Cystinuria genotypes predicted from excretion patterns.

Genotypes of 17 patients with cystinuria were predicted from data based on excretion rates of the families' obligate carriers. The methodology differed from that used by other investigators as it did not employ intestinal biopsy studies or loading dose measurements. The Type I form was more common than either Type II or Type III and frequently occurred in combination to give compound heterozygous genotypes with the Type III form.     

Modified endoplasmic reticulum in taste bud cells of the Japanese monkey

Type III cells (receptor cells) in taste buds of vallate papillae in the Japanese monkey often have one or more cytoplasmic bodies composed of modified smooth endoplasmic reticulum in the form of concentric smooth-surfaced cisternae, up to 18 in number. The most peripheral cisternae may be in continuity with rough endoplasmic reticulum (RER). Type II cells have dilated RER cisternae that often contain crystalline plates with an axial periodicity that ranges from 17 to 27 nm. These observations show that both type III and type II cells of the Japanese monkey possess the cytoplasmic machinery to carry out several secretory functions.     

Increased cerebroside concentration in plasma and erythrocytes in Gaucher disease: Significant differences between Type I and Type III

A method was developed for the determination of cerebrosides in 1 ml of plasma or 1 ml of packed erythrocytes. At least 90% of the cerebroside fraction consisted of glucosylceramide. In the erythrocytes, nothing but glucosylceramide was identified. The method was applied to plasma samples from 25 controls, 34 Gaucher Type III obligate carriers, 16 Gaucher Type III patients, 7 Gaucher Type I patients and 7 patients with myelogenous or lymphatic leukemia, as well as to erythrocyte samples from 20 controls, 6 Gaucher Type III obligate carriers, 16 Gaucher Type III patients and 6 Gaucher Type I patients. The concentration of plasma cerebroside was 11.4±4.2 (S.D.) in controls, 11.8 ± 2.6 in Gaucher Type III carriers, 30.4 ± 7.7 in Gaucher Type III patients and 21.8 ± 6.7 μmol/l in Gaucher Type I patients. The Gaucher patients had Significantly increased (p <0.001) plasma cerebroside values, while the plasma cerebroside concentration of the leukemic patients was only slightly increased, 14.7 ± 5.7 μmol/l. In the packed erythrocyte pellet the corresponding values were: Controls 2.9 ± 0.7, Gaucher Type III carriers 2.9 ± 0.7, Gaucher Type III patients 9.2 ± 2.4 and Gaucher Type I patients 6.5 ± 2.7 μmol/l. The phospholipid concentration was the same in all the three Gaucher groups and was not significantly different from that in the controls.     

Another mechanism for the defect in type III collagen accumulation in Ehlers-Danlos syndrome type IV: increased intracellular degradation of the procollagen

The nature of type III collagen was examined in the skin and cultured skin fibroblasts from a patient with Ehlers-Danlos syndrome type IV. Although the culture medium contained a much lower amount of Type III collagen than the controls, the cells contained an apparently normal amount of Type III collagen. The patient's Type III procollagen showed no abnormalities in apparent molecular weight, the peptide length as examined by cyanogen bromide cleavage, the genomic DNA size including its C- and N-propeptide portion, mRNA size, or thermal stability; but a pulse-chase study revealed prolonged retention of the type III collagen in the cells. Degradation of Type III procollagen was induced by cell extracts but did not occur in the extracellular space and was inhibited in intact cells by the addition of ammonium chloride or leupeptin to the culture medium. Fluorescent staining showed a characteristic granular deposition of Type III procollagen in the peripheral region of the cytoplasm but no granular deposition of Type I procollagen. These results offer new insight into the mechanism of the decreased amount of Type III collagen in the tissue of patients with Ehlers-Danlos syndrome type IV.     

An immunohistochemical and serum ELISA study of type I and III procollagen aminopropeptides in primary biliary cirrhosis.

