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Biomedical subjects

J Brinkman

Publications and source records attributed to J Brinkman.

At least 19 recordsLinked to original sources
PubMed2005

Plasma chitotriosidase and CCL18: early biochemical surrogate markers in type B Niemann-Pick disease.

Type B Niemann-Pick disease (NPD) is a nonneuronopathic lysosomal storage disorder which is characterized by accumulation of sphingomyelin-laden macrophages. The availability of plasma markers for storage cells may be of great value in facilitating therapeutic decisions. Given the similarity of the storage cells in NPD and Gaucher disease, we studied Gaucher plasma markers (chitotriosidase and CCL18) in two siblings homozygous for the R228C mutation in acid sphingomyelinase (ASM) and a type B course of NPD. The older sibling, first examined at the age of 9 months, showed marked hepatosplenomegaly and pulmonary involvement. The younger sibling has mild asymptomatic hepatosplenomgaly at the age of 5 months. Analysis of plasma specimens revealed markedly increased levels of chitotriosidase and CCL18 in the older sibling. In the younger child also, plasma chitotriosidase and CCL18 were clearly elevated above normal values almost immediately after birth and rapidly increased further. Histochemistry confirmed production of CCL18 by foam cells. In conclusion, plasma chitotriosidase and CCL18 may also serve as markers for the formation of pathological lipid-laden macrophages in type B NPD, in analogy to Gaucher disease. The availability of sensitive plasma surrogate markers may be of great value for monitoring the efficacy of enzyme supplementation therapy that is currently being developed.

Bone Marrow Cells↗
PubMed2001

Cyclopentenyl cytosine induces apoptosis and increases cytarabine-induced apoptosis in a T-lymphoblastic leukemic cell-line.

Cyclopentenyl cytosine (CPEC) is a nucleoside-analogue that decreases the concentrations of cytidine triphosphate (CTP) and deoxycytidine triphosphate (dCTP) in leukemic cells by inhibiting the enzyme CTP synthetase, resulting in a decreased synthesis of RNA and DNA. Low concentrations of dCTP facilitate the phosphorylation of 1-beta-D arabinofuranosyl cytosine (araC) and the incorporation of arabinofuranosyl cytosine triphosphate (araCTP) into DNA. Apoptosis and necrosis were analyzed by flow cytometric detection of fluorescence-labeled Annexin V in a human T-lymphoblastic MOLT-3 cell-line after incubations with CPEC and/or araC. CPEC induced apoptosis and necrosis in a concentration- (50-300 nM) and time-dependent (8-16 h) way. The observed necrosis proved to be secondary to apoptosis as the caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (zVAD-fmk) completely blocked the CPEC-induced apoptosis and necrosis. Coincubation of various concentrations of CPEC and araC for 16h showed a significant additive effect on the occurrence of apoptosis and (secondary) necrosis. In contrast, a preincubation with 37.5 nM of CPEC for 24 h, which by itself caused only minor apoptosis (4%), followed by a coincubation for 16 h with 62.5 nM of araC (7% of apoptotic cells), showed a synergistic effect on the induction of apoptosis (27%, P<0.001). Growth-inhibition experiments with CPEC and araC under various conditions showed an additive effect on the araC-induced growth-inhibition after 48 h. The results indicate that the cytotoxicity of araC can be increased in T-lymphoblasts by CPEC.

Annexin A5↗
PubMed1999

Cytokine production in acute versus chronic human Schistosomiasis mansoni: the cross-regulatory role of interferon-gamma and interleukin-10 in the responses of peripheral blood mononuclear cells and splenocytes to parasite antigens.

The contribution of interleukin (IL)-10 and interferon (IFN)-gamma to the regulation of type 1 and type 2 cytokine responses was investigated in Brazilians with different clinical forms of schistosomiasis mansoni. Cells from members of a family with acute intestinal schistosomiasis responded to schistosomal soluble egg antigen (SEA) or soluble adult worm antigen preparation (SWAP) with greater amounts of IFN-gamma than did cells from several patients with chronic intestinal schistosomiasis; IL-10 levels were similar. Neutralization of IL-10 had no effect on the SEA-specific IFN-gamma response in patients with acute infection, whereas SWAP-induced IFN-gamma was increased in both groups. Anti-IL-10 also up-regulated SEA-specific IFN-gamma protein and mRNA responses in most splenocyte cultures from hepatosplenic schistosomiasis patients but had no effect on antigen-specific IL-4 or IL-5 production. Neutralization of IFN-gamma resulted in a comparable increase in SWAP-specific IL-10 and IL-5, while IL-4 was not affected. These studies demonstrate that early disease in schistosomiasis is associated with a significant IFN-gamma response and that IL-10 contributes to the suppression of that response during both early and chronic infection.

