluated. The incidence of persistent proteinuria increased rapidly between 10 and 19 years of diabetes duration, and only a few new cases occurred thereafter. Patients whose ages at onset of IDDM were 9-17 years (n = 167) and 18-29 years (n = 90) had rapid development of persistent proteinuria compared to the 0 to 8-year group (n = 116) (p < 0.02 and p < 0.003, respectively). Females (n = 233) developed persistent proteinuria to a greater extent until 24 years of diabetes duration than males (n = 140) (p = 0.17). Development of proteinuria did not vary according to calendar year of diagnosis of IDDM or diabetes duration at the first visit. Renal insufficiency (serum creatinine of 2.0 mg/dL or greater) followed the onset of proteinuria; 60% of the patients with the onset of IDDM between 1951 and 1969 developed renal insufficiency 10 years after the onset of proteinuria, whereas 30% of patients with the onset of IDDM after 1970 developed this condition. Development of renal insufficiency did not vary according to sex, age at onset of IDDM, or age at onset of proteinuria. Renal failure requiring dialysis therapy occurred within 4 years after renal insufficiency. In conclusion, development of diabetic nephropathy in Japanese IDDM exhibits three stages. The onset of proteinuria appears to be influenced by age at onset of IDDM and sex.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMedDate not supplied

Management and design of the maintenance of SAM mouse strains: an animal model for accelerated senescence and age-associated disorders.

The Senescence-Accelerated Mouse (SAM) was established by inbreeding and pedigree selection based on the life span, degree of senescence, as well as the incidence and degree of several age-associated disorders. At first, SAM strains were developed under conventional conditions, but now some strains are also maintained under specific pathogen-free conditions. There are many methods used to maintain such strains of mice; our methods will be introduced as one example of how to develop and maintain strains of mice used in aging research.

Aging↗

PubMedDate not supplied

Role of connexin (gap junction) genes in cell growth control and carcinogenesis.

Gap junctional intercellular communication (GJIC) is considered to play a key role in the maintenance of tissue independence and homeostasis in multicellular organisms by controlling the growth of GJIC-connected cells. Gap junction channels are composed of connexin molecules and, so far, more than a dozen different connexin genes have been shown to be expressed in mammals. Reflecting the importance of GJIC in various physiological functions, deletion of different connexin genes from mice results in various disorders, including cancers, heart malformation or conduction abnormality, cataract, etc. The possible involvement of aberrant GJIC in abnormal cell growth and carcinogenesis has long been postulated and recent studies in our own and other laboratories have confirmed that expression and function of connexin genes play an important role in cell growth control. Thus, almost all malignant cells show altered homologous and/or heterologous GJIC and are often associated with aberrant expression or localization of connexins. Aberrant localization of connexins in some tumour cells is associated with lack of function of cell adhesion molecules, suggesting the importance of cell-cell recognition for GJIC. Transfection of connexin genes into tumorigenic cells restores normal cell growth, supporting the idea that connexins form a family of tumour-suppressor genes. Some studies also show that specific connexins may be necessary to control growth of specific cell types. We have produced various dominant-negative mutants of Cx26, Cx32 and Cx43 and showed that some of them prevent the growth control exerted by the corresponding wild-type genes. However, we have found that connexins 32, 37 and 43 genes are rarely mutated in tumours. In some of these studies, we noted that connexin expression per se, rather than GJIC level, is more closely related to growth control, suggesting that connexins may have a GJIC-independent function. We have recently created a transgenic mouse strain in which a mutant Cx32 is specifically overexpressed in the liver. Studies with such mice indicate that Cx32 plays a key role in liver regeneration after partial hepatectomy. A decade ago, we proposed a method to enhance killing of cancer cells by diffusion of therapeutic agents through GJIC. Recently, we and others have shown that GJIC is responsible for the bystander effect seen in HSV-tk/ganciclovir gene therapy. Thus, connexin genes can exert dual effects in tumour control: tumour suppression and a bystander effect for cancer therapy.

Animals↗

PubMedDate not supplied

Development of a method for embedded-culture of pig pancreatic islet-like cell clusters in agarose containing maltose-carrying polystyrene (HEVM) and nicotinamide.

A method for embedded-culture of islet-like cell clusters (ICCs) from neonatal pig pancreas is described. The procedure is based on a sequential treatment of the pancreas with a proteolytic enzyme and ethylenediaminetetraacetate (EDTA). During the exposure to EDTA-Dispase, small pieces of pancreas were gradually digested, with gentle stirring. Under- and over-digested pancreatic cell clusters were separated from the pancreatic fragments by filtration, and formed whole islet-like cell clusters in RPMI 1640 containing 11.0 mM D-glucose and 10% fetal bovine serum (FBS). The ICCs were embedded in agarose with or without a gel containing a random copolymer hydroxethylmethacrylate-vinylbenzyl maltonamide (HEVM) of hydroxethylmethacrylate-(HEMA)-vinylbenzyl maltonamide (VMA) and nicotinamide. They remained morphologically intact and a physiological response to acute stimulation with glucose was obtained when they were embedded in the agarose containing HEVM and nicotinamide. These findings suggest that ICCs in agarose containing HEVM and nicotinamide could be a useful tool for morphological, biochemical and molecular biological studies, and also as a potential source of material for transplantation.

Animals↗