By means of ELISA methodology, the aminopropeptides of Type I and Type III procollagen were measured in the serum of a group of patients with primary biliary cirrhosis. The corresponding liver biopsies were graded blindly for degrees of fibrosis and inflammation. When available, paraffin-embedded liver specimens underwent immunoperoxidase staining for mature Type I and III collagen as well as the aminopropeptides of Type I and III procollagen. Regardless of the degree of fibrosis or inflammation, serum levels of the aminopropeptide of Type I remained within normal limits. In contrast, serum levels of the aminopropeptide of Type III procollagen were elevated uniformly. Immunohistochemistry demonstrated that the aminopropeptide of Type III procollagen persists extracellularly. This finding may explain the previously reported relationship between levels of inflammation and serum levels of the Type III aminopropeptide.     

Mouse glomerular culture.

A method is described for the culture of isolated intact mouse glomeruli. Cultures showed adherent glomeruli after 2 days and from 2-4 days a monolayer of cells began to develop around the points of adherence. The predominant cell (Type I) was 80-200 micrometer in diameter with cytoplasmic extensions, later becoming polyhedral and often multinucleated. Type II spindle cells, 70-100 micrometer in length, were less prominent in the earlier stages and later formed sheaves between Type I cells. Small phagocytic Type III cells, 10-20 micrometer in diameter, were not prominent in cultures from normal kidneys and tended to form small clusters on top of the Type I cell monolayer.     

Another family with tricho-rhino-phalangeal syndrome type III (Sugio-Kajii syndrome)

Tricho-rhino-phalangeal syndrome Type III (TRPS III) is a newly defined genetic entity. Only 9 patients in a family and one sporadic patient have been reported. We add another family in which 4 individuals in 3 generations are affected with this autosomal dominant trait. Although they manifested short stature, sparse hair, “pear-shaped” nose, and coneshaped epiphyses, sharing these findings with TRPS Type I, the presence of a severe form of generalized shortness of all phalanges and metacarpals, and the absences of mental deficiency and exostoses in this family distinguish the disorder from the TRPS Types I and II. Their manifestations are quite similar to those of the patients reported as TRPS III (Sugio-Kajii syndrome). © 1994 Wiley-Liss, Inc.     

骨肉瘤肿瘤性骨样组织分型的立体计量学与预后的研究

The diagnostic criteria of neoplastic osteoid were established by means of stereological study of 70 cases of osteosarcoma. According to the different histological features, the authors suggest that osteosarcomas are to be classified into three types: Type I (mature osteoid type), Type II (intermediate differentiated osteoid type) and Type III (immature osteoid type). 50 patients out of the 70 had been followed up for years. The five-year survival rate in 12 patients with Type I was 92%; in 18 patients with Type II and 20 patients with Type III, none of them survived more than five years after operation. Statistically significant difference was found between individuals with Type I and Type II, or with Type I and Type III. However, there was no statistically significant difference between the histological types according to Dahlin. The results showed that our classification given in this paper may be preferable to the Dahlin's for evaluation of prognosis.     

Prenatal development of growth hormone-producing cells in the rat anterior pituitary as studied by immunogold electron microscopy

The existence of three morphologically different types of GH cells in the rat anterior Pituitary glands has been reported previously. Among these three types, Type III which contains the smallest granules has been considered to be immature, because this type occurs more frequently in neonatal rats than in adults. In this study, the prenatal development of GH cells in the rat fetus was observed by immunoelectron microscopy. In the rat fetus at 18.5 days of gestation, Type III cells were most numerous (48.5%), followed by Type II cells (45.5%). Type I cells were almost absent from these fetal pituitaries. At 20.5 days Type II cells exceeded Type III in frequency, and Type I cells also increased to about 35%. These results indicate that Type III cells are the most immature type of GH cells, and might transform into Type II and, in turn, to Type I, as the rats mature. Images indicating active secretory functions such as granule formation in the Golgi apparatus and/or GERL, exocytosis and crinophagy were observed in the GH cells even in the fetal stage.     