Acute Disease↗
PubMed1997

Crohn's disease presenting with Fournier's gangrene and enterovesical fistula.

Our purpose is to make a case for early operative intervention. A 37-year-old man presented with a large periurethral abscess and Fournier's gangrene. During the ensuing evaluation and treatment, he was found to have previously undiagnosed Crohn's disease with a complex enterovesical fistula. This case stands in contrast to other reports that downplay the morbidity of enterovesical fistula associated with Crohn's disease and advise medical management until gastrointestinal complications require operative intervention.

Abdominal Abscess↗
PubMed1996

Identification of genes from a 500-kb region at 7q11.23 that is commonly deleted in Williams syndrome patients.

Williams syndrome (WS) is a multisystem developmental disorder caused by the deletion of contiguous genes at 7q11.23. Hemizygosity of the elastin (ELN) gene can account for the vascular and connective tissue abnormalities observed in WS patients, but the genes that contribute to features such as infantile hypercalcemia, dysmorphic facies, and mental retardation remain to be identified. In addition, the size of the genomic interval commonly deleted in WS patients has not been established. In this study we report the characterization of a 500-kb region that was determined to be deleted in our collection of WS patients. A detailed physical map consisting of cosmid, P1 artificial chromosomes, and yeast artificial chromosomes was constructed and used for gene isolation experiments. Using the techniques of direct cDNA selection and genomic DNA sequencing, three known genes (ELN, LIMK1, and RFC2), a novel gene (WSCR1) with homology to RNA-binding proteins, a gene with homology to restin, and four other putative transcription units were identified. LIMK1 is a protein kinase with two repeats of the LIM/double zinc finger motif, and it is highly expressed in brain. RFC2 is the 40-kDa ATP-binding subunit of replication factor C, which is known to play a role in the elongation of DNA catalyzed by DNA polymerase delta and epsilon. LIMK1 and WSCR1 may be particularly relevant when explaining cognitive defects observed in WS patients.

Amino Acid Sequence↗
PubMed1994

Extensive mobilization of the urethral plate and urethra for repair of hypospadias: the modified Barcat technique.

The modified Barcat technique was used to treat 168 patients with hypospadias during the last 5 years. The technique, which is applicable for distal hypospadias, uses apposing fully mobilized meatal based skin flaps. Cosmetic and functional results are excellent, with only 3.5% of the patients requiring reoperation. Because the surgical technique does not depend on the configuration of the glans, depth of the urethral groove, caliber of the urethral meatus or even whether the patient has been circumcised, it is particularly suitable for training residents who can perform a single operation to correct a wide variety of cosmetic deformities.

Child↗
PubMed1988

Optical quantitation of natural caries in smooth surfaces of extracted teeth.

An optical instrument is described which quantitates incipient smooth surface caries lesions in vivo. The possible role of such quantitation in caries management and in clinical caries research is discussed. The instrument uses a bundle of small fibres in an 'optical needle' with a flat end that is placed on the lesion. Half the fibres are used to illuminate the lesion and the other half to collect the light backscattered by the lesion interior. In this geometry, lesions reflect much more light than does sound enamel. The instrument has been validated against natural lesions in extracted teeth, and the depth of these lesions and their mineral loss were measured by microradiography. The correlation coefficient between these two parameters was 0.96 and the correlation between optical measurement and lesion depth 0.71.

Calibration↗
PubMed1985

Responses of precentral cells during cooling of post-central cortex in conscious monkeys.

A cooling plate was implanted over the forelimb representation in area 2 of the post-central region of cerebral cortex in two monkeys. Recordings were made of the discharges of thirty-seven movement-related neurones (thirty-four precentral and three post-central) in the forelimb motor representation of the cerebral cortex during active and passively imposed limb movements before, during and after cooling area 2 and local surrounding regions. Perfusion of the cooling plate with ice-cooled water for 3-5 min caused marked clumsiness of the conscious animal's forelimb movement and anaesthesia of the contralateral hand. Cooling of area 2 did not reduce the responses of area 4 cells to passive joint movements, nor did it alter the over-all pattern of activity of these cells during self-initiated lever pulling while that could still be performed. Cooling of area 2 did cause a significant increase in background cellular discharge in area 4 while the animal was at rest. Afferent impulses which are generated by passive joint movement and which have been shown to influence cells in area 4 of the conscious monkey at short latencies are probably not transmitted through cortico-cortical connexions from area 2.

Animals↗
PubMed1980

'Long-loop' reflexes can be obtained in spinal monkeys.