The gross anatomy of the extrathoracic course of the intercostobrachial nerve

Recent reports emphasize the importance of preserving the intercostobrachial nerve (ICBN) during surgical procedures (i.e., mastectomy, axillary clearance). However, a limited number of scientific reports explore the surgical anatomy of this nerve. We dissected 100 adult human formalin-fixed cadavers (200 axillae). In all the cadavers the ICBN was present with variant contributions from intercostal nerves T1, T2, T3, and T4. The arrangements of the ICBN were typed as I through VIII. The components of Type I (45% or 90 of our specimens) included a branch to the posterior antebrachial cutaneous nerve, a branch to the anterior and lateral parts of the axilla, a branch to the medial side of the arm, and a branch to the medial antebrachial cutaneous nerve. Type II (25%) describes the ICBN arising from T2 and giving off a branch to the brachial plexus. In Type III (10%), lateral cutaneous branches of T2 and T3 fuse as a common trunk and then split immediately after exiting the intercostal space to form an ICBN. In type IV (5%), T2 and T3 join distally to form an ICBN that ends as its terminal branches. Type V (5%): T3 joins T2 from the same intercostal space proximally, with Type VI (3%) showing a very proximal branching of the sensory terminal nerves. Type VII (5%) displayed a contribution from T3 and a branch to the brachial plexus with multiple terminating branches. A contribution from T3 and T4 and a branch to the brachial plexus with multiple branches of termination comprised Type VIII (2%).     

Machado-Joseph disease in a Sicilian-American family

Machado-Joseph disease (MJD) is an autosomal dominant motor system degeneration which was originally described in Portuguese-American families. Large pedigrees have been found on the east and west coasts of the United States in which 4 main syndromes are described. Type I disease presents with pyramidal and extrapyramidal findings usually in individuals in the second or third decades of life. Type II disease, which is the most common form of presentation, includes true cerebellar deficits associated with other motor features. Type III is late-onset in the fifth through the seventh decades of life presenting with pancerebellar deficits with motor and sensory polyneuropathy. A rare presentation is Type IV with parkinsonian features with mild cerebellar deficits and a distal motor sensory neuropathy or amyotrophy. A family is described here with typical MJD who are of Italian origin. It thus indicates a wider distribution of this gene which now clearly has entered a second Italian-American family.     

Molecular analysis of the AGL gene: Identification of 25 novel mutations and evidence of genetic heterogeneity in patients with Glycogen Storage Disease Type III

PurposeGlycogen Storage Disease Type III (limit dextrinosis; Cori or Forbes disease) is an autosomal recessive disorder of glycogen metabolism caused by deficient activity of glycogen debranching enzyme in liver and muscle (Glycogen Storage Disease Type IIIa) or liver only (Glycogen Storage Disease Type IIIb). These two clinically distinct phenotypes are caused by mutations in the same gene (amylo-1,6-glucosidase or AGL). Although most patients with Glycogen Storage Disease Type III have private mutations, common mutations have been identified in some populations, and two specific mutations in exon 3, c.18_19delGA (p.Gln6HisfsX20) and c.16C>T (p.Gln6X), are associated with the Glycogen Storage Disease Type IIIb phenotype.MethodsTo further examine the heterogeneity found in Glycogen Storage Disease Type III patients, we have sequenced the AGL gene in 34 patients with a clinically and/or biochemically confirmed diagnosis of Glycogen Storage Disease Type III.ResultsWe have identified 38 different mutations (25 novel and 13 previously reported) and have compiled a list of all mutations previously reported in the literature.DiscussionWe conclude that Glycogen Storage Disease Type III is a highly heterogeneous disorder usually requiring full gene sequencing to identify both pathogenic mutations. The finding of at least one of the two exon 3 mutations in all of the Glycogen Storage Disease Type IIIb patients tested allows for diagnosis of this subtype without the need for a muscle biopsy.     