Extensor muscles of the fore- and hindlimb were stretched in the lightly anaesthetized monkey (Macaca fascicularis) and cat. The resulting electromyogram contained a short latency peak consistent with a monosynaptic, segmental pathway; this peak was identified as the M1 peak of Tatton et al. [21]. A longer latency peak, identified as M2 and said to involve a pathway including supraspinal centres, was also present. After spinal section at a high cervical level, the electromyogram was reduced in amplitude, but both short (M1) and longer latency (M2) peaks were present. It is concluded that neither the cerebral cortex nor the cerebellum are necessary parts of the neural circuitry generating longer latency components of the electromyographic response to muscle stretch.

Animals↗
PubMed1979

Clinical pharmacists as allied health care providers to psychiatric patients.

The effect of clinical pharmacy services on the quality and economy of health care provided to psychiatric patients at a Veterans Administration outpatient clinic was evaluated. Twenty-one patients were selected from the Day Treatment Center, of these, 19 patients completed the study. In providing health care to these psychiatric patients, the clinical pharmacist used a systemized approach including data gathering, evaluation, plan of action, and follow-up. In addition, medication groups and weekly staff meetings were incorporated into the patient treatment plan. Following a 3-month study period, the impact of clinical pharmacy services was evaluated. The provision of allied health care to psychiatric patients by clinical pharmacists resulted in a decreased incidence and severity of adverse drug effects, fewer drug use problems, a reduction in the total number of drugs prescribed, improved patient drug knowledge, and reduced expenditures for health care without compromising the patient's mental functioning.

California↗
PubMed1978

Deficient influence of peripheral stimuli on precentral neurones in monkeys with dorsal column lesions.

1. Four male monkeys (M. fascicularis) were trained in a movement performance task which involved pulling a horizontal lever into a target zone and then collecting, from one of a variety of positions, a small food reward. The same animals were also trained to sit quietly and accept passive manipulation and natural stimulation of the arm and hand while remaining relaxed. 2. After complete bilateral section of the cuneate fasciculi or division of a major part of these dorsal column afferents at C1-C2 or at C5 level, the animals were still able to perform movement tasks normally. Disturbance of discrimination ability was revealed after vision was occluded it the animal was required to detect differences in texture with only a small cutaneous area in contact with the object (e.g. using only the tip of the index finger). Contactual-placing reactions could be performed in the absence of vision and the movements the animal made in these reactions were well controlled and appropriately directed. Minimal disturbance of contact placing was noticed if the surface touched was on the hand or fingers or if the reaction involved crossed placing. 3. An examination of the natural discharges of 342 percentral neurones revealed that the patterns of activity exhibited in relation to complex movements were indistinguishable from patterns recorded in normal monkeys carrying out similar tasks. 4. Discharges of ninety-one of 321 precentral neurones could be produced by appropriate natural stimuli delivered within the cell's afferent input zone at the periphery. The zone from which a given cell could be influenced was usually limited and its location could be on any part of the contralateral forelimb. However, all but nine of these responses were found in animals in which a small proportion of the cuneate fibres remained intact. In an animal with histologically proven complete section of the cuneate faciculi very few (nine of 171) precentral neurones were influenced by natural activation of peripheral receptors in the forelimb. The zones from which these few afferent inputs were found could all have been proximal to the level of the cuneate lesion. 5. The very small number of responding pre-central neurones found in an animal with complete section of the cuneate fasciculi made it likely that the dorsal columns provide the major pathway for effects from circumscribed peripheral receptors in the forelimb to influence precentral neurones. However, even in an animal with complete interruption of cuneate fibres, a proportion of post-central neurones could still be influenced by natural activation of peripheral receptors within restricted regions of the forelimb. Hence the 'sensory' cortex was still in receipt of afferent projections which could be revealted readily by the tests used. 6...

Action Potentials↗
PubMed1978

Supplementary motor area of the monkey: activity of neurones during performance of a learned motor task.

1. Recordings were made of the natural dischages of neurones in the supplementary motor area (SMA) of conscious monkeys trained to perform a stereotyped motor task with either hand. 2. Eighty % of the total population of cells showed modulation of their activity during particular movements of either limb. Two thirds of this group had a similar pattern of modulation regardless of whether the contralateral or ipsilateral hand was used. 3. The number of cells whose activity was related to movements of distal joints was approximately equal to that whose discharges occurred with proximal movements. 4. Only 5% of cells tested sent their axons into the pyramidal tract, and only 15% of units investigated showed responses to passive manipulation of the limbs. The effective afferent input usually was of a rather complex kind. 5. The findings suggest that the discharges of a large number of neurones in SMA are changing during particular movements of either arm, and that only a small number of cells receive afferent sensory input. These results contrast with those obtained in the primary motor area and suggest a different role for SMA the control of movement.

Action Potentials↗