Isolated invasive Aspergillus tracheobronchitis: a clinical study of 19 cases

Isolated invasive Aspergillus tracheobronchitis (iIATB) is an uncommon clinical form of invasive Aspergillosis in which Aspergillus infection is limited entirely or predominantly to the tracheobronchial tree. In the present study, we retrospectively analyzed the medical records of 19 patients who had histological documented iIATB in the Department of Respiratory Medicine of Changhai Hospital between October 2000 and February 2008. Malignancy was the most common underlying disease, which existed in 14 patients (73.7%) in our series. Most patients had impaired airway structures or defence functions, whereas the systemic immune status was relatively normal. Only three patients (15.8%) had neutropenia. The clinical manifestations and chest radiograph were non-specific. We classified iIATB into four different forms according to the bronchoscopic features of intraluminal lesions: superficial infiltration type (Type I, n = 4), full-layer involvement type (Type II, n = 2), occlusion type (Type III, n = 6) and mixed type (Type IV, n = 7). Type IV was the largest group in our study, followed by Type III. All patients with iIATB of Type IV had definite airway occlusion. Fourteen patients (73.7%) had a good response to antifungal treatments and five (26.3%) died as a result of the progression of Aspergillosis, all of whom had full-layer invasion of the involved bronchi. In conclusion, we found that iIATB could occur in moderately or non-immunocompromised patients with impaired airway structures or defence functions and may be an early period of invasive pulmonary Aspergillosis. Most of the iIATB patients had a favourable prognosis with early diagnosis and effective antifungal treatment. The morphological features of intraluminal lesions might be of prognostic value.     

Hemolymph cells and the platelet-like structures of the land slug, Incilaria bilineata (Gastropoda: Pulmonata)

3 morphologically distinct hemolymph cell-types, Types I, II and III, were found by light and electron microscopy of hemolymph from the land slug, Incilaria bilineata. In addition, vast numbers of the platelet-like structures were present in the collected hemolymph. Type I cells were macrophage-like, Type II cells were lymphocyte-like and Type III cells were fibroblast-like. Among these hemolymph cells, only Type I cells could recognize foreign materials and phagocytose them. Type I cells, whether from circulating hemolymph or from the heart-kidney region (regarded as a hemopoietic organ), could be maintained for only 4 d in cultivation because the cells gradually divided within 3 or 4 d. Thus, the platelet-like structures appear to be derived from Type I cells, which readily fragmentize and function by clamping onto foreign materials.     

The ultrastructure of hemolymph cells of the land slug, Incilaria fruhstorferi Collinge (Gastropoda: Pulmonata)

3 morphologically distinct hemolymph cell-types, Type I, II and III, were found in the hemolymph of the land slug, large Japanese native slug, Incilaria fruhstorferi Collinge. Type I cell, measuring approximately 35 microns in diameter, had extensive pseudopodia with supporting ribs and a kidney-shaped or lobulated nucleus. Sometimes it possessed long filopodia (approximately 50 microns) with branched fibers. It contained residual bodies, multivesicular bodies, Golgi apparatus, free ribosomes and glycogen-like deposits. Type II cell, approximately 5 microns in diameter, did not form large pseudopodia, had a higher nucleus to cytoplasm ratio. It contained scattered free ribosomes surrounding the round nucleus. Type III cell, approximately 75 X 15 microns, was a fibroblast-like cell. It contained microfibrils at the rim of perinuclear cytoplasm and possessed collagen-like fibers outside of the cytoplasmic membrane. Numerous plate-like structures, which had not been reported yet, were usually observed. They, measuring 1 to 5 microns in diameter, were oval, but when in contact with glass, they possessed long and fine fibers. They lacked nucleus.     

Neurofilament content is correlated with branch length in developing collateral branches of Xenopus spinal cord neurons

During development, axons form interstitial collateral branches, which are initially dynamic but gradually stabilize as the projection sharpens. The initial outgrowth of collaterals is characterized by transitions in growth dynamics that occur at different lengths. Below 10 microm, collateral branches start out as unstable, thin filopodia. Above 30 microm, the branches stabilize. Although the relationship between branch length and the presence of microfilaments and microtubules has been well characterized, relatively less is known about the development of the neurofilament cytoskeleton in collateral branches. In the main axon, successive stages of outgrowth are accompanied by changes in the polypeptide composition of neurofilaments (NFs), which shifts from being rich in Type III neuronal intermediate filament proteins (nIFs) to progressively favoring Type IV subunits. To characterize the NF composition of developing collateral branches, antibodies to peripherin (a Type III nIF) and NF-M (a Type IV nIF) were used to stain newly differentiating embryonic Xenopus laevis spinal cord neurons in culture. In contrast to what happens in the main axon, staining for both subunits coincided in collaterals. Branches shorter than 10 microm seldom had NFs, whereas all branches longer than 30 microm did. In branches that had NFs staining either extended all the way to branch tip or terminated approximately 10mum from it. These lengths correspond remarkably well with lengths associated with branch stabilization. Given that NFs are the most stable of the cytoskeletal polymers, we speculate that they may contribute to this stabilization.     

Detection of early invasion on the basis of basement membrane destruction in small adenocarcinomas of the lung and its clinical implications.

To evaluate the correlation between the degree of basement membrane (BM) preservation and clinicopathological characteristics in the replacement-growth type (lepidic growth type) of small peripheral adenocarcinomas of the lung, the BM components of 72 surgically resected replacement-growth type adenocarcinomas of the lung, 2 cm or less in diameter, were evaluated immunohistochemically by using a monoclonal antibody to Type IV collagen and polyclonal antibodies to 7S collagen and laminin. The tumors were classified into the following three distinctive histological types according to the condition of the elastic framework: Type I, bronchioloalveolar carcinoma without fibrotic foci; Type II, sclerosing bronchioloalveolar carcinoma without elastic framework destruction; and Type III, sclerosing bronchioloalveolar carcinoma with elastic framework destruction. The BM was well preserved in the area of bronchioloalveolar spread along fully expanded alveoli in all tumor types; however, BM preservation was significantly lost in the areas of collapsed alveoli in Type III tumors. There were no BM component staining reactions in the scarred regions of Type III tumors. In addition, lymph node metastasis was significantly greater in Type III tumors and BM-destroyed tumors. We concluded that the BM was largely destroyed by tumor cell invasion in the scarred region of Type III adenocarcinomas. Type III tumors had discontinuous BMs in the area of collapsed alveoli, indicating that this BM-destructive pattern must be the first step in tumor invasion. Type I and II tumors were concluded to be noninvasive adenocarcinomas, because their BM components were well preserved and they had a good outcome.     

The electrodiagnostic characteristics of Glycogen Storage Disease Type III

PurposeGlycogen Storage Disease Type III, also known as debrancher deficiency or Cori disease, is an autosomal recessive disorder recognized for both its hepatic and muscle manifestations. The neuromuscular manifestations of Glycogen Storage Disease Type III are not well characterized. In this study, we attempt to better define the disorder.MethodsThe medical records of 40 patients with Glycogen Storage Disease Type III seen at Duke University during 1990–2009 were reviewed. The medical records of all patients with nerve conduction studies and/or electromyography were examined.ResultsTwelve patients with Glycogen Storage Disease Type III (aged 5–55 years) had undergone nerve conduction studies ± electromyography. Three of these cases are presented in detail. Nine patients had Glycogen Storage Disease Type IIIa, two patients had Glycogen Storage Disease Type IIIb, and the clinical subtype of one patient was unknown. All had nerve conduction studies and of those nerves tested, abnormalities in the median motor response were most common, corresponding to previously described, intrinsic hand muscle weakness. Electromyography was performed in eight patients and myopathic findings were present in six individuals. Abnormal electrodiagnostic findings were more common in older patients. The two patients with Glycogen Storage Disease Type IIIb had electrodiagnostic evidence of nerve involvement with minor myopathic findings.ConclusionsThe neuromuscular manifestations of Glycogen Storage Disease Type III include myopathy and neuropathy and are more likely to occur with increasing age, even in those diagnosed with Glycogen Storage Disease Type IIIb. Intrinsic hand muscle weakness is likely due to a combination of nerve and muscle dysfunction, a finding that may have implications for treatment.     

Responses to tones and noise of single cells in dorsal cochlear nucleus of unanesthetized cats.

1. Single-unit responses in the dorsal cochlear nucleus of unanesthetized, decerebrate cats have been divided into two categoreis. These have been differentiated on the basis of responses to best-frequency tones. Type IV units responded to best-frequency tones with excitation from threshold to about 20 or 30 dB above threshold; at higher levels, their response was inhibitory. In a few cases, the excitatory area near threshold was not seen and in a few others, the response became excitatory again at high levels. Type IV units could be divided into two groups based on the length of time that inhibition was maintained in response to long tones. Type IV units are not seen in anesthetized cats. 2. Type II/III units responded to best-frequency tones of all levels with excitation. Nonmonotonic rate versus level functions were seen in type II/III units, but they were of much less drastic character; the discharge rate of nonmonotonic type II/III units was still well above spontaneous rate for tones 50 dB above threshold. Type II/III units defined in this way were found to have, on the average, lower rates of spontaneous activity and higher thresholds than type IV units. 3. Type II/III units responded weakly to broad-band noise in comparison to auditory nerve fibers and many of them did not respond at all to noise. Type IV units, with best frequencies above 0.9 kHz, gave excitatory responses to noise. 4. The inhibitory response areas of type IV units could be divided into two areas: a central inhibitory area in the vicinity of best frequency where on- and off-discharges and afterdischarges were seen; and inhibitory side bands at higher and lower frequencies where simple inhibitory responses were seen. In four units, it was possible to show that the central inhibitory area was converted to an excitatory area after administration of an anesthetic dose of pentobarbital. 5. Most type II/III and type IV units could be excited or inhibited by stimuli in the contralateral ear. Broad-band noise was a more effective contralateral stimulus than tones at the ipsilateral best frequency. 6. On the basis of the properties of type II/III and type IV cells, it is suggested that type II/III responses are recorded from interneurons which provide a large share of the inhibitory imput to type IV cells.     

Factor XI deficiency in Ashkenazi Jews in Israel

BACKGROUND AND METHODS. Severe factor XI deficiency, which is relatively common among Ashkenazi Jews, is associated with injury-related bleeding of considerable severity. Three point mutations--a splice-junction abnormality (Type I), Glu117----Stop (Type II), and Phe283----Leu (Type III)--have been described in six patients with factor XI deficiency. Clinical correlations with these mutations have not been carried out. We determined the relative frequency of the mutations and their association with plasma levels of factor XI clotting activity and bleeding, analyzing the mutations with the polymerase chain reaction and restriction-enzyme digestion. RESULTS. The Type II and Type III mutations had similar frequencies among 43 Ashkenazi Jewish probands with severe factor XI deficiency; these two mutations accounted for 49 percent and 47 percent, respectively, of a total of 86 analyzed alleles. Among 40 of the probands and 12 of their relatives with severe factor XI deficiency, patients homozygous for Type III mutation had a significantly higher level of factor XI clotting activity (mean [+/- SD] percentage of normal values, 9.7 +/- 3.8 percent; n = 13) than those homozygous for Type II mutation (1.2 +/- 0.5 percent, n = 16) or compound heterozygotes with Type II/III mutation (3.3 +/- 1.6 percent, n = 23), as well as significantly fewer episodes of injury-related bleeding. Each of these three groups had a similarly increased proportion of episodes of bleeding complications after surgery at sites with enhanced local fibrinolysis, such as the urinary tract, or during tooth extraction. CONCLUSIONS. Type II and Type III mutations are the predominant causes of factor XI deficiency among Ashkenazi Jews. Genotypic analysis, assay for factor XI, and consideration of the type and location of surgery can be helpful in planning operations in patients with this disorder.